Central Nervous System
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Jul 13 – Jul 20, 2026
Multi-antigen-targeting T cells in pediatric central nervous system tumors: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1 trial evaluated the safety and feasibility of autologous, trivalent T cells targeting WT1, PRAME, and survivin in pediatric patients with central nervous system tumors. Researchers determined the maximum tolerated dose at 8 x 10^7 cells/m^2, noting that treatment was generally well-tolerated despite one grade 5 dose-limiting toxicity involving tumor edema. Clinical results showed a median overall survival of 13.7 months for diffuse intrinsic pontine glioma and a median progression-free survival of 5.0 months for relapsed malignancies. These findings demonstrate the feasibility of multi-antigen-targeting T cells and provide preliminary signals of efficacy, including one complete response and long-term survival in select patients.
10.1038/s41591-026-04449-9
Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1 trial evaluated the anti-LAG-3 antibody relatlimab alone or with anti-PD-1 nivolumab in 46 patients with recurrent glioblastoma (GBM). The primary safety endpoint was met; maximum tolerated doses were 800 mg monotherapy and 160 mg/240 mg combination therapy, with grade 3-4 adverse events in 6 of 23 combination patients. Exploratory efficacy signals showed 12-month overall survival of 34.8% with monotherapy and 52.2% with combination therapy, with increased intratumoral CD8+ T cell infiltration after neoadjuvant dosing. These findings demonstrate acceptable safety and preliminary activity, supporting further study of dual checkpoint blockade in GBM, directly addressing interest in cancer-focused research.
10.1038/s41591-026-04475-7
Jul 06 – Jul 13, 2026
Intracranial Injection of Investigational Ex Vivo Expanded and Activated Gamma-Delta T Cells Engineered With a Methylguanine-DNA Methyltransferase-Expressing Lentivector in Patients With Primary Glioblastoma.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This study investigated a novel approach for newly diagnosed glioblastoma (GBM) using genetically modified, temozolomide (TMZ)-resistant gamma-delta (γδ) T cells (DeltEx DRI) delivered intracranially via a Rickham catheter, combined with TMZ. In 13 treated patients, no dose-limiting toxicities, cytokine release syndrome, or neurotoxicity were observed. The median progression-free survival (mPFS) was 9.9 months for all patients (16.1 months for repeated doses), and median overall survival (mOS) was 15.6 months. This investigational immunotherapy shows promising safety and early efficacy signals for a challenging cancer, glioblastoma, suggesting a potential new, well-tolerated treatment strategy warranting further investigation.
10.1200/JCO-25-02463
Jun 29 – Jul 06, 2026
Temozolomide Versus Radiotherapy as First-Line Therapy for Low-Grade Glioma: Mature Results of a Randomized Phase III Trial (EORTC 22033-26033/NCIC-CTG/TROG/MRC-CTU).
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This randomized Phase III trial compared temozolomide versus standard radiotherapy as first-line therapy for 478 patients with clinical high-risk WHO grade 2 low-grade gliomas. Overall, there was no significant difference in progression-free or overall survival between treatment arms. However, in tumors without IDH mutations (n=64), overall survival significantly favored the temozolomide arm (4.7 vs 2.5 years; HR 0.47, p=0.0068). This study provides crucial insights into optimal first-line treatment strategies for low-grade gliomas, emphasizing the necessity of molecular classification for tailored cancer management and challenging the prognostic value of age alone.
10.1200/JCO-25-02735
Novel strategies to overcome the blood-brain barrier in triple-negative breast cancer brain metastases.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This review article advocates a paradigm shift for treating triple-negative breast cancer (TNBC) brain metastases by actively targeting and exploiting blood-brain barrier (BBB) biology. Synthesizing preclinical and clinical evidence, it delineates TNBC-specific BBB breach mechanisms and evaluates emerging therapies via a three-pillar framework: physical/focal BBB disruption, biological BBB exploitation, and microenvironmental modulation. The review provides a translational roadmap for unmet clinical needs in this aggressive cancer subtype. It emphasizes that integrated, BBB-centric strategies are crucial to improving patient outcomes, offering new avenues for clinical practice.
10.1016/S1470-2045(26)00146-4
Dose escalation with intraoperative radiotherapy in newly diagnosed glioblastoma (INTRAGO-II): an open-label, multicentre, randomised, controlled, phase 3 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This multicentre, phase 3 randomized trial (INTRAGO-II) evaluated whether adding 30 Gy of intraoperative radiotherapy (IORT) to standard chemoradiotherapy improves outcomes in 298 patients with newly diagnosed glioblastoma. Results showed no significant difference in median progression-free survival between the IORT group (11.0 months) and the standard-of-care group (11.4 months; HR 1.1, p=0.47). Local recurrence remained the predominant failure pattern in both groups (~71%), while IORT was associated with higher rates of serious adverse events, including seizures (13% vs 7%) and radiation necrosis (7% vs 2%). These findings suggest that local dose intensification via IORT does not provide clinical benefit for resectable glioblastoma and should not be integrated into standard practice.
10.1016/S1470-2045(26)00235-4
Jun 15 – Jun 22, 2026
Tumor-targeted interferon-α gene therapy for glioblastoma: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1 trial evaluated Temferon, a genetically engineered autologous stem cell therapy delivering interferon-α2 to the glioblastoma (GBM) tumor microenvironment via myeloid cells. In 24 newly diagnosed GBM patients with unmethylated MGMT promoter, no dose-limiting toxicities occurred, and busulfan conditioning was selected for further study. Median overall survival was 16.7 months and progression-free survival 8.1 months from diagnosis, with maintained performance status and quality of life. Temferon is safe and tolerable, offering a novel immunotherapy approach for GBM, a cancer with poor prognosis.
10.1038/s41591-026-04419-1
Jun 08 – Jun 15, 2026
Neuroepithelial Tumor with AAV Integration after Intracisternal Magna Vector Delivery.
NEW ENGL J MED · Q1 JOURNAL - RANK #2/332TOP-TIER
This case report describes a 5-year-old boy with MPSI who developed a neuroepithelial tumor four years after receiving intracisternal AAV9 gene therapy. Molecular analysis revealed clonal integration of rearranged AAV vector elements into the PLAG1 gene, leading to a chimeric transcript. The tumor was successfully resected, and the patient maintained advanced cognitive function, indicating MPSI mitigation. This finding highlights a rare but serious oncogenic risk of AAV integration in pediatric gene therapy, directly relevant to cancer-focused clinical interest.
10.1056/NEJMoa2601608
Jun 01 – Jun 08, 2026
SEZ6-targeting antibody-drug conjugate ABBV-706 in advanced small cell lung cancer and solid tumors: a phase 1 trial.
NAT MED · Q1 JOURNAL - RANK #1/195TOP-TIER
This phase 1 trial evaluated ABBV-706, a SEZ6-targeting antibody-drug conjugate, in 288 patients with advanced solid tumors, specifically focusing on relapsed/refractory small cell lung cancer (R/R SCLC). In the R/R SCLC cohort, the objective response rate was 52%, with a median overall survival of 12.4 months at the 1.8 mg/kg dose. Safety data showed grade 3 or higher treatment-related adverse events in 61% of patients, primarily anemia and fatigue, which were dose-dependent. These findings establish 1.8 mg/kg every three weeks as the recommended phase 2 dose, offering a promising new therapeutic strategy for neuroendocrine-derived cancers.
10.1038/s41591-026-04452-0
May 25 – Jun 01, 2026
Longitudinal Risk for Suicidal Self-Directed Violence Among Veterans With Cancer.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
This national cohort study assessed longitudinal risks and methods for suicidal self-directed violence (SSDV) among 292,271 veterans with invasive solid or hematologic cancer (2014-2023) using registries. Overall, 2400 SSDV events occurred (203 per 100,000 person-years), with poisoning most common (26%). High rates were found in patients with CNS, pancreas, head and neck, liver and biliary system, and thyroid cancers, advanced cancer (261 per 100,000 person-years), severe frailty, chronic mental illness, and high pain scores. Risks persisted five years post-diagnosis for younger (≤45 years), unmarried, advanced cancer, and CNS cancer patients, highlighting vulnerable subgroups. This emphasizes the critical need for systematic tracking of suicidal behaviors and tailored screening strategies within comprehensive cancer care, especially for these high-risk populations.
10.1001/jamaoncol.2026.1459
Long-Term Analysis of NRG Oncology RTOG 0539: A Phase II Trial of Observation for Low-Risk Meningioma and Radiotherapy for Intermediate- and High-Risk Meningioma.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This phase II trial evaluated a risk-adapted management strategy for WHO grade 1-3 meningioma, utilizing observation for low-risk patients and specific radiotherapy doses (54 Gy or 60 Gy) for intermediate- and high-risk cohorts. At a 12-year median follow-up, 10-year progression-free survival rates were 85.2% for low-risk, 72.2% for intermediate-risk, and 42.5% for high-risk groups, while overall survival reached 94.1%, 84.7%, and 51.1%, respectively. The study demonstrates that observation is viable for low-risk tumors, while radiotherapy provides structured control for more aggressive grades, despite grade 3+ toxicities occurring in up to 15.1% of high-risk patients. These long-term results establish definitive benchmarks for meningioma management and validate risk-stratification protocols in neuro-oncology practice.
10.1200/JCO-25-01441
May 18 – May 25, 2026
Treatment Effect Reanalysis of the Randomized Individual Screening Trial of Innovative Glioblastoma Therapy in Newly Diagnosed Glioblastoma With External Control Data.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This study reanalyzed three experimental arms of the INSIGhT platform trial for newly diagnosed glioblastoma by comparing internal control data with propensity score-matched external control data from real-world and clinical sources. Results showed no survival benefit for abemaciclib (HR 1.00; 95% CI, 0.75–1.34), neratinib (HR 0.93; 95% CI, 0.70–1.24), or CC-115 (HR 0.88; 95% CI, 0.41–1.88), which mirrored the original trial’s internal control findings. For clinicians treating glioblastoma, the study demonstrates that carefully matched external controls can produce reliable treatment effect estimates in early-phase testing of experimental therapies. These findings suggest that hybrid randomized designs leveraging external data may accelerate oncology drug development, provided comprehensive data on potential confounders are available to mitigate bias.
10.1200/JCO-25-01586
May 11 – May 18, 2026
MRI-guided adaptive radiotherapy for high grade glioma (UNITED): a single-centre, single-arm, non-inferiority, phase 2 trial.
LANCET ONCOL · Q1 JOURNAL - RANK #8/326TOP-TIER
This phase 2 trial evaluated the safety of a small-margin (5 mm), MRI-guided adaptive radiotherapy approach using a 1.5 T MR-Linac for 98 patients with glioblastoma. The primary outcome demonstrated a marginal failure risk of only 4% (95% CI 0–8), successfully meeting non-inferiority criteria compared to historical controls using larger margins. By utilizing weekly gadolinium-enhanced online adaptation, clinicians can significantly reduce the volume of irradiated healthy brain tissue without increasing the risk of local recurrence. These results support the feasibility of margin de-escalation in high-grade glioma treatment, potentially reducing treatment-related toxicity while maintaining oncological control.
10.1016/S1470-2045(26)00088-4