Purpose: Isocitrate dehydrogenase (IDH)-mutant gliomas are usually treated with radiotherapy and chemotherapy, which increases the risk for neurocognitive sequelae during patients’ most productive years. We report our experience using off-label first-in-class mutant IDH1 inhibitor ivosidenib and its impact on tumor volume in IDH-mutant gliomas. Experimental Design: We retrospectively analyzed patients ages ≥18 years with radiation/chemotherapy-naïve, mutant IDH1, nonenhancing, radiographically active, grade 2/3 gliomas, and ≥2 pretreatment and ≥2 on-treatment ivosidenib MRIs. T2/FLAIR-based tumor volumes, growth rates, and progression-free survival (PFS) were analyzed. log-linear mixed-effect modeling of growth curves adjusted for grade, histology, and age was performed. Results: We analyzed 116 MRIs of 12 patients [10 males, median age 46 years (range: 26–60)]: 8 astrocytomas (50% grade 3) and 4 grade 2 oligodendrogliomas. Median on-drug follow-up was 13.2 months [interquartile range (IQR): 9.7–22.2]. Tolerability was 100%. A total of 50% of patients experienced ≥20% tumor volume reduction on-treatment and absolute growth rate was lower during treatment (−1.2 ± 10.6 cc/year) than before treatment (8.0 ± 7.7 cc/year; P ≤ 0.05). log-linear models in the Stable group (n = 9) showed significant growth before treatment (53%/year; P = 0.013), and volume reduction (−34%/year; P = 0.037) after 5 months on treatment. After treatment, volume curves were significantly lower than before treatment (after/before treatment ratio 0.5; P < 0.01). Median time-to-best response was 11.2 (IQR: 1.7–33.4) months, and 16.8 (IQR: 2.6–33.5) months in patients on drug for ≥1 year. PFS at 9 months was 75%. Conclusions: Ivosidenib was well tolerated and induced a high volumetric response rate. Responders had significant reduction in tumor growth rates and volume reductions observed after a 5-month delay. Thus, ivosidenib appears useful to control tumor growth and delay more toxic therapies in IDH-mutant nonenhancing indolently growing gliomas. See related commentary by Lukas and Horbinski, p. 4709

The overall survival rate of brain malignancies such as glioblastoma is currently a little under two years, at most, and treatment options for malignant brain tumors have demonstrated limited efficacy. The current standard of care to treat brain cancer includes surgical resection, radiation, and chemotherapy. Historically, an observed interaction between malignancies and concurrent viral infection has shown therapeutic potential that can perhaps be better leveraged in brain cancer with the technological advances that we have today. We aim to discuss a variety of viral vector designs to harness their oncolytic potential and explore how some of these ideas have performed in clinical trials. In our review, three major viral candidates that have gained traction in this field of research—Herpes simplex virus-1, adenovirus, and poliovirus—are highlighted. How the field has manipulated aspects of their virology and combined these viral platforms with other immune modulating strategies to treat both adult and pediatric tumors is also surveyed. Finally, the work exploring the possibility of other neurotropic viral candidates has been elaborated. More insight into the biological interactions between tumor, brain, and body is needed to address this particularly difficult clinical challenge. While there is still no clear, effective treatment for brain malignancies, the utilization of oncolytic viruses shows potential both as a treatment and as a tool to better understand the immune microenvironment of this pathology.

Tumor microenvironment (TME) is characterized by a milieu of distinct cell types that exist in heterogenous transcriptional states across tumors. Functional interactions among these cell states drive tumor progression and therapy response. Systematic characterization of functional cell-state interactions (CSIs) remains challenging due to the paucity of scRNA-seq cohorts with clinical information on one hand, and the lack of cellular context in bulk RNA-seq cohorts on the other. We present CSI-TME, a computational pipeline that extends the concept of gene interactions, such as synthetic lethality, to cell states, to infer prognostic CSIs by directly leveraging large cohorts of bulk transcriptomic datasets. Applied CSI-TME to IDH-mutant gliomas, we identified a highly reproducible cell-state interaction network (CSIN) that is predominantly pro-tumor and differentially activated in IDH-mut astrocytoma versus oligodendroglioma. Malignant cell states within the CSIN resemble multiple neuronal lineages, including astrocyte-like and oligodendrocyte-progenitor-like programs, and reveal key interactions between glioma stem cells and T cells. CSIN stratifies patient response to immune-checkpoint blockade therapy. Roughly 20% of CSIs involve direct ligand–receptor communication, and co-localize in spatial-transcriptomic datasets, most notably for a pro-tumorigenic interaction between tip-like endothelial cells and hypoxic malignant cells supported by multiple ligand–receptor interactions. Interestingly, anti-tumor CSIs correlated with oncogenic mutations are preferentially active in early stages of cancer, hinting at tissue homeostatic response. Overall, CSI-TME is a novel approach that, leveraging clinical bulk transcriptomic data, identifies prognostic CSIs and therapeutic ligand–receptor targets, while providing novel insight into how interactions among the cell states shape the TME in IDH-mutant glioma.

Background: Primary malignant brain tumors (PBT) impose substantial burdens on patients and caregivers. Caregivers are essential in the delivery of outpatient care for patients with PBT but experience high levels of fatigue, distress, and health decline. Although exercise is known to improve outcomes in cancer patients, interventions tailored specifically to the PBT patient–caregiver dyad remain limited. Dyadic intervention, as well as exercise oncology, are emerging areas of active research in neuro-oncology. This scoping review incorporates both principles to evaluate the existing literature on exercise interventions on primary brain tumor patient–caregiver dyads. Methods: We conducted a comprehensive search of MEDLINE (PubMed), Embase, CINAHL (EBSCO), Rehabilitation & Sports Medicine (EBSCO), and Cochrane Central (Ovid) in December 2025 for studies involving exercise interventions that included adult PBT patients and caregivers. Results: Of the 1126 records screened, eight studies were included: four yoga-based interventions (three feasibility trials and one ongoing multicenter RCT), one pilot ski-based intervention, and three aerobic and resistance training-based interventions (two qualitative and one ongoing trial). The interventions were safe and feasible, with high adherence and retention. The preliminary reported benefits included improvements in fatigue, sleep, quality of life, and caregiver distress for the dyads. Videoconference delivery was effective, particularly during the COVID-19 pandemic. The eight included studies comprised 5–67 dyads, with four being single-arm feasibility studies. Conclusions: Current literature on dyadic exercise intervention in neuro-oncology consists primarily of small-scale feasibility and pilot studies. Initial findings have demonstrated that such interventions are safe. However, preliminary efficacy remains limited due to the risk of bias and lack of statistical power. Larger randomized clinical trials with objective endpoints are needed to define efficacy and guide evidence-based protocols.

Supplementary Table 2 - Raw data for growth modeling.

Purpose:Isocitrate dehydrogenase (IDH)-mutant gliomas are usually treated with radiotherapy and chemotherapy, which increases the risk for neurocognitive sequelae during patients’ most productive years. We report our experience using off-label first-in-class mutant IDH1 inhibitor ivosidenib and its impact on tumor volume in IDH-mutant gliomas.Experimental Design:We retrospectively analyzed patients ages ≥18 years with radiation/chemotherapy-naïve, mutant IDH1, nonenhancing, radiographically active, grade 2/3 gliomas, and ≥2 pretreatment and ≥2 on-treatment ivosidenib MRIs. T2/FLAIR-based tumor volumes, growth rates, and progression-free survival (PFS) were analyzed. log-linear mixed-effect modeling of growth curves adjusted for grade, histology, and age was performed.Results:We analyzed 116 MRIs of 12 patients [10 males, median age 46 years (range: 26–60)]: 8 astrocytomas (50% grade 3) and 4 grade 2 oligodendrogliomas. Median on-drug follow-up was 13.2 months [interquartile range (IQR): 9.7–22.2]. Tolerability was 100%. A total of 50% of patients experienced ≥20% tumor volume reduction on-treatment and absolute growth rate was lower during treatment (−1.2 ± 10.6 cc/year) than before treatment (8.0 ± 7.7 cc/year; P ≤ 0.05). log-linear models in the Stable group (n = 9) showed significant growth before treatment (53%/year; P = 0.013), and volume reduction (−34%/year; P = 0.037) after 5 months on treatment. After treatment, volume curves were significantly lower than before treatment (after/before treatment ratio 0.5; P < 0.01). Median time-to-best response was 11.2 (IQR: 1.7–33.4) months, and 16.8 (IQR: 2.6–33.5) months in patients on drug for ≥1 year. PFS at 9 months was 75%.Conclusions:Ivosidenib was well tolerated and induced a high volumetric response rate. Responders had significant reduction in tumor growth rates and volume reductions observed after a 5-month delay. Thus, ivosidenib appears useful to control tumor growth and delay more toxic therapies in IDH-mutant nonenhancing indolently growing gliomas.See related commentary by Lukas and Horbinski, p. 4709