Journal of Neuro-Oncology最新文献

Background: Recurrent high‑grade glioma (HGG)-including glioblastoma-remains lethal, with median survival of approximately 6-10 months after first progression, although patients with IDH mutant tumors often have better survival. Recent ASCO/SNO data and expanding trial data are reshaping available treatment strategies.

Methods: We review evidence for alkylators and anti‑angiogenic therapy; summarize targeted options for rare, actionable alterations; review immuno‑oncology combinations and cellular therapies; highlight DNA damage response (DDR)/radiosensitization strategies and discuss advances in blood-brain barrier modulation and locoregional delivery. We propose a patient‑centered algorithm that prioritizes trial enrollment, biomarker‑guided approaches, steroid stewardship, and quality of life.

Results: Lomustine, temozolomide rechallenge, and bevacizumab remain commonly used but provide modest benefit. Targeted agents show meaningful activity only in select subsets (BRAF V600E, NTRK). DDR-directed agents such as ATM/ATR inhibitors show early promise. Immunotherapy advances center on rationale combinations, oncolytic viruses, and locoregionally delivered CAR-T/TCR platforms. Blood-Brain-Barrier (BBB) modulation strategies and adaptive trials are broadening access to innovative therapies. The 2025 landscape features meaningful, if incremental, options-alongside the first ever FDA‑approved therapy for H3K27M‑mutant diffuse midline glioma at relapse-and a pipeline of rational combinatorial approaches poised to refine outcomes for selected patients. This article concentrates on medical options and intentionally omits extended discussions of surgery and radiation beyond their integration with systemic therapies at recurrence.

Conclusions: Despite poor overall outcomes, incremental progress across targeted, immune, and delivery-based approaches supports a patient centered strategy emphasizing clinical-trial enrollment, molecular profiling and symptom focused care.

Glioblastoma (GBM) remains associated with poor outcomes, with a median survival of 15-18 months despite maximal safe resection, radiotherapy, and temozolomide. Therapeutic development has increasingly centered on overcoming drug resistance, intratumoral diversity, and restricted delivery across the blood-brain barrier. Progress in targeted therapy includes evaluation of EGFR inhibitors, multitarget tyrosine kinase inhibitors, and FGFR-directed agents, while rare molecularly defined subsets such as BRAF V600E and NTRK fusions offer tumor-agnostic precision approaches. JAK/STAT inhibition, PARP blockade, and PI3K/AKT/mTOR pathway modulation remain under investigation, although clinical benefit has been inconsistent. In parallel, precision oncology platforms incorporating multi-omic profiling, patient-derived organoids, and functional drug testing are refining therapy selection and supporting rational drug combinations. Adaptive clinical trial frameworks such as GBM AGILE and INSIGhT are accelerating the evaluation of novel agents within stratified cohorts,while emerging approaches including ChemoID-guided therapy, radiogenomic profiling, and digital modeling are beginning to influence translational endpoints. Immunotherapy continues to be an active area of research, though efficacy has thus far been limited. Immune checkpoint inhibitors have not yet demonstrated significant survival benefits as monotherapy, but combination strategies with vaccines, oncolytic viruses, and engineered cellular therapies are under evaluation. CAR T-cell therapies are advancing toward bispecific and armored constructs with locoregional delivery, while oncolytic viruses such as DNX-2401 and PVSRIPO demonstrate potential for durable responses in select patients. Looking ahead, progress is likely to arise from biomarker-informed, multimodal regimens that integrate targeted agents, next-generation immunotherapies, and precision-guided strategies, while embedding translational endpoints into trial design to address the complex biology and therapeutic resistance of GBM.

Purpose: To apply free water elimination (FWE) tractometry to a real-world clinical imaging dataset to quantify pathology-specific patterns of white matter involvement and peritumoral tissue alterations in diffuse gliomas.

Methods: The University of California San Francisco Preoperative Diffuse Glioma MRI dataset was analyzed using FWE tractometry. Twenty major white matter tracts were reconstructed and each divided into 100 equidistant nodes. Direct tumor involvement was quantified across enhancing tumor, necrotic core, and edema regions. Remote white matter tissue properties were assessed through hemispheric asymmetry analysis of free water-corrected fractional anisotropy (FW-FA), mean diffusivity (FW-MD), and free water fraction (FWF) in non-tumor involved regions at standardized distances from radiological tumor margins.

Results: 459 patients with unilateral glioma were included (361 glioblastoma, 87 astrocytoma, 11 oligodendroglioma). Glioblastoma demonstrated greater direct white matter involvement in enhancing tumor and necrotic core compared to astrocytoma and oligodendroglioma (q < 0.001, q = 0.01, respectively). Beyond radiological tumor margins, glioblastoma and astrocytoma exhibited decreased FW-FA, while oligodendroglioma showed increased FW-FA (q = 0.008, q = 0.04, respectively). Distance-based analysis revealed that this effect was most prominent in the proximal peritumoral region and diminished with increasing distance from tumor margins.

Conclusion: Using FWE tractometry on a large clinical repository, we identified distinct pathology-specific patterns of white matter alteration. Glioblastoma showed extensive direct involvement and peritumoral microstructural changes, while oligodendroglioma demonstrated relatively preserved white matter architecture near tumor margins. These patterns reflect expected biological differences and provide a reproducible framework for characterizing extent of white matter involvement, with potential applications in presurgical planning and understanding recurrence patterns.

Background: High grade gliomas are aggressive intrinsic brain tumors with limited treatment options and a universally poor prognosis. In recent years, significant progress has been made in understanding the genetic and molecular underpinnings of high grade gliomas and their interactions with the tumor microenvironment, including vasculature, immune cells, neurons, and glia, and, consequently, in the development of novel molecularly targeted therapies and immunotherapies.

Methods: Here, we review ongoing work in the clinical development of new therapeutic strategies for high grade gliomas, discuss ongoing challenges, and highlight emerging opportunities for targeted intervention, with particular focus on molecularly targeted and immunotherapy in recent and ongoing clinical trials.

Results: We discuss relevant molecular targets in high grade glioma, including IDH, VEGF, RTK signaling (EGFR, PI3K/Akt, Ras/Raf/MEK), p53, CDKN2A/B, CDK4/6, MGMT, PARP, TERT, and ATRX, as well as contemporary immunotherapeutic strategies including immune checkpoint inhibition (including classical and emerging targets), cell-based immunotherapy (CAR-T cells, TCR therapy, TIL therapy, and other engineered cell therapies), cancer vaccines, oncolytic viruses, as well as emerging mechanisms including cancer neuroscience-based therapies.

Conclusions: High grade glioma is a networked disease, involving numerous interconnected molecular and microenvironmental phenomena from tumor-intrinsic pathways and antigenicity to immune recognition and attack to neuronal modulation of both tumor and immune signaling. Emerging therapies harness several of these intersectional mechanisms, often simultaneously, and together offer hope for the future of clinical treatment of these devastating cancers.

Purpose: Accurately mapping higher cognitive functions remains a challenge both intraoperatively and preoperatively. This study is the first to preoperatively evaluate the bihemispheric cortical and subcortical networks by preoperative nTMS-based mapping of a verbal semantic association task, based on the intraoperatively established Pyramids and Palm Trees Test (PPTT).

Methods: The PPTT was integrated into the established workflow of preoperative nTMS-based mapping. Fibertracking (FT) was performed using a fractional anisotropy (FA) threshold set at 50% of the maximum FA and a minimum fiber length (FL) of 100 mm.

Results: The study included 20 patients with right-sided gliomas. Overall error rates in the lesional (right) hemisphere were 0.108 ± 0.053, compared to 0.098 ± 0.047 in the contralateral (left) hemisphere (p = 0.215). Semantic errors were observed more frequently in the right hemisphere (right: 0.0275 ± 0.015, left: 0.016 ± 0.015; p = 0.01). Tractography-based network analysis demonstrated comparable network properties regarding fiber volumes (left: 36 ± 16 (14-83) cm³, right: 33 ± 15 (9-65) cm³; p = 0.492), fiber lengths (left: 120 ± 10 (106-140) mm, right: 116 ± 9 (105-144) mm; p = 0.185)) and mean FA values (left: 0.37 ± 0.04 (0.32-0.45), right: 0.37 ± 0.04(0.25-0.41); p = 0.353) between hemispheres.

Conclusion: The PPTT, when used as a verbal semantic association task, enables a function-based identification of the bihemispheric network underlying semantic association and complex language processing. Function-based FT revealed an extensive right-hemispheric network, comparable in volume, mean FA and fiber length to the left hemisphere. These findings suggest that bihemispheric networks are crucial in higher cognitive functions, including semantic processing during complex language tasks.

Clinical trial number: The trial was registered on clinicaltrials.gov (NCT06401057) on January 7th 2024.

Background: Accurate brain tumor diagnosis guides effective management, with large excision biopsy as the gold standard. Intra-operative cytologic smear techniques offer rapid analysis, particularly useful in resource-limited settings. The aim of this study was to evaluate the diagnostic accuracy and clinical utility of intra-operative cytologic smear techniques in brain tumor surgery at the University Teaching Hospital of Kigali (CHUK).

Objectives: To evaluate the diagnostic accuracy and clinical utility of intra-operative cytologic smear compared to large excision biopsy in brain tumor surgery at CHUK.

Methods: A prospective cross-sectional study involving 77 patients with radiologically confirmed brain tumors undergoing surgery at CHUK. Squash cytology diagnoses were compared with final histopathology diagnoses for concordance.

Results: Squash cytology showed 89.6% agreement with histopathology. Major tumor types such as gliomas and meningiomas were reliably identified, facilitating timely surgical decisions.

Conclusions: Intra-operative squash cytology is a rapid and reliable adjunct to large biopsy, improving brain tumor management in low-resource settings. Integration of advanced techniques could enhance diagnostic precision further.