ESMO Open最新文献

{"title":"Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with pancreatic cancer","authors":"D. Tai ,&nbsp;T. Conroy ,&nbsp;J.J.X. Lee ,&nbsp;C.E. Chee ,&nbsp;C.-Y. Hao ,&nbsp;I. Wijaya ,&nbsp;S. Aggarwal ,&nbsp;M. Ueno ,&nbsp;H.-C. Jeung ,&nbsp;N.M. Hashim ,&nbsp;J. Tan Chun Bing ,&nbsp;L.-T. Chen ,&nbsp;K. Korphaisarn ,&nbsp;S. Tanasanvimon ,&nbsp;W.-C. Chou ,&nbsp;E. Cargullo ,&nbsp;N.F.A. Muin ,&nbsp;M.A. Lee ,&nbsp;A. Ohba ,&nbsp;S. Bondarde ,&nbsp;M. Ducreux","doi":"10.1016/j.esmoop.2025.105826","DOIUrl":"10.1016/j.esmoop.2025.105826","url":null,"abstract":"<div><div>The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with pancreatic cancer, published in November 2023, were adapted in December 2024, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with pancreatic cancer. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with pancreatic cancer representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Singapore Society of Oncology (SSO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different regions of Asia. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with pancreatic cancer across the different countries of Asia, drawing on the evidence provided by both Western and Asian trials. Attention is drawn to the disparity in drug approvals and reimbursement strategies between the different countries.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105826"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257791","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":"Venous thromboembolic event risk with PARP inhibitors in solid tumors: a systematic review and meta-analysis","authors":"S.C. Yazgan ,&nbsp;E. Yekedüz ,&nbsp;E. Akkuş ,&nbsp;M. Sun ,&nbsp;S. Gillessen ,&nbsp;K. Fizazi ,&nbsp;R.R. McKay ,&nbsp;C. Ay ,&nbsp;E. Castro ,&nbsp;N. Agarwal ,&nbsp;T.K. Choueiri ,&nbsp;Y. Ürün","doi":"10.1016/j.esmoop.2025.105811","DOIUrl":"10.1016/j.esmoop.2025.105811","url":null,"abstract":"<div><h3>Background</h3><div>Poly (ADP-ribose) polymerase inhibitors (PARPi) are linked to thrombotic events, but the thrombosis risk in various cancers is unclear. This study evaluates the incidence and risk of venous thromboembolic events (VTEs) in patients with solid tumors treated with PARPi.</div></div><div><h3>Materials and methods</h3><div>This meta-analysis included randomized controlled phase II and III clinical trials in which patients with prostate, breast, ovarian, pancreatic, glioblastoma, small-cell lung (SCLC), and non-small-cell lung (NSCLC) cancers were treated with PARPi as monotherapy or in combination. The primary endpoint was to assess the frequency and risk of VTEs in patients treated with PARPi, while the secondary endpoint compared the incidence across different cancer subtypes.</div></div><div><h3>Results</h3><div>The analysis included 15 008 patients from 38 studies: 8805 in the PARPi group and 6203 in the control group. There were 11 ovarian cancer (<em>n</em> = 4348), 8 prostate cancer (<em>n</em> = 3872), 9 breast cancer (<em>n</em> = 4448), 4 NSCLC (<em>n</em> = 1063), and 3 SCLC (<em>n</em> = 583) studies, and 1 study each for pancreatic cancer (<em>n</em> = 50), glioblastoma (<em>n</em> = 123), and gastric (<em>n</em> = 521) cancer. The incidence of any-grade VTEs with PARPi was observed to be 2.4%, compared with 1.6% in controls, suggesting a possible increase in risk [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.00-1.88, <em>P</em> = 0.050]. This association appeared to be more pronounced in patients with prostate cancer (OR 1.98, 95% CI 1.06-3.70, <em>P</em> = 0.030) and pancreatic cancer (OR 7.22, 95% CI 1.40-37.25, <em>P</em> = 0.020).</div></div><div><h3>Conclusions</h3><div>While our findings indicate a possible association between PARPi and VTE risk in certain cancer types, this risk appears to be influenced by factors such as cancer subtype and treatment combinations. The overall contribution of PARPi monotherapy to VTE risk may be limited, and the results should be interpreted with caution due to study heterogeneity, wide CIs, and the absence of patient-level data.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105811"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198689","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":"Expression of antibody–drug conjugate targets in soft tissue sarcomas","authors":"F. Bertucci ,&nbsp;P. Finetti ,&nbsp;L. Mescam ,&nbsp;A. Monneur ,&nbsp;A. Frejafon ,&nbsp;A. Le Cesne ,&nbsp;I. Treilleux ,&nbsp;A. Italiano ,&nbsp;M. Brahmi ,&nbsp;J.-Y. Blay ,&nbsp;E. Mamessier","doi":"10.1016/j.esmoop.2025.105837","DOIUrl":"10.1016/j.esmoop.2025.105837","url":null,"abstract":"<div><h3>Background</h3><div>Soft tissue sarcomas (STSs) are aggressive and heterogeneous tumors with few efficient systemic therapies. Antibody–drug conjugates (ADCs) represent an emerging therapeutic option in oncology. Their efficacy is dependent on the expression of the ADC target on tumor cells. Very few data are available on ADC target expression in STSs.</div></div><div><h3>Materials and methods</h3><div>We analyzed the mRNA expression of 62 targets and 60 genes potentially involved in resistance/response to ADC in 1664 clinical primary tumors, including 476 liposarcomas (LPSs) 341 leiomyosarcomas, 330 undifferentiated pleomorphic sarcomas, 286 gastrointestinal stromal tumors, 126 synovial sarcomas, and 105 myxofibrosarcomas. Tumor expression in each type was compared with expression in 7414 normal tissue samples. To confirm the results at the protein level, we applied immunohistochemistry (IHC) to four ADC targets in another series of STS samples.</div></div><div><h3>Results</h3><div>Expression profiles of ADC targets were heterogeneous across and within all STS types. All types expressed multiple ADC targets. An overexpression rate of at least 25% of samples in at least one type was observed for 41 targets. The high target overexpression rate in some STS types suggested numerous new therapeutic opportunities not currently studied in clinical trials, such as PTK7 overexpressed in 81% of LPSs. In addition, co-expression of ADC-target pairs and of targets with signatures of vulnerability to immune checkpoint inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors, and cyclin-dependent kinase (CDK)4/6 inhibitors was evidenced in the different pathological types, suggesting opportunities for testing ADC-based combinations. Finally, we showed heterogeneous expression profiles of potential ADC resistance/response genes between and within STS types. IHC confirmed the mRNA results for the four tested targets.</div></div><div><h3>Conclusion</h3><div>STSs express multiple target genes relevant for ADC treatment and expression varies between and within the pathological types. This comprehensive ADC target landscape, based on the largest molecular epidemiology study in STS, should help clinicians and drug developers for further evaluation of ADCs across STS types.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105837"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227276","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":"Artificial intelligence defines spatial patterns of tumor-infiltrating lymphocytes highly associated with outcome – a pan-GI cancer study","authors":"C. Chen ,&nbsp;H.A. Mejbel ,&nbsp;T. Pathak ,&nbsp;A. Krasinskas ,&nbsp;M. Reid ,&nbsp;G. Corredor ,&nbsp;P. Fu ,&nbsp;J.E. Willis ,&nbsp;A. Madabhushi","doi":"10.1016/j.esmoop.2025.105757","DOIUrl":"10.1016/j.esmoop.2025.105757","url":null,"abstract":"<div><h3>Background</h3><div>Gastrointestinal (GI) cancers (including esophagus, stomach, colon, rectum, pancreas and liver) account for more than one-quarter of all cancer diagnoses and 35% of cancer-related fatalities worldwide. Quantification of tumor-infiltrating lymphocytes (TILs) is a known cancer prognostic marker. In this study, we used computer vision and machine learning [artificial intelligence (AI)] approaches to evaluate the prognostic significance of computational pathology features relating to spatial arrangement and diversity in the appearance of TILs and cancer nuclei across five different types of GI cancers: colon, stomach, pancreas, and rectum adenocarcinoma and liver hepatocellular carcinoma.</div></div><div><h3>Patients and methods</h3><div>The study comprises &gt;1700 patients from four different sites. Pathomic features (2236) were extracted from hematoxylin–eosin stained whole slide images and the top 9 features were selected by Least Absolute Shrinkage and Selection Operator (LASSO) Cox model. The top prognostic features identified were related to the spatial relationships between TILs and the closest cancer nuclei and tumor nuclei shape and texture features captured within local cellular clusters.</div></div><div><h3>Results</h3><div>Our trained model identified that ‘low-risk’ patients have significantly better overall survival than those identified as ‘high risk’ with a hazard ratio (HR) of 2.28 [95% confidence interval (CI) 1.32-3.93, <em>P</em> = 0.0032] in liver hepatocellular carcinoma; an HR of 2.79 (95% CI 1.66-4.68, <em>P</em> = 0.0001) in pancreatic adenocarcinoma; an HR of 5.85 (95% CI 2.53-15.5, <em>P</em> = 0.0002) in rectal adenocarcinoma; an HR of 1.81 (95% CI 1.07-3.07, <em>P</em> = 0.0268) in gastric adenocarcinoma. Across three different external validation sets of colorectal cancer (CRC) patients, our model yielded an HR of 2.32 (95% CI 1.67-3.23, <em>P</em> &lt; 0.0001) in The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COAD), an HR of 2.32 (95% CI 1.67-3.23, <em>P</em> &lt; 0.0001) in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)-COAD, and an HR of 3.38 (95% CI 1.99-5.71, <em>P</em> &lt; 0.0001) in the Emory dataset. Multivariable survival analysis showed that our trained model was prognostic independent of stage, age, race, and sex.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that the spatial relationships of TILs and cancer nuclei are prognostic of survival across multiple GI cancer types.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105757"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206005","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":"Letter to the Editor: Improving chemotherapy-induced peripheral neuropathy in cancer patients using a combined qigong and self-administered acupressure intervention: a randomized controlled trial","authors":"Y. Zhou,&nbsp;Y. Liu,&nbsp;D. Zhang,&nbsp;M. Cai","doi":"10.1016/j.esmoop.2025.105835","DOIUrl":"10.1016/j.esmoop.2025.105835","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105835"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205946","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":"Characterization of early-onset gastritis during zolbetuximab-containing chemotherapy in CLDN18.2-positive gastric cancer","authors":"K. Yamamoto ,&nbsp;Y. Owaki ,&nbsp;I. Nakayama ,&nbsp;N. Sakamoto ,&nbsp;M. Ishizaka ,&nbsp;T. Kadota ,&nbsp;D. Okemoto ,&nbsp;Y. Matsubara ,&nbsp;Y. Miyashita ,&nbsp;A. Kobayashi ,&nbsp;U. Okazaki ,&nbsp;K. Seguchi ,&nbsp;T. Hosokai ,&nbsp;T. Ogura ,&nbsp;S. Mishima ,&nbsp;D. Kotani ,&nbsp;A. Kawazoe ,&nbsp;T. Hashimoto ,&nbsp;Y. Kuboki ,&nbsp;H. Bando ,&nbsp;K. Shitara","doi":"10.1016/j.esmoop.2025.105805","DOIUrl":"10.1016/j.esmoop.2025.105805","url":null,"abstract":"<div><h3>Background</h3><div>Zolbetuximab, a monoclonal antibody targeting claudin 18.2 (CLDN18.2), plus chemotherapy has become a standard treatment for CLDN18.2-positive advanced gastric cancer and is frequently associated with early-onset gastrointestinal (GI) toxicities. While zolbetuximab-induced gastritis has been observed in preclinical studies, it has not been previously reported in patients.</div></div><div><h3>Patients and methods</h3><div>We retrospectively analyzed patients with human epidermal growth factor receptor 2 (HER2)-negative, CLDN18.2-positive, advanced gastric or gastroesophageal junction cancer who underwent endoscopy during first-line zolbetuximab-containing chemotherapy. Patients who had undergone prior total gastrectomy were excluded. We evaluated associations between gastritis and clinical outcomes including GI toxicities and serum albumin level.</div></div><div><h3>Results</h3><div>Among 58 eligible patients, gastritis was observed in 52 (89.7%) at a median of 7.8 weeks after treatment initiation. Characteristic endoscopic findings included mucosal erythema (100%), white exudate (63.4%), edema (28.8%), and erosions or ulcerations (26.9%). The distribution of gastritis was predominantly diffuse (76.9%) rather than scattered (23.1%), commonly involving multiple gastric regions (90.4%). Patients with diffuse gastritis experienced significantly higher rates of any-grade anorexia compared with those without gastritis (97.5% versus 50.0%, <em>P</em> = 0.005) and more profound serum albumin decline [median decrease –1.2 g/dl, interquartile range (IQR) –1.525 to –0.9 g/dl versus –0.7 g/dl, IQR –0.8 to –0.6 g/dl; <em>P</em> = 0.012]. No patients discontinued treatment due to gastritis. Among 32 patients who underwent follow-up endoscopy during ongoing treatment, improvement was confirmed in 25 patients, and no cases exhibited unresolved gastritis beyond 18 weeks.</div></div><div><h3>Conclusions</h3><div>Early-onset transient gastritis frequently occurred following zolbetuximab-containing therapy and was significantly associated with anorexia and hypoalbuminemia. A deeper understanding of gastritis underlying unique GI toxicities may provide insight into effective management.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105805"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206008","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":"Adverse events associated with sequential immune checkpoint inhibitor and alectinib in patients with ALK-rearranged advanced non-small-cell lung cancer","authors":"J.M. Cheung ,&nbsp;S. Waliany ,&nbsp;B.Y. Yeap,&nbsp;J.L. Peterson,&nbsp;A. Liu,&nbsp;A. Do,&nbsp;J. Liang,&nbsp;J.J. Lin","doi":"10.1016/j.esmoop.2025.105842","DOIUrl":"10.1016/j.esmoop.2025.105842","url":null,"abstract":"<div><h3>Background</h3><div>ALK tyrosine kinase inhibitors (TKIs) are the standard first-line therapy for <em>ALK</em>-rearranged [<em>ALK</em> fusion-positive (ALK+)] advanced non-small-cell lung cancer (NSCLC). In real-world practice, patients may receive immune checkpoint inhibitors (ICIs) before initiating ALK TKIs. We aimed to assess the frequency of treatment-related adverse events (TRAEs) associated with this sequential approach.</div></div><div><h3>Patients and methods</h3><div>We retrospectively analyzed alectinib-associated TRAEs in patients with advanced ALK+ NSCLC who received alectinib as their first TKI, with or without prior ICI exposure.</div></div><div><h3>Results</h3><div>We identified 166 patients, of whom 12 had prior ICI exposure. From alectinib initiation, the 12-month cumulative incidence in patients with versus without prior ICI was as follows: all-grade pneumonitis, 25.0% versus 4.6%; transaminase elevation, 25.0% versus 14.4%; and rash, 43.3% versus 5.9%. Competing-risks regression detected a higher risk of all-grade pneumonitis [hazard ratio (HR) 5.2], all-grade rash (HR 7.8), and grade ≥3 rash (HR 8.9) in patients with versus without prior ICI. Alectinib required discontinuation or hospitalization for TRAEs in 25.0% and 16.7% of patients with prior ICI, respectively, compared with 7.8% and 3.2% of patients without prior ICI.</div></div><div><h3>Conclusions</h3><div>Alectinib after ICI was associated with higher risks of pneumonitis and rash, and numerically higher risk of grade ≥3 hepatotoxicity, leading to increased rates of alectinib interruption and steroid use. These findings underscore the importance of expedited genotyping to guide treatment selection and avoid unwarranted ICI exposure.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105842"},"PeriodicalIF":8.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250455","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":"BOS172738, a selective RET inhibitor, for the treatment of patients with RET-altered tumors including RET-fusion-positive non-small-cell lung cancer and RET-mutant medullary thyroid cancer: a phase I dose-escalation/expansion multicenter study","authors":"P. Schöffski ,&nbsp;A. Gazzah ,&nbsp;J. Trigo ,&nbsp;A. Italiano ,&nbsp;P. Gougis ,&nbsp;V. Subbiah ,&nbsp;J.-Y. Shih ,&nbsp;H.H. Loong ,&nbsp;B. Doger ,&nbsp;M. Keegan ,&nbsp;B. Jeglinski ,&nbsp;K. Andreas ,&nbsp;B.C. Cho","doi":"10.1016/j.esmoop.2025.105543","DOIUrl":"10.1016/j.esmoop.2025.105543","url":null,"abstract":"<div><h3>Background</h3><div>This phase I dose-escalation (part A)/dose-expansion (part B) study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of BOS172738 [a selective rearranged during transfection (RET) inhibitor] in patients with <em>RET</em>-altered tumors including <em>RET</em>-fusion-positive non-small-cell lung cancer (NSCLC) and <em>RET</em>-mutant medullary thyroid cancer (MTC).</div></div><div><h3>Patients and methods</h3><div>Adult patients with advanced solid tumors with <em>RET</em> gene alteration received BOS172738 10-150 mg orally once daily in part A, and the recommended phase II dose (RP2D) in part B. Primary endpoints included safety (Common Terminology Criteria for Adverse Event v.4.03) and tolerability, and in part A, determining the maximum tolerated dose (MTD) and RP2D. Secondary endpoints included objective response rate (ORR; RECIST v.1.1), disease control rate (DCR), progression-free survival, duration of response (DoR), and pharmacokinetic assessments. Exploratory endpoints involved pharmacodynamic biomarkers.</div></div><div><h3>Results</h3><div>A total of 117 patients were enrolled (67 part A, 50 part B). Patients had advanced disease, were heavily pretreated, and 21% had brain metastases. In part A, three patients had dose-limiting toxicities, but MTD was not reached, with 75 mg recommended for part B. At final cut-off (November 2023), 85% had BOS172738-related treatment-emergent adverse events [54% grade ≥3, most common: blood creatine phosphokinase increased (25%), neutrophil count decreased (10%), and anemia (9%)]. In <em>RET</em>-fusion-positive NSCLC, 28% had an objective response and 59% disease control, with a median DoR (mDoR) of 10.17 months. In <em>RET</em>-mutant MTC, 30% had an objective response, and DCR was 74%, with a mDoR of 19.15 months.</div></div><div><h3>Conclusions</h3><div>BOS172738 showed preliminary efficacy and a manageable safety profile in <em>RET</em>-altered tumors, including those resistant to prior therapies and in patients with brain metastases.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105543"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120045","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":"Letter to the editor: The immunologic landscape of HRAS-mutant head and neck squamous-cell carcinoma","authors":"D. Zhang,&nbsp;Y. Liu,&nbsp;M. Li,&nbsp;Y. Zhou,&nbsp;M. Cai","doi":"10.1016/j.esmoop.2025.105831","DOIUrl":"10.1016/j.esmoop.2025.105831","url":null,"abstract":"","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105831"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119919","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":"Genomic and transcriptomic analyses of residual invasive triple-negative breast cancer after neoadjuvant chemotherapy in the prospective MIRINAE trial (a randomized phase II trial of adjuvant atezolizumab plus capecitabine compared to capecitabine; KCSG-BR18-21)","authors":"S.-A. Im ,&nbsp;K. Park ,&nbsp;J. Koh ,&nbsp;C. Park ,&nbsp;K.H. Jung ,&nbsp;J. Lee ,&nbsp;H.K. Ahn ,&nbsp;A. Lee ,&nbsp;S.H. Sim ,&nbsp;M.H. Kim ,&nbsp;J.H. Kim ,&nbsp;J.H. Kim ,&nbsp;K.E. Lee ,&nbsp;K.H. Park ,&nbsp;J. Bae ,&nbsp;M.H. Lee ,&nbsp;S. Lim ,&nbsp;H.J. Kim ,&nbsp;D.-W. Lee ,&nbsp;J.H. Jeong ,&nbsp;I.H. Park","doi":"10.1016/j.esmoop.2025.105804","DOIUrl":"10.1016/j.esmoop.2025.105804","url":null,"abstract":"<div><h3>Background</h3><div>Profiling residual disease after neoadjuvant chemotherapy (NAC) might identify molecular target and tumor microenvironmental features to guide adjuvant therapy. We explored the characteristics of residual triple-negative breast cancer (TNBC) in the prospective MIRINAE trial (KCSG-BR18-21), a phase II study evaluating adjuvant atezolizumab plus capecitabine versus capecitabine in TNBC without pathological complete response after NAC (NCT03756298) through multi-omics analyses.</div></div><div><h3>Materials and methods</h3><div>Residual TNBC samples were analyzed for tumor-infiltrating lymphocytes (TILs), programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC), and Lunit SCOPE IO immune phenotype (IP). Mutations were assessed by FoundationOne®CDx, and RNAseq was conducted for molecular subtyping and gene expression analyses.</div></div><div><h3>Results</h3><div>Three hundred and five patients were analyzed, and ypTNM (post-neoadjuvant pathological tumor–node–metastasis) stages were stage I (28.0%), II (48.7%), and III (23.3%). High TILs were observed in 27.1% and PD-L1 IHC was positive in 39.5%. Pathogenic alterations in <em>TP53</em>, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), and homologous recombination repair (HRR) pathways were observed in 86.3%, 27.1%, and 11.9%. Most patients were basal-like (51.1%) by PAM50, and mesenchymal (MES; 36.7%) or basal-like immune suppressed (BLIS; 30.3%) by TNBC molecular classification. TIL-high group was enriched with the basal-like immune-activated (BLIA) subtype (37.5%), with up-regulation of immune response-related gene sets. Nineteen patients (6.2%) recurred within 6 months of surgery (6.2%), mostly being basal-like (85.7%) or BLIS (64.3%), with low TILs and desert IP. Up-regulations of <em>CCNE1</em>, <em>CD44</em>, and <em>BRD4</em> along with DNA replication-related gene sets were associated with early recurrence.</div></div><div><h3>Conclusion</h3><div>Residual TNBCs after standard NAC were predominantly basal-like or MES/BLIS subtypes with variable tumor microenvironment (TME). Early recurrence was associated with immune-cold TME, and further analyses on each treatment arm will provide deeper insights into the role of adjuvant immunotherapy.</div></div>","PeriodicalId":11877,"journal":{"name":"ESMO Open","volume":"10 10","pages":"Article 105804"},"PeriodicalIF":8.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119918","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}