Neuro-oncology advances最新文献

Background: Cognitive changes are common following primary brain tumor (PBT), impacting employment, independence, relationships, and quality of life (QoL). Despite this, tailored cognitive interventions are unavailable within Australia. The La Trobe and Caulfield Hospital (LaTCH) group cognitive rehabilitation program has demonstrated efficacy for older adults without PBT. Efficacy for people with PBT was examined using a telehealth adaption of LaTCH.

Methods: A Type 1 hybrid-implementation design randomized controlled trial (RCT) with waitlist control (WLC) was used. Adults > 3-months post-PBT diagnosis, and > 1-month post-radiation were randomized to (1) Intervention [6-week group sessions; 2 hours/week], delivered over Zoom (n = 3-7/group) or (2) WLC (intervention offered at 16 weeks). Primary outcomes were self-perceived memory (ability, strategy knowledge and use, satisfaction) and general cognitive function; secondary outcomes included QoL, fatigue, mood, and objective cognition (attention, working memory, processing speed, memory, executive function). Linear mixed models analyzed between-group differences post-intervention and 6 weeks later (maintenance).

Results: Sixty participants (M(SD) age = 49.0 (10.4) years, 57% female, 55% high-grade glioma) were randomized (29 intervention, 31 WLC). The intervention group reported significantly improved perceived memory ability, satisfaction, strategy use, and strategy knowledge. Effect sizes were moderate-large (ηp² 0.06-0.21), and maintained for memory ability (t = 4.26, P < .001, ηp² = 0.18), satisfaction (t = 2.23, P = .028, ηp² = 0.18), and strategy knowledge (t = 2.92, P = .004, ηp² = 0.09). Secondary outcomes exhibited no intervention effect.

Conclusions: Telehealth-delivered LaTCH-BRAINS improved subjective memory-related outcomes for people with PBT, demonstrating promise as a cognitive rehabilitation approach for people with PBT reporting memory decline.

Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN 12622000189729p), registered on 03/02/2022 (Appendix A).

[This corrects the article DOI: 10.1093/noajnl/vdaf049.].

Background: The 2021 WHO Classification of Tumors of the Central Nervous System, 5th edition (WHO CNS5), introduced revised diagnostic criteria for pediatric brain tumors (BTs), redefining pediatric-type diffuse high-grade gliomas (pHGGs) into 4 subtypes: diffuse midline glioma, H3 K27-altered (DMG-H3K27), diffuse hemispheric glioma, H3 G34-mutant (DHG-H3G34), diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (DpHGG-H3wt/IDHwt), and infant-type hemispheric glioma (IHG). This study revisits prior diagnoses of HGGs and primitive neuroectodermal tumors (PNETs) in children and incorporates next-generation sequencing (NGS) to classify tumors according to the revised criteria and analyze their clinicogenomic characteristics and outcomes.

Methods: A retrospective review of pediatric patients diagnosed with glioblastoma (GBM), anaplastic astrocytoma, anaplastic oligoastrocytoma (AOA), gliomatosis cerebri, or PNET between 1997 and 2023 was conducted. Cases underwent pathology review, immunohistochemistry (IHC), and BT-targeted NGS for reclassification per WHO CNS5. An additional 20 patients diagnosed with pHGG via genetics-integrated diagnosis since 2020 were included. Clinical characteristics, genomic alterations, and outcomes were analyzed.

Results: Among the 78 reviewed cases, 41 were reclassified as pHGGs. TP53 mutations were the most prevalent, particularly in DpHGG-H3wt/IDHwt, which showed associations with cancer predisposition syndrome (CPS). Two patients with Li-Fraumeni syndrome (LFS) developed DpHGG-H3wt/IDHwt adjacent to prior radiation fields. The 2-year overall survival (OS) rates were lowest in DpHGG-H3wt/IDHwt (23.2%) and highest in IHG (92.3%). Long-term survival was observed in IHG patients, with a 5-year OS rate of 73.8%, indicating the need for different adjuvant treatment strategies compared to other pHGGs.

Conclusions: BT-targeted NGS facilitates the reclassification of pHGGs, revealing associations with CPS. Routine germline sequencing is warranted, and accurate molecular diagnosis enables a shift in treatment strategies tailored to specific pHGG subtypes.

Background: Isocitrate dehydrogenase-mutant astrocytomas (A-IDHm) with the homozygous deletion of cyclin-dependent kinase 2A/B (CDKN2A/B-HD) have been classified as grade 4 in the WHO 2021 classification (WHO2021). This study aimed to find survival differences in subgroups stratified by CDKN2A/B status and traditional histological grades (hGs).

Methods: The frequency and prognostication of CDKN2A/B-HD in primary A-IDHm were analyzed based on hGs. A systematic review and meta-analysis were performed following the PRISMA guidelines using three databases (registration CRD42024570409). Effect sizes were evaluated using the hazard ratio (HR) and restricted mean survival time (RMST) for overall survival (OS).

Results: Thirty-three articles with 3739 A-IDHm patients were included. The pooled frequencies of CDKN2A/B-HD were 3.3% [95% confidence interval (CI): 1.9-5.8], 11.0% [CI: 8.6-14.0], and 39.1% [CI: 34.0-44.5] in hG-II, hG-III, and hG-IV, respectively, after excluding the outliers. CDKN2A/B-HD significantly impaired OS in patients with hG-III (pooled HR (pHR), 3.61; CI, 2.72-4.78) and hG-IV (pHR, 1.93; CI, 1.43-2.61), and it was not evident in hG-II due to the paucity of the data. pHR showed better survival in patients with grade-2 tumors over grade-3 (WHO2021) (pHR 1.44, CI 1.09-1.90, P = .01, 1184 patients), although the RMST difference was only 7.1 months at 100 months (N = 1162). Among the grade-4 tumors, CDKN2A/B-HD hG-IV had the worst survival (RMST at 60 months, 32 months).

Conclusion: The prognosis of A-IDHm can be stratified by hG and CDKN2A/B-HD. However, evidence is insufficient for the classification of hG-II with CDKN2A/B-HD.

The activation of cellular death programs does not necessarily predetermine an inevitable outcome. Identifying the precise moment when a cell irreversibly transitions from life to death presents a significant challenge in its assessment and measurement. In this review, we explore the critical alterations in cellular structures that have been proposed as the point-of-no-return. Using glioblastoma as a model-one of the most aggressive and lethal tumor types with a remarkable ability to evade cell death-we highlight the challenge of reaching the point-of-no-return. Glioblastoma cells often exhibit impaired function of the apoptotic endonuclease, DFF40/CAD/CPAN, leading to incomplete apoptosis and genomic instability. The sublethal activation of DFF40/CAD/CPAN not only allows tumor cells to survive but can also drive more aggressive phenotypes and enhance therapeutic resistance. We underscore the need to reassess glioblastoma treatment strategies from broad cytotoxic approaches to more targeted therapies that exploit specific vulnerabilities within regulated cell death (RCD) pathways.

Despite the emerging role of artificial intelligence (AI) in glioma grading, its clinical adoption remains in its early stages. This meta-analysis aims to assess the role of AI in differentiating glioma grades using magnetic resonance imaging (MRI). Twenty-five studies matched the inclusion criteria and were included after systematic searches through "PubMed" electronic database. The quality of the included studies was assessed utilizing Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). A bivariate random-effects model was employed to estimate the pooled effect of the sensitivity and specificity, followed by an estimation of the summary receiver operating characteristic (SROC) curve. The overall results suggest relatively high sensitivity and specificity among the assessed AI methods for discriminating glioma grades. Convolutional Neural Networks (CNN) demonstrated the highest diagnostic accuracy, with a sensitivity of 93% (95% CI: 88%-97%) and specificity of 92% (95% CI: 90%-94%). This meta-analysis highlights the potential role of AI models based on MRI in supporting clinicians in glioma grading.

Background: Glioblastoma is known for its highly immunosuppressive microenvironment, hindering the efficacy of immunotherapies. Noninvasive imaging like immuno-positron emission tomography (PET) offers the potential for visualizing immune dynamics within glioblastoma, potentially aiding in patient selection and treatment monitoring. This systematic review evaluates immuno-PET tracers currently under investigation for the noninvasive visualization of the immune environment in glioblastoma.

Methods: A literature search was conducted in PubMed and Web of Science up to March 2025, using keywords related to glioblastoma, immuno-PET, immune compartments, and specific tracers. Studies were screened based on predefined inclusion and exclusion criteria, focusing on the development, characterization, or application of immuno-PET tracers targeting immune cells or immune checkpoint molecules in glioblastoma.

Results: Nineteen studies met the inclusion criteria, exploring tracers targeting immune checkpoints and immune cell populations. Full-length antibodies demonstrated higher tumor specificity and retention compared to smaller fragments but showed longer circulation times. Peptide-based tracers and affibodies offered improved pharmacokinetics with rapid clearance and lower nonspecific uptake but encountered hurdles in ensuring adequate tumor targeting and retention. Advancements included dual-modal tracers combining PET and near-infrared fluorescence imaging for enhanced diagnostic and intraoperative applications.

Conclusions: Significant progress has been made in developing immuno-PET tracers for noninvasive visualization of immune reactions in glioblastoma. Challenges persist in clinical translation due to issues like blood-brain barrier permeability and safety profiles. Continued research and clinical evaluations are essential to harness the potential of immuno-PET in improving glioblastoma diagnosis, assessment of treatment response, and guiding personalized immunotherapy strategies, ultimately aiming to enhance patient outcomes.

Central nervous system (CNS) tumors require specialized care to promote better patient survival outcomes and life quality. Before this paper, there were no published guidelines identifying what constitutes specialized, comprehensive CNS tumor treatment and care in the United States. Consequently, members of several CNS tumor patient advocacy and not-for-profit organizations established a set of Guiding Principles by which adult CNS tumor treatment programs could be evaluated for the availability of specialized services offered. These Guiding Principles for CNS tumor treatment programs are the first tool of its kind in the United States. Patient advocacy and not-for-profit organizations that support the CNS tumor population can use these guiding principles to help patients and their loved ones make more informed decisions about where to seek treatment and care.