Steven D. Chang, MD

All Publications

• Evidence for endothelial-to-mesenchymal transition in human brain arteriovenous malformations. Clinical and translational medicine Shoemaker, L. D., McCormick, A. K., Allen, B. M., Chang, S. D. 2020

  Abstract

  BACKGROUND: Brain arteriovenous malformations (AVMs) are rare, potentially devastating cerebrovascular lesions that can occur in both children and adults. AVMs are largely sporadic and the basic disease biology remains unclear, limiting advances in both detection and treatment. This study aimed to investigate human brain AVMs for endothelial-to-mesenchymal transition (EndMT), a process recently implicated in cerebral cavernous malformations (CCMs).METHODS: We used 29 paraffin-embedded and 13 fresh/frozen human brain AVM samples to profile expression of panels of EndMT-associated proteins and RNAs. CCMs, a cerebrovascular disease also characterized by abnormal vasculature, were used as a primary comparison, given that EndMT specifically contributes to CCM disease biology. AVM-derived cell lines were isolated from three fresh, surgical AVM samples and characterized by protein expression.RESULTS: We observed high collagen deposition, high PAI-1 expression, and expression of EndMT-associated transcription factors such as KLF4, SNAI1, and SNAI2 and mesenchymal-associated markers such as VIM, ACTA2, and S100A4. SMAD-dependent TGF-beta signaling was not strongly activated in AVMs and this pathway may be only partially involved in mediating EndMT. Using serum-free culture conditions, we isolated myofibroblast-like cell populations from AVMs that expressed a unique range of proteins associated with mature cell types and with EndMT. Conditioned medium from these cells led to increased proliferation of HUVECs and SMCs.CONCLUSIONS: Collectively, our results suggest a role for EndMT in AVM disease. This may lead to new avenues for disease models to further our understanding of disease mechanisms, and to the development of improved diagnostics and therapeutics.

  View details for DOI 10.1002/ctm2.99

  View details for PubMedID 32564509

• Stereotactic radiosurgery for head and neck paragangliomas: a systematic review and meta-analysis. Neurosurgical review Fatima, N., Pollom, E., Soltys, S., Chang, S. D., Meola, A. 2020

  Abstract

  Head and neck paragangliomas (HNPs) are rare, usually benign hyper vascularized neuroendocrine tumors that traditionally have been treated by surgery, with or without endovascular embolization, or, more recently stereotactic radiosurgery (SRS). The aim of our study is to determine the clinical and radiographic effectiveness of SRS for treatment of HNPs. A systematic search of electronic databases was performed, and 37 articles reporting 11,174 patients (1144 tumors) with glomus jugulare (GJT: 993, 86.9%), glomus tympanicum (GTT: 94, 8.2%), carotid body tumors (CBTs: 28, 2.4%), and glomus vagale (GVT: 16, 1.4%) treated with SRS definitively or adjuvantly were included. The local control (LC) was estimated from the pooled analysis of the series, and its association with SRS technique as well as demographic and clinical factors was analyzed. The median age was 56years (44-69years). With a median clinical and radiological follow-up of 44months (9-161months), LC was 94.2%. Majority of the patients (61.0%) underwent Gamma Knife Radiosurgery (GKS), but there was no statistically significant difference in LC depending upon the SRS technique (p=0.9). Spearmen's correlation showed that LC was strongly and negatively correlated with multiple parameters, which included female gender (r=-0.4, p=0.001), right-sided tumor (r=-0.3, p=0.03), primary SRS (r=-0.5, p≤0.001), and initial clinical presentation of hearing loss (r=-0.4, p=0.001). To achieve a LC ≥90%, a median marginal dose (Gy) of 15 (range, 12-30Gy) was required. The results corroborate that SRS in HNPs is associated with good clinical and radiological outcome.

  View details for DOI 10.1007/s10143-020-01292-5

  View details for PubMedID 32318920

• Stereotactic Radiosurgery for Benign Spinal Tumors. Neurosurgery clinics of North America Meola, A., Soltys, S., Schmitt, A., Gerszten, P. C., Chang, S. D. 2020; 31 (2): 231–35

  Abstract

  Benign spinal tumors are rare clinical conditions, including meningiomas, schwannomas, and neurofibromas. Although these tumors are usually treated with open surgical resection, spinal stereotactic radiosurgery may be a safe and effective alternative to surgery in selected patients.

  View details for DOI 10.1016/j.nec.2019.12.003

  View details for PubMedID 32147014

• Arterial-spin labeling MRI identifies residual cerebral arteriovenous malformation following stereotactic radiosurgery treatment JOURNAL OF NEURORADIOLOGY Heit, J. J., Thakur, N. H., Iv, M., Fischbein, N. J., Wintermark, M., Dodd, R. L., Steinberg, G. K., Chang, S. D., Kapadia, K. B., Zaharchuk, G. 2020; 47 (1): 13–19

  View details for DOI 10.1016/j.neurad.2018.12.004

  View details for Web of Science ID 000515216000004

• A Phase I/II Trial of 5-Fraction Stereotactic Radiosurgery with 5-mm Margins with Concurrent Temozolomide in Newly Diagnosed Glioblastoma: Primary Outcomes. Neuro-oncology Azoulay, M., Chang, S. D., Gibbs, I. C., Hancock, S. L., Pollom, E. L., Harsh, G. R., Adler, J. R., Harrahar, C., Li, G., Hayden Gephart, M., Nagpal, S., Thomas, R. P., Recht, L. D., Jacobs, L. R., Modlin, L. A., Wynne, J., Seiger, K., Fujimoto, D., Usoz, M., von Eyben, R., Choi, C. Y., Soltys, S. G. 2020

  Abstract

  We sought to determine the maximum tolerated dose (MTD) of 5-fraction stereotactic radiosurgery (SRS) with 5-mm margins delivered with concurrent temozolomide in newly diagnosed glioblastoma.We enrolled adult patients with newly diagnosed glioblastoma to 5 days of SRS in a 3+3 design on 4 escalating dose levels: 25, 30, 35, and 40 Gy. Dose limiting toxicity (DLT) was defined as CTCAE Grade 3-5 acute or late CNS toxicity, including adverse radiation effect (ARE), the imaging correlate of radiation necrosis.From 2010 to 2015, 30 patients were enrolled. The median age was 66 years (range 51-86 years). The median target volume was 60 cm3 (range 14.7-137.3 cm3). DLT occurred in 2 patients: one for post-treatment cerebral edema and progressive disease at 3 weeks (Grade 4, Dose 40 Gy); another patient died 1.5 weeks following SRS from post-operative complications (Grade 5, Dose 40 Gy). Late grade 1-2 ARE occurred in 8 patients at a median of 7.6 months (range 3.2-12.6 months). No grade 3-5 ARE occurred. With a median follow-up of 13.8 months (range 1.7-64.4 months), the median survival times were: PFS 8.2 months (95%CI 4.6-10.5), OS 14.8 months (95%CI 10.9-19.9), MGMT hypermethylated 19.9 months (95%CI 10.5-33.5) vs. 11.3 months (95%CI 8.9-17.6) for no/unknown hypermethylation (p=0.03), and 27.2 months (95%CI 11.2-48.3) if late ARE occurred vs. 11.7 months (95%CI 8.9-17.6) for no ARE (p=0.08).The per-protocol MTD of 5-fraction SRS with 5-mm margins with concurrent temozolomide was 40 Gy in 5 fractions. ARE was limited to grade 1-2 and did not statistically impact survival.

  View details for DOI 10.1093/neuonc/noaa019

  View details for PubMedID 32002547

• Evaluating Surgical Resection Extent and Adjuvant Therapy in the Management of Gliosarcoma. Frontiers in oncology Jin, M. C., Liu, E. K., Shi, S., Gibbs, I. C., Thomas, R., Recht, L., Soltys, S. G., Pollom, E. L., Chang, S. D., Hayden Gephart, M., Nagpal, S., Li, G. 2020; 10: 337

  Abstract

  Introduction: Gliosarcomas are clinically aggressive tumors, histologically distinct from glioblastoma. Data regarding the impact of extent of resection and post-operative adjuvant therapy on gliosarcoma outcomes are limited. Methods: Patients with histologically confirmed gliosarcoma diagnosed between 1999 and 2019 were identified. Clinical, molecular, and radiographic data were assembled based on historical records. Comparisons of categorical variables used Pearson's Chi-square and Fisher's exact test while continuous values were compared using the Wilcoxon signed-rank test. Survival comparisons were assessed using Kaplan-Meier statistics and Cox regressions. Results: Seventy-one gliosarcoma patients were identified. Secondary gliosarcoma was not associated with worse survival when compared to recurrent primary gliosarcoma (median survival 9.8 [3.8 to 21.0] months vs. 7.6 [1.0 to 35.7], p = 0.7493). On multivariable analysis, receipt of temozolomide (HR = 0.02, 95% CI 0.001-0.21) and achievement of gross total resection (GTR; HR = 0.13, 95% CI 0.02-0.77) were independently prognostic for improved progression-free survival (PFS) while only receipt of temozolomide was independently associated with extended overall survival (OS) (HR = 0.03, 95% CI 0.001-0.89). In patients receiving surgical resection followed by radiotherapy and concomitant temozolomide, achievement of GTR was significantly associated with improved PFS (median 32.97 [7.1-79.6] months vs. 5.45 [1.8-26.3], p = 0.0092) and OS (median 56.73 months [7.8-104.5] vs. 14.83 [3.8 to 29.1], p = 0.0252). Conclusion: Multimodal therapy is associated with improved survival in gliosarcoma. Even in patients receiving aggressive post-operative multimodal management, total surgical removal of macroscopic disease remains important for optimal outcomes.

  View details for DOI 10.3389/fonc.2020.00337

  View details for PubMedID 32219069

  View details for PubMedCentralID PMC7078164

• Intracranial Tumor Control Following Immune-Related Adverse Events and Discontinuation of Immunotherapy for Melanoma. World neurosurgery Zhang, M., Rodrigues, A. J., Bhambhvani, H. P., Fatemi, P., Pollom, E. L., Gibbs, I. C., Thomas, R. P., Soltys, S. G., Hancock, S. L., Chang, S. D., Reddy, S. A., Gephart, M. H., Li, G. 2020

  Abstract

  Immunotherapy for melanoma patients with brain metastasis has significantly improved outcomes; however, they have also been characterized by potentially dangerous immune-related adverse events (IRAEs). Several reports suggest these reactions can precede improved treatment responses. We sought to identify if such association exists for intracranial disease control.We conducted a retrospective chart review of melanoma patients who underwent immunotherapy treatment following diagnosis of brain metastasis. The study cohort was then stratified into two groups based on their history of developing an IRAE that prompted discontinuation of that regimen. The primary outcome variable included intracranial progression-free survival (PFS). Kaplan-Meier and Cox proportional hazard analysis were used to evaluate survival and predictors of outcomes.Fifty-two patients met inclusion criteria, seventeen of whom experienced severe IRAEs that led to discontinuation of immunotherapy. Median intracranial PFS was 19.9 vs 10.5 months (p = 0.053) in patients who did and did not experience severe IRAEs prompting discontinuation, respectively. No additional outcome benefits were identified for systemic PFS or overall survival, mean (33.1 months and 27.6 months, respectively). Multivariable analysis identified BRAF mutation status as a negative prognosticator of brain progression (p = 0.013, HR = 3.90). Initial treatment with BRAF inhibitor was also a negative predictor of all-cause mortality (p = 0.015, HR = 10.73) CONCLUSION: Immune related adverse events may signify an underlying immunogenic response that has intracranial disease control benefits. Despite their associated side effects, immunotherapies continue to demonstrate promising outcomes as a first-line agent for melanoma with brain metastasis.

  View details for DOI 10.1016/j.wneu.2020.08.124

  View details for PubMedID 32853767

• Stereotactic Radiosurgery for Resected Brain Metastases - Does the Surgical Corridor Need to be Targeted? Practical radiation oncology Shi, S., Sandhu, N., Jin, M., Wang, E., Liu, E., Jaoude, J. A., Schofield, K., Zhang, C., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G., Gephart, M. H., Pollom, E. L., Soltys, S. G. 2020

  Abstract

  Although consensus guidelines for post-resection stereotactic radiosurgery (SRS) for brain metastases recommend the surgical corridor leading to the resection cavity be included in the SRS plan, no study has reported patterns of tumor recurrence based on inclusion or exclusion of the corridor as a target. We reviewed tumor control and toxicity outcomes of post-resection SRS for deep brain metastases based on whether or not the surgical corridor was targeted.We retrospectively reviewed patients who had resected brain metastases treated with SRS between 2007 and 2018 and included only 'deep' tumors (defined as located ≥1.0 cm from the pial surface prior to resection).In 66 deep brain metastases in 64 patients, the surgical corridor was targeted in 43 (65%). There were no statistical differences in the cumulative incidences of progression at 12-months for targeting vs. not targeting the corridor, respectively, for: overall local failure 2% (95% Confidence Interval [CI],0-11%) vs. 9% (95% CI,1-25%; p=0.25), corridor failure 0% (95% CI,0-0%) vs. 9% (95% CI,1-25%; p=0.06), cavity failure 2% (95% CI,0-11%) vs. 0% (95% CI,0-0%; p=0.91), adverse radiation effect 5% (95% CI,1-15%) vs. 13% (95% CI,3-30%; p=0.22). Leptomeningeal disease (7% (95% CI,2-18%) vs. 26% (95% CI,10-45%; p=0.03)) was higher in those without the corridor targeted.Omitting the surgical corridor in post-operative SRS for resected brain metastases was not associated with statistically significant differences in corridor or cavity recurrence or adverse radiation effect. As seen in recent prospective trials of post-resection SRS, the dominant pattern of progression is within the resection cavity; omission of the corridor would yield a smaller SRS volume that could allow for dose escalation to potentially improve local cavity control.

  View details for DOI 10.1016/j.prro.2020.04.009

  View details for PubMedID 32428766

• Predictors of visual functional outcome following treatment for cavernous sinus meningioma. Journal of neurosurgery Fatima, N., Ding, V. Y., Han, S. S., Chang, S. D., Meola, A. 2020: 1–12

  Abstract

  Cavernous sinus meningioma (CSM) can affect visual function and require expeditious treatment to prevent permanent visual loss. Authors of this retrospective study sought to determine the factors associated with visual functional outcomes in CSM patients treated with surgery, stereotactic radiosurgery (SRS), or stereotactic radiation therapy (SRT), alone or in combination.Consecutive patients with CSM who had presented at an academic tertiary care hospital from 2000 to 2018 were identified through retrospective chart review. Visual function-visual eye deficit (VED), optic disc (OD) appearance, intraocular pressure (IOP), and extraocular movement (EOM)-was assessed before and after treatment for CSM. VED with visual acuity (VA) ≤ 20/200 and visual field defect ≥ -11 dB, pale OD appearance in the ipsilateral or contralateral eye, increased ipsilateral IOP, and/or EOM restriction were defined as a poor visual functional outcome. Multivariable logistic regression was used to evaluate the associations between pretreatment visual functional assessment and posttreatment visual outcomes.The study cohort included 44 patients (73% female; median age 55 years), with a median clinical follow-up of 14 months. Ipsilateral VED improved, remained stable, or worsened, respectively, in 0%, 33.4%, and 66.6% of the patients after subtotal resection (STR) alone; in 52.6%, 31.6%, and 15.8% after STR plus radiation treatment; in 28.5%, 43.0%, and 28.5% after gross-total resection (GTR) alone; and in 56.3%, 43.7%, and 0% after radiation treatment (SRS or SRT) alone. Contralateral VED remained intact in all the patients after STR alone and those with radiation treatment (SRS or SRT) alone; however, it improved, remained stable, or worsened in 10.5%, 84.2%, and 5.3% after STR plus radiation treatment and in 43.0%, 28.5%, and 28.5% after GTR alone. EOM remained intact, fully recovered, remained stable, and worsened, respectively, in 0%, 50%, 50%, and 0% of the patients after STR alone; in 36.8%, 47.4%, 15.8%, and 0% of the patients after STR with radiation treatment; in 57.1%, 0%, 28.6%, and 14.3% of the patients after GTR alone; and in 56.2%, 37.5%, 6.3%, and 0% of the patients after radiation treatment (SRS or SRT) alone.In multivariable analyses adjusted for age, tumor volume, and treatment modality, initial ipsilateral poor VED (OR 10.1, 95% CI 1.05-97.2, p = 0.04) and initial ipsilateral pale OD appearance (OR 21.1, 95% CI 1.6-270.5, p = 0.02) were associated with poor ipsilateral VED posttreatment. Similarly, an initial pale OD appearance (OR 15.7, 95% CI 1.3-199.0, p = 0.03), initial poor VED (OR 21.7, 95% CI 1.2-398.6, p = 0.03), and a higher IOP in the ipsilateral eye (OR 55.3, 95% CI 1.7-173.9, p = 0.02) were associated with an ipsilateral pale OD appearance posttreatment. Furthermore, a higher initial ipsilateral IOP (OR 35.9, 95% CI 3.3-400.5, p = 0.004) was indicative of a higher IOP in the ipsilateral eye posttreatment. Finally, initial restricted EOM was indicative of restricted EOM posttreatment (OR 20.6, 95% CI 18.7-77.0, p = 0.02).Pretreatment visual functional assessment predicts visual outcomes in patients with CSM and can be used to identify patients at greater risk for vision loss.

  View details for DOI 10.3171/2020.2.JNS193009

  View details for PubMedID 32413851

• Local control and toxicity outcomes of stereotactic radiosurgery for spinal metastases of gastrointestinal origin. Journal of neurosurgery. Spine Sandhu, N., Benson, K. R., Kumar, K. A., Eyben, R. V., Chang, D. T., Gibbs, I. C., Hancock, S. L., Meola, A., Chang, S. D., Li, G., Hayden-Gephart, M., Soltys, S. G., Pollom, E. L. 2020: 1–8

  Abstract

  Colorectal cancer (CRC) and other gastrointestinal (GI) cancers are believed to have greater radioresistance than other histologies. The authors report local control and toxicity outcomes of stereotactic radiosurgery (SRS) to spinal metastases from GI primary cancers.A retrospective single-center review was conducted of patients with spinal metastases from GI primary cancers treated with SRS from 2004 to 2017. Patient demographics and lesion characteristics were summarized using medians, interquartile ranges (IQRs), and proportions. Local failure (LF) was estimated using the cumulative incidence function adjusted for the competing risk of death and compared using Gray's test for equality. Multivariable analyses were conducted using Cox proportional hazard models, adjusting for death as a competing risk, on a per-lesion basis. Patients were stratified in the Cox model to account for repeated measures for clustered outcomes. Median survival was calculated using the Kaplan-Meier method.A total of 74 patients with 114 spine lesions were included in our analysis. The median age of the cohort was 62 years (IQR 53-70 years). Histologies included CRC (46%), hepatocellular carcinoma (19%), neuroendocrine carcinoma (13%), pancreatic carcinoma (12%), and other (10%). The 1- and 2-year cumulative incidence rates of LF were 24% (95% confidence interval [CI] 16%-33%) and 32% (95% CI 23%-42%), respectively. Univariable analysis revealed that older age (p = 0.015), right-sided primary CRCs (p = 0.038), and single fraction equivalent dose (SFED; α/β = 10) < 20 Gy (p = 0.004) were associated with higher rates of LF. The 1-year cumulative incidence rates of LF for SFED < 20 Gy10 versus SFED ≥ 20 Gy10 were 35% and 7%, respectively. After controlling for gross tumor volume and prior radiation therapy to the lesion, SFED < 20 Gy10 remained independently associated with worse LF (hazard ratio 2.92, 95% CI 1.24-6.89, p = 0.014). Toxicities were minimal, with pain flare observed in 6 patients (8%) and 15 vertebral compression fractures (13%).Spinal metastases from GI primary cancers have high rates of LF with SRS at a lower dose. This study found that SRS dose is a significant predictor of failure and that prescribed SFED ≥ 20 Gy10 (biological equivalent dose ≥ 60 Gy10) is associated with superior local control.

  View details for DOI 10.3171/2020.1.SPINE191260

  View details for PubMedID 32114530

• Long-Term Update of Stereotactic Radiosurgery for Benign Spinal Tumors NEUROSURGERY Chin, A. L., Fujimoto, D., Kumar, K. A., Tupper, L., Mansour, S., Chang, S. D., Adler, J. R., Gibbs, I. C., Hancock, S. L., Dodd, R., Li, G., Gephart, M., Ratliff, J. K., Tse, V., Usoz, M., Sachdev, S., Soltys, S. G. 2019; 85 (5): 708–16

  View details for DOI 10.1093/neuros/nyy442

  View details for Web of Science ID 000493569500063

• Long-Term Hearing Outcomes Following Stereotactic Radiosurgery in Vestibular Schwannoma Patients-A Retrospective Cohort Study Santa Maria, P. L., Shi, Y., Gurgel, R. K., Corrales, C., Soltys, S. G., Santa Maria, C., Murray, K., Chang, S. D., Blevins, N. H., Gibbs, I. C., Jackler, R. K. OXFORD UNIV PRESS INC. 2019: 550–59

  View details for DOI 10.1093/neuros/nyy407

  View details for Web of Science ID 000491255600014

• Stereotactic Radiosurgery for Small Cell Lung Cancer Brain Metastases Bagshaw, H. P., Taggarsi, R. S., Moding, E. J., Fawaz, Z. S., Von Eyben, R., Pollom, E., Chang, S. D., Gibbs, I. C., Hancock, S. L., Soltys, S. G. ELSEVIER SCIENCE INC. 2019: E70–E71

  View details for DOI 10.1016/j.ijrobp.2019.06.2323

  View details for Web of Science ID 000485671500158

• Spinal Cord Tolerance Guided by Stereotactic Radiosurgical Treatment of Intramedullary Arteriovenous Malformations Obeid, J. P., Muftuoglu, Y., Chang, S. D., Soltys, S. G. ELSEVIER SCIENCE INC. 2019: E124

  View details for DOI 10.1016/j.ijrobp.2019.06.2245

  View details for Web of Science ID 000485671500280

• Vertebral Compression Fracture Rates after Stereotactic Radiosurgery for Spinal Metastases Usoz, M., Dhillon, J., Kumar, K. A., Von Eyben, R., White, E. C., Ho, C. K., Azoulay, M., Fujimoto, D. K., Gibbs, I. C., Chang, S. D., Hancock, S. L., Pollom, E., Soltys, S. G. ELSEVIER SCIENCE INC. 2019: E126–E127

  View details for DOI 10.1016/j.ijrobp.2019.06.2250

  View details for Web of Science ID 000485671500285

• Factors Associated with Treatment Failure and Radiation Necrosis Following Cavity Radiosurgery for Resected Brain Metastases Wang, E. H., Shi, S., Sandhu, N., Liu, E., Jin, M., Schofield, K., Zhang, C., Jaoude, J., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G., Hayden, M., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2019: E92

  View details for DOI 10.1016/j.ijrobp.2019.06.2271

  View details for Web of Science ID 000485671500206

• Stereotactic Radiosurgery for Resected Brain Metastases: Single-Institutional Experience of over 500 Cavities Shi, S., Sandhu, N., Wang, E. H., Liu, E., Jaoude, J., Jin, M., Schofield, K., Zhang, C., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G., Hayden, M., Soltys, S. G., Pollom, E. ELSEVIER SCIENCE INC. 2019: E90

  View details for DOI 10.1016/j.ijrobp.2019.06.2266

  View details for Web of Science ID 000485671500201

• Multimodal management of arteriovenous malformations of the basal ganglia and thalamus: factors affecting obliteration and outcome JOURNAL OF NEUROSURGERY Madhugiri, V. S., Teo, M. C., Westbroek, E. M., Chang, S. D., Marks, M. P., Do, H. M., Levy, R. P., Steinberg, G. K. 2019; 131 (2): 410–19

  View details for DOI 10.3171/2018.2.JNS172511

  View details for Web of Science ID 000478642100011

• Ultrasmall theranostic gadolinium-based nanoparticles improve high-grade rat glioma survival. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Dufort, S., Appelboom, G., Verry, C., Barbier, E. L., Lux, F., Brauer-Krisch, E., Sancey, L., Chang, S. D., Zhang, M., Roux, S., Tillement, O., Le Duc, G. 2019

  Abstract

  We formulated an ultra-small, gadolinium-based nanoparticle (AGuIX) with theranostic properties to simultaneously enhance MRI tumor delineation and radiosensitization in a glioma model. The 9L glioma cells were orthotopically implanted in 10-week-old Fischer rats. The intra-tumoral accumulation of AGuIX was quantified using MRI T1-maps. Rats randomized to intervention cohorts were subsequently treated with daily temozolomide for five consecutive days before radiotherapy treatment. Collectively, a series of 32 rats were divided into untreated (n = 7), temozolomide-only (n = 7), temozolomide and MRT (n = 9), AGuIX and MRT (n = 7), and triple therapy (temozolomide, AGuIX NPs, and MRT; n = 9) cohorts. AGuIX nanoparticles achieved a maximum intra-tumoral concentration (expressed as concentration of Gd3+) at 1 h after intravenous injection, reaching a mean of 227.9 ± 60 muM. This was compared to concentrations of 10.5 ± 9.2 muM and 62.9 ± 24.7 muM in the contralateral hemisphere and cheek, respectively. There was a slower washout in the intra-tumor region, with sustained tumor-to-contralateral ratio of AGuIX, up to 14-fold, for each time point. The combination of AGuIX or temozolomide with MRT improved the median survival time (40 days) compared to the MeST of control rats (25 days) (p < 0.002). There was a trend towards further increased survival when the three treatments were combined (MeST of 46 days). This study demonstrated the selective accumulation of AGuIX in high grade glioma, as well as the potential survival benefits when combined with chemoradiation.

  View details for DOI 10.1016/j.jocn.2019.05.065

  View details for PubMedID 31281087

• Commentary: Peritumoral Edema/Tumor Volume Ratio: A Strong Survival Predictor for Posterior Fossa Metastases NEUROSURGERY Chow, K. H., Meola, A., Chang, S. D. 2019; 85 (1): E18–E19

  View details for DOI 10.1093/neuros/nyy281

  View details for Web of Science ID 000484356700006

• Stereotactic radiosurgery in large intracranial meningiomas: a systematic review. World neurosurgery Fatima, N., Meola, A., Pollom, E., Chaudhary, N., Soltys, S., Chang, S. 2019

  Abstract

  Gross total resection (GTR) of large intracranial meningiomas (LIMs) can be challenging and cause significant morbidity and mortality. The aim of this systematic review is to determine the clinical effectiveness and safety of Stereotactic Radiosurgery (SRS) either as primary or adjuvant therapy for LIMs, with tumor ≥2.5 cm in maximum dimension (tumor volume ≥8.1 cm3). A total of 452 tumors in 496 patients [350 females (69.3%) and 146 males (30.6%)] with median age 60 years (48 to 65 years) were included. The median tumor volume at the time of diagnosis was 16.7 cm3 (10 to 53.3cm3). The tumors were typically located in the skull-base (77.2%), while only 14.6% were in the supratentorial space. The median follow-up after SRS was 54 months (18-90 months). 87.8% of patients were treated with single session gamma knife radiosurgery (SS GKS), while the remaining 12.1% patients received non-single session (non-SS) GKS. Of 452 LIMs assessed for clinical response, 45.1% showed improvement, and 15.7% deteriorated after SRS. Radiographic tumor control at last follow-up (2-7.5 years) ranged from 84% to 100%. Overall, radiation-induced toxicity occurred in 23% of patients; with the most common adverse effect being cranial nerve neuropathy (5.5%) and peritumoral edema (PTE) (5.3%). Sub-group analysis revealed that there is 2-fold higher likelihood of improvement in clinical symptoms in patients with non-SS GKS than SS GKS [OR: 2.47; 95% (1.38-4.44); p=0.002].SRS is safe and effective in the treatment of LIMs as primary or adjuvant treatment. Further prospective studies are required to validate our results.

  View details for DOI 10.1016/j.wneu.2019.06.064

  View details for PubMedID 31226450

• Adverse Radiation Effect and Disease Control in Patients Undergoing Stereotactic Radiosurgery and Immune Checkpoint Inhibitor Therapy for Brain Metastases WORLD NEUROSURGERY Koenig, J. L., Shi, S., Sborov, K., Gensheimer, M. F., Le, G., Nagpal, S., Chang, S. D., Gibbs, I. C., Soltys, S. G., Pollom, E. L. 2019; 126: E1399–E1411

  View details for DOI 10.1016/j.wneu.2019.03.110

  View details for Web of Science ID 000469222400177

• Efficacy and toxicity of particle radiotherapy in WHO grade II and grade III meningiomas: a systematic review. Neurosurgical focus Wu, A., Jin, M. C., Meola, A., Wong, H., Chang, S. D. 2019; 46 (6): E12

  Abstract

  OBJECTIVEAdjuvant radiotherapy has become a common addition to the management of high-grade meningiomas, as immediate treatment with radiation following resection has been associated with significantly improved outcomes. Recent investigations into particle therapy have expanded into the management of high-risk meningiomas. Here, the authors systematically review studies on the efficacy and utility of particle-based radiotherapy in the management of high-grade meningioma.METHODSA literature search was developed by first defining the population, intervention, comparison, outcomes, and study design (PICOS). A search strategy was designed for each of three electronic databases: PubMed, Embase, and Scopus. Data extraction was conducted in accordance with the PRISMA guidelines. Outcomes of interest included local disease control, overall survival, and toxicity, which were compared with historical data on photon-based therapies.RESULTSEleven retrospective studies including 240 patients with atypical (WHO grade II) and anaplastic (WHO grade III) meningioma undergoing particle radiation therapy were identified. Five of the 11 studies included in this systematic review focused specifically on WHO grade II and III meningiomas; the others also included WHO grade I meningioma. Across all of the studies, the median follow-up ranged from 6 to 145 months. Local control rates for high-grade meningiomas ranged from 46.7% to 86% by the last follow-up or at 5 years. Overall survival rates ranged from 0% to 100% with better prognoses for atypical than for malignant meningiomas. Radiation necrosis was the most common adverse effect of treatment, occurring in 3.9% of specified cases.CONCLUSIONSDespite the lack of randomized prospective trials, this review of existing retrospective studies suggests that particle therapy, whether an adjuvant or a stand-alone treatment, confers survival benefit with a relatively low risk for severe treatment-derived toxicity compared to standard photon-based therapy. However, additional controlled studies are needed.

  View details for DOI 10.3171/2019.3.FOCUS1967

  View details for PubMedID 31153145

• Magnetic Particle Imaging in Neurosurgery WORLD NEUROSURGERY Meola, A., Rao, J., Chaudhary, N., Song, G., Zheng, X., Chang, S. D. 2019; 125: 261–70

  View details for DOI 10.1016/j.wneu.2019.01.180

  View details for Web of Science ID 000466491700202

• Adverse Radiation Effect and Disease Control in Patients Undergoing Stereotactic Radiosurgery and Immune Checkpoint Inhibitor Therapy for Brain Metastases. World neurosurgery Koenig, J. L., Shi, S., Sborov, K., Gensheimer, M. F., Li, G., Nagpal, S., Chang, S. D., Gibbs, I. C., Soltys, S. G., Pollom, E. L. 2019

  Abstract

  BACKGROUND: Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are increasingly used together to manage brain metastases (BMs). We assessed adverse radiation effect, disease control, and overall survival in patients with BMs who received SRS with anti-CTLA-4 and/or anti-PD-1/PD-L1 therapies.METHODS: We retrospectively reviewed the records of patients with intact or resected BMs treated with SRS and ICIs within 5 months of SRS between 2010 and 2018. Patients were defined as receiving 'concurrent' SRS and ICI if a dose of ICI was given within 4 weeks of SRS. Local failure (LF), distant intracranial failure (DIF), extracranial failure (EF), and adverse radiation effect (ARE) were assessed using cumulative incidence rates and competing risk regressions with death as a competing risk. Overall survival was assessed using the Kaplan-Meier method and Cox proportional hazards models.RESULTS: A total of 97 patients with 580 BMs were included in our analysis. Competing risk analyses demonstrated that concurrent SRS-ICI therapy is associated with higher rates of ARE (6.4% vs 2.0% at 1 year; multivariable HR 4.47; 95% CI, 1.57-12.73; p=0.005), lower rates of EF (69.7% vs 80.8% at 1 year; multivariable HR 0.60; 95% CI, 0.42-0.87; p=0.007), and better overall survival (48.6% vs 25.4% at 1 year; multivariable HR 0.57; 95% CI, 0.33-0.99; p=0.044) as compared to non-concurrent therapy. SRS-ICI timing was not associated with LF or DIF.CONCLUSIONS: Concurrent SRS-ICI therapy has a tolerable adverse event profile and may improve extracranial disease control and overall survival, supporting concurrent use in the management of BMs.

  View details for PubMedID 30902777

• "Magnetic Particle Imaging (MPI) in Neurosurgery". World neurosurgery Meola, A., Rao, J., Chaudhary, N., Song, G., Zheng, X., Chang, S. D. 2019

  Abstract

  Magnetic particle imaging (MPI) is a novel radiation-free tomographic imaging method that provides a background-free, signal attenuation-free, direct quantification of the spatial distribution of superparamagnetic iron-oxide nanoparticles (SPIONs) with high temporal resolution (milliseconds), high spatial resolution (< 1 mm), and extreme sensitivity (mumol). The technique is based on non-linear magnetization of the SPIONs when exposed to an oscillating magnetic field. MPI was first described in 2001. Since then, the technique has been applied to experimental imaging of diseases affecting different organs in the human body. The aim of this paper is to review the potential applications of MPI in the field of neurosurgery. MPI has been used for the detection the loco-regional invasion of brain tumors, tracking and monitoring the viability of neural stem cells implanted for neuro-regenerative purposes, diagnosis of cerebral ischemia, and diagnosis and morpho-functional assessment of brain aneurysms. Currently, MPI is at a pre-clinical stage. In the future, human-sized MPI scanners, along with the optimal toxicity profile of SPIONs will allow diagnostic applications in neurosurgical diseases.

  View details for PubMedID 30738942

• In Reply: Commentary: Peritumoral Edema to Tumor Volume Ratio: A Strong Survival Predictor for Posterior Fossa Metastases. Neurosurgery Meola, A., Chow, K. K., Chang, S. D. 2019

  View details for PubMedID 30629229

• Stereotactic Radiosurgery for Pediatric and Adult Intracranial and Spinal Ependymomas. Stereotactic and functional neurosurgery Shi, S., Jin, M. C., Koenig, J., Gibbs, I. C., Soltys, S. G., Chang, S. D., Li, G., Hayden Gephart, M., Hiniker, S. M., Pollom, E. L. 2019: 1–6

  Abstract

  We report efficacy and toxicity outcomes with stereotactic radiosurgery (SRS) for intracranial and spinal ependymoma.We analyzed adult and pediatric patients with newly diagnosed or recurrent intracranial or spinal ependymoma lesions treated with SRS at our institution. Following SRS, local failure (LF) was defined as failure within or adjacent to the SRS target volume, while distant failure (DF) was defined as failure outside of the SRS target volume. Time to LF and DF was analyzed using competing risk analysis with death as a competing risk.Overall survival (OS) was calculated from the date of first SRS to the date of death or censored at the date of last follow-up using the Kaplan-Meier method.Twenty-one patients underwent SRS to 40 intracranial (n = 30) or spinal (n = 10) ependymoma lesions between 2007 and 2018, most commonly with 18 or 20 Gy in 1 fraction. Median follow-up for all patients after first SRS treatment was 54 months (range 2-157). The 1-year, 2-year, and 5-year rates of survival among patients with initial intracranial ependymoma were 86, 74, and 52%, respectively. The 2-year cumulative incidences of LF and DF after SRS among intracranial ependymoma patients were 25% (95% CI 11-43) and 42% (95% CI 22-60), respectively. No spinal ependymoma patient experienced LF, DF, or death within 2 years of SRS. Three patients had adverse radiation effects.SRS is a viable treatment option for intracranial and spinal ependymoma with excellent local control and acceptable toxicity.

  View details for DOI 10.1159/000502653

  View details for PubMedID 31590165

• Milestones in stereotactic radiosurgery for the central nervous system. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Mitrasinovic, S., Zhang, M., Appelboom, G., Sussman, E., Moore, J. M., Hancock, S. L., Adler, J. R., Kondziolka, D., Steinberg, G. K., Chang, S. D. 2019; 59: 12–19

  Abstract

  INTRODUCTION: Since Lars Leksell developed the first stereotactic radiosurgery (SRS) device in 1951, there has been growth in the technologies available and clinical indications for SRS. This expansion has been reflected in the medical literature, which is built upon key articles and institutions that have significantly impacted SRS applications. Our aim was to identify these prominent works and provide an educational tool for training and further inquiry.METHOD: A list of search phrases relating to central nervous system applications of stereotactic radiosurgery was compiled. A topic search was performed using PubMed and Scopus databases. The journal, year of publication, authors, treatment technology, clinical subject, study design and level of evidence for each article were documented. Influence was proposed by citation count and rate.RESULTS: Our search identified a total of 10,211 articles with the top 10 publications overall on the study of SRS spanning 443-1313 total citations. Four articles reported on randomized controlled trials, all of which evaluated intracranial metastases. The most prominent subtopics included SRS for arteriovenous malformation, glioblastoma, and acoustic neuroma. Greatest representation by treatment modality included Gamma Knife, LINAC, and TomoTherapy.CONCLUSIONS: This systematic reporting of the influential literature on SRS for intracranial and spinal pathologies underscores the technology's rapid and wide reaching clinical applications. Moreover the findings provide an academic guide to future health practitioners and engineers in their study of SRS for neurosurgery.

  View details for PubMedID 30595165

• Arterial-Spin Labeling MRI Identifies Residual Cerebral Arteriovenous Malformation Following Stereotactic Radiosurgery Treatment. Journal of neuroradiology. Journal de neuroradiologie Heit, J. J., Thakur, N. H., Iv, M., Fischbein, N. J., Wintermark, M., Dodd, R. L., Steinberg, G. K., Chang, S. D., Kapadia, K. B., Zaharchuk, G. 2019

  Abstract

  Brain arteriovenous malformation (AVM) treatment by stereotactic radiosurgery (SRS) is effective, but AVM obliteration following SRS may take two years or longer. MRI with arterial spin labeling (ASL) may detect brain AVMs with high sensitivity. We determined whether brain MRI with ASL may accurately detect residual AVM following SRS treatment.We performed a retrospective cohort study of patients who underwent brain AVM evaluation by DSA between June 2010 and June 2015. Inclusion criteria were: (1) AVM treatment by SRS, (2) follow - up MRI with ASL at least 30 months after SRS, (3) DSA within 3 months of the follow-up MRI with ASL, and (4) no intervening AVM treatment between the MRI and DSA. Four neuroradiologists blindly and independently reviewed follow-up MRIs. Primary outcome measure was residual AVM indicated by abnormal venous ASL signal.15 patients (12 females, mean age 29 years) met inclusion criteria. There were three posterior fossa AVMs and 12 supratentorial AVMs. Spetzler-Martin (SM) Grades were: SM1 (8%), SM2 (33%), SM3 (17%), SM4 (25%), and SM5 (17%). DSA demonstrated residual AVM in 10 patients. The pooled sensitivity, specificity, positive predictive value, and negative predictive value of venous ASL signal for predicting residual AVM were 100% (95% CI: 0.9-1.0), 95% (95% CI: 0.7-1.0), 98% (95% CI: 0.9-1.0), and 100% (95% CI: 0.8-1.0), respectively. High inter-reader agreement as found by Fleiss' Kappa analysis (k = 0.92; 95% CI: 0.8-1.0; p < 0.0001).ASL is highly sensitive and specific in the detection of residual cerebral AVM following SRS treatment.

  View details for PubMedID 30658138

• Stereotactic radiosurgery for resected brain metastases: single-institutional experience of over 500 cavities. International journal of radiation oncology, biology, physics Shi, S., Sandhu, N., Jin, M. C., Wang, E., Jaoude, J. A., Schofield, K., Zhang, C., Liu, E., Gibbs, I. C., Hancock, S. L., Chang, S. D., Li, G., Hayden-Gephart, M., Adler, J. R., Soltys, S. G., Pollom, E. L. 2019

  Abstract

  Post-operative stereotactic radiosurgery (SRS) has less detrimental impact on cognition and quality of life compared to whole brain radiotherapy (WBRT) and is increasingly used for resected brain metastases (BMs). Post-operative SRS techniques are not standardized, and there is a concern for a different pattern of failure following post-operative SRS compared to WBRT. We aim to study the efficacy, toxicity, and failure pattern of post-operative SRS.We retrospectively reviewed outcomes of patients with resected BMs treated with post-operative SRS between 2007 and 2018. Overall survival (OS) and cumulative incidences of local failure (LF), overall distant intracranial failure [distant parenchymal failure (DPF), nodular leptomeningeal disease (nLMD), classical leptomeningeal disease (cLMD)], and adverse radiation effect (ARE) were reported. Neurological death was determined for patients with leptomeningeal disease (LMD).A total of 442 patients with 501 resected BMs were treated over 475 total SRS courses. Median clinical follow-up and OS after SRS were 10.1 months [interquartile range (IQR) 3.6-20.7 months] and 13.9 months [95% confidence interval (CI) 11.8-15.2 months], respectively. At 12 months, event rates were 7% (95% CI 5%-10%) for LF, 9% (95% CI 7%-12%) for ARE, 44% (95% CI 40%-49%) for overall distant intracranial failure, 37% (95% CI 33%-42%) for DPF and 13% (95% CI 10%-17%) for LMD. The overall incidence of LMD was 15.8% (53% cLMD, 46% nLMD). cLMD was associated with shorter survival than nLMD (2.0 versus 11.2 months, p<0.01) and a higher proportion of neurological death (67% versus 41%, p=0.02). A total of 15% of patients ultimately received WBRT.We report the largest clinical experience of post-operative SRS for resected BMs, showing excellent local control and low toxicity. Intracranial failure was predominantly distant, with a rising incidence of LMD.

  View details for DOI 10.1016/j.ijrobp.2019.11.022

  View details for PubMedID 31785338

• Stereotactic Radiosurgery for Large Benign Intracranial Tumors. World neurosurgery Fatima, N., Meola, A., Pollom, E., Chang, S. D., Soltys, S. 2019

  Abstract

  Historically, it is stated that large intracranial tumors, herein defined as a maximum dimension of > 3cm or tumor volume >14.2 cm3, are not candidates for Stereotactic Radiosurgery (SRS). We report outcomes of patients with large benign intracranial tumors treated with SRS.With IRB approval, we retrospectively identified 74 patients with large benign intracranial tumors (59 meningiomas, 9 vestibular schwannomas, and 6 glomus jugulare tumors) treated with robotic SRS (2007-2018). Patients received definitive SRS in 47.3% of the cases, adjuvant to surgical resection in 44.6%, and salvage following past radiation treatment in 8.1%. A median tumor volume of 16.0 cm3 (10.1-65.5 cm3) received a median dose of 24.0 Gy (14.0-30.0 Gy) in a median of 3 fractions (1-5), for a median single fraction equivalent dose (SFED) (with alpha/beta of 3) of 14.8 Gy (11.3-18.0 Gy). The Kaplan-Meier estimate of tumor local control (LC) was calculated from date of SRS.With a median clinical follow-up of 32.8 months (0.6-125.9 months) and median radiological follow-up of 28.5 months (0.6-121.4 months), LC was 96.5% (95%CI:92.4-100%) at 3-years and 91.7% (95%CI:87.6-95.7%) at 5-years. Adverse radiation effect (ARE) was seen in 10 patients (13.5%) at a median of 13.5 months (7.8-34.5 months). ARE occurred in 9% of those with prior treatment compared to 5% radiation-naïve (p=0.23). With 236.4 person-years of follow-up, no secondary malignancies were seen.Despite the historical adage, we find that SRS provides high rates of LC for these large tumors, with rates of ARE similar to historical reports of SRS for smaller benign tumors.

  View details for DOI 10.1016/j.wneu.2019.10.005

  View details for PubMedID 31605862

• Clinical efficacy of frameless stereotactic radiosurgery in the management of spinal metastases from thyroid carcinoma. Spine Hariri, O., Takayanagi, A., Lischalk, J., Desai, K., Florence, T. J., Yazdian, P., Chang, S. D., Vrionis, F., Adler, J. R., Quadri, S. A., Desai, A. 2019

  Abstract

  MINI: Study evaluates the efficacy of CyberKnife® (CK) SRS for thyroid spinal metastases (SM). Patients with SMs from thyroid carcinoma that were treated with CK SRS between 2003 and 2013were identified. CK can be safely used to treat SMs from thyroid cancer with a high rate of local control.A retrospective data review.To evaluate the efficacy of CyberKnife® SRS for thyroid SMs.Thyroid carcinoma is an infrequent cause of spinal metastasis (SM). The absolute efficacy of stereotactic radiosurgery (SRS) generally and CyberKnife® (CK) in particular remains poorly characterized for thyroid SM. The current study is the first to specifically evaluate the efficacy of CyberKnife® SRS for thyroid SMs.A retrospective review of patients at our institution between 2003 and 2013 was done. Details about tumor location, radiographic findings before and after CK SRS, tumor recurrence, prescription isodose level, total and maximum dose, number of fractions, and gross tumor volume coverage were similarly collected. For comparison with other studies, the biologically effective dose (BED) and the equivalent total dose in 2Gy fractions (EQD2) were calculated. Each patient was assessed for survival and local disease control from the time of the first CK session and survival analysis was carried out using the Kaplan-Meier method. Risk factors for local failure were assessed using multivariate logistic regression.A total of 12 patients with 32 spinal metastases from thyroid carcinoma that were treated with CK SRS were identified. Survival for 1, 2, and 3 years was 55%, 44%, and 33%, and local control was 67%, 56%, and 34% respectively. The study found that the single strongest factor associated with local control was prior radiotherapy (β-coefficient -27.72, p = 0.01). No complications occurred in the immediate or late follow-up period.This was the first study to specifically investigate the efficacy of CK for treatment of thyroid SMs. Our findings suggest that CK can be safely used to treat spinal SMs from thyroid cancer and is associated with a high rate of local control.4.

  View details for DOI 10.1097/BRS.0000000000003087

  View details for PubMedID 31261273

• Stereotactic radiosurgery versus stereotactic radiotherapy in the management of intracranial meningiomas: a systematic review and meta-analysis. Neurosurgical focus Fatima, N., Meola, A., Pollom, E. L., Soltys, S. G., Chang, S. D. 2019; 46 (6): E2

  Abstract

  OBJECTIVEStereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have been used as a primary treatment or adjuvant to resection in the management of intracranial meningiomas (ICMs). The aim of this analysis is to compare the safety and long-term efficacy of SRS and SRT in patients with primary or recurrent ICMs.METHODSA systematic review of the literature comparing SRT and SRS in the same study was conducted using PubMed, the Cochrane Library, Google Scholar, and EMBASE from January 1980 to December 2018. Randomized controlled trials, case-control studies, and cohort studies (prospective and retrospective) analyzing SRS versus SRT for the treatment of ICMs in adult patients (age > 16 years) were included. Pooled and subgroup analyses were based on the fixed-effect model.RESULTSA total of 1736 patients from 12 retrospective studies were included. The treatment modality used was: 1) SRS (n = 306), including Gamma Knife surgery (n = 36), linear accelerator (n = 261), and CyberKnife (n = 9); or 2) SRT (n = 1430), including hypofractionated SRT (hFSRT, n = 268) and full-fractionated SRT (FSRT, n = 1162). The median age of patients at the time of treatment was 59 years. The median follow-up duration after treatment was 35.5 months. The median tumor volumes at the time of treatment with SRS, hFSRT, and FSRT were 2.84 cm3, 5.45 cm3, and 12.75 cm3, respectively. The radiographic tumor control at last follow-up was significantly worse in patients who underwent SRS than SRT (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.27-0.82, p = 0.007) with 7% less volume of tumor shrinkage (OR 0.93, 95% CI 0.61-1.40, p = 0.72). Compared to SRS, the radiographic tumor control was better achieved by FSRT (OR 0.46, 95% CI 0.26-0.80, p = 0.006) than by hFSRT (OR 0.81, 95% CI 0.21-3.17, p = 0.76). Moreover, SRS leads to a significantly higher risk of clinical neurological worsening during follow-up (OR 2.07, 95% CI 1.06-4.06, p = 0.03) and of immediate symptomatic edema (OR 4.58, 95% CI 1.67-12.56, p = 0.003) with respect to SRT. SRT could produce a better progression-free survival at 4-10 years compared to SRS, but this was not statistically significant (p = 0.29).CONCLUSIONSSRS and SRT are both safe options in the management of ICMs. However, SRT carries a better radiographic tumor control rate and a lower incidence of posttreatment symptomatic worsening and symptomatic edema, with respect to SRS. However, further prospective studies are still needed to validate these results.

  View details for DOI 10.3171/2019.3.FOCUS1970

  View details for PubMedID 31153149

• Long-term follow up data on difficult to treat intracranial arteriovenous malformations treated with the CyberKnife. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Gupta, R., Moore, J. M., Amorin, A., Appelboom, G., Chaudhary, N., Iyer, A., Steinberg, G. K., Chang, S. D., Soltys, S., Gibbs, I. 2018

  Abstract

  INTRODUCTION: The CyberKnife, a frameless, robotic, stereotactic device, has been developed to radiosurgically treat arteriovenous malformations (AVMs). While most AVMs are obliterated within two-to-three years, a subset remain recalcitrant; long-term data on these difficult to treat AVMs are limited in the neurosurgical literature.MATERIALS AND METHODS: A retrospective analysis of all patients who underwent CyberKnife treatment for intracranial AVMs at a single U.S. institution between 2002 and 2012, whose AVMs had failed to obliterate within 48 months or longer from the treatment start date, were eligible for inclusion.RESULTS: Eleven patients (9 AVMs; 7 males, 2 females) were followed for an average of 85.2 months (range 56.2-119.4). The median lesion size was 3.5 cm (range: 2.8-8.0 cm) and median Spetzler-Martin grade was 3 (range: 2-5). All AVMs were treated with one radiation dose (median prescribed dose was 18.0 Gy; median Dmax: 23.7 Gy). Six (66.7%) were obliterated in a median time of 84 months (range: 52-94 months), while 3 (33.3%) remained active after a median of 90.8 months (range 69.7-119.4). Transient, post-radiosurgery adverse radiation effects occurred in 5 (55.6%) cases. One (11.1%) patient had an acute hemorrhage from the AVM after radiosurgery. Four (44.4%) patients underwent repeat radiosurgery and/or embolization. Three of these lesions eventually obliterated, while 1 did not.CONCLUSION: The median time to obliteration was 84 months. Two-thirds of AVMs which persisted for over 4 years following initial radiosurgery treatment eventually obliterated. Transient post-radiosurgery adverse effects were common; delayed hemorrhages were rare in our case series.

  View details for PubMedID 30587419

• Radiographic Rate and Clinical Impact of Pseudarthrosis in Spine Radiosurgery for Metastatic Spinal Disease. Cureus Zhang, M., Appelboom, G., Ratliff, J. K., Soltys, S. G., Adler, J. R., Park, J., Chang, S. D. 2018; 10 (11): e3631

  Abstract

  Purpose Pseudarthrosis within the spine tumor population is increased from perioperative radiation and complex stabilization for invasive and recurrent pathology. We report the radiographic and clinical rates of pseudarthrosis following multiple courses of instrumented fusion and perioperative stereotactic radiosurgery (SRS). Methods We performed a single institution review of 418 patients treated with non-isocentric SRS for spine between October 2002 and January 2013, identifying those with spinal instrumentation and greater than six months of follow-up. Surgical history, radiation planning, and radiographic outcomes were documented. Results Eleven patients whomet criteria for inclusion underwent 21 sessions of spinal SRS and 16 instrumented operations. Radiographic follow-up was 48.9 months; 3/11 (27%) were with radiographic hardware failure, and one (9%) separate case ultimately warranted externalization due to tumor recurrence. SRS was administered to treat progression of disease in 12/21 (57%) procedures, and residual lesions in 7/11 (64%) procedures. Following first and second SRS, 8/11 (73%) and 2/7 (29%) patients were with symptomatic improvement, respectively. Conclusion Risk of pseudarthrosis following SRS for patients with oncologic spinal lesions will become increasingly apparent with the optimized management of and survival from spinal pathologies. We highlight how the need for local control outpaces the risk of instrumentation failure.

  View details for PubMedID 30705790

• Toxicity of Radiosurgery for Brainstem Metastases WORLD NEUROSURGERY Patel, A., Dong, T., Ansari, S., Cohen-Gadol, A., Watson, G. A., de Moraes, F., Nakamura, M., Murovic, J., Chang, S. D., Hatiboglu, M., Chun, C., Miller, J. C., Lautenschlaeger, T. 2018; 119: E757–E764

  Abstract

  Although stereotactic radiosurgery (SRS) is an effective modality in the treatment of brainstem metastases (BSM), radiation-induced toxicity remains a critical concern. To better understand how severe or life-threatening toxicity is affected by the location of lesions treated in the brainstem, a review of all available studies reporting SRS treatment for BSM was performed.Twenty-nine retrospective studies investigating SRS for BSM were reviewed.The rates of grade 3 or greater toxicity, based on the Common Terminology Criteria for Adverse Events, varied from 0 to 9.5% (mean 3.4 ± 2.9%). Overall, the median time to toxicity after SRS was 3 months, with 90% of toxicities occurring before 9 months. A total of 1243 cases had toxicity and location data available. Toxicity rates for lesions located in the medulla were 0.8% (1/131), compared with midbrain and pons, respectively, 2.8% (8/288) and 3.0% (24/811).Current data suggest that brainstem substructure location does not predict for toxicity and lesion volume within this cohort with median tumor volumes 0.04-2.8 cc does not predict for toxicity.

  View details for PubMedID 30096494

• Cavernous malformations are rare sequelae of stereotactic radiosurgery for brain metastases. Acta neurochirurgica Seiger, K., Pendharkar, A. V., Samghabadi, P., Chang, S. D., Cho, N., Choi, C. Y., Wang, C., Gephart, M. H., Soltys, S. G. 2018

  Abstract

  The development of cavernous malformations many years following conventionally fractionated brain irradiation is well recognized and commonly reported. However, cavernous malformation induction following stereotactic radiosurgery (SRS) is largely unreported. Herein, we describe two cases of cavernous malformation formation years following SRS for brain metastases. A 20-year-old woman with breast cancer brain metastases received treatment with whole brain radiotherapy (WBRT), then salvage SRS 1.4years later for progression of a previously treated metastasis. This lesion treated with SRS had hemorrhagic enlargement 3.0years after SRS. Resection revealed a cavernous malformation. A 25-year-old woman had SRS for a brain metastasis from papillary thyroid carcinoma. Resection of a progressive, hemorrhagic lesion within the SRS field 2years later revealed both recurrent carcinoma as well as cavernous malformation. As patients with brain metastases live longer following SRS, our cases highlight that the differential diagnosis of an enlarging enhancing lesion within a previous SRS field includes not only cerebral necrosis and tumor progression but also cavernous malformation induction.

  View details for PubMedID 30328524

• Bilateral Vestibular Schwannomas in Neurofibromatosis Type 2. The New England journal of medicine Meola, A., Chang, S. D. 2018; 379 (15): 1463

  View details for PubMedID 30304657

• Long-Term Hearing Outcomes Following Stereotactic Radiosurgery in Vestibular Schwannoma Patients-A Retrospective Cohort Study. Neurosurgery Santa Maria, P. L., Shi, Y., Gurgel, R. K., Corrales, C. E., Soltys, S. G., Santa Maria, C., Murray, K., Chang, S. D., Blevins, N. H., Gibbs, I. C., Jackler, R. K. 2018

  Abstract

  BACKGROUND: An understanding of the hearing outcomes is needed for treatment counseling for patients with vestibular schwannomas (VS).OBJECTIVE: To determine long-term hearing results following stereotactic radiosurgery (SRS) for VS and identify any influential variables.METHODS: Tertiary hospital retrospective cohort.RESULTS: There were 579 tumors (576 patients) treated with SRS. Eighty-two percent (473) of tumors had ≥1 yr and 59% (344 ≥3 yr follow-up. In the 244 tumor ears, with measurable hearing before SRS who were followed ≥1 yr, 14% (31) had improved hearing, 13% (29) unchanged hearing, and 74% (158) had worsened hearing. In 175 patients with ≥3 yr follow-up and who had measurable hearing pretreatment, 6% (11 ears) improved hearing, 31% (54 ears) unchanged hearing, and 63% (110 ears) had worsened hearing. Patients with tumors with larger target volumes (P=0.040) and with neurofibromatosis type 2 (NF2; P=0.017) were associated with poorer hearing (P=0.040). Patients with word recognition scores (WRS) of 50% or poorer had tumors with a larger volume (P=0.0002), larger linear size (P=0.032), and NF2 (P=0.045). Traditionally reported hearing outcomes using the Gardner Robertson maintenance of PTA ≤50 db or WRS ≥50% were 48% at 3 yr, which overestimates hearing outcomes compared to the above reporting standards.CONCLUSION: Hearing declines over time in VS treated with SRS in a high proportion of cases. The frequency and magnitude of long-term hearing decline following SRS argues against prophylactic radiation for small tumors in hearing ears with undetermined growth behavior.

  View details for PubMedID 30247723

• Multimodal management of arteriovenous malformations of the basal ganglia and thalamus: factors affecting obliteration and outcome. Journal of neurosurgery Madhugiri, V. S., Teo, M. K., Westbroek, E. M., Chang, S. D., Marks, M. P., Do, H. M., Levy, R. P., Steinberg, G. K. 2018: 1–10

  Abstract

  OBJECTIVEArteriovenous malformations (AVMs) of the basal ganglia and thalamus are particularly difficult lesions to treat, accounting for 3%-13% of all AVMs in surgical series and 23%-44% of malformations in radiosurgery series. The goal of this study was to report the results of multimodal management of basal ganglia and thalamic AVMs and investigate the factors that influence radiographic cure and good clinical outcomes.METHODSThis study was a retrospective analysis of a prospectively maintained database of all patients treated at the authors' institution. Clinical, radiological, follow-up, and outcome data were analyzed. Univariate and multivariate analyses were conducted to explore the influence of various factors on outcome.RESULTSThe results and data analysis pertaining to 123 patients treated over 32 years are presented. In this cohort, radiographic cure was achieved in 50.9% of the patients. Seventy-five percent of patients had good clinical outcomes (stable or improved performance scores), whereas 25% worsened after treatment. Inclusion of surgery and radiosurgery independently predicted obliteration, whereas nidus diameter and volume predicted clinical outcomes. Nidus volume/diameter and inclusion of surgery predicted the optimal outcome, i.e., good clinical outcomes with lesion obliteration.CONCLUSIONSGood outcomes are possible with multimodal treatment in these complex patients. Increasing size and, by extension, higher Spetzler-Martin grade are associated with worse outcomes. Inclusion of multiple modalities of treatment as indicated could improve the chances of radiographic cure and good outcomes.

  View details for PubMedID 30117771

• Commentary: Peritumoral Edema/Tumor Volume Ratio: A Strong Survival Predictor for Posterior Fossa Metastases. Neurosurgery Chow, K. K., Meola, A., Chang, S. D. 2018

  View details for PubMedID 29982666

• Quantitative analysis of the safety and efficacy of microvascular decompression for patients with trigeminal neuralgia above and below 65 years of age. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Wallach, J., Ho, A. L., Kim, L. H., Chaudhuri, A. A., Chaudhary, N., Vaz-Guimaraes, F., Chang, S. D. 2018

  Abstract

  For medically-refractory trigeminal neuralgia (TN), microvascular decompression (MVD) is the first-line treatment, and has demonstrated the greatest efficacy and durability. However, due to potential surgical complications, a bias may exist against performing MVD in elderly patients. We sought to determine through a quantitative analysis whether MVD in the elderly is a safe and effective procedure for TN. We completed a Pubmed/SCOPUS literature search up to 12/2016 for eligible studies on MVD for TN. Only research articles with age stratification of results were included. In this quantitative analysis, we analyzed the data for the six articles identified in the literature comparing MVD for a group of patients ≥65 years with an elderly group <65 years. A total of 1483 were included. 455 patients were ≥65 years (mean 70.8 years, range 65-89 years) and 1028 patients were <65 years (mean 53.4 years, range 19-64 years). Composite mean follow-up time was 51.6 months for the elderly group, and 55.1 months for the young group. Following MVD, each group had 1 mortality (p = 0.43). There were 21 serious morbidities in the elderly group (4.62%) and 32 in the young group (3.11%) (p = 0.11). In addition, 15 patients (1.46%) in the elderly group and 24 patients (1.62%) in the young group experienced a cerebrospinal fluid leak (p = 0.23). TN recurrence rates 9.23% in the young group and 13.33% in the elderly group (p = 0.070). In conclusion, for properly-selected surgical candidates, MVD should not be ruled out on the basis of age ≥65 years.

  View details for PubMedID 29954647

• Letter: Navigation-Linked Heads-Up Display in Intracranial Surgery: Early Experience. Operative neurosurgery (Hagerstown, Md.) Meola, A., Chang, S. D. 2018; 14 (6): E71–E72

  View details for PubMedID 29590481

• CyberKnife robotic radiosurgery in the multimodal management of acromegaly patients with invasive macroadenoma: a single center's experience JOURNAL OF NEURO-ONCOLOGY Sala, E., Moore, J. M., Amorin, A., Martinez, H., Bhowmik, A. C., Lamsam, L., Chang, S., Soltys, S. G., Katznelson, L., Harsh, G. R. 2018; 138 (2): 291–98

  Abstract

  Surgery is the primary treatment for acromegaly. However, surgery may not be curative of some tumors, particularly invasive macroadenomas. Adjuvant radiation, specifically robotic stereotactic radiosurgery (rSRS), may improve the endocrine outcome. We retrospectively reviewed hormonal and radiological data of 22 acromegalic patients with invasive macroadenomas treated with rSRS at Stanford University Medical Center between 2000 and 2016. Prior to treatment, the tumor's median maximal diameter was 19 mm (2.5-50 mm). Cavernous sinus invasion occurred in 19 patients (86.3%) and compression of the optic chiasm in 2 (9.0%). At last follow up, with an average follow up of 43.2 months, all patients had a reduction in their IGF-1 levels (median IGF-1% upper limit of normal (ULN) baseline: 136% vs last follow up: 97%; p = 0.05); 9 patients (40.9%) were cured, and 4 (18.1%) others demonstrated biochemical control of acromegaly. The median time to cure was 50 months and the mean interval to cure or biochemical control was 30.3 months (± 24 months, range 6-84 months). Hypopituitarism was present in 8 patients (36.3%) and new pituitary deficits occurred in 6 patients with a median latency of 31.6 ± 14.5 months. At final radiologic follow-up, 3 tumors (13.6%) were smaller and 19 were stable in size. The mean biologically effective dose (BED) was higher in subjects cured compared to those with persistent disease, 163 Gy3 (± 47) versus 111 Gy3 (± 43), respectively (p = 0.01). No patient suffered visual deterioration. Robotic SRS is a safe and effective treatment for acromegaly: radiation-induced visual complications and hypopituitarism is rare.

  View details for PubMedID 29429125

• Gold Nanoparticles for Brain tumor imaging: a Systematic Review FRONTIERS IN NEUROLOGY Meola, A., Rao, J., Chaudhary, N., Sharma, M., Chang, S. D. 2018; 9: 328

  Abstract

  Demarcation of malignant brain tumor boundaries is critical to achieve complete resection and to improve patient survival. Contrast-enhanced brain magnetic resonance imaging (MRI) is the gold standard for diagnosis and pre-surgical planning, despite limitations of gadolinium (Gd)-based contrast agents to depict tumor margins. Recently, solid metal-based nanoparticles (NPs) have shown potential as diagnostic probes for brain tumors. Gold nanoparticles (GNPs) emerged among those, because of their unique physical and chemical properties and biocompatibility. The aim of the present study is to review the application of GNPs for in vitro and in vivo brain tumor diagnosis.We performed a PubMed search of reports exploring the application of GNPs in the diagnosis of brain tumors in biological models including cells, animals, primates, and humans. The search words were "gold" AND "NP" AND "brain tumor." Two reviewers performed eligibility assessment independently in an unblinded standardized manner. The following data were extracted from each paper: first author, year of publication, animal/cellular model, GNP geometry, GNP size, GNP coating [i.e., polyethylene glycol (PEG) and Gd], blood-brain barrier (BBB) crossing aids, imaging modalities, and therapeutic agents conjugated to the GNPs.The PubMed search provided 100 items. A total of 16 studies, published between the 2011 and 2017, were included in our review. No studies on humans were found. Thirteen studies were conducted in vivo on rodent models. The most common shape was a nanosphere (12 studies). The size of GNPs ranged between 20 and 120 nm. In eight studies, the GNPs were covered in PEG. The BBB penetration was increased by surface molecules (nine studies) or by means of external energy sources (in two studies). The most commonly used imaging modalities were MRI (four studies), surface-enhanced Raman scattering (three studies), and fluorescent microscopy (three studies). In two studies, the GNPs were conjugated with therapeutic agents.Experimental studies demonstrated that GNPs might be versatile, persistent, and safe contrast agents for multimodality imaging, thus enhancing the tumor edges pre-, intra-, and post-operatively improving microscopic precision. The diagnostic GNPs might also be used for multiple therapeutic approaches, namely as "theranostic" NPs.

  View details for PubMedID 29867737

• Brainstem Dose Constraints in Nonisometric Radiosurgical Treatment Planning of Trigeminal Neuralgia: A Single-Institution Experience WORLD NEUROSURGERY Zhang, M., Lamsam, L. A., Schoen, M. K., Mehta, S. S., Appelboom, G., Adler, J. K., Soltys, S. G., Chang, S. D. 2018; 113: E399–E407

  Abstract

  CyberKnife stereotactic radiosurgery (SRS) for trigeminal neuralgia (TGN) administers nonisometric, conformational high-dose radiation to the trigeminal nerve with risk of subsequent hypoesthesia.We performed a retrospective, single-institution review of 66 patients with TGN treated with CyberKnife SRS to compare outcomes from 2 distinct treatment periods: standard dosing (n = 38) and reduced dosing (n = 28). Standard and reduced dosing permitted a maximum brainstem dose of 45 Gy and 25 Gy, respectively, each with a prescription dose of 60 Gy. Primary and secondary outcomes were Barrow Neurologic Institute pain and numbness scores. Maximum brainstem dose, prepontine nerve length, and treatment history were recorded for their predictive contributions by logistic regression.After matching, patients in the standard dosing and reduced dosing groups were followed for a median of 25 months and 19.5 months, respectively. Mean trigeminal nerve length was 8.55 mm in the standard dosing group and 9.46 mm in the reduced dosing group. Baseline rates of poorly controlled pain were 97% and 88%, respectively, which improved to 23.4% and 8.3%, respectively (P < 0.001 for both). The baseline rates of bothersome numbness were null in both groups, and increased to 25% in the standard group (P = 0.006) and to 21% in the reduced group (P = 0.07). Regression analyses suggested that reduced brainstem exposure (P = 0.01), as well as a longer trigeminal nerve (P = 0.01), were predictive of durable pain control.These outcomes demonstrate that a lower maximum brainstem dose can provide excellent pain control without affecting facial numbness. Longer nerves may achieve better long-term outcomes and help optimize individual plans.

  View details for PubMedID 29454124

• CyberKnife Radiosurgery in the Multimodal Management of Patients with Cushing Disease WORLD NEUROSURGERY Moore, J. M., Sala, E., Amorin, A., Martinez, H., Bhowmik, A. C., Chang, S. D., Soltys, S. G., Harsh, G. R., Katznelson, L. 2018; 112: E425–E430

  Abstract

  Surgery is the primary treatment for Cushing disease. When surgery is unsuccessful in normalizing hypercortisolism, adjuvant radiation, such as stereotactic radiosurgery, may be useful to improve biochemical control.This retrospective study included a cohort of consecutive patients treated with CyberKnife (CK) radiosurgery for active Cushing disease at Stanford Hospital and Clinics.As first-line treatment, all patients underwent transsphenoidal surgery with histologic demonstration of an adrenocorticotropic hormone-producing pituitary adenoma. CK was performed as adjuvant therapy for persistent or recurrent disease. The median time between surgery and CK was 14 ± 34 months. Before CK, median maximal diameter of tumors was 9 mm (range, 7-32 mm), with cavernous sinus invasion in all patients (100%) and abutment of the optic chiasm in 1 patient (14.2%). With an average follow-up of 55.4 months, normalization of hypercortisolism was achieved in 4 patients (57.1%): 2 patients (28.5%) achieved normalization of the hypothalamic-pituitary-adrenal axis without glucocorticoid replacement, and 2 patients developed hypoadrenalism (28.5%). The median time to biochemical remission was 12.5 months. Hypopituitarism occurred in only 1 patient (14.2%), and no patients had visual complications. Time between surgery and radiotherapy of <14 months was associated with a significantly improved biochemical remission rate (P = 0.02).In a cohort of patients with Cushing disease, we demonstrate that CK is an effective treatment with rare complications.

  View details for PubMedID 29355797

• Stereotactic radiosurgery for central nervous system hemangioblastoma: systematic review and meta-analysis JOURNAL OF NEURO-ONCOLOGY Pan, J., Jabarkheel, R., Huang, Y., Ho, A., Chang, S. D. 2018; 137 (1): 11–22

  Abstract

  Hemangioblastomas are rare, benign, vascular tumors of the central nervous system (CNS), often associated with von-hippel lindau (VHL) disease. Current therapeutic options include microsurgical resection or stereotactic radiosurgery (SRS). With no randomized controlled studies and minimal data beyond single-institution reviews, the optimal management approach for patients with CNS hemangioblastomas is unclear. We completed a Pubmed/SCOPUS literature search from January 1990 to January 2017 for eligible studies on SRS for CNS hemangioblastomas. Relevant articles were identified and reviewed in accordance to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. 26 studies met eligibility criteria for qualitative synthesis, representing 596 subjects and 1535 tumors. The Gamma Knife was the most published SRS method for CNS hemangioblastomas. After critical study appraisal for intra-study bias, 14 studies were used for quantitative meta-analysis of 5-year progression free survival (PFS). The pooled 5-year PFS across all eligible studies was 88.4%. No difference was observed between spine versus intracranial studies. Individual patient data (IPD) was extracted from 14 studies, representing 322 tumors. Univariate analysis of IPD revealed that VHL patients were younger, and had smaller tumors compared to those with sporadic disease. Adverse events were associated with increasing marginal dose, independent of tumor volume. VHL status, sex, radiosurgical method, tumor location, and tumor volume were not found to be significantly associated with tumor progression. Multiple studies show excellent tumor control at 5-year follow up, however, the long-term efficacy of SRS for CNS hemangioblastomas still needs to be investigated, and the studies exploring the role of SRS for early treatment of asymptomatic lesions is wanting.

  View details for PubMedID 29204841

• Silicon Valley new focus on brain computer interface: hype or hope for new applications? F1000Research Mitrasinovic, S., Brown, A. P., Schaefer, A. T., Chang, S. D., Appelboom, G. 2018; 7: 1327

  Abstract

  In the last year there has been increasing interest and investment into developing devices to interact with the central nervous system, in particular developing a robust brain-computer interface (BCI). In this article, we review the most recent research advances and the current host of engineering and neurological challenges that must be overcome for clinical application. In particular, space limitations, isolation of targeted structures, replacement of probes following failure, delivery of nanomaterials and processing and understanding recorded data. Neural engineering has developed greatly over the past half-century, which has allowed for the development of better neural recording techniques and clinical translation of neural interfaces. Implementation of general purpose BCIs face a number of constraints arising from engineering, computational, ethical and neuroscientific factors that still have to be addressed. Electronics have become orders of magnitude smaller and computationally faster than neurons, however there is much work to be done in decoding the neural circuits. New interest and funding from the non-medical community may be a welcome catalyst for focused research and development; playing an important role in future advancements in the neuroscience community.

  View details for PubMedID 30705750

• Long-Term Update of Stereotactic Radiosurgery for Benign Spinal Tumors. Neurosurgery Chin, A. L., Fujimoto, D., Kumar, K. A., Tupper, L., Mansour, S., Chang, S. D., Adler, J. R., Gibbs, I. C., Hancock, S. L., Dodd, R., Li, G., Gephart, M. H., Ratliff, J. K., Tse, V., Usoz, M., Sachdev, S., Soltys, S. G. 2018

  Abstract

  Stereotactic radiosurgery (SRS) for benign intracranial tumors is an established standard of care. The widespread implementation of SRS for benign spinal tumors has been limited by lack of long-term data.To update our institutional experience of safety and efficacy outcomes after SRS for benign spinal tumors.We performed a retrospective cohort study of 120 patients with 149 benign spinal tumors (39 meningiomas, 26 neurofibromas, and 84 schwannomas) treated with SRS between 1999 and 2016, with follow-up magnetic resonance imaging available for review. The primary endpoint was the cumulative incidence of local failure (LF), with death as a competing risk. Secondary endpoints included tumor shrinkage, symptom response, toxicity, and secondary malignancy.Median follow-up was 49 mo (interquartile range: 25-103 mo, range: 3-216 mo), including 61 courses with >5 yr and 24 courses with >10 yr of follow-up. We observed 9 LF for a cumulative incidence of LF of 2%, 5%, and 12% at 3, 5, and 10 yr, respectively. Excluding 10 tumors that were previously irradiated or that arose within a previously irradiated field, the 3-, 5-, and 10-yr cumulative incidence rates of LF were 1%, 2%, and 8%, respectively. At last follow-up, 35% of all lesions had decreased in size. With a total of 776 patient-years of follow-up, no SRS-related secondary malignancies were observed.Comparable to SRS for benign intracranial tumors, SRS provides longer term local control of benign spinal tumors and is a standard-of-care alternative to surgical resection.

  View details for PubMedID 30445557

• Impact of CyberKnife Radiosurgery on Median Overall Survival of Various Parameters in Patients with 1-12 Brain Metastases. Cureus Murovic, J., Ding, V., Han, S. S., Adler, J. R., Chang, S. D. 2017; 9 (12): e1926

  Abstract

  Introduction This study's objective is to assessvarious patient, tumor and imaging characteristics andto compare median overall survival(OS)of 150 patients with 1-12 brain metastases post-CyberKnife radiosurgery (CKRS) (Accuray, Sunnyvale, California) alone. Methods Charts of 150 patients, from 2009-2014, treated with only CKRS for brain metastases were reviewed retrospectively for patient, tumor, and imaging characteristics. Parameters included demographics, Eastern Cooperative Oncology Group (ECOG) performance scores, number and control of extracranial disease (ECD) sites, cause of death (COD), histology, tumor volume (TV), and post-CKRS whole brain radiotherapy (WBRT). The imaging characteristics assessed were time of complete response (CR), partial response (PR), stable imaging or local failure (LF), and distal brain failure (DBF). The primary tumor Ki-67s of the breast carcinoma brain metastasis patients, who had the longest median OS of any group, were recorded when available. Results The predominant age group for the 150-patient cohort was the younger 17-65 years of age category, which was represented by 94 (62.7%). The 150-patient group had slightly more males, 79 (52.7%). The majority of 111 (74%) patients had an ECOG score of 1, 39 (26%) had 1 ECD site and uncontrolled ECD occurred in 112 (74.7%). The main COD was ECD in 106 (70.7%). The prevalent tumor histology was non-small cell lung carcinoma (88 of 150, 58.7%). The most common TV was 0-0.5 ccs (48 of 150, 32%). The majority of 125 (83.3%) patients did not undergo post-CKRS WBRT. Imaging outcomes were local control (LC) (CR, PR, or stable imaging) in 119 (79.3%), of whom 38 (25.3%) had CR, 56 (37.3%)PR and 25 (16.7%)stable imaging; LF was the outcome in 31 (20.7%) and DBF occured in 83 (55.3%). The median OS was 13 months. Patients17-65 years of age had a median OS of 13 months, while those 66-88 years, had 12 months. Females versus males had median OSof 15 versus 12 months. The most prolonged median OS of 21.5 months occurred in those with an ECOG score of 0. Patients with two ECD sites had a median OS of 14.5 months, while those with controlled ECD, 20.5 months. Patients with breast cancer brain metastases had the longest median OS of 23 months. The median OS for each of three (0-0.5 ccs, 0.6-1.5 ccs, 1.6-4.0 ccs) of four CKRS TV quartiles was 13 months and for those with 4.1-28.5 ccs, 10 months. Median OSfor patients with versus without post-CKRS WBRT was 23 versus 12 months. The longest median OS of 18.5 months for post-CKRS imaging outcomes was in patients with CR; those with LF had a median OS of 11.5 months. Of nine patients with breast carcinoma brain metastases with available Ki-67s from primary tumor resections, the Ki-67 values were ≥ 34% for four patients with CR, PR and stable imaging outcomes, and < 34% for five patients with LF. Conclusions An ECOG score of 0, ECD control, breast carcinoma brain metastasis histology. undergoing WBRT post-CKRS and CR imaging outcomes, each resulted in a longer median OS. The Ki-67 proliferation indices from primary breast carcinoma resection correlated well with the brain imaging outcomes in a small preliminary study in the present study's breast carcinoma patients with brain metastases.

  View details for PubMedID 29464135

• Phase 1/2 Trial of 5-Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma: Health-Related Quality of Life Results. International journal of radiation oncology, biology, physics Pollom, E. L., Fujimoto, D., Wynne, J., Seiger, K., Modlin, L. A., Jacobs, L. R., Azoulay, M., von Eyben, R., Tupper, L., Gibbs, I. C., Hancock, S. L., Li, G., Chang, S. D., Adler, J. R., Harsh, G. R., Harraher, C., Nagpal, S., Thomas, R. P., Recht, L. D., Choi, C. Y., Soltys, S. G. 2017; 98 (1): 123-130

  Abstract

  We report a longitudinal assessment of health-related quality of life (HRQOL) in patients with glioblastoma (GBM) treated on a prospective dose escalation trial of 5-fraction stereotactic radiosurgery (25-40 Gy in 5 fractions) with concurrent and adjuvant temozolomide.HRQOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire core-30 (QLQ-C30) general, the EORTC quality of life questionnaire-brain cancer specific module (QLQ-BN20), and the M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Questionnaires were completed at baseline and at every follow-up visit after completion of radiosurgery. Changes from baseline for 9 predefined HRQOL measures (global quality of life, physical functioning, social functioning, emotional functioning, motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty) were calculated at every time point.With a median follow-up time of 10.4 months (range, 0.4-52 months), 139 total HRQOL questionnaires were completed by the 30 patients on trial. Compliance with HRQOL assessment was 76% at 12 months. Communication deficit significantly worsened over time, with a decline of 1.7 points per month (P=.008). No significant changes over time were detected in the other 8 scales of our primary analysis, including global quality of life. Although 8 patients (27%) experienced adverse radiation effects (ARE) on this dose escalation trial, it was not associated with a statistically significant decline in any of the primary HRQOL scales. Disease progression was associated with communication deficit, with patients experiencing an average worsening of 13.9 points per month after progression compared with 0.7 points per month before progression (P=.01).On this 5-fraction dose escalation protocol for newly diagnosed GBM, overall HRQOL remained stable and appears similar to historical controls of 30 fractions of radiation therapy. Tumor recurrence was associated with worsening communication deficit, and ARE did not correlate with a decline in HRQOL.

  View details for DOI 10.1016/j.ijrobp.2017.01.242

  View details for PubMedID 28586949

• Image-guided stereotactic radiosurgery for treatment of spinal hemangioblastoma NEUROSURGICAL FOCUS Pan, J., Ho, A. L., D'Astous, M., Sussman, E. S., Thompson, P. A., Tayag, A. T., Pangilinan, L., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2017; 42 (1)

  Abstract

  OBJECTIVE Stereotactic radiosurgery (SRS) has been an attractive treatment option for hemangioblastomas, especially for lesions that are surgically inaccessible and in patients with von Hippel-Lindau (VHL) disease and multiple lesions. Although there has been a multitude of studies examining the utility of SRS in intracranial hemangioblastomas, SRS has only recently been used for spinal hemangioblastomas due to technical limitations. The purpose of this study is to provide a long-term evaluation of the effectiveness of image-guided radiosurgery in halting tumor progression and providing symptomatic relief for spinal hemangioblastomas. METHODS Between 2001 and 2011, 46 spinal hemangioblastomas in 28 patients were treated using the CyberKnife image-guided radiosurgery system at the authors' institution. Fourteen of these patients also had VHL disease. The median age at treatment was 43.5 years (range 19-85 years). The mean prescription radiation dose to the tumor periphery was 21.6 Gy (range 15-35 Gy). The median tumor volume was 0.264 cm(3) (range 0.025-70.9 cm(3)). Tumor response was evaluated on serial, contrast-enhanced CT and MR images. Clinical response was evaluated by clinical and imaging evaluation. RESULTS The mean follow-up for the cohort was 54.3 months. Radiographic follow-up was available for 19 patients with 34 tumors; 32 (94.1%) tumors were radiographically stable or displayed signs of regression. Actuarial control rates at 1, 3, and 5 years were 96.1%, 92.3%, and 92.3%, respectively. Clinical evaluation on follow-up was available for 13 patients with 16 tumors; 13 (81.2%) tumors in 10 patients had symptomatic improvement. No patient developed any complications related to radiosurgery. CONCLUSIONS Image-guided SRS is safe and effective for the primary treatment of spinal hemangioblastomas and is an attractive alternative to resection, especially for those with VHL disease.

  View details for DOI 10.3171/2016.10.FOCUS16361

  View details for Web of Science ID 000392113200012

  View details for PubMedID 28041328

• Vorinostat and Concurrent Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases: A Phase 1 Dose Escalation Trial. International journal of radiation oncology, biology, physics Choi, C. Y., Wakelee, H. A., Neal, J. W., Pinder-Schenck, M. C., Yu, H. M., Chang, S. D., Adler, J. R., Modlin, L. A., Harsh, G. R., Soltys, S. G. 2017; 99 (1): 16–21

  Abstract

  To determine the maximum tolerated dose (MTD) of vorinostat, a histone deacetylase inhibitor, given concurrently with stereotactic radiosurgery (SRS) to treat non-small cell lung cancer (NSCLC) brain metastases. Secondary objectives were to determine toxicity, local failure, distant intracranial failure, and overall survival rates.In this multicenter study, patients with 1 to 4 NSCLC brain metastases, each ≤2 cm, were enrolled in a phase 1, 3 + 3 dose escalation trial. Vorinostat dose levels were 200, 300, and 400 mg orally once daily for 14 days. Single-fraction SRS was delivered on day 3. A dose-limiting toxicity (DLT) was defined as any Common Terminology Criteria for Adverse Events version 3.0 grade 3 to 5 acute nonhematologic adverse event related to vorinostat or SRS occurring within 30 days.From 2009 to 2014, 17 patients were enrolled and 12 patients completed study treatment. Because no DLTs were observed, the MTD was established as 400 mg. Acute adverse events were reported by 10 patients (59%). Five patients discontinued vorinostat early and withdrew from the study. The most common reasons for withdrawal were dyspnea (n=2), nausea (n=1), and fatigue (n=2). With a median follow-up of 12 months (range, 1-64 months), Kaplan-Meier overall survival was 13 months. There were no local failures. One patient (8%) at the 400-mg dose level with a 2.0-cm metastasis developed histologically confirmed grade 4 radiation necrosis 2 months after SRS.The MTD of vorinostat with concurrent SRS was established as 400 mg. Although no DLTs were observed, 5 patients withdrew before completing the treatment course, a result that emphasizes the need for supportive care during vorinostat administration. There were no local failures. A larger, randomized trial may evaluate both the tolerability and potential local control benefit of vorinostat concurrent with SRS for brain metastases.

  View details for PubMedID 28816142

• Patient Outcomes and Cerebral Infarction after Ruptured Anterior Communicating Artery Aneurysm Treatment. AJNR. American journal of neuroradiology Heit, J. J., Ball, R. L., Telischak, N. A., Do, H. M., Dodd, R. L., Steinberg, G. K., Chang, S. D., Wintermark, M., Marks, M. P. 2017; 38 (11): 2119–25

  Abstract

  Anterior communicating artery aneurysm rupture and treatment is associated with high rates of dependency, which are more severe after clipping compared with coiling. To determine whether ischemic injury might account for these differences, we characterized cerebral infarction burden, infarction patterns, and patient outcomes after surgical or endovascular treatment of ruptured anterior communicating artery aneurysms.We performed a retrospective cohort study of consecutive patients with ruptured anterior communicating artery aneurysms. Patient data and neuroimaging studies were reviewed. A propensity score for outcome measures was calculated to account for the nonrandom assignment to treatment. Primary outcome was the frequency of frontal lobe and striatum ischemic injury. Secondary outcomes were patient mortality and clinical outcome at discharge and at 3 months.Coiled patients were older (median, 55 versus 50 years;P= .03), presented with a worse clinical status (60% with Hunt and Hess Score >2 versus 34% in clipped patients;P= .02), had a higher modified Fisher grade (P= .01), and were more likely to present with intraventricular hemorrhage (78% versus 56%;P= .03). Ischemic frontal lobe infarction (OR, 2.9; 95% CI, 1.1-8.4;P= .03) and recurrent artery of Heubner infarction (OR, 20.9; 95% CI, 3.5-403.7;P< .001) were more common in clipped patients. Clipped patients were more likely to be functionally dependent at discharge (OR, 3.2;P= .05) compared with coiled patients. Mortality and clinical outcome at 3 months were similar between coiled and clipped patients.Frontal lobe and recurrent artery of Heubner infarctions are more common after surgical clipping of ruptured anterior communicating artery aneurysms, and are associated with poorer clinical outcomes at discharge.

  View details for PubMedID 28882863

• Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma. Cell reports Darmanis, S., Sloan, S. A., Croote, D., Mignardi, M., Chernikova, S., Samghababi, P., Zhang, Y., Neff, N., Kowarsky, M., Caneda, C., Li, G., Chang, S. D., Connolly, I. D., Li, Y., Barres, B. A., Gephart, M. H., Quake, S. R. 2017; 21 (5): 1399–1410

  Abstract

  Glioblastoma (GBM) is the most common primary brain cancer in adults and is notoriously difficult to treat because of its diffuse nature. We performed single-cell RNA sequencing (RNA-seq) on 3,589 cells in a cohort of four patients. We obtained cells from the tumor core as well as surrounding peripheral tissue. Our analysis revealed cellular variation in the tumor's genome and transcriptome. We were also able to identify infiltrating neoplastic cells in regions peripheral to the core lesions. Despite the existence of significant heterogeneity among neoplastic cells, we found that infiltrating GBM cells share a consistent gene signature between patients, suggesting a common mechanism of infiltration. Additionally, in investigating the immunological response to the tumors, we found transcriptionally distinct myeloid cell populations residing in the tumor core and the surrounding peritumoral space. Our data provide a detailed dissection of GBM cell types, revealing an abundance of information about tumor formation and migration.

  View details for PubMedID 29091775

• Comparison of porcine and bovine collagen dural substitutes in posterior fossa decompression for Chiari I malformation in adults. World neurosurgery Lee, C. K., Mokhtari, T., Connolly, I. D., Li, G., Shuer, L. M., Chang, S. D., Steinberg, G. K., Gephart, M. H. 2017

  Abstract

  Posterior fossa decompression surgeries for Chiari malformations are susceptible to post-operative complications such as pseudomeningocele, external cerebrospinal fluid (CSF) leak, and meningitis. Various dural substitutes have been employed to improve surgical outcomes.This study examined whether the collagen matrix dural substitute type correlated with the incidence of post-operative complications following posterior fossa decompression in adult patients with Chiari I malformations.A retrospective cohort study was conducted on 81 adult patients who underwent an elective decompressive surgery for treatment of symptomatic Chiari I malformations, with duraplasty involving a dural substitute derived from either bovine or porcine collagen matrix. Demographics and treatment characteristics were correlated with surgical outcomes.A total of 81 patients were included in the study. Compared to bovine dural substitute, porcine dural substitute was associated with a significantly higher risk of pseudomeningocele occurrence (OR 5.78, 95% CI 1.65-27.15; P = .01) and a higher overall complication rate (OR 3.70, 95% CI 1.23-12.71; P = .03) by univariate analysis. There was no significant difference in the rate of meningitis, repeat operations, or overall complication rate between the two dural substitutes. In addition, estimated blood loss was a significant risk factor for meningitis (P = .03). Multivariate analyses again demonstrated that porcine dural substitute was associated with pseudomeningocele occurrence, though the association with higher overall complication rate did not reach significance.Dural substitutes generated from porcine collagen, compared to those from bovine collagen, were associated with a higher likelihood of pseudomeningocele development in adult patients undergoing Chiari I malformation decompression and duraplasty.

  View details for PubMedID 28838875

• CyberKnife stereotactic radiosurgery for the treatment of symptomatic vertebral hemangiomas: a single-institution experience NEUROSURGICAL FOCUS Zhang, M., Chen, Y., Chang, S. D., Veeravagu, A. 2017; 42 (1)

  Abstract

  OBJECTIVE Symptomatic vertebral hemangiomas (SVHs) are a very rare pathology that can present with persistent pain or neurological deficits that warrant surgical intervention. Given the relative rarity and difficulty in assessment, the authors sought to present a dedicated series of SVHs treated using stereotactic radiosurgery (SRS) to provide insight into clinical decision making. METHODS A retrospective review of a single institution's experience with hypofractionated radiosurgery for SVH from 2004 to 2011 was conducted to determine the clinical and radiographic outcomes following SRS treatment. The authors report and analyze the treatment course of 5 patients with 7 lesions, 2 of which were treated primarily by SRS. RESULTS Of the 5 patients studied, 4 presented with a chief complaint of pain refractory to conservative measures. Three patients reported dysesthesias, and 2 reported upper-extremity weakness. Following radiosurgery, 4 of 5 patients exhibited improvement in their primary symptoms (3 for pain and 1 for weakness), achieving a clinical response after a mean period of 1 year. In 2 cases there was 20%-40% reduction in lesion size in the most responsive dimension as noted on images. All treatments were well tolerated. CONCLUSIONS SRS for SVH is a safe and feasible treatment strategy, comparable to prior radiotherapy studies, and in select cases may successfully confer delayed decompressive effects. Additional investigation will determine future patient selection and how conformal SRS treatment can best be administered.

  View details for DOI 10.3171/2016.9.FOCUS16372

  View details for Web of Science ID 000392113200013

  View details for PubMedID 28041316

• Impact of CyberKnife Radiosurgery on Overall Survival and Various Parameters of Patients with 1-3 versus ≥ 4 Brain Metastases. Cureus Murovic, J., Ding, V., Han, S. S., Adler, J. R., Chang, S. D. 2017; 9 (10): e1798

  Abstract

  Introduction This study's objective is to compare the overall survivals (OSs) and various parameters of patients with 1-3 versus ≥ 4 brain metastases post-CyberKnife radiosurgery (CKRS) (Accuray, Sunnyvale, California) alone. Methods Charts of 150 patients, from 2009-2014, treated with only CKRS for brain metastases were reviewed retrospectively for overall survival (OS) and patient, tumor, and imaging characteristics. Parameters included demographics, Eastern Cooperative Oncology Group (ECOG) performance scores, number and control of extracranial disease (ECD) sites, cause of death (COD), histology, tumor volume (TV), and post-CKRS whole brain radiotherapy (WBRT). The imaging characteristics assessed were time of complete response (CR), partial response (PR), stable imaging or local failure (LF), and distal brain failure (DBF). Patients and their data were divided into those with 1-3 (group 1) versus ≥ 4 brain metastases (group 2). For each CR and LF patient, absolute neutrophil count (ANC), absolute lymphocyte count (ALC)), and ANC/ALC ratio (NLR) were obtained, when available, at the time of CKRS. Results Both group 1 and group 2 had a median OS of 13 months. The patient median age for the 115 group 1 patients versus the 35 group 2 patients was 62 versus 56 years. Group 1 had slightly more males and group 2, females. The predominant ECOG score for each group was 1 and the number of ECD sites was one and two, respectively. Uncontrolled ECD occurred in the majority of both group 1 and group 2 patients. The main COD was ECD in both groups. The prevalent tumor histology for groups 1 and 2 was non-small cell lung carcinoma. Median TVs were 1.08 cc versus 1.42 cc for groups 1 and 2, respectively. The majority of patients in both groups did not undergo post-CKRS WBRT. Imaging outcomes were LC (CR, PR, or stable imaging) in 93 (80.9%) and 26 (74.3%) group 1 and 2 patients, of whom 32 (27.8%) and six (17.1%) had CR; 38 (33.0%) and 18 (51.4%), PR and 23 (20.0%) and two (5.7%), stable imaging; LF was the outcome in 22 (19.1%) and nine (25.7%) patients, and DBF occurred in 62 (53.9%) and 21 (60.0%), respectively. Uni- and multivariable analyses showed the independent parameters of a lower ECOG score, a greater number of ECD sites and uncontrolled ECD were significantly associated with greater mortality risk with and without accounting for other covariates. At CKRS, 19 group 1 and 2 CR patients had a mean ANC of 5.88 K/µL and a mean ALC of 1.31 K/µL and 13 (68%) of 19 had NLRs ≤ five, while 11 with LFs had a mean ANC of 5.22 K/µL and a mean ALC of 0.93 K/µL and seven (64%) had NLRs > five. An NLR ≤ five and high ALC was associated with a CR and an NLR > five and a low ALC with an LF. Conclusions Median OS post-CKRS was 13 months for both patients with 1-3 brain metastases and with ≥ 4. This is the only study in the literature to evaluate OS in patients with 1-3 and ≥ 4 brain metastases who were treated with CKRS alone. For groups 1 and 2 patients combined, 119 (79.3%) had LC and 38 (25.3%) had CR. The ANC, ALC, and NLR values are likely predictive of CR and LF outcomes.

  View details for PubMedID 29282442

  View details for PubMedCentralID PMC5741273

• Imaging changes over 18 months following stereotactic radiosurgery for brain metastases: both late radiation necrosis and tumor progression can occur. Journal of neuro-oncology Fujimoto, D., von Eyben, R., Gibbs, I. C., Chang, S. D., Li, G., Harsh, G. R., Hancock, S., Fischbein, N., Soltys, S. G. 2017

  Abstract

  Following stereotactic radiosurgery (SRS) for brain metastases, the median time range to develop adverse radiation effect (ARE) or radiation necrosis is 7-11 months. Similarly, the risk of local tumor recurrence following SRS is < 5% after 18 months. With improvements in systemic therapy, patients are living longer and are at risk for both late (defined as > 18 months after SRS) tumor recurrence and late ARE, which have not previously been well described. An IRB-approved, retrospective review identified patients treated with SRS who developed new MRI contrast enhancement > 18 months following SRS. ARE was defined as stabilization/shrinkage of the lesion over time or pathologic confirmation of necrosis, without tumor. Local failure (LF) was defined as continued enlargement of the lesion over time or pathologic confirmation of tumor. We identified 16 patients, with a median follow-up of 48.2 months and median overall survival of 73.0 months, who had 19 metastases with late imaging changes occurring a median of 32.9 months (range 18.5-63.2 months) after SRS. Following SRS, 12 lesions had late ARE at a median of 33.2 months and 7 lesions had late LF occurring a median of 23.6 months. As patients with cancer live longer and as SRS is increasingly utilized for treatment of brain metastases, the incidence of these previously rare imaging changes is likely to increase. Clinicians should be aware of these late events, with ARE occurring up to 5.3 years and local failure up to 3.8 years following SRS in our cohort.

  View details for PubMedID 29098569

• Biopsy versus resection for themanagement of low-grade gliomas COCHRANE DATABASE OF SYSTEMATIC REVIEWS Jiang, B., Chaichana, K., Veeravagu, A., Chang, S. D., Black, K. L., Patil, C. G. 2017

  Abstract

  This is an updated version of the original Cochrane review published in 2013, Issue 4.Low-grade gliomas (LGG) constitute a class of slow-growing primary brain neoplasms. Patients with clinically and radiographically suspected LGG have two initial surgical options, biopsy or resection. Biopsy can provide a histological diagnosis with minimal risk but does not offer a direct treatment. Resection may have additional benefits such as increasing survival and delaying recurrence, but is associated with a higher risk for surgical morbidity. There remains controversy about the role of biopsy versus resection and the relative clinical outcomes for the management of LGG.To assess the clinical effectiveness of biopsy compared to surgical resection in patients with a new lesion suspected to be a LGG.The following electronic databases were searched in 2012 for the first version of the review: Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11), MEDLINE (1950 to November week 3 2012), Embase (1980 to Week 46 2012). For this updated version, the following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 5), MEDLINE (Nov 2012 to June week 3 2016), Embase (Nov 2012 to 2016 week 26). All relevant articles were identified on PubMed and by using the 'related articles' feature. We also searched unpublished and grey literature including ISRCTN-metaRegister of Controled Trials, Physicians Data Query and ClinicalTrials.gov for ongoing trials.We planned to include patients of any age with a suspected intracranial LGG receiving biopsy or resection within a randomized clinical trial (RCT) or controlled clinical trial (CCT). Patients with prior resections, radiation therapy, or chemotherapy for LGG were excluded. Outcome measures included overall survival (OS), progression-free survival (PFS), functionally independent survival (FIS), adverse events, symptom control, and quality of life (QoL).A total of 1375 updated citations were searched and critically analyzed for relevance. This was undertaken independently by two review authors. The original electronic database searches yielded a total of 2764 citations. In total, 4139 citations have been critically analyzed for this updated review.No new RCTs of biopsy or resection for LGG were identified. No additional ineligible non-randomized studies (NRS) were included in this updated review. Twenty other ineligible studies were previously retrieved for further analysis despite not meeting the pre-specified criteria. Ten studies were retrospective or were literature reviews. Three studies were prospective, however they were limited to tumor recurrence and volumetric analysis and extent of resection. One study was a population-based parallel cohort in Norway, but not an RCT. Four studies were RCTs, however patients were randomized with respect to varying radiotherapy regimens to assess timing and dose of radiation. One RCT was on high-grade gliomas (HGGs) and not LGG. Finally, one RCT evaluated diffusion tensor imaging (DTI)-based neuro-navigation for surgical resection.Since the last version of this review, no new studies have been identified for inclusion and currently there are no RCTs or CCTs available on which to base definitive clinical decisions. Therefore, physicians must approach each case individually and weigh the risks and benefits of each intervention until further evidence is available. Some retrospective studies and non-randomized prospective studies do seem to suggest improved OS and seizure control correlating to higher extent of resection. Future research could focus on RCTs to determine outcomes benefits for biopsy versus resection.

  View details for DOI 10.1002/14651858.CD009319.pub3

  View details for Web of Science ID 000400759700029

  View details for PubMedID 28447767

• Embolization followed by Radiosurgery for the Treatment of Brain Arteriovenous Malformations (AVMs). World neurosurgery Marks, M. P., Marcellus, M. L., Santarelli, J., Dodd, R. L., Do, H. M., Chang, S. D., Adler, J. R., Mlynash, M., Steinberg, G. K. 2016

  Abstract

  Embolization has been proposed to reduce the size of the arteriovenous malformation (AVM) nidus in advance of radiosurgical treatment. Embolization followed by radiosurgery for brain AVMs, however, is controversial.We assessed the impact of embolization on nidal size before radiosurgical treatment and evaluated cure rates and complications by using embolization followed by radiosurgery.A retrospective review of our institutional AVM database identified 91 patients treated from 1995 to 2009 with embolization followed by radiosurgery. Pre- and postembolization AVM volumes were measured with angiography, and the modified radiation-based AVM scores (RBAS) also were calculated pre- and postembolization. RBAS determined from pre-embolization volumes were correlated with postradiosurgical obliteration.Median AVM volume declined from 18.8 mL (interquartile range, 10.2-32.2 mL) to 9.9 mL (3.1-19.2 mL) after embolization, P < 0.00003. Median RBAS scores decreased from 2.6 mL (1.8-3.9 mL) to 1.8 mL (1.0-2.8 mL), P < 0.00003. Two of 91 (2.2%) had new fixed deficits after embolization; however, no patient had new disabling deficits (modified Rankin Scale score >2). A total of 71 of 91 (79%) have had >3 years' follow-up, and 40 (56%) had complete obliteration, with 38 (53%) having excellent outcomes (complete obliteration without neurologic decline). Excellent outcome was seen in 90% of patients with modified RBAS score <1, 66% of patients with score 1-1.5, 50% patients with score 1.5-2, and 43% of patients with score >2.These data suggest that embolization of brain AVMs can safely and effectively reduce the treatment volume before radiosurgery. Combined therapy with embolization and radiosurgery does not appear to adversely affect rates of excellent outcome.

  View details for DOI 10.1016/j.wneu.2016.12.059

  View details for PubMedID 28017742

• Magnetic resonance perfusion image features uncover an angiogenic subgroup of glioblastoma patients with poor survival and better response to antiangiogenic treatment. Neuro-oncology Liu, T. T., Achrol, A. S., Mitchell, L. A., Rodriguez, S. A., Feroze, A., Kim, C., Chaudhary, N., Gevaert, O., Stuart, J. M., Harsh, G. R., Chang, S. D., Rubin, D. L. 2016

  Abstract

  In previous clinical trials, antiangiogenic therapies such as bevacizumab did not show efficacy in patients with newly diagnosed glioblastoma (GBM). This may be a result of the heterogeneity of GBM, which has a variety of imaging-based phenotypes and gene expression patterns. In this study, we sought to identify a phenotypic subtype of GBM patients who have distinct tumor-image features and molecular activities and who may benefit from antiangiogenic therapies.Quantitative image features characterizing subregions of tumors and the whole tumor were extracted from preoperative and pretherapy perfusion magnetic resonance (MR) images of 117 GBM patients in 2 independent cohorts. Unsupervised consensus clustering was performed to identify robust clusters of GBM in each cohort. Cox survival and gene set enrichment analyses were conducted to characterize the clinical significance and molecular pathway activities of the clusters. The differential treatment efficacy of antiangiogenic therapy between the clusters was evaluated.A subgroup of patients with elevated perfusion features was identified and was significantly associated with poor patient survival after accounting for other clinical covariates (P values <.01; hazard ratios > 3) consistently found in both cohorts. Angiogenesis and hypoxia pathways were enriched in this subgroup of patients, suggesting the potential efficacy of antiangiogenic therapy. Patients of the angiogenic subgroups pooled from both cohorts, who had chemotherapy information available, had significantly longer survival when treated with antiangiogenic therapy (log-rank P=.022).Our findings suggest that an angiogenic subtype of GBM patients may benefit from antiangiogenic therapy with improved overall survival.

  View details for DOI 10.1093/neuonc/now270

  View details for PubMedID 28007759

• Stereotactic radiosurgery for non-vestibular cranial nerve schwanommas. Journal of neuro-oncology D'Astous, M., Ho, A. L., Pendharkar, A., Choi, C. Y., Soltys, S. G., Gibbs, I. C., Tayag, A. T., Thompson, P. A., Adler, J. R., Chang, S. D. 2016: -?

  Abstract

  Non-vestibular cranial nerve schwannomas (NVCNS) are rare lesions, representing <10 % of cranial nerve schwannomas. The optimal treatment for NVCNS is often derived from vestibular schwannomas experience. Surgical resection has been referred to as the first line treatment for those benign tumors, but significant complication rates are reported. Stereotactic radiosurgery (SRS) has arisen as a mainstay of treatment for many benign tumors, including schwanommas. We retrospectively reviewed the outcomes of NVCNS treated by SRS to characterize tumor control, symptom relief, toxicity, and the role of hypo-fractionation of SRS dose. Eighty-eight (88) patients, with ninety-five (95) NVCNS were treated with either single or multi-session SRS from 2001 to 2014. Local control was achieved in 94 % of patients treated (median follow-up of 33 months, range 1-155). Complications were seen in 7.4 % of cases treated with SRS. At 1-year, 57 % of patients had improvement or resolution of their symptoms, while 35 % were stable and 8 % had worsening or increased symptoms. While 42 % received only one session, results on local control were similar for one or multiple sessions (p = 0.424). SRS for NVCNS is a treatment modality that provides excellent local control with minimal complication risk compared to traditional neurosurgical techniques. Tumor control obtained with a multi-session treatment was not significantly different from single session treatment. Safety profile was also comparable for uni or multi-session treatments. We concluded that, as seen in VS treated with CK SRS, radiosurgery treatment can be safely delivered in cases of NVCNS.

  View details for PubMedID 27752881

• A Phase I/II Trial of 5 Fraction Stereotactic Radiosurgery With 5-mm Margins With Concurrent and Adjuvant Temozolomide in Newly Diagnosed Supratentorial Glioblastoma Multiforme. International journal of radiation oncology, biology, physics Azoulay, M., Ho, C. K., Fujimoto, D. K., Modlin, L. A., Gibbs, I. C., Hancock, S. L., Li, G., Chang, S. D., Adler, J. R., Harsh, G. R., Nagpal, S., Thomas, R., Recht, L., Choi, C. Y., Soltys, S. G. 2016; 96 (2S): E131-E132

  View details for DOI 10.1016/j.ijrobp.2016.06.921

  View details for PubMedID 27673859

• The Role of Stereotactic Radiosurgery in the Reirradiation of Metastatic Spinal Tumors. International journal of radiation oncology, biology, physics Ho, C. K., Kumar, K. A., White, E. C., Azoulay, M., Fujimoto, D. K., Aggarwal, S., Gensheimer, M. F., Gibbs, I. C., Adler, J. R., Chang, S. D., Hancock, S. L., Choi, C. Y., Soltys, S. G. 2016; 96 (2S): E131-?

  View details for DOI 10.1016/j.ijrobp.2016.06.920

  View details for PubMedID 27673858

• The Outcome of Hypofractionated Stereotactic Radiosurgery for Large Vestibular Schwannomas. World neurosurgery Teo, M., Zhang, M., Li, A., Thompson, P. A., Tayag, A. T., Wallach, J., Gibbs, I. C., Soltys, S. G., Hancock, S. L., Chang, S. D. 2016; 93: 398-409

  Abstract

  Stereotactic radiosurgery (SRS) for large vestibular schwannomas (VS) remains controversial. We studied the tumor local control and toxicity rates after hypofractionated SRS for VS > 3 cm.A total of 587 patients with VS treated with SRS between 1998 and 2014 were reviewed retrospectively, and 30 Koos grade IV VSs were identified. There were 6 patients with neurofibromatosis 2 (NF2), 8 with cystic tumors, 22 with solid tumors, 19 who underwent primary CyberKnife (CK), and 11 with >3 cm after previous resection. Patients were treated by a median of 3 fractions at 18 Gy.After a median 97 months, the 3- and 10-year Kaplan-Meier estimates of local control were 85% and 80%, respectively, with 20% requiring salvage treatment. For patients who had previous tumor resection rather than primary CK, the estimates were 46% and 5%, respectively, with progression, and 3-year control rates of 71% and 94% (P = 0.008). Tumor control was also lower among NF2 versus non-NF2 patients (40% vs. 95%; P = 0.0014). Among patients with good clinical baselines before CK, 88% were functionally independent (modified Rankin Scale score, 0-2), 88% had good facial function (House-Brackmann grade I-II), and 38% had serviceable hearing (Gardner-Robertson grade I-II) at last follow-up. Hearing worsening was more likely among patients treated with primary CK (33% vs. 90%; P = 0.04).Overall, 80% of large VSs were adequately controlled by CK with 97 months of median follow-up. Patients with previous surgery and NF2 also appeared to have higher rates of tumor progression, and less favorable functional outcomes.

  View details for DOI 10.1016/j.wneu.2016.06.080

  View details for PubMedID 27368508

• Stereotactic radiosurgery for intramedullary spinal arteriovenous malformations JOURNAL OF CLINICAL NEUROSCIENCE Kalani, M. A., Choudhri, O., Gibbs, I. C., Soltys, S. G., Adler, J. R., Thompson, P. A., Tayag, A. T., Samos, C. H., Chang, S. D. 2016; 29: 162-167

  Abstract

  Spinal cord arteriovenous malformations (AVM) are rare lesions associated with recurrent hemorrhage and progressive ischemia. Occasionally a favorable location, size or vascular anatomy may allow management with endovascular embolization and/or microsurgical resection. For most, however, there is no good treatment option. Between 1997 and 2014, we treated 37 patients (19 females, 18 males, median age 30years) at our institution diagnosed with intramedullary spinal cord AVM (19 cervical, 12 thoracic, and six conus medullaris) with CyberKnife (Accuray, Sunnyvale, CA, USA) stereotactic radiosurgery. A history of hemorrhage was present in 50% of patients. The mean AVM volume of 2.3cc was treated with a mean marginal dose of 20.5Gy in a median of two sessions. Clinical and MRI follow-up were carried out annually, and spinal angiography was repeated at 3years. We report an overall obliteration rate of 19% without any post-treatment hemorrhagic events. In those AVM that did not undergo obliteration, significant volume reduction was noted at 3years. Although the treatment paradigm for spinal cord AVM continues to evolve, radiosurgical treatment is capable of safely obliterating or significantly shrinking most intramedullary spinal cord AVM.

  View details for DOI 10.1016/j.jocn.2015.12.005

  View details for Web of Science ID 000378449800032

  View details for PubMedID 26869363

• CyberKnife Stereotactic Radiosurgery for Atypical and Malignant Meningiomas. World neurosurgery Zhang, M., Ho, A. L., D'Astous, M., Pendharkar, A. V., Choi, C. Y., Thompson, P. A., Tayag, A. T., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2016; 91: 574-581 e1

  Abstract

  Recurrent World Health Organization (WHO) grade II and III meningiomas have traditionally been treated by surgery alone, but early literature suggests that adjuvant stereotactic radiosurgery may greatly improve outcomes. We present the long-term tumor control and safety of a hypofractionated stereotactic radiosurgery regimen.Prospectively collected data of 44 WHO grade II and 9 WHO grade III meningiomas treated by CyberKnife for adjuvant or salvage therapy were reviewed. Patient demographics, treatment parameters, local control, regional control, locoregional control, overall survival, radiation history, and complications were documented.For WHO grade II patients, recurrence occurred in 41%, with local, regional, and locoregional failure at 60 months recorded as 49%, 58%, and 36%. For WHO grade III patients, recurrence occurred in 66%, with local, regional, and locoregional failure at 12 months recorded as 57%, 100%, and 43%. The 60-month locoregional control rates for radiation naïve and experienced patients were 48% and 0% (P = 0.14). Overall, 7 of 44 grade II patients and 8 of 9 grade III patients had died at last follow-up. The 60-month and 12-month overall survival rates for grade II and III meningiomas were 87% and 50%, respectively. Serious complications occurred in 7.5% of patients.Stereotactic radiosurgery for adjuvant and salvage treatment of WHO grade II meningioma using a hypofractionated plan is a viable treatment strategy with acceptable long-term tumor control, overall survival, and complication rates. Future studies should focus on radiation-naïve patients and local management of malignant meningioma.

  View details for DOI 10.1016/j.wneu.2016.04.019

  View details for PubMedID 27108030

• Multiple Subsets of Brain Tumor Initiating Cells Coexist in Glioblastoma STEM CELLS Rennert, R. C., Achrol, A. S., Januszyk, M., Kahn, S. A., Liu, T. T., Liu, Y., Sahoo, D., Rodrigues, M., Maan, Z. N., Wong, V. W., Cheshier, S. H., Chang, S. D., Steinberg, G. K., Harsh, G. R., Gurtner, G. C. 2016; 34 (6): 1702-1707

  Abstract

  Brain tumor-initiating cells (BTICs) are self-renewing multipotent cells critical for tumor maintenance and growth. Using single-cell microfluidic profiling, we identified multiple subpopulations of BTICs co-existing in human glioblastoma, characterized by distinct surface marker expression and single-cell molecular profiles relating to distinct bulk tissue molecular subtypes. These data suggest BTIC subpopulation heterogeneity as an underlying source of intra-tumoral bulk tissue molecular heterogeneity, and will support future studies into BTIC subpopulation-specific therapies. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/stem.2359

  View details for Web of Science ID 000378089500025

  View details for PubMedID 26991945

• Dose-Response Modeling of the Visual Pathway Tolerance to Single-Fraction and Hypofractionated Stereotactic Radiosurgery SEMINARS IN RADIATION ONCOLOGY Hiniker, S. M., Modlin, L. A., Choi, C. Y., Atalar, B., Seiger, K., Binkley, M. S., Harris, J. P., Liao, Y. J., Fischbein, N., Wang, L., Ho, A., Lo, A., Chang, S. D., Harsh, G. R., Gibbs, I. C., Hancock, S. L., Li, G., Adler, J. R., Soltys, S. G. 2016; 26 (2): 97-104

  Abstract

  Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using α/β = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures. Both cases were meningiomas treated with 25Gy in 5 fractions, with a 3-fraction equivalent optic nerve Dmax of 19.2 and 22.2Gy. Fitting these data to a probit dose-response model enabled risk estimates to be made for these previously unvalidated optic pathway constraints: the Dmax limits of 12Gy in 1 fraction from QUANTEC, 19.5Gy in 3 fractions from Timmerman 2008, and 25Gy in 5 fractions from AAPM Task Group 101 all had less than 1% risk. In 262 patients with perioptic tumors treated with SRS, we found a risk of optic complications of less than 1%. These data support previously unvalidated estimates as safe guidelines, which may in fact underestimate the tolerance of the optic structures, particularly in patients without prior radiation. Further investigation would refine the estimated normal tissue complication probability for SRS near the optic apparatus.

  View details for DOI 10.1016/j.semradonc.2015.11.008

  View details for Web of Science ID 000373242700003

• Computational Identification of Tumor Anatomic Location Associated with Survival in 2 Large Cohorts of Human Primary Glioblastomas AMERICAN JOURNAL OF NEURORADIOLOGY Liu, T. T., Achrol, A. S., MITCHELL, L. A., Du, W. A., Loya, J. J., Rodriguez, S. A., Feroze, A., Westbroek, E. M., Yeom, K. W., Stuart, J. M., Chang, S. D., Harsh, G. R., Rubin, D. L. 2016; 37 (4): 621-628

  Abstract

  Tumor location has been shown to be a significant prognostic factor in patients with glioblastoma. The purpose of this study was to characterize glioblastoma lesions by identifying MR imaging voxel-based tumor location features that are associated with tumor molecular profiles, patient characteristics, and clinical outcomes.Preoperative T1 anatomic MR images of 384 patients with glioblastomas were obtained from 2 independent cohorts (n = 253 from the Stanford University Medical Center for training and n = 131 from The Cancer Genome Atlas for validation). An automated computational image-analysis pipeline was developed to determine the anatomic locations of tumor in each patient. Voxel-based differences in tumor location between good (overall survival of >17 months) and poor (overall survival of <11 months) survival groups identified in the training cohort were used to classify patients in The Cancer Genome Atlas cohort into 2 brain-location groups, for which clinical features, messenger RNA expression, and copy number changes were compared to elucidate the biologic basis of tumors located in different brain regions.Tumors in the right occipitotemporal periventricular white matter were significantly associated with poor survival in both training and test cohorts (both, log-rank P < .05) and had larger tumor volume compared with tumors in other locations. Tumors in the right periatrial location were associated with hypoxia pathway enrichment and PDGFRA amplification, making them potential targets for subgroup-specific therapies.Voxel-based location in glioblastoma is associated with patient outcome and may have a potential role for guiding personalized treatment.

  View details for DOI 10.3174/ajnr.A4631

  View details for Web of Science ID 000373346900014

• CyberKnife radiosurgery for brainstem metastases: Management and outcomes and a review of the literature. Journal of clinical neuroscience Liu, S., Murovic, J., Wallach, J., Cui, G., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2016; 25: 105-110

  Abstract

  To our knowledge this paper is the first to use recursive partitioning analysis (RPA) for brainstem metastasis (BSM) patient outcomes, after CyberKnife radiosurgery (CKRS; Accuray, Sunnyvale, CA, USA); nine similar previous publications used mainly Gamma Knife radiosurgery (Elekta AB, Stockholm, Sweden). Retrospective chart reviews from 2006-2013 of 949 CKRS-treated brain metastasis patients showed 54BSM patients (5.7%): 35 RPA Class II (65%) and 19 Class III (35%). There were 30 women (56%) and 24 men (44%). The median age was 59years (range 36-80) and median follow-up was 5months (range 1-52). Twenty-three patients (43%) had lung carcinoma BSM and 12 (22%) had breast cancer BSM. Fifty-four RPA Class II and III BSM patients had a median overall survival (OS) of 5months, and for each Class 8 and 2months, respectively. Of 36 RPA Class II and III patients with available symptoms (n=31) and findings (n=33), improvement/stability occurred in the majority for symptoms (86%) and findings (92%). Of 35 cases, 28 (80%) achieved BSM local control (LC); 13/14 with breast histology (93%) and 10/13 with lung histology (77%). All six RPA Class II and III patients with controlled extracranial systemic disease (ESD) experienced LC. Median tumor volume was 0.14cm(3); of 34 RPA Class II and III cases, 26 LC patients had a 0,13cm(3) median tumor volume while it was 0.27cm(3) in the eight local failures. Of 35 cases, single session equivalent dosages less than the median (n=13), at the 17.9Gy median (n=5) and greater than the median (n=17) had BSM LC in 10 (77%), four (80%) and 14 cases (82%), respectively. Univariate analysis showed Karnofsky Performance Score, RPA Class and ESD-control predicted OS. CKRS is useful for RPA Class II and III BSM patients with effective clinical and local BSM control.

  View details for DOI 10.1016/j.jocn.2015.10.013

  View details for PubMedID 26778047

• Stereotactic radiosurgery for metastasis to the craniovertebral junction preserves spine stability and offers symptomatic relief JOURNAL OF NEUROSURGERY-SPINE Azad, T. D., Esparza, R., Chaudhary, N., Chang, S. D. 2016; 24 (2): 241-247

  Abstract

  OBJECT Metastatic disease to the craniovertebral junction (CVJ) is rare but presents unique management challenges. To date, studies on using stereotactic radiosurgery (SRS) for CVJ metastases have been limited to case reports and small case series. The aim of this analysis was to evaluate the utility of SRS in the management of these secondary lesions. METHODS Clinical and radiological information from the charts of 25 patients with metastatic disease of the CVJ who were treated with SRS between 2005 and 2013 at the Stanford CyberKnife Center were retrospectively reviewed. RESULTS Seven male and 18 female patients with a median age of 58 years (range 34-94 years) were identified. The most common primary tumors were breast cancer (n = 5) and non-small cell lung cancer (n = 5), and the most frequent symptom was neck pain (n = 17). The average tumor volume treated was 15.9 cm(3) (range 0.16-54.1 cm(3)), with a mean marginal radiation dose of 20.3 Gy (range 15-25.5 Gy). The median follow-up was 18 months (range 1-81 months), though 1 patient was lost to follow-up. SRS provided radiographic tumor stability in over 80% of patients, offered pain alleviation in nearly two-thirds of patients, and produced no serious complications. Moreover, SRS preserved spinal stability in all but 1 patient, in whom pre-SRS stability was established. There was no evidence of radiation toxicity in the patient population. Median survival was 28 months (range 2-81 months), with survival of 13.3% at 5 years. CONCLUSIONS In the absence of unstable pathological fracture and spinal cord compression, metastatic tumors of the CVJ can be safely and effectively treated with SRS. This treatment option offers palliative pain relief and can halt tumor progression with only a low risk of complications or spinal instability.

  View details for DOI 10.3171/2015.6.SPINE15190

  View details for Web of Science ID 000368866000006

• Supracerebellar infratentorial sitting craniotomy for a pinealoblastoma. Neurosurgical focus Choudhri, O., Chang, S. D. 2016; 40 Video Suppl 1: 2016.1.FocusVid.15417

  Abstract

  Pinealoblastomas are WHO grade IV tumors of the pineal region and comprise up to 50% of all pineal parenchymal tumors. They are highly aggressive tumors that spread along the craniospinal axis and are most commonly seen in children. The standard of care involves maximal surgical resection and chemoradiation following tissue diagnosis. We present the rare case of a large pinealoblastoma in an 18-year-old girl who presented with headaches and Parinaud's syndrome from tectal compression. An attempt was made at endoscopic transventricular biopsy of the tumor at an outside hospital, but it was aborted given bleeding at the biopsy site. We performed a supracerebellar infratentorial approach in a sitting position to achieve a gross-total resection of the tumor. This video case illustrates techniques for setting up a sitting craniotomy and approaching a previously biopsied hemorrhagic pinealoblastoma. The venous conglomerate at the tentorial incisura was found to be enveloped by the tumor and a thickened arachnoid scar. Surgical anatomy of the third ventricle and the pineal region is illustrated in this case through the process of surgical dissection and tumor resection. The video can be found here: https://youtu.be/CzB0lFQ7AyI .

  View details for PubMedID 26722679

• Computational Identification of Tumor Anatomic Location Associated with Survival in 2 Large Cohorts of Human Primary Glioblastomas. AJNR. American journal of neuroradiology Liu, T. T., Achrol, A. S., Mitchell, L. A., Du, W. A., Loya, J. J., Rodriguez, S. A., Feroze, A., Westbroek, E. M., Yeom, K. W., Stuart, J. M., Chang, S. D., Harsh, G. R., Rubin, D. L. 2016

  Abstract

  Tumor location has been shown to be a significant prognostic factor in patients with glioblastoma. The purpose of this study was to characterize glioblastoma lesions by identifying MR imaging voxel-based tumor location features that are associated with tumor molecular profiles, patient characteristics, and clinical outcomes.Preoperative T1 anatomic MR images of 384 patients with glioblastomas were obtained from 2 independent cohorts (n = 253 from the Stanford University Medical Center for training and n = 131 from The Cancer Genome Atlas for validation). An automated computational image-analysis pipeline was developed to determine the anatomic locations of tumor in each patient. Voxel-based differences in tumor location between good (overall survival of >17 months) and poor (overall survival of <11 months) survival groups identified in the training cohort were used to classify patients in The Cancer Genome Atlas cohort into 2 brain-location groups, for which clinical features, messenger RNA expression, and copy number changes were compared to elucidate the biologic basis of tumors located in different brain regions.Tumors in the right occipitotemporal periventricular white matter were significantly associated with poor survival in both training and test cohorts (both, log-rank P < .05) and had larger tumor volume compared with tumors in other locations. Tumors in the right periatrial location were associated with hypoxia pathway enrichment and PDGFRA amplification, making them potential targets for subgroup-specific therapies.Voxel-based location in glioblastoma is associated with patient outcome and may have a potential role for guiding personalized treatment.

  View details for PubMedID 26744442

• Magnetic resonance perfusion image features uncover an angiogenic subgroup of glioblastoma patients with poor survival and better response to antiangiogenic treatment. Neuro-Oncology Liu, T. T., Achrol, A. S., Mitchell, L. A., Rodriguez, S. A., Feroze, A., Iv, M., Kim, C., Chaudhary, N., Gevaert, O., Stuart, J. M., Harsh, G. R., Chang, S. D., Rubin, D. L. 2016

  Abstract

  In previous clinical trials, antiangiogenic therapies such as bevacizumab did not show efficacy in patients with newly diagnosed glioblastoma (GBM). This may be a result of the heterogeneity of GBM, which has a variety of imaging-based phenotypes and gene expression patterns. In this study, we sought to identify a phenotypic subtype of GBM patients who have distinct tumor-image features and molecular activities and who may benefit from antiangiogenic therapies.Quantitative image features characterizing subregions of tumors and the whole tumor were extracted from preoperative and pretherapy perfusion magnetic resonance (MR) images of 117 GBM patients in 2 independent cohorts. Unsupervised consensus clustering was performed to identify robust clusters of GBM in each cohort. Cox survival and gene set enrichment analyses were conducted to characterize the clinical significance and molecular pathway activities of the clusters. The differential treatment efficacy of antiangiogenic therapy between the clusters was evaluated.A subgroup of patients with elevated perfusion features was identified and was significantly associated with poor patient survival after accounting for other clinical covariates (P values <.01; hazard ratios > 3) consistently found in both cohorts. Angiogenesis and hypoxia pathways were enriched in this subgroup of patients, suggesting the potential efficacy of antiangiogenic therapy. Patients of the angiogenic subgroups pooled from both cohorts, who had chemotherapy information available, had significantly longer survival when treated with antiangiogenic therapy (log-rank P=.022).Our findings suggest that an angiogenic subtype of GBM patients may benefit from antiangiogenic therapy with improved overall survival.

  View details for DOI 10.1093/neuonc/now270

• Dose-Response Modeling of the Visual Pathway Tolerance to Single-Fraction and Hypofractionated Stereotactic Radiosurgery. Seminars in radiation oncology Hiniker, S. M., Modlin, L. A., Choi, C. Y., Atalar, B., Seiger, K., Binkley, M. S., Harris, J. P., Liao, Y. J., Fischbein, N., Wang, L., Ho, A., Lo, A., Chang, S. D., Harsh, G. R., Gibbs, I. C., Hancock, S. L., Li, G., Adler, J. R., Soltys, S. G. 2016; 26 (2): 97–104

  Abstract

  Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using α/β = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures. Both cases were meningiomas treated with 25Gy in 5 fractions, with a 3-fraction equivalent optic nerve Dmax of 19.2 and 22.2Gy. Fitting these data to a probit dose-response model enabled risk estimates to be made for these previously unvalidated optic pathway constraints: the Dmax limits of 12Gy in 1 fraction from QUANTEC, 19.5Gy in 3 fractions from Timmerman 2008, and 25Gy in 5 fractions from AAPM Task Group 101 all had less than 1% risk. In 262 patients with perioptic tumors treated with SRS, we found a risk of optic complications of less than 1%. These data support previously unvalidated estimates as safe guidelines, which may in fact underestimate the tolerance of the optic structures, particularly in patients without prior radiation. Further investigation would refine the estimated normal tissue complication probability for SRS near the optic apparatus.

  View details for PubMedID 27000505

• Subfrontal trans-lamina terminalis approach to a third ventricular craniopharyngioma NEUROSURGICAL FOCUS Choudhri, O., Chang, S. D. 2016; 40

  View details for DOI 10.3171/2016.1.FocusVid.15416

  View details for Web of Science ID 000379788500004

• Supracerebellar infratentorial sitting craniotomy for a pinealoblastoma NEUROSURGICAL FOCUS Choudhri, O., Chang, S. D. 2016; 40

  View details for DOI 10.3171/2016.1.FocusVid.15417

  View details for Web of Science ID 000379788500005

• Subfrontal trans-lamina terminalis approach to a third ventricular craniopharyngioma. Neurosurgical focus Choudhri, O., Chang, S. D. 2016; 40 Video Suppl 1: 2016.1.FocusVid.15416

  Abstract

  Craniopharyngiomas are benign, partly cystic epithelial tumors that can rarely occur in a retrochiasmatic location with involvement of the third ventricle. The lamina terminalis is an important neurosurgical corridor to these craniopharyngiomas in the anterior portion of the third ventricle. We present a video case of a large midline suprasellar and third ventricular craniopharyngioma in a 32-year-old male with visual disturbances. The tumor was approached with a subfrontal translamina terminalis exposure, and a gross-total resection of the tumor was achieved. This surgery involved working through a lamina terminalis fenestration around the optic nerve, optic chiasm, optic tracts, and the anterior communicating artery complex. This video illustrates the techniques employed in performing a transbasal anterior skull base approach to the third ventricle and demonstrates vivid surgical anatomy of neurovascular structures around the lamina terminalis. The video can be found here: https://youtu.be/fCYMgx8SnKs .

  View details for PubMedID 26722678

• Stereotactic radiosurgery for metastasis to the craniovertebral junction preserves spine stability and offers symptomatic relief. Journal of neurosurgery. Spine Azad, T. D., Esparza, R., Chaudhary, N., Chang, S. D. 2015: 1-7

  Abstract

  OBJECT Metastatic disease to the craniovertebral junction (CVJ) is rare but presents unique management challenges. To date, studies on using stereotactic radiosurgery (SRS) for CVJ metastases have been limited to case reports and small case series. The aim of this analysis was to evaluate the utility of SRS in the management of these secondary lesions. METHODS Clinical and radiological information from the charts of 25 patients with metastatic disease of the CVJ who were treated with SRS between 2005 and 2013 at the Stanford CyberKnife Center were retrospectively reviewed. RESULTS Seven male and 18 female patients with a median age of 58 years (range 34-94 years) were identified. The most common primary tumors were breast cancer (n = 5) and non-small cell lung cancer (n = 5), and the most frequent symptom was neck pain (n = 17). The average tumor volume treated was 15.9 cm(3) (range 0.16-54.1 cm(3)), with a mean marginal radiation dose of 20.3 Gy (range 15-25.5 Gy). The median follow-up was 18 months (range 1-81 months), though 1 patient was lost to follow-up. SRS provided radiographic tumor stability in over 80% of patients, offered pain alleviation in nearly two-thirds of patients, and produced no serious complications. Moreover, SRS preserved spinal stability in all but 1 patient, in whom pre-SRS stability was established. There was no evidence of radiation toxicity in the patient population. Median survival was 28 months (range 2-81 months), with survival of 13.3% at 5 years. CONCLUSIONS In the absence of unstable pathological fracture and spinal cord compression, metastatic tumors of the CVJ can be safely and effectively treated with SRS. This treatment option offers palliative pain relief and can halt tumor progression with only a low risk of complications or spinal instability.

  View details for PubMedID 26516666

• Magnetic resonance image features identify glioblastoma phenotypic subtypes with distinct molecular pathway activities. Science translational medicine Itakura, H., Achrol, A. S., Mitchell, L. A., Loya, J. J., Liu, T., Westbroek, E. M., Feroze, A. H., Rodriguez, S., Echegaray, S., Azad, T. D., Yeom, K. W., Napel, S., Rubin, D. L., Chang, S. D., Harsh, G. R., Gevaert, O. 2015; 7 (303): 303ra138-?

  Abstract

  Glioblastoma (GBM) is the most common and highly lethal primary malignant brain tumor in adults. There is a dire need for easily accessible, noninvasive biomarkers that can delineate underlying molecular activities and predict response to therapy. To this end, we sought to identify subtypes of GBM, differentiated solely by quantitative magnetic resonance (MR) imaging features, that could be used for better management of GBM patients. Quantitative image features capturing the shape, texture, and edge sharpness of each lesion were extracted from MR images of 121 single-institution patients with de novo, solitary, unilateral GBM. Three distinct phenotypic "clusters" emerged in the development cohort using consensus clustering with 10,000 iterations on these image features. These three clusters--pre-multifocal, spherical, and rim-enhancing, names reflecting their image features--were validated in an independent cohort consisting of 144 multi-institution patients with similar tumor characteristics from The Cancer Genome Atlas (TCGA). Each cluster mapped to a unique set of molecular signaling pathways using pathway activity estimates derived from the analysis of TCGA tumor copy number and gene expression data with the PARADIGM (Pathway Recognition Algorithm Using Data Integration on Genomic Models) algorithm. Distinct pathways, such as c-Kit and FOXA, were enriched in each cluster, indicating differential molecular activities as determined by the image features. Each cluster also demonstrated differential probabilities of survival, indicating prognostic importance. Our imaging method offers a noninvasive approach to stratify GBM patients and also provides unique sets of molecular signatures to inform targeted therapy and personalized treatment of GBM.

  View details for DOI 10.1126/scitranslmed.aaa7582

  View details for PubMedID 26333934

  View details for PubMedCentralID PMC4666025

• Magnetic resonance image features identify glioblastoma phenotypic subtypes with distinct molecular pathway activities. Science translational medicine Itakura, H., Achrol, A. S., Mitchell, L. A., Loya, J. J., Liu, T., Westbroek, E. M., Feroze, A. H., Rodriguez, S., Echegaray, S., Azad, T. D., Yeom, K. W., Napel, S., Rubin, D. L., Chang, S. D., Harsh, G. R., Gevaert, O. 2015; 7 (303): 303ra138-?

  Abstract

  Glioblastoma (GBM) is the most common and highly lethal primary malignant brain tumor in adults. There is a dire need for easily accessible, noninvasive biomarkers that can delineate underlying molecular activities and predict response to therapy. To this end, we sought to identify subtypes of GBM, differentiated solely by quantitative magnetic resonance (MR) imaging features, that could be used for better management of GBM patients. Quantitative image features capturing the shape, texture, and edge sharpness of each lesion were extracted from MR images of 121 single-institution patients with de novo, solitary, unilateral GBM. Three distinct phenotypic "clusters" emerged in the development cohort using consensus clustering with 10,000 iterations on these image features. These three clusters--pre-multifocal, spherical, and rim-enhancing, names reflecting their image features--were validated in an independent cohort consisting of 144 multi-institution patients with similar tumor characteristics from The Cancer Genome Atlas (TCGA). Each cluster mapped to a unique set of molecular signaling pathways using pathway activity estimates derived from the analysis of TCGA tumor copy number and gene expression data with the PARADIGM (Pathway Recognition Algorithm Using Data Integration on Genomic Models) algorithm. Distinct pathways, such as c-Kit and FOXA, were enriched in each cluster, indicating differential molecular activities as determined by the image features. Each cluster also demonstrated differential probabilities of survival, indicating prognostic importance. Our imaging method offers a noninvasive approach to stratify GBM patients and also provides unique sets of molecular signatures to inform targeted therapy and personalized treatment of GBM.

  View details for DOI 10.1126/scitranslmed.aaa7582

  View details for PubMedID 26333934

• Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Shultz, D. B., Modlin, L. A., Jayachandran, P., von Eyben, R., Gibbs, I. C., Choi, C. Y., Chang, S. D., Harsh, G. R., Li, G., Adler, J. R., Hancock, S. L., Soltys, S. G. 2015; 92 (5): 993-999

  Abstract

  To report the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS).We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS.Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15 months (range, 3-98 months), the median OS from the time of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites.Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.

  View details for DOI 10.1016/j.ijrobp.2015.04.036

  View details for Web of Science ID 000357900600018

  View details for PubMedID 26194677

• Perspective on "the role of adjuvant radiotherapy after gross total resection of atypical meningiomas". World neurosurgery Veeravagu, A., Azad, T. D., Chang, S. D. 2015; 83 (5): 737-738

  View details for DOI 10.1016/j.wneu.2015.01.047

  View details for PubMedID 25681598

• Persistent trigeminal artery supply to an intrinsic trigeminal nerve arteriovenous malformation: A rare cause of trigeminal neuralgia. Journal of clinical neuroscience Choudhri, O., Heit, J. J., Feroze, A. H., Chang, S. D., Dodd, R. L., Steinberg, G. K. 2015; 22 (2): 409-412

  Abstract

  Infratentorial arteriovenous malformations (AVM) associated with the trigeminal nerve root entry zone are a known cause of secondary trigeminal neuralgia (TN). The treatment of both TN and AVM can be challenging, especially if the AVM is embedded within the trigeminal nerve. A persistent trigeminal artery (PTA) can rarely supply these intrinsic trigeminal nerve AVM. We present a 64-year-old man with TN from a right trigeminal nerve AVM supplied by a PTA variant. The patient underwent microvascular decompression and a partial resection of the AVM with relief of facial pain symptoms. His residual AVM was subsequently treated with CyberKnife radiosurgery (Accuray, Sunnyvale, CA, USA). A multimodality approach may be required for the treatment of trigeminal nerve associated PTA AVM and important anatomic patterns need to be recognized before any treatment. Herein, we report to our knowledge the third documented patient with a posterior fossa AVM supplied by a PTA and the first PTA AVM presenting as facial pain.

  View details for DOI 10.1016/j.jocn.2014.06.007

  View details for PubMedID 25070632

• The pathophysiology of cerebral radiation necrosis and the role of laser interstitial thermal therapy. World neurosurgery Murovic, J. A., Chang, S. D. 2015; 83 (1): 23-26

  View details for DOI 10.1016/j.wneu.2014.03.015

  View details for PubMedID 24631912

• Paraganglioma of the Filum Terminale: Case Report, Pathology and Review of the Literature. Cure¯us Kalani, M. A., Chang, S. D., Vu, B. 2015; 7 (10)

  Abstract

  Spinal paragangliomas are very rare neuroendocrine tumors often presenting with low back pain and radicular symptoms; once resected, they often show benign clinical outcomes. Radiographically spinal paragangliomas mimic more commonly described tumors, such as ependymomas, schwannomas, meningiomas, and even hemangiomas, but a "salt and pepper" appearance related to a serpiginous vascular structure is instructive. Indeed, the rarity of this tumor makes the diagnosis rather challenging radiographically. Graded as a WHO Grade I tumor, they are slow-growing with low proliferation indices. Gross total resection is the mainstay of operative treatment but is often limited by tumor adherence to functional nerves. Here, we present a case of this rare tumor and its management, including a review of the pathology and literature related to this tumor.

  View details for DOI 10.7759/cureus.354

  View details for PubMedID 26623209

  View details for PubMedCentralID PMC4652858

• A case of stereotactic radiation in skull base solitary fibrous tumor: more harm than good? Journal of neurological surgery reports Santa Maria, P. L., Abuzeid, W. M., Nayak, J. V., Chang, S. D., Blevins, N. H. 2014; 75 (2): e214-6

  Abstract

  Objective Due to its location, total resection of a skull base solitary fibrous tumor (SFT) can lead to morbidity with injury to lower cranial nerves, and a decision must be made between subtotal resection with possible stereotactic radiotherapy or total resection with cranial nerve morbidity. We report the long-term outcomes and review the literature of a case of stereotactic radiation in SFT to provide evidence for making this decision. Design A retrospective case review. Setting An academic tertiary referral center. Results We present a case with > 10 years follow-up of radiation following skull base SFT, initially misdiagnosed as schwannoma, where radiotherapy did not improve recurrence or metastatic behavior and led to complications during subsequent surgical resection. Conclusions SFT often masquerades as schwannoma, especially in the skull base. Careful immunohistochemistry, including CD34 expression, is critical to the diagnosis and management. This case highlights that total tumor resection of SFT remains the gold standard of treatment. Stereotactic radiation is not recommended in the management of skull base SFT.

  View details for DOI 10.1055/s-0034-1387196

  View details for PubMedID 25485216

  View details for PubMedCentralID PMC4242816

• Human brain arteriovenous malformations express lymphatic-associated genes ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY Shoemaker, L. D., Fuentes, L. F., Santiago, S. M., Allen, B. M., Cook, D. J., Steinberg, G. K., Chang, S. D. 2014; 1 (12): 982-995

  Abstract

  Brain arteriovenous malformations (AVMs) are devastating, hemorrhage-prone, cerebrovascular lesions characterized by well-defined feeding arteries, draining vein(s) and the absence of a capillary bed. The endothelial cells (ECs) that comprise AVMs exhibit a loss of arterial and venous specification. Given the role of the transcription factor COUP-TFII in vascular development, EC specification, and pathological angiogenesis, we examined human AVM tissue to determine if COUP-FTII may have a role in AVM disease biology.We examined 40 human brain AVMs by immunohistochemistry (IHC) and qRT-PCR for the expression of COUP-TFII as well as other genes involved in venous and lymphatic development, maintenance, and signaling. We also examined proliferation and EC tube formation with human umbilical ECs (HUVEC) following COUP-TFII overexpression.We report that AVMs expressed COUP-TFII, SOX18, PROX1, NFATC1, FOXC2, TBX1, LYVE1, Podoplanin, and vascular endothelial growth factor (VEGF)-C, contained Ki67-positive cells and heterogeneously expressed genes involved in Hedgehog, Notch, Wnt, and VEGF signaling pathways. Overexpression of COUP-TFII alone in vitro resulted in increased EC proliferation and dilated tubes in an EC tube formation assay in HUVEC.This suggests AVM ECs are further losing their arterial/venous specificity and acquiring a partial lymphatic molecular phenotype. There was significant correlation of gene expression with presence of clinical edema and acute hemorrhage. While the precise role of these genes in the formation, stabilization, growth and risk of hemorrhage of AVMs remains unclear, these findings have potentially important implications for patient management and treatment choice, and opens new avenues for future work on AVM disease mechanisms.

  View details for DOI 10.1002/acn3.142

  View details for Web of Science ID 000209815800003

  View details for PubMedCentralID PMC4284124

• Human brain arteriovenous malformations express lymphatic-associated genes. Annals of clinical and translational neurology Shoemaker, L. D., Fuentes, L. F., Santiago, S. M., Allen, B. M., Cook, D. J., Steinberg, G. K., Chang, S. D. 2014; 1 (12): 982-995

  Abstract

  Brain arteriovenous malformations (AVMs) are devastating, hemorrhage-prone, cerebrovascular lesions characterized by well-defined feeding arteries, draining vein(s) and the absence of a capillary bed. The endothelial cells (ECs) that comprise AVMs exhibit a loss of arterial and venous specification. Given the role of the transcription factor COUP-TFII in vascular development, EC specification, and pathological angiogenesis, we examined human AVM tissue to determine if COUP-FTII may have a role in AVM disease biology.We examined 40 human brain AVMs by immunohistochemistry (IHC) and qRT-PCR for the expression of COUP-TFII as well as other genes involved in venous and lymphatic development, maintenance, and signaling. We also examined proliferation and EC tube formation with human umbilical ECs (HUVEC) following COUP-TFII overexpression.We report that AVMs expressed COUP-TFII, SOX18, PROX1, NFATC1, FOXC2, TBX1, LYVE1, Podoplanin, and vascular endothelial growth factor (VEGF)-C, contained Ki67-positive cells and heterogeneously expressed genes involved in Hedgehog, Notch, Wnt, and VEGF signaling pathways. Overexpression of COUP-TFII alone in vitro resulted in increased EC proliferation and dilated tubes in an EC tube formation assay in HUVEC.This suggests AVM ECs are further losing their arterial/venous specificity and acquiring a partial lymphatic molecular phenotype. There was significant correlation of gene expression with presence of clinical edema and acute hemorrhage. While the precise role of these genes in the formation, stabilization, growth and risk of hemorrhage of AVMs remains unclear, these findings have potentially important implications for patient management and treatment choice, and opens new avenues for future work on AVM disease mechanisms.

  View details for DOI 10.1002/acn3.142

  View details for PubMedID 25574473

  View details for PubMedCentralID PMC4284124

• Outcomes following malignant degeneration of benign vestibular schwannomas after stereotactic radiosurgery. World neurosurgery Zhang, M., Chang, S. D. 2014; 82 (3-4): 346-349

  View details for DOI 10.1016/j.wneu.2014.03.005

  View details for PubMedID 24613663

• The Role of Radiosurgery for Infratentorial Arteriovenous Malformations WORLD NEUROSURGERY Iyer, A., Chang, S. D. 2014; 82 (1-2): E85–E86

  View details for PubMedID 24815735

• A literature review of key molecular genetic aberrations in meningiomas: a potential role in the determination of radiosurgery outcomes. World neurosurgery Murovic, J. A., Chang, S. D. 2014; 81 (5-6): 714-716

  View details for DOI 10.1016/j.wneu.2013.08.048

  View details for PubMedID 24012470

• Experience with intraoperative navigation and imaging during endoscopic transnasal spinal approaches to the foramen magnum and odontoid. Neurosurgical focus Choudhri, O., Mindea, S. A., Feroze, A., Soudry, E., Chang, S. D., Nayak, J. V. 2014; 36 (3): E4-?

  Abstract

  Object In this study the authors share their experience using intraoperative spinal navigation and imaging for endoscopic transnasal approaches to the odontoid in 5 patients undergoing C1-2 surgery for basilar invagination at Stanford Hospital and Clinics from 2010 to 2013. Methods Of these 5 patients undergoing C1-2 surgery for basilar invagination, 4 underwent a 2-tiered anterior C1-2 resection with posterior occipitocervical fusion during a first stage surgery, followed by endoscopic endonasal odontoidectomy in a separate setting. Intraoperative stereotactic navigation was performed using a surgical navigation system in all cases. Navigation accuracy, characterized as target registration error, ranged between 0.8 mm and 2 mm, with an average of 1.2 mm. Intraoperative imaging using a CT scanner was also performed in 2 patients. Results Endoscopic decompression of the brainstem was achieved in all patients, and no intraoperative complications were encountered. All patients were extubated within 24 hours after surgery and were able to swallow within 48 hours. After appropriate initial reconstruction of the defect at the craniocervical junction, no postoperative CSF leakage, arterial injury, or need for reoperation was encountered; 1 patient developed mild postoperative velopharyngeal insufficiency that resolved by the 6-month follow-up evaluation. There were no deaths and no patients required tracheostomy placement. The average inpatient stay after surgery varied between 72 and 96 hours, without extended intensive care unit stays for any patient. Conclusions Technologies such as intraoperative CT scanning and merged MRI/CT can provide the surgeon with detailed, virtual real-time information about the extent of complex endoscopic vertebral segment resection and brainstem decompression and lessens the prospect of revision or secondary procedures in this challenging surgical corridor. Moreover, patients experience limited morbidity and can tolerate early oral intake after transnasal endoscopic odontoidectomy. Essential to the successful undertaking of these endoscopic adventures is 1) an understanding of the endoscopic nasal, skull base, and neurovascular anatomy; 2) advanced and extended-length instrumentation including navigation; and 3) a team approach between experienced rhinologists and spine surgeons comfortable with endoscopic skull base techniques.

  View details for DOI 10.3171/2014.1.FOCUS13533

  View details for PubMedID 24580005

• Experience with intraoperative navigation and imaging during endoscopic transnasal spinal approaches to the foramen magnum and odontoid. Neurosurgical focus Choudhri, O., Mindea, S. A., Feroze, A., Soudry, E., Chang, S. D., Nayak, J. V. 2014; 36 (3): E4-?

  View details for DOI 10.3171/2014.1.FOCUS13533

  View details for PubMedID 24580005

• Co-occurrence of a cerebral cavernous malformation and an orbital cavernous hemangioma in a patient with seizures and visual symptoms: Rare crossroads for vascular malformations. Surgical neurology international Choudhri, O., Feroze, A. H., Lad, E. M., Kim, J. W., Plowey, E. D., Karamchandani, J. R., Chang, S. D. 2014; 5: S148-54

  Abstract

  Cerebral cavernous malformations (CCMs) are angiographically occult vascular malformations of the central nervous system. As a result of hemorrhage and mass effect, patients may present with focal neurologic deficits, seizures, and other symptoms necessitating treatment. Once symptomatic, most often from hemorrhage, CCMs are treated with microsurgical resection. Orbital cavernous hemangiomas (OCHs) are similar but distinct vascular malformations that present within the orbital cavity. Even though CCMs and OCHs are both marked by dilated endothelial-lined vascular channels, they are infrequently seen in the same patient.We provide a brief overview of the two related pathologies in the context of a patient presenting to our care with concomitant lesions, which were both resected in full without complication.This is the first known report that describes a case of concomitant CCM and OCH and explores the origins of two pathologies that are rarely encountered together in neurosurgical practice. Recognition of disparate symptomatologies is important for properly managing these patients.

  View details for DOI 10.4103/2152-7806.134810

  View details for PubMedID 25071938

  View details for PubMedCentralID PMC4109172

• Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Atalar, B., Modlin, L. A., Choi, C. Y., Adler, J. R., Gibbs, I. C., Chang, S. D., Harsh, G. R., Li, G., Nagpal, S., Hanlon, A., Soltys, S. G. 2013; 87 (4): 713-718

  Abstract

  We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients.We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other).With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004).In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

  View details for DOI 10.1016/j.ijrobp.2013.07.034

  View details for Web of Science ID 000325763300022

  View details for PubMedID 24054875

• Multi-Session Radiosurgery of Benign Intracranial Tumors NEUROSURGERY CLINICS OF NORTH AMERICA Yeung, J. T., Karim, S. A., Chang, S. D. 2013; 24 (4): 543-?

  Abstract

  Multi-session stereotactic radiosurgery (SRS) enables a high dose per fraction to be delivered to the tumor bed with rapid dose falloff that allows for sparing of critical structures, resulting in less radiation-associated toxicity. In this article, the authors review the basic concepts and techniques of multi-session SRS, indications for this technique, outcomes from single-session and multi-session SRS using 3 commonly treated benign intracranial tumors (meningiomas, vestibular schwannomas, pituitary adenomas), and discuss why multi-session SRS is an attractive approach for the treatment of these tumors.

  View details for DOI 10.1016/j.nec.2013.06.003

  View details for Web of Science ID 000326659600007

  View details for PubMedID 24093572

• Cochlea radiation dose correlates with hearing loss after stereotactic radiosurgery of vestibular schwannoma. World neurosurgery Hayden Gephart, M. G., Hansasuta, A., Balise, R. R., Choi, C., Sakamoto, G. T., Venteicher, A. S., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Adler, J. R., Chang, S. D. 2013; 80 (3-4): 359-363

  Abstract

  OBJECTIVE: For multisession radiosurgery, no published data relate the volume and dose of cochlear irradiation to quantified risk of hearing loss. We conducted a retrospective, dosimetric study to evaluate the relationship between hearing loss after stereotactic radiosurgery (SRS) and the dose-volume of irradiated cochlea. METHODS: Cochlear dose data were retrospectively collected on consecutive patients who underwent SRS (18 Gy in 3 sessions) for vestibular schwanoma between 1999 and 2005 at Stanford University Hospital. Inclusion criteria included Gardner-Robertson (GR) grade I or II hearing prior to radiosurgical treatment, complete audiograms, and magnetic resonance imaging (MRI) follow-up. A cochlea dose-volume histogram was generated for each of the 94 patients who qualified for this study. RESULTS: GR grade I-II hearing posttreatment was maintained in 74% of patients (70/94). Median time to last follow-up audiogram was 2.4 years (range 0.4-8.9) and to last MRI was 3.6 years (range 0.5-9.4). Each higher level of cochlear irradiation was associated with increased risk of hearing loss. Larger cochlear volume was associated with lower risk of hearing loss. Controlling for differences in cochlear volume among subjects, each additional mm(3) of cochlea receiving 10 to 16 Gy (single session equivalent doses of 6.6-10.1 Gy3) significantly increased the odds of hearing loss by approximately 5%. CONCLUSIONS: Larger cochlear volume is associated with lower risk of hearing loss following trisession SRS for vestibular schwannoma. Controlling for this phenomenon, higher radiation dose and larger irradiated cochlear volume are significantly associated with higher risk of hearing loss. This study confirms and quantifies the risk of hearing loss following trisession SRS for vestibular schwannoma.

  View details for DOI 10.1016/j.wneu.2012.04.001

  View details for PubMedID 22484770

• A critical analysis of the literature review in "Stereotactic radiosurgery for trigeminal pain secondary to benign skull base tumors" by Tanaka et al. and presentation of an algorithm for management of these tumors. World neurosurgery Murovic, J. A., Chang, S. D. 2013; 80 (3-4): 287-289

  View details for DOI 10.1016/j.wneu.2012.04.027

  View details for PubMedID 22548891

• CyberKnife radiosurgery for the management of skull base and spinal chondrosarcomas. Journal of neuro-oncology Jiang, B., Veeravagu, A., Feroze, A. H., Lee, M., Harsh, G. R., Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D. 2013; 114 (2): 209-218

  Abstract

  The use of CyberKnife (CK) stereotactic radiosurgery (SRS) for the management of central nervous system chondrosarcomas has not been previously reported. To evaluate outcomes of primary, recurrent, and metastatic chondrosarcomas of the skull base and spine treated with CK SRS, a retrospective observational study of 16 patients treated between 1996 and 2011 with CK SRS was performed using an IRB-approved database at Stanford University Medical Center. Twenty lesions (12 cranial, 8 spinal) across six males and ten females were analyzed. The median age at SRS was 51 years and median follow-up was 33 months. Median tumor volume was 11.0 cm³ and median marginal dosages were 22, 24, 26, 27, and 30 Gy for one to five fractionations, respectively. Overall Kaplan-Meier survival rates were 88, 88, 80, and 66 % at 1, 3, 5, and 10 years after initial presentation. Survival rates at 1, 3, and 5 years after CK were 81, 67, and 55 %, respectively. Actuarial tumor control was 41 ± 13 % at 60 months. At 36 months follow-up, tumor control was 80 % in primary lesions, 50 % in recurrent lesions, and 0.0 % in metastatic disease (p = 0.07). Tumor control was 58 % in cranial lesions and 38 % in spinal lesions. Radiation injury was reported in one patient. CK SRS appears to be a safe adjuvant therapy and offers moderate control for primary cranial chondrosarcoma lesions. There appears to be a clinically, albeit not statistically, significant trend towards poorer outcomes in similarly treated metastatic, recurrent, and spinal chondrosarcomas (p = 0.07). Lesions not candidates for single fraction SRS may be treated with hypofractionated SRS without increased risk for radiation necrosis.

  View details for DOI 10.1007/s11060-013-1172-9

  View details for PubMedID 23748573

• Volumetric Analysis of Intracranial Arteriovenous Malformations Contoured for CyberKnife Radiosurgery With 3-Dimensional Rotational Angiography vs Computed Tomography/Magnetic Resonance Imaging. Neurosurgery Veeravagu, A., Hansasuta, A., Jiang, B., Karim, A. S., Gibbs, I. C., Chang, S. D. 2013; 73 (2): 262-270

  Abstract

  BACKGROUND:: Accurate target delineation has significant impact on brain arteriovenous malformations (AVMs) obliteration, treatment success, and potential complications of stereotactic radiosurgery. OBJECTIVE:: We compare the nidal contouring of AVMs using fused images of contrasted computerized tomography (CT) and magnetic resonance (MRI) with matched images of three-dimensional (3-D) cerebral angiography for Cyberknife radiosurgery (CKRS) treatment planning. METHODS:: Between May 2009 and April 2012, 3-D cerebral angiography was integrated into CKRS target planning for thirty consecutive patients. The AVM nidal target volumes were delineated using fused CT and MRI scans versus fused CT, MRI, and 3-D cerebral angiography for each patient. RESULTS:: The mean volume of the AVM nidus contoured with the addition of 3-D cerebral angiography to the CT/MRI fusion (9.09 cm, 95% CI 5.39-12.8 cm) was statistically smaller than the mean volume contoured with CT/ MRI fused scans alone (14.1 cm, 95% CI 9.16-19.1 cm), with a mean volume difference of δ=5.01 cm (p=0.001). Diffuse AVM nidus was associated with larger mean volume differences in comparison to a compact nidus (δ=6.51 vs. 2.11 cm, p=0.02). The mean volume difference was not statistically associated with the patient's gender (male δ=5.61, female δ=5.06, p=0.84), prior hemorrhage status (yes δ=5.69, no δ=5.23, p=0.86), or prior embolization status (yes δ=6.80, no δ=5.95, p=0.11). CONCLUSION:: For brain AVMs treated with CKRS, the addition of 3-D cerebral angiography to CT/MRI fusions for diagnostic accuracy results in a statistically significant reduction in contoured nidal volume as compared to standard CT/MRI fusion-based contouring.

  View details for DOI 10.1227/01.neu.0000430285.00928.30

  View details for PubMedID 23615081

• Pituitary stalk Langerhans cell histiocytosis treated with CyberKnife radiosurgery. Clinical neurology and neurosurgery Hong, W., Murovic, J. A., Gibbs, I., Vogel, H., Chang, S. D. 2013; 115 (5): 573-577

  Abstract

  Langerhans cell histiocytosis (LCH) is a rare idiopathic disease that is characterized by clonal proliferation of Langerhans histiocytes in various parts of the body. These atypical cells have been found to infiltrate single or multiple organs, including bone, lungs, liver, spleen, lymph nodes, and skin. Central nervous system invasion in LCH patients has rarely been reported, especially in the adult population.We describe three histopathologically confirmed cases of adult LCH that involves both the pituitary stalk and hypothalamus, and report our limited experience of such cases in this location that has been treated with CyberKnife radio surgery.The treatment goal of controlling lesion growth is achieved by CyberKnife radiosurgery in this case series. All patients tolerated the treatment well without obvious complications.

  View details for DOI 10.1016/j.clineuro.2012.07.004

  View details for PubMedID 22835714

• Literature review of various treatment plans and outcomes for brain metastases from colorectal cancer. World neurosurgery Murovic, J. A., Chang, S. D. 2013; 79 (3-4): 435-436

  View details for DOI 10.1016/j.wneu.2011.12.071

  View details for PubMedID 22381286

• Cavity Volume Dynamics After Resection of Brain Metastases and Timing of Postresection Cavity Stereotactic Radiosurgery NEUROSURGERY Atalar, B., Choi, C. Y., Harsh, G. R., Chang, S. D., Gibbs, I. C., Adler, J. R., Soltys, S. G. 2013; 72 (2): 180-185

  Abstract

  An alternative treatment option to whole-brain irradiation after surgical resection of brain metastases is resection cavity stereotactic radiosurgery (SRS).To review the dynamics of cavity volume change after surgical resection with the goal of determining the optimal timing for cavity SRS.Preresection tumor, postresection/pre-SRS cavity, and post-SRS cavity volumes were measured for 68 cavities in 63 patients treated with surgery and postresection cavity SRS. Percent differences between volumes were calculated and correlation analyses were performed to assess volume changes before and after SRS.For the majority of tumors, the postresection cavity volume was smaller than the preresection tumor volume by a median percent volume change of -29% (range, -82% to 1258%), with larger preresection tumors resulting in greater cavity shrinkage (P < .001). To determine the optimal timing for cavity SRS, we examined cavity volume dynamics by comparing the early postresection (postoperative days 0-3) and treatment planning magnetic resonance imaging scans (median time to magnetic resonance imaging, 20 days; range, 9-33 days) and found no association between the postresection day number and volume change (P = .75). The volume decrease resulting from tumor resection was offset by the addition of a 2-mm clinical target volume margin, which is our current technique.The greatest volume change occurs immediately after surgery (postoperative days 0-3) with no statistically significant volume change occurring up to 33 days after surgery for most patients. Therefore, there is no benefit of cavity shrinkage in waiting longer than the first 1 to 2 weeks to perform cavity SRS.

  View details for DOI 10.1227/NEU.0b013e31827b99f3

  View details for Web of Science ID 000313734400028

  View details for PubMedID 23149969

• Aberrant expression of lymphatic-associated proteins in human brain arteriovenous malformations Shoemaker, L., Fuentes, L., Santiago, S., Steinberg, G., Chang, S. SPRINGER. 2013: 269–70

  View details for Web of Science ID 000312658800114

• Multisession CyberKnife radiosurgery for post-surgical residual and recurrent pituitary adenoma: preliminary result from one center. Journal of radiosurgery and SBRT Chen, Y. H., Chang, S. D., Ma, H. I., Chou, Y. C., Chao, H. L., Jen, Y. M., Ju, D. T. 2013; 2 (2): 105–17

  Abstract

  To evaluate the efficacy of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) for patients with pituitary adenoma.We conducted a retrospective review of all patients treated by image-guided radiosurgery at our institution between August 2007 and June 2009. Twentytwo patients with pituitary adenoma were identified. The median follow-up period from date of treatment was 30.8 + 7.7months. The median patient age was 56 years. The mean tumor volume was 4.1 + 2.8 mL (range, 0.8-16.0 mL), and the prescribed dose was 25 Gy (5 Gy x 5).Tumors were treated with a mean coverage of 95.1 ± 1.3%(range 90.2-99.1%), a mean conformality index of 1.4 ± 0.4 (range, 1.2-1.8), and a mean treatment isodose line of 76.4 ± 3.0%(range70-83%). The primary endpoints were radiographic and endocrinological tumor control. The local radiographic control rate in this series was 100% (22/22). Radiographic evidence of tumor necrosis developed in 3 patients (13.7%).CyberKnife multisession radiosurgery of 25 Gy (5 Gy x 5) provided excellent local control with acceptable adverse effect in patients with pituitary adenoma post-transsphenoidal resection. This preliminary study provides data that supports the belief that the optic nerve and chiasm tolerate the above dosing regimens in perichiasmatic pituitary adenomas, and this dosing regimen may achieve satisfactory radiographic and endocrinological tumor control for post-transsphenoidal resection.

  View details for PubMedID 29296349

• Robotic Skull Base Surgery via Supraorbital Keyhole Approach: A Cadaveric Study NEUROSURGERY Hong, W., Tsai, J., Chang, S. D., Sorger, J. M. 2013; 72: A33-A38

  View details for DOI 10.1227/NEU.0b013e318270d9de

  View details for Web of Science ID 000315848100007

• Spontaneous intracranial hypotension secondary to anterior thoracic osteophyte: Resolution after primary dural repair via posterior approach. International journal of surgery case reports Veeravagu, A., Gupta, G., Jiang, B., Berta, S. C., Mindea, S. A., Chang, S. D. 2013; 4 (1): 26-29

  Abstract

  Spontaneous intracranial hypotension (SIH) is an uncommon syndrome widely attributed to CSF hypovolemia, typically secondary to spontaneous CSF leak. Although commonly associated with postural headache and variable neurological symptoms, one of the most severe consequences of SIH is bilateral subdural hematomas with resultant neurological deterioration.We present the case of a patient diagnosed with SIH secondary to an anteriorly positioned thoracic osteophyte with resultant dural disruption, who after multiple attempts at nonsurgical management developed bilateral subdural hematomas necessitating emergent surgical intervention. The patient underwent a unilateral posterior repair of his osteophyte with successful anterior decompression. At 36months follow up, the patient reported completely resolved headaches with no focal neurological deficits.We outline our posterior approach to repair of the dural defect and review the management algorithm for the treatment of patients with SIH. We also examine the current hypotheses as to the origin, pathophysiology, diagnosis and treatment of this syndrome.A posterior approach was utilized to repair the dural defect caused by an anterior thoracic osteophyte in a patient with severe SIH complicated by bilateral subdural hematomas. This approach minimizes morbidity compared to an anterior approach and allowed for removal of the osteophyte and repair of the dural defect.

  View details for DOI 10.1016/j.ijscr.2012.06.009

  View details for PubMedID 23108168

  View details for PubMedCentralID PMC3537944

• Robotic skull base surgery via supraorbital keyhole approach: a cadaveric study. Neurosurgery Hong, W., Tsai, J., Chang, S. D., Sorger, J. M. 2013; 72: 33-38

  Abstract

  The supraorbital keyhole approach has been used in anterior skull base tumor and aneurysm surgery. However, there are debates regarding the safety and limitations of this kind of approach.To determine the feasibility and potential benefits of surgical robotic technology in minimally invasive neurosurgery.Two fresh cadaver heads were studied with the da Vinci Surgical System with 0° and 30° stereoscopic endoscopes to visualize neuroanatomy. The ability of the system to suture and place clips under the keyhole approach was tested.The da Vinci Surgical System was used throughout the supraorbital transeyebrow keyhole approach. With the use of standard microdissection techniques, the optic nerve, optic chiasm, carotid artery, and third cranial nerve were visualized. The sylvian fissure was then exposed from the proximal sylvian membrane to the distal M1 segment. With the EndoWrist microforceps, suturing can be achieved smoothly to close a defect created on the M2 artery. Although the benefits in adjusting clips during aneurysm surgery could be provided by an articulating applier, a proper robotic applier is not currently available.The minimally invasive supraorbital keyhole surgery can be achieved with the da Vinci Surgical System in cadaver models. This system provides neurosurgeons with broader vision and articulable instruments, which standard microsurgical systems do not provide. Further studies are necessary to evaluate the safety and benefits of using the da Vinci Surgical System in minimally invasive neurosurgery.

  View details for DOI 10.1227/NEU.0b013e318270d9de

  View details for PubMedID 23254810

• Outcomes After Stereotactic Radiosurgery and Various Adjuvant Treatments for Recurrent Glioblastoma Multiforme: A Current Literature Review and Comparison of Multiple Factors that Impact Outcome WORLD NEUROSURGERY Murovic, J. A., Chang, S. D. 2012; 78 (6): 588-591

  View details for DOI 10.1016/j.wneu.2012.06.005

  View details for Web of Science ID 000312950100013

  View details for PubMedID 22705758

• What Is the Optimal Treatment of Large Brain Metastases? An Argument for a Multidisciplinary Approach INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Choi, C. Y., Chang, S. D., Gibbs, I. C., Adler, J. R., Harsh, G. R., Atalar, B., Lieberson, R. E., Soltys, S. G. 2012; 84 (3): 688-693

  Abstract

  Single-modality treatment of large brain metastases (>2 cm) with whole-brain irradiation, stereotactic radiosurgery (SRS) alone, or surgery alone is not effective, with local failure (LF) rates of 50% to 90%. Our goal was to improve local control (LC) by using multimodality therapy of surgery and adjuvant SRS targeting the resection cavity.We retrospectively evaluated 97 patients with brain metastases >2 cm in diameter treated with surgery and cavity SRS. Local and distant brain failure (DF) rates were analyzed with competing risk analysis, with death as a competing risk. The overall survival rate was calculated by the Kaplain-Meier product-limit method.The median imaging follow-up duration for all patients was 10 months (range, 1-80 months). The 12-month cumulative incidence rates of LF, with death as a competing risk, were 9.3% (95% confidence interval [CI], 4.5%-16.1%), and the median time to LF was 6 months (range, 3-17 months). The 12-month cumulative incidence rate of DF, with death as a competing risk, was 53% (95% CI, 43%-63%). The median survival time for all patients was 15.6 months. The median survival times for recursive partitioning analysis classes 1, 2, and 3 were 33.8, 13.7, and 9.0 months, respectively (p = 0.022). On multivariate analysis, Karnofsky Performance Status (≥80 vs. <80; hazard ratio 0.54; 95% CI 0.31-0.94; p = 0.029) and maximum preoperative tumor diameter (hazard ratio 1.41; 95% CI 1.08-1.85; p = 0.013) were associated with survival. Five patients (5%) required intervention for Common Terminology Criteria for Adverse Events v4.02 grade 2 and 3 toxicity.Surgery and adjuvant resection cavity SRS yields excellent LC of large brain metastases. Compared with other multimodality treatment options, this approach allows patients to avoid or delay whole-brain irradiation without compromising LC.

  View details for DOI 10.1016/j.ijrobp.2012.01.028

  View details for Web of Science ID 000309560600051

  View details for PubMedID 22445007

• Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Modlin, L. A., Atalar, B., Choi, C. Y., Gibbs, I. C., Chang, S. D., Harsh, G. R., Adler, J. R., Soltys, S. G. ELSEVIER SCIENCE INC. 2012: S116–S117

  View details for Web of Science ID 000310542900291

• Stereotactic Radiosurgery for the Treatment of Spinal Metastases: Analysis of Tumor Control and Patterns of Failure 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D., Modlin, L. A., Choi, C. Y. ELSEVIER SCIENCE INC. 2012: S195–S195

  View details for Web of Science ID 000310542900488

• Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Choi, C. Y., Chang, S. D., Gibbs, I. C., Adler, J. R., Harsh, G. R., Lieberson, R. E., Soltys, S. G. 2012; 84 (2): 336-342

  Abstract

  Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity.We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competing risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests.The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients.Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.

  View details for DOI 10.1016/j.ijrobp.2011.12.009

  View details for Web of Science ID 000308062700035

  View details for PubMedID 22652105

• Intracranial hypotension producing reversible coma: a systematic review, including three new cases A review JOURNAL OF NEUROSURGERY Loya, J. J., Mindea, S. A., Yu, H., Venkatasubramanian, C., Chang, S. D., Burns, T. C. 2012; 117 (3): 615-628

  Abstract

  Intracranial hypotension is a disorder of CSF hypovolemia due to iatrogenic or spontaneous spinal CSF leakage. Rarely, positional headaches may progress to coma, with frequent misdiagnosis. The authors review reported cases of verified intracranial hypotension-associated coma, including 3 previously unpublished cases, totaling 29. Most patients presented with headache prior to neurological deterioration, with positional symptoms elicited in almost half. Eight patients had recently undergone a spinal procedure such as lumbar drainage. Diagnostic workup almost always began with a head CT scan. Subdural collections were present in 86%; however, intracranial hypotension was frequently unrecognized as the underlying cause. Twelve patients underwent one or more procedures to evacuate the collections, sometimes with transiently improved mental status. However, no patient experienced lasting neurological improvement after subdural fluid evacuation alone, and some deteriorated further. Intracranial hypotension was diagnosed in most patients via MRI studies, which were often obtained due to failure to improve after subdural hematoma (SDH) evacuation. Once the diagnosis of intracranial hypotension was made, placement of epidural blood patches was curative in 85% of patients. Twenty-seven patients (93%) experienced favorable outcomes after diagnosis and treatment; 1 patient died, and 1 patient had a morbid outcome secondary to duret hemorrhages. The literature review revealed that numerous additional patients with clinical histories consistent with intracranial hypotension but no radiological confirmation developed SDH following a spinal procedure. Several such patients experienced poor outcomes, and there were multiple deaths. To facilitate recognition of this treatable but potentially life-threatening condition, the authors propose criteria that should prompt intracranial hypotension workup in the comatose patient and present a stepwise management algorithm to guide the appropriate diagnosis and treatment of these patients.

  View details for DOI 10.3171/2012.4.JNS112030

  View details for Web of Science ID 000307627100031

  View details for PubMedID 22725982

• Esophageal tolerance to high-dose stereotactic ablative radiotherapy DISEASES OF THE ESOPHAGUS Abelson, J. A., Murphy, J. D., Loo, B. W., Chang, D. T., Daly, M. E., Wiegner, E. A., Hancock, S., Chang, S. D., Le, Q., Soltys, S. G., Gibbs, I. C. 2012; 25 (7): 623-629

  Abstract

  Dose-volume parameters are needed to guide the safe administration of stereotactic ablative radiotherapy (SABR). We report on esophageal tolerance to high-dose hypofractionated radiation in patients treated with SABR. Thirty-one patients with spine or lung tumors received single- or multiple-fraction SABR to targets less than 1 cm from the esophagus. End points evaluated include D(5cc) (minimum dose in Gy to 5 cm(3) of the esophagus receiving the highest dose), D(2cc) , D(1cc) , and D(max) (maximum dose to 0.01 cm(3) ). Multiple-fraction treatments were correlated using the linear quadratic and linear quadratic-linear/universal survival models. Three esophageal toxicity events occurred, including esophagitis (grade 2), tracheoesophageal fistula (grade 4-5), and esophageal perforation (grade 4-5). Chemotherapy was a cofactor in the high-grade events. The median time to development of esophageal toxicity was 4.1 months (range 0.6-6.1 months). Two of the three events occurred below a published D(5cc) threshold, all three were below a D(2cc) threshold, and one was below a D(max) threshold. We report a dosimetric analysis of incidental dose to the esophagus from SABR. High-dose hypofractionated radiotherapy led to a number of high-grade esophageal adverse events, suggesting that conservative parameters to protect the esophagus are necessary when SABR is used, especially in the setting of chemotherapy or prior radiotherapy.

  View details for DOI 10.1111/j.1442-2050.2011.01295.x

  View details for PubMedID 22168251

• CyberKnife stereotactic radiosurgery for the treatment of intramedullary spinal cord metastases JOURNAL OF CLINICAL NEUROSCIENCE Veeravagu, A., Lieberson, R. E., Mener, A., Chen, Y., Soltys, S. G., Gibbs, I. C., Adler, J. R., Tian, A. G., Chang, S. D. 2012; 19 (9): 1273-1277

  Abstract

  Spinal cord intramedullary metastases are uncommon and treatment options are limited. We reviewed our experience treating these lesions with radiosurgery to assess safety and efficacy, and to define preliminary treatment recommendations. With Institutional Review Board approval, we identified nine patients with 11 metastases treated with radiosurgery at Stanford University Hospital, between 2000 and 2010. We also reviewed all available published series discussing the treatment of spinal cord metastases. Our patients ranged in age from 33 years to 77 years (median 63 years) and included seven women and two men. Tumors ranged in size from 0.12 cm(3) to 6.4 cm(3) (median 0.48 cm(3)). Five were from breast cancer, two were non-small cell lung cancers, one was a cystic adenocarcinoma, and one was from an epithelioid hemangioepithelioma. All patients had neurologic deficits and multiple other metastases. We delivered 14 Gy to 27 Gy (median 21 Gy) in one to five (median 3) fractions. Complete follow-up was available for all nine patients. One patient remains alive 14 months after therapy. Of the eight deceased patients, survival ranged from one month and two days to nine months and six days (median four months and four days). There were no local recurrences or worsened neurological deficits. To our knowledge this is the largest reported series of spinal cord intramedullary metastases treated with radiosurgery. Survival was poor due to systemic disease, but radiosurgery appears to be safe and prevented local recurrences. With fewer sessions than conventional radiation and less morbidity than surgery, we feel radiosurgery is appropriate for the palliative treatment of these lesions.

  View details for DOI 10.1016/j.jocn.2012.02.002

  View details for Web of Science ID 000308730900014

  View details for PubMedID 22766103

• Management of intracranial and extracranial chordomas with CyberKnife stereotactic radiosurgery JOURNAL OF CLINICAL NEUROSCIENCE Jiang, B., Veeravagu, A., Lee, M., Harsh, G. R., Lieberson, R. E., Bhatti, I., Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D. 2012; 19 (8): 1101-1106

  Abstract

  Chordomas are rare, malignant bone tumors of the axial skeleton, occurring particularly at the cranial base or in the sacro-coccygeal region. Although slow growing, chordomas are locally aggressive and challenging to treat. We evaluate the outcomes of skull base and spinal chordomas in 20 patients treated with CyberKnife (CK) stereotactic radiosurgery (SRS) (Accuray, Sunnyvale, CA, USA) between 1994 and 2010 at Stanford Hospital. There were 12 males and eight females (10-78 years; median age: 51.5 years). Eleven patients received CK as primary adjuvant therapy and nine patients received CK for multiple recurrences. The average tumor volume treated was 16.1cm(3) (2.4-45.9 cm(3)), with a mean marginal dose of 32.5 Gy (18-50 Gy). Median follow-up was 34 months (2-131 months). Overall, tumor control was achieved in 11 patients (55%), with eight patients showing tumor size reduction. However, nine patients showed progression and eventually succumbed to the disease (mean time from CK to death was 26.3 months). Of the patients treated with CK as the primary adjuvant therapy, 81.8% had stable or improved outcomes. Only 28.6% of those treated with CK for recurrences had stable or improved outcomes. The overall Kaplan-Meyer survival at five years from the first CK treatment was 52.5%. Moderate tumor control rates can be achieved with few complications with CK SRS. Poor control is associated with complex multiple surgical resections, long delay between initial resection and CK therapy, and recurrently aggressive disease uncontrolled by prior radiation.

  View details for DOI 10.1016/j.jocn.2012.01.005

  View details for Web of Science ID 000306500400009

  View details for PubMedID 22727205

• Neurocognitive Changes in Pituitary Adenoma Patients After Fractionated External Beam Radiotherapy versus Gamma Knife Radiosurgery WORLD NEUROSURGERY Murovic, J., Chang, S. 2012; 78 (1-2)

  View details for DOI 10.1016/J.WNEU.2011.12.060

  View details for Web of Science ID 000307933400016

  View details for PubMedID 22381297

• Multimodality management of Spetzler-Martin Grade III arteriovenous malformations JOURNAL OF NEUROSURGERY Pandey, P., Marks, M. P., Harraher, C. D., Westbroek, E. M., Chang, S. D., Do, H. M., Levy, R. P., Dodd, R. L., Steinberg, G. K. 2012; 116 (6): 1279-1288

  Abstract

  Grade III arteriovenous malformations (AVMs) are diverse because of their variations in size (S), location in eloquent cortex (E), and presence of central venous drainage (V). Because they may have implications for management and outcome, the authors evaluated these variations in the present study.Between 1984 and 2010, 100 patients with Grade III AVMs were treated. The AVMs were categorized by Spetzler-Martin characteristics as follows: Type 1 = S1E1V1, Type 2 = S2E1V0, Type 3 = S2E0V1, and Type 4 = S3E0V0. The occurrence of a new neurological deficit, functional status (based on modified Rankin Scale [mRS] score) at discharge and follow-up, and radiological obliteration were correlated with demographic and morphological characteristics.One hundred patients (49 female and 51 male; age range 5-68 years, mean 35.8 years) were evaluated. The size of AVMs was less than 3 cm in 28 patients, 3-6 cm in 71, and greater than 6 cm in 1; 86 AVMs were located in eloquent cortex and 38 had central drainage. The AVMs were Type 1 in 28 cases, Type 2 in 60, Type 3 in 11, and Type 4 in 1. The authors performed embolization in 77 patients (175 procedures), surgery in 64 patients (74 surgeries), and radiosurgery in 49 patients (44 primary and 5 postoperative). The mortality rate following the management of these AVMs was 1%. Fourteen patients (14%) had new neurological deficits, with 5 (5%) being disabling (mRS score > 2) and 9 (9%) being nondisabling (mRS score ≤ 2) events. Patients with Type 1 AVMs (small size) had the best outcome, with 1 (3.6%) in 28 having a new neurological deficit, compared with 72 patients with larger AVMs, of whom 13 (18.1%) had a new neurological deficit (p < 0.002). Older age (> 40 years), malformation size > 3 cm, and nonhemorrhagic presentation predicted the occurrence of new deficits (p < 0.002). Sex, eloquent cortex, and venous drainage did not confer any benefit. In 89 cases follow-up was adequate for data to be included in the obliteration analysis. The AVM was obliterated in 78 patients (87.6%), 69 of them (88.5%) demonstrated on angiography and 9 on MRI /MR angiography. There was no difference between obliteration rates between different types of AVMs, size, eloquence, and drainage. Age, sex, and clinical presentation also did not predict obliteration.Multimodality management of Grade III AVMs results in a high rate of obliteration, which was not influenced by size, venous drainage, or eloquent location. However, the development of new neurological deficits did correlate with size, whereas eloquence and venous drainage did not affect the neurological complication rate. The authors propose subclassifying the Grade III AVMs according to their size (< 3 and ≥ 3 cm) to account for treatment risk.

  View details for DOI 10.3171/2012.3.JNS111575

  View details for PubMedID 22482792

• Stereotactic Radiosurgery as the Primary Treatment for New and Recurrent Paragangliomas: Is Open Surgical Resection Still the Treatment of Choice? WORLD NEUROSURGERY Lieberson, R. E., Adler, J. R., Soltys, S. G., Choi, C., Gibbs, I. C., Chang, S. D. 2012; 77 (5-6): 745-761

  Abstract

  Paragangliomas (PGs) or glomus tumors are rare, and publications comparing treatment alternatives are few. We sought to analyze our experience with stereotactic radiosurgery (SRS), review the literature, and develop treatment guidelines.We retrospectively examined the outcomes of 41 PGs in 36 patients treated with SRS at Stanford. Our data from medical records, telephone interviews, and imaging studies were combined with previously reported SRS data and compared to results following other treatments.With a median clinical follow-up of 4.8 years (3.9 years radiographic), local control was 100%. Complications included increase in preexistent vertigo in one patient and transient cranial neuropathies in two patients. Published surgical series describe a lower local control rate as well as more frequent and severe complications. Published radiation therapy (RT) series document a slightly lower local control rate than SRS, but SRS can be delivered more quickly and conveniently. Open surgery and other combinations of treatments appear to be required for several subpopulations of PG patients.We feel that SRS should be the primary treatment for most new and recurrent PGs. Even some very large PGs are appropriate for SRS. RT remains an appropriate option in some centers, especially those where SRS is not available. PGs occurring in the youngest patients, catecholamine secreting PGs, and PGs causing rapidly progressing neurologic deficits may be more appropriate for open resection. Metastatic PGs may benefit from combinations of chemotherapy and SRS or RT. Treatment guidelines are proposed.

  View details for DOI 10.1016/j.wneu.2011.03.026

  View details for Web of Science ID 000307523800038

  View details for PubMedID 22818172

• Stereotactic radiosurgery for central neurocytoma: a quantitative systematic review JOURNAL OF NEURO-ONCOLOGY Park, H., Chang, S. D. 2012; 108 (1): 115-121

  Abstract

  Central neurocytoma was originally described as a rare benign neuronal tumor. However, progression and local recurrences after surgery are well recognized. Stereotactic radiosurgery is another option for treatment of CN. In order to evaluate the efficacy of SRS, we performed a quantitative systematic review of the available data on SRS for CN. To identify eligible studies, systematic searches for all CNs treated with SRS were conducted in major scientific publication databases. English studies published prior to May 2011 were reviewed and summarized with reference to the inclusion and exclusion criteria. Tumor local control was analyzed. Heterogeneity and publication bias were assessed, and the summary control rate and 95%confidence interval (CI) were calculated from the raw data.Of 35 eligible studies, five with a total of 64 CNs were included in this quantitative analysis. Four studies reported a mean or median follow-up time of[60 months. The test of heterogeneity was non-significant among the included studies. Publication bias was observed as indicated by an asymmetric funnel plot. There was non-significance in Begg’s test and Egger’s test. The estimated cumulative rate of neuro-imaging tumor control was 91.1% (95%CI = 80.2–96.3%) at a mean follow-up of 59.3 months(range 6–140 months). The P-value was\0.0001 under a random-effect model. Sensitivity analysis showed a similar summary control rates (89.5–93.7%). Based on the summary local control rate of SRS for CN found in this quantitative analysis, we suggest that single session SRS is an effective and safe alternative therapy for recurrent or residual CN. However, the results of our analysis are limited by the predominance of case series studies due to scarcity of published research. Further randomized trials of CN patients via multicenter consortia should be considered for supplementing the weak points in our quantitative analysis.

  View details for DOI 10.1007/s11060-012-0803-x

  View details for Web of Science ID 000303469600013

  View details for PubMedID 22442020

• NORMAL TISSUE COMPLICATION PROBABILITY ESTIMATION BY THE LYMAN-KUTCHER-BURMAN METHOD DOES NOT ACCURATELY PREDICT SPINAL CORD TOLERANCE TO STEREOTACTIC RADIOSURGERY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Luxton, G., Choi, C. Y., Gibbs, I. C., Chang, S. D., Adler, J. R., Soltys, S. G. 2012; 82 (5): 2025-2032

  Abstract

  To determine whether normal tissue complication probability (NTCP) analyses of the human spinal cord by use of the Lyman-Kutcher-Burman (LKB) model, supplemented by linear-quadratic modeling to account for the effect of fractionation, predict the risk of myelopathy from stereotactic radiosurgery (SRS).From November 2001 to July 2008, 24 spinal hemangioblastomas in 17 patients were treated with SRS. Of the tumors, 17 received 1 fraction with a median dose of 20 Gy (range, 18-30 Gy) and 7 received 20 to 25 Gy in 2 or 3 sessions, with cord maximum doses of 22.7 Gy (range, 17.8-30.9 Gy) and 22.0 Gy (range, 20.2-26.6 Gy), respectively. By use of conventional values for α/β, volume parameter n, 50% complication probability dose TD(50), and inverse slope parameter m, a computationally simplified implementation of the LKB model was used to calculate the biologically equivalent uniform dose and NTCP for each treatment. Exploratory calculations were performed with alternate values of α/β and n.In this study 1 case (4%) of myelopathy occurred. The LKB model using radiobiological parameters from Emami and the logistic model with parameters from Schultheiss overestimated complication rates, predicting 13 complications (54%) and 18 complications (75%), respectively. An increase in the volume parameter (n), to assume greater parallel organization, improved the predictive value of the models. Maximum-likelihood LKB fitting of α/β and n yielded better predictions (0.7 complications), with n = 0.023 and α/β = 17.8 Gy.The spinal cord tolerance to the dosimetry of SRS is higher than predicted by the LKB model using any set of accepted parameters. Only a high α/β value in the LKB model and only a large volume effect in the logistic model with Schultheiss data could explain the low number of complications observed. This finding emphasizes that radiobiological models traditionally used to estimate spinal cord NTCP may not apply to the dosimetry of SRS. Further research with additional NTCP models is needed.

  View details for DOI 10.1016/j.ijrobp.2011.03.004

  View details for Web of Science ID 000301891300082

  View details for PubMedID 21531516

• Trigeminal neuralgia treatment dosimetry of the Cyberknife MEDICAL DOSIMETRY Ho, A., Lo, A. T., Dieterich, S., Soltys, S. G., Gibbs, I. C., Chang, S. G., Adler, J. R. 2012; 37 (1): 42-46

  Abstract

  There are 2 Cyberknife units at Stanford University. The robot of 1 Cyberknife is positioned on the patient's right, whereas the second is on the patient's left. The present study examines whether there is any difference in dosimetry when we are treating patients with trigeminal neuralgia when the target is on the right side or the left side of the patient. In addition, we also study whether Monte Carlo dose calculation has any effect on the dosimetry. We concluded that the clinical and dosimetric outcomes of CyberKnife treatment for trigeminal neuralgia are independent of the robot position. Monte Carlo calculation algorithm may be useful in deriving the dose necessary for trigeminal neuralgia treatments.

  View details for DOI 10.1016/j.meddos.2010.12.012

  View details for Web of Science ID 000301035000009

  View details for PubMedID 21723113

• Junctional Visual Field Loss in a Case of Wyburn-Mason Syndrome JOURNAL OF NEURO-OPHTHALMOLOGY Liu, A., Chen, Y., Chang, S., Liao, Y. J. 2012; 32 (1): 42-44

  Abstract

  A previously healthy girl failed a routine eye screening at the age of 6 years. Her visual fields showed generalized depression in the right eye and a superotemporal defect in the left eye, consistent with a junctional scotoma. Funduscopic examination and fluorescein angiography revealed markedly dilated tortuous vascular loops with arteriovenous communications consistent with retinal arteriovenous malformations (AVMs). MRI of the brain and cerebral angiography demonstrated right ophthalmic and right thalamic AVMs, with compression and atrophy of the right optic chiasm. This represents a case of Wyburn-Mason syndrome with a junctional scotoma.

  View details for DOI 10.1097/WNO.0b013e31821aeefb

  View details for Web of Science ID 000300607000009

  View details for PubMedID 21613961

• Clinical Neuroproteomics and Biomarkers: From Basic Research to Clinical Decision Making NEUROSURGERY Shoemaker, L. D., Achrol, A. S., Sethu, P., Steinberg, G. K., Chang, S. D. 2012; 70 (3): 518-525

  Abstract

  Clinical neuroproteomics aims to advance our understanding of disease and injury affecting the central and peripheral nervous systems through the study of protein expression and the discovery of protein biomarkers to facilitate diagnosis and treatment. The general premise of the biomarker field is that in vivo factors present in either tissue or circulating biofluids, reflect pathological changes, and can be identified and analyzed. This approach offers an opportunity to illuminate changes occurring at both the population and patient levels toward the realization of personalized medicine. This review is intended to provide research-driven clinicians with an overview of protein biomarkers of disease and injury for clinical use and to highlight methodology and potential pitfalls. We examine the neuroproteomic biomarker field and discuss the hallmarks and the challenges of clinically relevant biomarker discovery relating to central nervous system pathology. We discuss the issues in the maturation of potential biomarkers from discovery to Food and Drug Administration approval and review several platforms for protein biomarker discovery, including protein microarray and mass spectrometry-based proteomics. We describe the application of microfluidic technologies to the evolution of a robust clinical test. Finally, we highlight several biomarkers currently in use for cancer, ischemia, and injury in the central nervous system. Future efforts using these technologies will result in the maturation of existing and the identification of de novo biomarkers that could guide clinical decision making and advance diagnostic and therapeutic options for the treatment of neurological disease and injury.

  View details for DOI 10.1227/NEU.0b013e3182333a26

  View details for Web of Science ID 000300781700008

  View details for PubMedID 21866062

• Intramedullary spinal cord metastasis from prostate carcinoma: a case report. Journal of medical case reports Lieberson, R. E., Veeravagu, A., Eckermann, J. M., Doty, J. R., Jiang, B., Andrews, R., Chang, S. D. 2012; 6 (1): 139-?

  Abstract

  Although vertebral and epidural metastases are common, intradural metastases and intramedullary spinal cord metastases are rare. The indications for the treatment of intramedullary spinal cord metastases remain controversial. We present the first biopsy-proven case of an intramedullary spinal cord metastasis from adenocarcinoma of the prostate.Our patient was a 68-year-old right-handed Caucasian man with a Gleason grade 4 + 3 prostate adenocarcinoma who had previously undergone a prostatectomy, androgen blockade and transurethral debulking. He presented with new-onset saddle anesthesia and fecal incontinence. Magnetic resonance imaging demonstrated a spindle-shaped intramedullary lesion of the conus medullaris. Our patient underwent decompression and an excisional biopsy; the lesion's pathology was consistent with metastatic adenocarcinoma of the prostate. Postoperatively, our patient received CyberKnife® radiosurgery to the resection cavity at a marginal dose of 27Gy to the 85% isodose line. At three months follow-up, our patient remains neurologically stable with no new deficits or lesions.We review the literature and discuss the indications for surgery and radiosurgery for intramedullary spinal cord metastases. We also report the novel use of stereotactic radiosurgery to sterilize the resection cavity following an excisional biopsy of the metastasis.

  View details for DOI 10.1186/1752-1947-6-139

  View details for PubMedID 22657386

  View details for PubMedCentralID PMC3419088

• Potential application of hydrogen in traumatic and surgical brain injury, stroke and neonatal hypoxia-ischemia. Medical gas research Eckermann, J. M., Krafft, P. R., Shoemaker, L., Lieberson, R. E., Chang, S. D., Colohan, A. 2012; 2 (1): 11-?

  Abstract

  This article summarized findings of current preclinical studies that implemented hydrogen administration, either in the gas or liquid form, as treatment application for neurological disorders including traumatic brain injury (TBI), surgically induced brain injury (SBI), stroke, and neonatal hypoxic-ischemic brain insult (HI). Most reviewed studies demonstrated neuroprotective effects of hydrogen administration. Even though anti-oxidative potentials have been reported in several studies, further neuroprotective mechanisms of hydrogen therapy remain to be elucidated. Hydrogen may serve as an adjunct treatment for neurological disorders.

  View details for DOI 10.1186/2045-9912-2-11

  View details for PubMedID 22515516

  View details for PubMedCentralID PMC3353846

• Stereotactic radiosurgery for central neurocytoma: a quantitative systematic review. Journal of neuro-oncology Park, H. K., Chang, S. D. 2012

  Abstract

  Central neurocytoma was originally described as a rare benign neuronal tumor. However, progression and local recurrences after surgery are well recognized. Stereotactic radiosurgery is another option for treatment of CN. In order to evaluate the efficacy of SRS, we performed a quantitative systematic review of the available data on SRS for CN. To identify eligible studies, systematic searches for all CNs treated with SRS were conducted in major scientific publication databases. English studies published prior to May 2011 were reviewed and summarized with reference to the inclusion and exclusion criteria. Tumor local control was analyzed. Heterogeneity and publication bias were assessed, and the summary control rate and 95% confidence interval (CI) were calculated from the raw data. Of 35 eligible studies, five with a total of 64 CNs were included in this quantitative analysis. Four studies reported a mean or median follow-up time of >60 months. The test of heterogeneity was non-significant among the included studies. Publication bias was observed as indicated by an asymmetric funnel plot. There was non-significance in Begg's test and Egger's test. The estimated cumulative rate of neuro-imaging tumor control was 91.1% (95% CI = 80.2-96.3%) at a mean follow-up of 59.3 months (range 6-140 months). The P-value was <0.0001 under a random-effect model. Sensitivity analysis showed a similar summary control rates (89.5-93.7%). Based on the summary local control rate of SRS for CN found in this quantitative analysis, we suggest that single session SRS is an effective and safe alternative therapy for recurrent or residual CN. However, the results of our analysis are limited by the predominance of case series studies due to scarcity of published research. Further randomized trials of CN patients via multicenter consortia should be considered for supplementing the weak points in our quantitative analysis.

  View details for DOI 10.1007/s11060-012-0803-x

  View details for PubMedID 22302467

• A giant cell tumor of the cranial base treated by stereotactic radiosurgery Journal of Radiosurgery and SBRT Kim EY, Murovic JA, Gibbs IC, Shuer LM, Chang SD 2012; 1: 333-337
• Multisession Stereotactic Radiosurgery for Vestibular Schwannomas: Single-Institution Experience With 383 Cases NEUROSURGERY Hansasuta, A., Choi, C. Y., Gibbs, I. C., Soltys, S. G., Tse, V. C., Lieberson, R. E., Hayden, M. G., Sakamoto, G. T., Harsh, G. R., Adler, J. R., Chang, S. D. 2011; 69 (6): 1200-1209

  Abstract

  Single-session stereotactic radiosurgery (SRS) treatment of vestibular schwannomas results in excellent tumor control. It is not known whether functional outcomes can be improved by fractionating the treatment over multiple sessions.To examine tumor control and complication rates after multisession SRS.Three hundred eighty-three patients treated with SRS from 1999 to 2007 at Stanford University Medical Center were retrospectively reviewed. Ninety percent were treated with 18 Gy in 3 sessions, targeting a median tumor volume of 1.1 cm3 (range, 0.02-19.8 cm3).During a median follow-up duration of 3.6 years (range, 1-10 years), 10 tumors required additional treatment, resulting in 3- and 5-year Kaplan-Meier tumor control rates of 99% and 96%, respectively. Five-year tumor control rate was 98% for tumors < 3.4 cm3. Neurofibromatosis type 2-associated tumors were associated with worse tumor control (P = .02). Of the 200 evaluable patients with pre-SRS serviceable hearing (Gardner-Robertson grade 1 and 2), the crude rate of serviceable hearing preservation was 76%. Smaller tumor volume was associated with hearing preservation (P = .001). There was no case of post-SRS facial weakness. Eight patients (2%) developed trigeminal dysfunction, half of which was transient.Multisession SRS treatment of vestibular schwannomas results in an excellent rate of tumor control. The hearing, trigeminal nerve, and facial nerve function preservation rates reported here are promising.

  View details for DOI 10.1227/NEU.0b013e318222e451

  View details for Web of Science ID 000296794500024

  View details for PubMedID 21558974

• RADIOSURGERY OF GLOMUS JUGULARE TUMORS: A META-ANALYSIS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Guss, Z. D., Batra, S., Limb, C. J., Li, G., Sughrue, M. E., Redmond, K., Rigamonti, D., Parsa, A. T., Chang, S., Kleinberg, L., Lim, M. 2011; 81 (4): E497-E502

  Abstract

  During the past two decades, radiosurgery has arisen as a promising approach to the management of glomus jugulare. In the present study, we report on a systematic review and meta-analysis of the available published data on the radiosurgical management of glomus jugulare tumors.To identify eligible studies, systematic searches of all glomus jugulare tumors treated with radiosurgery were conducted in major scientific publication databases. The data search yielded 19 studies, which were included in the meta-analysis. The data from 335 glomus jugulare patients were extracted. The fixed effects pooled proportions were calculated from the data when Cochrane's statistic was statistically insignificant and the inconsistency among studies was <25%. Bias was assessed using the Egger funnel plot test.Across all studies, 97% of patients achieved tumor control, and 95% of patients achieved clinical control. Eight studies reported a mean or median follow-up time of >36 months. In these studies, 95% of patients achieved clinical control and 96% achieved tumor control. The gamma knife, linear accelerator, and CyberKnife technologies all exhibited high rates of tumor and clinical control.The present study reports the results of a meta-analysis for the radiosurgical management of glomus jugulare. Because of its high effectiveness, we suggest considering radiosurgery for the primary management of glomus jugulare tumors.

  View details for DOI 10.1016/j.ijrobp.2011.05.006

  View details for Web of Science ID 000309412300039

  View details for PubMedID 21703782

• CyberKnife stereotactic radiosurgical rhizotomy for refractory trigeminal neuralgia JOURNAL OF CLINICAL NEUROSCIENCE Tang, C., Chang, S. D., Tseng, K., Liu, M., Ju, D. 2011; 18 (11): 1449-1453

  Abstract

  Stereotactic radiosurgery (SRS) has been established as an option for the treatment of trigeminal neuralgia (TN). Here, we report our experience of CyberKnife®-based (Accuray, Sunnyvale, CA, USA) stereotactic rhizotomy on medically refractory patients to determine its clinical effectiveness. Between January 2007 and December 2009, 14 selected patients underwent SRS for TN at our CyberKnife Center. Patients were evaluated for pain relief using a visual analog scale (VAS) score, time to reach pain relief (latency), duration of pain control, decrease of pain medication, occurrence of new dysesthesia, and side effects at the 3-month, 6-month, 1-year and 2-year follow-up. A literature analysis revealed that compared with other SRS systems, which can provide a high rate of pain control, CyberKnife® stereotactic rhizotomy yielded an earlier onset of pain relief in our cohort.

  View details for DOI 10.1016/j.jocn.2011.03.012

  View details for Web of Science ID 000296402800005

  View details for PubMedID 21924911

• A rare case of an aldosterone secreting metastatic adrenocortical carcinoma and papillary thyroid carcinoma in a 31-year-old male. Rare tumors Wanta, S. M., Basina, M., Chang, S. D., Chang, D. T., Ford, J. M., Greco, R., Kingham, K., Merritt, R. E., Kunz, P. L. 2011; 3 (4)

  Abstract

  We report a rare synchronous presentation of adrenocortical carcinoma (ACC) and papillary thyroid carcinoma (PTC). A 31-year-old male first presented with a large left adrenal mass that was identified during the workup for refractory hypertension due to hyperaldosteronism. The mass was removed surgically with pathology showing ACC. The patient was then treated with adjuvant radiation therapy and mitotane chemotherapy. Four months post ACC resection, metastatic ACC to the right upper lung and PTC in the left lobe of the thyroid were found in surveillance imaging. He subsequently developed pulmonary, contralateral adrenal and brain metastases from his ACC. Li Fraumeni syndrome and Multiple Endocrine Neoplasia Type I (MEN I) were considered, but testing of both P53 and menin genes showed no mutation. We also performed a review of the literature and found three similar cases, however gene mutation analysis was not performed..

  View details for DOI 10.4081/rt.2011.e45

  View details for PubMedID 22355500

  View details for PubMedCentralID PMC3282450

• Images in clinical medicine. Orbital and cerebral arteriovenous malformations. New England journal of medicine Choudhri, O., Chang, S. D. 2011; 365 (13)

  View details for DOI 10.1056/NEJMicm1010443

  View details for PubMedID 21991915

• Stereotactic Radiosurgery Yields Long-term Control for Benign Intradural, Extramedullary Spinal Tumors NEUROSURGERY Sachdev, S., Dodd, R. L., Chang, S. D., Soltys, S. G., Adler, J. R., Luxton, G., Choi, C. Y., Tupper, L., Gibbs, I. C. 2011; 69 (3): 533-539

  Abstract

  The role of stereotactic radiosurgery in the treatment of benign intracranial lesions is well established. Although a growing body of evidence supports its role in the treatment of malignant spinal lesions, a much less extensive dataset exists for treatment of benign spinal tumors.To examine the safety and efficacy of stereotactic radiosurgery for treatment of benign, intradural extramedullary spinal tumors.From 1999 to 2008, 87 patients with 103 benign intradural extramedullary spinal tumors (32 meningiomas, 24 neurofibromas, and 47 schwannomas) were treated with stereotactic radiosurgery at Stanford University Medical Center. Forty-three males and 44 females had a median age of 53 years (range, 12-86). Twenty-five patients had neurofibromatosis. Treatment was delivered in 1 to 5 sessions (median, 2) with a mean prescription dose of 19.4 Gy (range, 14-30 Gy) to an average tumor volume of 5.24 cm (range, 0.049-54.52 cm).After a mean radiographic follow-up period of 33 months (range, 6-87), including 21 lesions followed for ≥ 48 months, 59% were stable, 40% decreased in size, and a single tumor (1%) increased in size. Clinically, 91%, 67%, and 86% of meningiomas, neurofibromas, and schwannomas, respectively, were symptomatically stable to improved at last follow-up. One patient with a meningioma developed a new, transient myelopathy at 9 months, although the tumor was smaller at last follow-up.As a viable alternative to microsurgical resection, stereotactic radiosurgery provides safe and efficacious long-term control of benign intradural, extramedullary spinal tumors with a low rate of complication.

  View details for DOI 10.1227/NEU.0b013e318218db23

  View details for Web of Science ID 000293586200003

  View details for PubMedID 21832967

• Management of Pediatric Intracranial Arteriovenous Malformations: Experience With Multimodality Therapy NEUROSURGERY Darsaut, T. E., Guzman, R., Marcellus, M. L., Edwards, M. S., Tian, L., Do, H. M., Chang, S. D., Levy, R. P., Adler, J. R., Marks, M. P., Steinberg, G. K. 2011; 69 (3): 540-556

  Abstract

  Successful management of pediatric arteriovenous malformations (AVMs) often requires a balanced application of embolization, surgery, and radiosurgery.To describe our experience treating pediatric AVMs.We analyzed 120 pediatric patients (< 18 years of age) with AVMs treated with various combinations of radiosurgery, surgery, and endovascular techniques.Between 1985 and 2009, 76 children with low Spetzler-Martin grade (1-3) and 44 with high-grade (4-5) AVMs were treated. Annual risk of hemorrhage from presentation to initial treatment was 4.0%, decreasing to 3.2% after treatment initiation until confirmed obliteration. Results for AVM obliteration were available in 101 patients. Initial single-modality therapy led to AVM obliteration in 51 of 67 low-grade (76%) and 3 of 34 high-grade (9%) AVMs, improving to 58 of 67 (87%) and 9 of 34 (26%), respectively, with further treatment. Mean time to obliteration was 1.8 years for low-grade and 6.4 years for high-grade AVMs. Disabling neurological complications occurred in 4 of 77 low-grade (5%) and 12 of 43 high-grade (28%) AVMs. At the final clinical follow-up (mean, 9.2 years), 48 of 67 patients (72%) with low-grade lesions had a modified Rankin Scale score (mRS) of 0 to 1 compared with 12 of 34 patients (35%) with high-grade AVMs. On multivariate analysis, significant risk factors for poor final clinical outcome (mRS ≥ 2) included baseline mRS ≥ 2 (odds ratio, 9.51; 95% confidence interval, 3.31-27.37; P < .01), left-sided location (odds ratio, 3.03; 95% confidence interval, 1.11-8.33; P = .03), and high AVM grade (odds ratio, 4.35; 95% confidence interval, 1.28-14.28; P = .02).Treatment of pediatric AVMs with multimodality therapy can substantially improve obliteration rates and may decrease AVM hemorrhage rates. The poor natural history and risks of intervention must be carefully considered when deciding to treat high-grade pediatric AVMs.

  View details for DOI 10.1227/NEU.0b013e3182181c00

  View details for PubMedID 21430584

• Successful Repair of a Gunshot Wound to the Head with Retained Bullet in the Torcular Herophili WORLD NEUROSURGERY Pricola, K. L., Zou, H., Chang, S. D. 2011; 76 (3-4)

  Abstract

  Nonlethal missile injuries to the dural venous sinus system are rare. To date successful repair of isolated penetrating injury to the torcular herophili has not been reported without significant associated morbidity. We report the case of a gunshot wound injury to the occipital region with retained bullet fragment in the confluence of the sinuses causing traumatic sinus venous thrombosis.Occipital and suboccipital craniotomy for removal of bullet in the torcula, repair of sinus defect, and repair of depressed skull bone fragments was performed.The procedure resulted in restoration of proximal and distal flow across the dural sinus system and preservation of torcular sinus patency with excellent neurological outcome. Technical considerations in the repair of penetrating torcular injuries are discussed.Gunshot wounds with retained bullet fragments in the torcula can be successfully repaired with preservation of neurological function after retrieval of metallic foreign body and restoration of venous sinus patency.

  View details for DOI 10.1016/j.wneu.2010.03.021

  View details for Web of Science ID 000296145700036

  View details for PubMedID 21986442

• CyberKnife Stereotactic Radiosurgery for Recurrent, Metastatic, and Residual Hemangiopericytomas JOURNAL OF HEMATOLOGY & ONCOLOGY Veeravagu, A., Jiang, B., Patil, C. G., Lee, M., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2011; 4

  Abstract

  Hemangiopericytoma is a rare and aggressive meningeal tumor. Although surgical resection is the standard treatment, hemangiopericytomas often recur with high incidences of metastasis. The purpose of this study was to evaluate the role of CyberKnife stereotactic radiosurgery (CK) in the management of recurrent, metastatic, and residual hemangiopericytomas.In a review of the Stanford radiosurgery database between 2002 and 2009, the authors found 14 patients who underwent CK therapy for recurrent, metastatic, and residual hemangiopericytomas. A total of 24 tumors were treated and the median patient age was 52 years (range 29-70 years) at the time of initial CK therapy. The median follow-up period was 37 months (10-73 months) and all patients had been previously treated with surgical resection. Mean tumor volume was 9.16 cm3 and the mean marginal and maximum radiosurgical doses to the tumors were 21.2 Gy and 26.8 Gy, respectively.Of the 24 tumors treated, 22 have clinical follow-up data at this time. Of those 22 tumors, 12 decreased in size (54.5%), 6 remained unchanged (27.3%), and 4 showed recurrence (18.2%) after CK therapy. Progression-free survival rate was 95%, 71.5%, and 71.5% at 1, 3, and 5 years after multiple CK treatments. The 5-year survival rate after CK was 81%.CK is an effective and safe management option for hemangiopericytomas. The current series demonstrates a tumor control of 81.8%. Other institutions have demonstrated similar outcomes with stereotactic radiosurgery, with tumor control ranging from 46.4% to 100%.

  View details for DOI 10.1186/1756-8722-4-26

  View details for Web of Science ID 000291817100001

  View details for PubMedID 21645367

  View details for PubMedCentralID PMC3118387

• Stereotactic Radiosurgery of Cranial Nonvestibular Schwannomas: Results of Single- and Multisession Radiosurgery NEUROSURGERY Choi, C. Y., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Sakamoto, G. T., Patel, D. A., Lieberson, R. E., Chang, S. D., Adler, J. R. 2011; 68 (5): 1200-1208

  Abstract

  Surgical resection of nonvestibular cranial schwannomas carries a considerable risk of postoperative complications. Stereotactic radiosurgery (SRS) offers a non-invasive treatment alternative. The efficacy and safety of multi-session SRS of nonvestibular cranial schwannomas has not been well studied.To analyze the results of single- and multi-session SRS of nonvestibular cranial schwannomas.From 2001 to 2007, 42 lesions in 40 patients were treated with SRS at Stanford University Medical Center, targeting schwannomas of cranial nerves IV (n = 1), V (n = 18), VII (n = 6), X (n = 5), XII (n = 2), jugular foramen (n = 8), and cavernous sinus (n = 2). SRS was delivered to a median marginal dose of 18 Gy (range, 15-33 Gy) in 1 to 3 sessions, targeting a median tumor volume of 3.2 cm (range, 0.1-23.7 cm). The median doses for treatments in 1 (n = 18), 2 (n = 9), and 3 (n = 15) sessions were 17.5, 20, and 18 Gy, respectively.With a median follow-up of 29 months (range, 6-84 months), tumor control was achieved in 41 of the 42 lesions. Eighteen of 42 lesions (43%) decreased in size; 23 tumors (55%) remained stable. There were 2 cases of new or worsening cranial nerve deficits in patients treated in single session; no patient treated with multi-session SRS experienced any cranial nerve toxicity (P = 0.18).SRS of nonvestibular cranial schwannomas provides excellent tumor control with minimal risk of complications. There was a trend towards decreased complications with multi-session SRS.

  View details for DOI 10.1227/NEU.0b013e31820c0474

  View details for Web of Science ID 000289230300033

  View details for PubMedID 21273918

• TOLERANCE OF THE SPINAL CORD TO STEREOTACTIC RADIOSURGERY: INSIGHTS FROM HEMANGIOBLASTOMAS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Daly, M. E., Choi, C. Y., Gibbs, I. C., Adler, J. R., Chang, S. D., Lieberson, R. E., Soltys, S. G. 2011; 80 (1): 213-220

  Abstract

  To evaluate spinal cord dose-volume effects, we present a retrospective review of stereotactic radiosurgery (SRS) treatments for spinal cord hemangioblastomas.From November 2001 to July 2008, 27 spinal hemangioblastomas were treated in 19 patients with SRS. Seventeen tumors received a single fraction with a median dose of 20 Gy (range, 18-30 Gy). Ten lesions were treated using 18-25 Gy in two to three sessions. Cord volumes receiving 8, 10, 12, 14, 16, 18, 20, 22, and 24 Gy and dose to 10, 100, 250, 500, 1000, and 2000 mm(3) of cord were determined. Multisession treatments were converted to single-fraction biologically effective dose (SFBED).Single-fraction median cord D(max) was 22.7 Gy (range, 17.8-30.9 Gy). Median V10 was 454 mm(3) (range, 226-3543 mm(3)). Median dose to 500 mm(3) cord was 9.5 Gy (range, 5.3-22.5 Gy). Fractionated median SFBED(3) cord D(max) was 14.1 Gy(3) (range, 12.3-19.4 Gy(3)). Potential toxicities included a Grade 2 unilateral foot drop 5 months after SRS and 2 cases of Grade 1 sensory deficits. The actuarial 3-year local tumor control estimate was 86%.Despite exceeding commonly cited spinal cord dose constraints, SRS for spinal hemangioblastomas is safe and effective. Consistent with animal experiments, these data support a partial-volume tolerance model for the human spinal cord. Because irradiated cord volumes were generally small, application of these data to other clinical scenarios should be made cautiously. Further prospective studies of spinal radiosurgery are needed.

  View details for DOI 10.1016/j.ijrobp.2010.01.040

  View details for Web of Science ID 000290006300031

  View details for PubMedID 21481724

• Predictors of Clinical and Angiographic Outcome After Surgical or Endovascular Therapy of Very Large and Giant Intracranial Aneurysms NEUROSURGERY Darsaut, T. E., Darsaut, N. M., Chang, S. D., Silverberg, G. D., Shuer, L. M., Tian, L., Dodd, R. L., Do, H. M., Marks, M. P., Steinberg, G. K. 2011; 68 (4): 903-915

  Abstract

  Risk factors for poor outcome in the treatment of very large (≥20-24 mm) and giant (≥25 mm) intracranial aneurysms remain incompletely defined.To present an aggregate clinical series detailing a 24-year experience with very large and giant aneurysms to identify and assess the relative importance of various patient, aneurysm, and treatment-specific characteristics associated with clinical and angiographic outcomes.The authors retrospectively identified 184 aneurysms measuring 20 mm or larger (85 very large, 99 giant) treated at Stanford University Medical Center between 1984 and 2008. Clinical data including age, presentation, and modified Rankin Scale (mRS) score were recorded, along with aneurysm size, location, and morphology. Type of treatment was noted and clinical outcome measured using the mRS score at final follow-up. Angiographic outcomes were completely occluded, occluded with residual neck, partly obliterated, or patent with modified flow.After multivariate analysis, risk factors for poor clinical outcome included a baseline mRS score of 2 or higher (odds ratio [OR], 0.23; 95% confidence interval [CI]: 0.08-0.66; P = .01), aneurysm size of 25 mm or larger (OR, 3.32; 95% CI: 1.51-7.28; P < .01), and posterior circulation location (OR, 0.18; 95% CI: 0.07-0.43; P < .01). Risk factors for incomplete angiographic obliteration included fusiform morphology (OR, 0.25; 95% CI: 0.10-0.66; P < .01), posterior circulation location (OR, 0.33; 95% CI: 0.13-0.83; P = .02), and endovascular treatment (OR, 0.14; 95% CI: 0.06-0.32; P < .01). Patients with incompletely occluded aneurysms experienced higher rates of posttreatment subarachnoid hemorrhage and had increased mortality compared with those with completely obliterated aneurysms.Our results suggest that patients with poor baseline functional status, giant aneurysms, and aneurysms in the posterior circulation had a significantly higher proportion of poor outcomes at final follow-up. Fusiform morphology, posterior circulation location, and endovascular treatment were risk factors for incompletely obliterated aneurysms.

  View details for DOI 10.1227/NEU.0b013e3182098ad0

  View details for PubMedID 21221025

• TECHNIQUE FOR TARGETING ARTERIOVENOUS MALFORMATIONS USING FRAMELESS IMAGE-GUIDED ROBOTIC RADIOSURGERY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hristov, D., Liu, L., Adler, J. R., Gibbs, I. C., Moore, T., Sarmiento, M., Chang, S. D., Dodd, R., Marks, M., Do, H. M. 2011; 79 (4): 1232-1240

  Abstract

  To integrate three-dimensional (3D) digital rotation angiography (DRA) and two-dimensional (2D) digital subtraction angiography (DSA) imaging into a targeting methodology enabling comprehensive image-guided robotic radiosurgery of arteriovenous malformations (AVMs).DRA geometric integrity was evaluated by imaging a phantom with embedded markers. Dedicated DSA acquisition modes with preset C-arm positions were configured. The geometric reproducibility of the presets was determined, and its impact on localization accuracy was evaluated. An imaging protocol composed of anterior-posterior and lateral DSA series in combination with a DRA run without couch displacement between acquisitions was introduced. Software was developed for registration of DSA and DRA (2D-3D) images to correct for: (a) small misalignments of the C-arm with respect to the estimated geometry of the set positions and (b) potential patient motion between image series. Within the software, correlated navigation of registered DRA and DSA images was incorporated to localize AVMs within a 3D image coordinate space. Subsequent treatment planning and delivery followed a standard image-guided robotic radiosurgery process.DRA spatial distortions were typically smaller than 0.3 mm throughout a 145-mm × 145-mm × 145-mm volume. With 2D-3D image registration, localization uncertainties resulting from the achievable reproducibility of the C-arm set positions could be reduced to about 0.2 mm. Overall system-related localization uncertainty within the DRA coordinate space was 0.4 mm. Image-guided frameless robotic radiosurgical treatments with this technique were initiated.The integration of DRA and DSA into the process of nidus localization increases the confidence with which radiosurgical ablation of AVMs can be performed when using only an image-guided technique. Such an approach can increase patient comfort, decrease time pressure on clinical and technical staff, and possibly reduce the number of cerebral angiograms needed for a particular patient.

  View details for DOI 10.1016/j.ijrobp.2010.05.015

  View details for PubMedID 20801584

• ECTOPIC ACROMEGALY DUE TO A PANCREATIC NEUROENDOCRINE TUMOR PRODUCING GROWTH HORMONE-RELEASING HORMONE ENDOCRINE PRACTICE Weiss, D. E., Vogel, H., Lopes, M. B., Chang, S. D., Katznelson, L. 2011; 17 (1): 79-84

  Abstract

  To present a case of acromegaly due to ectopic growth hormone-releasing hormone (GHRH) secretion from a pancreatic neuroendocrine tumor in the context of multiple endocrine neoplasia type 1 (MEN 1).We describe the clinical, imaging, and pathologic findings of the study patient.A 46-year-old woman presented with clinical and biochemical findings diagnostic of acromegaly. Magnetic resonance imaging showed a 1.2-cm sellar mass. Following resection of the macroadenoma, serum insulin-like growth factor 1 (IGF-1) and growth hormone (GH) levels remained unchanged. Pathologic examination revealed adenomatous changes, including a nonsecretory focus and a prolactin immunopositive area (GH stain negative in both). Octreotide long-acting release was ineffective. Search for an ectopic tumor included normal octreoscan and abdominal computed tomography. GHRH was greater than 1000 pg/mL. Repeated abdominal computed tomography documented a 6.2-cm mass in the tail and body of the pancreas. Distal pancreatectomy revealed a pancreatic neuroendocrine tumor that stained positive for GHRH. Postoperatively, serum GHRH and IGF-1 normalized. Re-evaluation of the initial pituitary pathologic specimen revealed additional somatotroph hyperplasia of the adjacent, normal pituitary gland. Primary hyperparathyroidism was diagnosed, and multigland parathyroid hyperplasia was noted at surgery. Genetic testing was positive for a mutation in the MEN1 gene.This patient's acromegaly was resistant to somatostatin analogue therapy, reflecting the negative octreoscan imaging. In addition, this case is novel because the patient presented with pituitary adenomatous changes, which were presumably associated with MEN 1 and/or possibly the elevated GHRH levels.

  View details for DOI 10.4158/EP10165.CR

  View details for PubMedID 20713338

• CyberKnife radiosurgery can control recurrent epidermoid cysts of the central nervous system. Journal of radiosurgery and SBRT Lieberson, R. E., Mener, A., Choi, C., Kalani, M. A., Soltys, S. G., Gibbs, I. C., Heit, G., Adler, J. R., Chang, S. D. 2011; 1 (3): 247–52

  Abstract

  Epidermoid cysts of the central nervous system may be difficult to resect and recurrent lesions may be impossible to control with open surgery. We identified three patients with recurrent epidermoids treated with radiosurgery at Stanford. One patient with a middle fossa lesion that had been resected twice in six years, presented with a 4.5 cubic centimeter recurrence and was treated with radiosurgery. Follow-up scans over three years showed no additional growth. Two patients had spinal lesions. One had undergone numerous, unsuccessful procedures in the three years before the radiosurgical treatment and subsequent open resection of a 3.8 cubic centimeter recurrence. His scans remain unremarkable eight years after treatment. The other, with acaudaequina mass, had required five open resections in 11 years. Following the last resection, the residual was treated radiosurgically. The lesion eventually increased in size, but became symptomatic only after seven years. A second course of radiosurgery was delivered. We believe that stereotactic radiosurgery can be safe for some epidermoid cysts of the central nervous system, decreases their growth rate, and may facilitate subsequent open surgery. It should be considered for select individuals with recurrent or unresectable lesions.

  View details for PubMedID 29296323

• A giant cell tumor of the cranial base treated by stereotactic radiosurgery JOURNAL OF RADIOSURGERY AND SBRT Kim, E., Murovic, J. A., Gibbs, I. C., Shuer, L. M., Chang, S. D. 2011; 1 (4): 333–37

  Abstract

  Giant cell tumors (GCTs) developing from the cranial bones are rare. Occurrence of these tumors in the vicinity of eloquent areas precludes complete excision. Fractionated external beam radiotherapy (FEBRT) has been used for those cases, but with inconsistent outcomes. The authors report a case of a patient with a GCT involving the left occiput which was successfully treated by CyberKnife stereotactic radiosurgery (CK RS). There was improvement in the neurological deficit and occipital pain without adjunctive treatment. This is the first report of stereotactic radiosurgery (SRS) adopted as a primary treatment modality for a cranial GCT.

  View details for PubMedID 29296334

• Cyberknife Stereotactic Radiosurgery for Treatment of Atypical (Who Grade II) Cranial Meningiomas NEUROSURGERY Choi, C. Y., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Jackson, P. S., Lieberson, R. E., Chang, S. D., Adler, J. R. 2010; 67 (5): 1180-1188

  Abstract

  The optimal management of subtotally resected atypical meningiomas is unknown.To perform a retrospective review of patients with residual or recurrent atypical meningiomas treated with stereotactic radiosurgery (SRS).Twenty-five patients were treated, either immediately after surgery (n = 15) or at the time of radiographic progression or treatment failure (n = 10). SRS was delivered to with a median marginal dose of 22 Gy (range, 16-30) in 1 to 4 fractions (median, 1), targeting a median tumor volume of 5.3 cm³ (range, 0.3-26.0).With a median follow-up time of 28 months (range, 3-67), the 12-, 24-, and 36-month actuarial local and regional control rates for all patients were 94%, 94%, 74%, and 90%, 90%, 62%, respectively. There were 2 cases of radiation toxicity. On univariate analysis, the number of recurrences before SRS (P = .046), late SRS (ie, waiting until tumor progression to initiate treatment) (P = .03), and age at treatment ≥ 60 years (P = .01) were significant predictors of recurrence. Of the 20 radiation-naïve patients, 2 patients failed with the targeted lesion and 3 elsewhere in the resection bed, resulting in 12-, 24- and 36-month actuarial local and regional control rates of 100%, 100%, 73% and 93%, 93%, 75%, respectively. The overall locoregional control rates at 12, 24, and 36 months were 93%, 93%, and 54%, respectively.Irradiation of the entire postoperative tumor bed may not be necessary for the majority of patients with subtotally resected atypical meningiomas. Patients in this series achieved outcomes comparable to that of historical control rates for larger volume, conventionally fractionated radiotherapy.

  View details for DOI 10.1227/NEU.0b013e3181f2f427

  View details for Web of Science ID 000283479500003

  View details for PubMedID 20871435

• STEREOTACTIC RADIOSURGERY FOR TREATMENT OF SPINAL METASTASES RECURRING IN CLOSE PROXIMITY TO PREVIOUSLY IRRADIATED SPINAL CORD INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Choi, C. Y., Adler, J. R., Gibbs, I. C., Chang, S. D., Jackson, P. S., Minn, A. Y., Lieberson, R. E., Soltys, S. G. 2010; 78 (2): 499-506

  Abstract

  As the spinal cord tolerance often precludes reirradiation with conventional techniques, local recurrence within a previously irradiated field presents a treatment challenge.We retrospectively reviewed 51 lesions in 42 patients treated from 2002 to 2008 whose spinal metastases recurred in a previous radiation field (median previous spinal cord dose of 40 Gy) and were subsequently treated with stereotactic radiosurgery (SRS).SRS was delivered to a median marginal dose of 20 Gy (range, 10-30 Gy) in 1-5 fractions (median, 2), targeting a median tumor volume of 10.3 cm(3) (range, 0.2-128.6 cm(3)). Converting the SRS regimens with the linear quadratic model (α/β = 3), the median spinal cord maximum single-session equivalent dose (SSED) was 12.1 Gy(3) (range, 4.7-19.3 Gy(3)). With a median follow-up of 7 months (range, 2-47 months), the Kaplan-Meier local control and overall survival rates at 6/12 months were 87%/73% and 81%/68%, respectively. A time to retreatment of ≤12 months and the combination of time to retreatment of ≤12 months with an SSED of <15 Gy(10) were significant predictors of local failure on univariate and multivariate analyses. In patients with a retreatment interval of <12 months, 6/12 month local control rates were 88%/58%, with a SSED of >15 Gy(10), compared to 45%/0% with <15 Gy(10), respectively. One patient (2%) experienced Grade 4 neurotoxicity.SRS is safe and effective in the treatment of spinal metastases recurring in previously irradiated fields. Tumor recurrence within 12 months may correlate with biologic aggressiveness and require higher SRS doses (SSED >15 Gy(10)). Further research is needed to define the partial volume retreatment tolerance of the spinal cord and the optimal target dose.

  View details for DOI 10.1016/j.ijrobp.2009.07.1727

  View details for Web of Science ID 000282147000028

  View details for PubMedID 20133079

• Frameless image guided robotic radiosurgery of arteriovenous malformation localized on spatially correlated digital subtraction and C-arm CT angiography images JOURNAL OF NEUROINTERVENTIONAL SURGERY Hristov, D., Adler, J. R., Gibbs, I. C., Dodd, R., Marks, M., Chang, S. D., Do, H. M. 2010; 2 (3): 252-254

  Abstract

  A case is reported of frameless image guided robotic radiosurgery for an arteriovenous malformation (AVM). C-arm CT (CACT) and concurrent digital subtraction angiography images were used for AVM localization within the CACT volume. Treatment planning was performed on CT images registered with the CACT dataset. During delivery, a robotic linear accelerator tracked the target based on localization with frequent stereoscopic x-ray imaging. This case demonstrates that a frameless approach to AVM radiosurgery is possible.

  View details for DOI 10.1136/jnis.2009.001941

  View details for PubMedID 21990637

• Peritumoral edema after stereotactic radiosurgery for meningioma JOURNAL OF CLINICAL NEUROSCIENCE Hsieh, C., Tsai, J., Chang, L., Lin, J., Chang, S. D., Ju, D. 2010; 17 (4): 529-531

  Abstract

  Peritumoral edema induced by radiosurgery after the treatment of intracranial meningioma has been reported and its mechanism remains unclear. A 65-year-old woman presented with a history of intermittent dizziness. A CT scan and MRI of the brain revealed an extra-axial space-occupying lesion in the left frontal region. She was treated by stereotactic radiosurgery (SRS). Seven months later, the patient began experiencing general weakness and drowsiness. She developed peritumoral edema around the left frontal tumor. Similarly, a 55-year-old woman complained of unstable gait and dizziness 1 month prior to admission. A CT scan and MRI of the brain revealed an extra-axial space-occupying lesion in the right posterior temporal region. Six months after SRS, this patient experienced deteriorated consciousness and general weakness. Peritumoral edema in the right temporal region was noted. We report these two patients, discuss possible causes and review the relevant literature.

  View details for DOI 10.1016/j.jocn.2009.06.035

  View details for Web of Science ID 000276014600030

  View details for PubMedID 20116255

• The role of radiosurgery in the treatment of craniopharyngiomas NEUROSURGICAL FOCUS Veeravagu, A., Lee, M., Jiang, B., Chang, S. D. 2010; 28 (4)

  Abstract

  The treatment of craniopharyngiomas is composed of an intricate balance of multiple modalities. Resection and radiotherapy have been combined to synergistically control tumor growth while preventing undue harm to crucial neurovascular structures. Although a craniopharyngioma is a benign lesion pathologically, it may induce severe neurological injury due to its location and rate of growth. More recently, the advent of targeted, fractionated radiotherapy has allowed for more aggressive tumor control while reducing the necessity for large resections. Initial studies have demonstrated significant tumor control in patients who are treated with resection combined with radiation therapy, versus surgery alone, with a lower rate of treatment-associated neurological deficits. In this review, a detailed account of the current studies evaluating the role of stereotactic radiosurgery in the management of craniopharyngiomas is presented. The authors also provide a short account of their experience to aid in defining the role of CyberKnife radiosurgery.

  View details for DOI 10.3171/2010.2.FOCUS09311

  View details for Web of Science ID 000276212900014

  View details for PubMedID 20367355

• SUCCESSFUL TREATMENT OF METASTATIC BRAIN TUMOR BY CYBERKNIFE: A CASE REPORT KAOHSIUNG JOURNAL OF MEDICAL SCIENCES Hsieh, C., Chang, C., Liu, M., Chang, L., Hueng, D., Chang, S. D., Ju, D. 2010; 26 (3): 144-149

  Abstract

  Stereotactic radiosurgery plays an important role in management of metastatic brain tumors, especially when the tumor has recurred after treatment with previous whole brain radiotherapy. Most metastatic brain tumors less than 1 cm(3) show a complete response after stereotactic radio-surgery. However, there are few reports of a dramatic change in the complete response of large metastatic brain tumors. Here, we report a case of adenocarcinoma of lung that had metastasized to the brain. Because the recurrence of the metastatic brain tumor measured approximately 3 cm in diameter, the tumor was previously treated with two prior craniotomies followed by whole brain radiation to the resection cavity. The tumor subsequently recurred and was treated with stereotactic radiosurgery (CyberKnife). A dramatic response was noted 3 months after radiosurgery with complete disappearance of the recurrent tumor.

  View details for Web of Science ID 000276378800005

  View details for PubMedID 20227654

• Clinical Management of Patients with Temporal Lobe Necrosis 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Krakow, T. E., Hara, W., Yun, S., Soltys, S., Chang, S., Fischbein, N., Loo, B., Le, Q. ELSEVIER SCIENCE INC. 2010: S455–S455

  View details for Web of Science ID 000288775701063

• Stereotactic Radiosurgery of the Post-operative Resection Cavity for Brain Metastases: Optimization of the Treatment Technique 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Soltys, S. G., Gibbs, I. C., Chang, S. D., Adler, J. R., Harsh, G. R., LIEBERSON, R. E., Choi, C. Y. ELSEVIER SCIENCE INC. 2010: S7–S7

  View details for Web of Science ID 000288775700015

• Radiosurgery of Glomus Jugulare Tumors: A Meta-analysis 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Guss, Z. D., Batra, S., Li, G., Chang, S. D., Parsa, A. T., Rigamonti, D., Kleinberg, L., Lim, M. ELSEVIER SCIENCE INC. 2010: S288–S289

  View details for Web of Science ID 000288775700624

• Survival following Stereotactic Radiosurgery for Newly Diagnosed and Recurrent Glioblastoma Multiforme: A Multicenter Experience 8th Meeting of the International-Stereotactic-Radiosurgery-Society Villavicencio, A. T., Burneikiene, S., Romanelli, P., McNeely, L., Lipani, J. D., Fariselli, L., McIntyre, M., Chang, S. D., Nelson, E. L., Broggi, G., Adler, J. R., Thramann, J. J. KARGER. 2010: 288–299

  View details for Web of Science ID 000288517800026

• Radiosurgery for glomus jugulare: history and recent progress NEUROSURGICAL FOCUS Guss, Z. D., Batra, S., Li, G., Chang, S. D., Parsa, A. T., Rigamont, D., Kleinberg, L., Lim, M. 2009; 27 (6)

  Abstract

  In this article the authors review the literature for recent studies of radiosurgical treatment for glomus jugulare. These studies demonstrate that radiosurgery results in similar glomus jugulare tumor control and a superior morbidity profile compared with surgical treatment. In addition, patients treated with radiosurgery usually remain stable clinically or improve. Given the indolent nature of these tumors, however, more follow-up is required to ensure that the immediate benefits are lasting. These preliminary reports demonstrate that the use of radiosurgery as a primary treatment for glomus jugulare should be extended to encompass more of the patients who are currently assigned to microsurgical treatment.

  View details for DOI 10.3171/2009.9.FOCUS09195

  View details for Web of Science ID 000272301500007

  View details for PubMedID 19951058

• MULTISESSION CYBERKNIFE STEREOTACTIC RADIOSURGERY OF LARGE, BENIGN CRANIAL BASE TUMORS: PRELIMINARY STUDY NEUROSURGERY Tuniz, F., Soltys, S. G., Choi, C. Y., Chang, S. D., Gibbs, I. C., Fischbein, N. J., Adler, J. R. 2009; 65 (5): 898-907

  Abstract

  Although radiosurgery plays an important role in managing benign cranial base lesions, the potential for increased toxicity with single-session treatment of large tumors is a concern. In this retrospective study, we report the intermediate-term rate of local control, morbidity, and clinical outcomes of patients with large cranial base tumors treated with multisession stereotactic radiosurgery with the CyberKnife (Accuray, Inc., Sunnyvale, CA).Between 1999 and 2008, 34 consecutive patients with large (>15 cm), benign cranial base tumors (21 meningiomas, 9 schwannomas, 4 glomus jugulare tumors) underwent primary or postoperative radiosurgical treatment using a multisession approach at Stanford University and were considered in this retrospective study. Forty-four percent of these patients had undergone previous subtotal surgical resection or radiotherapy. CyberKnife radiosurgery was delivered in 2 to 5 sessions (median, 3 sessions) to a median tumor volume of 19.3 cm (range, 15.8-69.3 cm). The median marginal dose was 24 Gy (range, 18-25 Gy) prescribed to a median 78% isodose line.After a median clinical follow-up of 31 months (range, 12-77 months), 21% of patients experienced clinical improvement of neurological symptoms, whereas neurological status remained unchanged among the rest. Four patients experienced prolonged use of glucocorticoids owing to transient neurological worsening and radiographic signs of radiation injury. No permanent neurotoxicity was seen. To date, all tumors remain locally controlled.Over our modest length of follow-up, multisession radiosurgery appears to be a safe and effective option for selected large, benign brain and cranial base lesions.

  View details for DOI 10.1227/01.NEU.0000359316.34041.A8

  View details for Web of Science ID 000270876100013

  View details for PubMedID 19834402

• Survival following stereotactic radiosurgery for newly diagnosed and recurrent glioblastoma multiforme: a multicenter experience NEUROSURGICAL REVIEW Villavicencio, A. T., Burneikiene, S., Romanelli, P., Fariselli, L., McNeely, L., Lipani, J. D., Chang, S. D., Nelson, E. L., McIntyre, M., Broggi, G., Adler, J. R. 2009; 32 (4): 417-424

  Abstract

  Despite decades of clinical trials investigating new treatment modalities for glioblastoma multiforme (GBM), there have been no significant treatment advances since the 1980s. Reported median survival times for patients with GBM treated with current modalities generally range from 9 to 19 months. The purpose of the current study is to retrospectively review the ability of CyberKnife (Accuray Incorporated, Sunnyvale, CA, USA) radiosurgery to provide local tumor control of newly diagnosed or recurrent GBM. Twenty patients (43.5%) underwent CyberKnife treatment at the time of the initial diagnosis and/or during the first 3 months of their initial clinical management. Twenty-six patients (56.5%) were treated at the time of tumor recurrence or progression. CyberKnife was performed in addition to the traditional therapy. The median survival from diagnosis for the patients treated with CyberKnife as an initial clinical therapy was 11.5 months (range, 2-33) compared to 21 months (range, 8-96) for the patients treated at the time of tumor recurrence/progression. This difference was statistically significant (Kaplan-Meier analysis, P = 0.0004). The median survival from the CyberKnife treatment was 9.5 months (range, 0.25-31 months) and 7 months (range, 1-34 months) for patients in the newly diagnosed and recurrent GBM groups (Kaplan-Meier analysis, P = 0.79), respectively. Cox proportional hazards survival regression analysis demonstrated that survival time did not correlate significantly with treatment parameters (Dmax, Dmin, number of fractions) or target volume. Survival time and recursive partitioning analysis class were not correlated (P = 0.07). Patients with more extensive surgical interventions survived longer (P = 0.008), especially those who underwent total tumor resection vs. biopsy (P = 0.004). There is no apparent survival advantage in using CyberKnife in initial management of glioblastoma patients, and it should be reserved for patients whose tumors recur or progress after conventional therapy.

  View details for DOI 10.1007/s10143-009-0212-6

  View details for Web of Science ID 000269860300009

  View details for PubMedID 19633875

• Non-surgical management of hormone-secreting pituitary tumors JOURNAL OF CLINICAL NEUROSCIENCE Patil, C. G., Hayden, M., Katznelson, L., Chang, S. D. 2009; 16 (8): 985-993

  Abstract

  Hormone-secreting pituitary tumors account for about 30% of all pituitary tumors. Successful long-term management of patients with these tumors frequently requires a multimodality team approach. Given that the role and efficacy of neurosurgical resection of hormone-secreting pituitary tumors is well described, we focus this review on the other important treatment modalities that are becoming increasingly crucial in the management of acromegaly, Cushing's disease and prolactinomas. Medical management with standard and novel drugs as well as the role and effectiveness of radiation therapy and radiosurgery are discussed in detail.

  View details for DOI 10.1016/j.jocn.2008.11.001

  View details for Web of Science ID 000268608000001

  View details for PubMedID 19443220

• STEREOTACTIC RADIOSURGICAL TREATMENT OF CRANIAL AND SPINAL HEMANGIOBLASTOMAS NEUROSURGERY Moss, J. M., Choi, C. Y., Adler, J. R., Soltys, S. G., Gibbs, I. C., Chang, S. D. 2009; 65 (1): 79-85

  Abstract

  Stereotactic radiosurgery has been used for nearly 2 decades to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. There is a paucity of long-term published radiosurgical treatment outcomes, particularly for spinal lesions, in a large patient population. The purpose of this study was to provide a long-term retrospective evaluation of radiosurgical hemangioblastoma treatment effectiveness, with a special emphasis on the relatively recent use of frameless, image-guided radiosurgery in the treatment of spinal lesions.From 1991 to 2007, 92 hemangioblastomas in 31 patients, 26 with von Hippel-Lindau disease, were treated with radiosurgery (27 tumors treated with frame-based linear accelerator radiosurgery, and 67 tumors were treated with CyberKnife radiosurgery). The mean patient age was 41 years (range, 18-81 years). The radiation dose to the tumor periphery averaged 23.4 Gy (range, 12-40 Gy). The mean tumor volume was 1.8 cm (range, 0.058-65.4 cm). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic, and magnetic resonance imaging scans.Clinical and radiographic follow-up data were available for 82 hemangioblastoma tumors. Only 13 (16%) of the treated hemangioblastomas progressed, whereas 18 tumors (22%) showed radiographic regression, and 51 tumors (62%) remained unchanged in size. With median follow-up of 69 months (range, 5-164 months), the actuarial local control rates at 36 and 60 months were 85% and 82%, respectively. Radiosurgery improved lesion-associated symptoms in 36 of 41 tumors. During the follow-up period, 9 patients died of causes unrelated to the progression of their treated hemangioblastomas, and 5 patients developed radiation necrosis.Stereotactic radiosurgery is safe and effective in the treatment of hemangioblastomas and is an attractive alternative to surgery for patients, including those with von Hippel-Lindau disease.

  View details for DOI 10.1227/01.NEU.0000348015.51685.D2

  View details for Web of Science ID 000268265600010

  View details for PubMedID 19574828

• Pathogenesis and radiobiology of brain arteriovenous malformations: implications for risk stratification in natural history and posttreatment course NEUROSURGICAL FOCUS Achrol, A. S., Guzman, R., Varga, M., Adler, J. R., Steinberg, G. K., Chang, S. D. 2009; 26 (5)

  Abstract

  Brain arteriovenous malformations (BAVMs) are an important cause of intracerebral hemorrhage (ICH) in young adults. Biological predictors of future ICH risk are lacking, and controversy exists over previous studies of natural history risk among predominantly ruptured BAVM cohorts. Recent studies have suggested that the majority of BAVMs are now diagnosed as unruptured lesions, and that the risk according to natural history among these lesions may be less than previously assumed. In the first part of this review, the authors discuss available data on the natural history of BAVMs and highlight the need for future studies that aim to develop surrogate biomarkers of disease progression that accurately predict future risk of ICH in BAVMs. The etiology of BAVM remains unknown. Recent studies have suggested a role for genetic factors in the pathogenesis of sporadic BAVM, which is further supported by reports of familial occurrence of BAVM and association with known systemic genetic disorders (such as Osler-Weber-Rendu disease, Sturge-Weber disease, and Wyburn-Mason syndrome). Molecular characterization of BAVM tissue demonstrates a highly angiogenic milieu with evidence of increased endothelial cell turnover. Taken together with a number of reports of de novo BAVM formation, radiographic growth after initial BAVM diagnosis, and regrowth after successful treatment of BAVM, these findings challenge the long-held assumption that BAVMs are static lesions of congenital origin. In the second part of this review, the authors discuss available data on the origins of BAVM and offer insights into future investigations into genetics and endothelial progenitor cell involvement in the pathogenesis of BAVM. Current treatment options for BAVM focus on removal or obliteration of the lesion in an attempt to protect against future ICH risk, including microsurgical resection, endovascular embolization, and stereotactic radiosurgery (SRS). In the third part of this review, the authors discuss available data on SRS in BAVMs and highlight the need for future studies on the radiobiology of BAVMs, especially in regard to biomarker detection for tracking SRS response during the latency period. Insights from future investigations in BAVM may not only prove important for the development of novel therapies and relevant biomarkers for BAVM, but could also potentially benefit a variety of other disorders involving new vessel formation in the CNS, including stroke, tumors, moyamoya disease, and other cerebrovascular malformations.

  View details for DOI 10.3171/2009.2.FOCUS0926

  View details for Web of Science ID 000265656800009

  View details for PubMedID 19409010

• CYBERKNIFE FOR BRAIN METASTASES OF MALIGNANT MELANOMA AND RENAL CELL CARCINOMA NEUROSURGERY Hara, W., Tran, P., Li, G., Su, Z., Puataweepong, P., Adler, J. R., Soltys, S. G., Chang, S. D., Gibbs, I. C. 2009; 64 (2): A26-A32

  Abstract

  To evaluate the efficacy of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) for patients with brain metastases of malignant melanoma and renal cell carcinoma.We conducted a retrospective review of all patients treated by image-guided radiosurgery at our institution between March 1999 and December 2005. Sixty-two patients with 145 brain metastases of renal cell carcinoma or melanoma were identified.The median follow-up period was 10.5 months. Forty-four patients had malignant melanoma, and 18 patients had renal cell carcinoma. The median age was 57 years, and patients were classified as recursive partitioning analysis Class 1 (6 patients), 2 (52 patients) or 3 (4 patients). Thirty-three patients had been treated systemically with either chemotherapy or immunotherapy, and 33 patients were taking corticosteroids at the time of treatment. The mean tumor volume was 1.47 mL (range, 0.02-35.7 mL), and the mean prescribed dose was 20 Gy (range, 14-24 Gy). The median survival after SRS was 8.3 months. Actuarial survival at 6 and 12 months was 57 and 37%, respectively. On multivariate analysis, Karnofsky Performance Scale score (P < 0.01) and previous immunotherapy/clinical trial (P = 0.01) significantly affected overall survival. One-year intracranial progression-free survival was 38%, and local control was 87%. Intracranial control was impacted by whole-brain radiotherapy (P = 0.01), previous chemotherapy (P = 0.01), and control of the primary at the time of SRS (P = 0.02). Surgical resection had no effect on intracranial or local control. Radiographic evidence of radiation necrosis developed in 4 patients (6%).CyberKnife radiosurgery provided excellent local control with acceptable toxicity in patients with melanoma or renal cell brain metastases. Initial SRS alone appeared to be a reasonable option, as survival was dictated by systemic disease.

  View details for DOI 10.1227/01.NEU.0000339118.55334.EA

  View details for Web of Science ID 000262797700009

  View details for PubMedID 19165071

• CYBERKNIFE STEREOTACTIC RADIOSURGICAL RHIZOTOMY FOR TRIGEMINAL NEURALGIA: ANATOMIC AND MORPHOLOGICAL CONSIDERATIONS NEUROSURGERY Borchers, J. D., Yang, H., Sakamoto, G. T., Howes, G. A., Gupta, G., Chang, S. D., Adler, J. R. 2009; 64 (2): A91-A95

  Abstract

  To search for correlations between specific anatomic, geometric, and morphological properties of the trigeminal nerve and the success of radiosurgical treatment and elimination of facial hypesthesia as a complication.Forty-six patients with at least 6 months of follow-up after CyberKnife (Accuray, Inc., Sunnyvale, CA) rhizotomy were retrospectively reviewed. Patients treated after 2004 were entered into the study after congruity in treatment parameters was established. Anatomic variations regarding the length of each nerve segment and angle of trigeminal nerve takeoff from brainstem to Meckel's cave in the axial and sagittal planes were studied. Dose distribution to surrounding critical structures (brainstem and trigeminal ganglion) was measured. After spatial relationships of involved structures and dose distributions were recorded, their relationship to treatment success, failure, or complication (primarily facial numbness) was tabulated.Forty-five patients (97.2%) experienced pain relief immediately or within weeks. Thirty-four patients maintained excellent outcome. Some degree of facial numbness developed in 18 patients (39.1%) and was mild in 11 of them (Grade II on the Barrow Neurological Institute scale). Patients with a sagittal-angle trigeminal nerve takeoff from the brainstem in the range of 150 to 170 degrees measured from the horizontal plane had a more favorable outcome (P = 0.03) than patients with less obtuse relationships to the proximal nerve origin. Patients who received higher doses of radiation to the brainstem/dorsal root entry zone of the trigeminal nerve experienced a higher rate of posttreatment facial anesthesia.There may be important anatomic and geometric relationships between the treated trigeminal nerve and surrounding critical structures that warrant pretreatment target volume placement and dose distribution considerations.

  View details for DOI 10.1227/01.NEU.0000340795.87734.70

  View details for Web of Science ID 000262797700017

  View details for PubMedID 19165080

• CYBERKNIFE IMAGE-GUIDED RADIOSURGERY FOREWORD NEUROSURGERY Adler, J. R., Chang, S. D. 2009; 64 (2): A1-A1

  View details for DOI 10.1227/01.NEU.0000312703.46158.54

  View details for Web of Science ID 000262797700001

  View details for PubMedID 19165065

• COST-UTILITY ANALYSIS OF THE CYBERKNIFE SYSTEM FOR METASTATIC SPINAL TUMORS NEUROSURGERY Papatheofanis, F. J., Williams, E., Chang, S. D. 2009; 64 (2): A73-A83

  Abstract

  Using decision analysis, a cost-utility study evaluated the cost-effectiveness of CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) in comparison to external beam radiation therapy in the treatment of metastatic spinal malignancies.The published literature provided evidence on the effectiveness of the comparator interventions in the absence of primary outcomes data. Costs of care were derived from Centers for Medicare and Medicaid Services fee schedules. A Markov model was constructed from the payer perspective to simulate the outcomes of patients undergoing nonchemotherapeutic interventions for metastatic spinal tumors. Because cancer therapies bear significant health and economic consequences, the impact of treatment-related toxicities was integrated into the model. Given the terminal nature of these conditions and the limited life expectancy of the patient population, the time horizon for the analysis was limited to 12 months.Patients treated with CyberKnife SRS gained an additional net health benefit of 0.08 quality-adjusted life year; the calculated cost of CyberKnife SRS was $1933 less than external beam radiation therapy for comparable effectiveness. The incremental cost per benefit for this strategy ($41 500 per quality-adjusted life year) met payers' willingness-to-pay criteria.Cost-utility analysis demonstrated that CyberKnife SRS was a superior, cost-effective primary intervention for patients with metastatic spinal tumors compared with conventional external beam radiation therapy.

  View details for DOI 10.1227/01.NEU.0000341205.37067.DE

  View details for Web of Science ID 000262797700015

  View details for PubMedID 19165078

• CYBERKNIFE RADIOSURGERY FOR TRIGEMINAL SCHWANNOMAS NEUROSURGERY Sakarnoto, G. T., Borchers, D. J., Xiao, F., Yang, H., Chang, S. D., Adler, J. R. 2009; 64 (2): A14-A18

  Abstract

  Trigeminal schwannomas (TS) are benign tumors that are managed by surgical resection and/or stereotactic radiosurgery. Most radiosurgical series report results using the gamma knife. The CyberKnife (Accuray, Inc., Sunnyvale, CA) is a frameless, robotic stereotactic radiosurgical system. In this series, we report our experience using the CyberKnife in the treatment of TS.We retrospectively reviewed the medical records and diagnostic imaging in 13 consecutive patients with TS who were treated with the CyberKnife from 2003 to 2007. Seven patients had a previous surgical resection. The mean tumor volume was 6.3 mL (range, 0.39-19.98 mL), and the mean marginal dose was 18.5 Gy. Six of the tumors were treated in a single session. The mean clinical follow-up period was 21.8 months (range, 7-53 months).In this series, the tumor control rate was 100%. The average reduction in tumor volume was 45% (range, 14-98%). A modest improvement in facial pain was noted in 4 of the 6 patients who presented with this symptom. One patient had improvement in facial numbness, and another had improvement in pretreatment headaches. One patient developed jaw weakness and facial dysesthesia, and another patient developed asymptomatic radiation necrosis.Although the length of follow-up is limited, we report our initial experience with CyberKnife treatment of TS. Our results demonstrate tumor control rates and clinical outcomes that parallel those of previous reports using gamma knife radiosurgery; however, long-term follow-up studies are needed.

  View details for DOI 10.1227/01.NEU.0000341629.57676.DB

  View details for Web of Science ID 000262797700007

  View details for PubMedID 19165068

• FORAMINAL NERVE SHEATH TUMORS: INTERMEDIATE FOLLOW-UP AFTER CYBERKNIFE RADIOSURGERY NEUROSURGERY Murovic, J. A., Gibbs, I. C., Chang, S. D., Mobley, B. C., Park, J., Adler, J. R. 2009; 64 (2): A33-A43

  Abstract

  To conduct a retrospective review of outcomes in 15 patients with 18 foraminal tumors, including 17 benign peripheral nerve sheath tumors and 1 malignant peripheral nerve sheath tumor, who underwent CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery at Stanford University Medical Center from 1999 to 2006.Symptoms and findings, neurofibromatosis (NF) association, previous radiation, imaging, dosimetry, tumor volume, central necrosis, and the relation of these factors to outcomes were evaluated.Before treatment, 1 asymptomatic patient had radiculopathic findings, 3 patients experienced local pain with intact neurological examinations, and 7 patients had radiculopathic complaints with intact (1 patient), radiculopathic (4 patients), or radiculomyelopathic examinations (2 patients). Five patients had myelopathic complaints and findings. Three patients had NF1-associated neurofibromas, 1 patient with NF2 had a schwannoma, and 1 patient had a schwannomatosis-related lesion. Two likely radiation-induced lesions, a neurofibroma and a malignant peripheral nerve sheath tumor, were observed. Prescribed doses ranging from 16 to 24 Gy, delivered in 1 to 3 fractions of 6 to 20 Gy, resulted in maximum tumor doses ranging from 20.9 to 30 Gy. Target volumes ranged from 1.36 to 16.9 mL. After radiosurgery, the asymptomatic case remained asymptomatic, and neurological findings improved. Thirteen of 15 symptomatic patients with (12 patients) or without (3 patients) neurological findings improved (3 cases after resection) or remained stable, and 2 patients worsened. Symptoms and examinations remained stable or improved in 8 (80%) of 10 patients with schwannomas and 3 (60%) of 5 patients with neurofibromas. Tumor volumes decreased in 12 (67%) of 18 tumors and increased in 3 tumors. Tumor volumes decreased in 8 of 10 schwannomas and 3 of 7 neurofibromas. Central necrosis developed in 8 (44%) of 18 tumors.CyberKnife radiosurgery resulted in pain relief and functional preservation in selected foraminal peripheral nerve sheath tumors and a malignant peripheral nerve sheath tumor. Symptomatic and neurological improvements were more noticeable with schwannomas. Myelopathic symptoms may necessitate surgical debulking before radiosurgery.

  View details for DOI 10.1227/01.NEU.0000341632.39692.9E

  View details for Web of Science ID 000262797700010

  View details for PubMedID 19165072

• NONISOCENTRIC RADIOSURGICAL RHIZOTOMY FOR TRIGEMINAL NEURALGIA NEUROSURGERY Adler, J. R., Bower, R., Gupta, G., Lim, M., Efron, A., Gibbs, I. C., Chang, S. D., Soltys, S. G. 2009; 64 (2): A84-A90

  Abstract

  Although stereotactic radiosurgery is an established procedure for treating trigeminal neuralgia (TN), the likelihood of a prompt and durable complete response is not assured. Moreover, the incidence of facial numbness remains a challenge. To address these limitations, a new, more anatomic radiosurgical procedure was developed that uses the CyberKnife (Accuray, Inc., Sunnyvale, CA) to lesion an elongated segment of the retrogasserian cisternal portion of the trigeminal sensory root. Because the initial experience with this approach resulted in an unacceptably high incidence of facial numbness, a gradual dose and volume de-escalation was performed over several years. In this single-institution prospective study, we evaluated clinical outcomes in a group of TN patients who underwent lesioning with seemingly optimized nonisocentric radiosurgical parameters.Forty-six patients with intractable idiopathic TN were treated between January 2005 and June 2007. Eligible patients were either poor surgical candidates or had failed previous microvascular decompression or destructive procedures. During a single radiosurgical session, a 6-mm segment of the affected nerve was treated with a mean marginal prescription dose of 58.3 Gy and a mean maximal dose of 73.5 Gy. Monthly neurosurgical follow-up was performed until the patient became pain-free. Longer-term follow-up was performed both in the clinic and over the telephone. Outcomes were graded as excellent (pain-free and off medication), good (>90% improvement while still on medication), fair (50-90% improvement), or poor (no change or worse). Facial numbness was assessed using the Barrow Neurological Institute Facial Numbness Scale score.Symptoms disappeared completely in 39 patients (85%) after a mean latency of 5.2 weeks. In most of these patients, pain relief began within the first week. TN recurred in a single patient after a pain-free interval of 7 months; all symptoms abated after a second radiosurgical procedure. Four additional patients underwent a repeat rhizotomy after failing to respond adequately to the first operation. After a mean follow-up period of 14.7 months, patient-reported outcomes were excellent in 33 patients (72%), good in 11 patients (24%), and poor/no improvement in 2 patients (4%). Significant ipsilateral facial numbness (Grade III on the Barrow Neurological Institute Scale) was reported in 7 patients (15%).Optimized nonisocentric CyberKnife parameters for TN treatment resulted in high rates of pain relief and a more acceptable incidence of facial numbness than reported previously. Longer follow-up periods will be required to establish whether or not the durability of symptom relief after lesioning an elongated segment of the trigeminal root is superior to isocentric radiosurgical rhizotomy.

  View details for DOI 10.1227/01.NEU.0000341631.49154.62

  View details for Web of Science ID 000262797700016

  View details for PubMedID 19165079

• Spinal Stereotactic Radiosurgery for Metastatic Tumor Recurrence within a Prior External Beam Irradiation Field 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Soltys, S. G., Gibbs, I. C., Adler, J. R., Chang, S. D., Jackson, P. S., LIEBERSON, R. E., Choi, C. Y. ELSEVIER SCIENCE INC. 2009: S126–S126

  View details for Web of Science ID 000270573600270

• Stereotactic Radiosurgery Yields Long-term Control for Benign Intradural, Extramedullary Spine Tumors 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Sachdev, S., Dodd, R. L., Chang, S. D., Soltys, S. G., Adler, J. R., Luxton, G., Choi, C. Y., Tupper, L. A., Gibbs, I. C. ELSEVIER SCIENCE INC. 2009: S101–S101

  View details for Web of Science ID 000270573600216

• Stereotactic radiosurgery for a cardiac sarcoma: A case report TECHNOLOGY IN CANCER RESEARCH & TREATMENT Soltys, S. G., Kalani, M. Y., Cheshier, S. H., Szabo, K. A., Lo, A., Chang, S. D. 2008; 7 (5): 363-367

  Abstract

  Pulmonary artery intimal sarcoma is an uncommon tumor with a poor prognosis. We report a case of a 75-year-old man with a pulmonary artery sarcoma, recurrent following surgical resection. To palliate symptoms of this recurrence, he underwent CyberKnife stereotactic radiosurgery with a clinical and radiographic response of his treated disease. No acute or sub-acute toxicity was seen until the patient's death due to metastatic disease 10 weeks following treatment. The feasibility and short-term safety of this technique are reviewed, with emphasis on the stereotactic planning considerations, such as mediastinal organ movement and radiation tolerance.

  View details for Web of Science ID 000259799000003

  View details for PubMedID 18783285

• Predictors of peritumoral edema after stereotactic radiosurgery of supratentorial meningiomas NEUROSURGERY Patil, C. G., Hoang, S., Borchers, D. J., Sakamoto, G., Soltys, S. G., Gibbs, I. C., Harsh, G. R., Chang, S. D., Adler, J. R. 2008; 63 (3): 435-440

  Abstract

  Anecdotal evidence suggests that radiosurgical ablation of parasagittal meningiomas may be associated with increased risk of subsequent edema. Potential predictors of postradiosurgical peritumoral edema, including parasagittal tumor location, tumor size, and treatment dose, were evaluated.We retrospectively reviewed records of 102 patients with 111 supratentorial meningiomas treated with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS). A median marginal dose of 18.0 Gy (range, 11.3-25.0 Gy) was delivered in 1 to 5 sessions (fractions). Potential predictors of posttreatment symptomatic edema were evaluated using Fisher's exact test.Of the 102 patients followed for a mean of 20.9 months (range, 6-77 mo), 15 (14.7%) developed symptomatic edema after SRS. Nine of 31 with parasagittal meningiomas (29.0%) and 6 of 80 with nonparasagittal supratentorial meningiomas (7.5%) developed symptomatic edema (P = 0.0053). Compared with patients with meningiomas in nonmidline supratentorial locations, patients with parasagittal meningiomas were more than 4 times as likely to develop symptomatic edema after SRS (odds ratio, 4.1; 95% confidence interval, 1.5-11.5). The 6-, 12-, and 18-month actuarial rates of symptomatic edema development were significantly greater for patients with parasagittal meningiomas than for patients with nonparasagittal meningiomas (17.8 versus 1.3%, 25.4 versus 5.8%, and 35.2 versus 7.8%, respectively).Patients with parasagittal meningiomas are at greater risk of developing peritumoral symptomatic edema after SRS. Close follow-up after SRS may be particularly important in such patients. These results highlight the need to pursue strategies that could decrease the incidence of postradiosurgical edema in patients with parasagittal meningioma.

  View details for Web of Science ID 000259625600010

  View details for PubMedID 18812954

• Excellent local control with stereotactic radiotherapy boost after external beam radiotherapy in patients with nasopharyngeal carcinoma 87th Annual Meeting of the American-Radium-Society Hara, W., Loo, B. W., Goffinet, D. R., Chang, S. D., Adler, J. R., Pinto, H. A., Fee, W. E., Kaplan, M. J., Fischbein, N. J., Le, Q. ELSEVIER SCIENCE INC. 2008: 393–400

  Abstract

  To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC).Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy.At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors.Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.

  View details for DOI 10.1016/j.ijrobp.2007.10.027

  View details for Web of Science ID 000255971100013

  View details for PubMedID 18164839

• Multimodality treatment of posterior fossa arteriovenous malformations JOURNAL OF NEUROSURGERY Kelly, M. E., Guzman, R., Sinclair, J., Bell-Stephens, T. E., Bower, R., Hamilton, S., Marks, M. P., Do, H. M., Chang, S. D., Adler, J. R., Levy, R. P., Steinberg, G. K. 2008; 108 (6): 1152-1161

  Abstract

  Posterior fossa arteriovenous malformations (AVMs) are relatively uncommon and often difficult to treat. The authors present their experience with multimodality treatment of 76 posterior fossa AVMs, with an emphasis on Spetzler-Martin Grades III-V AVMs.Seventy-six patients with posterior fossa AVMs treated with radiosurgery, surgery, and endovascular techniques were analyzed.Between 1982 and 2006, 36 patients with cerebellar AVMs, 33 with brainstem AVMs, and 7 with combined cerebellar-brainstem AVMs were treated. Natural history data were calculated for all 76 patients. The risk of hemorrhage from presentation until initial treatment was 8.4% per year, and it was 9.6% per year after treatment and before obliteration. Forty-eight patients had Grades III-V AVMs with a mean follow-up of 4.8 years (range 0.1-18.4 years, median 3.1 years). Fifty-two percent of patients with Grades III-V AVMs had complete obliteration at the last follow-up visit. Three (21.4%) of 14 patients were cured with a single radiosurgery treatment, and 4 (28.6%) of 14 with 1 or 2 radiosurgery treatments. Twenty-one (61.8%) of 34 patients were cured with multimodality treatment. The mean Glasgow Outcome Scale (GOS) score after treatment was 3.8. Multivariate analysis performed in the 48 patients with Grades III-V AVMs showed radiosurgery alone to be a negative predictor of cure (p = 0.0047). Radiosurgery treatment alone was not a positive predictor of excellent clinical outcome (GOS Score 5; p > 0.05). Nine (18.8%) of 48 patients had major neurological complications related to treatment.Single-treatment radiosurgery has a low cure rate for posterior fossa Spetzler-Martin Grades III-V AVMs. Multimodality therapy nearly tripled this cure rate, with an acceptable risk of complications and excellent or good clinical outcomes in 81% of patients. Radiosurgery alone should be used for intrinsic brainstem AVMs, and multimodality treatment should be considered for all other posterior fossa AVMs.

  View details for DOI 10.3171/JNS/2008/108/6/1152

  View details for PubMedID 18518720

• Radiation therapy and CyberKnife radiosurgery in the management of craniopharyngiomas NEUROSURGICAL FOCUS Lee, M., Kalani, M. Y., Cheshier, S., Gibbs, I. C., Adler, J. R., Chang, S. D. 2008; 24 (5)

  Abstract

  Many benign intracranial tumors are amenable to radiotherapy treatment including meningiomas, schwannomas, pituitary tumors, and craniopharyngiomas. The authors present their experience in the treatment of craniopharyngiomas in 16 patients using frameless CyberKnife stereotactic radiosurgery (SRS). The authors discuss the role of radiation therapy in the management of these tumors, and more specifically, the role of CyberKnife SRS.Sixteen patients were treated for residual or recurrent craniopharyngioma between 2000 and 2007 with CyberKnife SRS at Stanford University Medical Center. All patients underwent magnetic resonance imaging and visual and neuroendocrine evaluations before and at regular intervals after SRS. A multisession treatment regimen and a nonisocentric treatment plan for each patient were used with a mean marginal dose of 21.6 Gy and a mean maximal dose of 29.9 Gy.There were adequate clinical data to assess outcomes in 11 of 16 patients. Evaluation of patients between 13 and 71 years of age (mean 34.5 years) with a mean follow-up period of 15.4 months revealed no deterioration in visual or neuroendocrine function. Tumor shrinkage was achieved in 7 of these 11 patients, and tumor control in another 3. One patient had cystic enlargement of the residual tumor.The authors' early experience with the application of CyberKnife SRS to residual or recurrent craniopharyngiomas has been positive; control or shrinkage of the tumor was achieved in 91% of patients, with no visual or neuroendocrine complications. Longer-term follow-up with a larger group of patients is required to fully evaluate the safety and effectiveness of this treatment modality.

  View details for DOI 10.3171/FOC/2008/24/5/E4

  View details for Web of Science ID 000256374300004

  View details for PubMedID 18447743

• The use of TLD and Gafchromic film to assure submillimeter accuracy for image-guided radiosurgery MEDICAL DOSIMETRY Ho, A. K., Gibbs, I. C., Chang, S. D., Main, B., Adler, J. R. 2008; 33 (1): 36-41

  Abstract

  The Cyberknife is an image-guided radiosurgical system. It uses a compact X-band 6-MV linear accelerator mounted on a robotic arm to deliver radiosurgical doses. While routine quality assurance (QA) is essential for any radiosurgery system, QA plays an even more vital role for the Cyberknife system, due to the complexity of the system and the wide range of applications. This paper presents a technique for performing quality assurance using thermoluminescence detectors (TLDs) and Gafchromic films that is intended to be specific for the Cyberknife. However, with minor modification, the proposed method can also be used for QA of other radiosurgery systems. Our initial QA procedure for the CyberKnife utilized a 30 x 30 x 11-cm solid water phantom containing a planar array of slots for 1x 1 x 1-mm TLDs on a 2-mm grid. With the objective of significantly simplifying CyberKnife QA, a new procedure for verification was developed, which uses much fewer TLDs than the prior solid water phantom technique. This new method requires only that the system target dose to the center of a cluster of 7 TLDs. In a prior study with Gafchromic films, conducted at 3 different Cyberknife facilities, the mean clinically relevant error was demonstrated to be 0.7 mm. A similar Gafchromic film analysis replicated these error measurements as part of the present investigation. It cannot be emphasized enough the importance of implementing routine QA to verify the accuracy of any radiosurgery system. Our quality assurance procedure tests the treatment planning system, as well as the entire treatment delivery including the image targeting system and the robot system. Either TLDs or Gafchromic films may be used for QA test of a radiosurgery system. Using both methods for measurement has the advantage independently verifying the accuracy of the system. This approach, which is routinely in used at our institution, has repeatedly confirmed the submillimeter targeting accuracy of our Cyberknife.

  View details for DOI 10.1016/j.meddos.2007.04.009

  View details for Web of Science ID 000253610200006

  View details for PubMedID 18262121

• Cyberknife radiosurgery for trigeminal neuralgia treatment: A preliminary multicenter experience NEUROSURGERY Villavicencio, A. T., Lim, M., Burneikiene, S., Romanelli, P., Adler, J. R., McNeely, L., Chang, S. D., Fariselli, L., McIntyre, M., Bower, R., Broggi, G., Thramann, J. J. 2008; 62 (3): 647-654

  Abstract

  Radiosurgery has gained acceptance as a treatment option for trigeminal neuralgia. We report our preliminary multicenter experience treating trigeminal neuralgia with the CyberKnife (Accuray, Inc., Sunnyvale, CA).A total of 95 patients were treated for idiopathic trigeminal neuralgia between May 2002 and October 2005. Radiosurgical dose and volume parameters were retrospectively analyzed in relation to pain response, complications, and recurrence of symptoms. Optimal treatment parameters were identified for patients who had excellent and sustained pain relief with no complications, including severe or moderate hypesthesia.Excellent pain relief was initially experienced by 64 out of 95 patients (67%). The median time to pain relief was 14 days (range, 0.3-180 d). Posttreatment numbness occurred in 45 (47%) of the patients treated. Using higher radiation doses and treating longer segments of the nerve led to both better pain relief and a higher incidence of hypesthesia. The presence of posttreatment numbness was predictive of better pain relief. The overall rate of complications was 18%. At the mean follow-up time of 2 years, 47 of the 95 patients (50%) had sustained pain relief, all of whom were completely off pain medications.The results of this study suggest the following optimal radiosurgical treatment parameters for treatment of idiopathic trigeminal neuralgia: a median maximal dose of 78 Gy (range, 70-85.4 Gy) and a median length of the nerve treated of 6 mm (range, 5-12 mm).

  View details for DOI 10.1227/01.NEU.0000297129.08066.137

  View details for Web of Science ID 000255268500023

  View details for PubMedID 18425011

• Visual field preservation after multisession cyberknife radiosurgery for perioptic lesions. Neurosurgery Adler, J. R., Gibbs, I. C., Puataweepong, P., Chang, S. D. 2008; 62: 733-743

  Abstract

  The restricted radiation tolerance of the anterior visual pathways represents a unique challenge for ablating adjacent lesions with single-session radiosurgery. Although preliminary studies have recently demonstrated that multisession radiosurgery for selected perioptic tumors is both safe and effective, the number of patients in these clinical series was modest and the length of follow-up limited. The current retrospective study is intended to help address these shortcomings.Forty-nine consecutive patients with meningioma (n = 27), pituitary adenoma (n = 19), craniopharyngioma (n = 2), or mixed germ cell tumor (n = 1) situated within 2 mm of a "short segment" of the optic apparatus underwent multisession image-guided radiosurgery at Stanford University Medical Center. Thirty-nine of these patients had previous subtotal surgical resection, and six had previously been treated with conventional fractionated radiotherapy (6). CyberKnife radiosurgery was delivered in two to five sessions to an average tumor volume of 7.7 cm3 and a cumulative average marginal dose of 20.3 Gy. Formal visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months.After a mean visual field follow-up of 49 months (range, 6-96 mo), vision was unchanged postradiosurgery in 38 patients, improved in eight (16%), and worse in three (6%). In each instance, visual deterioration was accompanied by tumor progression that ultimately resulted in patient death. However, one of these patients, who had a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, initially experienced early visual loss without significant tumor progression after both a previous course of radiotherapy and three separate sessions of radiosurgery. After a mean magnetic resonance imaging follow-up period of 46 months, tumor volume was stable or smaller in all other cases. Two patients died of unrelated nonbrain causes.Multisession radiosurgery resulted in high rates of tumor control and preservation of visual function in this group of perioptic tumors. Ninety-four percent of patients retained or improved preradiosurgical vision. This intermediate-term experience reinforces the findings from earlier studies that suggested that multisession radiosurgery can be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions immediately adjacent to short segments of the optic apparatus.

  View details for DOI 10.1227/01.neu.0000316277.14748.63

  View details for PubMedID 18596432

• Neurologic complications of arteriovenous malformation embolization using liquid embolic agents AMERICAN JOURNAL OF NEURORADIOLOGY Jayaraman, M. V., Marcellus, M. L., Hamilton, S., Do, H. M., Campbell, D., Chang, S. D., Steinberg, G. K., Marks, M. P. 2008; 29 (2): 242-246

  Abstract

  Embolization of arteriovenous malformations (AVMs) is commonly used to achieve nidal volume reduction before microsurgical resection or stereotactic radiosurgery. The purpose of this study was to examine the overall neurologic complication rate in patients undergoing AVM embolization and analyze the factors that may determine increased risk.We performed a retrospective review of all patients with brain AVMs embolized at 1 center from 1995 through 2005. Demographics, including age, sex, presenting symptoms, and clinical condition, were recorded. Angiographic factors including maximal nidal size, presence of deep venous drainage, and involvement of eloquent cortex were also recorded. For each embolization session, the agent used, number of pedicles embolized, the percentage of nidal obliteration, and any complications were recorded. Complications were classified as the following: none, non-neurologic (mild), transient neurologic deficit, and permanent nondisabling and permanent disabling deficits. The permanent complications were also classified as ischemic or hemorrhagic. Modified Rankin Scale (mRS) scores were collected pre- and postembolization on all patients. Univariate regression analysis of factors associated with the development of any neurologic complication was performed.Four hundred eighty-nine embolization procedures were performed in 192 patients. There were 6 Spetzler-Martin grade I (3.1%), 26 grade II (13.5%), 71 grade III (37.0%), 57 grade IV (29.7%), and 32 grade V (16.7%) AVMs. Permanent nondisabling complications occurred in 5 patients (2.6%) and permanent disabling complications or deaths occurred in 3 (1.6%). In addition, there were non-neurologic complications in 4 patients (2.1%) and transient neurologic deficits in 22 (11.5%). Five of the 8 permanent complications (2.6% overall) were ischemic, and 3 of 8 (1.6% overall) were hemorrhagic. Of the 178 patients who were mRS 0-2 pre-embolization, 4 (2.3%) were dependent or dead (mRS >2) at follow-up. Univariate analysis of risk factors for permanent neurologic deficits following embolization showed that basal ganglia location was weakly associated with a new postembolization neurologic deficit.Embolization of brain AVMs can be performed with a high degree of technical success and a low rate of permanent neurologic complications.

  View details for DOI 10.3174/ajnr.A0793

  View details for Web of Science ID 000253345200013

  View details for PubMedID 17974613

• Stereotactic radiosurgery of the postoperative resection cavity for brain metastases INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Soltys, S. G., Adler, J. R., Lipani, J. D., Jackson, P. S., Choi, C. Y., Puataweepong, P., White, S., Gibbs, I. C., Chang, S. D. 2008; 70 (1): 187-193

  Abstract

  The purpose of this study was to analyze results of adjuvant stereotactic radiosurgery (SRS) targeted at resection cavities of brain metastases without whole-brain irradiation (WBI).Patients who underwent SRS to the tumor bed, deferring WBI after resection of a brain metastasis, were retrospectively identified.Seventy-two patients with 76 cavities treated from 1998 to 2006 met inclusion criteria. The SRS was delivered to a median marginal dose of 18.6 Gy (range, 15-30 Gy) targeting an average tumor volume of 9.8 cm(3) (range, 0.1-66.8 cm(3)). With a median follow-up of 8.1 months (range, 0.1-80.5 months), 65 patients had follow-up imaging assessable for control analyses. Actuarial local control rates at 6 and 12 months were 88% and 79%, respectively. On univariate analysis, increasing values of conformality indices were the only treatment variables that correlated significantly with improved local control; local control was 100% for the least conformal quartile compared with 63% for the remaining quartiles. Target volume, dose, and number of sessions were not statistically significant.In this retrospective series, SRS administered to the resection cavity of brain metastases resulted in a 79% local control rate at 12 months. This value compares favorably with historic results with observation alone (54%) and postoperative WBI (80-90%). Given the improved local control seen with less conformal plans, we recommend inclusion of a 2-mm margin around the resection cavity when using this technique.

  View details for DOI 10.1016/j.ijrobp.2007.06.068

  View details for Web of Science ID 000251867700026

  View details for PubMedID 17881139

• Treatment of intraorbital lesions using the Accuray CyberKnife system. Orbit (Amsterdam, Netherlands) Hirschbein, M. J., Collins, S., Jean, W. C., Chang, S. D., Adler, J. R. 2008; 27 (2): 97-105

  Abstract

  The goal of this study was to better understand the safety and efficacy of CyberKnife image-guided radiosurgery for lesions immediately adjacent to the optic nerves.This retrospective, non-comparative, interventional case series included 16 patients (6 women and 10 men) with lesions located wholly within the orbit. Thirteen cases involved tumors (31% benign and 69% malignant), two cases presented with chronic orbital inflammation and one patient had intraorbital tissue growth secondary to Graves disease. Staged radiosurgical ablation was performed using CyberKnife image-guided technology. The main outcome measures analyzed were change in tumor/neoplasm size, pain, visual field preservation and visual acuity, which were followed for up to 15 months.Twelve patients had a postoperative MRI, which revealed either a decrease or stabilization of tumor size. In the five lymphoma cases there was complete disappearance of the tumor. Pretreatment pain resolved in all 10 patients who reported it before the procedure; improvement in pain typically occurred within 1-2 weeks of radiosurgery. All 16 patients had a visual evaluation performed after the procedure: of these, 15 had no change in their visual field and one reported improvement. Visual acuity was preserved in 13 patients and improved in two, while one patient developed diplopia.Staged CyberKnife radiosurgery is an effective option for the treatment of intraorbital lesions that controls tumor size, relieves pain, and preserves vision. The long-term safety of this treatment remains to be confirmed.

  View details for DOI 10.1080/01676830601177471

  View details for PubMedID 18415869

• Radiosurgery for glomus Jugulare tumors TECHNOLOGY IN CANCER RESEARCH & TREATMENT Lim, M., Bower, R., Nangiana, J. S., Adler, J. R., Chang, S. D. 2007; 6 (5): 419-423

  Abstract

  Results for treating glomus jugulare tumors with radiosurgery have been limited by short follow-up and small number of patients. We report our experience using LINAC or CyberKnife in 21 tumors with a median follow-up of 66 months (Mean follow-up of 60 months). In addition, we have a subset of eight patients that were followed out for more than 10 years. Patients were treated with doses ranging from 1400 cGy to 2700 cGy. We retrospectively assessed patients for efficacy and post treatment side effects. All patients had stable neurological symptoms, and two patients experienced transient ipsilateral tongue weakness and hearing loss, both of which subsequently resolved. One patient experienced transient ipsilateral vocal cord paresis; however, this patient received previous external beam radiotherapy. All tumors remained stable or decreased in size by MRI exam. Our results support radiosurgery as an effective and safe method of treatment for glomus jugulare tumors with low morbidity as evidenced by a larger number of patients and long term follow-up.

  View details for Web of Science ID 000250211600007

  View details for PubMedID 17877430

• Cyberknife radiosurgery for lesions of the foramen magnum TECHNOLOGY IN CANCER RESEARCH & TREATMENT Cheshier, S. H., Hanft, S. J., Adler, J. R., Chang, S. D. 2007; 6 (4): 329-335

  Abstract

  The region of the foramen magnum (FM) presents an especially difficult area for therapeutic intervention. Indeed, this location is challenging to access surgically, particularly in the case of intramedullary and anterior lesions. Therefore, the potential for morbidity associated with therapy to the foramen magnum, most frequently in the form of lower cranial nerve deficits, has encouraged the search for methods that can effectively treat lesions of this region while sparing the important neighboring structures. We report our experience in the use of Cyberknife radiosurgery as a treatment option for these lesions. Thirty-five patients (17 men, 18 women; mean age, 51 yr; range, 18-83) with 35 lesions either spanning or approximating the foramen magnum were treated with the CyberKnife radiosurgical system. Histologies were determined either by prior surgery or radiographic criteria and included 25 benign tumors (nine meningiomas, five schwannomas, four neurofibromas, three hemangioblastomas, two ependymomas, one chordomas, and one pilocytic astrocytoma) along with 10 malignant growths (nine metastases and one chondrosarcoma). Twenty-seven (77%) patients presented with at least one sign and/or symptom, while eight (23%) patients were completely asymptomatic. The most common symptoms were headache, limb numbness, and limb/truncal ataxia, all of which were reported by ten (29%) patients. Among cranial neuropathies, CN XII dysfunction was evident in four (11%) patients. The specific fractionation schedule (mean of 1.8 sessions; range, 1-5) was based on the size of the treated lesion. The mean dose utilized was 19 Gy. Radiographic follow-up was obtained for twenty-three (66%) patients. Nine of the twenty-three (39%) were stable in size, ten lesions decreased in size (43%), and four lesions increased in size (17%). In terms of symptom relief, follow-up was collected for twenty-four (69%) patients. Eleven (46%) of these patients experienced no change in their signs or symptoms, while seven (29%) patients experienced improvement. Six (25%) patients witnessed deterioration in their signs and symptoms. Overall, eighteen (75%) patients had their signs and symptoms either stabilize or improve. There were eleven (31%) deaths in our series, eight of which were related to the disease (though not directly related to CyberKnife treatment) and three of which were from unrelated causes. Complications directly related to CyberKnife radiosurgery were noted in four (11%) of the thirty-five patients. These included one case of temporary emesis immediately following treatment, one case of cystic enlargement two months out, and two cases of radiation necrosis (occurring 1.5 yrs and 2.5 yrs out from treatment). Cyberknife radiosurgery can be an effective treatment for many foramen magnum lesions.

  View details for Web of Science ID 000249073000010

  View details for PubMedID 17668941

• A 35-year-old woman with a dural-based mass. Brain pathology Haddix, T., Chang, S., Vogel, H. 2007; 17 (3): 331-332

  View details for PubMedID 17598829

• Surgical and endovascular management of symptomatic posterior circulation fusiform aneurysms JOURNAL OF NEUROSURGERY Coert, B. A., Chang, S. D., Do, H. M., Marks, M. P., Steinberg, G. K. 2007; 106 (5): 855-865

  Abstract

  Patients with fusiform aneurysms can present with subarachnoid hemorrhage (SAH), mass effect, ischemia, or unrelated symptoms. The absence of an aneurysm neck impedes the direct application of a clip and endovascular coil deployment. To evaluate the effects of their treatments, the authors retrospectively analyzed a consecutive series of patients with posterior circulation fusiform aneurysms treated at Stanford University Medical Center between 1991 and 2005.Forty-nine patients (mean age 53 years, male/female ratio 1.2:1) treated at the authors' medical center form the basis of the analysis. Twenty-nine patients presented with an SAH. The patients presenting without SAH had cranial nerve dysfunction (five patients), symptoms of mass effect (eight patients), ischemia (six patients), or unrelated symptoms (one patient). The aneurysms were located on the vertebral artery (VA) or posterior inferior cerebellar artery (PICA) (21 patients); vertebrobasilar junction (VBJ) or basilar artery (BA) (18 patients); and posterior cerebral artery (PCA) (10 patients). Pretreatment clinical grades were determined using the Hunt and Hess scale; for patients with unruptured aneurysms (Hunt and Hess Grade 0) functional subgrades were added. Outcome was evaluated using the Glasgow Outcome Scale (GOS) score during a mean follow-up period of 33 months. Overall long-term outcome was good (GOS Score 4 or 5) in 59%, poor (GOS Score 2 or 3) in 16%, and fatal (GOS Score 1) in 24% of the patients. In a univariate analysis, poor outcome was predicted by age greater than 55 years, VBJ location, pretreatment Hunt and Hess grade in patients presenting with SAH, and incomplete aneurysm thrombosis after endovascular treatment. In a multivariate analysis, age greater than 55 years was the confounding factor predicting poor outcome. Stratification by aneurysm location removed the effect of age. Of 13 patients with residual aneurysm after treatment, five (38%) subsequently died of SAH (three patients) or progressive mass effect/brainstem ischemia (two patients).Certain posterior circulation aneurysm locations (PCA, VA-PICA, and BA-VBJ) represent separate disease entities affecting patients at different ages with distinct patterns of presentation, treatment options, and outcomes. Favorable overall long-term outcome can be achieved in 90% of patients with PCA aneurysms, in 60% of those with VA-PICA aneurysms, and in 39% of those with BA-VBJ aneurysms when using endovascular and surgical techniques. The natural history of the disease was poor in patients with incomplete aneurysm thrombosis after treatment.

  View details for PubMedID 17542530

• Cyberknife targeting the pterygopalatine ganglion for the treatment of chronic cluster headaches. Neurosurgery Lad, S. P., Lipani, J. D., Gibbs, I. C., Chang, S. D., Adler, J. R., Henderson, J. M. 2007; 60 (3): E580-?

  Abstract

  Cluster headache (CH) is a severe unilateral and periorbital facial pain syndrome that is often associated with autonomic symptoms, including ipsilateral lacrimation, nasal congestion, conjunctival injection, miosis, ptosis, and eyelid edema. We evaluated the treatment of medically refractory CH with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery targeting the pterygopalatine ganglion.A 56-year-old man presented with a 20-year history of medically refractory CH. His symptoms were described as left-sided, severe, stabbing, burning, and often being associated with tearing and rhinorrhea. These headaches occurred virtually every morning and interfered with sleep, lifestyle, and work performance.The patient underwent two pterygopalatine nerve block trials, both of which resulted in the complete relief of headaches for a 24-hour period. Contrast-enhanced computed axial tomography and magnetic resonance imaging scans were fused for target identification and treatment planning. The target volume measured 0.296 cm3 and a single fraction of 45.50 Gy was delivered to the 78% isodose line with a maximum dose of 65 Gy. The patient kept a detailed diary of his headaches and was followed for 12 months after treatment.Results of CyberKnife targeting of the pterygopalatine ganglion in a patient with medically intractable CHs have revealed a significant decrease in the severity and frequency of headaches after a 12-month follow-up period. In addition, the patient has been able to reduce his medication intake, allowing for a significant decrease in medication-related side effects. Longer follow-up periods and additional studies are required to determine the long-term efficacy and late side effects of this treatment strategy.

  View details for PubMedID 17327771

• CyberKnife targeting the pterygopalatine ganglion for the treatment of chronic cluster headaches NEUROSURGERY Lad, S. P., Lipani, J. D., Gibbs, I. C., Chang, S. D., Adler, J. R., Henderson, J. M. 2007; 60 (3): 580-581

  Abstract

  Cluster headache (CH) is a severe unilateral and periorbital facial pain syndrome that is often associated with autonomic symptoms, including ipsilateral lacrimation, nasal congestion, conjunctival injection, miosis, ptosis, and eyelid edema. We evaluated the treatment of medically refractory CH with CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery targeting the pterygopalatine ganglion.A 56-year-old man presented with a 20-year history of medically refractory CH. His symptoms were described as left-sided, severe, stabbing, burning, and often being associated with tearing and rhinorrhea. These headaches occurred virtually every morning and interfered with sleep, lifestyle, and work performance.The patient underwent two pterygopalatine nerve block trials, both of which resulted in the complete relief of headaches for a 24-hour period. Contrast-enhanced computed axial tomography and magnetic resonance imaging scans were fused for target identification and treatment planning. The target volume measured 0.296 cm3 and a single fraction of 45.50 Gy was delivered to the 78% isodose line with a maximum dose of 65 Gy. The patient kept a detailed diary of his headaches and was followed for 12 months after treatment.Results of CyberKnife targeting of the pterygopalatine ganglion in a patient with medically intractable CHs have revealed a significant decrease in the severity and frequency of headaches after a 12-month follow-up period. In addition, the patient has been able to reduce his medication intake, allowing for a significant decrease in medication-related side effects. Longer follow-up periods and additional studies are required to determine the long-term efficacy and late side effects of this treatment strategy.

  View details for DOI 10.1227/01.NEU.0000255348.33582.DE

  View details for Web of Science ID 000244797000041

• A study of the accuracy of cyberknife spinal radiosurgery using skeletal structure tracking. Neurosurgery Ho, A. K., Fu, D., Cotrutz, C., Hancock, S. L., Chang, S. D., Gibbs, I. C., Maurer, C. R., Adler, J. R. 2007; 60 (2): ONS147-56

  Abstract

  New technology has enabled the increasing use of radiosurgery to ablate spinal lesions. The first generation of the CyberKnife (Accuray, Inc., Sunnyvale, CA) image-guided radiosurgery system required implanted radiopaque markers (fiducials) to localize spinal targets. A recently developed and now commercially available spine tracking technology called Xsight (Accuray, Inc.) tracks skeletal structures and eliminates the need for implanted fiducials. The Xsight system localizes spinal targets by direct reference to the adjacent vertebral elements. This study sought to measure the accuracy of Xsight spine tracking and provide a qualitative assessment of overall system performance.Total system error, which is defined as the distance between the centroids of the planned and delivered dose distributions and represents all possible treatment planning and delivery errors, was measured using a realistic, anthropomorphic head-and-neck phantom. The Xsight tracking system error component of total system error was also computed by retrospectively analyzing image data obtained from eleven patients with a total of 44 implanted fiducials who underwent CyberKnife spinal radiosurgery.The total system error of the Xsight targeting technology was measured to be 0.61 mm. The tracking system error component was found to be 0.49 mm.The Xsight spine tracking system is practically important because it is accurate and eliminates the use of implanted fiducials. Experience has shown this technology to be robust under a wide range of clinical circumstances.

  View details for PubMedID 17297377

• Hemorrhage rate in patients with Spetzler-Martin grades IV and V arteriovenous malformations - Is treatment justified? STROKE Jayaraman, M. V., Marcellus, M. L., Do, H. M., Chang, S. D., Rosenberg, J. K., Steinberg, G. K., Marks, M. P. 2007; 38 (2): 325-329

  Abstract

  We sought to examine the prospective annual risk of hemorrhage in patients harboring Spetzler-Martin grades IV and V arteriovenous malformations (AVMs) before and after initiation of treatment.Medical records of 61 consecutive patients presenting with Spetzler-Martin grades IV and V AVMs were retrospectively reviewed for demographics, angiographic features, presenting symptom(s), and time of all hemorrhage events, before or after treatment initiation. Pretreatment hemorrhage rates (excluding hemorrhages at presentation) and posttreatment rates were subsequently calculated. Modified Rankin Scale (mRS) scores before and after treatment were recorded.The annual pretreatment hemorrhage rate for all patients was 10.4% per year (95% CI, 2.2 to 15.4%), 13.9% (95% CI, 3.5 to 22.1%) in patients with hemorrhagic presentation and 7.3% (2.6 to 14.3%) in patients with nonhemorrhagic presentation. Posttreatment hemorrhage rates were 6.1% per year (95% CI, 2.5 to 13.2%) for all patients, 5.6% (95% CI, 2.1 to 11.8%) for patients presenting with hemorrhage and 6.4% (95% CI, 1.6 to 10.1%) in patients with nonhemorrhagic presentation. A noninferiority test showed that the posttreatment hemorrhage rate was less than or equal to the pretreatment hemorrhage rate (P<0.0001), with some indication that the reduction was greatest in patients with hemorrhagic presentation. Of the 62 patients, 51 (82%) had an mRS score of 0 to 2 before treatment, and 47 (76%) had an mRS score of 0 to 2 at the last follow-up after treatment.The annual rate of hemorrhage in grades IV and V AVMs is higher in this series than reported for all AVMs, which may reflect some referral bias in this single-center study. Nevertheless, initiation of treatment does not appear to increase the rate of subsequent hemorrhage. Treatment for these lesions may be warranted, given their poor natural history.

  View details for DOI 10.1161/01.STR.0000254497.24545.de

  View details for PubMedID 17194881

• Image-guided robotic radiosurgery for spinal metastases RADIOTHERAPY AND ONCOLOGY Gibbs, I. C., Kamnerdsupaphon, P., Ryu, M., Dodd, R., Kiernan, M., Change, S. D., Adler, J. R. 2007; 82 (2): 185-190

  Abstract

  To determine the effectiveness and safety of image-guided robotic radiosurgery for spinal metastases.From 1996 to 2005, 74 patients with 102 spinal metastases were treated using the CyberKnife at Stanford University. Sixty-two (84%) patients were symptomatic. Seventy-four percent (50/68) of previously treated patients had prior radiation. Using the CyberKnife, 16-25 Gy in 1-5 fractions was delivered. Patients were followed clinically and radiographically for at least 3 months or until death.With mean follow-up of 9 months (range 0-33 months), 36 patients were alive and 38 were dead at last follow-up. No death was treatment related. Eighty-four (84%) percent of symptomatic patients experienced improvement or resolution of symptoms after treatment. Three patients developed treatment-related spinal injury. Analysis of dose-volume parameters and clinical parameters failed to identify predictors of spinal cord injury.Robotic radiosurgery is effective and generally safe for spinal metastases even in previously irradiated patients.

  View details for DOI 10.1016/j.radonc.2006.11.023

  View details for Web of Science ID 000245151400011

  View details for PubMedID 17257702

• A study of the accuracy of CyberKnife spinal radiosurgery using skeletal structure tracking NEUROSURGERY Ho, A. K., Fu, D., Cotrutz, C., Hancock, S. L., Chang, S. D., Gibbs, I. C., Maurer, C. R., Adler, J. R. 2007; 60 (2): 147-156

  View details for DOI 10.1227/01.NEU.0000249248.55923.EC

  View details for Web of Science ID 000244230600037

• Efficacy and safety of CyberKnife radiosurgery for acromegaly. Pituitary Roberts, B. K., Ouyang, D. L., Lad, S. P., Chang, S. D., Harsh, G. R., Adler, J. R., Soltys, S. G., Gibbs, I. C., Remedios, L., Katznelson, L. 2007; 10 (1): 19-25

  Abstract

  Acromegaly is a disease characterized by GH hypersecretion, and is typically caused by a pituitary somatotroph adenoma. The primary mode of therapy is surgery, and radiotherapy is utilized as an adjuvant strategy to treat persistent disease. The aim of this study was to determine the efficacy and tolerability of CyberKnife stereotactic radiosurgery in acromegaly.A retrospective review of biochemical and imaging data for subjects with acromegaly treated with CyberKnife stereotactic radiosurgery between 1998 and 2005 at Stanford University Hospital.Nine patients with active acromegaly were treated with radiosurgery using the CyberKnife (CK).Biochemical response based on serum insulin-like growth factor-1 (IGF-1), anterior pituitary hormone function, and tumor size with MRI scans were analyzed.After a mean follow up of 25.4 months (range, 6-53 months), CK radiosurgery resulted in complete biochemical remission in 4 (44.4%) subjects, and in biochemical control with the concomitant use of a somatostatin analog in an additional subject. Smaller tumor size was predictive of treatment success: baseline tumor volume was 1.28 cc (+/- 0.81, SD) vs. 3.93 cc (+/- 1.54) in subjects with a normal IGF-1 vs. those with persistent, active disease, respectively (P = 0.02). The mean biologically effective dose (BED) was higher in subjects who achieved a normal IGF-1 vs. those with persistent, active disease, 172 Gy(3) (+/-28) vs. 94 Gy(3) (+/-17), respectively (P < 0.01). At least one new anterior pituitary hormone deficiency was observed after CK in 3 (33%) patients: two developed hypogonadism, and one developed panhypopituitarism.CK radiosurgery may be a valuable adjuvant therapy for the management of acromegaly.

  View details for PubMedID 17273921

• Efficacy and safety of CyberKnife radiosurgery for acromegaly. Pituitary Roberts, B. K., Ouyang, D. L., Lad, S. P., Chang, S. D., Harsh, G. R., Adler, J. R., Soltys, S. G., Gibbs, I. C., Remedios, L., Katznelson, L. 2007; 10 (1): 17

  View details for PubMedID 27519534

• Trigeminal Neuralgia: Treatment with the Cyberknife Revista Medica Lim M, Bower R, Adler JR, Chang SD 2007; 13 (1): 195-200
• Irradiation of glomus jugulare tumors: a historical perspective. Neurosurgical focus Li, G., Chang, S., Adler, J. R., Lim, M. 2007; 23 (6): E13-?

  Abstract

  Glomus jugulare tumors are rare, slow-growing vascular lesions that arise from the chief cells of the paraganglia within the jugular bulb. They can be associated with the tympanic branch of the glossopharyngeal nerve (Jacobsen nerve) or the auricular branch of the vagus nerve (Arnold nerve) and are also referred to as chemodectomas or nonchromaffin paragangliomas. Optimal treatment of these histologically benign tumors remains controversial. Surgery remains the treatment of choice, but can carry high morbidity rates. External-beam radiation was originally used for subtotal resections and in patients who were poor surgical candidates; however, radiosurgery has recently been introduced as an effective and safe treatment option for patients with these tumors. In this article the authors discuss the history of radiation therapy for glomus jugulare tumors, focusing on recent radiosurgical results.

  View details for PubMedID 18081478

• Cyberknife radiosurgery for arteriovenous malformations Rivista Medica Chang SD, Adler JR 2007; 13 (1): 71-77
• CyberKnife radiosurgical rhizotomy for the treatment of atypical trigeminal nerve pain. Neurosurgical focus Patil, C. G., Veeravagu, A., Bower, R. S., Li, G., Chang, S. D., Lim, M., Adler, J. R. 2007; 23 (6): E9-?

  Abstract

  Patients with atypical trigeminal neuralgia (TN) have unilateral pain in the trigeminal distribution that is dull, aching, or burning in nature and is constant or nearly constant. Studies of most radiosurgical and surgical series have shown lower response rates in patients with atypical TN. This study represents the first report of the treatment of atypical TN with frameless CyberKnife stereotactic radiosurgery (SRS).Between 2002 and 2007, 7 patients that satisfied the criteria for atypical TN and underwent SRS were included in our study. A 6-8-mm segment of the trigeminal nerve was targeted, excluding the proximal 3 mm at the brainstem. All patients were treated in a single session with a median maximum dose of 78 Gy and a median marginal dose of 64 Gy.Outcomes in 7 patients with a mean age of 61.6 years and a median follow-up of 20 months are reported. Following SRS, 4 patients had complete pain relief, 2 had minimal pain relief with some decrease in the intensity of their pain, and 1 patient experienced no pain relief. Pain relief was reported within 1 week of SRS in 4 patients and at 4 months in 2 patients. After a median follow-up of 28 months, pain did not recur in any of the 4 patients who had reported complete pain relief. Complications after SRS included bothersome numbness in 3 patients and significant dysesthesias in 1 patient.The authors have previously reported a 90% rate of excellent pain relief in patients with classic TN treated with CyberKnife SRS. Compared with patients with classic TN, patients with atypical TN have a lower rate of pain relief. Nevertheless, the nearly 60% rate of success after SRS achieved in this study is still comparable to or better than results achieved with any other treatment modality for atypical TN.

  View details for PubMedID 18081486

• Robotic radiosurgery for the treatment of radioresistant brain metastases 7th Congress of the European-Association-for-Neuro-Oncology (EANO) Hara, W., Li, G., Puataweepong, P., Adler, J., Chang, S., Gibbs, I. C. OXFORD UNIV PRESS INC. 2006: 486–86

  View details for Web of Science ID 000240877301365

• Visual field preservation after multisession CyberKnife radiosurgery for perioptic lesions NEUROSURGERY Adler, J. R., Gibbs, I. C., Puataweepong, P., Chang, S. D. 2006; 59 (2): 244-253

  Abstract

  The restricted radiation tolerance of the anterior visual pathways represents a unique challenge for ablating adjacent lesions with single-session radiosurgery. Although preliminary studies have recently demonstrated that multisession radiosurgery for selected perioptic tumors is both safe and effective, the number of patients in these clinical series was modest and the length of follow-up limited. The current retrospective study is intended to help address these shortcomings.Forty-nine consecutive patients with meningioma (n = 27), pituitary adenoma (n = 19), craniopharyngioma (n = 2), or mixed germ cell tumor (n = 1) situated within 2 mm of a "short segment" of the optic apparatus underwent multisession image-guided radiosurgery at Stanford University Medical Center. Thirty-nine of these patients had previous subtotal surgical resection, and six had previously been treated with conventional fractionated radiotherapy (6). CyberKnife radiosurgery was delivered in two to five sessions to an average tumor volume of 7.7 cm3 and a cumulative average marginal dose of 20.3 Gy. Formal visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months.After a mean visual field follow-up of 49 months (range, 6-96 mo), vision was unchanged postradiosurgery in 38 patients, improved in eight (16%), and worse in three (6%). In each instance, visual deterioration was accompanied by tumor progression that ultimately resulted in patient death. However, one of these patients, who had a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, initially experienced early visual loss without significant tumor progression after both a previous course of radiotherapy and three separate sessions of radiosurgery. After a mean magnetic resonance imaging follow-up period of 46 months, tumor volume was stable or smaller in all other cases. Two patients died of unrelated nonbrain causes.Multisession radiosurgery resulted in high rates of tumor control and preservation of visual function in this group of perioptic tumors. Ninety-four percent of patients retained or improved preradiosurgical vision. This intermediate-term experience reinforces the findings from earlier studies that suggested that multisession radiosurgery can be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions immediately adjacent to short segments of the optic apparatus.

  View details for DOI 10.1227/01.NEU.0000223512.09115.3E

  View details for Web of Science ID 000239763800017

  View details for PubMedID 16883165

• Multisession cyberknife radiosurgery for intramedullary spinal cord arteriovenous malformations NEUROSURGERY Sinclair, J., Chang, S. D., Gibbs, I. C., Adler, J. R. 2006; 58 (6): 1081-1088

  Abstract

  Intramedullary spinal cord arteriovenous malformations (AVMs) have an unfavorable natural history that characteristically involves myelopathy secondary to progressive ischemia and/or recurrent hemorrhage. Although some lesions can be managed successfully with embolization and surgery, AVM size, location, and angioarchitecture precludes treatment in many circumstances. Given the poor outlook for such patients, and building on the successful experience with radiosurgical ablation of cerebral AVMs, our group at Stanford University has used CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiosurgery (SRS) to treat selected spinal cord AVMs since 1997. In this article, we retrospectively analyze our preliminary experience with this technique.Fifteen patients with intramedullary spinal cord AVMs (nine cervical, three thoracic, and three conus medullaris) were treated by image-guided SRS between 1997 and 2005. SRS was delivered in two to five sessions with an average marginal dose of 20.5 Gy. The biologically effective dose used in individual patients was escalated gradually over the course of this study. Clinical and magnetic resonance imaging follow-up were carried out annually, and spinal angiography was repeated at 3 years.After a mean follow-up period of 27.9 months (range, 3-59 mo), six of the seven patients who were more than 3 years from SRS had significant reductions in AVM volumes on interim magnetic resonance imaging examinations. In four of the five patients who underwent postoperative spinal angiography, persistent AVM was confirmed, albeit reduced in size. One patient demonstrated complete angiographic obliteration of a conus medullaris AVM 26 months after radiosurgery. There was no evidence of further hemorrhage after CyberKnife treatment or neurological deterioration attributable to SRS.This description of CyberKnife radiosurgical ablation demonstrates its feasibility and apparent safety for selected intramedullary spinal cord AVMs. Additional experience is necessary to ascertain the optimal radiosurgical dose and ultimate efficacy of this technique.

  View details for DOI 10.1227/01.NEU.0000215891.25153.BA

  View details for Web of Science ID 000237785900023

  View details for PubMedID 16723887

• Cyberknife radiosurgery for benign intradural extramedullary spinal tumors NEUROSURGERY Dodd, R. L., Ryu, M. R., Kamnerdsupaphon, P., Gibbs, I. C., Chang, S. D., Adler, J. R. 2006; 58 (4): 674-684

  Abstract

  Microsurgical resection of benign intradural extramedullary spinal tumors is generally safe and successful, but patients with neurofibromatosis, recurrent tumors, multiple lesions, or medical problems that place them at higher surgical risk may benefit from alternatives to surgery. In this prospective study, we analyzed our preliminary experience with image-guided radiosurgical ablation of selected benign spinal neoplasms.Since 1999, CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery was used to manage 51 patients (median age, 46 yr; range, 12-86 yr) with 55 benign spinal tumors (30 schwannomas, nine neurofibromas, 16 meningiomas) at Stanford University Medical Center. Total treatment doses ranged from 1600 to 3000 cGy delivered in consecutive daily sessions (1-5) to tumor volumes that varied from 0.136 to 24.6 cm.Less than 1 year postradiosurgery, three of the 51 patients in this series (one meningioma, one schwannoma, and one neurofibroma) required surgical resection of their tumor because of persistent or worsening symptoms; only one of these lesions was larger radiographically. However, 28 of the 51 patients now have greater than 24 months clinical and radiographic follow-up. After a mean follow-up of 36 months, all of these later lesions were either stable (61%) or smaller (39%). Two patients died from unrelated causes. Radiation-induced myelopathy appeared 8 months postradiosurgery in one patient.Although more patients studied over an even longer follow-up period are needed to determine the long-term efficacy of spinal radiosurgery for benign extra-axial neoplasms, short-term clinical benefits were observed in this prospective analysis. The present study demonstrates that CyberKnife radiosurgical ablation of such tumors is technically feasible and associated with low morbidity.

  View details for DOI 10.1227/01.NEU.0000204128.84742.8F

  View details for Web of Science ID 000237047200026

  View details for PubMedID 16575331

• Stereotactic radiosurgery using CT cisternography and non-isocentric planning for the treatment of trigeminal neuralgia. Computer aided surgery Lim, M., Cotrutz, C., Romanelli, P., Schaal, D., Gibbs, I., Chang, S. D., Adler, J. R. 2006; 11 (1): 11-20

  Abstract

  Frame-based radiosurgical rhizotomy has been shown in clinical studies to be effective for managing trigeminal neuralgia (TN). To date, however, only a small pilot study has been published for the frameless, image-guided CyberKnife system. We present our preliminary experience with 29 trigeminal neuralgia patients treated with the frameless CyberKnife using X-ray image-guided targeting, a novel CT method for target definition, and non-isocentric planning.All 29 patients failed previous medical therapy and 14 had undergone prior surgical procedures. CT iohexal cisternography was used to identify the 6- to 8-mm segment of nerve to be lesioned. The marginal dose ranged from 60 to 70 Gy (median 66.4 Gy) as defined at an average 79th percentile. The corresponding Dmax varied from 71.4 to 86.4 Gy (median 77.91 Gy).After a median 10-month follow-up, 26 of 29 (90%) patients rated their pain control as excellent and 3 (10%) reported no improvement. Median time to improvement was 6 days. No or only minor progression in numbness was reported by 22 of 29 (76%) patients, 4 of 29 (14%) patients reported worsening, and 3 of 29 (10%) reported the onset of severe ipsilateral facial numbness. Two patients whose target volume inadvertently included the semi-lunar ganglion developed painful dysethesias in the distribution of their numbness.Although the optimal dose and length of nerve to be lesioned are still being refined, this preliminary experience suggests that image-guided robotic radiosurgery can effectively lesion the trigeminal nerve. Further follow-up is needed to determine whether our method has advantages over the more commonly used procedure for radiosurgical trigeminal rhizotomy.

  View details for PubMedID 16531338

• Visual field preservation after curative multi-modality treatment of occipital lobe artemovenous malformations NEUROSURGERY Sinclair, J., Marks, M. P., Levy, R. P., Adler, J. R., Chang, S. D., Lopez, J. R., Do, H. M., Bell-Stephens, T. E., Lim, M., Steinberg, G. K. 2005; 57 (4): 655-666

  Abstract

  Occipital lobe arteriovenous malformations (AVMs) provide challenging management decisions because of their proximity to the visual cortex and optic radiations. Preservation of visual function throughout treatment is the mainstay of therapeutic planning. We reviewed visual field (VF) outcomes of all patients who received curative treatment for occipital AVMs at Stanford University to evaluate the efficacy of different treatment strategies.We conducted a retrospective review of 55 patients with occipital AVMs treated at Stanford University between 1984 and 2003. Clinical presentation, AVM morphology, and treatment modality were correlated with VF function before and after therapeutic intervention.Of 55 patients, 48 (87.3%) underwent multimodality AVM treatment (7 patients < 3 yr from radiosurgery were excluded from final analysis). One patient died from intracerebral hemorrhage 11 months post-radiosurgery, and five patients deferred further treatment. Forty-two patients (87.5%) were cured, with no residual AVM on final angiography. Curative therapeutic modalities used included embolization alone (2 patients), microsurgery alone (6 patients), microsurgery with radiosurgery (1 patient), microsurgery with embolization (23 patients), radiosurgery with embolization (4 patients), and embolization with radiosurgery and microsurgery (6 patients). Mean follow-up was 5.8 years including treatment. VF follow-up was available in all 42 patients. Twenty-eight (66.7%) patients experienced no change in VFs, six (14.3%) patients with previously abnormal VFs improved, and eight (19.0%) patients showed worsening of VFs (although none developed a new homonymous VF deficit). Duration of treatment was related to VF outcome in patients who presented without a history of AVM-related hemorrhage.Occipital AVMs can be safely cured using multimodality strategies with minimal risk to visual function despite the proximity of these lesions to the visual cortex and associated pathways.

  View details for DOI 10.1227/01.NEU.0000175547.05291.85

  View details for PubMedID 16239877

• Staged stereotactic irradiation for acoustic neuroma NEUROSURGERY Chang, S. D., Gibbs, I. C., Sakamoto, G. T., Lee, E., Oyelese, A., Adler, J. R. 2005; 56 (6): 1254-1261

  Abstract

  Stereotactic radiosurgery has proven effective in the treatment of acoustic neuromas. Prior reports using single-stage radiosurgery consistently have shown excellent tumor control, but only up to a 50 to 73% likelihood of maintaining hearing at pretreatment levels. Staged, frame-based radiosurgery using 12-hour interfraction intervals previously has been shown by our group to achieve excellent tumor control while increasing the rate of hearing preservation at 2 years to 77%. The arrival of CyberKnife (Accuray, Inc., Sunnyvale, CA) image-guided radiosurgery now makes it more practical to treat acoustic neuroma with a staged approach. We hypothesize that such factors may further minimize injury of adjacent cranial nerves. In this retrospective study, we report our experience with staged radiosurgery for managing acoustic neuromas.Since 1999, the CyberKnife has been used to treat more than 270 patients with acoustic neuroma at Stanford University. Sixty-one of these patients have now been followed up for a minimum of 36 months and form the basis for the present clinical investigation. Among the treated patients, the mean transverse tumor diameter was 18.5 mm, whereas the total marginal dose was either 18 or 21 Gy using three 6- or 7-Gy fractions. Audiograms and magnetic resonance imaging were obtained at 6-months intervals after treatment for the first 2 years and then annually thereafter.Of the 61 patients with a minimum of 36 months of follow-up (mean, 48 mo), 74% of patients with serviceable hearing (Gardner-Robinson Class 1-2) maintained serviceable hearing at the last follow-up, and no patient with at least some hearing before treatment lost all hearing on the treated side. Only one treated tumor (2%) progressed after radiosurgery; 29 (48%) of 61 decreased in size and 31 (50%) of the 61 tumors were stable. In no patients did new trigeminal dysfunction develop, nor did any patient experience permanent injury to their facial nerve; two patients experienced transient facial twitching that resolved in 3 to 5 months.Although still preliminary, these results indicate that improved tumor dose homogeneity and a staged treatment regimen may improve hearing preservation in acoustic neuroma patients undergoing stereotactic radiosurgery.

  View details for DOI 10.1227/01.NEU.0000159650.79833.2B

  View details for Web of Science ID 000229690300018

  View details for PubMedID 15918941

• Revascularization of the posterior circulation SKULL BASE-AN INTERDISCIPLINARY APPROACH Coert, B. A., Chang, S. D., Marks, M. P., Steinberg, G. K. 2005; 15 (1): 43-62

  Abstract

  The primary objective of revascularization procedures in the posterior circulation is the prevention of vertebrobasilar ischemic stroke. Specific anatomical and neurophysiologic characteristics such as posterior communicating artery size affect the susceptibility to ischemia. Current indications for revascularization include symptomatic vertebrobasilar ischemia refractory to medical therapy and ischemia caused by parent vessel occlusion as treatment for complex aneurysms. Treatment options include endovascular angioplasty and stenting, surgical endarterectomy, arterial reimplantation, extracranial-to-intracranial anastomosis, and indirect bypasses. Pretreatment studies including cerebral blood flow measurements with assessment of hemodynamic reserve can affect treatment decisions. Careful blood pressure regulation, neurophysiologic monitoring, and neuroprotective measures such as mild brain hypothermia can help minimize the risks of intervention. Microscope, microinstruments and intraoperative Doppler are routinely used. The superficial temporal artery, occipital artery, and external carotid artery can be used to augment blood flow to the superior cerebellar artery, posterior cerebral artery, posterior inferior cerebellar artery, or anterior inferior cerebellar artery. Interposition venous or arterial grafts can be used to increase length. Several published series report improvement or relief of symptoms in 60 to 100% of patients with a reduction of risk of future stroke and low complication rates.

  View details for PubMedID 16148983

• The Cyberknife: Potential in patients with central nervous system tumors American Journal of Cancer Chang SD 2005; 4 (6): 383-393
• Stereotactic radiosurgery using CT cisternography and non-isocentric planning for the treatment of trigeminal neuralgia 14th Meeting of the World-Society-for-Stereotactic-and-Functional-Neurosurgery Romanelli, P., Lim, M., Isidori, A., Chang, S. D., Adler, J. R. MEDIMOND PUBLISHING CO. 2005: 219–223

  View details for Web of Science ID 000233855700038

• CyberKnife radiosurgery for idiopathic trigeminal neuralgia. Neurosurgical focus Lim, M., Villavicencio, A. T., Burneikiene, S., Chang, S. D., Romanelli, P., McNeely, L., McIntyre, M., Thramann, J. J., Adler, J. R. 2005; 18 (5): E9-?

  Abstract

  Gamma knife surgery is an accepted treatment option for trigeminal neuralgia (TN). The safety and efficacy of CyberKnife radiosurgery as a treatment option for TN, however, has not been established.Forty-one patients were treated between May 2002 and September 2004 for idiopathic TN at Stanford University and the Rocky Mountain CyberKnife Center. Patients with atypical pain, multiple sclerosis, or previous radiosurgical treatment or a follow-up duration of less than 6 months were excluded. Patients were evaluated for the level of pain control, response rate, time to pain relief, occurrence of hypesthesia, and time to pain recurrence with respect to the length of the nerve treated and the maximum and the minimum dose to the nerve margin. Thirty-eight patients (92.7%) experienced initial pain relief at a median of 7 days after treatment (range, 24 hours-4 months). Pain control was ranked as excellent in 36 patients (87.8%), moderate in two (4.9%), and three (7.3%) reported no change. Six (15.8%) of the 38 patients with initial relief experienced a recurrence of pain at a median of 6 months (range 2-8 months). Long-term response after a mean follow-up time of 11 months was found in 32 (78%) of 41. Twenty-one patients (51.2%) experienced numbness after treatment.CyberKnife radiosurgery for TN has high rates of initial pain control and short latency to pain relief compared with those reported for other radiosurgery systems. The doses used for treatment were safe and effective. Higher prescribed doses were not associated with improvement in pain relief or recurrence rate. The hypesthesia rate was related to the length of the trigeminal nerve treated.

  View details for PubMedID 15913285

• Efficacy and safety of stereotactic radiosurgery for glomus jugulare tumors. Neurosurgical focus Lim, M., Gibbs, I. C., Adler, J. R., Chang, S. D. 2004; 17 (2): E11-?

  Abstract

  Since the mid-1990s the use of radiosurgery for glomus jugulare tumors has grown in popularity. Despite its increased use, follow-up periods for radiosurgery are short and the numbers of patients reported are small. To add to the available information, the authors report their experience with the application of linear accelerator (LINAC) or CyberKnife modalities in 13 patients with 16 tumors.All patients were treated with frame-based LINAC or CyberKnife radiosurgery, with doses ranging from 1400 to 2700 cGy. Patients were retrospectively assessed for posttreatment side effects, which included hearing loss, tongue weakness, and vocal hoarseness. The patients' most recent magnetic resonance (MR) images were also assessed for changes in tumor size. The median follow-up duration was 41 months and the mean follow-up period was 60 months. All tumors remained stable or decreased in size on follow-up MR images. All patients had stable neurological symptoms, and one experienced transient ipsilateral tongue weakness and hearing loss, both of which subsequently resolved. One patient experienced transient ipsilateral vocal cord paresis; however, this individual had received previous external-beam radiation therapy.The authors' findings continue to support radiosurgery as an effective and safe method of treatment for glomus jugulare tumors that results in low rates of morbidity.

  View details for PubMedID 15329026

• Preliminary visual field preservation after staged CyberKnife radiosurgery for perioptic lesions NEUROSURGERY Pham, C. J., Chang, S. D., Gibbs, I. C., Jones, P., Heilbrun, M. P., Adler, J. R. 2004; 54 (4): 799-810

  Abstract

  The limited radiation tolerance of the optic nerves and the optic chiasm makes it a challenge to treat immediately adjacent lesions with radiosurgery. Staged or hypofractionated radiosurgery has the virtue of combining the accuracy and conformality of radiosurgery with the normal tissue-sparing benefits of fractionation. We describe a consecutive series of patients with meningiomas and pituitary adenomas abutting the anterior visual pathways who were treated with staged, image-guided radiosurgery.Thirty-four patients with either meningiomas (20 patients) or pituitary adenomas (14 patients) within 2 mm of the optic apparatus were treated. Several patients had previously been treated with conventional fractionated radiotherapy (5 patients) or subtotal surgical resection (23 patients). Radiosurgery was delivered in two to five stages to a cumulative average marginal dose of 20.0 Gy. Visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months after treatment.The mean follow-up period was 29 months (range, 15-62 mo). Pre- and posttreatment vision was unchanged in 20 patients, improved in 10, and worse in 3. One patient died during follow-up as a result of an unrelated cardiac event. Visual loss was accompanied by tumor progression in two cases. In a third patient with a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, injury to one optic nerve occurred after both a prior course of radiotherapy and three separate sessions of radiosurgery.Staged radiosurgery resulted in high rates of tumor control and preservation of visual function. Ninety-one percent of patients retained their presurgical vision. Staged radiosurgery may be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions adjacent to the optic apparatus.

  View details for DOI 10.1227/01.NEU.0000114261.18723.6A

  View details for Web of Science ID 000220769100004

  View details for PubMedID 15046645

• Radiation tolerance of the spinal cord to staged radiosurgery 6th Meeting of the International-Stereotactic-Radiosurgery-Society Gibbs, I. C., Chang, S. D., Pham, C., Adler, J. R. KARGER. 2004: 22–28

  View details for Web of Science ID 000221523300003

• Quality assurance of the cyberknife fiducial and skull tracking systems 6th Meeting of the International-Stereotactic-Radiosurgery-Society Ho, A., Cotrutz, C., Chang, S. D., Adler, J. R., Gibbs, I. C. KARGER. 2004: 255–259

  View details for Web of Science ID 000221523300028

• Temporal pattern of pain relief using Cyberknife radiosurgery for trigeminal neuralgia: A preliminary report Radiosurgery Romanelli P, Chang SD, Gibbs IC, Heit G, Adler JR 2004; 5: 181-189
• Basic quality assurance of the Cyberknife system Radiosurgery Ho AK, Cotrutz C, Chang SD, Adler JR, Gibbs IC 2004; 5: 255-259
• Radiation tolerance of the spinal cord to staged radiosurgery Radiosurgery Gibbs IC, Chang SD, Pham C, Adler JR 2004; 5: 22-28
• Temporal pattern of pain relief using cyberknife radiosurgery for trigeminal neuralgia: A preliminary report 6th Meeting of the International-Stereotactic-Radiosurgery-Society Romanelli, P., Chang, S., Gibbs, I. C., Heit, G., Adler, J. R. KARGER. 2004: 181–189

  View details for Web of Science ID 000221523300021

• Stereotactic radiosurgery for hemangiomas and ependymomas of the spinal cord. Neurosurgical focus Ryu, S. I., Kim, D. H., Chang, S. D. 2003; 15 (5): E10-?

  Abstract

  The optimal treatment for intramedullary spinal tumors is controversial, because both resection and conventional radiation therapy are associated with potential morbidity. Stereotactic radiosurgery can theoretically deliver highly conformal, high-dose radiation to surgically untreatable lesions while simultaneously mitigating radiation exposure to large portions of the spinal cord. The purpose of this study was to evaluate the authors' initial experience with frameless stereotactic radiosurgery for intramedullary spinal tumors.Between 1998 and 2003, 10 intramedullary spinal tumors were treated with stereotactic radiosurgery at the authors' institution. Seven hemangioblastomas and three ependymomas were treated in four men and three women. These patients either had recurrent tumors, had undergone several previous surgeries, had medical contraindications to surgery, or had declined open resection. Conformal treatment planning delivered a prescribed dose of 1800 to 2500 cGy (mean 2100 cGy) to the lesions in one to three stages. No significant treatment-related complications have been recorded. The mean radiographic and clinical follow-up duration was 12 months (range 1-24 months). One ependymoma and two hemangioblastomas were smaller on follow-up neuroimaging. The remaining tumors were stable at the time of follow-up imaging.Stereotactic radiosurgery for intramedullary spinal tumors is feasible and safe in selected cases and may prove to be another therapeutic option for these challenging lesions.

  View details for PubMedID 15323467

• Radiosurgery and radiotherapy for sacral tumors. Neurosurgical focus Gibbs, I. C., Chang, S. D. 2003; 15 (2): E8-?

  Abstract

  Sacral tumors represent a small subset of spinal lesions and typically include chordomas, metastases, other primary bone tumors, and benign schwannomas. Resection is the standard treatment for many sacral tumors, but many types of sacral lesions have the potential for recurrence after excision. In these cases, adjuvant radiotherapy is often beneficial. Although conventional radiotherapy plays an important role in the management of spinal lesions, the radiation doses required for adequate local control of many sacral lesions generally exceed the tolerance doses of normal tissues, thus limiting its definitive role in the management of sacral tumors. Recent advances in the field of stereotactic radiosurgery have allowed precise targeting of the sacrum. In this report the authors review the use of these two forms of radiation treatment and their role in managing sacral tumors.

  View details for PubMedID 15350039

• Improved local control with stereotactic radiosurgical boost in patients with nasopharyngeal carcinoma 44th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Le, Q. T., Tate, D., Koong, A., Gibbs, I. C., Chang, S. D., Adler, J. R., Pinto, H. A., Terris, D. J., Fee, W. E., Goffinet, D. R. ELSEVIER SCIENCE INC. 2003: 1046–54

  Abstract

  Treatment of nasopharyngeal carcinoma using conventional external beam radiotherapy (EBRT) alone is associated with a significant risk of local recurrence. Stereotactic radiosurgery (STR) was used to boost the tumor site after EBRT to improve local control.Forty-five nasopharyngeal carcinoma patients received a STR boost after EBRT at Stanford University. Seven had T1, 16 had T2, 4 had T3, and 18 had T4 tumors (1997 American Joint Commission on Cancer staging). Ten had Stage II, 8 had Stage III, and 27 had Stage IV neoplasms. Most patients received 66 Gy of EBRT delivered at 2 Gy/fraction. Thirty-six received concurrent cisplatin-based chemotherapy. STR was delivered to the primary site 4-6 weeks after EBRT in one fraction of 7-15 Gy.At a medium follow-up of 31 months, no local failures had occurred. The 3-year local control rate was 100%, the freedom from distant metastasis rate was 69%, the progression-free survival rate was 71%, and the overall survival rate was 75%. Univariate and multivariate analyses revealed N stage (favoring N0-N1, p = 0.02, hazard ratio HR 4.2) and World Health Organization histologic type (favoring type III, p = 0.002, HR 13) as significant factors for freedom from distant metastasis. World Health Organization histologic type (p = 0.004, HR 10.5) and age (p = 0.01, HR 1.07/y) were significant factors for survival. Late toxicity included transient cranial nerve weakness in 4, radiation-related retinopathy in 1, and asymptomatic temporal lobe necrosis in 3 patients who originally had intracranial tumor extension.STR boost after EBRT provided excellent local control in nasopharyngeal carcinoma patients. The incidence of late toxicity was acceptable. More effective systemic treatment is needed to achieve improved survival.

  View details for DOI 10.1016/S0360-3016(03)00117-2

  View details for Web of Science ID 000183937500018

  View details for PubMedID 12829140

• Multimodality treatment of giant intracranial arteriovenous malformations NEUROSURGERY Chang, S. D., Marcellus, M. L., Marks, M. P., Levy, R. P., Do, H. M., Steinberg, G. K. 2003; 53 (1): 1-11

  Abstract

  Giant arteriovenous malformations (AVMs) (i.e., those greater than 6 cm at maximum diameter) are difficult to treat and often carry higher treatment morbidity and mortality rates than do smaller AVMs. In this study, we reviewed the treatment, angiographic results, and clinical outcomes in 53 patients with giant AVMs who were treated at Stanford between 1987 and 2001.The patients selected included 20 males (38%) and 33 females (62%). Their presenting symptoms were hemorrhage (n = 20; 38%), seizures (n = 18; 34%), headaches (n = 8; 15%), and progressive neurological deficits (n = 7; 13%). One patient was in Spetzler-Martin Grade III, 9 were in Spetzler-Martin Grade IV, and 43 were in Spetzler-Martin Grade V. The mean AVM size was 6.8 cm (range, 6-15 cm). AVM venous drainage was superficial (n = 7), deep (n = 20), or both (n = 26). At presentation, 31 patients (58%) were graded in excellent neurological condition, 17 were graded good (32%), and 5 were graded poor (9%).The patients were treated with surgery (n = 27; 51%), embolization (n = 52; 98%), and/or radiosurgery (n = 47; 89%). Most patients received multimodality treatment with embolization followed by surgery (n = 5), embolization followed by radiosurgery (n = 23), or embolization, radiosurgery, and surgery (n = 23). Nineteen patients (36%) were completely cured of their giant AVMs, 90% obliteration was achieved in 4 patients (8%), less than 90% obliteration was achieved in 29 patients (55%) who had residual AVMs even after multimodality therapy, and 1 patient was lost to follow-up. Of the 33 patients who either completed treatment or were alive more than 3 years after undergoing their most recent radiosurgery, 19 patients (58%) were cured of their AVMs. The long-term treatment-related morbidity rate was 15%. The clinical results after mean follow-up of 37 months were 27 excellent (51%), 15 good (28%), 3 poor (6%), and 8 dead (15%).The results in this series of patients with giant AVMs, which represents the largest series reported to date, suggest that selected symptomatic patients with giant AVMs can be treated successfully with good outcomes and acceptable risk. Multimodality treatment is usually necessary to achieve AVM obliteration.

  View details for PubMedID 12823868

• The efficacy of linear accelerator stereotactic radiosurgery in treating glomus jugulare tumors TECHNOLOGY IN CANCER RESEARCH & TREATMENT Lim, M., Gibbs, I. C., Adler, J. R., Martin, D. P., Chang, S. D. 2003; 2 (3): 261-265

  Abstract

  Treatment of glomus jugulare tumors with radiosurgery has grown in acceptance since the first reported treatment in 1995, but only a few centers have reported their experiences with limited follow up time. We report our experience with stereotactic radiosurgery in nine patients with ten glomus tumors. All patients were treated either with frame based LINAC or Cyberknife with doses ranging from 1600 cGy to 2500 cGy. Three patients received no previous therapy and one patient received additional external beam radiation for concomitant treatment of carotid body tumors. Patients were then followed for post treatment side effects in addition to change in tumor size by MRI evaluation. The median clinical follow-up time was 26 months (mean 54 months), median radiographic follow-up was 21.5 months (mean 46 months), with a range from 3 to 126 months. The results from our center demonstrated nine of ten tumors to be stable in size by MRI exam, and one tumor which regressed in size. Nine patients had stable neurological symptoms, and one patient experienced transient ipsilateral tongue weakness and hearing loss, both of which subsequently resolved. Our results continue to support radiosurgery as a suitable form of treatment for glomus jugulare tumors as evidenced by results from this four and a half year follow-up.

  View details for Web of Science ID 000183918300008

  View details for PubMedID 12779355

• The role of radiosurgery for hemangiopericytomas. Neurosurgical focus Chang, S. D., Sakamoto, G. T. 2003; 14 (5)

  Abstract

  Hemangiopericytomas represent a small subset of meningeal tumors. Despite their relatively uncommon nature, they are aggressive tumors known for recurrence. Resection is the standard treatment in most, although regrowth and metastases are common even after resection. The authors evaluate the role of stereotactic radiosurgery in the treatment of recurrent hemangiopericytomas.In a review of the Stanford radiosurgery patient database between 1989 and 2002, the authors found eight patients with recurrent hemangiopericytoma who underwent stereotactic radiosurgery. The mean age of this population was 45.1 years (range 24-67 years). All patients had been previously treated with resection, and five patients (63%) had undergone conventional radiotherapy. The mean radiosurgery dose to the tumor margin was 20.5 Gy (range 16-24 Gy). The mean clinical and radiographic follow-up period was 44 months (range 8-77 months). Of the eight tumors treated with radiosurgery, six decreased in size and two ultimately progressed. There were no radiosurgery-related complications.Stereotactic radiosurgery of hemangiopericytomas can result in increased tumor control and should be considered as a treatment option for patients in whom the diagnosis has been established and in whom residual tumor is demonstrated postoperatively. Close clinical and radiographic follow-up evaluation is necessary in this patient population because of the high rate of local recurrence and distant metastases.

  View details for PubMedID 15669810

• Parent vessel occlusion for vertebrobasilar fusiform and dissecting aneurysms AMERICAN JOURNAL OF NEURORADIOLOGY Leibowitz, R., Do, H. M., Marcellus, M. L., Chang, S. D., Steinberg, G. K., Marks, M. P. 2003; 24 (5): 902-907

  Abstract

  Previous reports of outcome with permanent vessel occlusion (PVO) for large, giant, or fusiform aneurysms in the posterior circulation have been limited. We undertook this study to evaluate the perioperative (within 30 days) and follow-up outcomes for patients treated with permanent occlusion of the vertebral artery for vertebrobasilar fusiform and dissecting aneurysms.Thirteen consecutive patients were studied. Two groups were defined for the study. Group I patients underwent PVO to achieve complete thrombosis of the aneurysm. Group II patients underwent PVO to reduce flow to the aneurysm where complete thrombosis was not desirable. Modified Rankin scores were obtained at presentation and at follow-up (follow-up range, 1-76 months; mean, 22.0 months).All group I aneurysms were shown to be thrombosed on the angiograms obtained at the immediate follow-up examinations. Improvement in outcome scores was achieved by all group I patients. Improvement in Rankin scores after endovascular treatment was statistically significant (P =.026). All group II patients had complete occlusion of the vertebral artery; however, continued filling of the fusiform aneurysm was still observed. Four patients in group II died during the follow-up period. Two of these deaths were attributable to the aneurysms. Of the remaining three patients, two experienced clinical worsening and one remained stable.In this series, PVO for chronic fusiform and acute dissecting aneurysms of the vertebrobasilar system proved to be a useful therapeutic endovascular technique. Long-term outcomes suggest that patients with aneurysms involving only one vertebral artery, where complete thrombosis can be achieved, have better clinical outcomes than those who have aneurysms involving the basilar artery or both vertebral arteries, where complete thrombosis cannot achieved by using PVO.

  View details for Web of Science ID 000183021100024

  View details for PubMedID 12748092

• Patterns of patient movement during frameless image-guided radiosurgery INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Murphy, M. J., Chang, S. D., Gibbs, I. C., Le, Q. T., Hai, J., Kim, D., Martin, D. P., Adler, J. R. 2003; 55 (5): 1400-1408

  Abstract

  Image-guided radiosurgery aligns the treatment beam to the target site by using a radiographic imaging system to locate anatomic landmarks associated with the treatment target. Because the procedure is performed without a rigid frame, the precision of dose alignment can be affected by patient movement. Movement is limited by noninvasive restraints and compensated by remeasuring the target position at short intervals throughout treatment and then realigning the beam. Frameless image-guided radiosurgery has been used at our institution to treat 250 cranial, 23 spinal, 9 lung, and 3 pancreas cases involving malignant and benign tumors as well as vascular malformations. We have analyzed the target position records for all of these cases to assess the frequency, magnitude, and case-by-case patterns of patient movement.The position of the treatment site during image-guided radiosurgery was measured at approximately 1-2-min intervals, on average, using orthogonal amorphous silicon X-ray cameras and an image registration process that determined all six degrees of freedom in the target's position. The change in position from one measurement to the next was indicative of patient movement.The treatment site position along each axis of translation was observed to vary by an average of 0.45 mm for the cranium, 0.53 mm for the cervical spine, 0.53 mm for the lumbar and thoracic spine, 1.06 mm for the lung, and 1.50 mm for the pancreas. Half of all cranial cases showed systematic drifting of the target away from the initial setup position.Using noninvasive restraints and supports, short-term movement of the head and spine during image-guided radiosurgery was limited to a radius of 0.8 mm, which satisfies the prevailing standard for radiosurgical dose alignment precision, but maintaining this margin of error throughout a treatment fraction requires regular monitoring of the target site's position.

  View details for DOI 10.1016/S0360-3016(02)04597-2

  View details for PubMedID 12654453

• An analysis of the accuracy of the Cyberknife: A robotic nameless stereotactic radiosurgical system NEUROSURGERY Chang, S. D., Main, W., Martin, D. P., Gibbs, I. C., Heilbrun, M. P. 2003; 52 (1): 140-146

  Abstract

  The use of stereotactic radiosurgical systems to treat intracranial and extracranial tumors and other lesions requires a high degree of accuracy in target identification and localization. The purpose of this study was to evaluate the total system accuracy of the CyberKnife (Accuray, Inc., Sunnyvale, CA), a frameless, image-guided, stereotactic radiosurgery system.Clinically relevant accuracy or application accuracy of the CyberKnife radiosurgery system is based on 1) the beam delivery accuracy, which combines the robot and the camera image tracking system, and 2) target localization accuracy, which combines computed tomographic (CT) imaging and treatment planning. Clinically relevant accuracy can be measured by delivering a radiation dose to phantoms, in which the target is defined on a set of CT images using all components of the CyberKnife system, including the treatment planning software, the robot, the camera tracking system, and the linear accelerator. Clinically relevant accuracy was measured in head phantoms loaded with packs of radiochromic film. The accuracy measured is the displacement of the dose contours from the treatment plan to that measured in the radiosurgically exposed phantom.Measurements of mean errors of the second-generation CyberKnife system at Stanford University Medical Center, installed in 2001, ranged from 0.7 mm for a CT slice thickness of 0.625 mm to 1.97 mm for a CT slice thickness of 3.75 mm.The frameless, image-guided, second-generation CyberKnife radiosurgery system has a clinically relevant accuracy of 1.1 +/- 0.3 mm when CT slice thicknesses of 1.25 mm are used. CyberKnife precision is comparable to published localization errors in current frame-based radiosurgical systems.

  View details for DOI 10.1227/01.NEU.0000039162.72141.18

  View details for Web of Science ID 000180195800031

  View details for PubMedID 12493111

• Image-guided spinal stereotactic radiosurgery TECHNIQUES IN NEUROSURGERY Ryu, S. I., Kim, D. H., Martin, D. P., Chang, S. D., Adler, J. R. 2003; 8 (1): 56-64

  View details for Web of Science ID 000181739000008

• Cyberknife radiosurgery for trigeminal neuralgia Meeting of the American-Society-for-Stereotactic-and-Functional-Neurosurgery Romanelli, P., Heit, G., Chang, S. D., Martin, D., Pham, C., Adler, J. KARGER. 2003: 105–9

  Abstract

  We present preliminary results using Cyberknife radiosurgery as a noninvasive treatment for trigeminal neuralgia (TN).Ten patients with medically refractory TN who were deemed unsuitable for conventional surgery underwent Cyberknife radiosurgery using CT cisternography for localization.Pain relief was achieved in 7 patients, in 5 of them within 24-72 h after irradiation.Cyberknife radiosurgery can achieve early-onset pain relief in a subset of TN patients. Improvements using this technique include the absence of a stereotactic ring, potentially improved targeting accuracy produced by CT cisternography and improved dose homogeneity.

  View details for DOI 10.1159/000075112

  View details for Web of Science ID 000188386000016

  View details for PubMedID 14742972

• Extracranial radiosurgery using the CyberKnife TECHNIQUES IN NEUROSURGERY Romanelli, P., Chang, S. D., Koong, A., Adler, J. R. 2003; 9 (3): 226-231

  View details for Web of Science ID 000186833600015

• Downregulation of cerebrospinal fluid production in patients with chronic hydrocephalus JOURNAL OF NEUROSURGERY Silverberg, G. D., Huhn, S., Jaffe, R. A., Chang, S. D., Saul, T., Heit, G., Von Essen, A., Rubenstein, E. 2002; 97 (6): 1271-1275

  Abstract

  The goal of this study was to determine the effect of hydrocephalus on cerebrospinal fluid (CSF) production rates in patients with acute and chronic hydrocephalus.The authors studied CSF production both in patients presenting with acute and chronic hydrocephalus, and patients with Parkinson disease (PD) of a similar mean age, whose CSF production was known to be normal. A modification of the Masserman method was used to measure CSF production through a ventricular catheter. The CSF production rates (means +/- standard deviations) in the three groups were then compared. The patients with PD had a mean CSF production rate of 0.42 +/- 0.13 ml/minute; this value lies within the normal range measured using this technique. Patients with acute hydrocephalus had a similar CSF production rate of 0.4 +/- 0.13 ml/minute, whereas patients with chronic hydrocephalus had a significantly decreased mean CSF production rate of 0.25 +/- 0.08 ml/minute.The authors postulate that chronic increased intracranial pressure causes downregulation of CSF production.

  View details for Web of Science ID 000179901000004

  View details for PubMedID 12507122

• Assessment of low-flow CSF drainage as a treatment for AD - Results of a randomized pilot study NEUROLOGY Silverberg, G. D., Levinthal, E., SULLIVAN, E. V., Bloch, D. A., Chang, S. D., Leverenz, J., Flitman, S., Winn, R., Marciano, F., Saul, T., Huhn, S., Mayo, M., McGuire, D. 2002; 59 (8): 1139-1145

  Abstract

  This prospective, randomized, controlled study was designed to investigate the safety, feasibility, and preliminary efficacy of long-term CSF drainage via a low-flow ventriculoperitoneal shunt in subjects suffering from AD.Twenty-nine subjects selected for probable AD (National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's Disease and Related Dementias Association criteria) were screened to exclude normal pressure hydrocephalus or other etiologies of dementia and randomized to treatment (shunt) or no treatment groups. The study endpoint was the comparison of group performance on psychometric testing at quarterly intervals for 1 year. Shunted subjects had CSF withdrawn for MAP-tau and Abeta((1-42)) assays at the same time intervals.There was no mortality from the surgical procedure, and no patient sustained a subdural hematoma. Five notable postoperative adverse events, which resolved without permanent neurologic deficit, were reported in the shunt group. Group mean Mattis Dementia Rating Scale total scores showed little change over the year in the shunt-treatment group, in contrast to a decline in the control group (p = 0.06). Mini-Mental State Examination mean scores supported a trend in favor of shunt treatment (p = 0.1). There was a concomitant decrease in ventricular CSF concentrations of AD biomarkers MAP-tau and Abeta((1-42)).The surgical procedure and the device are reasonably safe. Adverse events were consistent with shunt procedures for hydrocephalus in this older population. The endpoint data show a trend in favor of the treated group. A larger, randomized, double-blinded, controlled, clinical trial is underway.

  View details for Web of Science ID 000178726700007

  View details for PubMedID 12391340

• Image guided stereotactic radiosurgery for lesions in proximity to the anterior visual pathways: a preliminary report. Technology in cancer research & treatment Mehta, V. K., Lee, Q., Chang, S. D., Cherney, S., Adler, J. R. 2002; 1 (3): 173-180

  Abstract

  The incidence of optic neuropathy after stereotactic radiosurgery (SRS) is related to the total dose, fraction size, and treatment volume. Theoretically, fractionated SRS can decrease this risk. In this paper, we report our technique for fractionated SRS and assess its potential role in the management of tumors located adjacent to the anterior visual pathways. Since 1997, thirteen patients (median age: 50, range 21-76) with lesions in close proximity to the anterior visual pathways were treated on the CyberKnife image guided SRS system (Accuray, Inc., Sunnyvale, CA). The CyberKnife is a 6MV linear accelerator mounted on a robotic arm which can monitor and adjust to changes in the target position in real time thus eliminating skeletal frame immobilization and allowing for convenient multi-fraction SRS treatments. Magnetic Resonance Imaging (MRI) and computerized tomography (CT) imaging for treatment planning were obtained with the patients head immobilized in an aquaplast mask. After image fusion, the target and critical structures were delineated. Two to five fractions were prescribed with approximately a 24-hour interfraction interval. The patients received 25 Gy in 5 fractions (n=5), 21 Gy in 3 fractions (n=5), or 20 Gy in 2 fractions (n=3) to the 75-95% isodose line. Ten of the thirteen patients had good pretreatment vision. In nearly all instances, the volume of the optic nerve that received 80% of the prescribed dose was < 0.05 cm3. In all instances, the volume of the optic nerve that received 50% of the prescribed dose was 0.03 cm3 of optic nerve. With median follow up of 18 months (range 12 to 54), four patients have had improvement in their vision. No visual deterioration has been observed in any of the other patients. In addition, there has been no tumor progression within the treated field. Fractionated SRS using the CyberKnife is technically feasible and may decrease the risk of optic neuropathy. Greater patient accrual and longer follow up will be necessary to further determine the clinical benefit of this approach.

  View details for PubMedID 12622510

• The role of radiosurgery in the treatment of giant arteriovenous malformations 5th Meeting of the International-Stereotactic-Radiosurgery-Society Chang, S. D., Levy, R. P., Marks, M. P., Marcellus, M., Steinberg, G. K. KARGER. 2002: 42–53

  View details for Web of Science ID 000176153400006

• Image-guided radiosurgery in the treatment of spinal metastases. Neurosurgical focus MURPHY, M. J., Chang, S., Gibbs, I., Le, Q. T., Martin, D., Kim, D. 2001; 11 (6)

  Abstract

  The authors describe a new method for treating metastatic spinal tumors in which noninvasive, image-guided, frameless stereotactic radiosurgery is performed. Stereotactic radiosurgery delivers a high dose of radiation in a single or limited number of fractions to a lesion while maintaining delivery of a low dose to adjacent normal structures.Image-guided radiosurgery was developed by coupling an orthogonal pair of real-time x-ray cameras to a dynamically manipulated robot-mounted linear accelerator that guides the radiation beam to treatment sites associated with radiographic landmarks. This procedure can be conducted in an outpatient setting without the use of framebased skeletal fixation. The system relies on skeletal landmarks or implanted fiducial markers to locate treatment targets. Four patients with spinal metastases underwent radiosurgery with total prescription doses of 1000 to 1600 cGy in one or two fractions. Alignment of the treatment dose with the target volume was accurate to within 1.5 mm. During the course of each treatment fraction, patient movement was less than 0.5 mm on average. Dosimetry was highly conformal, with a demonstrated ability to deliver 1600 cGy to the perimeter of an irregular target volume while keeping exposure to the cord itself below 800 cGy.These experiences indicate that frameless radiosurgery is a viable therapeutic option for metastatic spine disease.

  View details for PubMedID 16463998

• The cerebrospinal fluid production rate is reduced in dementia of the Alzheimer's type NEUROLOGY Silverberg, G. D., Heit, G., Huhn, S., Jaffe, R. A., Chang, S. D., Bronte-Stewart, H., Rubenstein, E., Possin, K., Saul, T. A. 2001; 57 (10): 1763-1766

  Abstract

  To evaluate the production rate of CSF in patients with differing disease states.The authors measured the production rate of CSF in three groups of patients: five patients with PD below age 60 (aged 51 +/- 4 years, mean +/- SD), nine with PD over age 60 (aged 69 +/- 6 years, mean +/- SD), and seven with dementia of the Alzheimer's type (AD) (aged 72 +/- 9 years, mean +/- SD). This method, based on the Masserman technique, employs ventricular rather than a lumbar access to the CSF space. Furthermore, the volume of CSF removed during the procedure is only 3 mL rather than 10 mL.These measurements indicate that the mean rate of CSF production in patients with PD under age 60 was 0.47 +/- 0.13 mL/minute, in patients with PD aged 60 or older the mean rate was 0.40 +/- 0.12 mL/minute, and in patients with AD the mean rate was 0.20 +/- 0.06 mL/minute.These results indicate that the rate of CSF production in patients with PD is normal, and that the rate of CSF production in patients with AD is markedly reduced.

  View details for Web of Science ID 000172334700006

  View details for PubMedID 11723260

• Image-guided hypo-fractionated stereotactic radiosurgery to spinal lesions NEUROSURGERY Ryu, S. I., Chang, S. D., Kim, D. H., MURPHY, M. J., Le, Q. T., Martin, D. P., Adler, J. R. 2001; 49 (4): 838-846

  Abstract

  This article demonstrates the technical feasibility of noninvasive treatment of unresectable spinal vascular malformations and primary and metastatic spinal tumors by use of image-guided frameless stereotactic radiosurgery.Stereotactic radiosurgery delivers a high dose of radiation to a tumor volume or vascular malformation in a limited number of fractions and minimizes the dose to adjacent normal structures. Frameless image-guided radiosurgery was developed by coupling an orthogonal pair of x-ray cameras to a dynamically manipulated robot-mounted linear accelerator that guides the therapy beam to treatment sites within the spine or spinal cord, in an outpatient setting, and without the use of frame-based fixation. The system relies on skeletal landmarks or implanted fiducial markers to locate treatment targets. Sixteen patients with spinal lesions (hemangioblastomas, vascular malformations, metastatic carcinomas, schwannomas, a meningioma, and a chordoma) were treated with total treatment doses of 1100 to 2500 cGy in one to five fractions by use of image-guided frameless radiosurgery with the CyberKnife system (Accuray, Inc., Sunnyvale, CA). Thirteen radiosurgery plans were analyzed for compliance with conventional radiation therapy.Tests demonstrated alignment of the treatment dose with the target volume within +/-1 mm by use of spine fiducials and the CyberKnife treatment planning system. Tumor patients with at least 6 months of follow-up have demonstrated no progression of disease. Radiographic follow-up is pending for the remaining patients. To date, no patients have experienced complications as a result of the procedure.This experience demonstrates the feasibility of image-guided robotic radiosurgery for previously untreatable spinal lesions.

  View details for PubMedID 11564244

• Posterior cerebral circulation revascularization NEUROSURGERY CLINICS OF NORTH AMERICA Chang, S. D., Ryu, S. I., Steinberg, G. K. 2001; 12 (3): 519-?

  Abstract

  Posterior circulation revascularization has evolved as a method to treat selected patients with vertebrobasilar ischemia who have inaccessible atherosclerotic occlusive disease and who have failed maximal medical therapy. In addition, complex unclippable aneurysms of the posterior circulation are another indication for revascularization of the vertebrobasilar territory. Careful preoperative evaluation and meticulous attention to detail intraoperatively yield good patient outcomes with minimal morbidity and mortality. This article reviews the vascular anatomy of the posterior circulation and the indications, preoperative evaluation, operative techniques, clinical outcomes, and alternative treatments for patients requiring posterior circulation revascularization procedures.

  View details for Web of Science ID 000169857500006

  View details for PubMedID 11390312

• Current status and optimal use of radiosurgery ONCOLOGY-NEW YORK Chang, S. D., Adler, J. R. 2001; 15 (2): 209-216

  Abstract

  The field of stereotactic radiosurgery is rapidly advancing as a result of both improvements in radiosurgical equipment and better physician understanding of the clinical applications of stereotactic radiosurgery. This article will review recent developments in the field of radiosurgery, including advances in our understanding of the treatment of brain metastases and arteriovenous malformations, as well as the use of stereotactic radiosurgery as a boost following conventional radiation for nasopharyngeal carcinoma to minimize the rate of local recurrence. In addition, improved understanding of the radiobiology of normal neurologic structures adjacent to tumors undergoing radiosurgery has led to the use of fractionated stereotactic radiosurgery for the treatment of acoustic neuromas and tumors bordering the anterior visual pathways. Finally, a breakthrough in radiosurgery involving the development and use of frameless, image-guided stereotactic radiosurgery has allowed for both dose homogeneity and treatment of intracranial lesions based on nonisocentric treatment algorithms that result in improved target conformality. This same frameless radiosurgical system has also expanded the scope of radiosurgery to include the treatment of extracranial lesions throughout the body.

  View details for Web of Science ID 000167070000017

  View details for PubMedID 11252934

• Stereotactic radiosurgery and hypofractionated stereotactic radiotherapy for residual or recurrent cranial base and cervical chordomas. Neurosurgical focus Chang, S. D., Martin, D. P., Lee, E., Adler, J. R. 2001; 10 (3): E5-?

  Abstract

  In patients with chordomas the lesions often recur. Furthermore, the location of some chordomas within the base of the skull and the cervical spine can prevent complete resection from being achieved. Previous series have shown that stereotactic radiosurgery can be used as a treatment for residual chordomas with good overall results. The authors review their experience in using linear accelerator (LINAC) stereotactic radiosurgery to treat patients with recurrent and/or residual cranial base and cervical chordomas.Ten patients with chordomas (eight with cranial base and two with cervical lesions [below C-2]) underwent LINAC stereotactic radiosurgery. The mean patient age was 49 years (range 30-73 years). There were seven men and three women. Three patients had undergone one prior surgery, five had undergone two previous surgeries, and two had undergone three prior operations. The mean radiation dose was 19.4 Gy (range 18-24 Gy), and the maximum intratumoral dose averaged 27 Gy (range 24.1-33.1 Gy). The mean secondary collimator size was 14.4 mm (range 7.5-20 mm). The volume of the tumor treated ranged from 1.1 to 21.5 ml. In five patients a standard frame-based LINAC radiosurgery system was used, whereas in the other five the CyberKnife, a frameless image-guided LINAC radiosurgical system, was used. All patients were available for follow-up review, which averaged 4 years (range 1-9 years). Over the course of follow up, one chordoma (10%) was smaller in size, seven were stable, and two chordomas progressed (one in a patient who underwent reoperation and a second course of stereotactic radiosurgery, and the second in a patient who underwent reoperation alone). There were no new neurological deficits noted following radiosurgery in the eight of 10 patients in whom there was no tumor progression, and no patient developed radiation-induced necrosis.Stereotactic radiosurgery can be used to treat patients with recurrent or residual chordomas with excellent tumor control rates. Longer follow-up review in larger series is warranted to confirm these findings.

  View details for PubMedID 16734408

• Robotics and radiosurgery - The cyberknife STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Chang, S. D., Adler, J. R. 2001; 76 (3-4): 204-208

  Abstract

  The Cyberknife is a dedicated image-guided robotic radiosurgical device. While clinical results with intracranial lesions are comparable to frame-based radiosurgical techniques, recent experience demonstrates the potential to broadly expand the scope of radiosurgery to many extracranial sites.

  View details for Web of Science ID 000178706800015

  View details for PubMedID 12378098

• Image-guided extracranial radiosurgery 7th International Meeting on Progress in Radio-Oncology (ICRO/OGRO 7) Sattah, M., Guerrero, T., Chang, S., Martin, D., Le, Q. T., Gibbs, I., Adler, J. MEDIMOND S R L. 2001: 153–162

  View details for Web of Science ID 000176997100020

• AAEM news and comments Muscle & nerve Chang, Lopez, Steinberg 2000; 23 (9): 1450-1451

  View details for PubMedID 10951454

• Reply Muscle & nerve Chang, Lopez, Steinberg 2000; 23 (9): 1446-?

  View details for PubMedID 10951453

• Acquired cerebral arteriovenous malformation induced by an anaplastic astrocytoma: An interesting case NEUROLOGICAL RESEARCH Harris, O. A., Chang, S. D., Harris, B. T., Adler, J. R. 2000; 22 (5): 473-477

  Abstract

  High grade gliomas foster an environment rich in angiogenic factors that promote neovascularity. We report a case of a cerebral arteriovenous malformation, which developed in the setting of a high grade astrocytoma. The patient presented with complaints of confusion and left hemiparesis. An initial cerebral angiogram was normal. Repeat angiography six weeks later demonstrated an extremely vascular lesion with arteriovenous shunting involving the right thalamus and occipital lobe. Histopathologic evaluation of open biopsy and autopsy specimens demonstrated a high grade astrocytoma in association with an arteriovenous malformation. Immunohistochemical staining with VEGF was diffusely positive. A possible role for the hyperangiogenic environment of a high grade astrocytoma resulting in the development of an arteriovenous malformation is discussed.

  View details for Web of Science ID 000088406000007

  View details for PubMedID 10935219

• Microsurgical resection of brainstem, thalamic, and basal ganglia angiographically occult vascular malformations NEUROSURGERY Steinberg, G. K., Chang, S. D., Gewirtz, R. J., Lopez, J. R. 2000; 46 (2): 260-270

  Abstract

  To evaluate the clinical results for patients who underwent resection of angiographically occult vascular malformations (AOVMs) of the brainstem, thalamus, or basal ganglia, successfully resected after it exhibited rebleeding and presented to a pial surface.Between January 1990 and May 1998, 56 patients with 57 deep AOVMs underwent 63 operations, at Stanford University Medical Center, to treat AOVMs of the brainstem (42 AOVMs), thalamus (5 AOVMs), or basal ganglia (10 AOVMs). The surgical approach was suboccipital midline (27 operations), far lateral suboccipital (10 operations), transsylvian (9 operations), interhemispheric transcallosal or infracallosal (8 operations), infratentorial supracerebellar (6 operations), or subtemporal (3 operations). Four patients experienced recurrent bleeding from the same lesion after surgical resection, requiring a second operation. One patient required a planned second operation, using a different approach, to completely resect the lesion, and one patient underwent two surgical procedures to resect two separate brainstem AOVMs. One patient initially underwent exploration but not resection of her AOVM, because it did not present to a pial or ependymal surface. The AOVM was successfully resected after it exhibited rebleeding and presented to a pial surface.The immediate outcomes after surgery were unchanged for 31 patients (55%), worsened for 16 (29%), and improved for 9 (16%). The long-term outcomes were unchanged for 24 patients (43%), compared with their presenting grade, worse for 3 (5%), and improved for 29 (52%). Patients who had undergone previous radiotherapy or radiosurgery to treat these lesions experienced more difficult postoperative courses, and radiation necrosis was observed for two patients.AOVMs of the brainstem, thalamus, and basal ganglia can be safely removed, with a long-term neurological morbidity rate of only 5% and a complete lesion resection rate of 93% after the initial planned resection. The use of cranial base surgical approaches and intraoperative electrophysiological monitoring contributes to successful clinical outcomes.

  View details for Web of Science ID 000085191800002

  View details for PubMedID 10690715

• Stereotactic radiosurgery in patients with multiple brain metastases. Neurosurgical focus Chang, S. D., Lee, E., Sakamoto, G. T., Brown, N. P., Adler, J. R. 2000; 9 (2)

  Abstract

  Patients with multiple brain metastases are often treated primarily with fractionated whole-brain radiation therapy (WBRT). In previous reports the authors have shown that patients with four or fewer brain metastases can benefit from stereotactic radiosurgery in addition to fractionated WBRT. In this paper the authors review their experience using linear accelerator stereotactic radiosurgery to treat patients with multiple brain metastases.Fifty-three patients with 149 brain metastases underwent stereotactic radiosurgery. The mean age of patients was 53.1 years (range 20-78 years). There were 23 men and 30 women. The primary tumor location was lung (27 patients), melanoma (10), breast (six), ovary (six), and other (four). All patients harbored at least two metastatic tumors treated with radiosurgery; 27 patients (51%) harbored two lesions, 17 (32%) three lesions, eight (15%) four lesions, and one patient (2%) harbored five lesions. The mean radiation dose administered was 19.6 Gy (range 14-30 Gy), and the mean secondary collimator size was 15.7 mm (range 7.5-40 mm). One hundred thirty-two (89%) of the 149 treated tumors were available for review on magnetic resonance (MR) imaging at 3 months posttreatment. Fifty-two percent were smaller in size, 31% were stable, 9% had increased in size, and 8% had disappeared. New metastatic tumors appeared in 12 (23%) of the 53 patients on MR imaging within 6 months posttreatment. Radiation-induced necrosis occurred at the site of eight (5.4%) of the 149 tumors at 6 months. Seven tumors (4.7%) subsequently required surgical resection for either tumor progression (four cases) or worsening edema from radiation-induced necrosis (three cases). Median actuarial survival was 9.6 months.Stereotactic radiosurgery can be used to treat patients with up to four brain metastases with a 91% rate of either decrease or stabilization in tumor size and a low rate of radiation-induced necrosis. In the authors' study only a small number of patients subsequently required surgical resection of a treated lesion.

  View details for PubMedID 16836289

• The treatment of giant intracranial arteriovenous malformations using multimodality therapy Chang, S. D., Lopez, J. R., Levy, R. P., Marks, M. P., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 2000: 324–24

  View details for Web of Science ID 000084589100304

• Treatment of intracranial arteriovenous malformations in the elderly population Chang, S. D., Lopez, J. R., Marks, M. P., Levy, R. P., Adler, J. R., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 2000: 325–25

  View details for Web of Science ID 000084589100308

• Image-guided robotic radiosurgery: Clinical and radiographic results with the CyberKnife 4th International-Stereotactic-Radiosurgery-Society Congress Chang, S. D., MURPHY, M. J., Martin, D. P., Hancock, S. L., Doty, J. R., Adler, J. R. KARGER. 2000: 23–33

  View details for Web of Science ID 000170815200003

• Current treatment of patients with multiple brain metastases. Neurosurgical focus Chang, S. D., Adler, J. R. 2000; 9 (2)

  Abstract

  The management of patients with multiple brain metastases remains a difficult challenge for neurosurgeons. This patient population has a poor prognosis when compared with those harboring a solitary brain metastasis, and historically treatment has generally consisted of administering whole-brain radiotherapy once the diagnosis of multiple brain metastases is made. Resection can be useful in a subset of patients with multiple metastases in whom one or two of the lesions are symptomatic, as this may provide rapid reduction of mass effect and edema. Furthermore, the authors of recent studies have shown that stereotactic radiosurgery can be used in certain patients with multiple brain metastases as part of the treatment regimen. In this review the authors outline the treatment options and indications as well as a management strategy for the treatment of patients with multiple brain metastases.

  View details for PubMedID 16836291

• Intraoperative electrical stimulation for identification of cranial nerve nuclei 45th Annual Meeting of the American-Association-for-Electrodiagnostic-Medicine Chang, S. D., Lopez, J. R., Steinberg, G. K. JOHN WILEY & SONS INC. 1999: 1538–43

  Abstract

  The purpose of this study was to evaluate the feasibility and usefulness of cranial nerve nuclei monitoring during resection of brainstem cavernous malformations. Eleven patients with brainstem cavernous malformations underwent resection of their malformations utilizing cranial nerve nuclei monitoring. Cranial nerves V and VII were monitored by placing electrodes in muscle groups innervated by these nerves and recording manipulation-induced neurotonic discharges and triggered electromyographic (EMG) activity, after electrical stimulation of the corresponding brainstem nuclei. Seven of 11 procedures (64%) with cranial nerve nuclei monitoring were noted to have cranial nerve nuclei activity corresponding to manipulation of the nuclei. The cavernous malformation was completely resected in 5 of 7 cases with cranial nerve nuclei activity and in all 4 cases without activity. In the remaining 2 cases, the cavernous malformation was not resected due to the proximity of the monitored cranial nerve nuclei to the cavernous malformation and to increasing neurotonic activity as the cavernous malformation was approached. None of the 11 patients had new permanent postoperative deficits corresponding to the cranial nerve nuclei monitored; 1 patient had a transient partial facial palsy lasting 2 days. Preliminary results indicate that cranial nerve nuclei monitoring proves useful in preserving neurologic function and reducing surgical morbidity during resection of brainstem cavernous malformations, particularly indicating when lesion resection places these nuclei at risk.

  View details for Web of Science ID 000083306000008

  View details for PubMedID 10514231

• The usefulness of electrophysiological monitoring during resection of central nervous system vascular malformations. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Chang, S. D., Lopez, J. R., Steinberg, G. K. 1999; 8 (6): 412-422

  Abstract

  Goal: The purpose of this study was to evaluate the usefulness of electrophysiological monitoring during the resection of vascular malformations. Methods: Between September 1994 and April 1996, we surgically resected vascular malformations (31 arteriovenous malformations, 22 angiographically occult vascular malformations) from 53 patients (56 procedures) and used intraoperative evoked potential monitoring. Somatosensory evoked potentials (SSEPs) were monitored in 54 procedures (96%), and brain stem auditory evoked potentials (BAEPs) in 17 (30%). The neurological status of the patients was evaluated before and after surgery. Findings: Five of the 54 patients (9%) monitored with SSEPs had SSEP changes (4 transient, 1 persistent) coinciding with new clinical neurological deficits in 4 patients (all transient). In all 4 patients who had transient SSEP changes, the changes resolved with adjustment or removal of clips on feeding vessels (2 patients) or with elevating mean arterial pressure (MAP) (2 patients). Forty-seven patients (91%) had neither SSEP or neurological examination alterations. One of 17 patients (6%) monitored with BAEPs had neurological and persistent BAEP changes, 15 (88%) had neither BAEP or neurological changes, and 1 (6%) had a neurological change despite no change in BAEP (false negative). The sensitivity of SSEP and BAEP for predicting a new postoperative deficit (transient or prolonged) in this series was 86% (6/7); specificity was 98% (55/56). Clinical outcome was excellent in 41 patients, good in 11 and poor in 1 (no patients died) and was largely related to pretreatment grade. Conclusion: SSEPs and BAEPs predict the likelihood of clinical neurological injury during resection of vascular malformations with high sensitivity and specificity and may prove a useful adjunct in treating these lesions.

  View details for PubMedID 17895195

• Stereotactic radiosurgical boost following radiotherapy in primary nasopharyngeal carcinoma: Impact on local control 39th Annual Meeting of ASTRO Tate, D. J., Adler, J. R., Chang, S. D., Marquez, S., Eulau, S. M., Fee, W. E., PINTO, H., Goffinet, D. R. ELSEVIER SCIENCE INC. 1999: 915–21

  Abstract

  Treatment of patients with nasopharyngeal carcinoma using external beam radiation therapy (EBRT) alone results in significant local recurrence. Although intracavitary brachytherapy can be used as a component of management, it may be inadequate if there is extension of disease to the skull base. To improve local control, stereotactic radiosurgery was used to boost the primary tumor site following fractionated radiotherapy in patients with nasopharyngeal carcinoma.Twenty-three consecutive patients were treated with radiosurgery following radiotherapy for nasopharyngeal carcinoma from 10/92 to 5/98. All patients had biopsy confirmation of disease prior to radiation therapy; Stage III disease (1 patient), Stage IV disease (22 patients). Fifteen patients received cisplatinum-based chemotherapy in addition to radiotherapy. Radiosurgery was delivered using a frame-based LINAC as a boost (range 7 to 15 Gy, median 12 Gy) following fractionated radiation therapy (range 64.8 to 70 Gy, median 66 Gy).All 23 patients (100%) receiving radiosurgery as a boost following fractionated radiation therapy are locally controlled at a mean follow-up of 21 months (range 2 to 64 months). There have been no complications of treatment caused by radiosurgery. However, eight patients (35%) have subsequently developed regional or distant metastases.Stereotactic radiosurgical boost following fractionated EBRT provides excellent local control in advanced stage nasopharynx cancer and should be considered for all patients with this disease. The treatment is safe and effective and may be combined with cisplatinum-based chemotherapy.

  View details for Web of Science ID 000083624000013

  View details for PubMedID 10571198

• Intracranial nasal dermoid sinus cyst associated with colloid cyst of the third ventricle - Case report and new concepts PEDIATRIC NEUROSURGERY Cheng, M. L., Chang, S. D., Pang, D. L., Adler, J. R. 1999; 31 (4): 201-206

  Abstract

  A case of a 16-year-old male with both a nasal dermoid sinus cyst (NDSC) and a third ventricle colloid cyst is presented. The NDSC was excised via a single-stage combined intracranial-extracranial approach and the third ventricle colloid cyst was resected endoscopically. The pathogenetic theories of NDSC and third ventricle colloid cyst are discussed, and an embryological explanation for the simultaneous development of the two lesions in this patient is explored. This case is best classified among congenital developmental malformations in a category we propose to call 'anterior neuropore corridor defects.'

  View details for Web of Science ID 000085112900007

  View details for PubMedID 10705930

• Correlation of magnetic resonance characteristics and histopathological type of angiographically occult vascular malformations NEUROSURGERY Vanefsky, M. A., Cheng, M. L., Chang, S. D., Norbash, A., Snipe, J., Marks, M. P., Steinberg, G. K. 1999; 44 (6): 1174-1180

  View details for Web of Science ID 000080588400007

• Symptomatic vasospasm after resection of a suprasellar pilocytic astrocytoma: Case report and possible pathogenesis SURGICAL NEUROLOGY Chang, S. D., Yap, O. W., Adler, J. R. 1999; 51 (5): 521-526

  Abstract

  Cerebral vasospasm from pathology other than subarachnoid hemorrhage is uncommon. A case of severe vasospasm after resection of a suprasellar pilocytic astrocytoma is reported.A 45-year-old male presented with headache, left facial numbness, bilateral visual loss, and ataxia. Evaluation revealed a large suprasellar tumor, which was resected. Pathologic examination showed pilocytic astrocytoma. The patient developed hemiparesis and aphasia on the fifth postoperative day. Vascular spasm was documented on angiography and by transcranial Doppler.Intraarterial papaverine resulted in moderate angiographic improvement. Attempts to open middle cerebral artery branches with angioplasty were unsuccessful. The patient subsequently developed a left middle cerebral artery infarct.To our knowledge, this is the first description of vasospasm after resection of an astrocytoma. Possible mechanisms contributing to this unusual complication after resection of tumors are discussed.

  View details for Web of Science ID 000080147200021

  View details for PubMedID 10321883

• Recanalization and rupture of a giant vertebral artery aneurysm after Hunterian ligation: Case report NEUROSURGERY Chang, S. D., Marks, M. P., Steinberg, G. K. 1999; 44 (5): 1117-1120

  Abstract

  Recanalization and subsequent rupture of giant aneurysms of the posterior circulation after Hunterian ligation is an extremely rare event that has been noted to occur with basilar apex, basilar trunk, and vertebrobasilar junction aneurysms. We report the case of a giant, previously unruptured right vertebral artery aneurysm, which recanalized from the contralateral vertebral artery and subsequently ruptured after previously performed angiography showed complete thrombosis of the aneurysm.A 72-year-old woman presented with headaches, ataxia, and lower extremity weakness. A giant 3-cm right vertebral artery aneurysm was found during the patient evaluation.Because of the size of the aneurysm and the absence of a discrete neck, Hunterian ligation was performed. After treatment, angiograms showed no filling of the aneurysm from either the right or left vertebral artery. Nine days later, after the patient developed lethargy and nausea, repeat angiography showed that a small portion of the aneurysmal base had recanalized. The next day, the patient had a massive subarachnoid hemorrhage and subsequently died.We think that this is a previously undescribed complication associated with direct arterial ligation of giant vertebral artery aneurysms. Patients with aneurysms treated using Hunterian ligation need to be followed up closely. Even aneurysms that have minimal recanalization are at risk for subarachnoid hemorrhage.

  View details for PubMedID 10232546

• The use of electrophysiological monitoring in the intraoperative management of intracranial aneurysms JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY Lopez, J. R., Chang, S. D., Steinberg, G. K. 1999; 66 (2): 189-196

  Abstract

  Somatosensory evoked potentials (SSEPs) and brainstem auditory evoked potentials (BAEPs) have been increasingly utilised during surgery for intracranial aneurysms to identify cerebral ischaemia. Between July 1994 and April 1996, we surgically treated 70 aneurysms in 49 consecutive patients (58 operations) with the aid of intraoperative evoked potential monitoring. This study sought to evaluate the usefulness of SSEP and BAEP monitoring during intracranial aneurysm surgery.Mean patient age was 51.9 (range 18-79) years. The sizes of the aneurysms were 3-4 mm (15), 5-9 mm (26), 10-14 mm (11), 15-19 mm (seven), 20-24 mm (six), and >25 mm (five). SSEPs were monitored in 58 procedures (100%) and BAEPs in 15 (26%). The neurological status of the patients was evaluated before and after surgery.Thirteen of the 58 procedures (22%) monitored with SSEPs had SSEP changes (12 transient, one persistent); 45 (78%) had no SSEP changes. Three of 15 patients (20%) monitored with BAEPs had changes (two transient, one persistent); 12 (80%) had no BAEP changes. Of the 14 patients with transient SSEP or BAEP changes, these changes resolved with adjustment or removal of aneurysm clips (nine), elevating MAP (four), or retractor adjustment (one). Mean time from precipitating event to electrophysiological change was 8.9 minutes (range 3-32), and the mean time for recovery of potentials in patients with transient changes was 20.2 minutes (range 3-60). Clinical outcome was excellent in 39 patients, good in five, and poor in three (two patients died), and was largely related to pretreatment grade.SSEPs and BAEPs are useful in preventing clinical neurological injury during surgery for intracranial aneurysms and in predicting which patients will have unfavourable outcomes.

  View details for Web of Science ID 000078450800011

  View details for PubMedID 10071098

  View details for PubMedCentralID PMC1736209

• Image-guided robotic radiosurgery Neurosurgery Adler, J. R., Murphy, M. J., Chang, S. D., Hancock, S. L. 1999; 44 (6): 1299–1306; discussion 1306–1307

  Abstract

  PURPOSE: To describe the design and performance of a novel frameless system for radiosurgery. This technology, called image-guided radiosurgery (IGR), eliminates the need for stereotactic frame fixation by relating the identified lesion to radiographic landmarks. CONCEPT: IGR uses a lightweight x-band linear accelerator, computer-controlled robotic arm (Fanuc manipulator [Fanuc Robotics North America, Inc., Rochester Hills, MI]), paired orthogonal x-ray imagers, and a computer workstation that performs rapid image-to-image registration. During radiosurgery, the x-ray imaging system determines the location of the lesion and communicates these coordinates to the robot, which adjusts the pointing of the linear accelerator beam to maintain alignment with the target. RATIONALE: Existing stereotactic techniques require rigid cranial fixation to establish and maintain a system of reference for targeting. Such frames cause pain for the patient, limit the use of fractionation, and necessitate a prolonged period of general anesthesia if children are to be treated. Furthermore, skeletal or any other type of rigid fixation is difficult to achieve beyond the cranium. IGR was designed to overcome these limitations, which are inherent to nearly all current radiosurgical methods. DISCUSSION: Preliminary testing and early clinical experience have demonstrated the practicality and potential of the IGR concept and have identified the most important directions for improvement. For example, an IGR prototype accurately tracked target displacements in three dimensions but showed reduced accuracy when confronted by rotational movements. This observation led to development of a new generation of tracking algorithm that promises to improve tracking in all six dimensions. Further experience indicated that improvements in the quality of the x-ray images were needed to allow the system to locate and treat target sites outside the cranium. Consequently, a new x-ray imaging technology with superior resolution and increased sensitivity has been added to the system. These improvements should make it possible to apply IGR techniques to a variety of targets located throughout the body. This article describes and critiques the components of the IGR and summarizes our preliminary clinical experience.

  View details for PubMedID 10371630

• The use of electrophysiologic monitoring during intracranial cerebrovascular surgery: A cost-benefit analysis Chang, S. D., Lopez, J. R., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 1999: 257–57

  View details for Web of Science ID 000077934200205

• Management of the radiosurgery patient: Causes and treatment of adverse sequelae 32nd San Francisco Cancer Symposium Chang, S. D., Adler, J. R. KARGER. 1999: 155–165

  View details for Web of Science ID 000171088100014

• Treatment of cavernous sinus tumors with linear accelerator radiosurgery SKULL BASE SURGERY Chang, S. D., Doty, J. R., Martin, D. P., Hancock, S. L., Adler, J. R. 1999; 9 (3): 195-199

  Abstract

  Since 1989, 79 patients with benign or malignant cavernous sinus tumors, have been treated at Stanford University with linear accelerator (linac) radiosurgery. Radiosurgery has been used as (1) a planned second-stage procedure for residual tumor following surgery, (2) primary treatment for patients whose medical conditions preclude surgery, (3) palliation of malignant lesions, and (4) definitive treatment for small, well-localized, poorly accessible tumors. Mean patient age was 52 years (range, 18 to 88); there were 28 males and 51 females. Sixty-one patients had benign tumors; 18 had malignant tumors. Mean tumor volume was 6.8 cm(3) (range 0.5 to 22.5 cm(3)) covered with an average of 2.3 isocenter (range, 1 to 5). Radiation dose averaged 17.1 Gy. Mean follow-up was 46 months. Tumor control or shrinkage, or both, varied with pathology. Radiographic tumor improvement was most pronounced in malignant lesions, with greater than 85% showing reduction in tumor size; benign tumors (meningiomas and schwannomas) had a 63% control rate and 37% shrinkage rate, with none enlarging. We concluded that stereotactic radiosurgery is a valuable tool in managing cavernous sinus tumors. There was excellent control and stabilization of benign tumors and palliation of malignant lesions.

  View details for Web of Science ID 000083016700004

  View details for PubMedID 17171089

  View details for PubMedCentralID PMC1656740

• Correlation of magnetic resonance characteristics and histopathological type of angiographically occult vascular malformations Neurosurgery Vanefsky, M. A., Cheng, M. L., Chang, S. D., Norbash, A., Snipe, J., Marks, M. P., Steinberg, G. K. 1999; 44 (6): 1174–80; discussion 1180–81

  Abstract

  OBJECTIVE: Histological and radiological classification of vascular malformations has previously been attempted in an effort to understand their nature and predict their biological behavior. There exists a subgroup of vascular malformations that are angiographically occult and share a common magnetic resonance imaging (MRI) appearance but may differ in their behavior. We sought to determine any correlation between MRI features and final histopathological diagnosis. METHODS: We reviewed our series of 72 patients with angiographically occult vascular malformations operated on at Stanford University Medical Center between 1988 and 1993. Radiographic magnetic resonance images and histopathological specimens were retrospectively evaluated for various diagnostic features. RESULTS: Our data indicate that lesions exhibiting a ring of hemosiderin are associated with the presence of a cavernous malformation (CM) component (86% of CMs versus 33% of non-CM lesions). A lesion associated with edema, mass effect, or a single prominent blood product on MRI correlates with the presence of an arteriovenous malformation (AVM) component. Sixty-three percent of AVMs and 80% of lesions with partial AVM components showed edema, compared with 8% of CMs and 0% of venous malformations. Sixty percent of AVMs and 63% of lesions with partial AVM components showed a single prominent blood product, compared with 8% of CMs and 0% of venous malformations. Finally, 60% of AVMs exhibited mass effect, compared with 20% of CMs. Additionally, an expansile hemorrhage is suggestive of an AVM. CONCLUSION: This study is the first to demonstrate that a particular MRI appearance of an angiographically occult vascular malformation is suggestive of an AVM component. This may have important implications with regard to the behavior of the lesion and planning of future treatment.

  View details for PubMedID 10371616

• Treatment of nasopharyngeal carcinoma: Stereotactic radiosurgical boost following fractionated radiotherapy Meeting of the American-Society-for-Stereotactic-and-Functional-Neurosurgery Chang, S. D., Tate, D. J., Goffinet, D. R., Martin, D. P., Adler, J. R. KARGER. 1999: 64–67

  Abstract

  Treatment of patients with nasopharyngeal carcinoma (NPC) using external beam radiation therapy (XRT) alone results in significant local recurrence. To improve local control, stereotactic radiosurgery (SRS) was used to boost radiation to the primary tumor site following XRT in 23 patients with NPC. SRS was delivered utilizing a frame-based linear accelerator as a boost (range 7-15 Gy, median 12 Gy) following XRT (range 64.8- 70 Gy, median 66 Gy). In all 23 patients (100%) receiving SRS following XRT local control was achieved at a mean follow-up of 21 months (range 2-64 months). There have been no complications of treatment caused by SRS. However, 8 patients (35%) have subsequently developed regional or distant metastases. SRS boost following XRT provides excellent local control in NPC and should be considered for patients with skull base involvement.

  View details for Web of Science ID 000087727900012

  View details for PubMedID 10853100

• Clinical experience with image-guided robotic radiosurgery (the Cyberknife) in the treatment of brain and spinal cord tumors NEUROLOGIA MEDICO-CHIRURGICA Chang, S. D., Murphy, M., Geis, P., Martin, D. P., Hancock, S. L., Doty, J. R., Adler, J. R. 1998; 38 (11): 780-783

  Abstract

  The Cyberknife is an image-guided "frameless" dedicated radiosurgical device. This instrument has several distinct advantages over frame-based systems, including improved patient comfort, increased treatment degrees of freedom, and the potential to target extracranial lesions. Clinical results thus far with respect to the treatment of malignant intracranial tumors has been promising. Additionally, the Cyberknife will likely revolutionize the application of radiosurgery to extracranial sites. A description of the components, treatment planning, and clinical results of the Cyberknife will be reviewed.

  View details for Web of Science ID 000077103400031

  View details for PubMedID 9919913

• Microsurgical resection of incompletely obliterated intracranial arteriovenous malformations following stereotactic radiosurgery NEUROLOGIA MEDICO-CHIRURGICA Chang, S. D., Steinberg, G. K., Levy, R. P., Marks, M. P., Frankel, K. A., Shuster, D. L., Marcellus, M. L. 1998; 38: 200-207

  Abstract

  Radiosurgery is effective in obliterating small arteriovenous malformations (AVMs), but less successful in thrombosing larger AVMs. This study reviewed patients who underwent surgical resection of their large AVMs following failed radiosurgical obliteration. AVMs from 36 patients (aged 7 to 64 years, mean 29.9) were surgically resected 1 to 11 years after radiosurgery. Initial AVM volumes were 0.7 to 117 cm3 (mean 21.6 cm3), and radiosurgical doses ranged from 4.6 to 45 Gray equivalent (GyE) (mean 21.1 GyE). Thirty AVMs (83%) were located in eloquent tissue. Venous drainage was deep (14), superficial (13), or both (9). Spetzler grades were II (2), III (12), IV (18), and V (4). Nine patients suffered rehemorrhage after radiosurgery but prior to surgery, while three patients developed radiation necrosis. Twenty-seven patients underwent endovascular embolization prior to surgery. During microsurgical resection, the AVMs were found to be significantly less vascular and more easily resected, compared to AVMs in patients who had not received radiosurgery. Histology showed endothelial proliferation with hyaline and mineralization in vessel walls. Partial or complete thrombosis of some AVM vessels, and evidence of vessel and brain necrosis were noted in many cases. Clinical outcome was excellent or good in 34 cases, with two patients dying of rebleeding from residual AVM. Five patients were neurologically worse following microsurgical resection. Final outcome was largely related to the pretreatment grade. Radiosurgery several years prior to surgical resection appears useful in treating unusually large and complex AVMs.

  View details for PubMedID 10235006

• Bilateral cavernous malformations resulting from cranial irradiation of a choroid plexus papilloma NEUROLOGICAL RESEARCH Chang, S. D., Vanefsky, M. A., Havton, L. A., Silverberg, G. D. 1998; 20 (6): 529-532

  Abstract

  We report a case of multiple parietal cavernous malformations in a thirteen year old female who received cranial irradiation following incomplete resection of a choroid plexus papilloma. The cavernous malformations, which developed within the prior parietal radiation ports, were diagnosed nine years after the patients' radiation treatment when the patient presented with increasing frequency of seizures. Family history was negative for familial cavernous malformations. Due to the worsening frequency of seizures, the patient underwent resection of these two cavernous malformations with diagnosis confirmed by pathology. Post-operative, there was a significant reduction in seizure frequency. The origin and pathophysiology of cavernous malformations remains controversial. Cranial radiation treatment for tumors, particularly in children, may possibly lead to the development of these lesions, as occurred in this case. This is, to our knowledge, the first case of multiple cavernous malformations occurring within a previous radiation field following radiotherapy for a neoplasm.

  View details for Web of Science ID 000075190700009

  View details for PubMedID 9713844

• Stereotactic radiosurgery of angiographically occult vascular malformations: 14-year experience NEUROSURGERY Chang, S. D., Levy, R. P., Adler, J. R., Martin, D. P., Krakovitz, P. R., Steinberg, G. K. 1998; 43 (2): 213-220

  Abstract

  Radiosurgery is generally effective in obliterating true arteriovenous malformations, but less is known about its effects on angiographically occult vascular malformations (AOVMs). Since July 1983, 57 patients with surgically inaccessible AOVMs of the brain were treated using helium ion (47 patients) or linear accelerator (10 patients) radiosurgery. This study retrospectively evaluates the response of these AOVMs to treatment.All patients presented with previous hemorrhage. The mean patient age was 35.6 years (range, 13-71 yr). The mean AOVM volume was 2.25 cm3 (range, 0.080-15.2 cm3), treated with a mean of 18.0 Gy equivalent (physical dose x relative biological effectiveness, which is 1.3 for helium ion Bragg peak) (range, 7.0-40 Gy equivalent). The Drake scale scores before treatment were as follows: excellent (25 patients), good (26 patients), and poor (6 patients). The mean follow-up period was 7.5 years (range, 9 mo-13.8 yr).Eighteen patients (32%) bled symptomatically (20 hemorrhages) after radiosurgery. Sixteen hemorrhages occurred within 36 months after radiosurgery (9.4% annual bleed rate; 16 hemorrhages/171 patient yr); 4 hemorrhages occurred more than 36 months after treatment (1.6% annual bleed rate; 4 hemorrhages/257 patient yr) (P < 0.001). Complications included symptomatic radiation edema (four patients, 7%), necrosis (one patient, 2%), and increased seizure frequency (one patient, 2%). Eight patients underwent surgical resection of their AOVMs 8 to 59 months after radiosurgery because of subsequent hemorrhage. The Drake scale scores after treatment were as follows: excellent (25 patients), good (24 patients), poor (3 patients), and dead (5 patients, 3 of whom died as a result of causes unrelated to the AOVMs or radiosurgery).Radiosurgery may be useful for AOVMs located in surgically inaccessible regions of the brain. A significant decrease in bleed rate exists more than 3 years after treatment compared with the bleed rate within 3 years of treatment. Because current neuroradiological techniques are not able to image obliterative response in these slow-flow vascular lesions, longer term clinical follow-up is required.

  View details for Web of Science ID 000074979500010

  View details for PubMedID 9696072

• Acute hearing loss following fractionated stereotactic radiosurgery for acoustic neuroma - Report of two cases JOURNAL OF NEUROSURGERY Chang, S. D., Poen, J., Hancock, S. L., Martin, D. P., Adler, J. R. 1998; 89 (2): 321-325

  Abstract

  Two cases of acute hearing loss are reported following fractionated stereotactic radiosurgery for acoustic neuroma. Both patients had neurofibromatosis type 2 and were treated with a peripheral tumor dose of 21 Gy delivered in three fractions (7 Gy each) with a minimum interfraction interval of 10 hours. One patient who had previously undergone surgical resection of the treated tumor presented with only rudimentary hearing in the treated ear secondary to an abrupt decrease in hearing prior to treatment. That patient reported total loss of hearing before complete delivery of the third fraction. The second patient had moderately impaired hearing prior to treatment; however, within 10 hours after delivery of the final fraction, he lost all hearing. Both patients showed no improvement in response to glucocorticoid therapy. Possible explanations for this phenomenon are presented.

  View details for Web of Science ID 000074994900022

  View details for PubMedID 9688131

• Clinical uses of radiosurgery ONCOLOGY-NEW YORK Chang, S. D., Adler, J. R., Hancock, S. L. 1998; 12 (8): 1181-?

  Abstract

  Radiosurgery uses stereotactic targeting methods to precisely deliver highly focused, large doses of radiation to small intracranial tumors and arteriovenous malformations (AVMs). This article reviews the most common clinical applications of radiosurgery and the clinical results reported from a number of series using either a cobalt-60 gamma knife or linear accelerator as radiation sources. Radiosurgery is used to treat malignant tumors, such as selected cases of brain metastases and malignant gliomas (for which stereotactic radiosurgical boosts are utilized in conjunction with fractionated radiation therapy), as well as benign tumors, such as meningiomas, acoustic neuromas, and pituitary adenomas. Treatment of small AVMs is also highly effective. Although radiosurgery has the potential to produce complications, the majority of patients experience clinical improvement with less morbidity than occurs with surgical resection.

  View details for Web of Science ID 000075449300014

  View details for PubMedID 11236310

• Arteriovenous malformations after radiosurgery JOURNAL OF NEUROSURGERY Chang, S. D., Steinberg, G. K. 1998; 89 (1): 170-170

  View details for Web of Science ID 000074325600035

  View details for PubMedID 9647195

• Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery NEUROSURGERY Chang, S. D., Meisel, J. A., Hancock, S. L., Martin, D. P., McManus, M., Adler, J. R. 1998; 43 (1): 28-34

  Abstract

  Stereotactic radiosurgery is increasingly being used to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. The purpose of this study was to retrospectively evaluate the effectiveness of radiosurgery in the treatment of hemangioblastomas.From 1989 to 1996, 29 hemangioblastomas in 13 patients with von Hippel-Lindau disease were treated with linear accelerator-based radiosurgery. The mean patient age was 40 years (range, 31-57 yr). The radiation dose to the tumor periphery averaged 23.2 Gy (range, 18-40 Gy). The mean tumor volume was 1.6 cm3 (range, 0.07-65.4 cm3). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic and magnetic resonance imaging scans. The mean follow-up period was 43 months (range, 11-84 mo).Only one (3%) of the treated hemangioblastomas progressed. Five tumors (17%) disappeared, 16 (55%) regressed, and 7 (24%) remained unchanged in size. Five of nine patients with symptoms referable to treated hemangioblastomas experienced symptomatic improvement. During the follow-up period, one patient died as a result of progression of untreated hemangioblastomas in the cervical spine. Three patients developed radiation necrosis, two of whom were symptomatic.Although follow-up monitoring is limited, stereotactic radiosurgery provides a high likelihood of local control of hemangioblastomas and is an attractive alternative to multiple surgical procedures for patients with von Hippel-Lindau disease.

  View details for Web of Science ID 000074274500016

  View details for PubMedID 9657185

• LINAC radiosurgery for cavernous sinus meningiomas STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Chang, S. D., Adler, J. R., Martin, D. P. 1998; 71 (1): 43-50

  Abstract

  Radiosurgery is increasingly used to treat unresectable cavernous sinus tumors. Since 1989, 24 patients with cavernous sinus meningiomas have been treated at Stanford University Medical Center with linear accelerator (LINAC) radiosurgery. The mean age of the patients was 47.8 years (range 28-78). The mean volume treated was 6. 83 cm3 (range 0.45-22.45 cm3), covered with an average of 2.3 isocenters (range 1-5). Radiation dose averaged 17.7 Gy (range 14-20 Gy). This group of patients was retrospectively studied by sending clinical questionnaires to both the patient/family and referring physicians, and reviewing clinic charts. In addition, follow-up imaging studies were obtained to measure residual tumor volume. Follow-up averaged 45.6 months (range 19-80). Tumor control (stabilization) following radiosurgery was noted in 15 (63%) and tumor shrinkage in 9 (37%). Seven meningiomas (29%) showed evidence of central tumor necrosis on MRI imaging 1-3 years after radiosurgery. Neurologic status was improved in 10 patients (42%) and unchanged in 12 patients (50%). There was 1 case of symptomatic brain necrosis and 1 case of radiation edema (asymptomatic). All other complications were transient, including 4 cases of trigeminal hypesthesia and 1 case of worsening diplopia. The 2-year actuarial tumor control rate was 100%. Although follow-up is still short, this experience corroborates prior reports that radiosurgery can be used to treat selected small cavernous sinus meningiomas with good to excellent clinical results and minimal morbidity.

  View details for PubMedID 10072673

• Cranial nerve nuclei monitoring during resection of brainstem cavernous malformations: Preliminary results Chang, S. D., Lopez, J. R., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 1998: 276–76

  View details for Web of Science ID 000071417100075

• Management of intracranial aneurysms. Vascular medicine Chang, S. D., Steinberg, G. K. 1998; 3 (4): 315-326

  Abstract

  Intracranial aneurysms are lesions commonly encountered by neurosurgeons, usually as a result of subarachnoid hemorrhage. The preferred treatment of these aneurysms is either surgical clipping or endovascular coiling, both of which eliminate the aneurysm from the normal circulation to prevent aneurysmal enlargement or additional hemorrhage. Despite advances over the last several decades in the understanding of intracranial aneurysms, morbidity from treatment of these lesions remains significant. This review will discuss the epidemiology, anatomy and pathophysiology, clinical and radiographic diagnosis, various treatment options, and potential complications from aneurysm treatment.

  View details for PubMedID 10102672

• Treatment of cranial base meningiomas with linear accelerator radiosurgery NEUROSURGERY Chang, S. D., Adler, J. R. 1997; 41 (5): 1019-1025

  Abstract

  Radiosurgery is increasingly being used to treat cranial base tumors. Since 1989, 55 patients with cranial base meningiomas were treated at Stanford University Medical Center with linear accelerator radiosurgery. An analysis of the clinical and radiographic results of this patient population was the focus of this study.The mean patient age was 55.1 years (range, 28-82 yr). The mean tumor volume was 7.33 cm3 (range, 0.45-27.65 cm3). The radiation dose averaged 18.3 Gy (range, 12-25 Gy), delivered with an average of 2.2 isocenters (range, 1-5). Patients were evaluated retrospectively through clinic notes from follow-up examinations, and residual tumor volume was measured during follow-up imaging studies. The length of follow-up averaged 48.4 months (range, 17-81 mo).Tumor stabilization after radiosurgery was noted in 38 patients (69%), shrinkage in 16 patients (29%), and enlargement in only 1 patient (2%). The results of follow-up magnetic resonance imaging demonstrated decreased central contrast uptake in 11 meningiomas (20%), possibly indicating evidence of central tumor necrosis or tumor vessel obliteration. Neurological status was improved in 15 patients in the series (27%) and unchanged in 34 patients (62%). Three patients (5%) died during the follow-up period, all as a result of causes other than tumor progression. Three patients (5%) developed new permanent symptoms (one patient with seizures, one patient with mild right hemiparesis, and one patient with both vagal and hypoglossal nerve palsy). All other complications were transient, including partial trigeminal nerve palsy in seven patients and diplopia in three patients. The 2-year actuarial tumor control rate was 98%.Although our follow-up period is short, this experience corroborates previous reports that radiosurgery can be used to ablate selected small cranial base meningiomas, with good clinical results and modest morbidity.

  View details for Web of Science ID A1997YE15600007

  View details for PubMedID 9361055

• Mixed arteriovenous malformation and capillary telangiectasia: A rare subset of mixed vascular malformations - Case report JOURNAL OF NEUROSURGERY Chang, S. D., Steinberg, G. K., Rosario, M., Crowley, R. S., Hevner, R. F. 1997; 86 (4): 699-703

  Abstract

  In this report, the authors discuss the case of a patient with a mixed cerebrovascular malformation in which an arteriovenous malformation (AVM) was associated with a capillary telangiectasia. Recent reports have contained reviews of various subsets of mixed malformations. To the authors' knowledge, however, this is the first report of a mixed vascular malformation with both arterial and capillary components. The patient underwent complete resection of the AVM after presenting with a clinical hemorrhage. She required a second operation to resect the capillary telangiectasia after new symptoms developed several months following the first procedure. The authors conclude that a mixed AVM-capillary telangiectasia is a rare but distinct entity.

  View details for Web of Science ID A1997WP02000017

  View details for PubMedID 9120635

• Stereotactic radiosurgery of arteriovenous malformations: Pathologic changes in resected tissue CLINICAL NEUROPATHOLOGY Chang, S. D., Shuster, D. L., Steinberg, G. K., Levy, R. P., Frankel, K. 1997; 16 (2): 111-116

  Abstract

  Both stereotactic radiosurgery and microsurgery are treatment modalities for arteriovenous malformations (AVM), and more recently, multimodality treatment using these approaches has been utilized. We surgically resected AVMs from 33 patients (ages 7-64 years old, mean age 30.4) 1-11 years after radiosurgery. AVM volumes were 0.8-117 cm3 (mean 21.6 cm3), and doses ranged from 4.6-45 GyE (mean 21.2 GyE). AVMs resected were submitted for pathologic review. Each AVM was evaluated for the following radiation changes, and the number of AVMs demonstrating these changes were noted: endothelial proliferation (27), hyaline (18) and calcium (10) in AVM vessel walls, partial (9) or complete (24) thrombosis of some AVM vessels, and necrosis of vessels (15) and adjacent brain tissue (11). A semiquantitative scale (mild, moderate, severe) incorporating the aforementioned changes present in each case classified the extent of radiation-induced change. There was a significant correlation (r = 0.624, p < 0.01) between extent of radiation change and dose of radiation received. There was no absolute radiation dose threshold below which radiation-induced changes were absent. However, all but one patient receiving greater than 20 GyE developed moderate to severe radiation vascular changes and the 3 patients treated with greater than 30 GyE all had severe radiation-induced changes. Radiation changes in AVMs following stereotactic radiosurgery appear to be dose-related. The correlation of dose to extent of radiation change may allow the determination of the optimal dose of radiation to treat AVMs.

  View details for Web of Science ID A1997WR10700012

  View details for PubMedID 9101115

• The cyberknife: A frameless robotic system for radiosurgery XIIth Meeting of the World Society for Stereotactic and Functional Neurosurgery Adler, J. R., Chang, S. D., MURPHY, M. J., Doty, J., Geis, P., Hancock, S. L. KARGER. 1997: 124–28

  Abstract

  The Cyberknife is a unique instrument for performing frameless stereotactic radiosurgery. Rather than using rigid immobilization, the Cyberknife relies on an image-to-image correlation algorithm for target localization. Furthermore, the system utilizes a novel, light-weight, high-energy radiation source. The authors describe the technical specifications of the Cyberknife and summarize the initial clinical experience.

  View details for Web of Science ID 000074800300019

  View details for PubMedID 9711744

• The use of electrophysiologic monitoring during resection of arteriovenous malformations and angiographically occult vascular malformations Chang, S. D., Lopez, J. R., Steinberg, G. K. LIPPINCOTT WILLIAMS & WILKINS. 1997: 172–72

  View details for Web of Science ID A1997WB81400222

• Surgical resection of large incompletely treated intracranial arteriovenous malformations following stereotactic radiosurgery JOURNAL OF NEUROSURGERY Steinberg, G. K., Chang, S. D., Levy, R. P., Marks, M. P., Frankel, K., Marcellus, M. 1996; 84 (6): 920-928

  Abstract

  Although radiosurgery is effective in obliterating small arteriovenous malformations (AVMs), it has a lower success rate for thrombosing larger AVMs. The authors surgically resected AVMs from 33 patients ranging in age from 7 to 64 years (mean 30.4 years) 1 to 11 years after radiosurgery. Initial AVM volumes were 0.8 to 117 cm3 (mean 21.6 cm3), and doses ranged from 4.6 to 45 GyE (mean 21.2 GyE). Of 27 AVMs in eloquent or critical areas, 10 were located in language, motor, sensory, or visual cortex, 11 in the basal ganglia/thalamus, one each in the brainstem, hypothalamus, and cerebellum, and three in the corpus callosum. Venous drainage was deep in 13, superficial in 12, or both in eight lesions. Spetzler-Martin grades were II in one, III in 12, IV in 16, and V in four patients. Eight patients experienced rebleeding after radiosurgery but prior to surgery. Three patients developed radiation necrosis and 25 underwent endovascular embolization prior to surgery. At surgery the AVMs were found to be markedly less vascular, partially thrombosed, and more easily resected, compared to those seen in patients who had not undergone radiosurgery. Pathological investigation showed endothelial proliferation with hyaline and calcium in vessel walls. There was partial or complete thrombosis of some AVM vessels and evidence of vessel and brain necrosis in many cases. Complete resection was achieved in 28 patients and partial resection in five. Clinical outcome was excellent or good in 31 cases, and two patients died of rebleeding from residual AVM. Four patients' conditions worsened following microsurgical resection. Final clinical outcome was largely related to the pretreatment grade. Radiosurgery several years prior to open microsurgery may prove to be a useful adjunct in treating unusually large and complex AVMs.

  View details for PubMedID 8847585