Intraoperative motor mapping is essential for maximum safe resection of peri-Rolandic gliomas. While both awake and asleep techniques have demonstrated efficacy in preserving neurological function, comparative outcomes across WHO 2021 molecular tumor subtypes remain poorly defined. We compare outcomes between these mapping modalities in glioblastoma (GBM) and IDH-mutant gliomas. A 130-patient cohort undergoing peri-Rolandic glioma resection with intraoperative motor mapping at a single institution was analyzed. Patients were stratified by mapping modality (awake n = 54, asleep n = 76) and tumor subtype (WHO 2021). Within the asleep cohort, handheld probe (HHP-DCS, n = 61) and subdural electrode direct cortical stimulation (SDE-DCS, n = 12) were compared. The primary outcome was new or worsening neurological deficits at 3 months. Secondary outcomes included Karnofsky Performance Status (KPS), hospital length of stay, discharge disposition, and survival in GBM patients. Three-month deficit rates were comparable between awake and asleep mapping (5.6
Introduction Hemangioblastomas (HGB) are the most common primary intra-axial tumors in the posterior fossa in adults, with an overall occurrence of 7-10%. They occur sporadically or as part of von Hippel-Lindau (VHL) disease. The role of stereotactic radiosurgery (SRS) as a minimally invasive treatment in larger HGB (>2cc) has not been thoroughly investigated. Methods This multi-center study retrospectively analyzed data from 91 patients with large HGB (>2cc) treated between 1993 and 2023. Patients were stratified into VHL-associated and sporadic groups, with assessments including radiosurgical parameters, tumor response, overall survival (OS), and progression-free survival (PFS). Results Patients with VHL-associated HGB were younger at diagnosis (median: 33 years vs. 52 years, p < 0.001) and presented more frequently with multiple tumors (68.8% vs. 23.2%, p < 0.001). Cerebellar lesions were the most common location (70%), followed by brainstem lesions (21%). The median target tumor volume was smaller in VHL cases (3.49 cc vs. 6.5 cc, p = 0.038). Tumor control was achieved in 70% of cases across groups, with no significant differences in outcomes between VHL and sporadic cases. OS (170 months for VHL and 199 months for sporadic cases) and PFS (108 months for both groups) were comparable. Radiation necrosis was observed in 8.8% of patients. Conclusions SRS may provide favorable tumor control with low morbidity in both VHL-associated and sporadic cases of larger HGB (>2 cc).Future studies should compare SRS with resection for larger HGB and explore molecular predictors of favorable response to SRS.
BACKGROUND AND OBJECTIVES:Even with multimodal therapy, glioblastoma invariably recurs. Reirradiation with stereotactic radiosurgery (SRS) and reoperation are frequent salvage treatment options for recurrent glioblastoma (rGBM) isocitrate dehydrogenase-wildtype. No study has compared the safety and efficacy of these treatments in a homogeneous rGBM population. In this study, we evaluate gamma knife (GK)-SRS vs reoperation in rGBM. METHODS:This retrospective study evaluated surgically accessible rGBM between 2005 and 2022. All patients received adjuvant radiotherapy and were evaluated for GK-SRS or reoperation on recurrence. Cox multivariable analysis and propensity-score matching were performed to address confounders in outcomes. Post-recurrence survival (PRS) was the primary endpoint. RESULTS:We identified 119 patients. Among these, 38 underwent GK-SRS and 81 underwent reoperation. Although patients undergoing GK-SRS had improved PRS and overall survival compared with reoperation, they had significant differences in baseline characteristics, particularly in tumor volume (reoperation group: 8.7 cm3 [IQR = 3.4-17.8 cm3] vs GK-SRS 1.7 cm3 [IQR = 0.2-6 cm3], P < .001). Given these significant differences, a propensity-score matching accounting for tumor volume and Karnofsky performance status was performed, comparing patients in which equipoise between GK-SRS and resection existed (GK-SRS 2.5 cm3 vs reoperation 2.6 cm3 and Karnofsky performance status 80 for both). Among these patients (23 in each group), PRS (19.2 months vs 15.1 months, P = .617) and overall survival (31.9 months vs 25.5 months, P = .176) were similar. Nevertheless, complications remained higher in the reoperation group (26.1% vs 4.3%, P = .040). CONCLUSION:In patients with small, surgically accessible first recurrent glioblastoma, GK-SRS achieved survival outcomes comparable to reoperation after matching for key baseline differences, while demonstrating a lower complication rate. These findings support GK-SRS as a reasonable local salvage option in carefully selected low-volume recurrences.
Re-irradiation with stereotactic radiosurgery (SRS) is an increasingly used treatment for recurrent high-grade glioma (HGG). We analyzed the patterns of failure after salvage SRS to better identify which patients would most benefit. We reviewed all patients who received SRS for recurrent HGG over 12 years at our institution. Pattern of failure was defined by the distance of recurrence from the SRS isodose line. Overall-survival (OS), progression-free survival (PFS), and local-failure-free survival (LFS) were estimated using Kaplan-Meier methods, and regression model analysis was performed to analyze clinical predictors of failure. 146 patients with HGG underwent SRS treatment to 410 target lesions. The median target volume was 3.3 cm3 and median total dose was 18 Gy. Sixty-one (41.8
ABSTRACT:BackgroundThe oncological role of resection in elderly patients with glioblastoma remains controversial. We evaluated the value of resection in patients ≥65 years with (1) newly diagnosed and (2) recurrent glioblastoma by comparing the prognostic relevance of extent of resection to patients <65 years. METHODS:The international RANO resect group retrospectively collected patients with newly diagnosed and recurrent IDH-wildtype glioblastoma from ten neuro-oncological centers. Associations of residual tumor with molecular and clinical markers and survival were analyzed. RESULTS:A total of 1260 patients with newly diagnosed glioblastoma were identified, including 512 patients ≥65 years. Lower postoperative contrast-enhancing tumor volumes were favorably associated with survival on uni- and multivariate analyses; however, the associations with outcome were more pronounced in younger patients. Only in patients <65 years, supramaximal resection was associated with more favorable survival (40 vs 20 months, P = .001). In 310 patients with first recurrence (≥65 years: 92), maximal resection of contrast-enhancing tumor was associated with favorable outcomes, particularly in younger patients. Neither older nor younger patients had favorable outcome associations of supramaximal resection in the recurrent setting. All findings were confirmed in propensity-score-matched analyses to minimize confounding effects of inherent differences in demographic and clinical markers (including second-line treatments) between older and younger patients. CONCLUSIONS:While complete contrast-enhancing tumor resection is prognostic for favorable outcomes in older patients, associations of supramaximal resection with improved outcomes were only retained in younger patients with newly diagnosed disease. Those findings support stratified surgical approaches.
Mutations in isocitrate dehydrogenase (IDH) genes, specifically IDH1 and IDH2, are frequently observed in diffuse gliomas (DG) and define distinct molecular subtypes, namely IDH-wildtype and IDH-mutant. Abnormal expression of extracellular vesicle-derived microRNAs (EV-miRNAs) in the cerebrospinal fluid (CSF) of DG patients may serve as minimally invasive diagnostic and prognostic biomarkers. To investigate this potential, we employed miRNA-sequencing (miRNA-seq), quantitative real-time PCR (qRT-PCR), and multivariable logistic regression (MLR) to identify differentially expressed microRNAs (DE-miRNAs) in CSF samples from DG patients. qRT-PCR analysis demonstrated that EV-miR-21-5p effectively differentiated CSF from glioblastoma (GBM) patients versus controls (p = 0.012, AUC = 0.84) and IDH-mutant gliomas versus controls (p = 0.003, AUC = 0.93). MLR identified five miRNAs (miR-150-5p, miR-142-3p, miR-19b-3p, miR-99a-5p, and miR-27b-3p) that accurately distinguished IDH-wildtype from IDH-mutant gliomas (AUC = 1.00), while GBM CSF was reliably separated from controls (AUC = 1.00) based on significantly reduced levels of nine miRNAs, including miR-1298-5p, miR-1911-5p, miR-195-5p, miR-196a-5p, miR-26a-5p, miR-26b-5p, miR-30a-3p, miR-30a-5p, and miR-30e-5p. Notably, miR-142-3p alone achieved complete discrimination of IDH-mutant gliomas from controls (AUC = 1.00). Ingenuity Pathway Analysis (IPA) revealed that miR-16-5p and other miRNAs with seed AGCAGCA formed the largest interaction network in GBM, while disease enrichment analysis using Database for Annotation, Visualization, and Integrated Discovery (DAVID) confirmed that the 1000 predicted mRNA targets of DE-miRNAs in GBM were disease relevant. Collectively, these findings identify a robust panel of CSF-derived miRNAs capable of distinguishing IDH-mutant gliomas, GBM, and non-tumor states, supporting the potential of EV-miRNAs as minimally invasive biomarkers for the molecular characterization of diffuse gliomas.
Purpose Butterfly glioblastoma (bGBM) is an aggressive variant of glioblastoma(GBM) characterized by invasion of both hemispheres through the corpus callosum.The cause of its poor prognosis remains unclear, whether due to complex anatomy orintrinsic molecular traits. In this cohort, we aim to identify the genetic features of bGBMand factors associated with its prognosis. Methods We retrospectively identified GBM patients from our institutional database and groupedthem into non-butterfly glioblastoma (non-bGBM) and bGBM. Clinical features,genomic profiles, and survival outcomes were compared using statistical analysis. Results We analyzed 324 GBM patients, including 36 with bGBM. Confusion was a commonpresenting symptom in bGBM (p = 0.005), and these tumors rarely invaded thetemporal lobes (p = 0.0004). bGBM was associated with higher mutation rates in CDK6 (13.64% vs. 3.11%, p = 0.04), PIK3R1 (22.73% vs. 7.64%, p = 0.03), and TSC2 (9.09% vs. 0.69%, p = 0.02); however, these results were not significant after adjustment for multiple comparisons. Median overall survival was significantly shorter in bGBM patients.(9 months) compared to non-bGBM (18 months, p = 0.001). Conclusions This study provides novel insights into the genetic blueprint of bGBM. Further research with larger cohorts is needed to validate these findings and better understand the molecular features of bGBM.
BACKGROUND AND OBJECTIVES:Glioblastoma (GBM) isocitrate dehydrogenase-wildtype remains a devastating brain tumor with a poor prognosis despite optimal treatment. Even after supramaximal or complete contrast-enhancing (CE) resection, patient outcomes vary significantly, with some experiencing short-term survival (STS) and others long-term survival (LTS). This study aims to identify clinical and molecular markers predicting the survival of patients with GBM in these high-resection categories. METHODS:We retrospectively analyzed patients with newly diagnosed GBM who underwent supramaximal or complete CE resection, followed by next-generation sequencing at our institution (2009-2025). Patients were categorized as STS (survival ≤12 months), non-STS (survival >12 months), or LTS (survival ≥36 months). We compared clinical, radiological, and molecular features between these groups to identify potential prognostic markers. RESULTS:Among 85 patients who met the inclusion criteria, 24 (28%) were STSs and 61 were non-STS (from which 16 [18.8%] were LTSs), with no significant molecular differences observed between these groups. On comparing STS and LTS patients, CDKN2A/B loss (83.3% vs 43.8%, P = .01) and EGFR amplification (58.3% vs 25%, P = .05) were more frequent in STS patients vs LTS. Tumor location varied, with STS patients having more frontal lobe tumors (45.8%) and LTS patients having more temporal lobe tumors (62.5%). A trend, although not statistically significant, toward increased nonlocal recurrence rates was observed in STS patients (27.2%). CONCLUSION:Despite aggressive extent of resection in GBM, the prevalence of STS patients remains notable at ∼28% and survival beyond 3 years remains limited at ∼18.8%. CDKN2A/B loss and EGFR amplification might correlate with shortened survival after supramaximal or complete CE resection. The impact of nonlocal recurrence remains uncertain among STSs. These findings highlight the need for collaborative studies to advance understanding of the biology of GBM as their behavior differs despite aggressive surgical and medical therapies.
The gut microbiome and central nervous system (CNS) communicate through multiple pathways collectively termed the brain-gut axis. Surgical procedures, particularly those involving the CNS, represent a significant physiological stressor that may influence this communication network. This commentary examines published literature on perioperative changes in gut microbiome composition, explores the proposed mechanistic pathways underlying brain-gut interactions during surgical stress, and reviews preliminary clinical evidence for microbiome-targeted interventions for patients in the perioperative setting. The existing research, while still in early stages, points to the gut microbiome as an area that may warrant consideration in perioperative care strategies.
Craniopharyngioma is histologically benign yet locally aggressive, with frequent recurrence. Long-term multicenter outcomes after stereotactic radiosurgery (SRS) remain incompletely defined. We performed a retrospective multi-institutional cohort study through the International Radiosurgery Research Foundation including 296 patients from 13 centers. Median age at first SRS was 33.6 years. Median tumor volume was 1.32 cm³ and median margin dose was 12.0 Gy. The primary endpoint was local control (LC); secondary endpoints were progression-free survival (PFS) and overall survival (OS). Kaplan–Meier methods estimated outcomes, and Cox proportional hazards models evaluated predictors of LC. Actuarial 1-, 5-, and 10-year LC was 93.5
2076 Background: Glioblastoma (GBM) is a poor-prognosis brain malignancy with median overall survival (mOS) of ~12-18 months despite aggressive standard of care (SOC) treatment. DOC1021 is an autologous dendritic cell (DC)-based immunotherapy generated by tandem loading with autologous tumor-derived mRNA and lysate, enabling broad antigen presentation. DOC1021 leverages p38MAPK and mTORC1 signaling cascades to initiate cDC1-like skewing of monocyte-derived DC, leading to potent downstream development of CD8 + tissue-homing, cytolytic effector memory cells. Methods: This pooled analysis includes newly diagnosed and recurrent IDH-wt patients from two clinical trials (Phase I Study 8148 [NCT04552886] and Expanded Access Protocol EAP0001), treated with DOC1021 after resection and SOC chemoradiation. DOC1021, prepared from mobilized peripheral blood mononuclear cells (PBMC) loaded consecutively with autologous amplified tumor mRNA and tumor lysate, was administered bilaterally near deep cervical lymph node chains every other week for 3 administrations with weekly pegylated-IFN. Study 8148 (n=18) evaluated 4 dose levels (3.5 x 10 6 to 36 x 10 6 cells), while Study EAP0001 (n=7) administered only the highest dose level (36 x 10 6 cells). Patients with subtotal resection or pre-treatment progression were not excluded. Blood was collected before and after DOC1021 to assess peripheral immune responses. Results: Among the pooled population (N=25), median age was 58 years (range 47-75), 88% MGMT unmethylated, 24% partially resected, and 16% recurrent disease. There were no dose-limiting toxicities, and a similar safety profile between studies. Common AEs included mild, flu-like symptoms and injection-site reactions. One patient in the EAP study experienced grade 3 cerebral edema after the first DOC1021 dose that fully resolved and subsequent DOC1021 doses were completed per protocol. At the time of analysis, 7 of 21 newly diagnosed patients remain alive ~9-30 months post-surgery. Among recurrent patients (n=4), 2 patients remain alive ~16-20 months after second resection. Pseudo-progression within ~6 months of vaccination was commonly observed. Analysis of post-vaccination PBMC indicated expansion of CD4 + (17/20 patients, mean +28.6%, p=0.0006) and CD8 + (15/20 patients, mean +26.8%, p=0.001) central memory T-cell (T CM ) compartments as well as substantial upregulation of CD127 expression on circulating CD8 + T cells (18/20; mean MFI +72.2%, p=0.03). Conclusions: Collectively, the data show that DOC1021 plus SOC is well-tolerated, feasible, and potentially efficacious in a challenging population that included subtotal resections, pre-treatment progression, and majority MGMT unmethylated. A multi-center, randomized, open-label Phase 2 trial (NCT06805305) in newly diagnosed GBM is now enrolling to compare DOC1021+SOC vs SOC treatment alone. Clinical trial information: NCT04552886 .
Stereotactic radiosurgery (SRS) is used in selected patients with craniopharyngioma, yet counseling and follow-up planning often rely on population-level local control rates rather than individualized expectations over time. To develop and internally validate a multicenter survival model to predict imaging-defined time to progression after SRS for craniopharyngioma. We analyzed a multicenter IRRF registry of SRS-treated craniopharyngioma patients. Imaging progression was defined by the overall last imaging response (PD vs. non-PD), with censoring at last imaging follow-up when progression was not observed. A Random Survival Forest (RSF) model was evaluated using 5-fold out-of-fold cross-validation. Performance was assessed using the concordance index, time-dependent AUC at 12, 24, and 60 months with bootstrap 95
Glioblastoma isocitrate dehydrogenase (IDH)-wildtype (GBM) has been reclassified based on molecular and phenotypic features. Intratumoral hemorrhage is a phenotypic subtype with poorly understood molecular and clinical characteristics. We aimed to characterize the molecular profile and outcomes of hemorrhagic glioblastoma (hGBM) compared with non-hGBM. A retrospective analysis of GBMs with pre-operative and post-operative MRI and comprehensive next-generation sequencing of 205 genes was performed. Patients were classified as hGBM or non-hGBM using the Visually Accessible Rembrandt Images criteria. Univariable and multivariable survival analyses were performed. Genes were compared using the Fisher-exact test and corrected for multiple comparisons with the Benjamini-Hochberg method. 176 patients were included, of whom 105 had hGBM. Compared to non-hGBMs, hGBMs were more likely Hispanic (20.0
2063 Background: Optimal management of recurrent glioblastoma remains ill-defined. While re-resection is frequently provided as local salvage therapy, stereotactic radiosurgery (SRS) might represent a treatment approach for small, focal recurrences. We comparatively evaluated outcomes after re-resection and SRS for first recurrence of IDH-wildtype glioblastoma. Methods: Adult patients with first radiographic recurrence of IDH-wildtype glioblastoma (WHO 2021 classification) were identified. Information on patients managed with re-resection were collected through the international eight-center database of the RANO resect group, and patients managed with SRS were collected by twelve centers from the IRRF study group. Survival after recurrence was analyzed using Kaplan–Meier estimates and Cox proportional hazards models. Inverse probability of treatment weighting (IPTW) was applied to mitigate baseline imbalances. Results: Overall, 567 patients were included (re-resection: n = 310; SRS: n = 257). Compared with SRS, patients managed with re-resection were younger and had larger contrast-enhancing recurrence volumes. Despite those baseline differences, overall survival did not differ between treatment modalities (10.2 [95%CI 9.3–11.7] vs. 11.1 [10.3–12.8] months; HR 1.12, 95%CI 0.93–1.35; p = 0.231). Also, no survival differences between treatment groups were observed when effects of potential baseline confounders including tumor volume were minimized using IPTW. Notably, among patients typically not considered SRS candidates due to tumor volumes >10 cm³ ( n = 234), maximal re-resection of the enhancing tumor (RANO class 1–2) was associated with survival comparable to SRS-treated low-volume tumors ≤10 cm³ (9.1 [7.7–11.5] vs. 11.0 [9.9–12.8] months; HR 1.27, 0.95–1.69; p = 0.106) whereas incomplete re-resection (RANO class 3) was associated with less favourable survival. In the subgroup of patients with focal recurrences in whom local physicians from the IRRF consortium perceived clinical equipoise between treatment modalities but eventually performed SRS ( n = 112), IPTW-adjusted analyses demonstrated no significant difference in overall survival compared with re-resected patients (HR 0.90, 0.65–1.25; p = 0.539). Conclusions: While complete re-resection is prognostic in recurrent glioblastoma, SRS might represent a reasonable therapeutic approach for selected individuals with small low volume tumor recurrence. Given substantial baseline differences between patients treated with re-resection and SRS and potential treatment provider bias, prospective trials are warranted to guide nuanced decision-making.
Despite multimodal therapy, glioblastomas invariably recur. In focal recurrent glioblastoma IDH-wildtype (rGBM), local therapy options include laser interstitial thermal therapy (LITT) and stereotactic radiosurgery (SRS), but their relative utilities are unknown. The goal of this study is to compare the efficacy of these two treatment modalities in a homogeneous rGBM population. We conducted a retrospective study of patients undergoing surgical procedures for rGBM between 2010 and 2025. All patients underwent either LITT or SRS at first recurrence. Survival outcomes were assessed with univariable log-rank tests and multivariate Cox regression models. A propensity-score matching (PSM) was performed to address confounders. 57 patients were identified; of these, 10 underwent LITT, and 47 underwent SRS. There was no difference in post-recurrence survival (PRS) between groups (11.5 months vs. 13.4 months, p = 0.824). There were no surgical complications in the LITT cohort. In the SRS cohort, there were two symptomatic radiation necrosis cases (0
OBJECTIVE:Resections of the supplementary motor area (SMA) in the dorsomedial frontal cortex (DMFC) have traditionally been thought to result in predictable postoperative motor deficits termed the "SMA syndrome." However, the true incidence, etiology, and duration of these deficits seem overstated in the modern era. Herein, the authors aimed to critically evaluate and reassess the SMA syndrome in the context of surgical navigation, retractorless surgery, and contemporary motor mapping and monitoring techniques. METHODS:The authors retrospectively reviewed the electronic medical records of all patients who underwent DMFC resections for tumors or epilepsy between 2004 and 2025 at a single institution. Patients with insufficient data were excluded from the study. Compiled data included demographics, presenting symptoms, surgical characteristics, intraoperative mapping, postoperative motor function, postoperative complications, and follow-up visits up to 12 weeks. RESULTS:Eighty patients were eligible for study inclusion. New postoperative motor deficits occurred in 33.8% of patients (27/80); however, when cases with concomitant involvement of the primary motor cortex or cingulate gyrus were excluded, the incidence of SMA-specific deficits was only 10.0% (8/80). Moreover, 81.5% of new deficits (22/27) resolved by a median of 13 days, and 51.9% (14/27) recovered very rapidly. Patients with new deficits were more likely to have right hemisphere resections (p = 0.033). Motor strip involvement (p = 0.019) and postoperative complications (p = 0.042) were also associated with new deficits. No association was found with the use of intraoperative mapping, percentage of resected SMA, or other clinical characteristics. As expected, patients with new deficits experienced a longer postoperative hospital course (p = 0.023) and were more often discharged to inpatient rehabilitation (p = 0.012). Permanent deficits occurred in 6.3% of patients (5/80) and were more often associated with preoperative weakness (p = 0.047) and a major postoperative complication (p = 0.013). CONCLUSIONS:These findings challenge the classic perspectives on SMA syndrome. When resections are confined to the SMA, postoperative deficits are uncommon, mild, and resolved rapidly. Persistent deficits reflect injury to adjacent eloquent regions rather than injury from the SMA resection itself. With gravity-based retraction, modern navigation, and functional mapping, DMFC lesions can be resected more safely than in the past. Study findings support redefining SMA syndrome and expanding the role of mapping-guided resections in this region.
There is a critical need for better strategies to diagnose and monitor patients with gliomas. Liquid biopsies are less invasive than tissue biopsies and are amenable to serial collection at multiple timepoints. However, the analysis of circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) from patients with gliomas remains underutilized in clinical practice due to technical challenges. We collected CSF samples from 43 patients with various types of gliomas and evaluated ctDNA derived from CSF with a next generation sequencing (NGS) panel interrogating 600 cancer-related genes. Total cell-free DNA (cfDNA) concentration obtained from CSF (0.4-5 mL) ranged from 0.09 to 60 ng/µL. Mutations were detected in 26/43 (60
Several molecular alterations have been identified to provide prognosis for patients with isocitrate dehydrogenase (IDH)-mutant astrocytoma. However, contemporary baseline survival data with respect to their molecular alterations are lacking. The prognostic value of histologic grading remains controversial. This was a retrospective multi-site study of adult IDH-mutant diffuse astrocytoma patients. Overall survival (OS) was estimated using the Kaplan-Meier method. Associations between OS and measures of interest were evaluated using Cox proportional hazards regression models. We identified 241 eligible patients. The most frequent mutations were IDH1 (98%), TP53 (91%), ATRX (70%), ARID1A (8%), BRCA2 (6%), TSC2 (6%), CDKN2A (6%), and CREBBP (6%). IDH2 mutations were identified in 2%. By univariate analysis, age > 40 (hazard ratio [HR], 2.03; 95% CI, 1.20-3.45; p = .009) was associated with worse OS. Wildtype BRCA2 compared with mutated BRCA2 (HR, 0.42; 95% CI, 0.20-0.90; p = .024) and Central Nervous System World Health Organization (CNS WHO) grade 2 astrocytoma compared with grade 3 disease (HR, 0.40; 95% CI, 0.21-0.78; p = .007) were associated with better OS. In multivariable analysis, age > 40 (HR, 2.06; 95% CI, 1.18-3.59; p = .011) was associated with worse OS and CNS WHO grade 2 (HR, 0.42; 95% CI, 0.21-0.83; p = .012) remained associated with improved OS. We identified an association between increased tumor mutation burden (TMB) and worse OS. Age and CNS WHO grade remain essentials for risk stratification among IDH-mutant astrocytoma patients. Further studies are warranted to determine the prognostic implications of BRCA2 mutations and TMB.
In the past decade, studies have reclassified infiltrating glioblastomas (GBM) IDH-wildtype utilizing molecular and phenotypic features. Cystic GBMs are one such phenotypic subtype whose genetic and clinical characteristics remain incompletely understood. The goal of this study was to genetically characterize cystic GBMs and examine patient outcomes as compared to non-cystic GBMs. Retrospective analysis of GBM IDH-wildtype with pre-operative and post-operative MRI and comprehensive next-generation sequencing were performed with evaluation of 205 genes. Tumors were evaluated by their cystic characteristics. Benjamini-Hochberg’s false discovery rate (BH-FDR) was performed for multiple comparison adjustments. Univariable and multivariable analysis for survival was performed. 176 GBM IDH-WT patients met the inclusion criteria. Of these, 17 patients were identified as having a cystic component. Compared to non-cystic GBMs, cystic GBMs had a higher incidence of mutation in PDGFRA (41.2