Background:Salvage therapies for adults with recurrent ependymoma are limited. A prior retrospective review of patients with recurrent ependymomas treated with bevacizumab and carboplatin reported a 75% radiographic response rate. This prospective single-arm, open-label Phase 2 study was designed to assess clinical efficacy of this regimen. Methods:Twenty-two patients were evaluated in this CERN Adult Clinical Trials network study. Adult patients (age ≥18) with recurrent ependymomas received carboplatin (AUC = 5-6) every 4 weeks and bevacizumab 10mg/kg every 2 weeks for 6 cycles, after which carboplatin was discontinued, while bevacizumab could be continued at physician's discretion. Imaging of areas involved and patient-reported outcomes (PRO) with the MD Anderson Symptom Inventory (brain and/or spine modules) were assessed at baseline and every 2 cycles. Results:With a median follow-up time of 25.9 months (mo), the primary endpoint of 12-mo progression-free survival rate (PFS-12) greater than 50% was reached, with a rate of 76.4% (95% CI, 52.2, 89.4). The median PFS of this cohort was 18.0 mo. Two patients achieved objective partial responses (9.1%). There were no treatment-related grade ≥4 toxicities. Brain tumor responders (radiographic objective response or stable disease) experienced improved cognitive and neurological symptoms, while spine tumor patients reported worsening symptom outcomes regardless of response. Conclusions:Treatment with carboplatin and bevacizumab in adult recurrent ependymomas met the PFS-12 clinical efficacy endpoint. However, symptomatic worsening in spinal tumors suggests imaging stability and symptom improvement in brain disease may be related to bevacizumab pseudo-response.

Abstract Background Survivors of primary brain tumors (SPBT) frequently struggle to return to work. This study investigated work status and outcomes after tele-based vocational cognitive rehabilitation (t-VCR) in SPBT. Methods We retrospectively reviewed adults (≤65 years) with SPBT at an academic medical center who completed objective cognitive and patient-reported outcome measures between 5/2018 and 5/2022. Participants were grouped by employment status and compared on demographic and clinical characteristics. Work outcomes were analyzed in a subgroup who underwent t-VCR during standard clinical care. t-VCR treatment response was defined as return to work, increase to full-time work, or graduation from a workplace improvement plan versus baseline. Analyses used t-tests, chi-square, and McNemar tests, with content analysis identifying key interventions in responders. Results Of 77 participants, 35 were working and 42 were unemployed upon referral. Unemployment was associated with worsened verbal learning and memory (P < .003). Among the 28 people who received t-VCR (mean-10 sessions), 82% returned to work after t-VCR. In those who had improved work status, content analysis identified t-VCR interventions, including executive and organizational skills training, mental health counseling, job simulations/accommodations, and fatigue/stimulation education were most common. Conclusion Worsened verbal learning and memory were associated with unemployment, highlighting the impact these cognitive symptoms can have on occupational functioning. Work status improved in the context of t-VCR and warrants further study. Among participants who demonstrated improvement, t-VCR was delivered as a multimodal, individualized intervention that addressed cognitive, emotional, fatigue, and practical workplace-related challenges.

Glioblastoma (GBM) is the most common malignant primary brain tumour and is associated with poor prognosis. Platelet-related factors have been linked to outcomes in GBM, but evidence remains inconsistent. This review evaluates their prognostic value for survival. We conducted a systematic review and meta-analysis of studies on preoperative thrombocytic factors in GBM. PubMed, MEDLINE, and Embase were searched from inception to January 2025 using MeSH terms. Eligible studies included observational cohort studies of adults (≥ 16 years) with WHO grade 4 diffuse astrocytoma (GBM), ≥ 30 participants, and ≥ 3 months’ follow-up after resection. Random-effects meta-analysis using restricted maximum likelihood with Hartung–Knapp adjustment was used to pool hazard ratios (HRs) of high vs. low parameters on overall survival (OS). Study quality was assessed with the Newcastle-Ottawa Scale. 21 studies were included. 13 (n = 2609) reported HRs of high vs. low platelet: lymphocyte ratio (PLR, median threshold = 150), with high PLR significantly associated with worse OS (pooled HR = 1.46, 95

PURPOSE:GBM AGILE (ClinicalTrials.gov identifier: NCT03970447) is a phase II/III Bayesian adaptive platform registration trial testing multiple arms against a common control; the primary end point is overall survival (OS). Regorafenib, a multikinase inhibitor, showed OS benefit in recurrent (RD) glioblastoma in the phase II REGOMA trial and entered GBM AGILE as the first investigational arm. METHODS:Patient subtypes included in the regorafenib arm of GBM AGILE were newly diagnosed unmethylated (NDU) and RD glioblastoma. Prospective defined sets of subtypes, or arm signatures, were NDU, RD, and all (NDU + RD). As the first investigational arm in GBM AGILE, regorafenib was equally randomized to the control arm. Treatment in the control arm is temozolomide + radiotherapy (in newly diagnosed) or lomustine (in RD). Efficacy was assessed by OS hazard ratio (HR), arm/control, and demonstrated when the Bayesian probability of benefit (HR <1.00) was ≥98%. Analysis was performed monthly for limited efficacy, which occurs when the Bayesian predictive power is <25% for all signatures, and determines stopping enrollment. Follow-up continued for 12 months after accrual stopped. RESULTS:When the predictive power was <25% in all predefined signatures for regorafenib, accrual stopped for limited efficacy. The final analysis did not demonstrate OS improvement in the regorafenib arm in RD nor NDU glioblastoma. Median HRs were 1.05 (NDU), 1.07 (RD), and 1.07 (all) with final probabilities of benefit (HR <1.00) of 0.421 (NDU), 0.312 (RD), and 0.296 (all). Regorafenib was associated with increased toxicity relative to control. CONCLUSION:GBM AGILE did not show superiority of regorafenib over control in RD (lomustine) or NDU (temozolomide + radiotherapy) glioblastoma, yet caused increased toxicities. Regorafenib has been removed from National Comprehensive Cancer Network guidelines as a treatment option for RD.

Background:Glioblastoma (GBM) has limited effective salvage therapy options. The combination of the Type 1B topoisomerase/HIF1α inhibitor topotecan and the tyrosine kinase inhibitor pazopanib has shown promise in solid tumors and may be effective in recurrent GBM. Methods:Patients with recurrent GBM who were bevacizumab-naïve (Group A, 9 patients) or had previous bevacizumab (BEV) (Group B, 22 patients) started daily oral pazopanib (600 mg) and topotecan (0.25 mg). The primary objective was progression-free survival (PFS) at 6 months for Group A and 3 months for Group B patients. Secondary objectives included median progression-free and overall survival (OS), safety, tolerability, and toxicity as measured by patient-reported outcomes (PROs) and adverse event documentation. Results:Group A enrolled 9 evaluable patients and closed to accrual early when interim primary objectives were not met (PFS-6 11%). Group B enrolled 22 evaluable patients and narrowly met its primary objective (PFS-3 18%). Median PFS and OS endpoints demonstrated equivalent to slight improvement upon historical metrics, respectively. The regimen was tolerable and safe save for high frequency of hypertension, with PROs data showing stability or worsening in parallel with tumor stability or progression, respectively. Conclusions:These findings suggest the regimen is safe and tolerable to GBM patients. The regimen was ineffective in bevacizumab-naïve patients and only narrowly met its predetermined endpoint in patients with prior BEV. These results do not support the combination regimen as tested in this protocol for further investigation in GBM.

Abstract Background: Developing safe and effective CAR-T therapy for glioblastoma (GBM) has been hindered by antigen heterogeneity, on-target off-tumor toxicity, and CAR-T cell exhaustion. We have developed a novel synthetic Notch (synNotch) receptor-based “prime-and-kill” dual antigen recognition T cell circuit. EGFRvIII, which is expressed by a subset of GBM cells, primes the T-cells to express a CAR that recognizes IL-13Rα2 and EphA2, which are broadly expressed in GBM, thereby eradicating GBM cells expressing either EphA2 or IL-13Rα2 (E-SYNC T-cells). We developed a Phase I clinical trial to evaluate the safety of intravenously infused E-SYNC T-cells. Methods: The study has 2 sequential patient cohorts. Cohort 1 is a 2-level dose-escalation cohort, targeting newly diagnosed patients with EGFRvIII-mutant, MGMT-unmethylated GBM. The E-SYNC cells are manufactured by ex vivo transduction of autologous T-cells with a lentiviral E-SYNC vector, and then intravenously infused after lymphodepleting chemotherapy. Cohort 2 will be a tissue analysis cohort. At the time of recurrence, participants will receive an infusion of E-SYNC T-cells at the maximum tolerated/recommended dose from Cohort 1 prior to a planned clinical surgical resection. The primary objective is safety; secondary objectives are feasibility and (for Cohort 2 only) to determine the priming status of E-SYNC T-cells in the GBM tissues and peripheral blood. We are currently enrolling patients in cohort 1. Results: Autologous E-SYNC cells have been successfully manufactured for 9 patients. To date, we have treated six patients at dose level 1 (DL1: 5x107 CAR+ cells) and two patients at dose level 2 (DL2: 1.5x108CAR+ cells), with no serious adverse events or dose-limiting toxicities. Two of six patients at DL1 remain progression-free for 20 months and 15 months since the initial resection. Digital PCR-based evaluation of the peripheral blood demonstrated the post-infusion persistence of E-SYNC T-cells for at least 40 weeks. Serum analyses show post-infusion increases in CCL2, CCL5, CXCL9, and CCL22. In two patients who recurred within two months following the infusion, the recurrent tumor tissues showed the loss of EGFRvIII, despite the infiltration of E-SYNC cells. Conclusions: We have safely treated eight patients with EGFRvIII+ GBM with autologous E-SYNC cells, with no significant toxicity thus far. Considering the poor prognosis of MGMT-unmethylated GBM patients, the progression-free survival in two patients is promising. To overcome the loss of EGFRvIII as the priming signal, we are also developing a second-generation synNotch-CAR study using Brevican, a brain-specific extracellular matrix protein, to induce the CAR expression (Simic, Watchmaker et al., Science, 386, 2024). Citation Format: Payal B. Watchmaker, Jennifer L. Clarke, Ricardo Almeida, Akane Yamamichi, Abigail Hansen, Harika T. Gopi, Karishma Kumar-Wessel, Megna Reddy, David Y. Oh, Jacob S. Young, Nicholas Butowski, Nancy A. Oberheim Bush, Jennie W. Taylor, John de Groot, Joanna Phillips, Annette M. Molinaro, Brain R. Shy, Wendell Lim, Hideho Okada. First-in-human trial of E-SYNC T-cells, an autologous anti-EGFRvIII SynNotch receptor-induced anti-EphA2/IL13Ra2 CAR T-cells, in adult patients with EGFRvIII+ glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT042.

Cell-based immunotherapies have emerged as promising strategies for brain tumors, offering the potential for targeted and durable antitumor responses. However, their efficacy has been limited by challenges unique to the central nervous system, including suboptimal delivery routes and an immunosuppressive tumor microenvironment that impairs cell function. Focused ultrasound (FUS) is a noninvasive technology that, when combined with intravenously administered microbubbles, can transiently and reversibly increase blood-brain barrier permeability. FUS has improved drug delivery to brain tumors in clinical trials and offers compelling opportunities to enhance trafficking, activation, and control of therapeutic cells. Despite this potential, critical questions remain regarding the timing and sequencing of FUS with cell therapies, the impact of FUS on the tumor and neuroimmune microenvironments, strategies to mitigate acute and delayed toxicities, and methods to tune potency to maximize tumor specificity while minimizing bystander tissue injury. To address these challenges, the Focused Ultrasound Foundation convened a multidisciplinary roundtable in March 2025. Experts in neuro-oncology, neuroimmunology, cell therapy, neurosurgery, and FUS participated. Discussions focused on cell delivery routes, pharmacokinetics and blood-brain barrier opening, tumor microenvironment and CNS inflammation, FUS-induced immune modulation, clinical trial design, and approaches to safety monitoring and cell control. In this review, we summarize the discussions and key messages from the roundtable, which may serve as a foundation for advancing FUS-enhanced cell therapy for brain tumors in a collaborative manner.

Abstract Background: Glioblastoma recurrence is inevitable despite aggressive surgical resection of contrast enhancing (CE) tumor. Unlike the deep molecular characterization of CE glioblastoma, unresected infiltrating tumor, representing minimal residual disease (MRD) has not been well profiled. Increasingly, clinical trials are being conducted in the MRD setting for glioblastoma patients, necessitating understanding of unresected infiltrating tumor for targeted therapeutic development. Methods: Visium HD spatial transcriptomics was used to profile a cohort of newly diagnosed, treatment-naïve glioblastoma patients that underwent supramaximal resection, with both core and infiltrating in situ components. Spatial profiles generated expression signatures of infiltrative and CE tumor. For in silico prediction of therapeutics targeting the MRD, expression signatures of infiltrative and CE tumor were compared with drug perturbation signatures from the NIH L1000 database using the sRGES method to predict reversal of disease expression patterns. IC50 data from human cell lines were aggregated from the Genomics of Drug Sensitivity in Cancer or individual study data while blood-brain barrier (BBB) penetrance was predicted using the CNS-MPO approach. Findings: Infiltrative tumor expression profiles were enriched for genes corresponding to neural and oligodendrocyte progenitor like cells. In contrast CE glioblastoma displayed mesenchymal and astrocytic programs, suggesting spatial concentration of glioblastoma states within MRD and CE tumor. For CE glioblastoma, proteasome inhibitors and glucocorticoid receptor agonists were predicted to have the highest antitumor activity. In contrast, histone deacetylase inhibitors (HDACi) were highly ranked for MRD while exhibiting low predicted efficacy in CE tumor. Synergy analysis of drug candidates provided multiple dual treatment options for both the CE and MRD contexts. Conclusions: Cumulatively, these data indicate that the resected tumor does not reflect the MRD state, providing clarity on why targeted therapeutics for glioblastoma have not been particularly successful. Spatial profiling of the MRD demonstrates vulnerability to unique drug targets, which if utilized in the correct setting could confer greater survival benefit. Citation Format: Harrshavasan Congivaram, Shashwat Tripathi, Mateo Gomez, Katy McCortney, Ching Man Wai, Ruochen Du, Thomas K. Sears, Jianzhong Zhang, Daniel J. Brat, Craig M. Horbinski, Mark W. Youngblood, Jared T. Ahrendsen, Adam M. Sonabend, Stephen T. Magill, Matthew C. Tate, Maciej S. Lesniak, Sean Sachdev, Timothy Sita, Priya Kumthekar, Karan Dixit, Robin Buerki, Ditte Primdahl, Mustafa Khasraw, John de Groot, David A. Reardon, Rimas V. Lukas, Roger Stupp, Amy B. Heimberger. In silico screening of therapeutics candidates targeting minimal residual disease in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2496.

Cognitive impairment is common in primary brain tumors (PBT), with evidence for cognitive rehabilitation (CR), although with few studies of self-sustaining clinical programs. We conducted a retrospective analysis of a CR program to understand treatment engagement and goal attainment by cognitive and clinical characteristics in those referred with subjective complaints. We retrospectively reviewed records of adults with stable PBT and cognitive complaints referred to neuropsychological evaluation and +/- CR with cognitive and emotional assessments completed upon referral. Impairment type was defined as: absolute ≥ -1.5 SD on ≥ 2 tests, or relative ≥ -1.5 from premorbid intellect on ≥ 2 tests. SMART (Specific, Measurable, Achievable, Relevant, Time-bound) goal (partial or full) attainment was tracked with CR engagement defined as completing ≥ 2 sessions. Chi-square was used to evaluate associations with a two-sided <0.05 p-value threshold. We identified 177 patients with PBT referred between May 2018 to May 2022. The mean age was 50 (SD=13.5); 76% had ≥16 years of education; median time since diagnosis was 35.2 months (IQR=85.4); 14% glioblastoma; 56% IDH-mutant; 34% grade 2; 74% prior radiotherapy; and 62% not working. Among those referred, 21% demonstrated relative and 73% absolute impairment (73% with impaired processing speed, 71% executive functioning, and 63% verbal learning). Of those referred and recommended, 124 (87%) engaged in CR (median 8 visits, IQR=9); 57% fully and 25% partially met their goals. CR engagement and goal achievement were not significantly associated with cognitive and emotional findings upon referral or other clinical factors (all p≥0.05). We confirm that subjective complaints in PBT often have objective impairments and underscore the value of premorbid estimates, especially in highly educated patients. Our data demonstrates high rates of CR engagement when offered. Additional study is warranted to understand treatment response, durability, and the mechanism of action.

Purpose While immunotherapy has transformed treatment in multiple solid tumors, its efficacy in high-grade glioma remains limited. Understanding the molecular and clinical factors that influence glioma’s response to immunotherapy is essential to improving outcomes. Methods We identified patients with recurrent glioblastoma or astrocytoma, IDH-mutant grade 4, who had been treated with checkpoint inhibitor (CPI), virus therapy, or cell therapy and determined the association between their molecular, clinical, and demographic characteristics and survival outcomes. Results We identified 66 patients, 57 glioblastoma and 9 astrocytoma, IDH-mutant grade 4; 38 were treated with CPI, 22 with virus therapy, and 6 with cell therapy. PIK3CA mutation was associated with shorter PFS and OS (p = 0.022, 0.073, respectively) among all patients and a shorter OS among CPI-treated patients (p = 0.004). Tumor tissue without the mutation had less PD-1 expression in CD3+/CD8 + T cells. In CPI-treated patients, IDH1/2 mutation was associated with a shorter OS (p = 0.002), and mutations in RB1 and TERT promoter were associated with a shorter PFS (p-value = 0.00056, 0.022, respectively). Length of CPI therapy of more than 6 months was associated with increased PFS and OS (p = 0.048, 0.062, respectively), while steroid use at baseline was associated with a shorter OS (p = 0.00023). Multifocal disease was associated with shorter PFS and OS durations (p = 0.0017, 0.0013, respectively) among all patients. Conclusions In high-grade glioma, PIK3CA, IDH1/2, RB1, and TERT promoter mutations may be associated with a poor response to immunotherapy. Our results may provide the rationale for clinical trials combining PI3K and IDH inhibitors with CPI in high-grade glioma.

GBM AGILE (Glioblastoma Adaptive, Global, Innovative Learning Environment) is a multi-arm, international, seamless Phase 2/3 response adaptive randomization (RAR) platform trial designed to efficiently identify investigational therapies that improve overall survival and confirm efficacious therapies and biomarker signatures to support registration. GBM AGILE is a collaboration among academic investigators, patient organizations, and industry to support new drug applications for newly diagnosed and recurrent glioblastoma. The primary objective of GBM AGILE is to identify therapies that improve overall survival in patients with newly diagnosed or recurrent glioblastoma. Operating under a Master Protocol, GBM AGILE allows multiple drugs from different companies to be evaluated simultaneously and/or over time against a common control. Investigational therapies are added as information about promising drugs is identified, while other therapies are removed as they complete evaluation. RAR is used within subtypes of the disease to assign participants to investigational arms based on their performance. GBM AGILE has screened over 2300 patients and enrollment continues to be robust. In addition to the efficient evaluation of investigational arms, a goal of GBM AGILE is to expand knowledge of glioblastoma to support advancements in treatment using the data collected within the trial (learning environment). Over 7 million data points are currently available for inclusion in the development of a longitudinal model. Such a model may be able to inform randomization by providing earlier and continuous information regarding patient and arm performance. In addition, serial magnetic resonance imaging scans and biospecimens from baseline through patient progression are being collected for further analysis. An initial 500 baseline tissue samples are being characterized by genome sequencing and transcriptome analysis. NCT number: NCT03970447.

Background:Cognitive impairments are common in lower-grade gliomas (grades 1-3), but treatment options are limited. Tele-cognitive rehabilitation offers a potential solution. We conducted an interim pilot study to assess the feasibility, satisfaction, and early efficacy of tele-cognitive rehabilitation. Methods:We enrolled adults with stable LrGG (≥6 months posttreatment) who had subjective and objective cognitive impairments (>1 SD below-average in ≥2 domains). Participants received 3 months of individual Goal Management Training (GMT), app-based ReMind, or texting. Cognition and patient-reported outcomes were assessed at baseline (T1), postintervention (T2), and 9 months postbaseline (T3). We assessed enrollment, adherence, and satisfaction. Adherence was defined as ≥80% of participants completing ≥80% of the protocol; satisfaction as ≥6/7 for GMT and texting, and ≥4/5 for ReMind on a self-report Likert question. We used ANOVA, reliable change indices, and qualitative analytics. Results:Thirty-nine participants were eligible and 33 prospectively enrolled for the study; an 85% enrollment (17-GMT, 8-ReMind, 8-texting; 46.8 median age, 64.8 months from diagnosis, 55% had astrocytoma, and 76% had prior radiotherapy). Eighty-two percent of GMT (adequate), 100% of texting (adequate), and for ReMind 33% of retraining and 50% of compensation (inadequate) completed ≥80% of the protocol. GMT (mean: 6.75/7) and ReMind (mean: 4.5/5) satisfaction were adequate, and texting (mean: 4.5/7) was inadequate. Working memory improved from T1-to-T2 (P = .02, η² = 0.32) in 26% of the GMT group. Conclusions:GMT demonstrates adequate feasibility, satisfaction, and may yield improvements in working memory, while texting and ReMind had challenges in acceptability or feasibility. Individual (tele) GMT warrants further investigation in LrGG.

The infiltrative and diffuse nature of gliomas makes complete resection unfeasible. Unfortunately, regions of brain parenchyma with residual, infiltrative tumor are protected by the blood-brain barrier (BBB), making systemic chemotherapies, small-molecule inhibitors, and immunotherapies of limited efficacy. Low-frequency focused ultrasound (FUS) in combination with intravascular microbubbles can be used to disrupt the BBB transiently and selectively within the tumor and peritumoral region. This technology can be leveraged either to improve access for a wide variety of therapeutic agents to the tumor-infiltrated parenchyma or to allow for the release of tumor biomarkers into the systemic circulation for disease monitoring. Furthermore, high-frequency FUS has the potential to serve as an ablative treatment option. This review aimed to summarize the benefits of FUS in the treatment of gliomas.

While checkpoint inhibitor therapy (CPI) has transformed treatment in multiple solid tumors, its efficacy in glioblastoma (GBM) remains limited. Understanding the molecular and clinical factors that influence glioblastoma’s response to CPI is essential to improving outcomes. We identified patients with recurrent GBM, who had been treated with CPI and determined the association between their molecular, clinical, and demographic characteristics and survival outcomes. We identified 35 patients with recurrent GBM treated with CPI. PIK3CA mutation was associated with a statistically significant shorter OS duration, calculated from CPI initiation (p-value = 0.014). Tumor tissue without the mutation had less PD-1 expression in CD3+/CD8 + T cells. RB1 and TERT promoter mutations were associated with shorter PFS durations (p-value = 0.009, 0.053, respectively). Length of CPI therapy of more than 6 months was associated with increased PFS and OS (p-value = 0.069, 0.088, respectively), while steroid use at baseline was associated with a shorter OS (p-value = 0.0016). Multifocal disease was associated with shorter PFS and OS durations (p-value = 0.0011, 0.0015, respectively) among all patients. In glioblastoma, PIK3CA, RB1, TERT promoter mutations, steroid use prior to start of CPI, and multifocal disease may be associated with a poor response to CPI while increased length of CPI may be associated with improved response. Our results may provide the rationale for clinical trials combining PI3K inhibitors with CPI in glioblastoma. The small sample size and retrospective nature of the study carries selection bias and/or confounding effects and larger studies need to be done to validate these results.

The prognosis of patients with glioblastoma (GBM) remains poor despite current treatments. Targeted therapy in GBM has been the subject of intense investigation but has not been successful in clinical trials. The reasons for the failure of targeted therapy in GBM are multifold and include a lack of patient selection in trials, the failure to identify driver mutations, and poor blood-brain barrier penetration of investigational drugs. Here, we describe a case of a durable complete response in a newly diagnosed patient with GBM with leptomeningeal dissemination and PTPRZ1-MET fusion who was treated with tepotinib, a brain-penetrant MET inhibitor. This case of successful targeted therapy in a patient with GBM demonstrates that early molecular testing, identification of driver molecular alterations, and treatment with brain-penetrant small molecule inhibitors have the potential to change the outcome in select patients with GBM.

Laser interstitial thermal therapy (LITT) has emerged as a minimally invasive neurosurgical technique for achieving precise, MR-guided thermal ablation of intracranial lesions. LITT offers a viable alternative for lesions that are deep-seated or located in eloquent regions where conventional surgery poses significant risk. In adult neuro-oncology, LITT is well-established, particularly for recurrent high-grade gliomas and post-radiation metastases. In pediatric neuro-oncology, LITT has been most widely adopted for treating hypothalamic hamartomas, where it achieves high rates of seizure freedom with minimal morbidity. However, its use for oncologic control in pediatric brain tumors remains limited, with published evidence confined to retrospective series with heterogeneous tumor types. Recent studies suggest potential for LITT not only in cytoreduction but also in enhancing drug delivery via transient blood-brain barrier disruption and in promoting antitumor immunity through hyperthermia-induced immunogenic cell death. We review the principles, clinical applications, and imaging features of LITT, with a focus on pediatric brain tumors. Illustrative cases are presented, and the need for prospective, multi-center trials is emphasized to better define LITT’s therapeutic role and optimize its integration with emerging chemo- and immunotherapy strategies.

Preoperative stereotactic radiation therapy (SRT) vs postoperative SRT logistics and toxic effects provides clinically significant data on management outcomes. To determine preoperative SRT logistics and safety profile compared with postoperative in patients with brain metastases. This single-institution phase 3 randomized clinical trial included patients 18 years and older and undergoing a planned surgical resection. Patients were required to have an Eastern Cooperative Oncology Group Performance Status score of 2 or greater and be candidates for SRT within 30 days of surgical resection. Patients with radiosensitive histologies (eg, small cell lung cancer and lymphoma), brain metastasis of unknown primary, and/or radiographic evidence of leptomeningeal disease were excluded. Data were collected from December 2018 to August 2023, and data were analyzed from September 2023 to December 2024. Patients were randomized 1:1. Patients randomized to the preoperative SRT cohort underwent SRT (in 1 to 5 fractions) followed by surgical resection within 1 month of radiation therapy. Patients randomized to the postoperative SRT cohort underwent resection followed by postoperative SRT within 1 month of surgery. Outcomes reported focus on nonprimary end point analysis of the trial, including comparative toxic effect outcomes of preoperative vs postoperative SRT postprocedural events, feasibility of preoperative SRT, and radiation therapy management. Of 103 patients, 56 (54.4%) were male, and the median (range) age was 59 (26-83) years. Of 103 patients, 83 (80.6%) completed both radiation and surgery for brain metastases while in the study. Of these, 70 patients (84%) had 1 to 4 brain metastases at enrollment, 11 (13%) had 5 to 10 lesions, and 2 (2%) had more than 10 lesions. In the preoperative stereotactic radiosurgery (SRS)/SRT cohort, 45 (88%) completed both treatments compared with 38 (73%) in the postoperative SRS/SRT arm. There were no statistically significant differences between treatment groups in 30-day postoperative morbidity or postprocedural events. The median (range) time between surgery and SRT was significantly shorter in the preoperative arm (6 [0-24] days) compared with the postoperative arm (22 [12-42] days; P < .001). The median (range) time from randomization to receiving both brain-directed therapies was 10 (4-31) days in the preoperative arm compared with 32.5 (19-55) days for the postoperative arm (P < .001). In this randomized clinical trial, preoperative SRT had comparable safety to postoperative SRT and resulted in shorter time to treatment completion, potentially facilitating expedited care. ClinicalTrials.gov Identifier: NCT03741673