Publications from the Li Lab

Professor of Neurosurgery and, by courtesy, of Neurology and of Otolaryngology - Head & Neck Surgery (OHNS)


  • An integrated risk model stratifying seizure risk following brain tumor resection among seizure-naive patients without antiepileptic prophylaxis. Neurosurgical focus Jin, M. C., Parker, J. J., Prolo, L. M., Wu, A., Halpern, C. H., Li, G., Ratliff, J. K., Han, S. S., Skirboll, S. L., Grant, G. A. 2022; 52 (4): E3


    The natural history of seizure risk after brain tumor resection is not well understood. Identifying seizure-naive patients at highest risk for postoperative seizure events remains a clinical need. In this study, the authors sought to develop a predictive modeling strategy for anticipating postcraniotomy seizures after brain tumor resection.The IBM Watson Health MarketScan Claims Database was canvassed for antiepileptic drug (AED)- and seizure-naive patients who underwent brain tumor resection (2007-2016). The primary event of interest was short-term seizure risk (within 90 days postdischarge). The secondary event of interest was long-term seizure risk during the follow-up period. To model early-onset and long-term postdischarge seizure risk, a penalized logistic regression classifier and multivariable Cox regression model, respectively, were built, which integrated patient-, tumor-, and hospitalization-specific features. To compare empirical seizure rates, equally sized cohort tertiles were created and labeled as low risk, medium risk, and high risk.Of 5470 patients, 983 (18.0%) had a postdischarge-coded seizure event. The integrated binary classification approach for predicting early-onset seizures outperformed models using feature subsets (area under the curve [AUC] = 0.751, hospitalization features only AUC = 0.667, patient features only AUC = 0.603, and tumor features only AUC = 0.694). Held-out validation patient cases that were predicted by the integrated model to have elevated short-term risk more frequently developed seizures within 90 days of discharge (24.1% high risk vs 3.8% low risk, p < 0.001). Compared with those in the low-risk tertile by the long-term seizure risk model, patients in the medium-risk and high-risk tertiles had 2.13 (95% CI 1.45-3.11) and 6.24 (95% CI 4.40-8.84) times higher long-term risk for postdischarge seizures. Only patients predicted as high risk developed status epilepticus within 90 days of discharge (1.7% high risk vs 0% low risk, p = 0.003).The authors have presented a risk-stratified model that accurately predicted short- and long-term seizure risk in patients who underwent brain tumor resection, which may be used to stratify future study of postoperative AED prophylaxis in highest-risk patient subpopulations.

    View details for DOI 10.3171/2022.1.FOCUS21751

    View details for PubMedID 35364580

  • Factors for differential outcome across cancers in clinical molecular-targeted fluorescence imaging. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Zhou, Q., van den Berg, N. S., Kang, W., Pei, J., Nishio, N., van Keulen, S., Engelen, M. A., Lee, Y. J., Hom, M., Vega Leonel, J. C., Hart, Z., Vogel, H., Cayrol, R., Martin, B. A., Roesner, M., Shields, G., Lui, N., Hayden Gephart, M., Raymundo, R. C., Yi, G., Granucci, M., Grant, G. A., Li, G., Rosenthal, E. L. 2022


    Clinical imaging performance using a fluorescent antibody was compared across three cancers to elucidate physical and biological factors contributing to differential translation of epidermal growth factor receptor (EGFR) expression to macroscopic fluorescence in tumors. Methods: Thirty-one patients with high-grade glioma (HGG, n = 5), head-and-neck squamous cell carcinoma (HNSCC, n = 23) or lung adenocarcinoma (LAC, n = 3) were systemically infused with 50 mg panitumumab-IRDye800, 1 - 3 days prior to surgery. Intraoperative open-field fluorescent images of the surgical field were acquired, where imaging device settings and operating room lighting conditions were tested on tissue-mimicking phantoms. Fluorescence contrast and margin size were measured on resected specimen surface. Antibody distribution and EGFR immunoreactivity were characterized in macroscopic and microscopic histological structures. Integrity of the blood-brain barrier (BBB) was examined via tight junction protein (claudin-5) expression with immunohistochemistry. Stepwise multivariate linear regression of biological variables was performed to identify independent predictors of panitumumab-IRDye800 concentration in tissue. Results: Optimally acquired at the lowest gain for tumor detection with ambient light, intraoperative fluorescence imaging enhanced tissue-size dependent tumor contrast by 5.2-fold, 3.4-fold and 1.4-fold in HGG, HNSCC and LAC, respectively. Tissue surface fluorescence target-to-background ratio correlated with margin size and identified 78 - 97% of at-risk resection margins ex vivo. In 4 µm-thick tissue sections, fluorescence detected tumor with 0.85 - 0.89 areas under the receiver operating characteristic curves. Preferential breakdown of BBB in HGG improved tumor specificity of intratumoral antibody distribution relative to that of EGFR (96% vs 80%) despite its reduced concentration (3.9 ng/mg tissue) compared to HNSCC (8.1 ng/mg) and LAC (6.3 ng/mg). Cellular EGFR expression, tumor cell density, plasma antibody concentration and delivery barrier were independently associated with local intratumoral panitumumab-IRDye800 concentration with 0.62 goodness-of-fit of prediction. Conclusion: In multi-cancer clinical imaging of receptor-ligand based molecular probe, plasma antibody concentration, delivery barrier, as well as intratumoral EGFR expression driven by cellular biomarker expression and tumor cell density, led to heterogeneous intratumoral antibody accumulation and spatial distribution while tumor size, resection margin, and intraoperative imaging settings substantially influenced macroscopic tumor contrast.

    View details for DOI 10.2967/jnumed.121.263674

    View details for PubMedID 35332092

  • 18F-FSPG PET/CT Imaging of System xC- Transporter Activity in Patients with Primary and Metastatic Brain Tumors. Radiology Wardak, M., Sonni, I., Fan, A. P., Minamimoto, R., Jamali, M., Hatami, N., Zaharchuk, G., Fischbein, N., Nagpal, S., Li, G., Koglin, N., Berndt, M., Bullich, S., Stephens, A. W., Dinkelborg, L. M., Abel, T., Manning, H. C., Rosenberg, J., Chin, F. T., Sam Gambhir, S., Mittra, E. S. 2022: 203296


    Background The PET tracer (4S)-4-(3-[18F]fluoropropyl)-l-glutamate (18F-FSPG) targets the system xC- cotransporter, which is overexpressed in various tumors. Purpose To assess the role of 18F-FSPG PET/CT in intracranial malignancies. Materials and Methods Twenty-six patients (mean age, 54 years ± 12; 17 men; 48 total lesions) with primary brain tumors (n = 17) or brain metastases (n = 9) were enrolled in this prospective, single-center study ( identifier: NCT02370563) between November 2014 and March 2016. A 30-minute dynamic brain 18F-FSPG PET/CT scan and a static whole-body (WB) 18F-FSPG PET/CT scan at 60-75 minutes were acquired. Moreover, all participants underwent MRI, and four participants underwent fluorine 18 (18F) fluorodeoxyglucose (FDG) PET imaging. PET parameters and their relative changes were obtained for all lesions. Kinetic modeling was used to estimate the 18F-FSPG tumor rate constants using the dynamic and dynamic plus WB PET data. Imaging parameters were correlated to lesion outcomes, as determined with follow-up MRI and/or pathologic examination. The Mann-Whitney U test or Student t test was used for group mean comparisons. Receiver operating characteristic curve analysis was used for performance comparison of different decision measures. Results 18F-FSPG PET/CT helped identify all 48 brain lesions. The mean tumor-to-background ratio (TBR) on the whole-brain PET images at the WB time point was 26.6 ± 24.9 (range: 2.6-150.3). When 18F-FDG PET was performed, 18F-FSPG permitted visualization of non-18F-FDG-avid lesions or allowed better lesion differentiation from surrounding tissues. In participants with primary brain tumors, the predictive accuracy of the relative changes in influx rate constant Ki and maximum standardized uptake value to discriminate between poor and good lesion outcomes were 89% and 81%, respectively. There were significant differences in the 18F-FSPG uptake curves of lesions with good versus poor outcomes in the primary brain tumor group (P < .05) but not in the brain metastases group. Conclusion PET/CT imaging with (4S)-4-(3-[18F]fluoropropyl)-l-glutamate (18F-FSPG) helped detect primary brain tumors and brain metastases with a high tumor-to-background ratio. Relative changes in 18F-FSPG uptake with multi-time-point PET appear to be helpful in predicting lesion outcomes. Clinical trial registration no. NCT02370563 © RSNA, 2022 Online supplemental material is available for this article.

    View details for DOI 10.1148/radiol.203296

    View details for PubMedID 35191738

  • Intracranial Response to Combination BRAF and MEK Inhibitor Therapy in Patients with Metastatic Melanoma Hui, C., Wu, Y., Liu, K., Sandhu, N., Blomain, E., Binkley, M., Gephart, M., Chang, S., Li, G., Reddy, S., Gibbs, I., Soltys, S., Pollom, E. LIPPINCOTT WILLIAMS & WILKINS. 2021: S48-S49
  • Tumor treating fields induce DNA damage and apoptosis in medulloblastoma. Nitta, R. T., Li, G. AMER ASSOC CANCER RESEARCH. 2021
  • Risk of secondary neoplasms after external-beam radiation therapy treatment of pediatric low-grade gliomas: a SEER analysis, 1973-2015. Journal of neurosurgery. Pediatrics Rodrigues, A. J., Jin, M. C., Wu, A., Bhambhvani, H. P., Li, G., Grant, G. A. 2021: 1-9


    Although past studies have associated external-beam radiation therapy (EBRT) with higher incidences of secondary neoplasms (SNs), its effect on SN development from pediatric low-grade gliomas (LGGs), defined as WHO grade I and II gliomas of astrocytic or oligodendrocytic origin, is not well understood. Utilizing a national cancer registry, the authors sought to characterize the risk of SN development after EBRT treatment of pediatric LGG.A total of 1245 pediatric patient (aged 0-17 years) records from 1973 to 2015 were assembled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable subdistribution hazard regression models were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Cumulative incidence analyses measured the time to, and rate of, SN development, stratified by receipt of EBRT and controlled for competing mortality risk. The Fine and Gray semiparametric model was used to estimate future SN risk in EBRT- and non-EBRT-treated pediatric patients.In this study, 366 patients received EBRT and 879 did not. Forty-six patients developed SNs after an LGG diagnosis, and 27 of these patients received EBRT (OR 3.61, 95% CI 1.90-6.95; p < 0.001). For patients alive 30 years from the initial LGG diagnosis, the absolute risk of SN development in the EBRT-treated cohort was 12.61% (95% CI 8.31-13.00) compared with 4.99% (95% CI 4.38-12.23) in the non-EBRT-treated cohort (p = 0.013). Cumulative incidence curves that were adjusted for competing events still demonstrated higher rates of SN development in the EBRT-treated patients with LGGs. After matching across available covariates and again adjusting for the competing risk of mortality, a clear association between EBRT and SN development remained (subhazard ratio 2.26, 95% CI 1.21-4.20; p = 0.010).Radiation therapy was associated with an increased risk of future SNs for pediatric patients surviving LGGs. These data suggest that the long-term implications of EBRT should be considered when making treatment decisions for this patient population.

    View details for DOI 10.3171/2021.1.PEDS20859

    View details for PubMedID 34144522

  • Management of brain tumors presenting in pregnancy: a case series and systematic review Management of brain tumors presenting in pregnancy: a case series and systematic review Rodrigues, A. 2021; 3 (1)
  • EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial Theranostics Zhou, Q., van den Berg, N. S., Rosenthal, E. L., Iv, M., Zhang, M., Vega Leonel, J. C., Walters, S., Nishio, N., Granucci, M., Raymundo, R., Yi, G., Vogel, H., Cayrol, R., Lee, Y., Lu, G., Hom, M., Kang, W., Hayden Gephart, M., Recht, L. D., Nagpal, S., Thomas, R. P., Patel, C. B., Grant, G. A., Li, G. 2021; 11 (15): 7130-7143

    View details for DOI 10.7150/thno.60582

  • In Vivo Evaluation of Near-Infrared Fluorescent Probe for TIM3 Targeting in Mouse Glioma. Molecular imaging and biology Zhang, M., Zhou, Q., Huang, C., Chan, C. T., Wu, W., Li, G., Lim, M., Gambhir, S. S., Daldrup-Link, H. E. 2021


    Current checkpoint inhibitor immunotherapy strategies in glioblastoma are challenged by mechanisms of resistance including an immunosuppressive tumor microenvironment. T cell immunoglobulin domain and mucin domain 3 (TIM3) is a late-phase checkpoint receptor traditionally associated with T cell exhaustion. We apply fluorescent imaging techniques to explore feasibility of in vivo visualization of the immune state in a glioblastoma mouse model.TIM3 monoclonal antibody was conjugated to a near-infrared fluorescent dye, IRDye-800CW (800CW). The TIM3 experimental conjugate and isotype control were assessed for specificity with immunofluorescent staining and flow cytometry in murine cell lines (GL261 glioma and RAW264.7 macrophages). C57BL/6 mice with orthotopically implanted GL261 cells were imaged in vivo over 4 days after intravenous TIM3-800CW injection to assess tumor-specific uptake. Cell-specific uptake was then assessed on histologic sections.The experimental TIM3-800CW, but not its isotype control, bound to RAW264.7 macrophages in vitro. Specificity to RAW264.7 macrophages and not GL261 tumor cells was quantitatively confirmed with the corresponding clone of TIM3 on flow cytometry. In vivo fluorescence imaging of the 800CW signal was localized to the intracranial tumor and significantly higher for the TIM3-800CW cohort, relative to non-targeting isotype control, immediately after tail vein injection and for up to 48 h after injection. Resected organs of tumor bearing mice showed significantly higher uptake in the liver and spleen. TIM3-800CW was seen to co-stain with CD3 (13%), CD11b (29%), and CD206 (26%).We propose fluorescent imaging of immune cell imaging as a potential strategy for monitoring and localizing immunologically relevant foci in the setting of brain tumors. Alternative markers and target validation will further clarify the temporal relationship of immunosuppressive effector cells throughout glioma resistance.

    View details for DOI 10.1007/s11307-021-01667-0

    View details for PubMedID 34846678

  • Defining and Describing Treatment Heterogeneity in New-Onset Idiopathic Lower Back and Extremity Pain Through Reconstruction of Longitudinal Care Sequences. The spine journal : official journal of the North American Spine Society Jin, M. C., Azad, T. D., Fatemi, P., Ho, A. L., Vail, D., Zhang, Y., Feng, A. Y., Kim, L. H., Bentley, J. P., Stienen, M. N., Li, G., Desai, A. M., Veeravagu, A., Ratliff, J. K. 2021


    Despite established guidelines, long-term management of surgically-treated low back pain (LBP) and lower extremity pain (LEP) remains heterogeneous. Understanding care heterogeneity could inform future approaches for standardization of practices.To describe treatment heterogeneity in surgically-managed LBP and LEP.Retrospective study of a nationwide commercial database spanning inpatient and outpatient encounters for enrollees of eligible employer-supplied healthcare plans (2007-2016).A population-based sample of opioid-naïve adult patients with newly-diagnosed LBP or LEP were identified. Inclusion required at least 12-months of pre-diagnosis and post-diagnosis continuous follow-up.Included treatments/evaluations include conservative management (chiropractic manipulative therapy, physical therapy, epidural steroid injections), imaging (x-ray, MRI, CT), pharmaceuticals (opioids, benzodiazepines), and spine surgery (decompression, fusion).Primary outcomes-of-interest were 12-month net healthcare expenditures (inpatient and outpatient) and 12-month opioid usage.Analyses include interrogation of care sequence heterogeneity and temporal trends in sequence-initiating services. Comparisons were conducted in the framework of sequence-specific treatment sequences, which reflect the personalized order of healthcare services pursued by each patient. Outlier sequences characterized by high opioid use and costs were identified from frequently observed surgical treatment sequences using Mahalanobis distance.A total of 2,496,908 opioid-naïve adult patients with newly-diagnosed LBP or LEP were included (29,519 surgical). In the matched setting, increased care sequence heterogeneity was observed in surgical patients (0.51 vs 0.12 previously-unused interventions/studies pursued per month). Early opioid and MRI use has decreased between 2008 and 2015 but is matched by increases in early benzodiazepine and x-ray use. Outlier sequences, characterized by increased opioid use and costs, were found in 5.8% of surgical patients. Use of imaging prior to conservative management was common in patients pursuing outlier sequences compared to non-outlier sequences (96.5% vs 63.8%, p<0.001). Non-outlier sequences were more frequently characterized by early conservative interventions (31.9% vs 7.4%, p<0.001).Surgically-managed LBP and LEP care sequences demonstrate high heterogeneity despite established practice guidelines. Outlier sequences associated with high opioid usage and costs can be identified and are characterized by increased early imaging and decreased early conservative management. Elements that may portend suboptimal longitudinal management could provide opportunities for standardization of patient care.

    View details for DOI 10.1016/j.spinee.2021.05.019

    View details for PubMedID 34033933

  • Focused ultrasound: growth potential and future directions in neurosurgery. Journal of neuro-oncology Zhang, M., Rodrigues, A., Zhou, Q., Li, G. 2021


    Over the past two decades, vast improvements in focused ultrasound (FUS) technology have made the therapy an exciting addition to the neurosurgical armamentarium. In this time period, FUS has gained US Food and Drug Administration (FDA) approval for the treatment of two neurological disorders, and ongoing efforts seek to expand the lesion profile that is amenable to ultrasonic intervention. In the following review, we highlight future applications for FUS therapy and compare its potential role against established technologies, including deep brain stimulation and stereotactic radiosurgery. Particular attention is paid to tissue ablation, blood-brain-barrier opening, and gene therapy. We also address technical and infrastructural challenges involved with FUS use and summarize the hurdles that must be overcome before FUS becomes widely accepted in the neurosurgical community.

    View details for DOI 10.1007/s11060-021-03820-9

    View details for PubMedID 34410576

  • Obesity in Patients Undergoing Lumbar Degenerative Surgery-A Retrospective Cohort Study of Postoperative Outcomes. Spine Varshneya, K., Wadhwa, H., Stienen, M. N., Ho, A. L., Medress, Z. A., Aikin, J., Li, G., Desai, A., Ratliff, J. K., Veeravagu, A. 2021; 46 (17): 1191-1196


    Retrospective cohort studying using a national, administrative database.The aim of this study was to determine the postoperative complications and quality outcomes of patients with and without obesity undergoing surgical management for lumbar degenerative disease (LDD).Obesity is a global epidemic that negatively impacts health outcomes. Characterizing the effect of obesity on LDD surgery is important given the growing elderly obese population.This study identified patients with who underwent surgery for LDD between 2007 and 2016. Patients were stratified based on whether the patient had a concurrent diagnosis of obesity at time of surgery. Propensity score matching (PSM) was then utilized to mitigate intergroup differences between patients with and without obesity. Patients who underwent three or more levels surgical correction, were under the age of 18 years, or those with any previous history of trauma or tumor were excluded from this study. Baseline comorbidities, postoperative complication rates, and reoperation rates were determined.A total of 67,215 patients underwent primary lumbar degenerative surgery, of which 22,405 (33%) were obese. After propensity score matching, baseline covariates of the two cohorts were similar. The complication rate was 8.3% in the nonobese cohort and 10.4% in the obese cohort (P < 0.0001). Patients with obesity also had longer lengths of stay (2.7 days vs. 2.4 days, P < 0.05), and higher rates of reoperation and readmission at all time-points through the study follow-up period to their nonobese counterparts (P < 0.05). Including payments after discharge, lumbar degenerative surgery in patients with obesity was associated with higher payments throughout the 2-year follow-up period (

  • Phase I/II Dose-Escalation Trial of 3-Fraction Stereotactic Radiosurgery for Resection Cavities From Large Brain Metastases: Health-related Quality of Life Outcomes. American journal of clinical oncology Rahimy, E., Dudley, S. A., von Eyben, R., Pollom, E. L., Seiger, K., Modlin, L., Wynne, J., Fujimoto, D., Jacobs, L. R., Chang, S. D., Gibbs, I. C., Hancock, S. L., Adler, J. R., Li, G., Choi, C. Y., Soltys, S. G. 2021; 44 (11): 588-595


    We investigated differences in quality of life (QoL) in patients enrolled on a phase I/II dose-escalation study of 3-fraction resection cavity stereotactic radiosurgery (SRS) for large brain metastases.Eligible patients had 1 to 4 brain metastases, one of which was a resection cavity 4.2 to 33.5 cm3. European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaires core-30 (QLQ-30) and brain cancer specific module (QLQ-BN20) were obtained before SRS and at each follow-up. Nine scales were analyzed (global health status; physical, social, and emotional functioning; motor dysfunction, communication deficit, fatigue, insomnia, and future uncertainty). QoL was assessed with mixed effects models. Differences ≥10 points with q-value (adjusted P-value to account for multiplicity of testing) <0.10 were considered significant.Between 2009 and 2014, 50 enrolled patients completed 277 QoL questionnaires. Median questionnaire follow-up was 11.8 months. After SRS, insomnia demonstrated significant improvement (q=0.032, -17.7 points at 15 mo post-SRS), and future uncertainty demonstrated significant worsening (q=0.018, +9.9 points at 15 mo post-SRS). Following intracranial progression and salvage SRS, there were no significant QoL changes. The impact of salvage whole brain radiotherapy could not be assessed because of limited data (n=4 patients). In the 28% of patients that had adverse radiation effect, QoL had significant worsening in 3 metrics (physical functioning, q=0.024, emotional functioning q=0.001, and future uncertainty, q=0.004).For patients treated with 3-fraction SRS for large brain metastasis cavities, 8 of 9 QoL metrics were unchanged or improved after initial SRS. Intracranial tumor progression and salvage SRS did not impact QoL. Adverse radiation effect may be associated with at least short-term QoL impairments, but requires further investigation.

    View details for DOI 10.1097/COC.0000000000000868

    View details for PubMedID 34670228

  • Financial Toxicity in Patients with Brain and Spine Metastases. World neurosurgery Koenig, J. L., Sandhu, N. n., Sborov, K. n., Sabolch, A. n., Usoz, M. n., Li, G. n., Gephart, M. H., Chang, S. n., Hiniker, S. n., Soltys, S. G., Pollom, E. L. 2021


    Financial toxicity associated with cancer treatment has a deleterious impact on patient outcomes but has not been well-characterized among patients with metastatic cancers. We characterize the extent of financial toxicity among this population and identify factors associated with financial toxicity.We prospectively surveyed adult patients with brain and spine metastases who received radiosurgery at a large academic medical center between January 2018 and December 2019. Financial toxicity was measured with the Personal Financial Wellness (PFW) Scale.In total, 93 patients were included with a median survival of 17.7 months. Most patients had private insurance (47%) or Medicare with supplemental insurance (42%) while 11% of patients were uninsured or insured by Medicaid/Medicare/Veterans Affairs. 60% of patients were primary income earners of which 52% had dependents. The median PFW score was 7.0 (interquartile range, 5.1-9.1) with financial toxicity reported in 23 (25%) patients. After adjusting for age and education level, private insurance (OR 0.28; p=0.080) was associated with a lower likelihood of financial toxicity. At least one emergency department visit (OR 3.87; p=0.024) and a cancer-related change in employment status (OR 3.63; p=0.036) were associated with greater likelihood of reporting financial toxicity.Most poor prognosis cancer patients with brain and spine metastases treated at a tertiary center are primary income earners and experience financial toxicity. Further studies are warranted to assess the longitudinal impact of financial toxicity in patients with metastatic cancer, particularly those with at least one emergency department visit and a cancer-related change in employment status.

    View details for DOI 10.1016/j.wneu.2021.04.103

    View details for PubMedID 33940276

  • Status epilepticus after intracranial neurosurgery: incidence and risk stratification by perioperative clinical features. Journal of neurosurgery Jin, M. C., Parker, J. J., Zhang, M. n., Medress, Z. A., Halpern, C. H., Li, G. n., Ratliff, J. K., Grant, G. A., Fisher, R. S., Skirboll, S. n. 2021: 1–13


    Status epilepticus (SE) is associated with significant mortality, cost, and risk of future seizures. In one of the first studies of SE after neurosurgery, the authors assess the incidence, risk factors, and outcome of postneurosurgical SE (PNSE).Neurosurgical admissions from the MarketScan Claims and Encounters database (2007 through 2015) were assessed in a longitudinal cross-sectional sample of privately insured patients who underwent qualifying cranial procedures in the US and were older than 18 years of age. The incidence of early (in-hospital) and late (postdischarge readmission) SE and associated mortality was assessed. Procedural, pathological, demographic, and anatomical covariates parameterized multivariable logistic regression and Cox models. Multivariable logistic regression and Cox proportional hazards models were used to study the incidence of early and late PNSE. A risk-stratification simulation was performed, combining individual predictors into singular risk estimates.A total of 197,218 admissions (218,217 procedures) were identified. Early PNSE occurred during 637 (0.32%) of 197,218 admissions for cranial neurosurgical procedures. A total of 1045 (0.56%) cases of late PNSE were identified after 187,771 procedure admissions with nonhospice postdischarge follow-up. After correction for comorbidities, craniotomy for trauma, hematoma, or elevated intracranial pressure was associated with increased risk of early PNSE (adjusted OR [aOR] 1.538, 95% CI 1.183-1.999). Craniotomy for meningioma resection was associated with an increased risk of early PNSE compared with resection of metastases and parenchymal primary brain tumors (aOR 2.701, 95% CI 1.388-5.255). Craniotomies for infection or abscess (aHR 1.447, 95% CI 1.016-2.061) and CSF diversion (aHR 1.307, 95% CI 1.076-1.587) were associated with highest risk of late PNSE. Use of continuous electroencephalography in patients with early (p < 0.005) and late (p < 0.001) PNSE rose significantly over the study time period. The simulation regression model predicted that patients at high risk for early PNSE experienced a 1.10% event rate compared with those at low risk (0.07%). Similarly, patients predicted to be at highest risk for late PNSE were significantly more likely to eventually develop late PNSE than those at lowest risk (HR 54.16, 95% CI 24.99-104.80).Occurrence of early and late PNSE was associated with discrete neurosurgical pathologies and increased mortality. These data provide a framework for prospective validation of clinical and perioperative risk factors and indicate patients for heightened diagnostic suspicion of PNSE.

    View details for DOI 10.3171/2020.10.JNS202895

    View details for PubMedID 33990087

  • Improved survival and disease control following pembrolizumab-induced immune-related adverse events in high PD-L1 expressing non-small cell lung cancer with brain metastases. Journal of neuro-oncology Zhang, M. n., Rodrigues, A. J., Pollom, E. L., Gibbs, I. C., Soltys, S. G., Hancock, S. L., Neal, J. W., Padda, S. K., Ramchandran, K. J., Wakelee, H. A., Chang, S. D., Lim, M. n., Hayden Gephart, M. n., Li, G. n. 2021


    Immune checkpoint inhibitors have become standard of care for many patients with non-small cell lung cancer (NSCLC). These agents often cause immune-related adverse events (IRAEs), which have been associated with increased overall survival (OS). Intracranial disease control and OS for patients experiencing IRAEs with metastatic NSCLC and brain metastases have not yet been described.We performed a single-institution, retrospective review of patients with NSCLC and existing diagnosis of brain metastasis, who underwent pembrolizumab treatment and developed any grade IRAE. The primary outcome of the study was intracranial time to treatment failure (TTF), defined from time of pembrolizumab initiation to new intracranial disease progression or death. Kaplan-Meier and Cox proportional hazard analyses were performed.A total of 63 patients with NSCLC brain metastasis were identified, and 24 developed IRAEs. Patients with any grade IRAEs had longer OS (21 vs. 10 months, p = 0.004), systemic TTF (15 vs. 4 months, p < 0.001) and intracranial TTF (14 vs. 5 months, p = 0.001), relative to patients without IRAEs. Presence of IRAEs and high PD-L1 (≥ 50%), but not absent/moderate PD-L1 (0-49%), had a positive association for OS, systemic TTF, and intracranial TTF. Following multivariable analysis, IRAE experienced on pembrolizumab was an independent predictor of OS, systemic TTF, and intracranial TTF.In our series of patients with NSCLC and brain metastases treated with pembrolizumab, IRAE presence was associated with a significant increase in OS, systemic TTF, and intracranial TTF. Future studies with increased cohorts will clarify how IRAEs should be interpreted among molecular subtypes.

    View details for DOI 10.1007/s11060-020-03686-3

    View details for PubMedID 33415659

  • Management of brain tumors presenting in pregnancy: a case series and systematic review. American journal of obstetrics & gynecology MFM Rodrigues, A. J., Waldrop, A. R., Suharwardy, S., Druzin, M. L., Iv, M., Ansari, J. R., Stone, S. A., Jaffe, R. A., Jin, M. C., Li, G., Hayden-Gephart, M. 2021; 3 (1): 100256


    Patients who present with brain tumors during pregnancy require unique imaging and neurosurgical, obstetrical, and anesthetic considerations. Here, we review the literature and discuss the management of patients who present with brain tumors during pregnancy. Between 2009 and 2019, 9 patients were diagnosed at our institution with brain tumors during pregnancy. Clinical information was extracted from the electronic medical records. The median age at presentation was 29 years (range, 25-38 years). The most common symptoms at presentation included headache (n=5), visual changes (n=4), hemiparesis (n=3), and seizures (n=3). The median gestational age at presentation was 20.5 weeks (range, 11-37 weeks). Of note, 8 patients (89%) delivered healthy newborns, and 1 patient terminated her pregnancy. In addition, 5 patients (56%) required neurosurgical procedures during pregnancy (gestational ages, 14-37 weeks) because of disease progression (n=2) or neurologic instability (n=3). There was 1 episode of postneurosurgery morbidity (pulmonary embolism [PE]) and no surgical maternal mortality. The median length of follow-up was 15 months (range, 6-45 months). In cases demonstrating unstable or progressive neurosurgical status past the point of fetal viability, neurosurgical intervention should be considered. The physiological and pharmacodynamic changes of pregnancy substantially affect anesthetic management. Pregnancy termination should be discussed and offered to the patient when aggressive disease necessitates immediate treatment and the fetal gestational age remains previable, although neurologically stable patients may be able to continue the pregnancy to term. Ultimately, pregnant patients with brain tumors require an individualized approach to their care under the guidance of a multidisciplinary team.

    View details for DOI 10.1016/j.ajogmf.2020.100256

    View details for PubMedID 33451609

  • An Analysis of Public Interest in Elective Neurosurgical Procedures during the COVID-19 Pandemic through Online Search Engine Trends. World neurosurgery Feng, A. Y., Garcia, C. A., Jin, M. C., Ho, A. L., Li, G. n., Grant, G. n., Ratliff, J. n., Skirboll, S. L. 2021


    In the wake of the COVID-19 pandemic, the Centers for Medicare & Medicaid Services (CMS) has recommended the temporary cessation of all elective surgeries. The effects on patients' interest of elective neurosurgical procedures are currently unexplored.Using Google Trends (GT), search terms of seven different neurosurgical procedure categories (Trauma, Spine, Tumor, Movement Disorder, Epilepsy, Endovascular, and Miscellaneous) were assessed in terms of relative search volume (RSV) between January 2015 and September 2020. Analyses of search terms were performed for over the short-term (Feb 18th, 2020-Apr 18th, 2020), intermediate-term (Jan 1st, 2020-May 31st, 2020) and long-term (Jan 2015-Sept 2020). State-level interest during phase I re-opening (Apr 28th, 2020-May 31st, 2020) was also evaluated.In the short-term, RSV of four categories (epilepsy, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. In the intermediate-term, RSV of five categories (miscellaneous, epilepsy, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. In the long-term, RSV of nearly all categories (endovascular, epilepsy, miscellaneous, movement disorder, spine, and tumor) were significantly lower in the post-CMS announcement period. Only the movement disorder procedure category had significantly higher RSV in states that reopened early.With the recommendation for cessation of elective surgeries, patient interest in overall elective neurosurgical procedures have dropped significantly. With gradual reopening, there has been a resurgence in some procedure types. GT has proven to be a useful tracker of patient interest and may be utilized by neurosurgical departments to facilitate outreach strategies.

    View details for DOI 10.1016/j.wneu.2020.12.143

    View details for PubMedID 33412316

  • FIRST-IN-HUMAN FLUORESCENCE GUIDED SURGERY OF HIGH-GRADE GLIOMAS USING PANITUMUMAB-IRDYE800 Zhou, Q., van den Berg, N., Nishio, N., Lu, G., Chirita, S., Raymundo, R., Yi, G., Vogel, H., Cayrol, R., Rosenthal, E., Li, G. OXFORD UNIV PRESS INC. 2020: 52
  • The Effect of Socioeconomic Status on Age at Diagnosis and Overall Survival in Patients with Intracranial Meningioma. The International journal of neuroscience Brewster, R., Deb, S., Pendharkar, A. V., Ratliff, J., Li, G., Desai, A. 2020: 1–12


    Background: Intracranial meningiomas are the most common primary tumors of the central nervous system. How socioeconomic status (SES) impacts treatment access and outcomes for brain tumor subtypes is an emerging area of research. Few studies have examined the relationship between SES and meningioma survival and management with reference to relevant clinical factors, including age at diagnosis. We studied the independent effects of SES on receiving surgery and survival probability in patients with intracranial meningiomaMethods: 54,282 patients diagnosed with intracranial meningioma between 2003-2012 from the Surveillance, Epidemiology, and End Results (SEER) Program at the National Cancer Institute database were included. Patient SES was divided into tertiles. Patient age groups included "older" (>65, the median patient age) and "younger". Multivariable linear regression and Cox proportional hazards model were used with SAS v9.4. Results were adjusted for race, sex, and tumor grade. Kaplan Meier survival curves were constructed according to SES tertiles and age groups.Results: Meningioma prevalence increased with higher SES tertile. Higher SES tertile was also associated with younger age at diagnosis (OR= 0.890, p <0.05), an increased likelihood of undergoing gross total resection (GTR) (OR =1.112, p<0.05), and a trend towards greater 5-year survival probability (HR =1.773, p=0.0531). Survival probability correlated with younger age at diagnosis (HR =2.597, p<0.001), but not with GTR receipt.Conclusion: The findings from this national longitudinal study on patients with meningioma suggest that SES affects age at diagnosis and treatment access for intracranial meningiomas patients. Further studies are required to understand and address the mechanisms underlying these disparities.

    View details for DOI 10.1080/00207454.2020.1818742

    View details for PubMedID 32878534

  • Leptomeningeal spread with spinal involvement of pineal glioblastoma at initial presentation: A case report INTERDISCIPLINARY NEUROSURGERY-ADVANCED TECHNIQUES AND CASE MANAGEMENT Yerneni, K., Fatemi, P., Vogel, H., Li, G., Zygourakis, C. C. 2020; 21
  • Phase I study of BPM31510 and vitamin K in patients with high grade glioma recurrent after a bevacizumab-containing regimen. Nagpal, S., Thomas, R., Bertrand, S., Yerraballa, H., Iv, M., Li, G., Klotz, A., Kiebish, M. A., Narain, N. R., Sarangarajan, R., Granger, E., Recht, L. AMER SOC CLINICAL ONCOLOGY. 2020
  • A Comparative Analysis of Patients Undergoing Fusion for Adult Cervical Deformity by Approach Type. Global spine journal Varshneya, K., Medress, Z. A., Stienen, M. N., Nathan, J., Ho, A., Pendharkar, A. V., Loo, S., Aikin, J., Li, G., Desai, A., Ratliff, J. K., Veeravagu, A. 2020: 2192568220915717


    Retrospective cohort study.To provide insight into postoperative complications, short-term quality outcomes, and costs of the surgical approaches of adult cervical deformity (ACD).A national database was queried from 2007 to 2016 to identify patients who underwent cervical fusion for ACD. Patients were stratified by approach type-anterior, posterior, or circumferential. Patients undergoing anterior and posterior approach surgeries were additionally compared using propensity score matching.A total of 6575 patients underwent multilevel cervical fusion for ACD correction. Circumferential fusion had the highest postoperative complication rate (46.9% vs posterior: 36.7% vs anterior: 18.5%, P < .0001). Anterior fusion patients more commonly required reoperation compared with posterior fusion patients (P < .0001), and 90-day readmission rate was highest for patients undergoing circumferential fusion (P < .0001). After propensity score matching, the complication rate remained higher in the posterior, as compared to the anterior fusion group (P < .0001). Readmission rate also remained higher in the posterior fusion group; however, anterior fusion patients were more likely to require reoperation. At index hospitalization, posterior fusion led to 1.5× higher costs, and total payments at 90 days were 1.6× higher than their anterior fusion counterparts.Patients who undergo posterior fusion for ACD have higher complication rates, readmission rates, and higher cost burden than patients who undergo anterior fusion; however, posterior correction of ACD is associated with a lower rate of reoperation.

    View details for DOI 10.1177/2192568220915717

    View details for PubMedID 32875897

  • A Comparative Analysis of Patients Undergoing Fusion for Adult Cervical Deformity by Approach Type GLOBAL SPINE JOURNAL Varshneya, K., Medress, Z. A., Stienen, M. N., Nathan, J., Ho, A., Pendharkar, A. V., Loo, S., Aikin, J., Li, G., Desai, A., Ratliff, J. K., Veeravagu, A. 2020
  • Impact of World War I on brain mapping. Journal of neurosurgical sciences Shah, A., Jung, H., Li, G. 2020; 64 (1): 113–16


    Although much tragedy was experienced during World War I (WWI), the nature of the war and the advancements of weaponry led to a change in the quality and quantity of injuries which were conducive for study. This paper discusses how trauma during WWI led to advances in brain mapping from occipital injuries. Gordon Holmes was a British neurologist who was able to create a retinotopic map of the visual cortex from studying more than 400 cases of occipital injuries; his work has contributed immensely to our understanding of visual processing. There have been many extensions from Holmes' work in regard to how we analyze other sensory modalities and in researching how the brain processes complex stimuli such as faces. Aside from the scholastic benefit, brain mapping also has functional use and can be used for neurosurgical planning to preserve important structures. With the advent of more advanced modalities for analyzing the brain, there have been initiatives in total brain mapping which has added significantly to the body of work started by Holmes during WWI. This paper reviews the history during WWI that led to advances in brain mapping, the lasting scholastic and functional impact from these advancements, and future improvements.

    View details for DOI 10.23736/S0390-5616.16.03313-0

    View details for PubMedID 25963958

  • Lumboperitoneal and Ventriculoperitoneal Shunting for Idiopathic Intracranial Hypertension Demonstrate Comparable Failure and Complication Rates NEUROSURGERY Azad, T. D., Zhang, Y., Varshneya, K., Veeravagu, A., Ratliff, J. K., Li, G. 2020; 86 (2): 272–80
  • Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial. Clinical cancer research : an official journal of the American Association for Cancer Research Reardon, D. A., Desjardins, A. n., Vredenburgh, J. J., O'Rourke, D. M., Tran, D. D., Fink, K. L., Nabors, L. B., Li, G. n., Bota, D. A., Lukas, R. V., Ashby, L. S., Duic, J. P., Mrugala, M. M., Cruickshank, S. n., Vitale, L. n., He, Y. n., Green, J. A., Yellin, M. J., Turner, C. D., Keler, T. n., Davis, T. A., Sampson, J. H. 2020


    Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma.In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naïve patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2.Between May 2012 and 2014, 73 patients were randomized (36 rindopepimut, 37 control). Rindopepimut toxicity included transient, low-grade local reactions. As primary endpoint, PFS6 was 28% (10/36) for rindopepimut compared with 16% (6/37) for control (P = 0.12, one-sided). Secondary and exploratory endpoints also favored the rindopepimut group including a statistically significant survival advantage [HR, 0.53; 95% confidence interval (CI), 0.32-0.88; two-sided log-rank P = 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P = 0.38)], median duration of response [7.8 months (95% CI, 3.5-22.2) vs. 5.6 (95% CI, 3.7-7.4)], and ability to discontinue steroids for ≥6 months [33% (6/18) vs. 0% (0/19)]. Eighty percent of rindopepimut-treated patients achieved robust anti-EGFRvIII titers (≥1:12,800), which were associated with prolonged survival (HR = 0.17; 95% CI, 0.07-0.45; P < 0.0001).Our randomized trial supports the potential for targeted immunotherapy among patients with GBM, but the therapeutic benefit requires validation due to the small sample size and potential heterogeneity of bevacizumab response among recurrent patients with GBM.

    View details for DOI 10.1158/1078-0432.CCR-18-1140

    View details for PubMedID 32034072

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


    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

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


    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