Mass General Brigham Researchers Present Key Findings at SNO Meeting

Researchers from Mass General Brigham Cancer Institute will present research discoveries and outcomes from clinical trials in cancer at the 2025 Society for Neuro-Oncology (SNO) annual meeting, held November 19-23, in Honolulu.

Presentations from Mass General Brigham investigators include, among many, an update to a previous study on the benefits of stereotactic radiation vs. hippocampal avoidant on cognitive decline in patients with brain metastases; insight into the metabolic underpinnings of glioblastoma; and new data on the importance of tailored supportive care for patients with lung cancer and with brain metastases.

SNO brings together the global neuro-oncology community of scientists, clinician researchers, community practitioners, allied health personnel, trainees, patient advocates and industry partners.

Below are a few highlights from this year’s presentations. All times are in Hawaii Standard Time (HST).

Uncovering the metabolic programs underlying malignant cell state heterogeneity in glioblastoma
When: Friday, Nov. 21, 2025, 11:30 a.m.-12:30 p.m.
Who: Mario Luca Suva, MD, PhD, Mass General Brigham Cancer Institute
What: Glioblastoma (GBM) is an incurable and aggressive brain cancer marked by profound intra-tumoral heterogeneity. Malignant cells exist in four core transcriptional states: stem-like and more differentiated astrocytic or mesenchymal states. Using spatial transcriptomics, the researchers previously identified a layered tumor structure of these states, with hypoxia emerging as an organizing driver, implicating oxygen availability as a central factor in cell state dynamics. However, how these cellular states interact with each other and with the tumor microenvironment remains incompletely understood. To uncover state-specific vulnerabilities for reducing GBM cell state diversity, the team conducted a small-molecule screen in glioma sphere models using over 1,600 cysteine-reactive covalent inhibitors, assessing their effects on cell states via RNA-seq. Their small-molecule screen identified compounds that promote differentiation and are enriched for NRF2 activation, a master regulator of the antioxidant response. These findings provide deeper insight into the metabolic underpinnings of GBM cell states and support the rationale for combinatorial therapies aimed at reducing intratumoral heterogeneity that exploit their divergent dependencies.

The experience of patients with lung cancer with brain metastases: neurocognitive deficits and patient-reported functional difficulties and mood
When: Friday, Nov. 21, 2025, 11:30 a.m.-12:30 p.m.
Who: Mary Boulanger, MD, Mass General Brigham Cancer Institute
What: Brain metastases affect over 50% of patients with advanced lung cancer, though their impact on patients’ functioning and symptoms has not been well-described. The research team aimed to characterize and explore associations between neurocognitive deficits, functional difficulties, and mood. This is a cross-sectional study of patient-reported outcomes among patients with lung cancer with brain metastases at the time of evaluation for gamma knife radiosurgery, using a prospectively collected single-site registry. The team summarized patients’ demographic and clinical data, neurocognitive deficits per clinician exam, and patient-reported functioning (self-care, usual activities, mobility) and mood (anxiety/depression) using the European Quality of Life 5-Dimensions 3-Level Version. They used logistical regressions to assess associations between (1) the presence of neurocognitive deficits and functional difficulties and (2) the presence of functional difficulties and mood symptoms, adjusting for age, tobacco use, performance status, extracranial disease status, prior brain surgery, and prior radiation. Patients with lung cancer with brain metastases experience functional difficulties, particularly if they have motor deficits or gait dysfunction/incoordination. Patients also experience mood symptoms, especially if they have difficulties with usual activities. These findings highlight the need for tailored supportive care for patients with lung cancer with brain metastases.

Stereotactic radiation versus hippocampal avoidant whole brain radiation in patients with 5-20 brain metastases: Cognitive outcomes of 12-month survivors
When: Friday, Nov. 21, 2025, 1-2:30 p.m.
Who: Michael Parsons, PhD, Mass General Brigham Cancer Institute
What: (This talk will be featured at the plenary stage.) Compared to whole brain radiation (WBRT), stereotactic radiation (SRS/SRT) and Hippocampal Avoidant (HA-WBRT) produce superior neurocognitive function (NCF) outcomes for brain metastasis survivors. In a multi-center, phase 3 randomized clinical trial comparing SRS/SRT to HA-WBRT in patients with 5-20 brain metastases (NCT03075072), the researchers found reduced symptom burden and NCF decline in the SRS/SRT arm. The current study examines the secondary endpoint, NCF outcome, in 12-month survivors. This analysis demonstrates significantly reduced risk of cognitive decline for 1-year survivors of 5-20 brain metastases treated with SRS/SRT vs HS-WBRT. Implications and predictors of long-term outcomes are discussed.

Integrated multiomic profiling identifies genomic and immune microenvironmental changes as candidate resistance mechanisms to PD-1 blockade in high-grade meningiomas
When: Saturday, Nov. 22, 2025, 3:15-4:15 p.m.
Who: David Gritsch, MD, PhD, Mass General Brigham Cancer Institute
What: High-grade meningiomas (HGMs) are aggressive tumors with limited systemic treatment options and poor long-term survival. A recent phase 2 trial (NCT03279692) of pembrolizumab demonstrated clinical benefit in a subset of HGMs (Brastianos et al. Nature Communications 2022), highlighting the need to identify biomarkers of response. To address this, the researchers performed genomic and immune profiling of tumor and plasma samples from 25 patients treated with pembrolizumab as part of this trial. Their findings suggest that loss of chromosome 9p, in combination with CDKN2A deletion, defines a hyperproliferative, immune-cold subset of HGMs that are resistant to PD-1 blockade, nominating 9p loss as a potential biomarker of immunotherapy resistance and a candidate driver of immune exclusion.

Alliance A071601: Phase II trial of BRAF/MEK inhibition in recurrent papillary craniopharyngiomas
When: Saturday, Nov. 22, 2025, 4:30-5:30 p.m.
Who: Priscilla Brastianos, MD, Mass General Brigham Cancer Institute
What: Craniopharyngiomas, a rare brain tumor along the pituitary-hypothalamic axis, can cause significant clinical sequelae. Genetic analysis of craniopharyngiomas revealed that 95% of papillary craniopharyngiomas (PCP) have BRAF V600E mutations. This research team previously reported that BRAF/MEK inhibition was associated with significant anti-tumor activity in newly diagnosed PCP patients. The team has now evaluated the efficacy of vemurafenib/cobimetinib in a separate cohort of patients on this trial with recurrent PCP whose tumors progressed after prior radiation.

Clinical Presentation, Management and Outcome of Tumor inflammation-associated neurotoxicity (TIAN) in CNS lymphoma treated with CD19-CAR T-cell therapy
When: Sunday, Nov. 23, 2025, 11 a.m.-12 p.m.
Who: Jorg Dietrich, MD, PhD, Mass General Brigham Cancer Institute
What: (This work was recently published in Blood.) Tumor inflammation-associated neurotoxicity (TIAN) has been proposed as a unique complication of immunotherapy in brain tumor patients. Here, the researchers report the first comprehensive characterization of TIAN in CNS lymphoma (CNSL) patients treated with CD19-directed chimeric antigen receptor T-cells (CD19-CAR). TIAN occurred in 10/56 (17.9%) CNSL with clinical onset at a median 3.5 days (range: 1-9) after CD19-CAR infusion. It was less frequently associated with cytokine release syndrome (60% vs 100%, p = 0.009) than immune effector cell-associated neurotoxicity syndrome (ICANS). Although symptoms were usually transient and fully reversible, TIAN was associated with a fatal outcome in one patient. Larger CNS tumor volume at baseline allowed the identification of patients at risk for TIAN (AUC: 0.847, p = 0.002). Maximizing Youden J statistics, a discriminatory tumor volume threshold >3.4cm3 was determined, which carried 87.5% sensitivity and 80.5% specificity. TIAN correlated with higher overall response rates to CD19-CAR (90% vs 52%, p = 0.036) and improved progression-free survival (Hazard ratio: 0.22; 95%-Confidence interval: 0.07-0.61, p = 0.006) on multivariate Cox proportional hazard regression. Post-mortem histopathological evaluation of a TIAN lesion revealed a dense macrophage population with central necrosis and peripheral reactive gliosis, accompanied by loss of white matter and intracytoplasmic myelin in foamy macrophages. Quantitative PCR confirmed the presence of CD19-CAR at the TIAN lesion site. Collectively, this work supports TIAN as a localized on-tumor, on-target neurotoxicity syndrome, closely related to pre-existing CNSL lesions and distinct from ICANS. CNS tumor volume at baseline may allow to identify patients at risk and may guide management.