ESMO Open最新文献

{"title":"Comment on: Atezolizumab plus bevacizumab in unresectable HCC: insights from the AMETHISTA trial interim analysis","authors":"W. Zhu , C. Fan , J. Qin , W. Zhou","doi":"10.1016/j.esmoop.2025.104546","DOIUrl":"10.1016/j.esmoop.2025.104546","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104546"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to: Atezolizumab plus bevacizumab in unresectable HCC: insights from the AMETHISTA trial interim analysis","authors":"L. Rimassa , C. Astolfi , F. Piscaglia","doi":"10.1016/j.esmoop.2025.104547","DOIUrl":"10.1016/j.esmoop.2025.104547","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104547"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ESMO Clinical Practice Guideline Express Update on the management of metastatic pancreatic cancer","authors":"T. Conroy , M. Ducreux , ESMO Guidelines Committee","doi":"10.1016/j.esmoop.2025.104528","DOIUrl":"10.1016/j.esmoop.2025.104528","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104528"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"131I-mIBG therapy in relapsed/refractory neuroblastoma: an old bridge to the future","authors":"M.A. De Ioris ,&nbsp;M.F. Villani ,&nbsp;F. Fabozzi ,&nbsp;F. Del Bufalo ,&nbsp;C. Altini ,&nbsp;M.G. Cefalo ,&nbsp;V. Cannata ,&nbsp;G. Del Baldo ,&nbsp;M. Pizzoferro ,&nbsp;I. Alessi ,&nbsp;F. Lanzaro ,&nbsp;C. Davide ,&nbsp;P. Tomà ,&nbsp;M.L. D’Andrea ,&nbsp;A. Di Giannatale ,&nbsp;A. Serra ,&nbsp;A. Mastronuzzi ,&nbsp;M.C. Garganese ,&nbsp;F. Locatelli","doi":"10.1016/j.esmoop.2025.104541","DOIUrl":"10.1016/j.esmoop.2025.104541","url":null,"abstract":"<div><h3>Background</h3><div>The prognosis of relapsed/refractory (R/R) neuroblastoma (NB) is still dismal. The role of iodine-131 meta-iodobenzylguanidine (¹³¹I-mIBG) treatment as a tool to reduce tumour burden before novel immunotherapies is not defined.</div></div><div><h3>Patients and methods</h3><div>Patients with R/R NB were included in a prospective observational study based on two infusions of ¹³¹I-mIBG plus melphalan (110 mg/m²), supported by autologous haematopoietic stem cell rescue. The activity of the first administration was 444 MBq (12 mCi/kg), while the second dose was modulated to reach a whole-body absorbed dose of 4 Gy. The International Neuroblastoma Response Criteria (INRC) were used for response.</div></div><div><h3>Results</h3><div>Twenty-six patients with a median age of 5.9 years (range 2.5-17.2 years) were treated. Twenty-three patients presented a bone/bone marrow involvement, and 21 patients presented an uptake at primary site or at soft-tissue sites. The median International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOPEN) skeletal score was 10 (range 1-70). The main recorded toxicities were haematological, with no toxic deaths and only one grade 4 mucositis. Hypothyroidism was reported in 6 patients of the 14 alive patients. The overall response rate was 48% [95% confidence interval (CI) 28% to 69%] with only one progression; after treatment the median SIOPEN skeletal score was 6 (range 0-70) with a median reduction of 35% (range 4.3%-100%). Overall, 52% (95% CI 32% to 73%) of patients achieved/maintained a SIOPEN skeletal score &lt;7 and a soft-tissue lesion &lt;5 cm was seen in 67% (95% CI 43% to 91%). After this treatment, 65% of patients underwent GD2-targeting chimeric antigen receptor (CAR)-T-cell therapy and 50%, high-dose chemotherapy with busulfan and melphalan. The 3-year overall survival was 55% (95% CI 33% to 73%) and event-free survival was 42% (95% CI 23% to 60%).</div></div><div><h3>Conclusion</h3><div>The ¹³¹I-mIBG therapy plus melphalan is confirmed to be effective to reduce/control tumour burden. Further studies are needed to clarify the role and timing of this treatment and to integrate its role in the strategy of CAR-T cells.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104541"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and clinical impact of germline pathogenic variants in breast cancer: a descriptive large single-center study","authors":"A. Rodriguez-Hernandez ,&nbsp;O. Martínez-Sáez ,&nbsp;F. Brasó-Maristany ,&nbsp;B. Conte ,&nbsp;R. Gómez ,&nbsp;I. García-Fructuoso ,&nbsp;B. Fratini ,&nbsp;E. Segui ,&nbsp;M. Potrony ,&nbsp;E. Sanfeliu ,&nbsp;S. Cobo ,&nbsp;P. Galvan ,&nbsp;L. Moreno ,&nbsp;E. Grau ,&nbsp;M.R. Aceituno ,&nbsp;J.A. Puig-Butille ,&nbsp;J. Oriola ,&nbsp;G. Goberna ,&nbsp;P. Blasco ,&nbsp;O. Castillo ,&nbsp;B. Adamo","doi":"10.1016/j.esmoop.2025.104543","DOIUrl":"10.1016/j.esmoop.2025.104543","url":null,"abstract":"<div><h3>Background</h3><div>Germline (likely) pathogenic variants (PVs) are identified in 5%-10% of patients with breast cancer (BC) and play a critical role in guiding clinical management, including the use of targeted therapies such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). High-risk genes such as <em>BRCA1, BRCA2</em>, and <em>PALB2</em>, and moderate-risk genes such as <em>CHEK2</em> and <em>ATM</em>, influence BC risk and treatment decisions. This study evaluates the prevalence and clinical impact of PVs in a large consecutive cohort.</div></div><div><h3>Materials and methods</h3><div>A retrospective analysis was conducted on 912 individuals with BC who underwent germline testing at the Hospital Clinic of Barcelona from 2016 to 2023. Genetic testing for 14 BC and Lynch syndrome genes was carried out using the TruSight Hereditary Cancer Panel. Statistical analyses were carried out to assess associations between germline results and clinical characteristics, including eligibility for PARPi therapy.</div></div><div><h3>Results</h3><div>Of the 912 individuals, 129 (14.1%) had a PV, with <em>BRCA2</em> (31.8%) and <em>BRCA1</em> (24%) being the most frequently altered genes. Additionally, 16.2% carried variants of uncertain significance, most commonly in <em>ATM</em> and <em>BRCA2</em> genes. Patients with PV were younger compared with PV-negative individuals (median age: 43.5 versus 48.2 years, <em>P</em> = 0.006), more likely to have bilateral BC (13.3% versus 5.8%, <em>P</em> = 0.002), and more frequently diagnosed with triple-negative BC (TNBC; 28.7% versus 20.8%, <em>P</em> = 0.046). Of those with PVs, 39.1% completed a bilateral mastectomy, 36.7% had a risk-reducing salpingo-oophorectomy, and 22.7% had both surgeries. PV detection was associated with higher stages at diagnosis (stage IV: 13.0% versus 5.9%, <em>P</em> &lt; 0.001). In the metastatic cohort, 12.9% received PARPi therapy, with 80.7% harboring <em>BRCA1/2</em> PVs. In early BC, 13.1% met the criteria for adjuvant PARPi.</div></div><div><h3>Conclusions</h3><div>The identification of germline PVs significantly influences surgical decisions and systemic therapies. Genetic testing for patients with BC optimizes care, particularly in selecting candidates for PARPi in both early and advanced BC, improving management and prevention strategies.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104543"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143807800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical cancer nutrition, from guidelines to clinical practice: a digital solution to patient-centred care","authors":"K.S. Hustad ,&nbsp;L.H. Koteng ,&nbsp;A. Urrizola ,&nbsp;J. Arends ,&nbsp;A. Bye ,&nbsp;O. Dajani ,&nbsp;L. Deliens ,&nbsp;M. Fallon ,&nbsp;M.J. Hjermstad ,&nbsp;M. Kohlen ,&nbsp;G.P. Kurita ,&nbsp;T. Lundeby ,&nbsp;N. Mitrea ,&nbsp;C. Payne ,&nbsp;S. Roselló-Keränen ,&nbsp;N. Warmbrodt ,&nbsp;A. de Wilde ,&nbsp;S. Kaasa ,&nbsp;J. de Vos-Geelen ,&nbsp;B.J.A. Laird ,&nbsp;R. Williams","doi":"10.1016/j.esmoop.2025.104529","DOIUrl":"10.1016/j.esmoop.2025.104529","url":null,"abstract":"<div><h3>Background</h3><div>Malnutrition affects 20%-70% of cancer patients, depending on tumour type, disease stage, and clinical setting. While nutritional care is essential for improving patients’ quality of life and clinical outcomes, it is not systematically integrated into routine cancer care. MyPath is a European Union project aiming to implement patient-centred care (PCC) at nine European cancer centres using implementation science. Multidisciplinary teams have developed standardised digitally supported PCC pathways based on patient-reported outcomes (PROs) with linked evidence-based management options. Through systematic assessment and management of common symptoms and psychosocial problems in cancer patients, MyPath aims to facilitate changes in clinical practice to improve PCC for all. As part of this, the MyPath Nutrition Care Pathway (NCP) aims to facilitate necessary clinical changes to routinely assess and address nutrition in all patients.</div></div><div><h3>Materials and methods</h3><div>Between September 2022 and August 2024, an international multidisciplinary team reviewed evidence-based nutrition guidelines to select relevant PROs and other variables necessary to systematically assess patients, allowing for tailored nutritional care.</div></div><div><h3>Results</h3><div>The MyPath NCP assessment relies on nutritional status (Malnutrition Screening Tool for malnutrition risk, modified Global Leadership Initiative on Malnutrition criteria for malnutrition, and body mass index/weight change for obesity/unintentional weight gain), health status (functional status, cancer diagnosis and prognosis, and prehabilitation needs), and inflammatory status (C-reactive protein levels). Based on this assessment, the digital solution suggests tailored, evidence-based nutritional interventions. Continuous monitoring through PROs and clinical consultations will customise care to patients’ dynamic nutritional needs. The first version of this digital solution will be piloted in 2025.</div></div><div><h3>Conclusions</h3><div>Inconsistent implementation of nutrition guidelines is a key challenge in cancer care. The MyPath NCP offers an accessible, patient-centred assessment and management system that integrates nutritional care into routine cancer care, providing a versatile solution that can be implemented across diverse health care settings.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104529"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of tarlatamab with 6-8-h outpatient versus 48-h inpatient monitoring during cycle 1: DeLLphi-300 phase 1 substudy","authors":"A.C. Chiang ,&nbsp;M.E. Olmedo Garcia ,&nbsp;J.W. Carlisle ,&nbsp;A. Dowlati ,&nbsp;N. Reguart ,&nbsp;E. Felip ,&nbsp;P.J. Jost ,&nbsp;N. Steeghs ,&nbsp;R. Stec ,&nbsp;S.M. Gadgeel ,&nbsp;H.H. Loong ,&nbsp;W. Jiang ,&nbsp;A. Hamidi ,&nbsp;A. Parkes ,&nbsp;L. Paz-Ares","doi":"10.1016/j.esmoop.2025.104538","DOIUrl":"10.1016/j.esmoop.2025.104538","url":null,"abstract":"<div><h3>Background</h3><div>Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3, has demonstrated promising survival outcomes in small-cell lung cancer (SCLC). Given the risk of cytokine release syndrome (CRS), initial clinical trials incorporated 48-72-h inpatient monitoring in cycle 1.</div></div><div><h3>Methods</h3><div>Patients with previously treated SCLC were enrolled into DeLLphi-300 part F, which evaluated the safety of tarlatamab 10 mg every 2 weeks (Q2W) with 6-8-h outpatient monitoring following cycle 1 doses. The primary endpoint, safety, was compared with patients from DeLLphi-300 part A receiving tarlatamab 10 mg Q2W with 48-h inpatient monitoring for cycle 1 doses.</div></div><div><h3>Results</h3><div>In cycle 1, the rates of treatment-related adverse events and hospitalizations, including emergency room visits, were similar between outpatient (<em>n</em> = 30) and inpatient (<em>n</em> = 58) groups (93% versus 100% and 27% versus 34%, respectively). The incidence of all grade and serious CRS during cycle 1 was similar between outpatient and inpatient groups (any grade: 60% versus 62%; serious: 17% versus 22%). The median time to CRS resolution was 3 days for both groups.</div></div><div><h3>Conclusions</h3><div>Safety outcomes, including hospitalization rates, were similar in this first-in-human study following tarlatamab 10 mg Q2W administration with 6-8-h outpatient versus 48-h inpatient monitoring in cycle 1.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104538"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive genomic and transcriptomic analysis enables molecularly guided therapy options in peritoneal and pleural mesothelioma","authors":"L. Möhrmann ,&nbsp;M. Werner ,&nbsp;M. Oleś ,&nbsp;L. Knol ,&nbsp;J.S. Arnold ,&nbsp;T. Mundt ,&nbsp;N. Paramasivam ,&nbsp;D. Richter ,&nbsp;M. Fröhlich ,&nbsp;B. Hutter ,&nbsp;J. Hüllein ,&nbsp;A. Jahn ,&nbsp;C. Scheffold ,&nbsp;E.E. Möhrmann ,&nbsp;D. Hanf ,&nbsp;S. Kreutzfeldt ,&nbsp;C.E. Heilig ,&nbsp;M.-V. Teleanu ,&nbsp;D.B. Lipka ,&nbsp;K. Beck ,&nbsp;H. Glimm","doi":"10.1016/j.esmoop.2025.104532","DOIUrl":"10.1016/j.esmoop.2025.104532","url":null,"abstract":"<div><h3>Introduction</h3><div>Peritoneal, pericardial and pleural mesothelioma (PeM/PcM/PM) are rare and aggressive diseases with limited survival. Molecularly guided therapy is currently not part of standard care.</div></div><div><h3>Methods</h3><div>This study integrates molecular and clinical data from 51 patients (among them 28 PM, one PcM, 21 PeM and one synchronous PeM/PM) enrolled in the National Center for Tumor Diseases and the German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER), a multicenter precision oncology registry trial addressing adults with rare advanced-stage cancers. Analysis comprised both somatic and germline whole exome sequencing/whole genome sequencing and transcriptome analysis leading to personalized treatment recommendations issued by a dedicated molecular tumor board. To assess clinical efficacy, progression-free survival (PFS) ratios comparing molecularly informed therapies (PFS2) to preceding systemic therapies (PFS1) were calculated. Efficacy of immune checkpoint inhibition applied during the observation period was assessed accordingly.</div></div><div><h3>Results</h3><div>Cancer-related genes altered in more than 5 out of 44 assessable patients were <em>BAP1</em>, <em>CDKN2A</em>, <em>NF2</em>, <em>SETD2</em> and <em>TP53</em>. Somatic (<em>n</em> = 23) or germline (<em>n</em> = 9) alterations in homologous recombination-related genes were detected in 27/44 patients. In 21/44 cases, they were supported by positive combined homologous recombination deficiency scores or BRCAness signature. Following American College of Medical Genetics and Genomics guidelines, (likely) pathogenic germline variants in autosomal dominant cancer predisposition genes were found in 8/51 patients. Molecular tumor board recommendations were issued in 46 cases and applied in 6 cases. Mean PFS ratio was 2.45 (<em>n</em> = 5). Median PFS2 was 6.5 months (<em>n</em> = 6), median PFS1 was 4.0 months (<em>n</em> = 5). A total of 27 patients received immune checkpoint inhibition during the observation period leading to a mean PFS ratio of 1.69 (<em>n</em> = 19).</div></div><div><h3>Conclusions</h3><div>In mesothelioma, comprehensive molecular analysis can provide valuable clinically actionable information. Molecularly informed therapy recommendations can lead to clinical benefit.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104532"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in individualization of systemic treatment for locoregionally advanced nasopharyngeal carcinoma: a systematic review","authors":"P. Blanchard ,&nbsp;F. De Felice ,&nbsp;M.L.K. Chua","doi":"10.1016/j.esmoop.2025.104513","DOIUrl":"10.1016/j.esmoop.2025.104513","url":null,"abstract":"<div><h3>Background</h3><div>The optimal treatment strategy (radiotherapy with induction, concurrent or adjuvant chemotherapy) for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains to be addressed. Identifying biomarkers related to precise prognostic risk stratification and treatment benefits gained have been explored in recent years.</div></div><div><h3>Methods</h3><div>We carried out a systematic review of the published literature covering these topics. Of 3732 references screened, 26 articles were found eligible for inclusion.</div></div><div><h3>Results</h3><div>Regarding the issue of treatment pathway in LA-NPC, induction chemotherapy is usually preferred over adjuvant chemotherapy. It is paramount to stress patient selection to identify those cases at high risk of relapse requiring systemic intensification. Concerning a role for Epstein–Barr virus (EBV) DNA-based personalized therapy, EBV DNA and its kinetics in plasma potentially represents a robust prognostic marker after (chemo)radiotherapy, but it is necessary to standardize test and cut-off levels.</div></div><div><h3>Conclusions</h3><div>This systematic review provides an overview of biomarker-guided systemic treatment designed to improve prognosis, including key aspects of current guidelines, biomolecular signature aspects and potential limitations between applicability to cancer treatment in endemic regions versus non-endemic regions.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104513"},"PeriodicalIF":7.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-cancer clinical and molecular landscape of MTAP deletion in nationwide and international comprehensive genomic data","authors":"H. Ikushima ,&nbsp;K. Watanabe ,&nbsp;A. Shinozaki-Ushiku ,&nbsp;K. Oda ,&nbsp;H. Kage","doi":"10.1016/j.esmoop.2025.104535","DOIUrl":"10.1016/j.esmoop.2025.104535","url":null,"abstract":"<div><h3>Background</h3><div>Early-phase clinical trials of protein arginine methyltransferase 5 (PRMT5) inhibitors as synthetic lethal strategies have shown promising efficacy in methylthioadenosine phosphorylase (<em>MTAP</em>)-deleted tumors. To refine and expand this promising therapeutic approach within the framework of precision oncology, it is critical to comprehensively characterize the clinical and molecular profiles of <em>MTAP</em>-deleted tumors.</div></div><div><h3>Materials and methods</h3><div>This pan-cancer retrospective cohort study analyzed clinico-genomic data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, which includes 99.7% of patients who underwent comprehensive genomic profiling (CGP) in Japan between June 2019 and November 2023. Machine learning and explainable artificial intelligence methods were applied to identify clinical predictors of MTAP deficiency. Findings were validated and compared using The Cancer Genome Atlas (TCGA) and American Association for Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE) datasets.</div></div><div><h3>Results</h3><div>Among 51 828 pan-cancer patients in the C-CAT cohort, <em>MTAP</em> deletion was observed in 4964 cases (9.6%), with a high prevalence in pancreatic (18.4%), biliary tract (15.6%), and lung (14.3%) cancers. <em>MTAP</em> deletion was associated with distinct clinical features, including male sex (56.0% versus 47.8%), older age (mean 62.4 versus 59.8 years), and shorter interval from diagnosis to CGP (median 380.0 versus 567.0 days). In pancreatic cancer, <em>MTAP</em> deletion was more common in <em>KRAS</em>-mutant tumors (19.8%) compared with <em>KRAS</em> wild-type tumors (8.9%). Across cancer types, <em>MTAP</em> deletion was less frequent in <em>RB1</em>-mutant tumors (pan-cancer: 3.2%, pancreatic: 7.6%, lung: 2.5%, biliary tract: 5.4%) than in <em>RB1</em> wild-type tumors (9.9%, 18.7%, 16.1%, 16.0%). These findings were validated using the TCGA (<em>n</em> = 9896) and GENIE (<em>n</em> = 178 034) datasets. In lung adenocarcinoma, <em>MTAP</em> deletion was found in 22.8% of <em>EGFR</em>-mutated tumors, 25.0% of <em>ALK</em>-translocated tumors, and 20.8% of <em>ROS1</em>-translocated tumors.</div></div><div><h3>Conclusions</h3><div><em>MTAP</em> deletion is associated with unique clinical and molecular features. These findings define the characteristics of <em>MTAP</em>-deleted cancers and provide a basis for synthetic lethal strategies in precision oncology.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104535"},"PeriodicalIF":7.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}