Publications from the Li Lab

Professor of Neurosurgery and, by courtesy, of Neurology and of Otolaryngology - Head & Neck Surgery (OHNS) at the Stanford University Medical Center

Publications

  • 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., Grant, G., Ratliff, J., Skirboll, S. L. 2021

    Abstract

    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

  • 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., 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., Hayden Gephart, M., Li, G. 2021

    Abstract

    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

    Abstract

    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

  • 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
  • PREOPERATIVE SINGLE FRACTION RADIOSURGERY VERSUS POSTOPERATIVE FRACTIONATED RADIOSURGERY FOR RESECTED BRAIN METASTASES: A BI-INSTITUTIONAL ANALYSIS OF SAFETY AND CLINICAL OUTCOMES Prabhu, R., Shi, S., Dhakal, R., Soltys, S., Burri, S., Asher, A., Gephart, M., Ward, M., Li, G., Heinzerling, J., Pollom, E. OXFORD UNIV PRESS INC. 2020: 184
  • 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

    Abstract

    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
  • Impact of World War I on brain mapping. Journal of neurosurgical sciences Shah, A., Jung, H., Li, G. 2020; 64 (1): 113–16

    Abstract

    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., Vredenburgh, J. J., O'Rourke, D. M., Tran, D. D., Fink, K. L., Nabors, L. B., Li, G., Bota, D. A., Lukas, R. V., Ashby, L. S., Duic, J. P., Mrugala, M. M., Cruickshank, S., Vitale, L., He, Y., Green, J. A., Yellin, M. J., Turner, C. D., Keler, T., Davis, T. A., Sampson, J. H. 2020

    Abstract

    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., 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

  • 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

  • Commentary: The Effects of Postoperative Neurological Deficits on Survival in Patients With Single Brain Metastasis. Operative neurosurgery (Hagerstown, Md.) Zhang, M., Li, G. 2020

    View details for DOI 10.1093/ons/opaa267

    View details for PubMedID 32860056

  • 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

    Abstract

    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

  • Stereotactic Radiosurgery After Resection of Brain Metastases: Changing Patterns of Care in the United States. World neurosurgery Chin, A. L., Li, G., Gephart, M. H., Sandhu, N., Nagpal, S., Soltys, S. G., Pollom, E. L. 2020

    Abstract

    Management of symptomatic brain metastases often includes surgical resection with postoperative radiotherapy. Postoperative whole brain radiotherapy (WBRT) improves intracranial control but detrimentally impacts quality of life and neurocognition. We sought to characterize the use in the United States of postoperative stereotactic radiosurgery (SRS), an evolving standard-of-care associated with reduced cognitive effects.With the MarketScan Commercial Claims and Encounters Database from 2007 to 2015, we identified patients aged 18-65 years treated with resection of a brain metastasis followed by SRS or WBRT within 60 days of surgery. Logistic regression estimated associations between co-variables (treatment year, age, sex, geographic region, place of service, insurance type, disease histology, comorbidity score, and median area household income and educational attainment) and SRS receipt.Of 4,007 patients included, 1,506 (37.6%) received SRS and 2,501 (62.4%) received WBRT. Postoperative SRS increased from 16.5% (2007-2008) to 56.8% (2014-2015). Patients residing in areas with a median household income or an educational attainment below 50th percentile were significantly less likely to receive SRS after controlling for treatment year and other demographic characteristics (p<0.01). Factors associated with higher odds of receiving SRS included younger age, female sex, melanoma histology, Western region location, hospital-based facility, and high-deductible health plan enrollment (p<0.05 for each).Postoperative SRS for brain metastases has increased from 2007 to 2015, with the majority of patients now receiving SRS over WBRT. Patients in areas of lower socioeconomic class were less likely to receive SRS, warranting further investigation of barriers to SRS adoption.

    View details for DOI 10.1016/j.wneu.2020.09.085

    View details for PubMedID 32971279

  • Safety and Stability of Antibody-Dye Conjugate in Optical Molecular Imaging. Molecular imaging and biology Pei, J., Juniper, G., van den Berg, N. S., Nisho, N., Broadt, T., Welch, A. R., Yi, G. S., Raymundo, R. C., Chirita, S. U., Lu, G., Krishnan, G., Lee, Y. J., Kapoor, S., Zhou, Q., Colevas, A. D., Lui, N. S., Poultsides, G. A., Li, G., Zinn, K. R., Rosenthal, E. L. 2020

    Abstract

    The development of molecularly targeted tracers is likely to improve the accuracy of diagnostic, screening, and therapeutic tools. Despite the many therapeutic antibodies that are FDA-approved with known toxicity, only a limited number of antibody-dye conjugates have been introduced to the clinic. Thorough evaluation of the safety, stability, and pharmacokinetics of antibody conjugates in the clinical setting compared with their parental components could accelerate the clinical approval of antibodies as agents for molecular imaging. Here we investigate the safety and stability of a near-infrared fluorescent dye (IRDye800CW) conjugated panitumumab, an approved therapeutic antibody, and report on the product stability, pharmacokinetics, adverse events, and QTc interval changes in patients.Panitumumab-IRDye800CW was made under good manufacturing practice (GMP) conditions in a single batch on March 26, 2014, and then evaluated over 4.5 years at 0, 3, and 6 months, and then at 6-month intervals thereafter. We conducted early phase trials in head and neck, lung, pancreas, and brain cancers with panitumumab-IRDye800CW. Eighty-one patients scheduled to undergo standard-of-care surgery were infused with doses between 0.06 to 2.83 mg/kg of antibody. Patient ECGs, blood samples, and adverse events were collected over 30-day post-infusion for analysis.Eighty-one patients underwent infusion of the study drug at a range of doses. Six patients (7.4 %) experienced an adverse event that was considered potentially related to the drug. The most common event was a prolonged QTc interval which occurred in three patients (3.7 %). Panitumumab-IRDye800CW had two OOS results at 42 and 54 months while meeting all other stability testing criteria.Panitumumab-IRDye800CW was safe and stable to administer over a 54-month window with a low rate of adverse events (7.4 %) which is consistent with the rate associated with panitumumab alone. This data supports re-purposing therapeutic antibodies as diagnostic imaging agents with limited preclinical toxicology studies.

    View details for DOI 10.1007/s11307-020-01536-2

    View details for PubMedID 32880818

  • Patterns of Care and Age-Specific Impact of Extent of Resection and Adjuvant Radiotherapy in Pediatric Pineoblastoma. Neurosurgery Jin, M. C., Prolo, L. M., Wu, A., Azad, T. D., Shi, S., Rodrigues, A. J., Soltys, S. G., Pollom, E. L., Li, G., Hiniker, S. M., Grant, G. A. 2020

    Abstract

    Pediatric pineoblastomas are highly aggressive tumors that portend poor outcomes despite multimodal management. Controversy remains regarding optimal disease management.To evaluate patterns of care and optimal clinical management of pediatric pineoblastoma.A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients diagnosed between 2004 and 2015 were queried from the National Cancer Database. Wilcoxon rank-sum statistics and chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate prognostic impact of covariates. Propensity-score matching was used to balance baseline characteristics.Older patients (age ≥ 4 yr) experienced improved overall survival compared to younger patients (age < 4 yr) (hazard ratio [HR] = 0.41; 95% CI 0.25-0.66). Older patients (adjusted odds ratio [aOR] = 5.21; 95% CI 2.61-10.78) and those residing in high-income regions (aOR = 3.16; 95% CI 1.21-8.61) received radiotherapy more frequently. Radiotherapy was independently associated with improved survival in older (adjusted HR [aHR] = 0.31; 95% CI 0.12-0.87) but not younger (aHR = 0.64; 95% CI 0.20-1.90) patients. The benefits of radiotherapy were more pronounced in patients receiving surgery than in those not receiving surgery (aHR [surgical patients] = 0.23; 95% CI 0.08-0.65; aHR [nonsurgical patients] = 0.46; 95% CI 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P = .041); extent of resection was not associated with survival in younger patients (P = .880).Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma.

    View details for DOI 10.1093/neuros/nyaa023

    View details for PubMedID 32110805

  • 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

  • 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

  • Costs and Complications Associated with Resection of Supratentorial Tumors with and without the Operative Microscope in the United States. World neurosurgery Zhang, Y., Zhang, M., Lin, M., Gephart, M. H., Veeravagu, A., Ratliff, J. K., Li, G. 2020

    Abstract

    The operative microscope, a commonly used tool in neurosurgery, is critical in many supratentorial tumor cases. However, use of operating microscope for supratentorial tumor varies by surgeon.To assess complication rates, readmissions, and costs associated with operative microscope use in supratentorial resections.A retrospective analysis was conducted using a national administrative database to identify patients with glioma or brain metastases who underwent supratentorial resection between 2007 and 2016. Univariate and multivariate analyses were used to assess 30-day complications, readmissions and costs between patients who underwent resection with and without use of microscope.The cohort included 12058 glioma patients and 5433 metastasis patients. Rates of microscope use varied by state from 19.0% to 68.6%. Microscope use was associated with

  • Impact of Proton Radiotherapy on Treatment Timing in Pediatric and Adult Patients with Central Nervous System Tumors Neuro-Oncology Practice Jin, M. C., Shi, S., Wu, A., Sandhu, N., Xiang, M., Soltys, S. G., Hiniker, S., Li, G., Pollom, E. L. 2020

    View details for DOI 10.1093/nop/npaa034

  • Treatment patterns and outcomes for cerebellar glioblastoma in the concomitant chemoradiation era: A National Cancer database study. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Zhang, M., Li, R., Pollom, E. L., Amini, A., Dandapani, S., Li, G. 2020; 82 (Pt A): 122–27

    Abstract

    Cerebellar glioblastoma (GB) is much rarer than its supratentorial counterpart, and potentially of different molecular origin. Prior database studies are of limited size and reported on patients who preceded the validation of temozolomide. Thus, we provide an updated population-based analysis of the treatment trends and outcomes since the standardization of GB adjuvant chemoradiation. Patients diagnosed with primary cerebellar and supratentorial GB were identified from the National Cancer Database spanning 2005-2015. Patients were characterized by demographics, extent of resection, and adjuvant chemotherapy or radiation status. Cohorts were primarily and secondarily assessed for overall survival by tumor site and treatment history, respectively. A total of 655 patients with cerebellar GB were identified (0.6%). Cerebellar GB patients, compared to supratentorial GB were more likely to undergo a biopsy or subtotal resection (13.4% vs 9.3% and 16.0% vs 13.4%, p-value < 0.001), and less likely to pursue adjuvant therapy (48.4% vs 52.7%, p-value < 0.001). Overall median survivals were 9.3 and 9.4 months, respectively. On multivariable analysis, gross total resection, radiation, and chemotherapy were found to be predictors of improved overall survival (HR 0.77, p = 0.038; HR 0.67, p < 0.001; and HR = 0.77, p = 0.030, respectively). While many management principles are currently shared between cerebellar and supratentorial GB, aggressive regimens appear less frequently prescribed. Survival continues to match supratentorial outcomes and may benefit from future, systemic guidance by distinguishing molecular features.

    View details for DOI 10.1016/j.jocn.2020.10.049

    View details for PubMedID 33317719

  • Adverse Events and Bundled Costs after Cranial Neurosurgical Procedures: Validation of the LACE Index Across 40,431 Admissions and Development of the LACE-Cranial Index. World neurosurgery Jin, M. C., Wu, A., Medress, Z. A., Parker, J. J., Desai, A., Veeravagu, A., Grant, G. A., Li, G., Ratliff, J. K. 2020

    Abstract

    Anticipating post-discharge complications following neurosurgery remains difficult. The LACE index, based on four hospitalization descriptors, stratifies patients by risk of 30-day post-discharge adverse events but has not been validated in a procedure-specific manner in neurosurgery. Our study sought to explore the utility of the LACE index in cranial neurosurgery population and to develop an enhanced model, LACE-Cranial.The Optum Clinformatics Database was used to identify cranial neurosurgery admissions (2004-2017). Procedures were grouped as trauma/hematoma/ICP, open vascular, functional/pain, skull base, tumor, or endovascular. Adverse events were defined as post-discharge death/readmission. LACE-Cranial was developed using a logistic regression framework incorporating an expanded feature set in addition to the original LACE components.A total of 40,431 admissions were included. Predictions of 30-day readmissions was best for skull-base (AUC=0.636) and tumor (AUC=0.63) admissions but was generally poor. Predictive ability of 30-day mortality was best for functional/pain admissions (AUC=0.957) and poorest for trauma/hematoma/ICP admissions (AUC=0.613). Across procedure types except for functional/pain, a high-risk LACE score was associated with higher post-discharge bundled payment costs. Incorporating features identified to contribute independent predictive value, the LACE-Cranial model achieved procedure-specific 30-day mortality AUCs ranging from 0.904 to 0.98. Prediction of 30-day and 90-day readmissions was also improved, with tumor and skull base cases achieving 90-day readmission AUCs of 0.718 and 0.717, respectively.While the unmodified LACE index demonstrates inconsistent classification performance, the enhanced LACE-Cranial model offers excellent prediction of short-term post-discharge mortality across procedure groups and significantly improved anticipation of short-term post-discharge readmissions.

    View details for DOI 10.1016/j.wneu.2020.10.103

    View details for PubMedID 33127572

  • 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

  • Functional Mapping for Glioma Surgery: A Propensity-matched Analysis of Outcomes and Cost. World neurosurgery Pendharkar, A. V., Rezaii, P. G., Ho, A. L., Sussman, E. S., Li, G., Desai, A. M. 2020

    Abstract

    To compare clinical outcomes and payments between glioma resections with and without functional mapping.The Thomas Reuters MarketScan national longitudinal database was used to identify patients undergoing resection of supratentorial primary malignant glioma with or without functional mapping between 2007-2016. Patients were stratified into mapped and unmapped (conventional) groups, and subsequently propensity-matched based on demographics, clinical comorbidities, and surgical characteristics (i.e., use of stereotactic navigation, microscope, intratumoral chemotherapy). Outcomes and charges were compared between matched groups using bivariate analyses.A total of 14,037 patients were identified, of which 796 (6.0%) received functional mapping. Propensity-matching (1:1) resulted in 796 mapped patients and 796 propensity-matched controls. Thirty-day postoperative rates of new-onset seizures, cerebral edema, hemorrhage, and neurological deficits were significantly lower for the functional mapping group (all p < 0.05). Functional mapping was also associated with shorter hospital length of stay (p = .0144), lower 30-day rates of emergency department visits (p = .0001) and fewer reoperations (p = .0068). Total costs of initial admission were not significantly different between groups.Intraoperative functional mapping during glioma resection was associated with decreased complications, reoperations, emergency department visits, and shorter lengths of stay. Furthermore, total charges of mapped resections were not significantly different from those of conventional resections. These findings support the utility of functional mapping for resection of supratentorial primary malignant gliomas.

    View details for DOI 10.1016/j.wneu.2020.01.197

    View details for PubMedID 32028000

  • Evaluating Shunt Survival Following Ventriculoperitoneal Shunting with and without Stereotactic Navigation in Previously Shunt-Naïve Patients. World neurosurgery Jin, M. C., Wu, A., Azad, T. D., Feng, A., Prolo, L. M., Veeravagu, A., Grant, G. A., Ratliff, J., Li, G. 2020

    View details for DOI 10.1016/j.wneu.2020.01.138

    View details for PubMedID 31996335

  • A PHASE 1 STUDY OF BPM31510 PLUS VITAMIN K IN SUBJECTS WITH HIGH-GRADE GLIOMA THAT HAS RECURRED ON A BEVACIZUMAB-CONTAINING REGIMEN Recht, L., Thomas, R., Bertrand, S., Yerballa, P., Li, G., Iv, M., Narain, N., Sarangarajan, R., Granger, E., Nagpal, S. OXFORD UNIV PRESS INC. 2019: 27
  • 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