Cerebellopontine Angle Meningiomas: A Multi-Institutional Cohort Study.

BACKGROUND AND OBJECTIVES: Cerebellopontine angle (CPA) meningiomas present challenges given their proximity to neurovascular structures. Postoperative complications and persistent symptoms can debilitate patients, and our ability to predict recovery course remains variable. Here, we examine the presentation, management, and outcomes of patients with CPA meningiomas. METHODS: We retrospectively reviewed CPA meningiomas resected at Mass General Brigham, using descriptive statistics and logistic regression to identify predictors of progression or recurrence. RESULTS: In total, 95 patients were identified (median age 59.1 years, 82.1% female) who presented most commonly with hearing loss (49.5%), ataxia (42.1%), and headaches (29.5%). The retrosigmoid (78.9%) or transmastoid retrosigmoid (17.9%) approaches were most frequently used for resection, with gross total resection (GTR) achieved in 62.1% of patients: Simpson grade 1 (32.6%), grade 2 (17.9%), and grade 3 (11.6%). Smaller tumor size (t = 3.17, P = .002) is associated with GTR. For tumors with intracanalicular invasion, drilling the internal auditory canal (IAC) was also associated with GTR (χ2 = 21.8, P < .001). Among cases with invasion, GTR was achieved in 88.5% of cases when the IAC was drilled vs 11.8% of cases when the IAC was not drilled. The cranial nerve VII/VIII complex was frequently inferior (45.6%) or superior (19.1%) to the meningioma. Postoperative hearing loss was stable (38.7%) or improved (54.8%) in most of patients at the final clinical follow-up (median: 39.4 months). 25.3% of patients had progression/recurrence, with some difference between World Health Organization grade 1 (median: 3.0 years, IQR: 2.9 years) and World Health Organization grade 2 (median: 1.6 years, IQR: 2.8 years) tumors. After multivariate adjustment, Simpson grade I (P = .02), Simpson grade II (P = .01), or being of older age (P = .003) were associated with lower odds of progression/recurrence. CONCLUSION: GTR remains critical to achieve optimal symptom control and reduce progression/recurrence rates for CPA meningiomas. Drilling the IAC is an important predictor of GTR in tumors with intracanalicular invasion.

Intracranial outcomes following neurosurgical resection in patients with brain metastases secondary to HER2-positive breast cancer versus other subtypes.

PURPOSE: Neurosurgical resection serves an important role in select patients with breast cancer and brain metastases but can delay systemic therapy and yield complications. Consequently, identification of patients most likely to benefit from surgery is important. Given the poorer long-term intracranial responses to radiotherapy sometimes observed in HER2-positive (HER2 +) patients, we investigated whether neurosurgical resection is differentially beneficial in this population. METHODS: We identified 633 patients with newly diagnosed brain metastases arising from breast cancer managed at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2010 and 2022. Patients were stratified by breast cancer subtype: HER2 + (N = 189), hormone receptor positive (HR +)/HER2- (N = 267), and triple negative (N = 177). Per-patient and per-metastasis outcomes were evaluated; interaction models assessing the impact of neurosurgical resection by subtype were constructed. RESULTS: Relative to HR + /HER2- subtype, omission of upfront neurosurgical resection in patients with HER2 + disease was associated with increased subsequent utilization of salvage stereotactic radiation, whole brain radiotherapy, and craniotomy (interaction HR 2.02 [95% CI, 1.04-3.93], p = 0.04; HR 3.92 [95% CI, 1.24-12.40], p = 0.02; HR 4.98 [95% CI, 1.34-18.58], p = 0.02, respectively). Tumors stemming from HER2 + versus HR + /HER2- primaries displayed increased local recurrence when upfront neurosurgical resection was omitted (interaction HR 3.62 [95% CI, 1.06-12.38], p = 0.04). No such associations were noted when comparing triple negative to HR + /HER2- subtype (p-interaction > 0.05 in all cases). CONCLUSION: Patients with HER2 + disease and brain metastases may disproportionately benefit from upfront neurosurgical resection relative to other subtypes. If validated, our results may suggest a lower threshold to consider surgery in brain metastases secondary to HER2 + breast cancer.

Automated ventricular segmentation and shunt failure detection using convolutional neural networks.

While ventricular shunts are the main treatment for adult hydrocephalus, shunt malfunction remains a common problem that can be challenging to diagnose. Computer vision-derived algorithms present a potential solution. We designed a feasibility study to see if such an algorithm could automatically predict ventriculomegaly indicative of shunt failure in a real-life adult hydrocephalus population. We retrospectively identified a consecutive series of adult shunted hydrocephalus patients over an eight-year period. Associated computed tomography scans were extracted and each scan was reviewed by two investigators. A machine learning algorithm was trained to identify the lateral and third ventricles, and then applied to test scans. Results were compared to human performance using Sørensen-Dice coefficients, calculated total ventricular volumes, and ventriculomegaly as documented in the electronic medical record. 5610 axial images from 191 patients were included for final analysis, with 52 segments (13.6% of total data) reserved for testing. Algorithmic performance on the test group averaged a Dice score of 0.809 ± 0.094. Calculated total ventricular volumes did not differ significantly between computer-derived volumes and volumes marked by either the first reviewer or second reviewer (p > 0.05). Algorithm detection of ventriculomegaly was correct in all test cases and this correlated with correct prediction of need for shunt revision in 92.3% of test cases. Though development challenges remain, it is feasible to create automated algorithms that detect ventriculomegaly in adult hydrocephalus shunt malfunction with high reliability and accuracy.

From Operating Room to Courtroom: Analyzing Malpractice Trajectories in Cranial Neurosurgery.

BACKGROUND AND OBJECTIVES: Nearly all neurosurgeons in the United States will be named defendants in a malpractice claim before retirement. We perform an assessment of national malpractice trends in cranial neurosurgery to inform neurosurgeons on current outcomes, trends over time, benchmarks for malpractice coverage needs, and ways to mitigate lawsuits. METHODS: The Westlaw Edge and LexisNexis databases were searched to identify medical malpractice cases relating to open cranial surgery between 1987 and 2023. Extracted data included date of verdict, jurisdiction, outcome, details of sustained injuries, and any associated award/settlement figures. RESULTS: Of 1550 cases analyzed, 252 were identified as malpractice claims arising from open cranial surgery. The median settlement amount was $950 000 and the average plaintiff ruling was $2 750 000. The highest plaintiff ruling resulted in an award of $28.1 million. Linear regression revealed no significant relationship between year and defendant win (P-value = .43). After adjusting for inflation, award value increased with time (P-value = .01). The most common cranial subspecialties were tumor (67 cases, 26.6%), vascular (54 cases, 21.4%), infection (23 cases, 9.1%), and trauma (23 cases, 9.1%). Perioperative complications was the most common litigation category (96 cases, 38.1%), followed by delayed treatment (40 cases, 15.9%), failure to diagnose (38 cases, 15.1%), and incorrect choice of procedure (29 cases, 11.5%). The states with most claims were New York (40 cases, 15.9%), California (24 cases, 9.5%), Florida (21 cases, 8.3%), and Pennsylvania (20 cases, 7.9%). CONCLUSION: Although a stable number of cases were won by neurosurgeons, an increase in award sizes was observed in the 37-year period assessed. Perioperative complications and delayed treatment/diagnosis were key drivers of malpractice claims.

Recurrent Glioblastoma-Molecular Underpinnings and Evolving Treatment Paradigms.

Glioblastoma is the most common and lethal central nervous system malignancy with a median survival after progression of only 6-9 months. Major biochemical mechanisms implicated in glioblastoma recurrence include aberrant molecular pathways, a recurrence-inducing tumor microenvironment, and epigenetic modifications. Contemporary standard-of-care (surgery, radiation, chemotherapy, and tumor treating fields) helps to control the primary tumor but rarely prevents relapse. Cytoreductive treatment such as surgery has shown benefits in recurrent glioblastoma; however, its use remains controversial. Several innovative treatments are emerging for recurrent glioblastoma, including checkpoint inhibitors, chimeric antigen receptor T cell therapy, oncolytic virotherapy, nanoparticle delivery, laser interstitial thermal therapy, and photodynamic therapy. This review seeks to provide readers with an overview of (1) recent discoveries in the molecular basis of recurrence; (2) the role of surgery in treating recurrence; and (3) novel treatment paradigms emerging for recurrent glioblastoma.

Evaluation of the safety, accuracy, and helpfulness of the GPT-4.0 Large Language Model in neurosurgery.

BACKGROUND: Although prior work demonstrated the surprising accuracy of Large Language Models (LLMs) on neurosurgery board-style questions, their use in day-to-day clinical situations warrants further investigation. This study assessed GPT-4.0's responses to common clinical questions across various subspecialties of neurosurgery. METHODS: A panel of attending neurosurgeons formulated 35 general neurosurgical questions spanning neuro-oncology, spine, vascular, functional, pediatrics, and trauma. All questions were input into GPT-4.0 with a prespecified, standard prompt. Responses were evaluated by two attending neurosurgeons, each on a standardized scale for accuracy, safety, and helpfulness. Citations were indexed and evaluated against identifiable database references. RESULTS: GPT-4.0 responses were consistent with current medical guidelines and accounted for recent advances in the field 92.8 % and 78.6 % of the time respectively. Neurosurgeons reported GPT-4.0 responses providing unrealistic information or potentially risky information 14.3 % and 7.1 % of the time respectively. Assessed on 5-point scales, responses suggested that GPT-4.0 was clinically useful (4.0 ± 0.6), relevant (4.7 ± 0.3), and coherent (4.9 ± 0.2). The depth of clinical responses varied (3.7 ± 0.6), and "red flag" symptoms were missed 7.1 % of the time. Moreover, GPT-4.0 cited 86 references (2.46 citations per answer), of which only 50 % were deemed valid, and 77.1 % of responses contained at least one inappropriate citation. CONCLUSION: Current general LLM technology can offer generally accurate, safe, and helpful neurosurgical information, but may not fully evaluate medical literature or recent field advances. Citation generation and usage remains unreliable. As this technology becomes more ubiquitous, clinicians will need to exercise caution when dealing with it in practice.

Pilot trial of perampanel on peritumoral hyperexcitability and clinical outcomes in newly diagnosed high-grade glioma.

Background: Glutamatergic neuron-glioma synaptogenesis and peritumoral hyperexcitability promote glioma growth in a positive feedback loop. The objective of this study was to evaluate the feasibility and estimated effect sizes of the AMPA-R antagonist, perampanel, on intraoperative electrophysiologic hyperexcitability and clinical outcomes. Methods: An open-label trial was performed comparing perampanel to standard of care (SOC) in patients undergoing resection of newly-diagnosed radiologic high-grade glioma. Perampanel was administered as a pre-operative loading dose followed by maintenance therapy until progressive disease or up to 12-months. SOC treatment involved levetiracetam for 7-days or as clinically indicated. The primary outcome of hyperexcitability was defined by intra-operative electrocorticography high frequency oscillation (HFO) rates. Seizure-freedom and overall survival (OS) were estimated by the Kaplan-Meier method. Tissue concentrations of perampanel, levetiracetam, and metabolites were measured by mass spectrometry. Results: HFO rates were similar between perampanel-treated and SOC cohorts. The trial was terminated early after interim analysis for futility, and outcomes assessed in 11 patients (7 perampanel-treated, 4 SOC). Over a median 281 days of post-enrollment follow-up, 27% of patients had seizures, including 14% treated with perampanel and 50% treated with SOC. OS in perampanel-treated patients was similar to a glioblastoma reference cohort (p=0.81). Glutamate concentrations in surface biopsies were positively correlated with HFO rates in adjacent electrode contacts and were not significantly associated with treatment assignment or drug concentrations. Conclusions: A peri-operative loading regimen of perampanel was safe and well-tolerated, with similar peritumoral hyperexcitability as in levetiracetam-treated patients. Maintenance anti-glutamatergic therapy was not observed to impact survival outcomes.

Emergent Coronary Thrombectomy for Acute Myocardial Infarction Immediately Following Craniotomy with Tumor Resection.

The management of perioperative acute myocardial infarction (AMI) following oncologic neurosurgery requires balancing competing risks of myocardial ischemia and postoperative bleeding. There are limited human data to establish the safest timing of antiplatelet or anticoagulation therapy following neurosurgical procedures. For patients with malignancy experiencing AMI in the acute postoperative period, staged percutaneous coronary intervention (PCI) with upfront coronary aspiration thrombectomy followed by delayed completion PCI may offer an opportunity for myocardial salvage while minimizing postoperative bleeding risks. CYP2C19 genotyping and platelet aggregation studies can help confirm adequate platelet inhibition once antiplatelet therapy is resumed.

Elevated risk of recurrence and retreatment for silent pituitary adenomas.

PURPOSE: Pituitary adenomas are the most common tumor of the pituitary gland and comprise nearly 15% of all intracranial masses. These tumors are stratified into functional or silent categories based on their pattern of hormone expression and secretion. Preliminary evidence supports differential clinical outcomes between some functional pituitary adenoma (FPA) subtypes and silent pituitary adenoma (SPA) subtypes. METHODS: We collected and analyzed the medical records of all patients undergoing resection of SPAs or FPAs from a single high-volume neurosurgeon between 2007 and 2018 at Brigham and Women's Hospital. Descriptive statistics and the Mantel-Cox log-rank test were used to identify differences in outcomes between these cohorts, and multivariate logistic regression was used to identify predictors of radiographic recurrence for SPAs. RESULTS: Our cohort included 88 SPAs and 200 FPAs. The majority of patients in both cohorts were female (48.9% of SPAs and 63.5% of FPAs). SPAs were larger in median diameter than FPAs (2.1 cm vs. 1.2 cm, p < 0.001). The most frequent subtypes of SPA were gonadotrophs (55.7%) and corticotrophs (30.7%). Gross total resection (GTR) was achieved in 70.1% of SPA resections and 86.0% of FPA resections (p < 0.001). SPAs had a higher likelihood of recurring (hazard ratio [HR] 3.2, 95% confidence interval [95%CI] 1.6-7.2) and a higher likelihood of requiring retreatment for recurrence (HR 2.5; 95%CI 1.0-6.1). Subset analyses revealed that recurrence and retreatment were more both likely for subtotally resected SPAs than subtotally resected FPAs, but this pattern was not observed in SPAs and FPAs after GTR. Among SPAs, recurrence was associated with STR (odds ratio [OR] 9.3; 95%CI 1.4-64.0) and younger age (OR 0.92 per year; 95%CI 0.88-0.98) in multivariable analysis. Of SPAs that recurred, 12 of 19 (63.2%) were retreated with repeat surgery (n = 11) or radiosurgery (n = 1), while the remainder were observed (n = 7).There were similar rates of recurrence across different SPA subtypes. CONCLUSION: Patients undergoing resection of SPAs should be closely monitored for disease recurrence through more frequent clinical follow-up and diagnostic imaging than other adenomas, particularly among patients with STR and younger patients. Several patients can be observed after radiographic recurrence, and the decision to retreat should be individualized. Longitudinal clinical follow-up of SPAs, including an assessment of symptoms, endocrine function, and imaging remains critical.

Positioning SUMO as an immunological facilitator of oncolytic viruses for high-grade glioma.

Oncolytic viral (OV) therapies are promising novel treatment modalities for cancers refractory to conventional treatment, such as glioblastoma, within the central nervous system (CNS). Although OVs have received regulatory approval for use in the CNS, efficacy is hampered by obstacles related to delivery, under-/over-active immune responses, and the "immune-cold" nature of most CNS malignancies. SUMO, the Small Ubiquitin-like Modifier, is a family of proteins that serve as a high-level regulator of a large variety of key physiologic processes including the host immune response. The SUMO pathway has also been implicated in the pathogenesis of both wild-type viruses and CNS malignancies. As such, the intersection of OV biology with the SUMO pathway makes SUMOtherapeutics particularly interesting as adjuvant therapies for the enhancement of OV efficacy alone and in concert with other immunotherapeutic agents. Accordingly, the authors herein provide: 1) an overview of the SUMO pathway and its role in CNS malignancies; 2) describe the current state of CNS-targeted OVs; and 3) describe the interplay between the SUMO pathway and the viral lifecycle and host immune response.

Inaugural Results of the Individualized Screening Trial of Innovative Glioblastoma Therapy: A Phase II Platform Trial for Newly Diagnosed Glioblastoma Using Bayesian Adaptive Randomization.

PURPOSE: The Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) is a phase II platform trial that uses response adaptive randomization and genomic profiling to efficiently identify novel therapies for phase III testing. Three initial experimental arms (abemaciclib [a cyclin-dependent kinase [CDK]4/6 inhibitor], neratinib [an epidermal growth factor receptor [EGFR]/human epidermal growth factor receptor 2 inhibitor], and CC-115 [a deoxyribonucleic acid-dependent protein kinase/mammalian target of rapamycin inhibitor]) were simultaneously evaluated against a common control arm. We report the results for each arm and examine the feasibility and conduct of the adaptive platform design. PATIENTS AND METHODS: Patients with newly diagnosed O6-methylguanine-DNA methyltransferase-unmethylated glioblastoma were eligible if they had tumor genotyping to identify prespecified biomarker subpopulations of dominant glioblastoma signaling pathways (EGFR, phosphatidylinositol 3-kinase, and CDK). Initial random assignment was 1:1:1:1 between control (radiation therapy and temozolomide) and the experimental arms. Subsequent Bayesian adaptive randomization was incorporated on the basis of biomarker-specific progression-free survival (PFS) data. The primary end point was overall survival (OS), and one-sided P values are reported. The trial is registered with ClinicalTrials.gov (identifier: NCT02977780). RESULTS: Two hundred thirty-seven patients were treated (71 control; 73 abemaciclib; 81 neratinib; 12 CC-115) in years 2017-2021. Abemaciclib and neratinib were well tolerated, but CC-115 was associated with ≥ grade 3 treatment-related toxicity in 58% of patients. PFS was significantly longer with abemaciclib (hazard ratio [HR], 0.72; 95% CI, 0.49 to 1.06; one-sided P = .046) and neratinib (HR, 0.72; 95% CI, 0.50 to 1.02; one-sided P = .033) relative to the control arm but there was no PFS benefit with CC-115 (one-sided P = .523). None of the experimental therapies demonstrated a significant OS benefit (P > .05). CONCLUSION: The INSIGhT design enabled efficient simultaneous testing of three experimental agents using a shared control arm and adaptive randomization. Two investigational arms had superior PFS compared with the control arm, but none demonstrated an OS benefit. The INSIGhT design may promote improved and more efficient therapeutic discovery in glioblastoma. New arms have been added to the trial.

Evaluating hematologic parameters in newly diagnosed and recurrent glioblastoma: Prognostic utility and clinical trial implications of myelosuppression.

Background: Glioblastoma (GBM) patients are treated with radiation therapy, chemotherapy, and corticosteroids, which can cause myelosuppression. To understand the relative prognostic utility of blood-based biomarkers in GBM and its implications for clinical trial design, we examined the incidence, predictors, and prognostic value of lymphopenia, neutrophil-to-lymphocyte ratio (NLR), and platelet count during chemoradiation (CRT) and recurrence. Methods: This cohort study included 764 newly diagnosed glioblastoma patients treated from 2005 to 2019 with blood counts prior to surgery, within 6 weeks of CRT, and at first recurrence available for automatic extraction from the medical record. Logistic regression was used to evaluate exposures and Kaplan-Meier was used to evaluate outcomes. Results: Among the cohort, median age was 60.3 years; 87% had Karnofsky performance status ≥ 70, 37.5% had gross total resection, and 90% received temozolomide (TMZ). During CRT, 37.8% (248/656) of patients developed grade 3 or higher lymphopenia. On multivariable analysis (MVA), high NLR during CRT remained an independent predictor for inferior survival (Adjusted Hazard Ratio [AHR] = 1.57, 95% CI = 1.14-2.15) and shorter progression-free survival (AHR = 1.42, 95% CI = 1.05-1.90). Steroid use was associated with lymphopenia (OR = 2.66,1.20-6.00) and high NLR (OR = 3.54,2.08-6.11). Female sex was associated with lymphopenia (OR = 2.33,1.03-5.33). At first recurrence, 28% of patients exhibited grade 3 or higher lymphopenia. High NLR at recurrence was associated with worse subsequent survival on MVA (AHR = 1.69, 95% CI = 1.25-2.27). Conclusions: High NLR is associated with worse outcomes in newly diagnosed and recurrent glioblastoma. Appropriate eligibility criteria and accounting and reporting of blood-based biomarkers are important in the design and interpretation of newly diagnosed and recurrent glioblastoma trials.

Metastatic pituitary tumors: an institutional case series.

PURPOSE: Pituitary carcinomas are a rare entity that respond poorly to multimodal therapy. Patients follow a variable disease course that remains ill-defined. METHODS: We present an institutional case series of patients treated for pituitary carcinomas over a 30-year period from 1992 to 2022. A systematic review was conducted to identify prior case series of patients with pituitary carcinomas. RESULTS: Fourteen patients with a mean age at pituitary carcinoma diagnosis of 52.5 years (standard deviation [SD] 19.4) met inclusion criteria. All 14 patients had tumor subtypes confirmed by immunohistochemistry and hormone testing, with the most common being ACTH-producing pituitary adenomas (n = 12). Patients had a median progression-free survival (PFS) of 1.4 years (range 0.7-10.0) and a median overall survival (OS) of 8.4 years (range 2.3-24.0) from pituitary adenoma diagnosis. Median PFS and OS were 0.6 years (range 0.0-2.2) and 1.5 years (range 0.1-9.6) respectively upon development of metastases. Most patients (n = 12) had locally invasive disease to the cavernous sinus, dorsum sellae dura, or sphenoid sinus prior to metastasis. Common sites of metastasis included the central nervous system, liver, lung, and bone. In a pooled analysis including additional cases from the literature, treatment of metastases with chemotherapy or a combination of radiation therapy and chemotherapy significantly prolonged PFS (p = 0.02), while failing to significantly improve OS (p = 0.14). CONCLUSION: Pituitary carcinomas are highly recurrent, heterogenous tumors with variable responses to treatment. Multidisciplinary management with an experienced neuro-endocrine and neuro-oncology team is needed given the unrelenting nature of this disease.

Critically reading machine learning literature in neurosurgery: a reader's guide and checklist for appraising prediction models.

OBJECTIVE: Machine learning (ML) has become an increasingly popular tool for use in neurosurgical research. The number of publications and interest in the field have recently seen significant expansion in both quantity and complexity. However, this also places a commensurate burden on the general neurosurgical readership to appraise this literature and decide if these algorithms can be effectively translated into practice. To this end, the authors sought to review the burgeoning neurosurgical ML literature and to develop a checklist to help readers critically review and digest this work. METHODS: The authors performed a literature search of recent ML papers in the PubMed database with the terms "neurosurgery" AND "machine learning," with additional modifiers "trauma," "cancer," "pediatric," and "spine" also used to ensure a diverse selection of relevant papers within the field. Papers were reviewed for their ML methodology, including the formulation of the clinical problem, data acquisition, data preprocessing, model development, model validation, model performance, and model deployment. RESULTS: The resulting checklist consists of 14 key questions for critically appraising ML models and development techniques; these are organized according to their timing along the standard ML workflow. In addition, the authors provide an overview of the ML development process, as well as a review of key terms, models, and concepts referenced in the literature. CONCLUSIONS: ML is poised to become an increasingly important part of neurosurgical research and clinical care. The authors hope that dissemination of education on ML techniques will help neurosurgeons to critically review new research better and more effectively integrate this technology into their practices.

An expanded role for surgery in grade 3 1p/19q co-deleted oligodendroglioma.

Background: Grade 3 1p/19q co-deleted oligodendroglioma is an uncommon primary CNS tumor with a high rate of progression and recurrence. This study examines the benefit of surgery after progression and identifies predictors of survival. Methods: This is a single-institution retrospective cohort study of consecutive adult patients with anaplastic or grade 3 1p/19q co-deleted oligodendroglioma diagnosed between 2001 and 2020. Results: Eighty patients with 1p/19q co-deleted grade 3 oligodendroglioma were included. The median age was 47 years (interquartile range 38-56) and 38.8% were women. All patients underwent surgery, including gross total resection (GTR) for 26.3% of patients, subtotal resection (STR) for 70.0% of patients, and biopsy for 3.8% of patients. Forty-three cases (53.8%) progressed at a median of 5.6 years, and the median overall survival (OS) was 14.1 years. Among 43 cases of progression or recurrence, 21 (48.8%) underwent another resection. Patients who underwent a second operation had improved OS (P = .041) and survival after progression/recurrence (P = .012), but similar time to subsequent progression as patients who did not have repeat surgery (P = .50). Predictors of mortality at initial diagnosis included a preoperative Karnofsky Performance Status (KPS) under 80 (hazard ratio [HR] 5.4; 95% CI 1.5-19.2), an STR or biopsy rather than GTR (HR 4.1; 95% CI 1.2-14.2), and a persistent postoperative neurologic deficit (HR 4.0; 95% CI 1.2-14.1). Conclusions: Repeat surgery is associated with increased survival, but not time to subsequent progression for progressing or recurrent 1p/19q co-deleted grade 3 oligodendrogliomas recur. Mortality is associated with a preoperative KPS under 80, lack of GTR, and persistent postoperative neurologic deficits after the initial surgery.

Evaluation of Standard Response Assessment in Neuro-Oncology, Modified Response Assessment in Neuro-Oncology, and Immunotherapy Response Assessment in Neuro-Oncology in Newly Diagnosed and Recurrent Glioblastoma.

PURPOSE: The Response Assessment in Neuro-Oncology (RANO) criteria are widely used in high-grade glioma clinical trials. We compared the RANO criteria with updated modifications (modified RANO [mRANO] and immunotherapy RANO [iRANO] criteria) in patients with newly diagnosed glioblastoma (nGBM) and recurrent GBM (rGBM) to evaluate the performance of each set of criteria and inform the development of the planned RANO 2.0 update. MATERIALS AND METHODS: Evaluation of tumor measurements and fluid-attenuated inversion recovery (FLAIR) sequences were performed by blinded readers to determine disease progression using RANO, mRANO, iRANO, and other response assessment criteria. Spearman's correlations between progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS: Five hundred twenty-six nGBM and 580 rGBM cases were included. Spearman's correlations were similar between RANO and mRANO (0.69 [95% CI, 0.62 to 0.75] v 0.67 [95% CI, 0.60 to 0.73]) in nGBM and rGBM (0.48 [95% CI, 0.40 to 0.55] v 0.50 [95% CI, 0.42 to 0.57]). In nGBM, requirement of a confirmation scan within 12 weeks of completion of radiotherapy to determine progression was associated with improved correlations. Use of the postradiation magnetic resonance imaging (MRI) as baseline scan was associated with improved correlation compared with use of the pre-radiation MRI (0.67 [95% CI, 0.60 to 0.73] v 0.53 [95% CI, 0.42 to 0.62]). Evaluation of FLAIR sequences did not improve the correlation. Among patients who received immunotherapy, Spearman's correlations were similar among RANO, mRANO, and iRANO. CONCLUSION: RANO and mRANO demonstrated similar correlations between PFS and OS. Confirmation scans were only beneficial in nGBM within 12 weeks of completion of radiotherapy, and there was a trend in favor of the use of postradiation MRI as the baseline scan in nGBM. Evaluation of FLAIR can be omitted. The iRANO criteria did not add significant benefit in patients who received immune checkpoint inhibitors.

Endoscopic endonasal transclival approach for a ventral brainstem epidermoid cyst: illustrative case.

BACKGROUND: Intracranial epidermoid cysts are benign, slow-growing malformations that most commonly arise at the skull base. Maximizing resection of the cyst contents and the capsule reduces long-term recurrence but can be made difficult by cyst wall adherence to critical neurovascular structures. Expanded endonasal approaches (EEAs) offer an alternative to traditional open transcranial approaches for accessible epidermoid cysts. In this case report, the authors demonstrate a transclival EEA for a large, ventral brainstem epidermoid cyst. OBSERVATIONS: A 41-year-old woman who presented with progressive headaches, diplopia, malaise, and fatigue was found to have a 4.7-cm midline, ventral brainstem epidermoid cyst. She underwent an expanded endonasal transclival approach that exposed the brainstem from the level of the dorsum sella to the tip of the basion. A near-total resection was completed with removal of all cyst contents and most of the capsular wall. Reconstruction was completed with Duragen, an autologous fat graft, and a nasoseptal flap. Postoperatively, she had a partial left cranial nerve VI palsy that remained stable 8 weeks after surgery. LESSONS: The expanded endoscopic transclival approach can facilitate effective resection of midline, ventral epidermoid cysts.