Neuro-oncology advances最新文献

{"title":"Genomic and clinical determinants of local and distant intracranial progression following surgical resection of brain metastases.","authors":"Neslihan Nisa Gecici, Ahmed Habib, Walaa Hamza, Maged T Ghoche, Rivka R Colen, Kalil G Abdullah, Pascal O Zinn","doi":"10.1093/noajnl/vdag228","DOIUrl":"10.1093/noajnl/vdag228","url":null,"abstract":"<p><strong>Background: </strong>The role of molecular alterations in predicting local and distant progression following brain metastasis resection is poorly understood. In this study, we investigated clinical and molecular predictors of intracranial progression following brain metastasis resection.</p><p><strong>Methods: </strong>A retrospective analysis of 228 patients who underwent brain metastasis resection at the University of Pittsburgh Medical Center was performed. Tumor specimens underwent next-generation sequencing using the UPMC Oncomine Comprehensive Assay. Bootstrap forest analysis was used to identify top genetic predictors by variable importance for local and distant progression. Cox proportional hazards models were used to identify independent predictors.</p><p><strong>Results: </strong>Local progression occurred in 110 patients (48.2%) and distant progression in 98 patients (43%). The most frequent genetic alterations were TP53 mutations (61.6%), KRAS mutations (31.2%), and CDKN2A/B copy number alterations (24.6%, 23.2%). For local progression, bootstrap forest analysis identified PTEN, STK11, KRAS, FGF3, and ATM alterations as top predictors. On multivariable analysis adjusting for primary malignancy type, independent predictors of local progression included RB1 mutations (HR 3.03, <i>P</i> = .003), PTEN copy number alterations (HR 0.25, <i>P</i> = .02), subtotal resection (HR 2.1, <i>P</i> = .04), and postoperative systemic therapy (HR 0.4, <i>P</i> = .002). For distant progression, PTEN, TERT, STK11, CDKN2AB, and TP53 alterations were top predictors. Postoperative systemic therapy (HR 0.45, <i>P</i> = .01) was the only independent predictor of distant progression in multivariable analysis.</p><p><strong>Conclusion: </strong>These findings suggest that integrating molecular profiling with clinical factors may contribute to intracranial progression risk stratification after brain metastasis resection, though expansion of the dataset with histology-stratified analyses is warranted to confirm these observations.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"8 1","pages":"vdag228"},"PeriodicalIF":4.6,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune subtypes and survival in patients with primary glioma.","authors":"Yu Fang, Jiwoong Kim, Zachary J Thompson, Youngchul Kim, Harshan Ravi, Asim M Mazin, Carlos M Moran Segura, Jonathan V Nguyen, Robert J Macaulay, Filippo Veglia, Reid C Thompson, Sajeel A Chowdhary, Kathleen M Egan, Natarajan Raghunand","doi":"10.1093/noajnl/vdag257","DOIUrl":"https://doi.org/10.1093/noajnl/vdag257","url":null,"abstract":"<p><strong>Background: </strong>The tumor microenvironment (TME) is a critical determinant of glioma response to therapies, including immunotherapy. We have classified the immune TME of gliomas by multiplex immunofluorescence (mIF).</p><p><strong>Methods: </strong>Tissue taken at initial resection from 354 patients with newly diagnosed glioma grades 2-4 were analyzed using 3 mIF panels of markers for T, B, and myeloid cells. Tumor cores were characterized by the relative abundances of: (i) 15 primary immune phenotypes, (ii) 96 secondary immune phenotypes, and (iii) 29 biologically meaningful multi-marker immune phenotypes.</p><p><strong>Results: </strong>Unsupervised cluster analysis of WHO grade 4 diffuse gliomas revealed four subtypes α, β, γ, and δ that were internally reproducible. Immune subtype α was characterized by high abundance of antigen-presenting cells (APCs) and low levels of MHC II^- monocytes. Subtype β was high in regulatory T cells and myeloid cells, but low in lymphocytes with effector functions. Subtype γ displayed high abundance of immune cell phenotypes, particularly lymphocytes with effector or helper functions. Subtype δ was low in immune phenotypes, with poorer outcomes. Grade 3 tumors could also be classified into α, β, γ, and δ subtypes, indicating generalizability of these immune TME subtypes across high-grade gliomas. Additionally, grade 2 tumors could be classified into subtypes ε, ρ and τ identified in grade 3 tumors.</p><p><strong>Conclusions: </strong>We have identified internally reproducible criteria for classifying gliomas according to the immune microenvironment, findings that could aid our understanding of the natural progression of low- and high-grade gliomas and inform the rational application of immune-oncologic therapeutic interventions.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"8 1","pages":"vdag257"},"PeriodicalIF":4.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149248333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EpiDirect enables rapid bisulfite-free MGMT promoter methylation testing in IDH-wildtype glioblastoma with high agreement across established assays.","authors":"Attila Németh, Carmen Selignow, Annika May, Kai Schmid, Hildegard Dohmen, Marco Stein, Joshua Trautner, Daniel Haag, Felix Sahm, Till Acker","doi":"10.1093/noajnl/vdag255","DOIUrl":"https://doi.org/10.1093/noajnl/vdag255","url":null,"abstract":"<p><p>MGMT promoter methylation is a critical biomarker for predicting alkylating chemotherapy response in IDH-wildtype glioblastoma. However, the lack of an accepted reference detection method complicates clinical implementation. Current assays differ in their target CpG sites, analytical procedures, and classification thresholds. Here, we present an expanded paired analytical comparison of EpiDirect, a bisulfite-free quantitative PCR (qPCR) assay, with 4 established or emerging methods in clinical glioblastoma samples: pyrosequencing, MGMT-STP27 derived from EPIC methylation array data, methylation-specific PCR (MSP), and methylation-specific digital PCR (MS-dPCR).</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"8 1","pages":"vdag255"},"PeriodicalIF":4.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149248281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination chemotherapy potentiates 5-aminolevulic acid-mediated photodynamic therapy killing of patient-derived glioma stem-like cells <i>in vitro</i>.","authors":"Alexa M Semonche, Tatiana Slepak, Ana Pascoini, Long Di, Anna Jermakowicz, Daniel G Eichberg, Chiara Pastori, Vratko Himic, Ashish H Shah, Ricardo J Komotar, Michael E Ivan","doi":"10.1093/noajnl/vdag250","DOIUrl":"10.1093/noajnl/vdag250","url":null,"abstract":"<p><strong>Background: </strong>5-aminolevulinic acid photodynamic therapy (5-ALA PDT) is a promising therapy for glioblastoma (GBM). 5-ALA induces tumor-selective accumulation of protoporphyrin IX (PPIX). Photoactivation of PPIX induces reactive oxygen species generation and tumor cell death. Glioma stem-like cells (GSC) are hypothesized to be resistant to standard therapies and contribute to GBM recurrence. Differential PPIX accumulation in GSC could lead to treatment resistance. We investigated if chemotherapeutics currently utilized in GBM treatment, temozolomide (TMZ) and bis-chloroethylnitrosurea (BCNU), could potentiate 5-ALA PDT killing of GSC.</p><p><strong>Methods: </strong>Patient-derived GSC lines were established. PPIX accumulation was assessed with flow cytometry. 5-ALA metabolic enzyme mRNA expression was measured with quantitative real-time PCR (qRT-PCR). BCNU or TMZ was co-administered with 5-ALA prior to laser irradiation. The effect of combination therapy was evaluated using Loewe combination index analysis.</p><p><strong>Results: </strong>Three GSC lines were exposed to 5-ALA <i>in vitro</i>. Peak PPIX fluorescence levels differed significantly between two cell lines (\"high-\" and \"low-fluorescing\" GSC); there were no significant differences in 5-ALA metabolism enzyme expression between these. PPIX fluorescence correlated with GSC susceptibility to 5-ALA PDT. TMZ did not affect 5-ALA PDT efficacy. BCNU and 5-ALA PDT worked synergistically in low-fluorescing, but not in high-fluorescing, GSC. In high-fluorescing GSC, BCNU upregulated heme-oxygenase 1 (HMOX1) expression, an enzyme that promotes PPIX catabolism.</p><p><strong>Conclusions: </strong>We report the effect of combination chemotherapy and 5-ALA PDT on GSC viability, demonstrating the potential for BCNU and 5-ALA PDT to work synergistically. We speculate that HMOX1 upregulation by BCNU could mitigate this effect.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"8 1","pages":"vdag250"},"PeriodicalIF":4.6,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does earlier diagnosis and treatment of brain tumors matter? Time-to-treatment intervals and tumor size at detection; impact on survival and other patient outcomes.","authors":"Ewan Gray, James M Cameron, Abigail Lishman, Peter Hall, Piyumanga Karunaratne, Giovanni Tramonti, Maheva Vallet, Luke Pike, Matthew J Baker, Paul M Brennan","doi":"10.1093/noajnl/vdag230","DOIUrl":"10.1093/noajnl/vdag230","url":null,"abstract":"<p><strong>Background: </strong>The importance of timely diagnosis of brain tumors is well recognized but how this translates to impact on important patient outcomes is not well described. This observational study aimed to quantify the effect of time-to-treatment interval and tumor size at diagnosis on six patient outcomes: tumor-specific survival, overall survival, new or worsened neurological deficit, 30-day mortality, recurrence, and inpatient length of stay.</p><p><strong>Methods: </strong>A retrospective cohort study including 1,196 patients from Southeast Scotland diagnosed with brain tumors between 2010 and 2020. Analysis was stratified by tumor type in three categories: Glioblastoma (GBM) and other grade 4 brain tumors, grade 1-3 tumors and brain metastases. Regression methods (Cox, Logistic & Linear) were used to estimate per day impact of time-to treatment and tumor size impact on outcomes.</p><p><strong>Results: </strong>The mean time from first presentation to treatment was 161 days (median: 57 days). Time-to-treatment results showed an association between longer intervals and reduced mortality. The mean tumor size was 4.06 cm (SD: 1.75cm). For GBM and grade 4 tumors, each 1cm increase in tumor size increased tumor-specific mortality risk by approximately 11% (HR: 1.11, 95%CI: 1.05-1.16) and increased all-cause mortality by 10% (HR: 1.10, 1.05-1.16). Associations between tumor size and the outcomes of brain tumor mortality, all-cause mortality and inpatient length of stay were consistent across tumor subgroups.</p><p><strong>Conclusions: </strong>Larger tumor size was consistently associated with increased hazard ratios for mortality. Applying these estimates together with estimates of mean tumor growth rates available in the literature, if a 6cm Glioblastoma tumor were diagnosed 3 months earlier, then we would expect a 17%-26% reduction in hazard of brain tumor mortality.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"8 1","pages":"vdag230"},"PeriodicalIF":4.6,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A re-visit of glioblastoma molecular subtypes utilizing the 2021 WHO classification of central nervous system tumors framework.","authors":"Geraldine Wen She Lee, M Tarek Elghetany, John Myseros, Seok-Gu Kang, Xiaonan Li, Wan-Yee Teo","doi":"10.1093/noajnl/vdag247","DOIUrl":"10.1093/noajnl/vdag247","url":null,"abstract":"<p><strong>Background: </strong>The 3-subtype transcriptional framework is an established approach for classifying glioblastoma (GBM). The 2021 World Health Organization (WHO) Classification redefined GBM as an isocitrate dehydrogenase-wildtype (IDH-WT) tumor. We evaluated the 3-subtype framework in context of the new diagnostic criteria of WHO-2021 Classification which defined GBM to be IDH-WT only, to establish subtype concordance, cross-platform reproducibility, and subtype-associated molecular characteristics.</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA) RNA-seq (<i>n</i> = 233) and Affymetrix HGU133A (<i>n</i> = 330) cohorts fulfilling WHO-2021 criteria for IDH-WT GBMs were classified using the published 500-gene classifier. Concordance with legacy TCGA 4-subtype assignments, cross-platform reproducibility, overall survival, and subtype-specific molecular characteristics were evaluated.</p><p><strong>Results: </strong>Among WHO-2021-defined GBMs, the 3-subtype framework demonstrated good concordance with legacy TCGA 4-subtype assignments (79.7%, Cohen's κ  =  0.69) and cross-platform reproducibility between RNA-seq and Affymetrix platforms (81.6%; κ  =  0.72). Legacy proneural (PN; 96.2%) and neural (NE; 70.6%) tumors predominantly mapped to the PN/NE subtype, whereas mesenchymal (MES) tumors largely retained their original subtype assignment (95.4%). The Classical (CL) subtype showed the lowest concordance with its original TCGA subtype assignment (59.4%), with frequent subtype-switching towards PN/NE and MES subtypes while retaining canonical molecular characteristics, including <i>EGFR</i> amplification and <i>CDKN2A/CDKN2B</i> homozygous deletion. MES subtype remained enriched for <i>NF1</i> alterations in the Affymetrix HGU133A cohort. Overall survival did not differ between 3 subtypes among WHO-2021-defined GBMs.</p><p><strong>Conclusion: </strong>This study provides an updated evaluation of the 3-subtype framework within WHO-2021-defined IDH-WT GBM. Based on WHO-2021 criteria, the framework preserved principal subtype assignment patterns, cross-platform reproducibility and established subtype-associated molecular characteristics.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"8 1","pages":"vdag247"},"PeriodicalIF":4.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating tumor DNA as a liquid biopsy for glioma detection in cerebrospinal fluid and plasma: A systematic review and meta-analysis.","authors":"Christian Amezquita-Contreras, Angel Bueno, Diego Arellano, Helen Ruvalcaba-Guerrero, William E Johnson, Antonio Dono, Yoshua Esquenazi, Leomar Y Ballester","doi":"10.1093/noajnl/vdag253","DOIUrl":"https://doi.org/10.1093/noajnl/vdag253","url":null,"abstract":"<p><strong>Introduction: </strong>Accurate molecular characterization of gliomas is essential for determining prognosis and guiding therapeutic decisions. In recent years, liquid biopsy for analysis of circulating tumor DNA (ctDNA) in blood or cerebrospinal fluid (CSF) has emerged as a promising, minimally invasive alternative. This study evaluates the existing literature on the utility of ctDNA detection in CSF and blood in patients with gliomas, with the goal of assessing its ability to identify mutations concordant with those detected in tumor tissue.</p><p><strong>Methods: </strong>A systematic search was conducted up to April 30, 2026, to identify cohorts that evaluated the effectiveness of ctDNA-based liquid biopsies for gliomas. The primary assessed outcomes were the sensitivity and specificity of the liquid biopsies using CSF or plasma. A pooled sensitivity analysis was performed, as well as summary receiver operating characteristic (SROC) curves.</p><p><strong>Results: </strong>Twenty-eight studies met the inclusion criteria, encompassing 613 patients. Meta-analysis of diagnostic performance revealed improved biomarker performance for CSF (Area under the curve [AUC] 0.95) ctDNA. Pooled sensitivity for ctDNA detection in patients with gliomas was higher in CSF 0.79 (95% CI, 0.69-0.85) than in plasma 0.29 (95% CI, 0.15-0.47), <i>P</i> < .0001.</p><p><strong>Conclusion: </strong>The literature demonstrates a promising performance of ctDNA analysis in patients with diffuse gliomas as a liquid biopsy strategy. CSF ctDNA analysis exhibited superior sensitivity compared to plasma ctDNA. This meta-analysis supports the utility of ctDNA, particularly CSF ctDNA, as a complementary diagnostic tool in neuro-oncology.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"8 1","pages":"vdag253"},"PeriodicalIF":4.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Encorafenib plus binimetinib in patients with BRAF-mutated melanoma brain metastases: Results from the BECARE (GEM-2002) trial.","authors":"Pablo Cerezuela-Fuentes, Miguel-Angel Berciano-Guerrero, Eva Muñoz-Couselo, Pedro Sanchez Mauriño, Regina García Galindo, Lourdes Gutiérrez Sanz, José Balsalobre Yago, Teresa Puértolas, Carlos Aguado, Silvia Sequero, Guillermo Crespo, Cristina Aguayo, Enrique Espinosa, Pedro López, Rafael López Castro, Joaquín Fra Rodríguez, Gretel Benítez, Alberto Jacobo Cunquero-Tomás, Alfonso Berrocal, Ainara Soria","doi":"10.1093/noajnl/vdag252","DOIUrl":"10.1093/noajnl/vdag252","url":null,"abstract":"<p><strong>Background: </strong>Encorafenib plus binimetinib (EB) is a standard treatment for BRAF^V600-mutated melanoma brain metastasis (MBM). However, there is limited evidence of EB use in MBM from clinical trials, and real-world data are scarce. This study aimed to determine the effectiveness and safety of EB in BRAF^V600-mutated MBM.</p><p><strong>Methods: </strong>BECARE-GEM-2002 was a retrospective study conducted in 24 hospitals in Spain, including patients treated according to standard clinical practice with EB as the 1st line or 2nd line of treatment after progression to immunotherapy, regardless of symptoms and corticosteroid use. Patients had measurable intracranial disease (≥5 mm on CT scan). Previous treatment with BRAF/MEK inhibitors was not allowed.</p><p><strong>Results: </strong>Between 2021 and 2025, 60 patients were included, 52 (86.7%) treated upfront and 8 (13.3%) after immune checkpoint inhibitors (ICIs) progression. The ORR was 58.3% (95% confidence interval [CI], 44.9-70.9), 65.4% (95% CI, 44.3-82.8) in asymptomatic, and 52.9% (95% CI, 35.1-70.2) in symptomatic MBM. Radiotherapy (RT) was administered prior to EB in 7 patients (11.7%) and concurrently in 17 (28.3%). Patients receiving RT showed an ORR of 76% (95% CI, 54.9-90.6). The median PFS was 7.4 months (95% CI, 6.2-9.7) and median OS was 10.6 months (95% CI, 9.2-15.0). Treatment-related adverse events of grade ≥3 were reported in 12 patients (20%), the most frequent being transaminitis (6.7%) and gastrointestinal hemorrhage (3.3%).</p><p><strong>Conclusions: </strong>EB was safely administered in the real world and showed clinically significant benefit in patients with BRAF^V600-mutant MBM, regardless of brain symptoms. The potential role of RT should be explored in prospective trials.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"8 1","pages":"vdag252"},"PeriodicalIF":4.6,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Value-based assessment of repeat surgery for recurrent glioma: A real-world quality-adjusted survival analysis.","authors":"Wanyu Qiao, Chen Luo, Tian Gan, Shuai Wu, Xian Xie, Jinsong Wu, Hugues Duffau, Jie Zhang, Ye Yao","doi":"10.1093/noajnl/vdag251","DOIUrl":"https://doi.org/10.1093/noajnl/vdag251","url":null,"abstract":"<p><strong>Background: </strong>Reoperation for recurrent glioma is widely practiced, yet clinical decision-making remains challenging due to substantial trade-offs between survival gain and postoperative functional burden. High-quality real-world evidence integrating survival and quality-of-life outcomes to inform reoperation decisions remains limited.</p><p><strong>Methods: </strong>We conducted a retrospective real-world cohort study of 1304 patients with recurrent glioma treated between 2010 and 2018. Propensity score matching was applied to balance baseline characteristics. Survival outcomes, quality-adjusted life years (QALYs), functional status, and prognostic factors associated with reoperation benefit were evaluated.</p><p><strong>Results: </strong>In the 1:1 propensity-matched cohort (140 reoperation vs 140 non-reoperation), reoperation was associated with a mean gain of 9.6 months in quality-adjusted life years (QALYs) and a 521-day longer overall survival. Postoperative functional status showed short-term improvement. In the glioblastoma subgroup, reoperation was associated with a numerical gain of 3.5 QALY months, although the confidence interval crossed zero, alongside a 218-day gain in overall survival. Predictive models based on preoperative characteristics demonstrated good discrimination in identifying patients likely to derive survival benefit beyond 6 months.</p><p><strong>Conclusion: </strong>This study provides real-world evidence that carefully selected patients with recurrent glioma may derive quality-adjusted survival benefits from reoperation, thereby supporting individualized surgical decision-making. These findings have implications for value-based surgical decision-making in recurrent glioma, particularly in healthcare systems where balancing survival benefit against functional outcomes and resource use is increasingly important.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"8 1","pages":"vdag251"},"PeriodicalIF":4.6,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linac-based stereotactic radiosurgery for brain metastases: Survival and salvage treatment in a contemporary cohort of 3893 patients.","authors":"Drew T Bergman, Mitchell I Parker, Henry Walch, Åse Ballangrud, Michalis Aristophanous, Melissa Zinovoy, Brandon S Imber, Gustav Cederquist, Christopher Jackson, Connor J Kinslow, Anthony Abaya, John J Cuaron, James Janopaul-Naylor, Atif Khan, Zachary R Moore, Boris A Mueller, Jacob Y Shin, Divya Yerramilli, Yoshiya Yamada, Yao Yu, Luke R G Pike","doi":"10.1093/noajnl/vdag242","DOIUrl":"10.1093/noajnl/vdag242","url":null,"abstract":"<p><strong>Background: </strong>Real-world outcomes after stereotactic radiosurgery (SRS) for brain metastases across the full burden spectrum are limited. We tested whether overall survival (OS) in higher-burden lesion groups is non-inferior to a 5-10 lesion reference and characterized salvage patterns, including whole-brain radiotherapy (WBRT).</p><p><strong>Methods: </strong>A total of 3893 consecutive patients received linac-based SRS (1-5 fractions) at seven sites of an NCI-designated cancer center network (2017-2026), stratified by lesion count (1, 2-4, 5-10, 11-20, >20). Multivariable Cox regression used 5-10 as reference; pre-specified non-inferiority testing (margin HR 1.30, one-sided α = 0.025) compared higher-burden groups. Cumulative incidences of salvage interventions used death as the competing event.</p><p><strong>Results: </strong>Median age 65 years; median follow-up 41.2 months. 77% had 1-4, 17% had 5-10, and 6% had >10 lesions (maximum 140). Median OS was 16.2, 11.0, 8.2, 8.7, and 6.5 months for the 1, 2-4, 5-10, 11-20, and >20 groups. OS was significantly better for 1 (HR 0.62, 0.55-0.69) and 2-4 (HR 0.81, 0.73-0.90) versus 5-10; non-inferiority was met for 11-20 (<i>P</i> < .001) but not >20 (<i>n</i> = 41, <i>P</i> = .20). CNS-directed systemic therapy was strongly protective (HR 0.62, 0.57-0.68); 21.7% of patients with ≤20 lesions survived ≥30 months. 12-month salvage WBRT incidence was 2.9%-6.3%; 24-month incidence was 6.7% versus 41.7% for a third SRS course.</p><p><strong>Conclusions: </strong>OS plateaued from 5 through 20 lesions, with non-inferiority to the 5-10 reference established for 11-20; the >20 group (<i>n</i> = 41) was underpowered and showed a directionally worse estimate that could not exclude a clinically meaningful decrement. Salvage WBRT was uncommon across all lesion-count groups (24-month cumulative incidence ≤7.3%; >90% of patients received no salvage WBRT), even after multiple SRS courses. These data support an SRS-first strategy guided by clinical factors rather than fixed lesion-count thresholds.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"8 1","pages":"vdag242"},"PeriodicalIF":4.6,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}