Neuro-oncology最新文献

{"title":"Spatially-resolved single-cell imaging of melanoma brain metastases identifies localized immune patterns predictive of immune checkpoint blockade response.","authors":"Stefanos Voglis, Daniel Schulz, Nils Eling, Natalie De Souza, Luca Regli, Marian Christoph Neidert, Marcus Czabanka, Michael Weller, Emilie Le Rhun, Daniela Mihic-Probst, Mitchell Levesque, Bernd Bodenmiller","doi":"10.1093/neuonc/noag128","DOIUrl":"10.1093/neuonc/noag128","url":null,"abstract":"<p><strong>Background: </strong>A subset of patients with advanced-stage melanoma with brain metastases responds intracranially to immune-checkpoint inhibitors (ICIs). We reasoned that features of the spatial architecture of the tumor microenvironment correlate with treatment responses.</p><p><strong>Methods: </strong>We used highly multiplexed single-cell imaging to characterize the TME in 44 samples of MBM patients; both treatment naïve subjects and subjects who had received ICI were included in the cohort. Samples were stained with a 42-plex metal-isotope tagged antibody panel and subsequently imaged using imaging mass cytometry. Downstream analysis focused on phenotypic and spatial characteristics of the tumor microenvironments of ICI responders and non-responders and on correlations of protein expression with overall and local progression-free survival.</p><p><strong>Results: </strong>Single-cell phenotyping identified more than 1.1 million cells, predominantly tumor (67%) and immune cells (29%). ICI responders exhibited higher baseline proportions of B cells, IDO+ macrophages, and specific T cell subsets (regulatory and exhausted/activated CD8+). Conversely, neutrophil infiltration was negatively associated with intracranial response and survival. Spatial analysis revealed that responders possess a more localized, clustered immune cell pattern compared to the dispersed patterns seen in non-responders. Modeling CD8+ T cell distribution showed that localized infiltration was positively associated with overall and local progression-free survival, while dispersed patterns correlated with poorer outcomes. Furthermore, ICI-pretreated samples showed higher immune-tumor co-localization than treatment-naïve samples.</p><p><strong>Conclusions: </strong>Our single-cell, spatially resolved characterization of the tumor microenvironment of human melanoma brain metastases demonstrated distinct phenotypic and spatial infiltration patterns of various immune cells that are associated with ICI response and survival outcomes.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2211-2223"},"PeriodicalIF":13.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between radiographic response and subsequent recurrence in brain metastases treated with radiation: Implications for response assessment criteria.","authors":"Benjamin Grobman, Nayan Lamba, Sandeep Purohit, Paul J Catalano, Kee-Young Shin, Shyam K Tanguturi, Rifaquat Rahman, Manmeet S Ahluwalia, Daphne A Haas-Kogan, Patrick Y Wen, Ayal A Aizer","doi":"10.1093/neuonc/noag106","DOIUrl":"10.1093/neuonc/noag106","url":null,"abstract":"<p><strong>Background: </strong>The Response Assessment in Neuro-Oncology Brain Metastasis (RANO-BM) criteria comprise the foundation for assessment of investigational approaches in brain metastases, including novel radiation-based techniques. We characterized the relationship between RANO-BM response and long-term tumor control, the primary objective of radiation, in patients with brain metastases.</p><p><strong>Methods: </strong>We identified 1454 patients with 4166 newly diagnosed brain metastases managed with radiation therapy between 2008 and 2022. Initial response (progressive disease, stable disease, partial response, or complete response) was assessed per metastasis by RANO-BM criteria. Multivariable Fine and Gray's competing risk regression identified patient and metastasis-level characteristics, including response, associated with local recurrence.</p><p><strong>Results: </strong>The study population had a median (IQR) of 3 (1-6) brain metastases. Per-metastasis, partial response was most common (n = 1662, 40%), followed by stable disease (n = 1304, 31%), complete response (n = 1023, 25%), and progressive disease (n = 177, 4%). Compared to partial response, complete response was associated with a lower likelihood of local recurrence (hazard ratio [HR] = 0.44, 95% CI: 0.31-0.63, P < .001), whereas stable disease was not (HR = 1.15, 95% CI: 0.91-1.45, P = .25). On subgroup analysis, the association between stable disease vs partial response and local recurrence was modality-dependent, with no difference after whole brain radiation noted but higher recurrence with stable disease after stereotactic radiation observed.</p><p><strong>Conclusions: </strong>In radiotherapeutically managed brain metastases, particularly those treated with whole brain radiation, the association between response and local control is weak, especially among the most common response categories of partial response and stable disease. If validated, trials and guidelines assessing novel radiotherapeutic approaches should focus on long-term local control.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2224-2233"},"PeriodicalIF":13.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"cIMPACT-NOW Update 12: Refining pathology-based risk stratification and grading for IDH-mutant gliomas.","authors":"Daniel J Brat, Kenneth Aldape, Pim J French, David N Louis, MacLean P Nasrallah, Guido Reifenberger, David E Reuss, Mehdi Touat, Martin J van den Bent, Pieter Wesseling, Dominique Figarella-Branger","doi":"10.1093/neuonc/noag108","DOIUrl":"10.1093/neuonc/noag108","url":null,"abstract":"<p><p>A working group of cIMPACT-NOW evaluated the literature on IDH-mutant gliomas for opportunities to improve pathology-based risk stratification and grading, especially at the interface of CNS WHO grades 2 and 3, since therapeutic decisions depend on risk assessment for clinical management. The group also evaluated newly described IDH-mutant glioma subgroups and considered multidisciplinary aspects of therapeutic decision-making. PDGFRA amplification was associated with highly aggressive clinical behavior of IDH-mutant astrocytomas, consistent with CNS WHO grade 4. Other genetic alterations associated with intermediate risk and most consistent with CNS WHO grade 3 included PIK3 mutations; EGFR alteration; MYCN amplification; and specific retinoblastoma pathway alterations, including CDK4, CDK6, and CCND2 amplification, RB1 homozygous deletion or mutation, and mutation of CDKN2A. DNA methylation signatures of G-CIMP-low or A_IDH_HG were consistent with CNS WHO grade 3 or 4, depending upon other grading criteria. We suggest a mitotic count of ≥3 per 2.4 mm2 could be considered as a CNS WHO grade 3 criterion. Our review did not uncover features to improve the grading of oligodendroglioma, IDH-mutant and 1p/19q-codeleted, although CNS WHO grade 3 tumors with elevated mitotic rates, yet lacking necrosis, microvascular proliferation, CDKN2A/B homozygous deletion, and MRI contrast enhancement, may be associated with extended survival. Implementing evidence-based criteria for risk stratification and grading will improve guidance for clinical decision-making.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2069-2089"},"PeriodicalIF":13.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147974476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging roles of cerebral pericytes in brain metastasis.","authors":"Chanawee Hirunpattarasilp, Herbert B Newton","doi":"10.1093/neuonc/noag110","DOIUrl":"10.1093/neuonc/noag110","url":null,"abstract":"<p><p>Brain metastases are a prevalent disease found in up to 40% of patients with solid cancers, and are associated with significant morbidity and mortality. Current treatment options for brain metastases are limited, especially because the tumor is protected by the blood-tumor barrier that prevents the penetration of chemotherapeutic agents. Understanding the brain metastatic process and the cells involved is required to discover new treatment approaches. One interesting therapeutic target is mural cells called pericytes, given their importance in maintaining the blood-brain barrier, regulating blood flow, modulating the immune response, and promoting angiogenesis in normal brain physiology. The role of cerebral pericytes in the initiation and maintenance of brain metastases is not well understood. In this review, we discuss the current understanding of the steps in the metastatic process and the roles of cerebral pericytes at each step, especially premetastatic niche formation, cancer cell extravasation, brain micrometastasis formation, and maintenance of macrometastasis and the tumor microenvironment. This study aims to provide a comprehensive understanding of the importance of brain pericytes in brain metastasis formation and maintenance, offer a perspective on the further investigations that are needed, and propose possible clinical implications for the treatment of brain metastases.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2092-2109"},"PeriodicalIF":13.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147974427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tempered optimism: Advances in the precision medicine era for pediatric low-grade glioma.","authors":"Chelsea Kotch, Sebastien Perreault, Phoebe Power, David J Adams, Kenneth Aldape, Robert A Avery, Pratiti Bandopadhayay, David Capper, Peter de Blank, Natacha Entz-Werle, Jason Fangusaro, Jordan R Hansford, Cynthia Hawkins, Thomas S Jacques, David T W Jones, Benjamin H Kann, Mariëtte E G Kranendonk, Adrian Levine, Keith L Ligon, Juan Pedro Martinez-Barbera, Lisethe Meijer, Till Milde, Sabine Mueller, Jean M Mulcahy Levy, Yoshiko Nakano, Roger J Packer, Stefan Pfister, Eric Raabe, Nathan J Robison, Uri Tabori, Kee Kiat Yeo, Anna Vinitsky, Yuan Zhu, Michael J Fisher, Darren Hargrave, Lindsay B Kilburn","doi":"10.1093/neuonc/noag111","DOIUrl":"10.1093/neuonc/noag111","url":null,"abstract":"<p><p>The clinical trial landscape of molecularly targeted treatments for pediatric low-grade glioma (pLGG) has created an exciting and hopeful era for both patients and clinicians alike. Despite numerous clinical trials investigating the use of targeted agents for pLGG, only two oral precision-based regimens for pLGG have received federal agency approval. However, enthusiasm surrounding recently completed early phase clinical trials has resulted in increased off-label prescribing practices beyond the federally-approved indications, despite a lack of phase 3 clinical trial data and an incomplete understanding of the long-term radiographic, functional outcomes, and toxicity for both approved and experimental therapies. These gaps in knowledge are critically important to consider when selecting therapies for patients with pLGG, as the prevention and reduction of late effects in pLGG survivors is crucial to prevent long-term morbidity. In this editorial by the clinical working group of the International pLGG Coalition, we discuss the landscape of molecularly targeted therapies for pLGG, outline the unanswered questions for the use of novel therapies in the management of pLGG, review the risks and benefits of early off-label use of targeted agents, and discuss the importance of patience and evidence-based clinical practice in the rapidly evolving era of precision medicine.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2110-2122"},"PeriodicalIF":13.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147974410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-sampling allows intra-tumoral heterogeneity querying and vulnerability profiling in glioblastoma.","authors":"Diogo Moniz Garcia, Wan-Hsin Lin, Daniel P Wickland, Erik Jessen, Erik H Middlebrooks, Lauren E Haydu, Mieu Brooks, Ryan W Feathers, Lindsey Kinsella, Chris Sereduk, Steven S Rosenfeld, Nhan L Tran, Kaisorn L Chaichana, Panos Z Anastasiadis, Alfredo Quiñones-Hinojosa","doi":"10.1093/neuonc/noag139","DOIUrl":"10.1093/neuonc/noag139","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) remains a devastating cancer with limited treatment options, largely due to its heterogeneity. While supramaximal resection has recently provided survival benefits, therapeutic profiling of different tumor compartments, particularly its infiltrative edge remains largely unexplored.</p><p><strong>Methods: </strong>Here, we leveraged magnetic resonance imaging (MRI)-guided multi-sampling, collecting 2 cores and 2 margins per case, to query GBM heterogeneity. Whole-exome and RNA-seq with drug testing in two patient-derived 3D models were used to reveal similarities and differences in genomic and transcriptomic makeups, cellular compositions, and drug responses across cores and margins. Bioinformatics interrogations further identified response biomarkers.</p><p><strong>Results: </strong>Mutation analysis showed that oncogenes exhibited a higher degree of spatial heterogeneity than tumor suppressor genes, regardless of MRI status. While the mesenchymal transcriptional subtype with extracellular matrix remodeling, stress response, and immune programs were preferentially enriched in enhancing cores, proneural tumors with neurological processes favored non-enhancing margins. Using a 15-drug GBM-targeted panel, ERK (ulixertinib) and PI3K pathway (paxalisib, CC-115) inhibitors showed preferential efficacy in enhancing cores and non-enhancing margins, respectively. The anti-apoptosis, pan-Bcl2 agent navitoclax and the epigenetic drug trotabresib represented the most effective, tumor-wide monotherapies. Importantly, drug combinations generally outperformed single agents across all regions.</p><p><strong>Conclusions: </strong>This work demonstrates the regional heterogeneity of therapeutic vulnerabilities in GBM ex vivo, showing various drugs with tumor-wide or MRI-enhancement informed activity. These findings offer preclinical bases of numerous monotherapies and drug combinations for future clinical trial design.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2136-2152"},"PeriodicalIF":13.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Final report of the SIOP-CNS-GCT II protocol for germinoma: Omitting radiotherapy boost is safe in localized disease in complete remission after chemotherapy.","authors":"Gabriele Calaminus, Claire Alapetite, Rolf D Kortmann, Thankamma Ajithkumar, Martin Zimmermann, Hervé J Brisse, Maria Luisa Garrè, Giovanni Morana, Thomas Czech, Andreas Peyrl, Nicolas U Gerber, Stefan Schönberger, Martin Heimbrodt, Celestina Saager, Yannik Rambau, Brigitte Bison, Didier Frappaz, Cecile Faure-Conter, Matthew J Murray, James C Nicholson","doi":"10.1093/neuonc/noag127","DOIUrl":"10.1093/neuonc/noag127","url":null,"abstract":"<p><strong>Background: </strong>For localized germinoma, whole-ventricular radiotherapy (WVRT) is standard-of-care in Europe; 24 Gray (Gy) with 16 Gy boost following chemotherapy. The SIOP-CNS-GCT-II trial aimed to examine the effect of response-adapted radiotherapy on patient outcome.</p><p><strong>Methods: </strong>Patients with localized germinoma received 4 courses of \"carboPEI\" chemotherapy, then 24 Gy WVRT if in complete remission (CR), with an additional 16 Gy tumor boost if residual disease was present. Metastatic cases received 24 Gy craniospinal radiotherapy (CSRT) with 16 Gy boost to all sites.</p><p><strong>Results: </strong>Between 2012 and 2018, 227 fully-staged germinoma patients were treated according to protocol. Five-year event-free (EFS) and overall survival (OS) for 166 localized germinoma were 0.94 ± 0.02 and 0.98 ± 0.01, respectively. Sixty-five of 166 (39.2%) were in CR after chemotherapy, of whom 64/65 received 24 Gy WVRT, only 2 of whom (2/64; 3.1%) relapsed. Of 90/166 patients in partial remission (PR) after chemotherapy, 88/90 received 24 Gy WVRT + 16 Gy; 2 relapsed (2/88; 2.3%). Of the 11 remaining patients, 8 had stable disease (SD) after chemotherapy; 7/8 received 24 Gy WVRT + 16 Gy boost and 1 received 24 Gy WVRT + 30 Gy boost because of a teratoma component; none relapsed. Three remaining patients with progressive disease (PD) during chemotherapy had variable treatments, due to differing histologies and disease spread; 1 relapsed. Five-year EFS and OS for 61 metastatic germinoma were 0.98 ± 0.02 and 1.00 ± 0.00, respectively, with 55/61 (90.2%) in CR and 5/61 (11.5%) in PR after 24 Gy CSRT + 16 Gy; 1 relapsed.</p><p><strong>Conclusions: </strong>Response-adapted radiotherapy for localized germinoma led to excellent survival outcomes. Further treatment de-escalation should be considered in future strategies to reduce treatment burden and late effects.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2234-2247"},"PeriodicalIF":13.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148157394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discrepancies in inter-rater agreement on resectability of recurrent glioblastoma: Complementary post-hoc analysis of the prospective, randomized DIRECTOR trial.","authors":"Philipp Karschnia, Nico Teske, Emilie Le Rhun, Hans-Georg Wirsching, Asgeir S Jakola, Constantin Roder, Daniel P Cahill, Einar O Vik-Mo, Mitchel S Berger, Jacob S Young, Wolfgang Wick, Ghazaleh Tabatabai, Joachim P Steinbach, Bogdana Suchorska, Katharine J Drummond, Lorenzo Bello, Marike L D Broekman, Michael A Vogelbaum, Yoshua Esquenazi, Oliver Schnell, Michael Weller, Joerg-Christian Tonn","doi":"10.1093/neuonc/noag103","DOIUrl":"10.1093/neuonc/noag103","url":null,"abstract":"<p><strong>Background: </strong>Tumor resection is a prerequisite in many studies of new glioblastoma therapeutics; however, no clear parameters for \"resectability\" exist. We evaluated inter-rater variability in assessing tumor resectability and potential associations between resectability and survival in a trial cohort of glioblastoma recurrence.</p><p><strong>Methods: </strong>DIRECTOR (NCT00941460; 9/2009-6/2012) evaluated two dose-dense temozolomide regimens for first recurrent glioblastoma, yielding similar outcomes between arms. Re-resection was allowed before initiation of systemic therapy by institutional decision. Eleven surgical neuro-oncologists (blinded to final outcomes) rated whether a \"meaningful resection\" was achievable for each recurrent IDH-wildtype glioblastoma based on imaging and clinical data.</p><p><strong>Results: </strong>MRI scans from 69 patients were available (median age: 58.2 ± 1.1 years, median survival: 10.0 months). Forty patients underwent re-resection (median age: 56.4 ± 1.7 years, median survival: 10.8 months). Surgical decision-making markedly varied between raters, ranging from 30 to 58 of 69 cases being classified as \"resectable\" (κ = 0.405). In patients who received re-resection, a \"meaningful resection\" was deemed feasible by >80% of raters in 30/40 cases (75.0%). For patients without re-resection, unanimous agreement on non-resectability occurred in only 3/29 cases (10.4%); and 5/29 tumors (17.2%) were considered resectable by >80% of raters. Knowledge of additional clinical factors virtually never changed MRI-based judgments. While patients who had a complete resection of contrast-enhancing tumor had favorable outcomes, a consensus on resectability by >80% of raters was not associated with prolonged overall survival.</p><p><strong>Discussion: </strong>Feasibility assessment for re-resection is heterogeneous among neurosurgeons, challenging single-surgeon evaluation of \"resectability.\" Those findings are limited by the number of surgical raters and the size of the DIRECTOR cohort.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2197-2210"},"PeriodicalIF":13.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRAM-01: A phase 2 study of trametinib for pediatric patients with neurofibromatosis type 1 and plexiform neurofibromas.","authors":"Dorsa Sadat Kiaei, Maxime Caru, Valérie Larouche, Emma Clini, Deepika Pugalenthi Saravanan, Sarah Lippé, Yves Théoret, Jean-Claude Décarie, Uri Tabori, Cynthia Hawkins, Benjamin Ellezam, Luis H Ospina, Léandra Desjardins, Marie-Élaine Métras, Serge Sultan, Édith Cantin, Marie-Ève Routhier, Chantal Mailloux, Marie-Claude Bertrand, Karim Estephan, Tara McKeown, Stéphanie Vairy, Geneviève Legault, Samuele Renzi, Éric Bouffet, Vijay Ramaswamy, Hallie Coltin, Lucie Lafay-Cousin, Juliette Hukin, Mélanie Alves, Tiffany Rent, Craig Erker, Nada Jabado, Mathieu Dehaes, Sébastien Perreault","doi":"10.1093/neuonc/noag112","DOIUrl":"10.1093/neuonc/noag112","url":null,"abstract":"<p><strong>Background: </strong>Plexiform neurofibromas (PNs) are observed in up to 50% of patients with neurofibromatosis type 1 (NF1). Trametinib has been used widely to treat PNs but limited data has been reported on its efficacy within a clinical trial. We conducted a phase 2 trial with trametinib for patients with NF1 and inoperable PNs.</p><p><strong>Methods: </strong>Patients with NF1 and inoperable PNs aged ≥1 month to ≤25 years when starting trametinib were eligible. Patients received trametinib once daily orally continuously for a maximum of 18 cycles of 28 days. Patients completed patient-reported outcome measures. Response evaluations were performed after cycle 3, 6, 12 and at the end of treatment and then every 6 months. The PN volumes were centrally quantified using a semi-automatic 3D segmentation method.</p><p><strong>Results: </strong>Forty-six patients were recruited. The median age was 11.1 years (range 0.7-19.8). The median baseline tumor volume was 104.6 ml (range 16.3 to 650.1 ml). Volumetric assessment demonstrated an overall response rate (volume decrease of ≥20%) in 47.8% (22/46) of patients. Median volume change was -19.3% (range -80.5 to 3.5). Forty-one patients (89.1%) completed the planned treatment. The 3 years progression free survival and the event free survival were respectively 73.1% (95% CI 53.3%-85.5%) and 47.1% (95% CI 28.8-63.5).</p><p><strong>Conclusions: </strong>We report outcomes and volumetric response of PNs treated with trametinib within a phase 2 trial. Based on these results, trametinib is effective and overall well tolerated.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2279-2288"},"PeriodicalIF":13.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147974430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The critical issue of grade 2 vs grade 3 in IDH-mutant gliomas.","authors":"Ho-Keung Ng","doi":"10.1093/neuonc/noag143","DOIUrl":"10.1093/neuonc/noag143","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2090-2091"},"PeriodicalIF":13.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}