Neuro-oncology advances最新文献

Background: High-grade gliomas (HGGs) require ongoing imaging to guide treatment, traditionally relying on labor-intensive and variable manual MRI measurements. While FDA-cleared artificial intelligence (AI) tools offer automated tumor volume segmentation, their clinical utility in decision-making remains understudied. This study assesses the utility and limitations of an FDA-cleared AI-based tool across public and institutional datasets, comparing its output with multidisciplinary tumor board (MDTB) assessments.

Methods: We applied the FDA-cleared, AI-based tool Neosoma HGG to quantify tumor volumes in 214 subjects from public datasets and 49 from an institutional cohort. AI-derived volumes were compared to expert manual and other AI-based measurements. Therapeutic response assessments using RANO criteria were evaluated against MDTB diagnoses. Segmentation times were analyzed using mixed-model regression.

Results: We analyzed 1648 MRI sequences of 95 HGG patients across three datasets. Contrast-enhancing (CE) tumor volumes were consistent across AI platforms, and Neosoma HGG significantly reduced segmentation time (pre-operative: 210.5s, post-operative: 179s vs. 15 s, P < .0001). AI-informed disease state assessments showed an overall moderate agreement with MDTB diagnoses for progressive disease (k = 0.45, P < .00001). Key discrepancies arose from limitation of Neosoma HGG in distinguishing pseudo-progression from tumor progression. T2-FLAIR-derived volumes varied significantly between AI platforms (P < .001), with discordances largely due to over-segmentation beyond the tumor region.

Conclusion: AI-based volumetric segmentation has the potential to improve efficiency and standardization in monitoring HGG, especially for CE tumor burden. However, moderate concordance with MDTB assessments and difficulties with FLAIR imaging underscore its current limitations. AI should serve as a clinical decision support tool, with further refinement needed to improve specificity and integrate multimodal imaging data.

Background: Immune checkpoint blockade (ICB) therapy has shown limited benefit in recurrent high-grade glioma (HGG), in part due to an immunosuppressive tumor microenvironment. Emotional distress (ED) is known to alter immune regulation, yet its role in shaping the response to ICB in glioma remains unexplored. We aimed to determine the association between pre-treatment ED and ICB efficacy in recurrent HGG (rHGG) and to explore the underlying mechanism using tumor in situ fluid circulating tumor DNA (TISF-ctDNA).

Methods: We prospectively enrolled 75 rHGG patients receiving tislelizumab, bevacizumab, and temozolomide. ED was evaluated using PHQ-9 and GAD-7 before undergoing ICB treatment. Clinical outcomes were compared between ED and No ED groups. TISF-ctDNA sequencing and immunohistochemical staining of tumor tissues were performed to identify pathway alterations and immune markers.

Results: Compared to No ED patients, ED patients had significantly shorter overall survival (15.8 vs. 32.3 months; HR = 2.40, P = .006) and progression-free survival (3.4 vs. 7.8 months; P = .049), along with lower objective response (10.7% vs. 48.5%, P = .002) and clinical benefit rates (39.3% vs. 69.7%, P = .017). TISF-ctDNA analysis revealed enrichment of AXON guidance, cAMP signaling, and HPV-related pathways in ED patients. ED was also associated with elevated systemic inflammatory markers (NLR, MLR, PLR; P < .05). IHC showed decreased infiltrating immune cells in tumors from ED patients.

Conclusions: Pretreatment ED is associated with impaired ICB efficacy in rHGG, potentially mediated by altered tumor signaling and reduced intratumoral immune cell infiltration. Psychological screening may enhance personalized immunotherapy strategies.

The evolution of amyloid PET in Alzheimer's disease illustrates the potential path of amino acid PET in neuro-oncology. Initially seen as of limited value, amyloid PET ultimately enhanced diagnostic accuracy, guided management, and became central once therapies demonstrated PET-measured efficacy. Amino acid PET for CNS tumors is at a similar turning point. It refines diagnosis, distinguishes progression from treatment effects, and supports treatment planning. As demand grows and tracer access improves, amino acid PET could follow amyloid PET's trajectory: emerging as a key tool in precision medicine and clinical management and as a surrogate endpoint in therapeutic trials.

Background: Adults with neurofibromatosis type 1 and plexiform neurofibroma (NF1-PN) experience multiple clinical symptoms and diverse manifestations, which place a burden on patients and impact quality of life. This qualitative study aimed to improve understanding of disease burden, healthcare experience, and unmet needs of adults with NF1-PN in the United States, from patient and caregiver perspectives.

Methods: Telephone interviews were conducted with adults who had a diagnosis of NF1-PN, or with caregivers, focusing on patient background, diagnosis, interactions with healthcare professionals, disease and symptom management, transition of care, and unmet needs.

Results: The study included 11 adult patients with NF1-PN and 2 caregivers; 85% of patients were diagnosed in childhood. Patients lived with multiple conditions associated with NF1, including pain disorders, psychiatric disorders, and chronic migraines. NF1-PN impacted daily living, work, school, relationships, and mental and emotional health. Most patients (82%) transitioned from pediatric to adult care, although there was variability in the transition experience. Some dropped out of care (23%) due to various factors, including time constraints, physician location, financial insecurity, lack of insurance, and perception of no available treatments/cure. Medical management primarily comprised medications to relieve symptoms associated with NF1 manifestations. Respondents identified a need to be more informed about their care. Improved treatment options for NF1-PN are desired, particularly medications that stop or slow PN growth.

Conclusions: The study demonstrated that NF1-PN has a profound impact on adult patients' lives. Several unmet needs exist for the adult population, including medications to treat the PN and its associated symptoms.

Background: Accurate glioma diagnosis relies on tissue biopsy, which is often challenging. Liquid biopsy offers an alternative, but single-component circulating free DNA (cfDNA) or circulating free RNA (cfRNA) approaches have limited comprehensiveness. We developed and validated GlioKit, a platform for simultaneous cfDNA and cfRNA extraction from cerebrospinal fluid (CSF) to enhance diagnostic coverage, and evaluated its accuracy by correlating CSF-derived molecular profiles with tumor characteristics.

Methods: We retrospectively analyzed 71 patients from the China Glioma Liquid Biopsy MultiOmics Atlas (C-Glioma) database, including 31 GBM, 36 IDH-mutant gliomas, and 4 diffuse midline gliomas (DMGs). Using GlioKit, we simultaneously extracted and analyzed CSF cfDNA and cfRNA, targeting 6 mutations (IDH1, IDH2, H3F3A, HIST1H3B, TERT, BRAF) and 2 fusions (EGFR, MET). Concordance between CSF-derived mutations and matched tumor tissue features was assessed overall and stratified by CSF collection method (lumbar puncture, surgery, or Ommaya reservoir).

Results: Among 71 glioma CSF samples, cfDNA mutations were detected in 55 (77%), cfRNA in 15 of 44 (34%). Overall, cfDNA-tumor concordance was 89%, and cfRNA was 73%. Subgroup analysis revealed cfDNA detection rates of 33/41 (surgery), 11/15 (Ommaya), and 11/15 (lumbar puncture); cfRNA detection rates were 5/25, 6/11, and 4/8, respectively. Corresponding concordance rates were cfDNA-30/33 (surgery), 10/11 (Ommaya), and 9/11 (lumbar puncture); cfRNA-4/5, 5/6, and 2/4.

Conclusions: Cerebrospinal fluid-derived cfDNA and cfRNA variations closely align with tumor genomic alterations, validating CSF as a minimally invasive source for glioma molecular subtyping. GlioKit has potential for glioma diagnosis and therapy planning.

Background: This postmarketing surveillance assessed the real-world safety and effectiveness of selumetinib in pediatric patients with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PN) in Japan.

Methods: The surveillance was initiated on November 16, 2022, the launch date of selumetinib in pediatric indication in Japan. All patients treated with selumetinib were eligible for enrollment. The observation period was set to 3 years from drug initiation (data cutoff for 1-year analysis: October 9, 2024). Patient characteristics and safety and effectiveness data were captured using case report forms.

Results: In total, 52 patients were included in the analysis (median [range] age, 13.0 [5-20] years; age <19 years, 49 [94.2%] patients; female, 28 [53.8%] patients; dermatological, neurological, and bone manifestations [DNB] classification stage 5, 30 [57.7%] patients; median disease duration [N = 49], 118.0 months). The median treatment duration was 52.1 weeks, and 46 (88.5%) patients were on selumetinib treatment at 1 year. Adverse drug reactions (ADRs) and serious ADRs were observed in 46 (88.5%) and 9 (17.3%) patients, respectively. The most common ADRs were diarrhoea (28.8%), dermatitis acneiform (26.9%), blood creatine phosphokinase increased (23.1%), and paronychia (19.2%). No fatal ADRs were reported. The median time to the first onset of any ADR was 0.492 months. Investigator's assessment, target PN size on imaging, patient's general self-assessment, and performance status generally indicated the effectiveness of selumetinib.

Conclusions: The safety profile of selumetinib was generally consistent with the findings of the phase 2 SPRINT trial and Japanese phase 1 trial. No new safety concerns were identified.

Background: Meningiomas affect up to 80% of patients with NF2-related schwannomatosis during their lifetime. They are managed by active monitoring, surgery, and stereotactic radiosurgery (SRS). This paper aims to synthesize the existing data, evaluate outcomes, and inform future trial design.

Methods: Systematic review and meta-analysis conducted using the PRISMA framework. Six databases were searched from inception to September 2025. Patient demographics, intervention data, and outcomes were collected and pooled analyses performed. Studies were appraised using the NIH quality assessment tool.

Results: Fifteen studies with 937 patients and 3637 meningiomas were included. The pooled proportion of female patients was 59.6% (95% confidence interval [CI]: 55.4-63.7). A total of 2082 tumors were monitored (mean follow-up 5.55-9.18 years) with a weighted mean growth rate of 0.508 cm³/year (95% CI: 0.0244-0.992) (available in 748 meningiomas). The weighted pooled proportion of monitored patients who developed de novo meningiomas across 3 studies was 24.6% (95% CI: 2.73-58.7). Surgical resection was performed in 203 meningiomas, with an under-reported postintervention follow-up and a pooled risk of tumor recurrence of 12.5% (95% CI: 7.98-17.9). Stereotactic radiosurgery was used in 665 meningiomas. The pooled risk of treated tumor progression was 6.29% (95% CI: 4.57-8.25), median follow-up 3.58 to 9.25 years. The pooled local control rates at 3 and 5 years were 97.1% (95% CI: 94.7-98.8) and 91.2% (95% CI: 88.4-93.6), respectively.

Conclusion: NF2-associated meningiomas are challenging to manage due to their multiplicity, high growth rate, and World Health Organization grade. Active monitoring, surgery, and SRS are viable treatment options. Here, we evaluate existing outcome data to guide future trial design.

Background: Glioblastoma (GBM) is an aggressive primary brain malignancy with limited therapeutic options and poor survival outcomes. Recent real-world studies and early-phase clinical trials evaluating metformin have yielded mixed findings. This study assessed the association between post-diagnosis metformin exposure and all-cause mortality in a large population-based cohort of older adults with GBM.

Methods: A retrospective cohort study was conducted utilizing the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Adults aged ≥66 years diagnosed with GBM between 2007 and 2018 were included, excluding those with other malignancies or diagnoses made by autopsy or death certificate. Metformin exposure was modeled as a time-varying covariate, defined by the first prescription filled after diagnosis. Cox models with time-dependent covariates estimated adjusted time-varying hazard ratios (HRs) for mortality in the overall cohort and selected subgroups.

Results: Among 16,069 eligible patients, 2,850 (17.7%) were exposed to metformin after diagnosis. Over half (55.8%) died within six months. In the full cohort, metformin exposure was not associated with mortality during the first three months (HR = 1.02; 95% CI: 0.91-1.14) but was linked to increased mortality between 3-9 months (HR = 1.22; 95% CI: 1.10-1.34) and beyond nine months (HR = 1.20; 95% CI: 1.09-1.14). A similar pattern was consistent across subgroup analyses.

Conclusions: In this large cohort of older adults with GBM, metformin exposure after diagnosis was not associated with reduced mortality and was linked to increased mortality beyond the initial three months. These findings underscore the need for prospective studies and randomized controlled trials to clarify metformin's role in GBM outcomes.

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.

Background: Aggressive meningiomas often display chromosomal abnormalities disrupting more than 20% of the genome, but the mechanisms that allow meningioma cells to thrive nevertheless are unknown.

Methods: This study used orthogonal small-molecule screens, gene expression analyses, DNA-binding analyses, epigenetic histone mark datasets, and orthotopic animal models to identify pathways essential for meningioma cell survival.

Results: Epigenetic buffering of proteotoxic stress by euchromatic histone methyltransferase 2 (EHMT2) enables meningioma cell survival. A high-throughput small-molecule screen and orthogonal gene expression analysis identified EHMT2 as important for meningioma growth. EHMT2 preferentially binds cis-regulatory elements affecting genes involved in protein processing in the endoplasmic reticulum (ER) in meningioma cells, and EHMT2 inhibition activates the ER stress apoptotic pathway. EHMT2 inhibition also decreases Sirtuin 1 (SirT1)-mediated activation of heat shock factor 1 (HSF1) transcriptional activity, thereby causing collapse of heat shock protein expression. The molecular chaperone and ER stress inhibitor, 4-phenylbutyric acid, abrogates meningioma cell death occurring after EHMT2 inhibition. Importantly, EHMT2 inhibition decreases meningioma growth in mice.

Conclusions: EHMT2/SirT1/HSF1-dependent mitigation of proteotoxic stress represents a promising therapeutic target in meningioma.