Pub Date : 2025-10-30DOI: 10.1001/jamaoncol.2025.4480
Fatemeh Hadizadeh, Ardita Koteci, Torgny Karlsson, Weronica E. Ek, Åsa Johansson
Importance Hormonal contraceptives are widely used but how breast cancer risk differs by hormonal content remains unclear. Objective To estimate the difference in breast cancer risk associated with different hormonal contraceptive formulations. Design, Setting, and Participants This Swedish nationwide, population-based cohort study was conducted using linked national registers. All adolescent girls and women aged 13 to 49 years residing in Sweden as of January 1, 2006, with no history of breast cancer, ovarian cancer, cervical cancer, uterine cancer, bilateral oophorectomy, or infertility treatment were included and followed up from 2006 to 2019. Individuals were censored on meeting an exclusion criterion, reaching age 50 years, or study end, whichever occurred first. Data were analyzed from November 2023 to August 2025. Exposure Ever use and duration of use of hormonal contraceptives, categorized by hormone formulations and route of administration. Main Outcomes and Measures Time-dependent Cox regression was used to estimate hazard ratios (HRs) with 95% CIs for incident cases of in situ and invasive breast cancer. Results Among 2 095 130 adolescent girls and women (median [IQR] age at diagnosis, 45 [41-48] years) who were followed up for 21 020 846 person-years, 16 385 breast cancer cases occurred. Ever use of any hormonal contraceptive was associated with increased breast cancer risk (HR, 1.24; 95% CI, 1.20-1.28), corresponding to 1 additional case per 7752 (95% CI, 5350-14 070) users, with both combined (HR, 1.12; 95% CI, 1.07-1.17) and progestin-only formulations (HR, 1.21; 95% CI, 1.17-1.25) being associated. Higher risk was associated with oral desogestrel-only formulations (HR, 1.18; 95% CI, 1.13-1.23) and oral desogestrel-combined formulations (HR, 1.19; 95% CI, 1.08-1.31), as well as implants containing etonogestrel, desogestrel’s active metabolite (HR, 1.22; 95% CI, 1.11-1.35), compared to levonorgestrel-containing combined pills (HR, 1.09; 95% CI, 1.03-1.15) and levonorgestrel, 52 mg, intrauterine system (HR, 1.13; 95% CI, 1.09-1.18). No statistically significant increased risk was observed for medroxyprogesterone acetate injection, etonogestrel vaginal ring, or combined oral drospirenone, despite having many users. Conclusions and Relevance Findings of this cohort study highlight that breast cancer risk varies substantially by progestin content in hormonal contraceptives, providing valuable insights to support more informed contraceptive prescription.
{"title":"Hormonal Contraceptive Formulations and Breast Cancer Risk in Adolescents and Premenopausal Women","authors":"Fatemeh Hadizadeh, Ardita Koteci, Torgny Karlsson, Weronica E. Ek, Åsa Johansson","doi":"10.1001/jamaoncol.2025.4480","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4480","url":null,"abstract":"Importance Hormonal contraceptives are widely used but how breast cancer risk differs by hormonal content remains unclear. Objective To estimate the difference in breast cancer risk associated with different hormonal contraceptive formulations. Design, Setting, and Participants This Swedish nationwide, population-based cohort study was conducted using linked national registers. All adolescent girls and women aged 13 to 49 years residing in Sweden as of January 1, 2006, with no history of breast cancer, ovarian cancer, cervical cancer, uterine cancer, bilateral oophorectomy, or infertility treatment were included and followed up from 2006 to 2019. Individuals were censored on meeting an exclusion criterion, reaching age 50 years, or study end, whichever occurred first. Data were analyzed from November 2023 to August 2025. Exposure Ever use and duration of use of hormonal contraceptives, categorized by hormone formulations and route of administration. Main Outcomes and Measures Time-dependent Cox regression was used to estimate hazard ratios (HRs) with 95% CIs for incident cases of in situ and invasive breast cancer. Results Among 2 095 130 adolescent girls and women (median [IQR] age at diagnosis, 45 [41-48] years) who were followed up for 21 020 846 person-years, 16 385 breast cancer cases occurred. Ever use of any hormonal contraceptive was associated with increased breast cancer risk (HR, 1.24; 95% CI, 1.20-1.28), corresponding to 1 additional case per 7752 (95% CI, 5350-14 070) users, with both combined (HR, 1.12; 95% CI, 1.07-1.17) and progestin-only formulations (HR, 1.21; 95% CI, 1.17-1.25) being associated. Higher risk was associated with oral desogestrel-only formulations (HR, 1.18; 95% CI, 1.13-1.23) and oral desogestrel-combined formulations (HR, 1.19; 95% CI, 1.08-1.31), as well as implants containing etonogestrel, desogestrel’s active metabolite (HR, 1.22; 95% CI, 1.11-1.35), compared to levonorgestrel-containing combined pills (HR, 1.09; 95% CI, 1.03-1.15) and levonorgestrel, 52 mg, intrauterine system (HR, 1.13; 95% CI, 1.09-1.18). No statistically significant increased risk was observed for medroxyprogesterone acetate injection, etonogestrel vaginal ring, or combined oral drospirenone, despite having many users. Conclusions and Relevance Findings of this cohort study highlight that breast cancer risk varies substantially by progestin content in hormonal contraceptives, providing valuable insights to support more informed contraceptive prescription.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"107 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145397618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1001/jamaoncol.2025.4141
Patricia A Ganz,Eric H Yang
{"title":"Do All Breast Cancer Survivors Need to See a Cardiologist?","authors":"Patricia A Ganz,Eric H Yang","doi":"10.1001/jamaoncol.2025.4141","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4141","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"44 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1001/jamaoncol.2025.4178
Ana Barac,Jiling Chou,Nawar Shara,Lie H Chen,Jiaxiao Shi,Rowan T Chlebowski,Amrita Mukherjee,Reina Haque,Arnold L Potosky
ImportanceWomen receiving breast cancer (BC) treatment are at risk for heart failure or cardiomyopathy (HF/CM). No standard method exists to identify women at risk who might benefit from preventive cardiac strategies and surveillance during and after treatment.ObjectiveTo develop and validate a model predicting the 10-year risk of developing HF/CM in women receiving systemic treatment for invasive early-stage BC to inform cardiac risk management.Design, Setting, and ParticipantsThis longitudinal cohort study of patients cared for in Kaiser Permanente Southern California, a vertically integrated health care system. The goal of the study was to predict the 10-year HF/CM risk using multivariable elastic-net Cox proportional hazards models. Women aged 18 to 79 years with newly diagnosed invasive local or regional BC from 2008 to 2020, with a median follow-up of 5.2 years, were included. The cohort was randomly split into derivation (60%) and validation (40%) cohorts. Data were analyzed from April 2024 to May 2025.ExposuresHF/CM risk predictors included age at BC diagnosis, race and ethnicity, area-level socioeconomic status, local and systemic BC treatments, cancer stage, obesity, and history of hypertension, diabetes, hyperlipidemia, smoking, and other CV conditions.Main Outcome and MeasuresIncident HF/CM events. Women were categorized into low-, moderate-, and high-risk groups based on the tertiles of the risk score in the derivation cohort.ResultsOf 26 044 women included in the total cohort, the median (IQR) age was 61 (52-68) years. The risk model had good calibration and high accuracy in predicting HF/CM risk in the 3 subgroups, with HF/CM risk in the validation cohort matching the estimates from the derivation for identifying women at low risk (1.7%; 95% CI, 1.1%-2.4%) and high risk (19.4%; 95% CI. 17.3%-21.5%) of HF/CM at 10 years. The model's discrimination ability was good, based on the time-dependent area under the curve of 0.79 at 10 years in the validation cohort.Conclusions and RelevanceThis risk prediction model among women with early-stage BC was able to prospectively identify those at risk of HF/CM over a 10-year period based on the selected BC treatment and clinical variables available at BC diagnosis. The model can be used to inform risk-guided cardiac management for these women.
{"title":"Risk Prediction Model for Development of Heart Failure or Cardiomyopathy After Breast Cancer Treatment.","authors":"Ana Barac,Jiling Chou,Nawar Shara,Lie H Chen,Jiaxiao Shi,Rowan T Chlebowski,Amrita Mukherjee,Reina Haque,Arnold L Potosky","doi":"10.1001/jamaoncol.2025.4178","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4178","url":null,"abstract":"ImportanceWomen receiving breast cancer (BC) treatment are at risk for heart failure or cardiomyopathy (HF/CM). No standard method exists to identify women at risk who might benefit from preventive cardiac strategies and surveillance during and after treatment.ObjectiveTo develop and validate a model predicting the 10-year risk of developing HF/CM in women receiving systemic treatment for invasive early-stage BC to inform cardiac risk management.Design, Setting, and ParticipantsThis longitudinal cohort study of patients cared for in Kaiser Permanente Southern California, a vertically integrated health care system. The goal of the study was to predict the 10-year HF/CM risk using multivariable elastic-net Cox proportional hazards models. Women aged 18 to 79 years with newly diagnosed invasive local or regional BC from 2008 to 2020, with a median follow-up of 5.2 years, were included. The cohort was randomly split into derivation (60%) and validation (40%) cohorts. Data were analyzed from April 2024 to May 2025.ExposuresHF/CM risk predictors included age at BC diagnosis, race and ethnicity, area-level socioeconomic status, local and systemic BC treatments, cancer stage, obesity, and history of hypertension, diabetes, hyperlipidemia, smoking, and other CV conditions.Main Outcome and MeasuresIncident HF/CM events. Women were categorized into low-, moderate-, and high-risk groups based on the tertiles of the risk score in the derivation cohort.ResultsOf 26 044 women included in the total cohort, the median (IQR) age was 61 (52-68) years. The risk model had good calibration and high accuracy in predicting HF/CM risk in the 3 subgroups, with HF/CM risk in the validation cohort matching the estimates from the derivation for identifying women at low risk (1.7%; 95% CI, 1.1%-2.4%) and high risk (19.4%; 95% CI. 17.3%-21.5%) of HF/CM at 10 years. The model's discrimination ability was good, based on the time-dependent area under the curve of 0.79 at 10 years in the validation cohort.Conclusions and RelevanceThis risk prediction model among women with early-stage BC was able to prospectively identify those at risk of HF/CM over a 10-year period based on the selected BC treatment and clinical variables available at BC diagnosis. The model can be used to inform risk-guided cardiac management for these women.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"136 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1001/jamaoncol.2025.4172
Lanwei Guo
{"title":"Power Limits in Body Mass Index, Activity, and Cancer Risk.","authors":"Lanwei Guo","doi":"10.1001/jamaoncol.2025.4172","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4172","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"69 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1001/jamaoncol.2025.4175
Lenat Joffe,Sedigheh Mirzaei,Lucie M Turcotte
{"title":"Power Limits in Body Mass Index, Activity, and Cancer Risk-Reply.","authors":"Lenat Joffe,Sedigheh Mirzaei,Lucie M Turcotte","doi":"10.1001/jamaoncol.2025.4175","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4175","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"20 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1001/jamaoncol.2025.4365
Daniel J Zheng,Gary Hettinger,Jonathan D Bender,Alexis C Boulter,Lusha Cao,Caitlin W Elgarten,Brian T Fisher,Cody Gathers,Yuan-Shung V Huang,Jennifer Ko,Kasey J Leger,Yimei Li,Regina Myers,Hari K Narayan,Jose Ortiz,Alix E Seif,Eleana Vasileiadi,Richard Aplenc,Kelly D Getz
{"title":"National Trends in Dexrazoxane and Cardiovascular Health Care Utilization for Children With Acute Myeloid Leukemia.","authors":"Daniel J Zheng,Gary Hettinger,Jonathan D Bender,Alexis C Boulter,Lusha Cao,Caitlin W Elgarten,Brian T Fisher,Cody Gathers,Yuan-Shung V Huang,Jennifer Ko,Kasey J Leger,Yimei Li,Regina Myers,Hari K Narayan,Jose Ortiz,Alix E Seif,Eleana Vasileiadi,Richard Aplenc,Kelly D Getz","doi":"10.1001/jamaoncol.2025.4365","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4365","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"51 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1001/jamaoncol.2025.4371
Christopher T Su,Scott D Ramsey,Veena Shankaran
{"title":"Can We Use Credit Data to Assess Cancer Financial Hardship?","authors":"Christopher T Su,Scott D Ramsey,Veena Shankaran","doi":"10.1001/jamaoncol.2025.4371","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4371","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"43 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1001/jamaoncol.2025.4092
Melvin L K Chua,Darren W T Lim
{"title":"Unexpected Results of Induction Chemotherapy vs Adjuvant Chemotherapy.","authors":"Melvin L K Chua,Darren W T Lim","doi":"10.1001/jamaoncol.2025.4092","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4092","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"130 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145296092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1001/jamaoncol.2025.4072
Mark Schuiveling,Isabella A J van Duin,Laurens S Ter Maat,Janneke C van der Weerd,Rik J Verheijden,Franchette van den Berkmortel,Christian U Blank,Gerben E Breimer,Femke H Burgers,Marye Boers-Sonderen,Alfons J M van den Eertwegh,Jan Willem B de Groot,John B A G Haanen,Geke A P Hospers,Ellen Kapiteijn,Djura Piersma,Gerard Vreugdenhil,Hans Westgeest,Anne M R Schrader,Josien P W Pluim,Paul J van Diest,Mitko Veta,Karijn P M Suijkerbuijk,Willeke A M Blokx
ImportanceEasy and accessible biomarkers associated with response to immune checkpoint inhibition (ICI)-treated melanoma are limited.ObjectiveTo evaluate artificial intelligence (AI)-detected tumor-infiltrating lymphocytes (TILs) on pretreatment melanoma metastases as a biomarker for response and survival in patients treated with ICIs.Design, Setting, and ParticipantsThis multicenter cohort study included patients with advanced melanoma treated with first-line anti-programmed cell death 1 protein (PD-1) with or without anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) between January 2016 and January 2023 at 11 melanoma treatment centers in the Netherlands. Data were analyzed from January to July 2025.ExposureAll patients received first-line anti-PD-1 with or without anti-CTLA-4.Main Outcomes and MeasuresThe percentage of TILs inside manually annotated tumor area in hematoxylin-eosin-stained pretreatment metastases was determined using the Hover-NeXt model trained and evaluated on an independent melanoma dataset containing 161 835 pathologist-verified manually annotated cells. The primary outcome was objective response rate (ORR); secondary outcomes were progression-free survival (PFS) and overall survival (OS). Correlation with manual TILs, scored according to the guidelines stated by the Immuno-Oncology Biomarkers Working Group, was evaluated with Spearman correlation coefficients. Logistic regression and Cox proportional regression were conducted, adjusted for age, sex, disease stage, ICI type, BRAF status, brain metastases, lactate dehydrogenase level, and performance status.ResultsOf 1202 included patients with advanced cutaneous melanoma, 445 (37.0%) were female and 757 (63.0%) were male, and the median (IQR) age was 67.0 (57.0-74.0) years. The median follow-up was 36.3 months (95% CI, 34.0-39.1). Metastatic melanoma specimens were available for 1202 patients, of whom 423 received combination therapy. The median (range) TIL percentage was 9.9% (0.3%-69.4%). A 10% increase in TILs was associated with increased ORR (adjusted odds ratio, 1.40; 95% CI, 1.23-1.59), PFS (adjusted hazard ratio, 0.85; 95% CI, 0.79-0.92), and OS (adjusted hazard ratio, 0.83; 95% CI, 0.76-0.91). Results were consistent for both patients treated with anti-PD-1 monotherapy and patients treated with combination treatment with anti-PD-1 plus anti-CTLA-4. When comparing manual TIL scoring with AI-detected TILs, associations with response and survival were consistently stronger for AI-detected TILs.Conclusions and RelevanceIn this cohort study, among patients with advanced melanoma, higher levels of AI-detected TILs on pretreatment hematoxylin-eosin slides were independently associated with improved ICI response and survival. Given the accessibility of TIL scoring on routine histology, TILs may serve as a biomarker for ICI outcomes. To facilitate broader validation, the Hover-NeXt architecture and model weights are publicly available.
{"title":"Artificial Intelligence-Detected Tumor-Infiltrating Lymphocytes and Outcomes in Anti-PD-1-Based Treated Melanoma.","authors":"Mark Schuiveling,Isabella A J van Duin,Laurens S Ter Maat,Janneke C van der Weerd,Rik J Verheijden,Franchette van den Berkmortel,Christian U Blank,Gerben E Breimer,Femke H Burgers,Marye Boers-Sonderen,Alfons J M van den Eertwegh,Jan Willem B de Groot,John B A G Haanen,Geke A P Hospers,Ellen Kapiteijn,Djura Piersma,Gerard Vreugdenhil,Hans Westgeest,Anne M R Schrader,Josien P W Pluim,Paul J van Diest,Mitko Veta,Karijn P M Suijkerbuijk,Willeke A M Blokx","doi":"10.1001/jamaoncol.2025.4072","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4072","url":null,"abstract":"ImportanceEasy and accessible biomarkers associated with response to immune checkpoint inhibition (ICI)-treated melanoma are limited.ObjectiveTo evaluate artificial intelligence (AI)-detected tumor-infiltrating lymphocytes (TILs) on pretreatment melanoma metastases as a biomarker for response and survival in patients treated with ICIs.Design, Setting, and ParticipantsThis multicenter cohort study included patients with advanced melanoma treated with first-line anti-programmed cell death 1 protein (PD-1) with or without anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) between January 2016 and January 2023 at 11 melanoma treatment centers in the Netherlands. Data were analyzed from January to July 2025.ExposureAll patients received first-line anti-PD-1 with or without anti-CTLA-4.Main Outcomes and MeasuresThe percentage of TILs inside manually annotated tumor area in hematoxylin-eosin-stained pretreatment metastases was determined using the Hover-NeXt model trained and evaluated on an independent melanoma dataset containing 161 835 pathologist-verified manually annotated cells. The primary outcome was objective response rate (ORR); secondary outcomes were progression-free survival (PFS) and overall survival (OS). Correlation with manual TILs, scored according to the guidelines stated by the Immuno-Oncology Biomarkers Working Group, was evaluated with Spearman correlation coefficients. Logistic regression and Cox proportional regression were conducted, adjusted for age, sex, disease stage, ICI type, BRAF status, brain metastases, lactate dehydrogenase level, and performance status.ResultsOf 1202 included patients with advanced cutaneous melanoma, 445 (37.0%) were female and 757 (63.0%) were male, and the median (IQR) age was 67.0 (57.0-74.0) years. The median follow-up was 36.3 months (95% CI, 34.0-39.1). Metastatic melanoma specimens were available for 1202 patients, of whom 423 received combination therapy. The median (range) TIL percentage was 9.9% (0.3%-69.4%). A 10% increase in TILs was associated with increased ORR (adjusted odds ratio, 1.40; 95% CI, 1.23-1.59), PFS (adjusted hazard ratio, 0.85; 95% CI, 0.79-0.92), and OS (adjusted hazard ratio, 0.83; 95% CI, 0.76-0.91). Results were consistent for both patients treated with anti-PD-1 monotherapy and patients treated with combination treatment with anti-PD-1 plus anti-CTLA-4. When comparing manual TIL scoring with AI-detected TILs, associations with response and survival were consistently stronger for AI-detected TILs.Conclusions and RelevanceIn this cohort study, among patients with advanced melanoma, higher levels of AI-detected TILs on pretreatment hematoxylin-eosin slides were independently associated with improved ICI response and survival. Given the accessibility of TIL scoring on routine histology, TILs may serve as a biomarker for ICI outcomes. To facilitate broader validation, the Hover-NeXt architecture and model weights are publicly available.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"47 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145296087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1001/jamaoncol.2025.4079
Seema A Khan,Justin Romanoff,Constantine Gatsonis,Habib Rahbar,Ruth Carlos,Sunil Badve,Jean Wright,Ralph L Corsetti,Constance D Lehman,Derrick W Spell,Linda K Han,John R Bumberry,Ilana Gareen,Bradley S Snyder,Lynne I Wagner,Kathy D Miller,Christopher Comstock,Joseph A Sparano
ImportanceBreast ductal carcinoma in situ (DCIS) requires personalized treatment given its variable natural history. This study reports the first prospective oncologic outcomes of radiotherapy decisions as guided by 12-gene molecular assay, the DCIS score (DS).ObjectiveTo assess surgical outcomes following preoperative breast magnetic resonance imaging (MRI) in women with DCIS and estimate 5-year and 10-year ipsilateral breast event (IBE) rates in participants given DS-based postoperative radiotherapy recommendations after local excision (WLE).Design, Setting, and ParticipantsWomen with screen-detected DCIS who were eligible for WLE were enrolled to a single-arm, multicenter trial conducted at 75 institutions within the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (March 2015 to April 2016) and received a preoperative breast MRI-guided surgical treatment. Those who underwent successful WLE were advised to omit radiotherapy for low DS (<39) and receive radiotherapy for intermediate/high DS (≥39). Those achieving WLE as final treatment and successful DS assay (n = 171) were included in a prespecified analysis. Participants were followed up every 6 months for DCIS or invasive IBE, and 5-year IBE rates were analyzed from July to November 2023.InterventionDS-based postoperative radiotherapy recommendations.Main Outcomes and MeasuresFive-year IBE rates, with 95% CIs.ResultsAmong the 339 participants, the mean (SD) age was 59.1 (10.1) years. A total of 171 women (50.4%) received WLE for pure DCIS with free surgical margins and had DS data available. A total of 159 (93.0%) adhered to DS-based radiotherapy recommendations; 7 of 82 patients (8.5%) with a low DS underwent radiotherapy, and 5 of 89 patients (5.6%) with an intermediate/high DS declined radiotherapy. Over median (range) follow-up of 5 (0.5-5.0) years, 8 of 171 women experienced IBEs (4.8%; 95% CI, 2.4%-9.4%). IBE rates were similar for participants with a low DS(5.1%; 95% CI, 1.9%-12.9%) and participants with an intermediate/high DS (4.5%; 95% CI, 1.7%-11.7%). Among the 159 women who had adhered to DS-based radiotherapy recommendations, IBE rates were similar for participants with a low DS (5.5%; 95% CI, 2.1%-14.1%) and intermediate/high DS (4.8%; 95% CI, 1.8%-12.3%).Conclusions and RelevanceThe findings of this prespecified analysis of a clinical trial suggest that DS-guided radiotherapy post-WLE for DCIS shows markedly lower 5-year IBE rates (approximately 5%) for intermediate/high DS than previously reported data following WLE alone. Despite a limited sample size, these data potentially provide support for radiotherapy use in patients with intermediate/high DS, and omission when DS is low, although confirmatory studies are needed.Trial RegistrationClinicalTrials.gov Identifier: NCT02352883.
{"title":"Radiotherapy With a 12-Gene Expression Assay for Ductal Carcinoma In Situ: A Randomized Clinical Trial.","authors":"Seema A Khan,Justin Romanoff,Constantine Gatsonis,Habib Rahbar,Ruth Carlos,Sunil Badve,Jean Wright,Ralph L Corsetti,Constance D Lehman,Derrick W Spell,Linda K Han,John R Bumberry,Ilana Gareen,Bradley S Snyder,Lynne I Wagner,Kathy D Miller,Christopher Comstock,Joseph A Sparano","doi":"10.1001/jamaoncol.2025.4079","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4079","url":null,"abstract":"ImportanceBreast ductal carcinoma in situ (DCIS) requires personalized treatment given its variable natural history. This study reports the first prospective oncologic outcomes of radiotherapy decisions as guided by 12-gene molecular assay, the DCIS score (DS).ObjectiveTo assess surgical outcomes following preoperative breast magnetic resonance imaging (MRI) in women with DCIS and estimate 5-year and 10-year ipsilateral breast event (IBE) rates in participants given DS-based postoperative radiotherapy recommendations after local excision (WLE).Design, Setting, and ParticipantsWomen with screen-detected DCIS who were eligible for WLE were enrolled to a single-arm, multicenter trial conducted at 75 institutions within the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (March 2015 to April 2016) and received a preoperative breast MRI-guided surgical treatment. Those who underwent successful WLE were advised to omit radiotherapy for low DS (<39) and receive radiotherapy for intermediate/high DS (≥39). Those achieving WLE as final treatment and successful DS assay (n = 171) were included in a prespecified analysis. Participants were followed up every 6 months for DCIS or invasive IBE, and 5-year IBE rates were analyzed from July to November 2023.InterventionDS-based postoperative radiotherapy recommendations.Main Outcomes and MeasuresFive-year IBE rates, with 95% CIs.ResultsAmong the 339 participants, the mean (SD) age was 59.1 (10.1) years. A total of 171 women (50.4%) received WLE for pure DCIS with free surgical margins and had DS data available. A total of 159 (93.0%) adhered to DS-based radiotherapy recommendations; 7 of 82 patients (8.5%) with a low DS underwent radiotherapy, and 5 of 89 patients (5.6%) with an intermediate/high DS declined radiotherapy. Over median (range) follow-up of 5 (0.5-5.0) years, 8 of 171 women experienced IBEs (4.8%; 95% CI, 2.4%-9.4%). IBE rates were similar for participants with a low DS(5.1%; 95% CI, 1.9%-12.9%) and participants with an intermediate/high DS (4.5%; 95% CI, 1.7%-11.7%). Among the 159 women who had adhered to DS-based radiotherapy recommendations, IBE rates were similar for participants with a low DS (5.5%; 95% CI, 2.1%-14.1%) and intermediate/high DS (4.8%; 95% CI, 1.8%-12.3%).Conclusions and RelevanceThe findings of this prespecified analysis of a clinical trial suggest that DS-guided radiotherapy post-WLE for DCIS shows markedly lower 5-year IBE rates (approximately 5%) for intermediate/high DS than previously reported data following WLE alone. Despite a limited sample size, these data potentially provide support for radiotherapy use in patients with intermediate/high DS, and omission when DS is low, although confirmatory studies are needed.Trial RegistrationClinicalTrials.gov Identifier: NCT02352883.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"11 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145296089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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