The latest medical research on Neuro Oncology

Glioblastoma remains incurable despite optimal multimodal management. The interim analysis of open label, single arm INDYGO pilot trial showed actuarial 12-months progression-free survival (PFS) of 60% (median 17.1 months), actuarial 12-months overall survival (OS) of 80% (median 23.1 months). We report updated, exploratory analyses of OS, PFS, and health-related quality of life (HRQOL) for patients receiving intraoperative photodynamic therapy (PDT) with 5-aminolevulinic acid hydrochloride (5-ALA HCl).

Ten patients were included (May 2017 - April 2021) for standardized therapeutic approach including 5-ALA HCl fluorescence-guided surgery (FGS), followed by intraoperative PDT with a single 200 J/cm2 dose of light. Postoperatively, patients received adjuvant therapy (Stupp protocol) then followed every 3 months (clinical and cerebral MRI) and until disease progression and/or death. Procedure safety and toxicity occurring during the first four weeks after PDT were assessed. Data concerning relapse, HRQOL and survival were prospectively collected and analyzed.

At the cut-off date (i.e., November 1st 2023), median follow-up was 23 months (9,7-71,4). No unacceptable or unexpected toxicities and no treatment-related deaths occurred during the study. Kaplan-Meier estimated 23.4 months median OS, actuarial 12-month PFS rate 60%, actuarial 12-month, 24-month, and 5-year OS rates 80%, 50% and 40%, respectively. Four patients were still alive (1 patient free of recurrence).

At 5 years-follow-up, intraoperative PDT with surgical maximal excision as initial therapy and standard adjuvant treatment suggests an increase of time to recurrence and overall survival in a high proportion of patients. Quality of life was maintained without any severe side effects.

NCT03048240. EudraCT number: 2016-002706-39.

The high fatality rate of glioblastoma (GBM) is attributed to glioblastoma stem cells (GSCs), which exhibit heterogeneity and therapeutic resistance. Metabolic plasticity of mitochondria is the hallmark of GSCs. Targeting mitochondrial biogenesis of GSCs is crucial for improving clinical prognosis in GBM patients.

SMYD2-induced PGC1α methylation and followed nuclear export is confirmed by co-immunoprecipitation, cellular fractionation, and immunofluorescence. The effects of SMYD2/PGC1α/CRM1 axis on GSCs mitochondrial biogenesis is validated by OCR, ECAR and intracranial glioma model.

PGC1α methylation causes disabled mitochondrial function to maintain the stemness, thereby enhancing radio-resistance of GSCs. SMYD2 drives PGC1α K224 methylation (K224me), which is essential for promoting the stem-like characteristics of GSCs. PGC1α K224me is preferred binding with CRM1, accelerating PGC1α nuclear export and subsequent dysfunction. Targeting PGC1α methylation exhibits significant radiotherapeutic efficacy and prolongs patient survival.

These findings unveil a novel regulatory pathway involving mitochondria that governs stemness in GSCs, thereby emphasizing promising therapeutic strategies targeting PGC1α and mitochondria for the treatment of GBM.

The term Gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features have not been established yet.

We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization.

Median overall survival (OS) was 15.5 months (interquartile range, 10.9-27.7) with a 2-years survival rate of 28%. Histopathological grading correlated significantly with median OS: CNS WHO grade II: 47.8 months (25.2-55.7); grade III: 15.9 months (11.4-26.3); grade IV: 10.4 months (8.8-14.4). By DNA methylation profiling (n=49), most tumors were classified as pediatric-type diffuse high-grade glioma (pedHGG), H3-/IDH-wildtype (n=31/49, 63.3%) with enriched subclasses pedHGG_RTK2 (n=19), pedHGG_A/B (n=6), and pedHGG_MYCN (n=5), but only one pedHGG_RTK1 case. Within the pedHGG, H3-/IDH-wildtype subgroup, recurrent alterations in EGFR (n=10) and BCOR (n=9) were identified. Additionally, we observed structural aberrations in chromosome 6 in 16/49 tumors (32.7%) across tumor types. In the pedHGG, H3-/IDH-wildtype subgroup TP53 alterations had a significant negative effect on OS.

Contrary to previous studies, our representative pediatric GC study provides evidence that GC has a strong predilection to arise on the background of specific molecular features (especially pedHGG_RTK2, pedHGG_A/B, EGFR and BCOR mutations, chromosome 6 rearrangements).

Frailty is an independent risk factor for adverse postoperative outcomes following intracranial meningioma resection (IMR). The role of the Risk Analysis Index (RAI) in predicting postoperative outcomes following IMR is nascent but may inform preoperative patient selection and surgical planning.

IMR patients from the Nationwide Inpatient Sample were identified using diagnostic and procedural codes (2019-2020). The relationship between preoperative RAI-measured frailty and primary outcomes (non-home discharge (NHD), in-hospital mortality) and secondary outcomes (extended length of stay (eLOS), complication rates) was assessed via multivariate analyses. The discriminatory accuracy of the RAI for primary outcomes was measured in area under the receiver operating characteristic (AUROC) curve analysis.

A total of 23,230 IMR patients (mean age = 59) were identified, with frailty statuses stratified by RAI score: 0-20 "robust" (R)(N = 10,665, 45.9%), 21-30 "normal" (N)(N = 8,895, 38.3%), 31-40 "frail" (F)(N = 2,605, 11.2%), and 41+ "very frail" (VF)(N = 1,065, 4.6%). Rates of NHD (R 11.5%, N 29.7%, F 60.8%, VF 61.5%), in-hospital mortality (R 0.5%, N 1.8%, F 3.8%, VF 7.0%), eLOS (R 13.2%, N 21.5%, F 40.9%, VF 46.0%), and complications (R 7.5%, N 11.6%, F 15.7%, VF 16.0%) significantly increased with increasing frailty thresholds (p < 0.001). The RAI demonstrated strong discrimination for NHD (C-statistic: 0.755) and in-hospital mortality (C-statistic: 0.754) in AUROC curve analysis.

Increasing RAI-measured frailty is significantly associated with increased complication rates, eLOS, NHD, and in-hospital mortality following IMR. The RAI demonstrates strong discrimination for predicting NHD and in-hospital mortality following IMR, and may aid in preoperative risk stratification.