Journal of Neuro-Oncology最新文献

Purpose: Immune checkpoint inhibitors (ICI) have transformed cancer therapy but remain of limited efficacy in pediatric central nervous system tumors, which are characterized by low tumor mutational burden, sparse antigen presentation, and profoundly immunosuppressive microenvironments.

Content: Across pediatric trials, ICI monotherapy targeting the PD-1/PD-L1 axis has largely failed to show substantive benefits, underscoring the need for biomarker-driven patient selection and the identification of synergistic vulnerabilities. Recent high-dimensional profiling reveals that pediatric central nervous system tumors are not uniformly "immune cold." Subsets such as DNA replication-repair-deficient high-grade gliomas exhibit robust neoantigen burden and durable responses to PD-1 blockade, whereas data from other tumor subsets including some gliomas, germ cell tumors and select medulloblastomas demonstrate potential latent immune reactivity. Translational strategies are being developed to overcome barriers impacting ICI efficacy by studying resistance mechanisms, some of which are unique to central nervous system tumors. Potentially useful strategies to improve ICI efficacy in childhood brain tumors may involve exploration of early or neoadjuvant use, targeting non-traditional checkpoints as combination treatments, metabolic and genomic targeting for immune reprogramming, advanced drug-delivery approaches, studying and modulating the gut microbiota, improve toxicity management by limiting systemic steroid use, and parallel innovations redefining immunotherapy response assessment using advanced imaging and liquid biopsies.

Conclusion: We provide an overview of the current checkpoint inhibitor landscape for pediatric brain tumors, highlight barriers and summarize possible approaches that can be efficaciously explored in future clinical trials.

Purpose: The impact of long-travel distances is unknown in grade 2 glioma (G2G) patients. Here, the onco-functional outcomes following awake surgery for IDH-mutated G2G were compared between loco-regional versus international patients.

Methods: G2G patients who underwent awake connectome-guided surgery and followed ≥ 1 year postoperatively were selected, with comparison across loco-regional patients (group 1) and foreigners (group 2).

Results: This consecutive cohort comprised 284 patients (mean age: 37.4 ± 9.6 years) with seizures in 225 cases (79.2%) and a mean KPS score of 95.1 ± 6.3. The preoperative mean tumor volume was 56.1 ± 46.8cc. The postoperative mean KPS score was 94.1 ± 6.5, with 0.3% of persistent deterioration, and 214 patients resuming employment (88.8%). The mean EOR was 92.2 ± 8.3%, with a mean residual tumor volume of 5.9 ± 8.7cc. There were 162 astrocytomas (57%) and 122 oligodendrogliomas. The mean follow-up was 7.3 ± 3.9 years with a median OS > 19 years. Foreigners (n = 151) had more preoperative intractable epilepsy (p = 0.05) with a higher rate of left gliomas (p = 0.019) in insular/paralimbic location (p = 0.031), while loco-regional patients (n = 133) had more right gliomas in frontal location (p = 0.028). The EOR was similar in both groups, whereas foreigners had less supratotal resections (p = 0.034). The KPS score was better in international patients at 3 months postoperatively (p = 0.008) although there was no difference in RTW proportion and median OS (> 19 years in both groups).

Conclusion: This original series demonstrates that, although international patients undergoing awake surgery for G2G may recover more quickly with less supramarginal resections, RTW rate and OS were similar. Traveling large distances is not associated with long-term onco-functional outcomes.