The Lancet Oncology最新文献

{"title":"Neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy in resectable and borderline resectable pancreatic cancer (PREOPANC-2): a multicentre, open-label, phase 3 randomised trial","authors":"Quisette P Janssen, Jacob L van Dam, Marlies L van Bekkum, Bert A Bonsing, Hendrik Bos, Koop P Bosscha, Stefan A W Bouwense, Lieke Brouwer-Hol, Anna M E Bruynzeel, Olivier R Busch, Peter-Paul L O Coene, Casper H J van Eijck, Jan Willem B de Groot, Brigitte C M Haberkorn, Ignace H J T de Hingh, Tom M Karsten, Geert Kazemier, Marion B van der Kolk, Mike S L Liem, Olaf J L Loosveld, Suzan Vrijaldenhoven","doi":"10.1016/s1470-2045(25)00363-8","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00363-8","url":null,"abstract":"<h3>Background</h3>The PREOPANC-2 trial aimed to evaluate whether neoadjuvant FOLFIRINOX improved overall survival compared with neoadjuvant gemcitabine-based chemoradiotherapy followed by adjuvant gemcitabine in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC).<h3>Methods</h3>In this investigator-initiated, open-label, nationwide, phase 3 randomised trial, patients aged 18 years or older with resectable or borderline resectable PDAC and a WHO performance status of 0 or 1 were enrolled across 19 Dutch centres. Patients in the FOLFIRINOX (FFX) group received FOLFIRINOX (85 mg/m<sup>2</sup> intravenous oxaliplatin, 180 mg/m<sup>2</sup> intravenous irinotecan, 400 mg/m<sup>2</sup> intravenous leucovorin, followed by a 400 mg/m<sup>2</sup> intravenous fluorouracil bolus and then continuous infusion at 2400 mg/m<sup>2</sup> intravenously over 46 h every 14 days for eight cycles) followed by surgery without adjuvant treatment. Patients in the chemoradiotherapy (CRT) group received three cycles of neoadjuvant gemcitabine (1000 mg/m<sup>2</sup> intravenously on days 1, 8, and 15 of each 28-day cycle and on days 1 and 8 only for cycles one and three) combined with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle only, followed by surgery and four cycles of adjuvant gemcitabine. Randomisation (1:1) was done using a minimisation technique and stratified by resectability status (resectable <em>vs</em> borderline resectable disease) and centre. The primary endpoint was overall survival in the modified intention-to-treat population, after excluding ineligible patients. Data on race and ethnicity were not collected. This trial is registered with EudraCT (2017-002036-17) and is complete.<h3>Findings</h3>From June 5, 2018, to Jan 28, 2021, 375 patients were randomly assigned to the FFX group (n=188) or the CRT group (n=187). Six patients (three per group) were excluded due to ineligibility (n=4) or immediate withdrawal of informed consent after randomisation (n=2). 208 (56%) of 369 patients were male and 161 (44%) were female. After a median follow-up of 42·3 months (IQR 35·7–48·7), median overall survival was 21·9 months (95% CI 17·7–27·0) in the FFX group versus 21·3 months (16·8–25·5) in the CRT group (HR 0·88 [95% CI 0·69–1·13], p=0·32). The most common grade 3–4 adverse events were neutropenia (43 [25%] of 175 in the FFX group <em>vs</em> 38 [22%] of 176 in the CRT group), diarrhoea (41 [23%] <em>vs</em> two [1%]), and leukopenia (14 [8%] <em>vs</em> 26 [15%]). Serious adverse events occurred in 85 (49%) patients in the FFX group compared with 75 (43%) in the CRT group (p=0·26). Adverse events of grades 3 or worse occurred in 117 (67%) patients in the FFX group versus 106 (60%) patients in the CRT group (p=0·20). Treatment-related deaths occurred in two (1%) patients in the FFX group (multi-organ failure and intestinal mucositis) and one (1%) patient in the CRT group (upper gastrointestina","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant approaches in non-metastatic pancreatic cancer: where do we stand?","authors":"","doi":"10.1016/s1470-2045(25)00421-8","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00421-8","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Principles for advancing healthy workplace cultures: an ASCO–COSA–ECO joint statement","authors":"Sabe Sabesan, Laura A Levit, Wim Ceelen, Mirjam Crul, Elizabeth Garrett-Mayer, M Kelsey Kirkwood, Wendy H Oldenmenger, Richard Price, Marissa Ryan, Ishwaria Subbiah, Csaba László Dégi, Eric P Winer","doi":"10.1016/s1470-2045(25)00474-7","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00474-7","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145043123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and activity of tarlatamab in combination with a PD-L1 inhibitor as first-line maintenance therapy after chemo-immunotherapy in patients with extensive-stage small-cell lung cancer (DeLLphi-303): a multicentre, non-randomised, phase 1b study","authors":"Kelly G Paulson, Sally C M Lau, Myung-Ju Ahn, Mor Moskovitz, Michael Pogorzelski, Simon Häfliger, Amanda Parkes, Yuyang Zhang, Ali Hamidi, Corbin G Thompson, Martin Wermke","doi":"10.1016/s1470-2045(25)00480-2","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00480-2","url":null,"abstract":"<h3>Background</h3>Tarlatamab is a delta-like ligand 3 (DLL3)-directed bispecific T-cell engager immunotherapy that has improved survival in patients with previously treated small-cell lung cancer (SCLC). We evaluated the safety and activity of tarlatamab in combination with atezolizumab or durvalumab as first-line maintenance therapy in patients with extensive-stage (ES)-SCLC.<h3>Methods</h3>In this multicentre, non-randomised, phase 1b study, patients aged 18 years and older, with Eastern Cooperative Oncology Group performance status of 0–1 and without disease progression after four to six cycles of platinum–etoposide chemotherapy plus a programmed cell death ligand 1 (PD-L1) inhibitor (if available), received tarlatamab 10 mg intravenously once every 2 weeks, after an initial tarlatamab 1 mg dose, with atezolizumab intravenously (1680 mg once every 4 weeks) or durvalumab intravenously (1500 mg once every 4 weeks) as maintenance until disease progression. Patients were enrolled from 30 centres in 13 countries. The primary objective was to evaluate safety and to determine the recommended phase 2 dose or maximum tolerated dose of tarlatamab in combination with a PD-L1 inhibitor through assessment of dose-limiting toxicities, treatment-emergent adverse events, treatment-related adverse events, and changes in vital signs, electrocardiograms, and clinical laboratory tests. All patients who received at least one dose of tarlatamab were included in the analyses. Because overall survival data were immature at the primary analysis, in this Article, we report a non-specified interim analysis to provide an updated examination of overall survival and longer-term safety. This study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT05361395</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>; the EU Clinical Trials registry, 2021-005462-17; and EudraCT, 2024-511021-58.<h3>Findings</h3>Between Aug 31, 2022, and Jan 30, 2024, 88 patients received tarlatamab with atezolizumab or durvalumab after standard-of-care first-line chemo-immunotherapy. The median time from start of standard-of-care first-line chemo-immunotherapy to start of tarlatamab maintenance was 3·6 months (IQR 3·2–4·3). The median follow-up from the start of maintenance was 18·4 months (15·2–23·0) and the median exposure to tarlatamab was 35 weeks (8–75). The most common grade 3–4 adverse events were hyponatraemia (nine [10%] of 88 patients), anaemia (seven [8%] of 88 patients), and neutropenia (six [7%] of 88 patients). Serious adverse events occurred in 50 (57%) of 88 patients. The most common serious adverse event","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): 10-year clinical outcomes and post-hoc analysis by molecular classification from a randomised phase 3 trial","authors":"Cathalijne C B Post, Stephanie M de Boer, Melanie E Powell, Linda Mileshkin, Dionyssios Katsaros, Paul Bessette, Alexandra Leary, Petronella B Ottevanger, Mary McCormack, Pearly Khaw, Romerai D'Amico, Anthony Fyles, Cyrus Chargari, Henry C Kitchener, Viet Do, Andrea Lissoni, Diane Provencher, Catherine Genestie, Hans W Nijman, Karen Whitmarsh, Carien L Creutzberg","doi":"10.1016/s1470-2045(25)00379-1","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00379-1","url":null,"abstract":"<h3>Background</h3>The PORTEC-3 trial investigated the benefit of chemoradiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We present the preplanned long-term analysis of the randomised PORTEC-3 trial with a post-hoc analysis including molecular classification of the tumours.<h3>Methods</h3>PORTEC-3 was an open-label, multicentre, randomised, international phase 3 trial. Women were eligible if they had high-risk endometrial cancer (either International Federation of Gynecology and Obstetrics 2009 stage I, grade 3, with deep myometrial invasion and/or lymphovascular space invasion; stage II–III; or stage I–III with serous or clear-cell histology), were aged 18 years or older, and had a WHO performance score of 0–2. Participants were randomly assigned (1:1) to receive pelvic radiotherapy (48·6 Gy in 1·8 Gy fractions) or chemoradiotherapy (radiotherapy combined with two cycles of cisplatin 50 mg/m² intravenously in weeks one and four, followed by four cycles of carboplatin area-under-the-curve 5 and paclitaxel 175 mg/m² intravenously at 3-week intervals). Randomisation was done by use of biased-coin minimisation with stratification for participating centre, lymphadenectomy, stage, and histological type. We report the primary outcomes of overall survival and recurrence-free survival at 10 years. We also report primary outcomes by molecular subgroup in a post-hoc analysis. Survival was analysed in the intention-to-treat population. The study is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT00411138</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>) and is now complete.<h3>Findings</h3>Between Nov 23, 2006, and Dec 20, 2013, 660 eligible and evaluable patients recruited at 103 centres in six clinical trial groups across seven countries were randomly assigned to chemoradiotherapy (n=330) or radiotherapy alone (n=330). Median follow-up was 10·1 years (IQR 9·8–11·0). Estimated 10-year overall survival was 74·4% (95% CI 69·8–79·4) in the chemoradiotherapy group and 67·3% (62·3–72·7) in the radiotherapy group (adjusted hazard ratio [HR] 0·73 [95% CI 0·54–0·97], p=0·032), and 10-year recurrence-free survival was 72·8% (67·2–77·6) versus 67·4% (61·7–72·4; adjusted HR 0·74 [95% CI 0·56–0·98], p=0·034). Molecular analysis was available for 411 (62%) patients (210 [64%] of 330 patients in the chemoradiotherapy group and 201 [61%] of 330 patients in the radiotherapy group), whose characteristics were similar to the overall trial population. Post-hoc analysis by molecular class showed that, for women with p53 abnormal tu","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metastasis-directed radiotherapy without systemic therapy for oligometastatic clear-cell renal-cell carcinoma: primary efficacy analysis of a single-arm, single-centre, phase 2 trial","authors":"Chad Tang, Alexander D Sherry, Aaron Seo, Kieko Hara, Haesun Choi, Suyu Liu, Xiaowen Sun, Anya Montoya, Ethan B Ludmir, Amishi Y Shah, Eric Jonasch, Amado J Zurita, Craig Kovitz, Omar Alhalabi, Sangeeta Goswami, Andrew W Hahn, Matthew T Campbell, Arianna Hernandez, Kevin T Nead, Peter Van Loo, Pavlos Msaouel","doi":"10.1016/s1470-2045(25)00380-8","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00380-8","url":null,"abstract":"<h3>Background</h3>Select patients with metastatic clear-cell renal-cell carcinoma can be treated without systemic therapy, yet few studies have explored this population. We investigated the efficacy of metastasis-directed therapy without systemic therapy in oligometastatic clear-cell renal-cell carincoma.<h3>Methods</h3>This investigator-initiated single-arm, phase 2 trial enrolled patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–2, histologically confirmed clear-cell renal-cell carcinoma, and one to five metastases. Patients remained off systemic therapy and underwent metastasis-directed therapy to all disease sites, with additional metastasis-directed therapy for limited progression. Co-primary endpoints were progression-free survival based on Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) in the per-protocol population (patients who received radiation to at least one metastatic lesion during their initial local treatment) and systemic therapy-free survival in the intention-to-treat population. Progression-free survival was defined as the interval from enrolment to the first instance of disease progression, according to RECIST 1.1, or clinical progression, or death from any cause. Systemic therapy-free survival was defined as time from enrolment to initiation of systemic therapy or death from clear-cell renal-cell carcinoma. A prespecified 24-month median systemic therapy-free survival was the threshold for success. Safety was analysed in the per-protocol population. This trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT03575611</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, and is closed to new patient enrolment.<h3>Findings</h3>Between July 13, 2018, and May 2, 2023, 121 patients were enrolled and included in the intention-to-treat population, of whom 120 received at least one round of definitive radiotherapy and were included in the per-protocol and safety populations. Median follow-up time for the 121 enrolled patients was 36·3 months (IQR 26·5–51·1). Median progression-free survival was 17·7 months (95% CI 14·9–22·4), and median systemic therapy-free survival time was 34·0 months (28·3–54·1). The median and lower bound of 95% CI of the median systemic therapy-free survival time exceeded the prespecified 24-month target. Eight (7%) of 120 patients had grade 3–4 adverse events at least possibly attributable to metastasis-directed therapy. The most common grade 3 event was pain near the treatment site (four events). The single grade 4 event was hyperglycaemia. There were no t","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequential metastasis-directed therapy in renal-cell carcinoma: promising, but unproven without randomised evidence","authors":"Xingzhe Li, Raquibul Hannan","doi":"10.1016/s1470-2045(25)00464-4","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00464-4","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"304 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indian parliamentary committee seeks price cap for cancer drugs","authors":"Karl Gruber","doi":"10.1016/s1470-2045(25)00540-6","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00540-6","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"127 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Call for reform of cancer treatment decision making","authors":"Talha Burki","doi":"10.1016/s1470-2045(25)00539-x","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00539-x","url":null,"abstract":"No Abstract","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of TERT promoter mutation on predicting meningioma outcomes: a multi-institutional cohort analysis","authors":"Karenna J Groff, Ruchit V Patel, Yang Feng, Hia S Ghosh, Miguel A Millares Chavez, Joseph O'Brien, William C Chen, Vijay Nitturi, Akshay V Save, Mark W Youngblood, Craig M Horbinski, James P Chandler, Felix Ehret, Chloe Gui, Justin Z Wang, Kristen Park, Sonia Ajmera, Marc Rosenblum, Abigail K Suwala, Catena Kresbach, Wenya Linda Bi","doi":"10.1016/s1470-2045(25)00422-x","DOIUrl":"https://doi.org/10.1016/s1470-2045(25)00422-x","url":null,"abstract":"&lt;h3&gt;Background&lt;/h3&gt;Molecular aberrations have been incorporated into tumour classification guidelines of meningioma. &lt;em&gt;TERT&lt;/em&gt;-promoter (&lt;em&gt;TERT&lt;/em&gt;p) mutation is associated with worse prognosis and is designated a WHO grade 3 biomarker. However, it remains unclear whether &lt;em&gt;TERT&lt;/em&gt;p mutation is context-dependent, with other co-occurring genetic alterations potentially driving its association with prognosis. We sought to characterise the role of &lt;em&gt;TERT&lt;/em&gt;p mutation in meningioma and guide &lt;em&gt;TERT&lt;/em&gt;p sequencing.&lt;h3&gt;Methods&lt;/h3&gt;We identified 1492 patients of all ages who had previously received surgery for meningioma across 14 medical centres in the USA, Canada, and Germany. Patients were eligible if they had post-surgical clinical or radiographical assessment of the resection site, and &lt;em&gt;TERT&lt;/em&gt;p status evaluated by Nov 1, 2024. Multi-modal profiling was used to assess &lt;em&gt;TERT&lt;/em&gt;p mutation, focal gene alterations—including &lt;em&gt;CDKN2A/B&lt;/em&gt; loss—and copy number alterations. An adjusted WHO grade was calculated for &lt;em&gt;TERT&lt;/em&gt;p-mutant meningiomas, incorporating all WHO criteria except &lt;em&gt;TERT&lt;/em&gt;p status. Kaplan–Meier curves and multivariable Cox proportional hazards models were used to quantify the effect of &lt;em&gt;TERT&lt;/em&gt;p mutation on the endpoints of overall survival and recurrence-free survival across adjusted WHO grade and co-occurring molecular alterations.&lt;h3&gt;Findings&lt;/h3&gt;64 (4·3%) of 1492 meningiomas were &lt;em&gt;TERT&lt;/em&gt;p-mutant and 1428 (95·7%) were &lt;em&gt;TERT&lt;/em&gt;p-wildtype. Of the &lt;em&gt;TERT&lt;/em&gt;p-mutant meningiomas, 33 (51·6%) were from female patients and 31 (48·4%) were from male patients, and the overall median age was 67 years (IQR 60–75). Of the wildtype meningiomas, 965 (67·6%) were from female patients and 463 (32·4%) were from male patients, and the overall median age of the patients was 59 years (IQR 48–70). Data on race was inconsistently reported and thus excluded. The &lt;em&gt;TERT&lt;/em&gt;p-mutant patients had a 5-year overall survival (49·4% [95% CI 33·7–72·4]) and 5-year recurrence-free survival (27·6% [95% CI 16·8–45·5]) resembling that of patients with WHO grade 3 &lt;em&gt;TERT&lt;/em&gt;p-wildtype tumours (5-year overall survival 32·3% [95% CI 17·2–60·5], p=0·28, 5-year recurrence-free survival 14·3% [5·8–35·2], p=0·28). However, the &lt;em&gt;TERT&lt;/em&gt;p-mutant group had heterogenous histological grading and was enriched for aggressive molecular features, with 1p loss present in 44 (77·2%) of 57 profiled tumours and &lt;em&gt;CDKN2A/B&lt;/em&gt; loss in 24 (41·4%) of the 58 profiled tumours. Adjusting tumour grade revealed a subset of &lt;em&gt;TERT&lt;/em&gt;p-mutant meningiomas that were more molecularly and clinically benign. Among &lt;em&gt;TERT&lt;/em&gt;p-mutant tumours, &lt;em&gt;CDKN2A/B&lt;/em&gt; loss played a defining role in stratifying tumour behaviour. Multivariable analysis confirmed this, with &lt;em&gt;CDKN2A/B&lt;/em&gt; loss being significantly associated with shorter overall survival (HR 3·04 [95% CI 1·67–5·52], p=0·00026) and faster time to recurrence (HR 5·22 ","PeriodicalId":22865,"journal":{"name":"The Lancet Oncology","volume":"118 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}