ESMO Open最新文献

{"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}

{"title":"Detection of minimal residual disease and prediction of recurrence in breast cancer using a plasma-only circulating tumor DNA assay","authors":"W. Janni ,&nbsp;B. Rack ,&nbsp;T.W.P. Friedl ,&nbsp;A.D. Hartkopf ,&nbsp;L. Wiesmüller ,&nbsp;K. Pfister ,&nbsp;F. Mergel ,&nbsp;A. Fink ,&nbsp;T. Braun ,&nbsp;F. Mehmeti ,&nbsp;N. Uhl ,&nbsp;A. De Gregorio ,&nbsp;J. Huober ,&nbsp;T. Fehm ,&nbsp;V. Müller ,&nbsp;T.A. Rich ,&nbsp;D.J. Dustin ,&nbsp;S. Zhang ,&nbsp;S.T. Huesmann","doi":"10.1016/j.esmoop.2025.104296","DOIUrl":"10.1016/j.esmoop.2025.104296","url":null,"abstract":"<div><h3>Background</h3><div>Detection of minimal residual disease (MRD) in early breast cancer (EBC) after curative-intent treatment may identify patients at risk for recurrence. Most circulating tumor DNA (ctDNA)-based MRD assays require knowledge of genomic alterations from tumor tissue. However, tissue availability may be limited in some patients. Here, we evaluated sensitivity and specificity for recurrence detection, using a plasma-only ctDNA MRD assay.</div></div><div><h3>Materials and methods</h3><div>For this pilot study, 47 plasma samples from 38 EBC patients were collected at 12 or 36 months post-diagnosis or at clinical recurrence. ctDNA presence was determined by a custom bioinformatics classifier that identifies tumor-derived somatic variants and methylation profiles specific to individual cancer types using a 5-Mb next-generation sequencing panel.</div></div><div><h3>Results</h3><div>ctDNA was detected at or before distant recurrence in 11/14 (79%) patients [sensitivity was 85% (11/13) among samples collected within 2 years from recurrence]. Lead time was evaluable in 4/6 (67%) samples collected before distant recurrence with detectable ctDNA and ranged from 3.4 to 18.5 months. ctDNA was not detected in samples from patients without recurrence (<em>n</em> = 13).</div></div><div><h3>Conclusions</h3><div>This study demonstrates the feasibility of MRD detection in EBC using a plasma-only multiomic ctDNA-based approach. Larger studies are ongoing to further validate the clinical performance of the assay and demonstrate its applications.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104296"},"PeriodicalIF":7.1,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681794","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":"Global health inequalities in female-specific cancers from 1990 to 2021: insights from the Global Burden of Disease Study 2021","authors":"X. Shu ,&nbsp;Y. Meng ,&nbsp;J. Yang ,&nbsp;S. Cui ,&nbsp;F. Kong","doi":"10.1016/j.esmoop.2025.104512","DOIUrl":"10.1016/j.esmoop.2025.104512","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104512"},"PeriodicalIF":7.1,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673527","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":"Authors response to Letter re: The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP) molecular complexity and response to targeted therapy","authors":"K. Verkerk ,&nbsp;E.E. Voest","doi":"10.1016/j.esmoop.2025.104515","DOIUrl":"10.1016/j.esmoop.2025.104515","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104515"},"PeriodicalIF":7.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669483","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":"How we treat patients with metastatic uveal melanoma","authors":"E.F. Saldanha ,&nbsp;M.F. Ribeiro ,&nbsp;I. Hirsch ,&nbsp;A. Spreafico,&nbsp;S.D. Saibil ,&nbsp;M.O. Butler","doi":"10.1016/j.esmoop.2025.104496","DOIUrl":"10.1016/j.esmoop.2025.104496","url":null,"abstract":"<div><div>Uveal melanoma is the most prevalent and aggressive intraocular malignancy affecting adults. Compared with cutaneous melanoma, uveal melanoma has distinct pathogenesis and molecular characteristics. Not surprisingly, it derives limited benefits from checkpoint inhibitors. Until recently, no systemic therapy had impacted survival outcomes for this patient population. Tebentafusp, a T-cell receptor-based molecule, is the first US Food and Drug Administration/European Medicines Agency-approved systemic therapy to improve the survival outcomes for uveal melanoma patients expressing HLA-A∗02:01. Only 45%-50% of this patient population will express the HLA-A∗02:01, however, and therefore are eligible to receive this novel treatment. Moreover, global access to tebentafusp is limited, and there are no guidelines to aid clinicians in decision-making regarding treatment. In this review, we outline our experience as Canada's largest tertiary referral centre in managing metastatic uveal melanoma patients and provide a comprehensive overview of the currently available treatment options, challenging scenarios, and ongoing clinical trials for patients with metastatic uveal melanoma.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104496"},"PeriodicalIF":7.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669485","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":"Corrigendum to “A phase II study of tepotinib in patients with advanced solid cancers harboring MET exon 14 skipping mutations or amplification (KCSG AL19-17)”","authors":"E.J. Kang ,&nbsp;Y. Yang ,&nbsp;S. Lee ,&nbsp;Y.J. Kim ,&nbsp;S.M. Lim ,&nbsp;M.-J. Ahn ,&nbsp;Y.J. Choi ,&nbsp;Y. Lee ,&nbsp;T.M. Kim ,&nbsp;I. Kim ,&nbsp;H.K. Ahn ,&nbsp;H.-C. Jeung ,&nbsp;S.I. Lee ,&nbsp;S.Y. Oh ,&nbsp;W.K. Bae ,&nbsp;H. Ryu ,&nbsp;K.H. Park ,&nbsp;K.H. Lee","doi":"10.1016/j.esmoop.2025.104302","DOIUrl":"10.1016/j.esmoop.2025.104302","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104302"},"PeriodicalIF":7.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669484","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":"Molecular tumour board in gastrointestinal cancers","authors":"L. Boscolo Bielo ,&nbsp;E. Crimini ,&nbsp;M. Repetto ,&nbsp;M. Barberis ,&nbsp;E. Battaiotto ,&nbsp;J. Katrini ,&nbsp;E. Martino ,&nbsp;G. Gaudio ,&nbsp;M. Lombardi ,&nbsp;C. Zanzottera ,&nbsp;G. Aurilio ,&nbsp;C. Belli ,&nbsp;Y. Zhan ,&nbsp;V. Fuorivia ,&nbsp;R.M. Marsicano ,&nbsp;J.D. Etessami ,&nbsp;P. Zagami ,&nbsp;A. Marra ,&nbsp;D. Trapani ,&nbsp;B. Taurelli Salimbeni ,&nbsp;G. Curigliano","doi":"10.1016/j.esmoop.2025.104510","DOIUrl":"10.1016/j.esmoop.2025.104510","url":null,"abstract":"<div><h3>Background</h3><div>Comprehensive genomic profiling (CGP) is being increasingly adopted in clinical practice to guide the use of molecularly guided treatment options (MGTOs). To optimize the integration of MGTOs in routine cancer care, molecular tumour boards (MTBs) have been established. Limited data are available to address the clinical value of implementing MTBs to inform treatment decision making in patients with gastrointestinal (GI) cancers.</div></div><div><h3>Materials and methods</h3><div>We retrospectively retrieved medical records from patients with advanced GI cancers discussed at the European Institute of Oncology’s MTB between August 2019 and December 2024. We evaluated clinical outcomes resulting from applying MGTOs in cancer care according to MTB recommendations, describing real-world progression-free (rwPFS) and overall survival (OS), and used the growth modulation index (GMI) (ratio of PFS^MTB to PFS^prior) to quantify the effectiveness of MTB’s recommended cancer treatment in extending PFS.</div></div><div><h3>Results</h3><div>Among 192 patients with GI cancers discussed at MTB, 139 (72.3%) received an MTB treatment recommendation. For patients with available follow-up data (<em>n</em> = 82), 31 patients (41.4%, 17.7% overall) received MGTOs, while 51 patients received standard treatments. Patients receiving MGTOs exhibited a longer rwPFS compared with cases receiving standard therapies [5.35 versus 3.55 months, hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.36-1.08, <em>P =</em> 0.08] and with unmatched cases showing actionable biomarkers but not treated with targeted agents (<em>n</em> = 31) (rwPFS 5.35 versus 2.40 months, HR 0.49, 95% CI 0.27-0.90, <em>P</em> = 0.02). The use of MGTOs resulted in a GMI of 1.12 (interquartile range 0.68-2.36). The European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT) tier I-III treatments resulted in a restricted mean PFS gain of 4.87 months compared with standard therapies (95% CI 1.02-8.72 months, <em>P =</em> 0.01). No OS difference was observed between patients receiving MGTOs and standard treatments (<em>P =</em> 0.89).</div></div><div><h3>Conclusions</h3><div>Our results suggest that MTB-informed clinical decision making could provide valuable clinical benefits and expanded therapeutic options in patients affected by advanced GI cancers.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104510"},"PeriodicalIF":7.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669486","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-related adverse events are associated with better event-free survival in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage triple-negative breast cancer","authors":"A. Rios-Hoyo ,&nbsp;J. Dai ,&nbsp;T. Noel ,&nbsp;K.R.M. Blenman ,&nbsp;T. Park ,&nbsp;L. Pusztai","doi":"10.1016/j.esmoop.2025.104494","DOIUrl":"10.1016/j.esmoop.2025.104494","url":null,"abstract":"<div><h3>Background</h3><div>Immune-related adverse events (irAEs) have been associated with improved outcomes in different tumors; however, their impact during neoadjuvant immune checkpoint inhibitor therapy and chemotherapy in triple-negative breast cancer (TNBC) remains unknown.</div></div><div><h3>Patients and methods</h3><div>This analysis included patients from a phase I/II single-arm clinical trial at Yale Cancer Center and its regional care centers. The study was conducted from December 2015 to December 2020. Eligible patients were adults aged ≥18 years with clinical stage I-III TNBC for whom systemic chemotherapy was indicated. Patients received durvalumab concomitant with nab-paclitaxel and dose-dense doxorubicin–cyclophosphamide. Durvalumab was not administered post-operatively. We examined the association of developing an irAE with pathologic complete response (pCR = ypT0/is, ypN0), residual cancer burden (RCB), event-free survival (EFS), and overall survival (OS). A landmark analysis from the time of surgery was also carried out.</div></div><div><h3>Results</h3><div>A total of 67 patients were eligible for toxicity and efficacy analysis; of these, 27 had irAEs of any grade and 13 had multiple irAEs. The median follow-up was 61 months (range 6.8-94.03 months). The most frequent irAEs were dermatologic (<em>n</em> = 14), endocrine (<em>n</em> = 13), and gastrointestinal (<em>n</em> = 5). Patients who experienced irAEs achieved a pCR or RCB 0-1 rate of 56% and 73%, respectively, compared with 40% and 55% in those without irAEs (<em>P</em> = 0.309 and 0.19). Development of irAE was also associated with significantly improved EFS [hazard ratio (HR) 0.25; 95% confidence interval (CI) 0.09-0.66, <em>P</em> = 0.024] and a trend for improved OS (HR 0.42; 95% CI 0.14-1.27, <em>P</em> = 0.17). Patients with more than one irAE had no EFS events. The landmark analysis showed similar results (EFS HR 0.19, <em>P</em> = 0.014; OS HR 0.4, <em>P</em> = 0.16).</div></div><div><h3>Conclusions</h3><div>The development of irAE was associated with numerically improved pCR rates, lower RCB, and significantly higher EFS in patients treated with neoadjuvant immune checkpoint therapy plus chemotherapy.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 4","pages":"Article 104494"},"PeriodicalIF":7.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643052","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}