ESMO Open最新文献

{"title":"Prognosis, clinicopathological characteristics, and treatment patterns of patients with ER-intermediate-positive breast cancer undergoing long-term follow-up","authors":"N. Matsumoto ,&nbsp;Y. Wanifuchi-Endo ,&nbsp;T. Fujita ,&nbsp;T. Asano ,&nbsp;M. Terada ,&nbsp;K. Nozawa ,&nbsp;M. Mori ,&nbsp;A. Isogai ,&nbsp;Y. Niwa ,&nbsp;H. Kato ,&nbsp;M. Komura ,&nbsp;T. Toyama","doi":"10.1016/j.esmoop.2025.104508","DOIUrl":"10.1016/j.esmoop.2025.104508","url":null,"abstract":"<div><h3>Background</h3><div>Estrogen receptor (ER) expression levels in breast cancer tissue predict the efficacy of endocrine therapy and the prognosis of breast cancer patients. Recently, it was reported that the prognosis of patients with ER-low-positive breast cancer was similar to that of ER-negative patients. This study aimed to investigate how ER expression levels impact the prognosis of patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer undergoing long-term follow-up.</div></div><div><h3>Patients and methods</h3><div>The correlation between ER expression levels and prognosis was retrospectively evaluated in a cohort of 3091 consecutive patients with HER2-negative early breast cancer who were treated at our institute between 1981 and 2022. The median follow-up period was 85.2 (range 0-480) months. The proportion of ER-expressing cells in breast cancer tissues was assessed by immunohistochemistry and used to classify patients into four categories: ER negative (&lt;1%), ER-low positive (1% ≤ ER &lt; 10%), ER-intermediate positive (10% ≤ ER &lt; 2/3), and ER-high positive (≥2/3).</div></div><div><h3>Results</h3><div>Patients with ER-intermediate-positive breast cancer had a prognosis similar to that of patients with ER-low-positive or ER-negative disease. By contrast, patients with ER-high-positive breast cancer had significantly longer disease-free survival (DFS) and overall survival (OS) times than the other groups. Multivariate analysis demonstrated that ER-intermediate positivity was an independent factor for poor prognosis for both DFS and OS in patients with HER2-negative early breast cancer. The distributions of tumor grades 1, 2, and 3 were nearly equal among the ER-intermediate-positive patients, whereas more than half of patients with ER-high-positive breast cancer had grade 1 tumors. By analyzing changes in prognosis over time, we found that the prognosis of patients with ER-high-positive breast cancer markedly improved over three decades, while that of patients with ER-intermediate-positive disease did not.</div></div><div><h3>Conclusions</h3><div>Patients with ER-intermediate-positive breast cancer differ from patients with ER-high-positive breast cancer, suggesting that the treatment of ER-positive breast cancer patients should be tailored based on ER expression levels.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104508"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739804","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":"Immune checkpoint inhibitors use in lung transplant recipients: a case series and systematic review of literature","authors":"N. Mahmoud ,&nbsp;G. Pamart ,&nbsp;C. Nardin ,&nbsp;A. Schuller ,&nbsp;S. Hirschi ,&nbsp;T. Dégot ,&nbsp;P.-E. Falcoz ,&nbsp;A. Olland ,&nbsp;C.-A. Tacquard ,&nbsp;R. Kessler ,&nbsp;B. Coiffard ,&nbsp;B. Renaud-Picard","doi":"10.1016/j.esmoop.2025.104537","DOIUrl":"10.1016/j.esmoop.2025.104537","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) are an innovative treatment that has improved long-term survival in several neoplastic diseases over the past decade. Solid organ transplant (SOT) recipients, particularly lung transplant (LTx) recipients, have been largely excluded from clinical trials evaluating the safety and efficiency of ICIs, because of the perceived high risk of allograft rejection. In this study, we sought to evaluate the use of ICIs for all neoplastic diseases in LTx patients in all French LTx centers and two Belgian centers. We found only a limited number of cases in which ICIs were suggested to two patients due to a lack of alternative treatments. In the first case, acute respiratory failure and death occurred, whereas in the second case, ICI treatment was well tolerated and resulted in a partial response. In addition, we presented the case of a third LTx patient in whom the use of ICIs was considered but not used due to the patient’s comorbidities. This last case highlights the difficulty of discussing the risk–benefit balance, which ultimately did not favor ICI treatment of this patient. Further multicenter randomized controlled trials are necessary to investigate the safety and efficacy of ICIs in LTx recipients.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104537"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739851","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":"Benefit from maintenance with PARP inhibitor in newly diagnosed ovarian cancer according to BRCA1/2 mutation type and site: a multicenter real-world study","authors":"C. Marchetti ,&nbsp;A. Fagotti ,&nbsp;R. Fruscio ,&nbsp;C. Cassani ,&nbsp;L. Incorvaia ,&nbsp;M.T. Perri ,&nbsp;C.M. Sassu ,&nbsp;C.A. Camnasio ,&nbsp;E. Giudice ,&nbsp;A. Minucci ,&nbsp;M. Seca ,&nbsp;E. Arbustini ,&nbsp;L. Vertechy ,&nbsp;M. De Bonis ,&nbsp;S.M. Boccia ,&nbsp;D. Giannarelli ,&nbsp;V. Salutari ,&nbsp;M. Distefano ,&nbsp;M.G. Ferrandina ,&nbsp;C. Nero ,&nbsp;D. Lorusso","doi":"10.1016/j.esmoop.2025.104533","DOIUrl":"10.1016/j.esmoop.2025.104533","url":null,"abstract":"<div><h3>Background</h3><div>Knowledge about the association between the <em>BRCA1/2</em> mutation type and location and response to poly (ADP-ribose) polymerase inhibitors (PARPis) as single agent in ovarian cancer is limited. This study aimed to investigate the effectiveness of PARPi based on functional domains (FD) [RING, BRCT, DNA-binding (BD), RAD51-BD] and types (frameshift, missense, nonsense, splicing) of <em>BRCA1/2</em> gene mutations in ovarian cancer.</div></div><div><h3>Materials and methods</h3><div>This multicenter real-world study retrospectively enrolled <em>BRCA1/2</em>-mutated ovarian cancer patients receiving olaparib maintenance between January 2010 and December 2022. Data were compared with historical series of patients who did not receive olaparib and analyzed based on the FD involved in <em>BRCA1/2</em> mutations. Progression-free survival was calculated from the date of the last platinum-based treatment until recurrence or last follow-up.</div></div><div><h3>Results</h3><div>After a median follow-up of 46 months (range 32-60 months), 140 patients who underwent olaparib maintenance were compared with 128 who did not. PARPi showed efficacy in the overall population. The no-exon 11 patients benefitted more from olaparib than exon 11 patients [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.25-0.93]. In the <em>BRCA1</em> group, patients with mutations in RING and BRCT domains had significant benefits from PARPi (HR 0.08, 95% CI 0.01-0.75; HR 0.10, 95% CI 0.02-0.38, respectively). Among <em>BRCA2</em>-mutated patients, RAD51-BD mutations were associated with higher response to olaparib (HR 0.23, 95% CI 0.10-0.52). According to the mutation type, the major effect of PARPi was in the missense group (HR 0.04, 95% CI 0.01-0.31). No patients with p.(Ala1708Glu) in the BRCT domain (<em>BRCA1</em>) receiving PARPi experienced recurring disease in the study period.</div></div><div><h3>Conclusions</h3><div><em>BRCA1/2</em>-mutated patients benefit from olaparib, but with variations according to the mutation type and FDs. <em>BRCA1</em>-mutated patients in the RING or BRCT and <em>BRCA2</em>-mutated in the RAD51-BD have the greatest benefit. Patients with missense mutations, especially those with p.(Ala1708Glu), have the most significant advantage from maintenance with PARPi.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104533"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143746999","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":"LUDICAS: sexual dysfunction in patients with lung cancer, a multicenter cross-sectional study☆","authors":"A.V. Ospina-Serrano ,&nbsp;A. Collazo-Lorduy ,&nbsp;E. Azkona-Uribelarrea ,&nbsp;P. Guillen-Sentís ,&nbsp;F. Aparisi ,&nbsp;R. López ,&nbsp;P. Cruz ,&nbsp;A. Valdivia ,&nbsp;P. Cordeiro ,&nbsp;A. Olivares-Hernández ,&nbsp;M. Blanco ,&nbsp;R. Casas-Cornejo ,&nbsp;E. Carcereny ,&nbsp;M. Dómine ,&nbsp;M. Antoñanzas ,&nbsp;A. Blasco-Cordellat ,&nbsp;D. Peralta ,&nbsp;M. Sereno ,&nbsp;A. Cardeña-Gutiérrez ,&nbsp;R. Romão ,&nbsp;M. Provencio-Pulla","doi":"10.1016/j.esmoop.2025.104539","DOIUrl":"10.1016/j.esmoop.2025.104539","url":null,"abstract":"<div><h3>Background</h3><div>Patients with lung cancer may suffer from sexual dysfunction (SD) related to oncological treatment. This is an under-recognized condition among clinicians. The aim of this study was to describe the prevalence of SD in a multicenter cohort of patients.</div></div><div><h3>Patients and methods</h3><div>This multicenter, cross-sectional, observational study was conducted between July 2023 and February 2024. Sexual function was assessed by patient-reported outcome (PRO) system using sex-specific questionnaire. Descriptive analysis and evaluation of differences between categorical variables were carried out. Associations between clinical characteristics and SD were assessed by logistic regression.</div></div><div><h3>Results</h3><div>Four hundred and forty-eight patients from 24 hospitals in Spain, Colombia, Argentina, and Portugal were included. Of these, 277 (61.83%) were male and 365 (81.48%) had metastatic disease. Two hundred and eighty-four patients (63.39%) reported the onset of SD following the initiation of oncological treatment. Males and females reported a high frequency of severe impairment of sexual response phases, which was twice as high in females (<em>P</em> <em>=</em> 0.001). Female sex was a factor for severe impairment of desire, arousal, and orgasm [odds ratio (OR) 3.72, 95% confidence interval (CI) 2.48-5.60, <em>P</em> <em>=</em> 0.001] and decreased sexual activity (OR 1.98, 95% CI:1.17-3.19, <em>P</em> = 0.01), in addition to age over 65 years (OR 3.86, 95% CI 1.01-15.25, <em>P</em> <em>=</em> 0.004) and high educational level (OR 0.29, 95% CI 0.09-0.94, <em>P</em> <em>=</em> 0.0040). Patients from Portugal and Latin America were more likely to report dissatisfaction with sexual activity (OR 3.75, 95% CI 1.06-13.22, <em>P</em> <em>=</em> 0.0039). Female sex (OR 3.53, 95% CI 1.88-6.6, <em>P</em> 0.001), smoking history (OR 1.77, 95% CI 1.01-4.01, <em>P</em> <em>=</em> 0.04), and obesity (OR 1.70 95% CI 1.01-3.16, <em>P</em> <em>=</em> 0.05) were associated with global sexual dissatisfaction.</div></div><div><h3>Conclusions</h3><div>Our patients with lung cancer had a high prevalence of SD after initiation of oncological treatment. There was remarkable sex disparity in the frequency and severity of this disorder as well as an important influence of sociocultural factors in the clinical presentation.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104539"},"PeriodicalIF":7.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760488","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 ,&nbsp;C. Astolfi ,&nbsp;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":"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":"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}

{"title":"Tocilizumab treatment for inflammatory dedifferentiated liposarcoma: pre- and post-treatment imaging and pathological changes","authors":"Y. Nishida ,&nbsp;S. Shimada","doi":"10.1016/j.esmoop.2025.104530","DOIUrl":"10.1016/j.esmoop.2025.104530","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104530"},"PeriodicalIF":7.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706267","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}