Pub Date : 2025-11-20DOI: 10.1001/jamaoncol.2025.4800
Nicholas G. Zaorsky, Yilun Sun, Abdenour Nabid, Almudena Zapatero, Michel Bolla, David Joseph, Philippe Maingon, Araceli Guerrero, Ana Alvarez Gonzalez, Carmen Gonzalez San-Segundo, Maria Ángeles Cabeza Rodríguez, Josep Maria Sole, Agustí Pedro Olivé, Allison Steigler, Luis Souhami, Nathalie Carrier, John G. Armstrong, Charles Gillham, Thomas M. Pisansky, Matthew Schipper, Howard M. Sandler, Jason A. Efstathiou, Colleen Lawton, Theo M. de Reijke, Gerhardt Attard, Soumyajit Roy, Scott C. Morgan, Shawn Malone, William A. Hall, Paul L. Nguyen, Jonathan E. Shoag, Randy A. Vince, Adam Calaway, Jorge A. Garcia, Pedro C. Barata, Prateek Mendiratta, Jason R. Brown, Luca Valle, Matthew Rettig, Robert T. Dess, William C. Jackson, Ting Martin, Angela Y. Jia, Michael Steinberg, Tahmineh Romero, Amar U. Kishan, Daniel E. Spratt
Importance The ideal duration of androgen deprivation therapy (ADT) for treating localized prostate cancer is unknown due to variable adherence and treatment durations tested in clinical trials. Objective To determine the ideal duration of ADT for patients with prostate cancer treated with radiotherapy. Data Sources This individual patient data meta-analysis of 13 randomized phase 3 clinical trials evaluated the use of radiotherapy alone or with ADT. It included patients with a median follow-up of 11.3 (IQR, 9.5-14.5) years and ADT duration of 0 to 36 months. Most patients (7392 [72%]) included had National Comprehensive Cancer Network high-risk or very high-risk disease. Study Selection For this meta-analysis, a systematic literature search from 1980 to 2020 was performed in trial registries (Cochrane Central Register of Controlled Trials and ClinicalTrials.gov), MEDLINE (1966-2020), Embase (1982-2020), Web of Science, and Scopus to identify trials. Data Extraction and Synthesis Intention-to-treat and as-treated analyses were performed. The number needed to treat to prevent 1 distant metastasis at 10 years was calculated based on prognostic risk group. The analyses were conducted from January 5 to August 15, 2023. Main Outcomes and Measures The primary end point for this study was overall survival, defined as time to death or last follow-up from randomization. Secondary end points included biochemical recurrence, distant metastasis (DM), prostate cancer–specific mortality, and other-cause mortality. Results The median (IQR) age among the 10 266 male patients was 70 (65-74) years. Longer durations of ADT were associated with nonlinear improvement in relative benefits of DM, prostate cancer–specific mortality, and overall survival, with reduced estimated benefits beyond 9 to 12 months of ADT based on the end point. There was a near-linear increase in other-cause mortality associated with long-term ADT use (hazard ratio, 1.28; 95% CI, 1.09-1.50; P = .002 for 28 vs 0 months of ADT). The optimal ADT duration based on 10-year DM was 0, 6, 12 months, and undefined for patients with 1 intermediate-risk factor, 2 or more intermediate-risk factors, and National Comprehensive Cancer Network high-risk and very high-risk disease, respectively. Conclusions and Relevance The results of this meta-analysis suggest that, for men with localized prostate cancer treated with definitive radiotherapy and ADT, there are relative and absolute benefits from increasing durations of ADT that help provide individualized risk estimates.
重要性雄激素剥夺疗法（ADT）治疗局限性前列腺癌的理想持续时间尚不清楚，因为在临床试验中测试了不同的依从性和治疗时间。目的探讨前列腺癌放疗患者ADT的理想时间。这项对13项随机3期临床试验的个体患者数据荟萃分析评估了单独放疗或ADT的使用。纳入的患者中位随访时间为11.3年（IQR, 9.5-14.5年），ADT持续时间为0 - 36个月。大多数患者（7392例[72%]）为国家综合癌症网络高危或极高危疾病。研究选择本荟萃分析在1980年至2020年的试验注册库（Cochrane Central Register of Controlled Trials and ClinicalTrials.gov）、MEDLINE（1966-2020）、Embase（1982-2020）、Web of Science和Scopus中进行了系统的文献检索，以确定试验。数据提取和合成进行了意向处理和已处理分析。根据预后风险组计算10年预防1例远处转移所需的治疗次数。分析时间为2023年1月5日至8月15日。本研究的主要终点是总生存期，定义为死亡时间或随机分组后的最后一次随访。次要终点包括生化复发、远处转移（DM）、前列腺癌特异性死亡率和其他原因死亡率。结果10266例男性患者中位（IQR）年龄为70（65 ~ 74）岁。较长的ADT持续时间与糖尿病的相对获益、前列腺癌特异性死亡率和总生存率的非线性改善相关，基于终点的ADT超过9至12个月的估计获益减少。长期ADT使用与其他原因死亡率呈近线性增加（ADT使用28个月vs 0个月的风险比为1.28；95% CI为1.09-1.50;P = 0.002）。基于10年DM的最佳ADT持续时间分别为0、6、12个月，对于具有1个中等危险因素、2个及以上中等危险因素和国家综合癌症网络高风险和非常高风险疾病的患者，ADT持续时间未定义。本荟萃分析的结果表明，对于接受明确放疗和ADT治疗的局限性前列腺癌患者，增加ADT持续时间有相对和绝对益处，有助于提供个体化风险评估。
{"title":"Optimal Duration of Androgen Deprivation Therapy With Definitive Radiotherapy for Localized Prostate Cancer","authors":"Nicholas G. Zaorsky, Yilun Sun, Abdenour Nabid, Almudena Zapatero, Michel Bolla, David Joseph, Philippe Maingon, Araceli Guerrero, Ana Alvarez Gonzalez, Carmen Gonzalez San-Segundo, Maria Ángeles Cabeza Rodríguez, Josep Maria Sole, Agustí Pedro Olivé, Allison Steigler, Luis Souhami, Nathalie Carrier, John G. Armstrong, Charles Gillham, Thomas M. Pisansky, Matthew Schipper, Howard M. Sandler, Jason A. Efstathiou, Colleen Lawton, Theo M. de Reijke, Gerhardt Attard, Soumyajit Roy, Scott C. Morgan, Shawn Malone, William A. Hall, Paul L. Nguyen, Jonathan E. Shoag, Randy A. Vince, Adam Calaway, Jorge A. Garcia, Pedro C. Barata, Prateek Mendiratta, Jason R. Brown, Luca Valle, Matthew Rettig, Robert T. Dess, William C. Jackson, Ting Martin, Angela Y. Jia, Michael Steinberg, Tahmineh Romero, Amar U. Kishan, Daniel E. Spratt","doi":"10.1001/jamaoncol.2025.4800","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4800","url":null,"abstract":"Importance The ideal duration of androgen deprivation therapy (ADT) for treating localized prostate cancer is unknown due to variable adherence and treatment durations tested in clinical trials. Objective To determine the ideal duration of ADT for patients with prostate cancer treated with radiotherapy. Data Sources This individual patient data meta-analysis of 13 randomized phase 3 clinical trials evaluated the use of radiotherapy alone or with ADT. It included patients with a median follow-up of 11.3 (IQR, 9.5-14.5) years and ADT duration of 0 to 36 months. Most patients (7392 [72%]) included had National Comprehensive Cancer Network high-risk or very high-risk disease. Study Selection For this meta-analysis, a systematic literature search from 1980 to 2020 was performed in trial registries (Cochrane Central Register of Controlled Trials and ClinicalTrials.gov), MEDLINE (1966-2020), Embase (1982-2020), Web of Science, and Scopus to identify trials. Data Extraction and Synthesis Intention-to-treat and as-treated analyses were performed. The number needed to treat to prevent 1 distant metastasis at 10 years was calculated based on prognostic risk group. The analyses were conducted from January 5 to August 15, 2023. Main Outcomes and Measures The primary end point for this study was overall survival, defined as time to death or last follow-up from randomization. Secondary end points included biochemical recurrence, distant metastasis (DM), prostate cancer–specific mortality, and other-cause mortality. Results The median (IQR) age among the 10 266 male patients was 70 (65-74) years. Longer durations of ADT were associated with nonlinear improvement in relative benefits of DM, prostate cancer–specific mortality, and overall survival, with reduced estimated benefits beyond 9 to 12 months of ADT based on the end point. There was a near-linear increase in other-cause mortality associated with long-term ADT use (hazard ratio, 1.28; 95% CI, 1.09-1.50; <jats:italic toggle=\"yes\">P</jats:italic> = .002 for 28 vs 0 months of ADT). The optimal ADT duration based on 10-year DM was 0, 6, 12 months, and undefined for patients with 1 intermediate-risk factor, 2 or more intermediate-risk factors, and National Comprehensive Cancer Network high-risk and very high-risk disease, respectively. Conclusions and Relevance The results of this meta-analysis suggest that, for men with localized prostate cancer treated with definitive radiotherapy and ADT, there are relative and absolute benefits from increasing durations of ADT that help provide individualized risk estimates.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"25 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145554826","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 : 2025-11-20DOI: 10.1001/jamaoncol.2025.4167
Matthew R. Cooperberg, John R. Bihn, John M. Culnan, Jennifer La, Sergey D. Goryachev, Daniel C. R. Chen, Oleg Soloviev, Grace Lee, June K. Corrigan, Kaitlin N. Swinnerton, Nicholas G. Nickols, Karlynn N. Dulberger, Pedro Barata, Rhonda L. Bitting, Mary T. Brophy, Heather H. Cheng, Amanda De Hoedt, Nhan V. Do, Stephen J. Freedland, Isla P. Garraway, J. Michael Gaziano, Susan Halabi, Richard L. Hauger, Stacy Loeb, David M. Nanus, Timothy R. Rebbeck, Matthew B. Rettig, Chong-Xian Pan, Kenute Myrie, Rachel B. Ramoni, Nathanael R. Fillmore, Channing J. Paller
This cohort study compares magnetic resonance imaging with confirmatory biopsy for patients with favorable-risk prostate cancer undergoing active surveilance.
这项队列研究比较了磁共振成像和确诊活检对积极监测的有利风险前列腺癌患者的影响。
{"title":"Magnetic Resonance Imaging or Confirmatory Biopsy for Patients With Prostate Cancer Receiving Active Surveillance","authors":"Matthew R. Cooperberg, John R. Bihn, John M. Culnan, Jennifer La, Sergey D. Goryachev, Daniel C. R. Chen, Oleg Soloviev, Grace Lee, June K. Corrigan, Kaitlin N. Swinnerton, Nicholas G. Nickols, Karlynn N. Dulberger, Pedro Barata, Rhonda L. Bitting, Mary T. Brophy, Heather H. Cheng, Amanda De Hoedt, Nhan V. Do, Stephen J. Freedland, Isla P. Garraway, J. Michael Gaziano, Susan Halabi, Richard L. Hauger, Stacy Loeb, David M. Nanus, Timothy R. Rebbeck, Matthew B. Rettig, Chong-Xian Pan, Kenute Myrie, Rachel B. Ramoni, Nathanael R. Fillmore, Channing J. Paller","doi":"10.1001/jamaoncol.2025.4167","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4167","url":null,"abstract":"This cohort study compares magnetic resonance imaging with confirmatory biopsy for patients with favorable-risk prostate cancer undergoing active surveilance.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"54 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145554775","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 : 2025-11-13DOI: 10.1001/jamaoncol.2025.4777
Chen Wang, Mengxi Du, Hanseul Kim, Long H. Nguyen, Qiao-Li Wang, David A. Drew, Emily R. Leeming, Neha Khandpur, Qi Sun, Xiaoyu Zong, Tae-Geun Gweon, Shuji Ogino, Kimmie Ng, Sarah Berry, Edward L. Giovannucci, Mingyang Song, Yin Cao, Andrew T. Chan
Importance Early-onset colorectal cancer (EOCRC) (diagnosed age &lt;50 years) incidence is increasing globally, in parallel with increased consumption of ultraprocessed foods (UPFs). The role of UPFs in early-onset colorectal neoplasia remains underexplored. Objective To evaluate the association between UPF consumption and risk of EOCRC precursors. Design, Setting, and Participants This prospective cohort study included participants of the Nurses’ Health Study II, an ongoing US prospective cohort of female registered nurses established in 1989. Participants were followed up from June 1, 1991, through June 1, 2015. Data were analyzed from October 2024 to July 2025. UPF intake, derived from food-frequency questionnaires administered every 4 years and classified using the Nova system, was modeled as quintiles of energy-adjusted servings per day. Of the nurses enrolled, those who had completed the baseline 1991 food-frequency questionnaire, undergone at least 1 lower endoscopy before age 50 years after baseline, had no history of cancer (except for nonmelanoma skin cancer) before endoscopy, and no colorectal polyp or inflammatory bowel disease were included. Main Outcomes and Measures Incidence of EOCRC precursors, including conventional adenomas and serrated lesions, confirmed via medical records and pathology reports. Multivariable logistic regression models with generalized estimating equations for clustered data were used to estimate adjusted odds ratios (AORs) and 95% CIs, accounting for known and putative risk factors. Results Among 29 105 female participants (mean [SD] age, 45.2 [4.5] years) over 24 years of follow-up, 1189 cases were documented of early-onset conventional adenomas and 1598 serrated lesions. UPFs provided 34.8% of total daily calories (median, 5.7 [IQR, 4.5-7.4] servings per day). Participants with higher UPF intake had an increased risk of early-onset conventional adenomas (highest vs lowest intake: AOR, 1.45; 95% CI, 1.19-1.77; overall P &lt; .001) but not serrated lesions (AOR, 1.04; 95% CI, 0.89-1.22; P = .48 for trend). Findings were consistent after further adjustment for body mass index, type 2 diabetes, dietary factors (fiber, folate, calcium, and vitamin D), and Alternative Healthy Eating Index–2010 score. Conclusions and Relevance In this study, higher UPF intake was associated with increased risk of early-onset colorectal conventional adenomas. These data highlight the important role of UPFs in early-onset colorectal tumorigenesis and support improving dietary quality as a strategy to mitigate the increasing burden of EOCRC.
{"title":"Ultraprocessed Food Consumption and Risk of Early-Onset Colorectal Cancer Precursors Among Women","authors":"Chen Wang, Mengxi Du, Hanseul Kim, Long H. Nguyen, Qiao-Li Wang, David A. Drew, Emily R. Leeming, Neha Khandpur, Qi Sun, Xiaoyu Zong, Tae-Geun Gweon, Shuji Ogino, Kimmie Ng, Sarah Berry, Edward L. Giovannucci, Mingyang Song, Yin Cao, Andrew T. Chan","doi":"10.1001/jamaoncol.2025.4777","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4777","url":null,"abstract":"Importance Early-onset colorectal cancer (EOCRC) (diagnosed age &amp;lt;50 years) incidence is increasing globally, in parallel with increased consumption of ultraprocessed foods (UPFs). The role of UPFs in early-onset colorectal neoplasia remains underexplored. Objective To evaluate the association between UPF consumption and risk of EOCRC precursors. Design, Setting, and Participants This prospective cohort study included participants of the Nurses’ Health Study II, an ongoing US prospective cohort of female registered nurses established in 1989. Participants were followed up from June 1, 1991, through June 1, 2015. Data were analyzed from October 2024 to July 2025. UPF intake, derived from food-frequency questionnaires administered every 4 years and classified using the Nova system, was modeled as quintiles of energy-adjusted servings per day. Of the nurses enrolled, those who had completed the baseline 1991 food-frequency questionnaire, undergone at least 1 lower endoscopy before age 50 years after baseline, had no history of cancer (except for nonmelanoma skin cancer) before endoscopy, and no colorectal polyp or inflammatory bowel disease were included. Main Outcomes and Measures Incidence of EOCRC precursors, including conventional adenomas and serrated lesions, confirmed via medical records and pathology reports. Multivariable logistic regression models with generalized estimating equations for clustered data were used to estimate adjusted odds ratios (AORs) and 95% CIs, accounting for known and putative risk factors. Results Among 29 105 female participants (mean [SD] age, 45.2 [4.5] years) over 24 years of follow-up, 1189 cases were documented of early-onset conventional adenomas and 1598 serrated lesions. UPFs provided 34.8% of total daily calories (median, 5.7 [IQR, 4.5-7.4] servings per day). Participants with higher UPF intake had an increased risk of early-onset conventional adenomas (highest vs lowest intake: AOR, 1.45; 95% CI, 1.19-1.77; overall <jats:italic toggle=\"yes\">P</jats:italic> &amp;lt; .001) but not serrated lesions (AOR, 1.04; 95% CI, 0.89-1.22; <jats:italic toggle=\"yes\">P</jats:italic> = .48 for trend). Findings were consistent after further adjustment for body mass index, type 2 diabetes, dietary factors (fiber, folate, calcium, and vitamin D), and Alternative Healthy Eating Index–2010 score. Conclusions and Relevance In this study, higher UPF intake was associated with increased risk of early-onset colorectal conventional adenomas. These data highlight the important role of UPFs in early-onset colorectal tumorigenesis and support improving dietary quality as a strategy to mitigate the increasing burden of EOCRC.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"88 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498652","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 : 2025-11-13DOI: 10.1001/jamaoncol.2025.4730
Cathy J. Bradley, Lindsay M. Sabik
This Viewpoint discusses the potential repercussions of Medicaid cuts, including losses of progress in prevention, care delivery, and treatment of patients with cancer.
本观点讨论了削减医疗补助计划的潜在影响，包括在预防、护理和癌症患者治疗方面的进展损失。
{"title":"Unwinding Progress—Medicaid Cuts and the Future of Cancer Care","authors":"Cathy J. Bradley, Lindsay M. Sabik","doi":"10.1001/jamaoncol.2025.4730","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4730","url":null,"abstract":"This Viewpoint discusses the potential repercussions of Medicaid cuts, including losses of progress in prevention, care delivery, and treatment of patients with cancer.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"24 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498654","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 : 2025-11-13DOI: 10.1001/jamaoncol.2025.4543
Joerg Herrmann, Ana Barac, Joseph Carver, Richard K. Cheng, Andres Daniele, Susan Dent, Elena Deych, Dae Hyun Lee, Daniel Lenihan, Darryl P. Leong, Jennifer Liu, Teresa Lopez-Fernandez, Alexander R. Lyon, Michael Fradley, Ariane V. S. Macedo, Meghan J. Mooradian, Anju Nohria, Charles Porter, Tienush Rassaf, Giselle Suero-Abreu, Aaron L. Sverdlov, Paaladinesh Thavendiranathan, Tomas G. Neilan, Joshua D. Mitchell
Importance The introduction of immune checkpoint inhibitor (ICI) therapy has improved cancer outcomes but at the cost of adverse events, mainly related to the immune system. Cardiovascular (CV) toxic effects, and especially myocarditis, are of particular concern and are the subject of this position statement by the International Cardio-Oncology Society with representation of experts from oncology, hematology, and cardiology. Observations CV toxic effects of ICI therapies include inflammation-associated diseases, such as myocarditis, pericarditis, and vasculitis, as well as the aggravation of chronic inflammatory conditions, such as atherosclerosis with acute ischemic complications (myocardial infarction and stroke). Patients taking ICI therapies can also develop cardiac dysfunction, stress-induced cardiomyopathy (Takotsubo or apical ballooning syndrome), and heart failure without inflammatory cell infiltration of the myocardium. Atrial and ventricular arrhythmias can emerge in the setting of a systemic inflammatory milieu, myocarditis, or ischemia. Of all potential CV adverse effects, myocarditis remains of highest concern, although fatality rates have declined over time with a broadening spectrum of presentations ranging from troponin elevation of uncertain significance to smoldering, nonsevere, and severe or fulminant myocarditis. Conclusions and Relevance Concerns for myocarditis continue to dominate the spectrum of CV toxic effects in patients receiving ICI therapy. Recommendations for management vary according to severity. Multidisciplinary collaborations remain key for managing acute toxic effects and future cancer treatment decisions, including ICI rechallenge. Ischemic heart disease constitutes the main differential diagnosis in these patients, while pericarditis can be concomitantly present, and atrial and ventricular arrhythmias can also complicate the clinical picture. Several gaps in knowledge are identified and require further research.
{"title":"Immune Checkpoint Inhibitor–Associated Cardiovascular Toxic Effects","authors":"Joerg Herrmann, Ana Barac, Joseph Carver, Richard K. Cheng, Andres Daniele, Susan Dent, Elena Deych, Dae Hyun Lee, Daniel Lenihan, Darryl P. Leong, Jennifer Liu, Teresa Lopez-Fernandez, Alexander R. Lyon, Michael Fradley, Ariane V. S. Macedo, Meghan J. Mooradian, Anju Nohria, Charles Porter, Tienush Rassaf, Giselle Suero-Abreu, Aaron L. Sverdlov, Paaladinesh Thavendiranathan, Tomas G. Neilan, Joshua D. Mitchell","doi":"10.1001/jamaoncol.2025.4543","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4543","url":null,"abstract":"Importance The introduction of immune checkpoint inhibitor (ICI) therapy has improved cancer outcomes but at the cost of adverse events, mainly related to the immune system. Cardiovascular (CV) toxic effects, and especially myocarditis, are of particular concern and are the subject of this position statement by the International Cardio-Oncology Society with representation of experts from oncology, hematology, and cardiology. Observations CV toxic effects of ICI therapies include inflammation-associated diseases, such as myocarditis, pericarditis, and vasculitis, as well as the aggravation of chronic inflammatory conditions, such as atherosclerosis with acute ischemic complications (myocardial infarction and stroke). Patients taking ICI therapies can also develop cardiac dysfunction, stress-induced cardiomyopathy (Takotsubo or apical ballooning syndrome), and heart failure without inflammatory cell infiltration of the myocardium. Atrial and ventricular arrhythmias can emerge in the setting of a systemic inflammatory milieu, myocarditis, or ischemia. Of all potential CV adverse effects, myocarditis remains of highest concern, although fatality rates have declined over time with a broadening spectrum of presentations ranging from troponin elevation of uncertain significance to smoldering, nonsevere, and severe or fulminant myocarditis. Conclusions and Relevance Concerns for myocarditis continue to dominate the spectrum of CV toxic effects in patients receiving ICI therapy. Recommendations for management vary according to severity. Multidisciplinary collaborations remain key for managing acute toxic effects and future cancer treatment decisions, including ICI rechallenge. Ischemic heart disease constitutes the main differential diagnosis in these patients, while pericarditis can be concomitantly present, and atrial and ventricular arrhythmias can also complicate the clinical picture. Several gaps in knowledge are identified and require further research.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"148 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145499062","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 : 2025-11-13DOI: 10.1001/jamaoncol.2025.4566
Ryan D. Chow, Ramy Sedhom, Ronac Mamtani
This retrospective cohort study examines the association of upfront treatment with enfortumab vedotin plus pembrolizumab with clinical outcomes for patients with advanced urothelial cancer.
{"title":"Reduced-Dose Enfortumab Vedotin, Treatment Continuity, and Survival in Urothelial Cancer","authors":"Ryan D. Chow, Ramy Sedhom, Ronac Mamtani","doi":"10.1001/jamaoncol.2025.4566","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4566","url":null,"abstract":"This retrospective cohort study examines the association of upfront treatment with enfortumab vedotin plus pembrolizumab with clinical outcomes for patients with advanced urothelial cancer.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"237 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145499063","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 : 2025-11-13DOI: 10.1001/jamaoncol.2025.4721
Matteo S. Carlino, Bo Gao, Michael Michael, Henry Marshall, Ashray Gunjur, Howard Chan, Rob Zielinski, Jane So, Samuel J. Harris, Damien Kee, Ian M. Collins, Wei-Sen Lam, Megan Lyle, Craig Underhill, Michael P. Brown, Rosemary Harrup, Shu-Fen Wong, John Grady, Mandy Ballinger, Elnaz Tavancheh, David M. Thomas, Jodie Palmer, Kylie Wilkie, Jonathan Cebon, Oliver Klein
Importance Mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) cancers constitute one of the most immunogenic tumors. Anti–programmed cell death 1 (PD-1) monotherapy provides durable responses in a third of patients with advanced dMMR/MSI-H noncolorectal cancers. Combined anti–PD-1/cytotoxic lymphocyte antigen 4 (CTLA-4) blockade using nivolumab and ipilimumab has shown superiority to anti–PD-1 monotherapy in other immunogenic cancers such as metastatic melanoma. The Combination Immunotherapy in Rare Cancers Under Investigation (MOST-CIRCUIT) is the first trial that investigated combined anti–PD-1/CTLA-4 blockade in advanced dMMR/MSI-H noncolorectal cancers. Objective To evaluate the efficacy and safety of combined anti–PD-1/CTLA-4 blockade using nivolumab and ipilimumab in advanced dMMR/MSI-H noncolorectal cancers. Design, Setting, and Participants The MOST-CIRCUIT prospective multicenter nonrandomized phase 2 clinical trial enrolled 52 patients with advanced dMMR/MSI-H into cohort D. Patients were enrolled from August 2021 to February 2024 across 17 Australian and New Zealand sites. The analysis itself took place in May 2025. Interventions Patients received nivolumab, 3 mg/kg, and ipilimumab, 1 mg/kg, every 3 weeks for 4 doses, followed by nivolumab, 480 mg, every 4 weeks for 96 weeks, until disease progression or the development of unacceptable toxic effects. Main outcome and Measures The co-primary end points were objective response rate (ORR) and 6-month progression-free survival (6-PFS) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, with the secondary end points being median overall survival (mOS), progression-free survival (PFS), and treatment-related toxic effects. Results Overall, 52 participants were included. The median (range) age of participants was 62 (29-84) years; 41 (79%) were female individuals and 11 (21%) were male individuals. Overall, 52 patients representing 17 tumor types were enrolled, with the most common tumor type being endometrial cancer (26 [50%]). Twenty-seven patients (52%) were pretreated for metastatic disease. ORR was 63% (95% CI, 50% to 75%) with the median duration of response not being reached and 79% of responses being ongoing. The median PFS and OS have not been reached and the 6-month PFS was 71% (95% CI, 57%-81%). Overall, 12 patients (23%) experienced a grade 3/4 immune-related adverse event. Conclusions and Relevance This nonrandomized clinical trial found that combined anti–PD-1/CTLA-4 blockade was associated with a high rate of durable responses in dMMR/MSI-H noncolorectal cancers, comparing favorably to published trials using anti–PD-1/programmed cell death ligand 1 monotherapy. Anti–PD-1/CTLA-4 blockade using nivolumab and ipilimumab may represent an alternative treatment option to monotherapy in this patient population. Trial Registration ClinicalTrials.gov registration:
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Pub Date : 2025-11-13DOI: 10.1001/jamaoncol.2025.4612
Casey M Cosgrove
{"title":"Dual Immune Checkpoint Blockade in Microsatellite Instability-High Cancers-Effective, but for Whom and When?","authors":"Casey M Cosgrove","doi":"10.1001/jamaoncol.2025.4612","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4612","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"8 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145499581","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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