Neuro-oncology advances最新文献

Background: Automated brain tumor segmentation on multi-parametric magnetic resonance imaging (mpMRI) is crucial in assessing patient outcomes and remains a challenge across Sub-Saharan Africa (SSA). Since 2012, the Brain Tumor Segmentation (BraTS) Challenge has evaluated state-of-the-art artificial intelligence (AI) methods to detect, characterize, and classify tumors. However, it is unclear if these methods can generalize, and hence be widely implemented, in SSA populations. To address this, the BraTS-Africa challenge was conducted in 2023 and 2024 to evaluate population-specific AI models for automated segmentation of brain tumors on mpMRI from the region.

Methods: Preoperative T1-weighted, T1-contrast enhanced, T2-weighted, and T2-FLAIR brain MRI scans of 115 patients diagnosed with adult diffuse glioma were curated, annotated, and utilized for the Challenge. Participants were invited to develop and validate their methods. The participating teams were evaluated using weighted Dice Score Coefficient (DSC) and 95% Hausdorff Distance (HD95).

Results: In the 2023 challenge a total of 9 teams with participants from 12 countries met the submission criteria and were ranked. The 2024 challenge featured 6 teams from 7 countries. Compared to 2023, the six top ranked methods from 2024 had higher DSC (9.4%) and lower HD95 (57.21%).

Conclusions: Together, the 2023 and 2024 challenges provided a unique opportunity to include brain mpMRI glioma cases from SSA in global efforts to develop and evaluate AI methods for the detection of glioma boundaries and their quantification, where the potential of AI solutions to transform healthcare into resource-limited settings is more likely.

Background: Ischemic complications remain a significant risk indicator of morbidity after meningioma surgery. While tumor size and extent of resection (EOR) are recognized risk factors, the prognostic impact of peritumoral brain edema volume (PTBEV) is not fully established. This study investigated whether preoperative tumor volume (TV) and PTBEV independently predict postoperative ischemia and neurological morbidity.

Methods: We retrospectively investigated 152 patients who underwent resection of intracranial meningiomas from 2008 to 2023. Preoperative post-contrast T1W and Fluid-Attenuated Inversion Recovery (FLAIR) MRI were used to quantify TV and PTBEV, and postoperative DWI within 72 hours post-surgery was used to identify ischemic lesions. Volumetric segmentation was performed in 3D Slicer™ and validated by five independent reviewers. Statistical analysis included Spearman's correlation, univariate and multivariate linear regression for predictors of postoperative ischemic volume (PIV), and binary logistic regression for new neurological deficits. The P value < .05 was considered significant.

Results: Median preoperative TV was 23.1 cm³ (IQR 9.3-48.4 cm³), and PTBEV was 3.5 cm³ (IQR 0.0-28.4 cm³). Median PIV was 1.5 cm³ (IQR 0.0-5.3). PIV correlated with preoperative TV (r = 0.393, P < .001) and PTBEV (r = 0.446, P < .001). Multivariate regression identified preoperative PTBEV (P < .001), preoperative TV (P = .015), and subtotal resection (STR) vs. GTR (P = .033) as independent predictors of postoperative ischemia. Overall, 11.8% of the patients developed new neurological deficits (1.3% permanent). Ischemic volumes >2 cm³ significantly increased risk of new neurological non-cranial nerve deficits (OR = 6.667, 95% CI 1.408-31.556, P = .017).

Conclusion: Preoperative tumor and edema volumes are independent predictors of postoperative ischemia. Even modest ischemic lesions (>2 cm³) can cause clinically relevant morbidity. Volumetric biomarkers should be integrated into surgical planning, with prospective multicenter validation warranted.

Neurofibromatosis type 1 (NF1)-associated tumors typically develop in the setting of biallelic inactivation of the NF1 gene and resultant overactivation of the Ras/mitogen-activated protein kinase signaling pathway. Mitogen-activated protein kinase kinase (MEK) inhibitors target the downstream effectors of Ras and have shown promising activity for NF1-associated tumors. Several recent and ongoing clinical trials have demonstrated both the safety and efficacy of MEK inhibitors for plexiform neurofibroma (PN) and low-grade glioma, with the phase 1/2 study of selumetinib supporting the first regulatory approval of a medical therapy for PN. The relative successes of MEK inhibitors for the treatment of PN have created an exciting and hopeful era for patients, families, and clinicians alike providing the momentum and significant interest in expanding the use of MEK inhibitors across tumor types in NF1. Herein, we review the landscape of past and present clinical trials and supporting evidence for the use of MEK inhibitors in NF1-associated tumors.

Background: In preclinical models, tumor treating fields (TTFields) therapy promotes homologous repair deficiency (HRD), inducing potential sensitivity to poly (ADP-ribose) polymerase (PARP) inhibition. The aim of this study was to determine whether TTFields combined with the brain-penetrant PARP inhibitor niraparib has clinical efficacy in patients with recurrent high-grade glioma (HGG).

Methods: We conducted a phase 2 trial of TTFields therapy concomitant with niraparib in patients with glioblastoma (n = 7) or IDH-mutant grade 4 astrocytoma (n = 2) that was recurrent after prior radiotherapy. Cohort A was a single-arm primary efficacy cohort with the Simon's 2-stage design. Cohort B was a surgical window-of-opportunity cohort in which TTFields were administered for 5-7 days prior to surgery and then resumed post-operatively with niraparib. The primary endpoint was disease control rate in cohort A, defined as objective response or stable disease (SD) lasting at least 16 weeks.

Results: The most common treatment-related adverse events were grade 1-2 dermatologic (scalp) toxicity in 67% of patients and grade 1-2 nausea in 67% of patients. In cohort A (n = 8), there were no objective responses, and 1 patient (12.5%) achieved SD lasting over 16 weeks. The efficacy benchmark to advance to Stage 2 was not achieved, and enrollment on Cohort A was terminated for futility. Cohort B (n = 1) was closed early due to slow accrual. In the single patient in Cohort B, TTFields-treated tumor tissue was negative for HRD.

Conclusions: The combination of niraparib and TTFields therapy for recurrent HGG was safe and well tolerated but did not demonstrate an efficacy signal.

Pilocytic astrocytoma (PA) is a benign tumor with a low risk of high-grade transformation. High-grade astrocytoma with piloid features (HGAP) is a recently recognized tumor entity that may arise de novo or from low-grade gliomas. Here, we report a patient harboring both a fourth ventricular PA and a spinal cord tumor. Methylation profiling classified the brain tumor as PA and the spinal tumor as HGAP. Both tumors shared a KIAA1549::BRAF fusion with identical DNA breakpoints, confirming a common clonal origin. The spinal tumor also showed complex chromosome copy number aberrations, including homozygous deletion of CDKN2A/B. These findings suggest additional molecular alterations associated with tumor progression within the piloid lineage. To our knowledge, this is the first report providing comprehensive, paired molecular characterization of both PA and HGAP in the same patient, offering insight into their potential evolutionary relationship.

Background: Dexamethasone (DEX) is routinely administered perioperatively to manage tumor-associated vasogenic edema in glioblastoma (GBM), yet increasing evidence suggests that corticosteroid exposure may adversely affect survival. The magnitude of this association during the initial neurosurgical phase of care remains unclear.

Methods: We performed a retrospective cohort study of patients with histologically confirmed IDH-wildtype GBM treated at a single tertiary center between 2009 and 2020. All perioperative DEX doses from admission to discharge were extracted from daily medical records. Patients were stratified based on the cumulative dose into low-dose exposure (<34 mg) and high-dose exposure (≥34 mg) groups using maximally selected rank statistics. Overall survival was analyzed using Kaplan-Meier estimates with log-rank test and multivariable Cox proportional hazards models. Adjustment variables were selected using a prespecified, causally informed framework to address confounding.

Results: A total of 420 patients were included. The majority (n = 341; 81.2%) received ≥34 mg DEX perioperatively. Median OS was 13.6 months in the high-dose group and 15.0 months in the low-dose group, with significantly shorter survival observed in the high-dose cohort (log-rank P = .0103). In the adjusted Cox model, cumulative DEX ≥ 34 mg remained independently associated with increased mortality (HR: 1.40, 95% CI: 1.07-1.83; P = .013).

Conclusions: Higher perioperative DEX doses were independently associated with shorter overall survival in GBM patients, emphasizing the need for judicious perioperative use with prompt tapering. Prospective studies are warranted to guide evidence-based DEX management in GBM care.

While CDKN2A loss is classically associated with cell cycle deregulation through the p16-Cdk4-Rb axis, our findings suggest an additional layer of metabolic vulnerability arising from altered NAD⁺ homeostasis in CDKN2A-deleted glioblastoma, revealing a metabolic-genetic interface for rationally revisiting NAD⁺ targeting strategies, moving beyond the broad inhibition approaches.

Intracranial germ cell tumors (GCTs) primarily affect children and young adults, with favorable outcomes through r adiotherapy and chemotherapy. However, radiation-induced secondary malignancies pose significant concerns in long-term survivors, particularly regarding optimal treatment strategies. We present a case of a 12-year-old Asian male initially diagnosed with pineal region GCTs who developed radiation-induced glioblastoma after 5 years of tumor-free survival. The secondary tumor was successfully treated with chemoradiotherapy combined with Tumor Treating Fields (TTFields), resulting in tumor regression and survival exceeding 3 years. This case demonstrates the potential efficacy of TTFields combined with chemoradiotherapy in treating radiation-induced glioblastoma in young patients and highlights the importance of long-term surveil-lance in pediatric tumor patients.

Background: Adult IDH-mutant brainstem gliomas (BSGs) are rare and appear molecularly distinct from H3K27-altered diffuse midline gliomas. We aimed to provide a comprehensive characterization by integrating an institutional cohort with a pooled individual-patient analysis.

Methods: Adults with IDH-mutant BSGs diagnosed at our institution were identified. A PRISMA-guided search of PubMed and Scopus captured additional cases. Individual-level demographic, radiographic, molecular, treatment, and outcome data were abstracted. Kaplan-Meier and log-rank testing evaluated survival associations with age, sex, WHO grade, surgery, chemoradiation, IDH variant, MGMT methylation, ATRX status, and location.

Results: Eighty-four patients were analyzed (n = 7 institutional, n = 77 literature-derived). Mean age was 37.8 years; 68.6% male. Most tumors involved the pons/medulla (90.4% astrocytomas; 68.7% WHO grade 2). Among evaluable cases, MGMT methylation was present in 47.5%, ATRX loss in 53.2%, and TP53 mutation in 84.3%. Non-canonical IDH variants accounted for 45.3% of cases. Median overall survival (OS) was 77.3 months. In multivariate analysis, non-canonical IDH variants independently predicted improved OS (HR = 0.37, P = .012), while surgical resection showed a strong clinical trend toward improved OS (HR = 0.48, P = .073). Chi-squared analysis confirmed no significant difference in high-grade tumor distribution between resection and biopsy groups (P = .52), suggesting the trend was not driven by selection bias.

Conclusions: Adult IDH-mutant BSGs represent a clinically meaningful subgroup with outcomes more favorable than H3K27-altered gliomas but shorter than supratentorial IDH-mutant gliomas. Their recurrent molecular features, including frequent non-canonical IDH variants, warrant study in larger cohorts to clarify biological significance, refine prognostication, and inform the potential role of IDH-targeted therapies.