Journal of Neuro-Oncology最新文献

Background: Whole brain radiotherapy (WBRT) is increasingly being replaced by high precision multimodality treatment including stereotactic radiotherapy (SRT) in patients with ≥ 4 brain metastases (BMs). The implications of this trend on survival rates are uncertain. Our study examines the time trends for survival rates of patients treated with radiotherapy for brain metastases during this era of shifting treatment paradigms.

Methods: Patients with newly diagnosed BMs treated with SRT or WBRT between 2010 and 2023 were included, regardless of the number of brain metastases or the primary malignancy. Patients were excluded if they had previously undergone cranial radiotherapy. Differences in survival between treatment years were evaluated using Log-rank tests. A P value of ≤ 0.05 (two-sided) was considered statistically significant.

Results: A total of 1106 patients were included for analysis. Of these, 832 (75%) were treated with SRT, while 274 (25%) were treated with WBRT. The median number of BMs was 2 (IQR 1-5), while 367 (33%) patients had ≥ 4 BMs. The proportion of patients with ≥ 4 BMs who were treated with linear accelerator-based SRT instead of WBRT increased over time: 2010-2014: 9 (11%); 2015-2019: 52 (31%); 2020-2023: 80 (68%). An improvement in survival rates of patients with ≥ 4 BMs was observed over time (median survival 2010-2014: 5 months; 2015-2019: 6 months; 2020-2023: 7 months, P < 0.001).

Conclusion: In patients treated for multiple (≥ 4) BMs, survival increased when radiotherapy modality shifted from WBRT to high precision multimodality treatment including SRT, resection, and systemic therapy.

Introduction: Cerebellar glioblastoma (cGBM) is a rare subtype, comprising of < 1% of patients with GBMs. This study sought to identify predictors of survival for patients with cGBM through an individual patient data (IPD) meta-analysis, focusing on the impact of chemoradiotherapy (CRT) and extent of resection (EOR).

Methods: Following PRISMA-IPD guidelines, we conducted a systematic review and Individual Patient Data (IPD) meta-analysis of 13 retrospective studies (113 adults) with IDH-wildtype cerebellar glioblastoma. Variables included demographics, tumor location, KPS, MGMT, TP53, extent of resection (GTR, STR, PR, biopsy), and CRT. Kaplan-Meier estimated OS and PFS; unadjusted and adjusted Cox models assessed predictors. Hazard ratios for CRT vs. monotherapy and GTR vs. incomplete resection were pooled in a two-stage random-effects model (Hartung-Knapp). Analyses used R (v4.4.2) and JMP Pro 17.

Results: Mean age was 54.9 years; 64% were male. GTR was performed in 37%, PR in 43%, STR in 11%, and biopsy in 10%. CRT was associated with improved OS (18 vs. 7 months; p = 0.02) and PFS (12 vs. 2.5 months; p = 0.0205) compared to monotherapy on Kaplan-Meier analysis. Two-stage IPD meta-analysis showed a 72% reduced risk of death with CRT (HR 0.28; 95% CI: 0.15-0.51; p = 0.0119), with similar significance in one-stage unadjusted Cox models (HR 0.49; 95% CI: 0.26-0.91; p = 0.0233). EOR comparisons were non-significant in meta-analyses, though GTR vs. biopsy showed early separation on Wilcoxon testing (p = 0.0422).

Conclusion: In this pooled IPD meta-analysis of cGBM, the use of CRT remained the only consistent and independent predictor of improved survival. GTR conferred a survival advantage over biopsy, likely reflecting the clinical benefit of debulking, however its advantage over subtotal resection was not statistically significant. These findings reinforce CRT as the maintstay of treatment highlighting the need for individualized strategies in cGBM. In selected cGBM patients, gross total surgical resection and adjuvant chemo-RT result in overall survival outcomes comparable with supratentorial GBM.

Clinical trial number: Not applicable.

Background: Diffuse midline gliomas, including diffuse intrinsic pontine gliomas, represent one of the most aggressive pediatric malignancies in the central nervous system with a uniformly poor prognosis. They can be consistently identified by mutations in histone H3 K27M, which are associated with aggressive tumor biology, marked resistance to therapies, and abysmal survival. The current review critically assesses the existing application of immunotherapeutic modalities in DMGs, emphasizing biological hurdles in efficacy, translation methodologies, and prospects in attaining sustained responses.

Methods: We examined preclinical and early clinical studies in DMGs for immune therapies such as peptide vaccines against H3K27M antigens, chimeric antigen receptor T-cell therapies, immune checkpoint modulation, and radioimmunotherapy. Current developments in the interface of cancer neuroscience and tumor interaction with neurons were incorporated in a manner relevant to immune suppression in the microenvironment of DMG. Although these tumors have traditionally shown poor immune reactivity because of low tumor mutational burden, immune-privileged sites, and a strongly suppressive tumor microenvironment, a variety of different immune therapeutic approaches have shown promising early efficacy. Of particular interest are neoantigen-targeted vaccines and CAR T-cell therapy using surface antigens. Preliminary findings suggest an important role for neuron-glioma synaptic and paracrine signaling in mediating tumor progression and immune evasion.

Conclusions: Immunotherapy for DMGs is moving from a conceptual state to a translational reality. A better understanding of the realm of tumor immune-neural crosstalk, combination therapies, and immune biology in pediatric patients will be critical in addressing resistance and providing durable control for these aggressive malignancies.

Background: Malignant glioma patients face unique end-of-life (EOL) challenges due to their aggressive disease course and early neurocognitive decline. This study aimed to compare EOL patterns between patients with malignant glioma and those with solid tumors referred for palliative care (PC).

Methods: We conducted a retrospective cohort study of adults with malignant glioma or five major solid tumors (lung, colorectal, gastric, liver, and pancreato-biliary) who received PC consultation at a South Korean tertiary hospital (2018-2022). Clinical data were linked to the National Health Insurance Service database. Outcomes included documentation of advance care planning (ACP) elements, healthcare utilization, and place of death, which were analyzed using multivariable regression.

Results: Compared with 4,283 individuals with solid tumors, those with malignant glioma (n = 229) were younger and referred to PC earlier. ACP documentation was substantially lower (20.1% vs. 58.0%; aOR, 0.13; 95% CI, 0.09-0.19), and only 21.4% of life-sustaining treatment decisions were documented as patient-determined versus 67.1% in solid tumors (aOR, 0.07; 95% CI, 0.04-0.12). Malignant glioma was also associated with fewer emergency visits (29.3% vs. 48.7%) and less chemotherapy (29.7% vs. 42.0%) but lower hospice use (62.0% vs. 73.1%; aOR, 0.57; 95% CI, 0.43-0.77). Medical costs were higher six months before death but lower in the final month among patients with malignant glioma compared with those with solid tumors. Death occurred more often in nursing care hospitals (20.5% vs. 6.8%, p < 0.0001) or at home/non-hospital settings (15.3% vs. 10.0%, p = 0.0106).

Conclusion: In this single-center cohort, malignant glioma patients were less likely to have documented ACP elements and more likely to die in nursing hospitals than those with solid tumors. Early ACP and tailored palliative strategies are essential.