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 <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 < .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:
{"title":"Nivolumab and Ipilimumab in Advanced Mismatch Repair–Deficient/Microsatellite Instability–High Noncolorectal Cancers","authors":"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","doi":"10.1001/jamaoncol.2025.4721","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4721","url":null,"abstract":"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: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"53 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145498653","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.2025.4612
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}
Pub Date : 2025-11-06DOI: 10.1001/jamaoncol.2025.4560
Chungsoo Kim, Michaela A. Dinan, Timothy J. Robinson, Joseph S. Ross, Ania M. Jastreboff, Harlan M. Krumholz, Yuan Lu
This cohort study compares incident and prevalent prescription rates of glucagon-like peptide-1 receptor agonists among adults with at least 1 obesity-related comorbidity and newly diagnosed cancer.
{"title":"Semaglutide and Tirzepatide Prescribing for Obesity in Patients With Preexisting Comorbid Cancers","authors":"Chungsoo Kim, Michaela A. Dinan, Timothy J. Robinson, Joseph S. Ross, Ania M. Jastreboff, Harlan M. Krumholz, Yuan Lu","doi":"10.1001/jamaoncol.2025.4560","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4560","url":null,"abstract":"This cohort study compares incident and prevalent prescription rates of glucagon-like peptide-1 receptor agonists among adults with at least 1 obesity-related comorbidity and newly diagnosed cancer.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"40 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447132","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 : 2025-11-06DOI: 10.1001/jamaoncol.2025.4521
Timothy P. Dougherty, Rainer J. Klement, Colin E. Champ
This Viewpoint discusses adverse effects associated with pharmacologic treatment of patients with cancer and overweight or obesity and emphasizes the importance of lifestyle modifications.
本观点讨论了与癌症和超重或肥胖患者的药物治疗相关的不良反应，并强调了改变生活方式的重要性。
{"title":"Muscle Mass, Fragility, Weight Loss, and Cancer Treatment","authors":"Timothy P. Dougherty, Rainer J. Klement, Colin E. Champ","doi":"10.1001/jamaoncol.2025.4521","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4521","url":null,"abstract":"This Viewpoint discusses adverse effects associated with pharmacologic treatment of patients with cancer and overweight or obesity and emphasizes the importance of lifestyle modifications.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"37 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447136","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 : 2025-11-06DOI: 10.1001/jamaoncol.2025.4551
Rohtesh S. Mehta, Rodney A. Sparapani, Christopher G. Kanakry, Shannon R. McCurdy, Jennifer Saultz, Aleksandr Lazaryan, Filippo Milano, Stephanie J. Lee
Importance Advanced age in unrelated donors (URDs) is a well-established risk factor in allogeneic hematopoietic cell transplant (HCT), leading registries to prioritize younger donors. However, this paradigm relevance is uncertain in the era of posttransplant cyclophosphamide (PTCy) for graft-vs-host disease (GVHD) prophylaxis, a strategy increasingly adopted for its effectiveness. Clarifying this association is crucial for optimizing donor selection and potentially expanding the donor pool. Objective To determine whether the association of older URD age with overall survival differs between patients receiving PTCy-based vs conventional calcineurin inhibitor (CNI)−based GVHD prophylaxis. Design, Setting, and Participants This was a multicenter cohort study using registry data from the Center for International Blood and Marrow Transplant Research for January 2017 through June 2021. Eligible participants were adult patients with acute leukemia or myelodysplastic syndrome who underwent an allogeneic HCT from a URD who was fully matched for 8 of 8 human leukocyte antigen loci (MUD) or mismatched for 7 of 8 human leukocyte antigen loci (MMUD). Data were analyzed from January to June 2025. Exposures GVHD prophylaxis regimen (PTCy-based vs CNI-based) and donor age (analyzed continuously and categorically). Main Outcomes and Measures Overall survival was the primary outcome, with associations assessed using a multipronged approach including least absolute shrinkage and selection operator (LASSO)−penalized Cox proportional hazards models, inverse probability of treatment weighting (IPTW), and XGBoost machine learning. Results The study analysis included 10 025 patients (mean [SD] age, 56.5 [14.4] years; 4379 female [43.7%] and 5646 male [56.3%] individuals) among whom 7272 (72.5%) had received MUD-CNI; 1681 (16.8%%) MUD-PTCy; 613 (6.1%) MMUD-PTCy; and 459 (4.6%) MMUD-CNI. Increasing donor age was associated with worse OS in CNI-based MUD (hazard ratio [HR], 1.004-1.009 per year increase) and MMUD (HR, 1.022-1.034) cohorts. Conversely, this association was not observed in the combined PTCy cohort (HR, 1.001-1.007). These findings were robust across standard and overlap weighted IPTW, LASSO-penalized models, and XGBoost analyses. The attenuated association in the PTCy cohort was primarily driven by a lack of association between donor age and nonrelapse mortality. Conclusions and Relevance The findings of this cohort study indicate that the association of donor age with URD HCT outcomes appears to be mitigated in the PTCy setting, suggesting that PTCy may counteract some of the adverse effects associated with increased unrelated donor age. This observation challenges existing paradigms and warrants validation in independent cohorts, and if validated, could substantially expand the donor pool.
{"title":"Unrelated Donor Age and Recipient Outcomes After Posttransplant Cyclophosphamide vs Conventional Prophylaxis","authors":"Rohtesh S. Mehta, Rodney A. Sparapani, Christopher G. Kanakry, Shannon R. McCurdy, Jennifer Saultz, Aleksandr Lazaryan, Filippo Milano, Stephanie J. Lee","doi":"10.1001/jamaoncol.2025.4551","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.4551","url":null,"abstract":"Importance Advanced age in unrelated donors (URDs) is a well-established risk factor in allogeneic hematopoietic cell transplant (HCT), leading registries to prioritize younger donors. However, this paradigm relevance is uncertain in the era of posttransplant cyclophosphamide (PTCy) for graft-vs-host disease (GVHD) prophylaxis, a strategy increasingly adopted for its effectiveness. Clarifying this association is crucial for optimizing donor selection and potentially expanding the donor pool. Objective To determine whether the association of older URD age with overall survival differs between patients receiving PTCy-based vs conventional calcineurin inhibitor (CNI)−based GVHD prophylaxis. Design, Setting, and Participants This was a multicenter cohort study using registry data from the Center for International Blood and Marrow Transplant Research for January 2017 through June 2021. Eligible participants were adult patients with acute leukemia or myelodysplastic syndrome who underwent an allogeneic HCT from a URD who was fully matched for 8 of 8 human leukocyte antigen loci (MUD) or mismatched for 7 of 8 human leukocyte antigen loci (MMUD). Data were analyzed from January to June 2025. Exposures GVHD prophylaxis regimen (PTCy-based vs CNI-based) and donor age (analyzed continuously and categorically). Main Outcomes and Measures Overall survival was the primary outcome, with associations assessed using a multipronged approach including least absolute shrinkage and selection operator (LASSO)−penalized Cox proportional hazards models, inverse probability of treatment weighting (IPTW), and XGBoost machine learning. Results The study analysis included 10 025 patients (mean [SD] age, 56.5 [14.4] years; 4379 female [43.7%] and 5646 male [56.3%] individuals) among whom 7272 (72.5%) had received MUD-CNI; 1681 (16.8%%) MUD-PTCy; 613 (6.1%) MMUD-PTCy; and 459 (4.6%) MMUD-CNI. Increasing donor age was associated with worse OS in CNI-based MUD (hazard ratio [HR], 1.004-1.009 per year increase) and MMUD (HR, 1.022-1.034) cohorts. Conversely, this association was not observed in the combined PTCy cohort (HR, 1.001-1.007). These findings were robust across standard and overlap weighted IPTW, LASSO-penalized models, and XGBoost analyses. The attenuated association in the PTCy cohort was primarily driven by a lack of association between donor age and nonrelapse mortality. Conclusions and Relevance The findings of this cohort study indicate that the association of donor age with URD HCT outcomes appears to be mitigated in the PTCy setting, suggesting that PTCy may counteract some of the adverse effects associated with increased unrelated donor age. This observation challenges existing paradigms and warrants validation in independent cohorts, and if validated, could substantially expand the donor pool.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"31 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447141","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 : 2025-11-06DOI: 10.1001/jamaoncol.2025.3601
Mohammad Amin Ansarian, Mahsa Fatahichegeni, Rui Xu, Ying Chen, Xiaoning Wang, Juan Ren, Huasheng Liu
Importance Acute myeloid leukemia (AML) is a severe hematologic cancer with complex genetic heterogeneity necessitating personalized treatment approaches. Artificial intelligence (AI) technologies may revolutionize risk stratification, diagnosis enhancement, and treatment planning in addressing critical gaps in AML management, particularly in low-resource health care environments. Observations This narrative review synthesizes existing AI applications in 3 primary areas of AML management. Machine learning algorithms integrating clinical, cytogenetic, and molecular data demonstrate greater prognostic accuracy than conventional European LeukemiaNet (ELN) guidelines. Deep learning approaches to image analysis yield excellent results for AML subtype identification from bone marrow smears (area under the receiver operating characteristic curve [AUROC]: 0.97) and genetic variant prediction (eg, NPM1 status [AUROC: 0.92]). AI-driven genomic analysis reveals novel prognostic signatures and therapeutic targets through advanced pattern recognition, with high-dimensional machine learning achieving greater than 99% accuracy in AML classification from transcriptomic data. Explainable AI models overcome the black box limitation through interpretable algorithms with Shapley Additive Explanations values and local interpretable model-agnostic explanation techniques. Federated learning approaches enable multi-institutional collaboration with protection of patient privacy, with 96.5% accuracy in leukemia classification on heterogeneous datasets. Conclusions and Relevance AI technologies hold potential to improve AML treatment through enhanced risk stratification, early detection capabilities, and individualized treatment optimization. The transition toward explainable AI models is essential to clinical readiness, with federated learning architectures resolving data scarcity concerns. Seamless integration requires harmonized data standards, robust regulatory frameworks, and equitable access to technology to fully realize the transformative potential of AI in improving outcomes for patients with AML globally.
{"title":"Emerging Artificial Intelligence Technologies for Risk Assessment and Management in Acute Myeloid Leukemia","authors":"Mohammad Amin Ansarian, Mahsa Fatahichegeni, Rui Xu, Ying Chen, Xiaoning Wang, Juan Ren, Huasheng Liu","doi":"10.1001/jamaoncol.2025.3601","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.3601","url":null,"abstract":"Importance Acute myeloid leukemia (AML) is a severe hematologic cancer with complex genetic heterogeneity necessitating personalized treatment approaches. Artificial intelligence (AI) technologies may revolutionize risk stratification, diagnosis enhancement, and treatment planning in addressing critical gaps in AML management, particularly in low-resource health care environments. Observations This narrative review synthesizes existing AI applications in 3 primary areas of AML management. Machine learning algorithms integrating clinical, cytogenetic, and molecular data demonstrate greater prognostic accuracy than conventional European LeukemiaNet (ELN) guidelines. Deep learning approaches to image analysis yield excellent results for AML subtype identification from bone marrow smears (area under the receiver operating characteristic curve [AUROC]: 0.97) and genetic variant prediction (eg, <jats:italic toggle=\"yes\">NPM1</jats:italic> status [AUROC: 0.92]). AI-driven genomic analysis reveals novel prognostic signatures and therapeutic targets through advanced pattern recognition, with high-dimensional machine learning achieving greater than 99% accuracy in AML classification from transcriptomic data. Explainable AI models overcome the black box limitation through interpretable algorithms with Shapley Additive Explanations values and local interpretable model-agnostic explanation techniques. Federated learning approaches enable multi-institutional collaboration with protection of patient privacy, with 96.5% accuracy in leukemia classification on heterogeneous datasets. Conclusions and Relevance AI technologies hold potential to improve AML treatment through enhanced risk stratification, early detection capabilities, and individualized treatment optimization. The transition toward explainable AI models is essential to clinical readiness, with federated learning architectures resolving data scarcity concerns. Seamless integration requires harmonized data standards, robust regulatory frameworks, and equitable access to technology to fully realize the transformative potential of AI in improving outcomes for patients with AML globally.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"28 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447131","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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