The intersection of race and social determinants of health on clinical outcome of glioblastoma patients.

OBJECTIVE: Resection, chemotherapy, radiation therapy, and tumor treating fields significantly increase the overall survival (OS) of glioblastoma (GBM) patients. Yet, cost and healthcare disparities might limit access. Multiple studies have attributed more than 80% of the GBM disease burden to White patients. The aim of this study was to explore the intersections of race and social determinants of health (SDoH) with healthcare access and outcomes of GBM patients in a large metropolitan area. METHODS: In this retrospective single-center study, the tumor registry at the authors' institution (2011-2019) was queried to identify a GBM cohort according to the updated WHO criteria. Data were supplemented by electronic health records to include demographics, outcome, National Cancer Institute Comorbidity Index (NCI-CI), and the Agency for Healthcare Research and Quality (AHRQ) socioeconomic status (SES) index. RESULTS: A total of 276 unique patients met the study inclusion criteria; 46% of the cohort was female, and 45% was non-White. This racial proportion differs from previous reports indicating that 80% of patients with GBM are White. The proportion of non-White patients in this study was similar to that of the general US population and significantly lower than that of New York City (p < 0.05). Non-White patients predominantly composed the lowest AHRQ SES index quartile, while White patients constituted the highest quartile (p < 0.001). White patients were older at diagnosis compared with non-White patients (63 vs 58 years, p = 0.001). Older age (p = 0.03), higher NCI-CI (p = 0.0006), and lack of insurance (p = 0.03) reduced the odds of a home discharge. Private insurance (p = 0.005), younger age (p = 0.02), and the highest ("wealthiest") AHRQ SES index quartile (p = 0.02) predicted a lower hospital length of stay (LOS). Patients who underwent gross-total resection had greater OS than those who received a subtotal resection or biopsy, independent of race and SDoH (1.68 vs 1.4 years, p = 0.022). CONCLUSIONS: This study is the first to report on race and SDoH of a cohort using the latest WHO criteria for GBM classification. In contrast to previous literature, the study cohort exhibits a higher proportion of non-White patients with GBM, similar to the representation of non-White individuals in the general US population. This study corroborates the impact of SDoH and not race on LOS and discharge location. Initiatives to identify and address these barriers are crucial for enhancing the care of all GBM patients.

Adult neuro-oncology trials in the United States over 5 decades: Analysis of trials completion rate to guide the path forward.

Background: Clinical trials are important to close the gap between therapeutic unmet needs and scientific advances in neuro-oncology. This study analyzes the landscape of neuro-oncology trials to identify completion rates and guide strategies for the path forward. Methods: US-registered adult neuro-oncology clinical trials were extracted from www.clinicaltrials.gov (1966-2019), including funding source, trial type, scope, phase, and subjects' demographics. Completed trials defined as those that had completed participants' examinations or intervention administration for the purpose of the final collection of data for the primary outcome were dichotomized against those that failed to reach completion. Univariate and multivariate analyses were used to detect differences across factors comparing the last 2 decades (2000-2009, 2010-2019). Results: Our search yielded 4522 trials, of which 1257 are eligible for this study. In 25 US states, neuro-oncology trial availability is <0.85/100,000 population. Comparing the past 2 decades, trial completion rate decreased from 88% to 64% (P < .001) and National Institutes of Health funding decreased from 47% to 24% (P < .001). Inclusion of subjects >65-year-old and women increased, while inclusion of Hispanic subjects decreased (P < .001). The top 2 reasons for lack of completion included accrual and operational difficulties. A larger proportion of women, non-Hispanic subjects, and older adults were enrolled in completed trials than in those that failed completion. Conclusions: Our study is the first report on the neuro-oncology clinical trial landscape in the United States and supports the development of strategies to further improve access to these trials. Additionally, attention is needed to identify and modify other factors contributing to lack of completion.

The Current Landscape of Neurosurgical Oncology in Low-Middle-Income Countries (LMIC): Strategies for the Path Forward.

OBJECTIVE: To promote global equity in research, innovation, and care, sharing knowledge and grasping current benchmarks is crucial. Despite LIC/LMIC constituting around 80% of the global population, their contribution to neurosurgery research is less than 5%. This study aims to assess the status of neurosurgical oncology in LIC/LMIC using published data, offering strategic insights for progress. METHODS: Conducting a retrospective bibliometric analysis via PubMed and Scopus databases, we documented reports published (2015-2021) by neurosurgical department-affiliated investigators in LICs/LMICs. World Bank classifications identified LIC and LMIC. Reviewed papers underwent further scrutiny based on independent and associated keyword lists. RESULTS: Our systematic approach revealed 189 studies from LMIC in 10 neurosurgery journals. Of these, 53% were case reports, with 88% focusing on brain pathologies and 12% on the spine. Intra-axial brain tumors (45.8%), extra-axial/skull base (38.4%), and metastasis (3.68%) were prominent. Among noncase report publications, surgical technique and outcome were common themes. India, Egypt, and Tunisia led in publications, with 94% appearing in journals with an impact factor below 5. No papers originated from LIC. CONCLUSIONS: This study reinforces existing findings that data from LMIC inadequately represent their populations, impeding a comprehensive understanding of their neurosurgical oncology landscape. Language barriers and data collection difficulties contribute to this gap. Addressing these challenges could significantly enhance progress in shaping the future of neurosurgical oncology in these regions.

The AANS/CNS Section on Tumors: a summary of 40 years of advocacy to advance the care of patients with brain and spine tumors.

The AANS/CNS Section on Tumors was founded 40 years ago in 1984 to assist in the education of neurosurgeons interested in neuro-oncology, and serves as a resource for other national organizations regarding the clinical treatment of nervous system tumors. The Section on Tumors was the first national physicians' professional organization dedicated to the study and treatment of patients with brain and spine tumors. Over the past 40 years, the Section on Tumors has built solid foundations, including establishing the tumor section satellite meetings, founding the Journal of Neuro-Oncology (the first medical journal dedicated to brain and spine surgical oncology), advancing surgical neuro-oncology education and research, promoting neurosurgical involvement in neuro-oncology clinical trials, and advocating for patients with brain and spine tumors. This review provides a synopsis of the Section on Tumors' history, its challenges, and its opportunities, drawing on the section's archives and input from the 17 section chairs who led it during its first 40 years.

The role of minimally invasive surgery within a multidisciplinary approach for patients with metastatic spine disease over a decade: A systematic review.

BACKGROUND: Metastatic spine disease (MSD) occurs commonly in cancer patients causing pain, spinal instability, devastating neurological compromise, and decreased quality of life. Oncological patients are often medically complex and frail, precluding them form invasive procedures. To address this issue, minimally invasive spinal surgery (MISS) techniques are desirable. The aim of this study is to review published peer-reviewed literature and ongoing clinical trials to provide current state of the art. METHODS: A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, assessing MISS in MSD patients for the period 2013-2023. Innovations under development were assessed by querying and reviewing data from currently enrolling U.S. registered clinical trials. RESULTS: From 3,696 articles, 50 studies on 3,196 patients focused on spinal oncology MISS. The most commonly reported techniques were vertebral augmentation (VA), percutaneous spinal instrumentation, and radiofrequency ablation (RFA). Surgical instrumentation/stabilization techniques were reported in 10/50 articles for a total of 410 patients. The majority of studies focused on pain as a primary outcome measure, with 28/50 studies reporting a significant improvement in pain following intervention. In the United States, 13 therapeutic trials are currently recruiting MSD patients. Their main focus includes radiosurgery, VA and/or RFA, and laser interstitial thermal therapy. CONCLUSIONS: Due to their medical complexity and increased fragility, MSD patients may benefit from minimally invasive approaches. These strategies are effective at mitigating pain and preventing neurological deterioration, while providing other advantages including ease to start/resume systemic/radiotherapy treatment(s).

Prognosis Individualized: Survival predictions for WHO grade II and III gliomas with a machine learning-based web application.

WHO grade II and III gliomas demonstrate diverse biological behaviors resulting in variable survival outcomes. In the context of glioma prognosis, machine learning (ML) approaches could facilitate the navigation through the maze of factors influencing survival, aiding clinicians in generating more precise and personalized survival predictions. Here we report the utilization of ML models in predicting survival at 12, 24, 36, and 60 months following grade II and III glioma diagnosis. From the National Cancer Database, we analyze 10,001 WHO grade II and 11,456 grade III cranial gliomas. Using the area under the receiver operating characteristic (AUROC) values, we deploy the top-performing models in a web application for individualized predictions. SHapley Additive exPlanations (SHAP) enhance the interpretability of the models. Top-performing predictive models are the ones built with LightGBM and Random Forest algorithms. For grade II gliomas, the models yield AUROC values ranging from 0.813 to 0.896 for predicting mortality across different timeframes, and for grade III gliomas, the models yield AUROCs ranging from 0.855 to 0.878. ML models provide individualized survival forecasts for grade II and III glioma patients across multiple clinically relevant time points. The user-friendly web application represents a pioneering digital tool to potentially integrate predictive analytics into neuro-oncology clinical practice, to empower prognostication and personalize clinical decision-making.

A Phase I Trial of VEGF-A Inhibition Combined with PD-L1 Blockade for Recurrent Glioblastoma.

Purpose: The treatment of glioblastoma (GBM) poses challenges. The use of immune checkpoint inhibition (ICI) has been disappointing as GBM is characterized by low mutational burden and low T-cell infiltration. The combination of ICI with other treatment modalities may improve efficacy. Patient and Methods: Patients with recurrent GBM were treated with avelumab, a human IgG1 antibody directed against PD-L1 (part A), or avelumab within a week after laser interstitial thermal therapy (LITT) and continuation of avelumab (part B). Bevacizumab was allowed to be combined with ICI to spare steroid use. The primary objective was to characterize the tolerability and safety of the regimens. The secondary objectives included overall survival, progression-free survival (PFS), signatures of plasma analytes, and immune cells. Results: A total of 12 patients (median age 64; range, 37-73) enrolled, five in part A and seven in part B. Two serious adverse events occurred in the same patient, LITT treated, not leading to death. The median survival from enrollment was 13 months [95% confidence interval (CI), 4-16 months] with no differences for part A or B. The median PFS was 3 months (95% CI, 1.5-4.5 months). The decrease in MICA/MICB, γδT cells, and CD4+ T cell EMRA correlated with prolonged survival. Conclusions: Avelumab was generally well tolerated. Adding bevacizumab to ICI may be beneficial by lowering cytokine and immune cell expression. The development of this combinatorial treatment warrants further investigation. Exploring the modulation of adaptive and innate immune cells and plasma analytes as biomarker signatures may instruct future studies in this dismal refractory disease. Significance: Our phase I of PD-L1 inhibition combined with LITT and using bevacizumab to spare steroids had a good safety profile for recurrent GBM. Developing combinatory treatment may help outcomes. In addition, we found significant immune modulation of cytokines and immune cells by bevacizumab, which may enhance the effect of ICI.

Third Ventricular Subependymomas: Clinical Features and Outcomes Over Two Decades.

BACKGROUND: Subependymomas are uncommon, benign slow-growing neoplasms of the central nervous system preferentially arising within the fourth and lateral ventricles. Third ventricle involvement has been described rarely. The aim of this study is to provide the first systematic review of third ventricular subependymomas (TVSE) by analyzing all reported cases over 2 decades and describing a case example. METHODS: MEDLINE and Embase databases were searched for the 20 years ending January 1, 2022, using relevant MeSH and non-MeSH terms, including "subependymoma" and "third ventricle." Methodology followed PRISMA guidelines. RESULTS: Of 804 identified studies, 131 met inclusion eligibility. The literature yielded 17 patients with TVSE plus our example (18 total). Of these patients, 83% (15/18) presented in adulthood (average age, 42 ± 19 years), of whom 73% were women. The pediatric cohort age was 5 ± 1 years, 67% (4/6) of whom were girls. The most common presenting symptom in both cohorts was headache (80%), followed by memory disturbances and vomitus. In adults, symptomatic tumors were approached by open craniotomy in all but 1 case, most using a transcallosal approach. Gross total resection was obtained in 73%. A ventriculoperitoneal shunt was inserted in 2/15 adult and 4/6 pediatric patients. Overall, both cohorts showed symptomatic improvement without disease recurrence. One patient died perioperatively. CONCLUSIONS: Subependymomas should be considered in the differential diagnosis of third ventricular tumors. The clinical presentation of TVSE mainly parallels hydrocephalus symptoms and, hence, awareness is of vital importance for timely treatment. The surgical goal should be gross total resection, which can be curative and offers greatest clinical improvement across the population.

Current Neurosurgical Care in Ethiopia Using the Lens of the Lancet Global Health Commission on High-Quality Health Systems.

BACKGROUND: Neurosurgery is a rapidly developing specialty in Ethiopia. Previous global neurosurgery studies have highlighted the need for synchronizing workforce increase with improving quality, access, and capacity to provide neurosurgical care. OBJECTIVE: To evaluate Ethiopia's neurosurgical system and highlight the critical interventions required for the sustained development of Ethiopian neurosurgery as part of a high-quality health system (HQHS). METHODS: A comprehensive survey was sent to all practicing neurosurgeons. Public databases on Ethiopian census reports and current road infrastructure were used for spatial analysis of neurosurgical access. RESULTS: The survey response rate was 90% (45/50). Most respondents were men (95.6%), aged 30 to 40 years (82%), who worked at national referral hospitals (71%). The reported annual caseload per practicing neurosurgeon was >150 cases for 40% of urban and 20% of rural neurosurgeons. Head and spine neurotrauma and tumors were the most common neurosurgical indications. Computed tomography scanner was the most widely available diagnostic equipment (62%). 76% of respondents indicated the presence of postoperative rehabilitation care at their institutions. Thirteen percent and 27% of the nation lived within a 2-hour and 4-hour driving distance from a neurosurgical center, respectively. CONCLUSION: The results highlight the need for vital improvements in neurosurgical capacity to sustain progress toward HQHS. Promoting sustained development in all components of HQHS can be achieved by diversifying the workforce and training residency candidates committed to practicing in underserved regions. Additional strategies might include establishing a national registry for neurosurgical data and implementing policy changes conducive to improving perihospital care and other health system components.

Diversity within the neurosurgical oncology workforce in the United States: A cross-sectional study with proposed strategies to pave the path forward.

BACKGROUND: Improving and fostering diversity within the neurosurgical workforce has become a high priority. This cross-sectional study aims to provide data on the diversity of neurosurgical oncology faculty (NSOF) in the US. METHODS: All 115 neurosurgery (NS) Accreditation Council for Graduate Medical Education (ACGME) accredited programs were included in this study. The academic rank, academic and clinical title(s), gender, race, and hiring date of neurosurgical faculty with a primary focus on neurosurgical oncology (NSOF) were recorded. Geographical distribution and "top 10" programs were tabulated according to published data. Underrepresented minorities in medicine (URiM) faculty were identified according to the AAMC definition. RESULTS: The NSOF workforce constitutes 21% of the total NS faculty. Of these, 10.1% are women and 9.9% are URiM (P < .001). Currently, 58% of neurosurgery programs (NSP) do not have URiM and/or women NSOF. The top 10 ranked NSP, according to Blue Ridge Institute for Medical Research, had a significantly less URiM NSOF (P = .019) than nontop 10 ranked programs. There was a decreasing trend in the proportion of URiM at higher academic ranks (P = .019). All of the URiM department chairs (3/113)-all men-and 1/3 women department chairs nationwide subspecialized in neurosurgical oncology. CONCLUSIONS: Neurosurgical oncology is a sought-after subspecialty attracting a fifth of neurosurgeons practicing in ACGME-accredited training programs. Changing demographics and the benefits of workforce diversity represent a great opportunity for our field to continue leading inclusion efforts and attracting the best and brightest.

The Cognitive Effects of Radiotherapy for Brain Metastases.

Brain metastases are the most common intracranial neoplasm and are seen in upwards of 10-30% of patients with cancer. For decades, whole brain radiation therapy (WBRT) was the mainstay of treatment in these patients. While WBRT is associated with excellent rates of intracranial tumor control, studies have demonstrated a lack of survival benefit, and WBRT is associated with higher rates of cognitive deterioration and detrimental effects on quality of life. In recent years, strategies to mitigate this risk, such as the incorporation of memantine and hippocampal avoidance have been employed with improved results. Furthermore, stereotactic radiosurgery (SRS) has emerged as an appealing treatment option over the last decade in the management of brain metastases and is associated with superior cognitive preservation and quality of life when compared to WBRT. This review article evaluates the pathogenesis and impact of cranial irradiation on cognition in patients with brain metastases, as well as current and future risk mitigation techniques.

Subspecialty and Training Preferences for U.S. Neurosurgery Faculty with International Training.

BACKGROUND: Academic neurosurgeons with international medical training play a large role in the U.S. neurosurgical workforce. We aimed to compare U.S.-trained neurosurgeons with internationally trained neurosurgeons to reveal differences in subspecialty preferences and training opportunities abroad. METHODS: We identified 1671 neurosurgeons from 115 Accreditation Council for Graduate Medical Education (ACGME)-accredited neurosurgical residency programs. Data on demographics, institution characteristics, and chosen subspecialty were collected, and faculty were divided based on location of training. Univariate analysis and multivariable logistic regression compared faculty characteristics between training locations. RESULTS: Compared with the U.S. medical school + U.S. residency group, the international medical graduate + U.S. residency group was more likely to subspecialize in oncology/skull base and vascular neurosurgery and complete a fellowship in the United States or internationally (P < 0.05). The international medical graduate + international residency group was more likely to subspecialize in oncology/skull base neurosurgery, more likely to complete an international fellowship, and less likely to practice general neurosurgery (P < 0.05). Neurosurgeons in pediatrics, radiosurgery, and vascular subspecialties were more likely to receive fellowship training in any location (P < 0.05). Additionally, functional neurosurgeons were more likely to complete fellowships internationally, spinal neurosurgeons were less likely to pursue international fellowships, and peripheral nerve neurosurgeons were more likely to have dual fellowship training in both the United States and abroad (P < 0.05). CONCLUSIONS: International medical training affected subspecialty choice and fellowship training. Internationally trained neurosurgeons more often specialized in oncology and vascular neurosurgery. Functional neurosurgeons were more likely to complete international fellowships, spine neurosurgeons were less likely to complete international fellowships, and peripheral nerve neurosurgeons more often had both U.S. and international fellowships.

Racial and Ethnical Diversity Within the Neurosurgery Resident and Faculty Workforce in the United States.

BACKGROUND: Promoting workplace diversity leads to a variety of benefits related to a broader range of perspectives and insights. Underrepresented in medicine (URiM), including African Americans, Latinx, and Natives (Americans/Alaskan/Hawaiians/Pacific Islanders), are currently accounting for approximately 40% of the US population. OBJECTIVE: To establish a snapshot of current URiM representation within academic neurosurgery (NS) programs and trends within NS residency. METHODS: All 115 NS residencies and academic programs accredited by the Accreditation Council for Graduate Medical Education in 2020 were included in this study. The National Residency Matching Program database was reviewed from 2011 to 2020 to analyze URiM representation trends over time within the NS resident workforce. The academic rank, academic and clinical title(s), subspecialty, sex, and race of URiM NS faculty (NSF) were obtained from publicly available data. RESULTS: The Black and Latinx NS resident workforce currently accounts for 4.8% and 5.8% of the total workforce, respectively. URiM NSF are present in 71% of the Accreditation Council for Graduate Medical Education-accredited NS programs and account for 8% (148 of 1776) of the workforce. Black and Latinx women comprise 10% of URiM NSF. Latinx NSFs are the majority within the URiM cohort for both men and women. URiM comprise 5% of all department chairs. All are men. Spine (26%), tumor (26%), and trauma (17%) were the top 3 subspecialties among URiM NSF. CONCLUSION: NS has evolved, expanded, and diversified in numerous directions, including race and gender representation. Our data show that ample opportunities remain to improve URiM representation within NS.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Management of Progressive Glioblastoma in Adults: Update of the 2014 Guidelines.

BACKGROUND: The Institute of Medicine best practice recommendation to review guidelines every 5 years is followed by the Congress of Neurological Surgeons Guidelines Committee. The aim of this work was to provide an updated literature review and evidence-based recommendations on the topic of diagnosis and treatment of patients with progressive glioblastoma (pGBM). OBJECTIVE: To review the literature published since the last guidelines on pGBM dated 2014, with literature search ending in June 2012. METHODS: PubMed, Embase, and Cochrane were searched for the period July 1, 2012, to March 31, 2019, using search terms and search strategies to identify pertinent abstracts. These were then screened using published exclusion/inclusion criteria to identify full-text review articles. Evidence tables were constructed using data derived from full-text reviews and recommendations made from the evidence derived. RESULTS: From the total 8786 abstracts identified by the search, 237 full-text articles met inclusion/exclusion criteria and were included in this update. Two new level II recommendations derived from this work. For the diagnosis of patients with GBM, the use of diffusion-weighted images is recommended to be included in the magnetic resonance images with and without contrast used for surveillance to detect pGBM. For the treatment of patients with pGBM, repeat cytoreductive surgery is recommended to improve overall survival. An additional 21 level III recommendations were provided. CONCLUSION: Recent published literature provides new recommendations for the diagnosis and treatment of pGBM. The Central Nervous System Guidelines Committee will continue to pursue timely updates to further improve the care of patients with diagnosis.https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-management-of-progressive-glioblastoma.

Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of cytotoxic chemotherapy and other cytotoxic therapies in the management of progressive glioblastoma in adults.

TARGET POPULATION: These recommendations apply to adult patients diagnosed with progressive glioblastoma (pGBM). QUESTION (Q1): In adult patients with pGBM does the use of temozolomide (TMZ) with alternative dosing or the use of TMZ in combination with other cytotoxic treatments result in increased overall survival compared to other chemotherapy? RECOMMENDATION: Level III: Adult patients with pGBM might derive benefit in treatment with TMZ, especially those who progress after more than 5 months of TMZ-treatment free interval. LEVEL III: Combination of TMZ with other cytotoxic agents such as nitrosourea, cisplatin, electrohyperthermia, or tamoxifen is not suggested in adult patients with pGBM as a stand-alone therapy. There is insufficient data to make a recommendation about which alternative TMZ dosing provides the best benefits. QUESTION (Q2): In adult patients with pGBM does the use of systemic or in situ nitrosourea result in increased overall survival compared to other chemotherapy? RECOMMENDATION: Level III: In the setting of pGBM, fotemustine is suggested in elderly patients with methylated MGMT promoter status. There is insufficient evidence to compare fotemustine to other nitrosoureas. There is insufficient evidence to make a recommendation about the use of in situ nitrosourea in patients with pGBM who underwent the Stupp regimen. QUESTION (Q3): In adult patients with pGBM does the use of platinum compounds and topoisomerase result in increased survival compared to other chemotherapy? RECOMMENDATION: Level III: Other chemotherapy including platinum compounds and topoisomerase inhibitors are not suggested to be used in adult patients with pGBM. LEVEL III: Other cytotoxic therapies like perillyl acohol or ketogenic diet are not suggested for use in adult patients with pGBM as a stand-alone therapy. QUESTION (Q4): In adult patients with pGBM does the use of tumor treating field (TTF) result in increased overall survival compared to chemotherapy? RECOMMENDATION: Level III: The use of TTF with other chemotherapy may be considered when treating adult patients with pGBM. There is insufficient evidence to recommend TTF to increase overall survival in adult patients with pGBM. QUESTION (Q5): In adult patients with pGBM does the use of oncolytic virotherapy result in increased survival compared to chemotherapy? RECOMMENDATION: Level III: Oncolytic virotherapy is not suggested in patients with pGBM.

Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of targeted therapies and immunotherapies in the management of progressive glioblastoma.

The following questions and recommendations are pertinent to the following: TARGET POPULATION: These recommendations apply to adults with progressive GBM who have undergone standard primary treatment with surgery and/or chemoradiation. QUESTION 1: In adults with progressive glioblastoma is the use of bevacizumab as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: Level III: Treatment with bevacizumab is suggested in the treatment of progressive GBM, as it provides improved disease control compared to historical controls as measured by best imaging response and progression free survival at 6 months, while not providing evidence for improvement in overall survival. QUESTION 2: In adults with progressive glioblastoma is the use of bevacizumab as combination therapy with cytotoxic agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: Level III: There is insufficient evidence to show benefit or harm of bevacizumab in combination with cytotoxic therapies in progressive glioblastoma due to a lack of evidence supporting a clearly defined benefit without significant toxicity. QUESTION 3: In adults with progressive glioblastoma is the use of bevacizumab as a combination therapy with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 4: In adults with progressive glioblastoma is the use of targeted agents as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 5: In adults with progressive glioblastoma is the use of targeted agents in combination with cytotoxic therapies superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 6: In adults with progressive glioblastoma is the use of immunotherapy monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 7: In adults with progressive glioblastoma is the use of immunotherapy in combination with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 8: In adults with progressive glioblastoma is the use of immunotherapy in combination with bevacizumab superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question.

5-Aminolevulinic acid for enhanced surgical visualization of high-grade gliomas: a prospective, multicenter study.

OBJECTIVE: Greater extent of resection (EOR) is associated with longer overall survival in patients with high-grade gliomas (HGGs). 5-Aminolevulinic acid (5-ALA) can increase EOR by improving intraoperative visualization of contrast-enhancing tumor during fluorescence-guided surgery (FGS). When administered orally, 5-ALA is converted by glioma cells into protoporphyrin IX (PPIX), which fluoresces under blue 400-nm light. 5-ALA has been available for use in Europe since 2010, but only recently gained FDA approval as an intraoperative imaging agent for HGG tissue. In this first-ever, to the authors' knowledge, multicenter 5-ALA FGS study conducted in the United States, the primary objectives were the following: 1) assess the diagnostic accuracy of 5-ALA-induced PPIX fluorescence for HGG histopathology across diverse centers and surgeons; and 2) assess the safety profile of 5-ALA FGS, with particular attention to neurological morbidity. METHODS: This single-arm, multicenter, prospective study included adults aged 18-80 years with Karnofsky Performance Status (KPS) score > 60 and an MRI diagnosis of suspected new or recurrent resectable HGG. Intraoperatively, 3-5 samples per tumor were taken and their fluorescence status was recorded by the surgeon. Specimens were submitted for histopathological analysis. Patients were followed for 6 weeks postoperatively for adverse events, changes in the neurological exam, and KPS score. Multivariate analyses were performed of the outcomes of KPS decline, EOR, and residual enhancing tumor volume to identify predictive patient and intraoperative variables. RESULTS: Sixty-nine patients underwent 5-ALA FGS, providing 275 tumor samples for analysis. PPIX fluorescence had a sensitivity of 96.5%, specificity of 29.4%, positive predictive value (PPV) for HGG histopathology of 95.4%, and diagnostic accuracy of 92.4%. Drug-related adverse events occurred at a rate of 22%. Serious adverse events due to intraoperative neurological injury, which may have resulted from FGS, occurred at a rate of 4.3%. There were 2 deaths unrelated to FGS. Compared to preoperative KPS scores, postoperative KPS scores were significantly lower at 48 hours and 2 weeks but were not different at 6 weeks postoperatively. Complete resection of enhancing tumor occurred in 51.9% of patients. Smaller preoperative tumor volume and use of intraoperative MRI predicted lower residual tumor volume. CONCLUSIONS: PPIX fluorescence, as judged by the surgeon, has a high sensitivity and PPV for HGG. 5-ALA was well tolerated in terms of drug-related adverse events, and its application by trained surgeons in FGS for HGGs was not associated with any excess neurological morbidity.

Making a match: trends in the application, interview, and ranking process for the neurological surgery residency programs.

OBJECTIVE: Neurosurgery is a highly competitive residency field with a match rate lower than that of other specialties. The aim of this study was to analyze trends associated with the residency match process from the applicants' and program directors' perspectives. METHODS: Between 2010 and 2020, the National Residency Matching Program (NRMP) Applicant and Program Director Surveys, the NRMP Charting Outcomes reports, and the Accreditation Council for Graduate Medical Education (ACGME) Data Resource Books were analyzed to identify the number of applicants interviewed and ranked in US programs, the applicants' ranking preferences, the program directors' preferential factors in offering interviews, and rank list order. Applicants were divided between US senior medical students and independent applicants. Each cohort was dichotomized for matched and unmatched applicants. RESULTS: Over the study period, 2935 applicants applied to neurosurgery residency, including 2135 US senior medical students and 800 independent applicants, with an overall match rate of 65%. Overall, matched applicants had a significantly higher number of publications (p < 0.05). Among US senior medical student applicants, the application-to-interview ratio more than doubled over the study period, yet the number of interview invitations received, interviews accepted, and programs ranked remained unchanged. In the US senior medical student cohort, the number of submitted applications, interview invitations, accepted interviews, and programs ranked did not significantly differ between matched and unmatched applicants. In both cohorts, applicants shifted ranking factors from a more academic focus in early years to more well-being in later years. Letters of recommendation and board scores were key factors for program directors while screening applicants for interviews and ranking. CONCLUSIONS: Neurosurgery residency continues to be a highly competitive field in medicine, with match rates of 65%. Recently, applicants have placed greater importance on ranking programs that value residents' well-being, as opposed to strictly academic factors. A data-driven understanding of factors important to applicants and program directors during the match process has the potential to improve resident candidate recruitment and overall resident-program fit, thereby improving well-being during residency, reducing the attrition rate, and overall enhancing the diversity of the neurosurgery resident workforce.

Introduction to special issue dedicated to the 35th anniversary of the joint section on tumors.

The American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Joint Section on Tumors was formed in December of 1984 as the first professional organization devoted to the study and treatment of brain tumors. One year earlier, the Journal of Neuro-Oncology had been established and went on to be sponsored by the Joint Section on Tumors. To celebrate the 35th anniversary of the founding of the Section, we are thrilled to bring you this special issue of Journal of Neuro-Oncology in which current leaders of the Joint Section on Tumors highlight their work and the work of others that have led to significant recent advances in the management of tumors of the central nervous system.