Pub Date : 2026-01-29DOI: 10.1001/jamaoncol.2025.6196
Suzanne G. Orchard, Galina Polekhina, John Zalcberg, Wendy Bernstein, Finlay Macrae, Jeanne Tie, Lucy Gately, Victoria Mar, Jeremy Millar, Luz Maria Rodriguez, G. J. van Londen, Aaron Kent, Emma Hiscutt, Wee Loon Ong, Erica T. Warner, Leslie Ford, Asad Umar, John J. McNeil, Mark Nelson, Nigel Stocks, Raj C. Shah, Brenda Kirpach, Anne Murray, Robyn L. Woods, Joanne Ryan, Rory Wolfe, Peter Gibbs, Andrew T. Chan
Importance Prior studies, largely among middle-aged adults, reported aspirin reduces cancer risk after 10 years, particularly for colorectal cancer (CRC). In contrast, the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial (RCT) reported that low-dose aspirin (LDA) treatment for a median of 4.7 years had no effect on overall cancer incidence but increased risk of incident late-stage cancer and cancer-related mortality. Objective To assess whether LDA is associated with cancer incidence and mortality in 10 years of follow-up in older adults (aged ≥70 years) and to assess the association with cancer after prior LDA exposure (legacy effects). Design, Setting, and Participants This community-based binational (Australian and US) cohort study included community-dwelling older adults (aged ≥70 years for Australian participants and ≥65 years for US minority group participants) free from overt cardiovascular disease, dementia, or independence-limiting physical disability. The cohort was derived from the ASPREE randomized clinical trial conducted from 2010 to 2017, with the observational extension study (ASPREE-XT) following up participants from 2018 to 2024. This study reports data from 2010 through 2022 (long-term outcomes) as well as reports analyses confined to the observation phase only (legacy analyses). Data were analyzed from May to November 2025. Intervention Daily 100-mg aspirin or placebo from randomization until cessation of study drug. Main Outcomes and Measures Outcomes were physician-adjudicated incident cancer, type, stage at diagnosis, and cancer mortality. Results In 19 114 community-dwelling older adults (mean [SD] age, 75.1 [4.5] years; 56.4% female), a total of 3448 incident cancers and 1173 cancer-related deaths occurred over 10 years of follow-up (median, 8.6 [IQR, 7.4-10.0] years) during ASPREE and ASPREE-XT. LDA was not associated with overall cancer incidence over the long term (hazard ratio [HR] = 0.98; 95% CI, 0.92-1.05), by stage at diagnosis or cancer type, including colorectal cancer (HR = 1.01; 95% CI, 0.84-1.21). However, LDA was associated with increased cancer-related mortality (HR = 1.15; 95% CI, 1.03-1.29). Among 14 907 participants without cancer during the RCT and consented into ASPREE-XT (median age, 78.6 years [IQR, 76.2-82.1]; 57.5% female), 1451 incident cancers and 376 cancer deaths occurred in the post-RCT period, during which original aspirin assignment during the RCT was not associated with differences in cancer incidence (HR = 0.91; 95% CI, 0.82-1.01) or cancer-related mortality (HR = 1.02; 95% CI, 0.83-1.25) compared with original placebo assignment. Conclusions and Relevance In this study, over a median of 8.6 years, LDA was not associated with incident cancer among older adults, but cancer mortality risk was significantly elevated. However, the elevated cancer mortality risk seen with aspirin for participants in the RCT period did not persist into the post-RCT observation period,
{"title":"Cancer Incidence and Mortality With Aspirin in Older Adults","authors":"Suzanne G. Orchard, Galina Polekhina, John Zalcberg, Wendy Bernstein, Finlay Macrae, Jeanne Tie, Lucy Gately, Victoria Mar, Jeremy Millar, Luz Maria Rodriguez, G. J. van Londen, Aaron Kent, Emma Hiscutt, Wee Loon Ong, Erica T. Warner, Leslie Ford, Asad Umar, John J. McNeil, Mark Nelson, Nigel Stocks, Raj C. Shah, Brenda Kirpach, Anne Murray, Robyn L. Woods, Joanne Ryan, Rory Wolfe, Peter Gibbs, Andrew T. Chan","doi":"10.1001/jamaoncol.2025.6196","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.6196","url":null,"abstract":"Importance Prior studies, largely among middle-aged adults, reported aspirin reduces cancer risk after 10 years, particularly for colorectal cancer (CRC). In contrast, the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial (RCT) reported that low-dose aspirin (LDA) treatment for a median of 4.7 years had no effect on overall cancer incidence but increased risk of incident late-stage cancer and cancer-related mortality. Objective To assess whether LDA is associated with cancer incidence and mortality in 10 years of follow-up in older adults (aged ≥70 years) and to assess the association with cancer after prior LDA exposure (legacy effects). Design, Setting, and Participants This community-based binational (Australian and US) cohort study included community-dwelling older adults (aged ≥70 years for Australian participants and ≥65 years for US minority group participants) free from overt cardiovascular disease, dementia, or independence-limiting physical disability. The cohort was derived from the ASPREE randomized clinical trial conducted from 2010 to 2017, with the observational extension study (ASPREE-XT) following up participants from 2018 to 2024. This study reports data from 2010 through 2022 (long-term outcomes) as well as reports analyses confined to the observation phase only (legacy analyses). Data were analyzed from May to November 2025. Intervention Daily 100-mg aspirin or placebo from randomization until cessation of study drug. Main Outcomes and Measures Outcomes were physician-adjudicated incident cancer, type, stage at diagnosis, and cancer mortality. Results In 19 114 community-dwelling older adults (mean [SD] age, 75.1 [4.5] years; 56.4% female), a total of 3448 incident cancers and 1173 cancer-related deaths occurred over 10 years of follow-up (median, 8.6 [IQR, 7.4-10.0] years) during ASPREE and ASPREE-XT. LDA was not associated with overall cancer incidence over the long term (hazard ratio [HR] = 0.98; 95% CI, 0.92-1.05), by stage at diagnosis or cancer type, including colorectal cancer (HR = 1.01; 95% CI, 0.84-1.21). However, LDA was associated with increased cancer-related mortality (HR = 1.15; 95% CI, 1.03-1.29). Among 14 907 participants without cancer during the RCT and consented into ASPREE-XT (median age, 78.6 years [IQR, 76.2-82.1]; 57.5% female), 1451 incident cancers and 376 cancer deaths occurred in the post-RCT period, during which original aspirin assignment during the RCT was not associated with differences in cancer incidence (HR = 0.91; 95% CI, 0.82-1.01) or cancer-related mortality (HR = 1.02; 95% CI, 0.83-1.25) compared with original placebo assignment. Conclusions and Relevance In this study, over a median of 8.6 years, LDA was not associated with incident cancer among older adults, but cancer mortality risk was significantly elevated. However, the elevated cancer mortality risk seen with aspirin for participants in the RCT period did not persist into the post-RCT observation period, ","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"4 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071493","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}
IMPORTANCE Programmed cell death 1 protein (PD-1) or programmed cell death 1 ligand 1 inhibitors plus chemotherapy is the current standard first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). However, the long-term survival benefits at the 5-year benchmark remain uncertain. OBJECTIVE To determine whether adding camrelizumab to chemotherapy significantly improved 5-year overall survival (OS) as first-line treatment for RM-NPC, compared with chemotherapy alone. DESIGN, SETTING, AND PARTICIPANTS The CAPTAIN-1st trial was a randomized, double-blind, phase 3 trial conducted at 28 hospitals in China. Between November 13, 2018, and November 29, 2019, patients with treatment-naive RM-NPC were enrolled. This secondary analysis of the CAPTAIN-1st trial was prespecified. Data analysis was conducted on June 1, 2025. INTERVENTIONS Patients were randomized (1:1) to receive camrelizumab or placebo in combination with gemcitabine and cisplatin for 4 to 6 cycles, followed by maintenance therapy with camrelizumab or placebo until disease progression, unacceptable toxic effects, or completion of 2 years of treatment. MAIN OUTCOME The primary end point, progression-free survival per independent review committee, has been reported previously. Herein, the secondary end point of OS is reported as prespecified in the protocol. RESULTS Among 263 randomized patients (134 in randomized to camrelizumab, 129 to placebo), baseline characteristics were generally balanced between groups, except for age. The mean (SD) age was 49 (11.25) years, and 218 patients (82.9%) were male individuals, 45 (17.1%) were female individuals. With a median survival follow-up of 63.5 (95% CI, 61.2-64.6) months for the camrelizumab group and 63.0 (95% CI, 60.8-64.6) months for the placebo group, 85 (63.4%) and 95 (73.6%) deaths occurred, respectively. Median OS was 34.5 months (95% CI, 29.4-45.7) with camrelizumab vs 26.6 months (95% CI, 19.8-33.5) with placebo (hazard ratio [HR], 0.74; 95% CI, 0.55-0.99; 2-sided <jats:italic>P</jats:italic> = .047). After adjusting for age imbalance, the HR was 0.65 (95% CI, 0.48-0.89; <jats:italic>P</jats:italic> = .01). The 5-year OS rates were 37.8% vs 24.2%, reflecting an absolute difference of 13.6% (95% CI, 2.4%-24.8%; <jats:italic>P</jats:italic> = .02) in favor of camrelizumab. The OS benefits were generally consistent across subgroups. In the camrelizumab group, patients who achieved rapid clearance of Epstein-Barr virus (EBV) DNA had significantly longer OS compared with those without EBV DNA clearance (HR, 0.32; 95% CI, 0.18-0.58; <jats:italic>P</jats:italic> &lt; .001). CONCLUSIONS AND RELEVANCE In this secondary analysis of a randomized clinical trial, the addition of camrelizumab to chemotherapy produced statistically significant and clinically meaningful 5-year OS benefits compared with chemotherapy alone in the first-line treatment of RM-NPC. These findings provided the first 5-year evidence supporting the ben
{"title":"Five-Year Outcome of Camrelizumab Plus Chemotherapy in Recurrent or Metastatic Nasopharyngeal Carcinoma","authors":"Yan Huang, Dongchen Sun, Huaqiang Zhou, Ting Zhou, Song Qu, Jingao Li, Chaosu Hu, Mingjun Xu, Weidong Li, Liangfang Shen, Hui Wu, Jinyi Lang, Guangyuan Hu, Zhanxiong Luo, Zhichao Fu, Shenhong Qu, Weineng Feng, Xiaozhong Chen, Shaojun Lin, Bo Xie, Xiaojiang Li, Yan Sun, Zhixiong Lin, Qin Lin, Feng Lei, Jianting Long, Jinsheng Hong, Xiaoming Huang, Lingzhi Zeng, Peiguo Wang, Xiaohui He, Shen Zhao, Gang Chen, Yaxiong Zhang, Yuanyuan Zhao, Wenfeng Fang, Chuanpei Huang, Xiaotong Li, Shaodong Hong, Li Zhang, Yunpeng Yang","doi":"10.1001/jamaoncol.2025.6245","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.6245","url":null,"abstract":"IMPORTANCE Programmed cell death 1 protein (PD-1) or programmed cell death 1 ligand 1 inhibitors plus chemotherapy is the current standard first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). However, the long-term survival benefits at the 5-year benchmark remain uncertain. OBJECTIVE To determine whether adding camrelizumab to chemotherapy significantly improved 5-year overall survival (OS) as first-line treatment for RM-NPC, compared with chemotherapy alone. DESIGN, SETTING, AND PARTICIPANTS The CAPTAIN-1st trial was a randomized, double-blind, phase 3 trial conducted at 28 hospitals in China. Between November 13, 2018, and November 29, 2019, patients with treatment-naive RM-NPC were enrolled. This secondary analysis of the CAPTAIN-1st trial was prespecified. Data analysis was conducted on June 1, 2025. INTERVENTIONS Patients were randomized (1:1) to receive camrelizumab or placebo in combination with gemcitabine and cisplatin for 4 to 6 cycles, followed by maintenance therapy with camrelizumab or placebo until disease progression, unacceptable toxic effects, or completion of 2 years of treatment. MAIN OUTCOME The primary end point, progression-free survival per independent review committee, has been reported previously. Herein, the secondary end point of OS is reported as prespecified in the protocol. RESULTS Among 263 randomized patients (134 in randomized to camrelizumab, 129 to placebo), baseline characteristics were generally balanced between groups, except for age. The mean (SD) age was 49 (11.25) years, and 218 patients (82.9%) were male individuals, 45 (17.1%) were female individuals. With a median survival follow-up of 63.5 (95% CI, 61.2-64.6) months for the camrelizumab group and 63.0 (95% CI, 60.8-64.6) months for the placebo group, 85 (63.4%) and 95 (73.6%) deaths occurred, respectively. Median OS was 34.5 months (95% CI, 29.4-45.7) with camrelizumab vs 26.6 months (95% CI, 19.8-33.5) with placebo (hazard ratio [HR], 0.74; 95% CI, 0.55-0.99; 2-sided <jats:italic>P</jats:italic> = .047). After adjusting for age imbalance, the HR was 0.65 (95% CI, 0.48-0.89; <jats:italic>P</jats:italic> = .01). The 5-year OS rates were 37.8% vs 24.2%, reflecting an absolute difference of 13.6% (95% CI, 2.4%-24.8%; <jats:italic>P</jats:italic> = .02) in favor of camrelizumab. The OS benefits were generally consistent across subgroups. In the camrelizumab group, patients who achieved rapid clearance of Epstein-Barr virus (EBV) DNA had significantly longer OS compared with those without EBV DNA clearance (HR, 0.32; 95% CI, 0.18-0.58; <jats:italic>P</jats:italic> &amp;lt; .001). CONCLUSIONS AND RELEVANCE In this secondary analysis of a randomized clinical trial, the addition of camrelizumab to chemotherapy produced statistically significant and clinically meaningful 5-year OS benefits compared with chemotherapy alone in the first-line treatment of RM-NPC. These findings provided the first 5-year evidence supporting the ben","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"279 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071471","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 : 2026-01-22DOI: 10.1001/jamaoncol.2025.6092
Brandon R Block,Jaanvi Mehta,Shayan Owji,Dan Feng,Thomas U Marron,Nicholas Gulati
{"title":"Morbidity and Mortality Outcomes of Dupilumab for Cutaneous Immune-Related Adverse Events.","authors":"Brandon R Block,Jaanvi Mehta,Shayan Owji,Dan Feng,Thomas U Marron,Nicholas Gulati","doi":"10.1001/jamaoncol.2025.6092","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.6092","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"20 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015354","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 : 2026-01-22DOI: 10.1001/jamaoncol.2025.6080
Rashidul Alam Mahumud,Yifu Chen,Md Shahjalal,Padam Kanta Dahal,Khorshed Alam
ImportanceAdjuvant immunotherapy is increasingly integrated into cancer care to reduce recurrence and improve survival. However, its high cost raises critical concerns regarding affordability and economic value across diverse health system contexts.ObjectiveTo synthesize published economic evaluations of adjuvant immunotherapy and assess cost-effectiveness outcomes, quality-adjusted life-year (QALY)/life-year (LY) gains, and methodologic approaches.Evidence ReviewA systematic search was conducted of PubMed, Scopus, Embase, and Web of Science for full economic evaluations published between January 1, 2015, and January 31, 2025. Eligible studies included cost-effectiveness or cost-utility analyses of adjuvant immunotherapy across any cancer type. Data were extracted on cancer type, treatment strategy (single vs combination therapy), treatment line, model structure, health utility instruments, funding sources, and cost-effectiveness outcomes. Methodologic quality was appraised using the Criteria for Health Economic Quality Evaluation 2023. Due to heterogeneity of health systems, findings were narratively synthesized.FindingsThe analysis included 69 studies covering a range of cancer types, most frequently non-small cell lung cancer and melanoma. Of these, 46 (67%) evaluated first-line therapy with single-agent checkpoint inhibitors. Higher QALY/LY gains were consistently reported among the adjuvant immunotherapy group (63 [91%]), particularly for non-small cell lung cancer, industry-funded studies, and combination regimens. More than half of the evaluations (40 [58%]) concluded that adjuvant immunotherapy was cost-effective, although results varied by cancer type, model assumptions, drug pricing, funding organizations, and country-specific thresholds. Markov modeling was the dominant analytic approach (46 [67%]) and EuroQol 5 Dimensions was the most commonly used health utility instrument (56 [81%]).Conclusions and RelevanceThis systematic review found that adjuvant immunotherapy was frequently associated with meaningful QALY/LY improvements and was often considered cost-effective in high-risk or first-line settings. However, economic value remains context-specific, shaped by treatment strategy, drug costs, and modeling assumptions. These findings support the selective, value-based adoption of adjuvant immunotherapy and underscore the need for transparent, standardized economic evaluations to guide reimbursement and policy decisions.
辅助免疫治疗越来越多地融入到癌症治疗中，以减少复发和提高生存率。然而，它的高成本引起了人们对不同卫生系统背景下可负担性和经济价值的严重关切。目的综合已发表的辅助免疫治疗的经济评价，评估成本-效果、质量调整生命年(QALY)/生命年（LY）收益和方法学方法。对PubMed、Scopus、Embase和Web of Science进行系统检索，获取2015年1月1日至2025年1月31日之间发表的完整经济评估。符合条件的研究包括任何癌症类型的辅助免疫治疗的成本-效果或成本-效用分析。数据包括癌症类型、治疗策略（单一与联合治疗）、治疗线、模式结构、卫生实用工具、资金来源和成本-效果结果。采用《卫生经济质量评价标准2023》对方法学质量进行评价。由于卫生系统的异质性，研究结果是叙述性综合的。该分析包括69项研究，涵盖了一系列癌症类型，最常见的是非小细胞肺癌和黑色素瘤。其中，46个（67%）评估了单药检查点抑制剂的一线治疗。在辅助免疫治疗组（63[91%]），特别是对于非小细胞肺癌、行业资助的研究和联合治疗方案，有更高的QALY/LY增益的报道。超过一半的评估（40项[58%]）得出结论认为辅助免疫治疗具有成本效益，尽管结果因癌症类型、模型假设、药物定价、资助组织和国家特定阈值而异。马尔可夫模型是主要的分析方法（46例[67%]），EuroQol 5 Dimensions是最常用的健康效用工具（56例[81%]）。结论和相关性本系统综述发现，辅助免疫治疗通常与有意义的QALY/LY改善相关，并且通常被认为在高风险或一线环境中具有成本效益。然而，经济价值仍然取决于具体情况，受治疗策略、药物成本和建模假设的影响。这些发现支持选择性的、基于价值的辅助免疫治疗的采用，并强调需要透明、标准化的经济评估来指导报销和政策决策。
{"title":"Cost-Effectiveness of Adjuvant Immunotherapy in Cancer Treatments: A Systematic Review.","authors":"Rashidul Alam Mahumud,Yifu Chen,Md Shahjalal,Padam Kanta Dahal,Khorshed Alam","doi":"10.1001/jamaoncol.2025.6080","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.6080","url":null,"abstract":"ImportanceAdjuvant immunotherapy is increasingly integrated into cancer care to reduce recurrence and improve survival. However, its high cost raises critical concerns regarding affordability and economic value across diverse health system contexts.ObjectiveTo synthesize published economic evaluations of adjuvant immunotherapy and assess cost-effectiveness outcomes, quality-adjusted life-year (QALY)/life-year (LY) gains, and methodologic approaches.Evidence ReviewA systematic search was conducted of PubMed, Scopus, Embase, and Web of Science for full economic evaluations published between January 1, 2015, and January 31, 2025. Eligible studies included cost-effectiveness or cost-utility analyses of adjuvant immunotherapy across any cancer type. Data were extracted on cancer type, treatment strategy (single vs combination therapy), treatment line, model structure, health utility instruments, funding sources, and cost-effectiveness outcomes. Methodologic quality was appraised using the Criteria for Health Economic Quality Evaluation 2023. Due to heterogeneity of health systems, findings were narratively synthesized.FindingsThe analysis included 69 studies covering a range of cancer types, most frequently non-small cell lung cancer and melanoma. Of these, 46 (67%) evaluated first-line therapy with single-agent checkpoint inhibitors. Higher QALY/LY gains were consistently reported among the adjuvant immunotherapy group (63 [91%]), particularly for non-small cell lung cancer, industry-funded studies, and combination regimens. More than half of the evaluations (40 [58%]) concluded that adjuvant immunotherapy was cost-effective, although results varied by cancer type, model assumptions, drug pricing, funding organizations, and country-specific thresholds. Markov modeling was the dominant analytic approach (46 [67%]) and EuroQol 5 Dimensions was the most commonly used health utility instrument (56 [81%]).Conclusions and RelevanceThis systematic review found that adjuvant immunotherapy was frequently associated with meaningful QALY/LY improvements and was often considered cost-effective in high-risk or first-line settings. However, economic value remains context-specific, shaped by treatment strategy, drug costs, and modeling assumptions. These findings support the selective, value-based adoption of adjuvant immunotherapy and underscore the need for transparent, standardized economic evaluations to guide reimbursement and policy decisions.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"396 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015351","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 : 2026-01-22DOI: 10.1001/jamaoncol.2025.5941
Bibek Aryal
{"title":"Make Every Cancer Case Count-A Call From the Mountains.","authors":"Bibek Aryal","doi":"10.1001/jamaoncol.2025.5941","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.5941","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"180 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015352","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 : 2026-01-15DOI: 10.1001/jamaoncol.2025.5934
Anne Rudbeck Juhl, Andreas Glenthøj, Børge Grønne Nordestgaard, Jesper Petersen, Michael Huy Cuong Pham, Klaus Fuglsang Kofoed, Jørgen Tobias Kühl, Andreas Fuchs, Per Ejlstrup Sigvardsen, Thomas Skårup Kristensen, Stig Egil Bojesen, Rasmus Rønnemoes, Jens Helby
Importance Splenomegaly is often detected incidentally, but it is unknown at which spleen length or volume risk of hematologic cancer or liver disease is substantially increased, and evidence lacks on when it is beneficial to evaluate individuals with splenomegaly for underlying disease. Objective To evaluate relative and absolute risks of hematologic cancers, cirrhosis, and liver cancer according to spleen length and volume in individuals with incidentally detected splenomegaly. Design, Setting, and Participants This prospective cohort study used data from 2 independent general population cohorts from Denmark and the UK. Participants had computed tomography or magnetic resonance imaging scans performed as part of study procedures from January 2012 to February 2020 for Danish individuals and from April 2014 to October 2021 for UK individuals. Data were analyzed from April 2024 to November 2025. Exposures Spleen volume and spleen length. Main Outcomes and Measures Hematologic cancers, cirrhosis, and liver cancer during a median follow-up of 5 years after the computed tomography or magnetic resonance imaging scans. Results Among 8459 included Danish individuals, 4821 (57.0%) were female, and the median (IQR) age at scan date was 61 (54-69) years; among 38 607 included UK individuals, 20 048 (51.9%) were female, and the median (IQR) age at scan date was 65 (58-70) years. Spleen length was measured in 8440 Danish individuals, and spleen volume was measured in 8226 Danish and 38 607 UK individuals. Relative risk of any hematologic cancer was increased for Danish individuals with spleen lengths above the 99th percentile (greater than 134 mm) compared with spleen lengths in the 26th to 74th percentile (hazard ratio, 5.11; 95% CI, 2.00-13.06) and more pronounced for spleen volume above the 99th percentile (greater than 433 mL for Danish individuals; hazard ratio, 11.08; 95% CI, 5.44-22.59; greater than 386 mL for UK individuals; hazard ratio, 11.82; 95% CI, 6.98-20.02). When studying absolute risks using clinically applicable cutoffs, 5-year risks of any hematologic cancer were moderately increased for spleen length of 130 to 139 mm or spleen volume of 400 to 499 mL. Individuals with spleen length of 140 mm or greater had even higher risk, as 5-year risks reached 23% in Danish men and 12% in Danish women 70 years and older. Individuals with spleen volume of 500 mL or greater had particularly high risk, with absolute 5-year risks for any hematologic cancer of 46% and 27% in Danish men and women 70 years and older, respectively, while 5-year risks were 21% and 18% in UK men and women 70 years and older, respectively. Furthermore, absolute 5-year risks of cirrhosis and liver cancer were substantially increased in UK individuals with spleen volume of 400 mL or greater, with 5-year risks for cirrhosis reaching 10.8% in men and 9.3% in women 70 years and older with spleen volume of 500 mL or greater. Five-year risks for liver cancer were 3.2% in men and 1.2% i
{"title":"Incidentally Detected Splenomegaly and Risk of Hematologic Cancer and Liver Disease","authors":"Anne Rudbeck Juhl, Andreas Glenthøj, Børge Grønne Nordestgaard, Jesper Petersen, Michael Huy Cuong Pham, Klaus Fuglsang Kofoed, Jørgen Tobias Kühl, Andreas Fuchs, Per Ejlstrup Sigvardsen, Thomas Skårup Kristensen, Stig Egil Bojesen, Rasmus Rønnemoes, Jens Helby","doi":"10.1001/jamaoncol.2025.5934","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.5934","url":null,"abstract":"Importance Splenomegaly is often detected incidentally, but it is unknown at which spleen length or volume risk of hematologic cancer or liver disease is substantially increased, and evidence lacks on when it is beneficial to evaluate individuals with splenomegaly for underlying disease. Objective To evaluate relative and absolute risks of hematologic cancers, cirrhosis, and liver cancer according to spleen length and volume in individuals with incidentally detected splenomegaly. Design, Setting, and Participants This prospective cohort study used data from 2 independent general population cohorts from Denmark and the UK. Participants had computed tomography or magnetic resonance imaging scans performed as part of study procedures from January 2012 to February 2020 for Danish individuals and from April 2014 to October 2021 for UK individuals. Data were analyzed from April 2024 to November 2025. Exposures Spleen volume and spleen length. Main Outcomes and Measures Hematologic cancers, cirrhosis, and liver cancer during a median follow-up of 5 years after the computed tomography or magnetic resonance imaging scans. Results Among 8459 included Danish individuals, 4821 (57.0%) were female, and the median (IQR) age at scan date was 61 (54-69) years; among 38 607 included UK individuals, 20 048 (51.9%) were female, and the median (IQR) age at scan date was 65 (58-70) years. Spleen length was measured in 8440 Danish individuals, and spleen volume was measured in 8226 Danish and 38 607 UK individuals. Relative risk of any hematologic cancer was increased for Danish individuals with spleen lengths above the 99th percentile (greater than 134 mm) compared with spleen lengths in the 26th to 74th percentile (hazard ratio, 5.11; 95% CI, 2.00-13.06) and more pronounced for spleen volume above the 99th percentile (greater than 433 mL for Danish individuals; hazard ratio, 11.08; 95% CI, 5.44-22.59; greater than 386 mL for UK individuals; hazard ratio, 11.82; 95% CI, 6.98-20.02). When studying absolute risks using clinically applicable cutoffs, 5-year risks of any hematologic cancer were moderately increased for spleen length of 130 to 139 mm or spleen volume of 400 to 499 mL. Individuals with spleen length of 140 mm or greater had even higher risk, as 5-year risks reached 23% in Danish men and 12% in Danish women 70 years and older. Individuals with spleen volume of 500 mL or greater had particularly high risk, with absolute 5-year risks for any hematologic cancer of 46% and 27% in Danish men and women 70 years and older, respectively, while 5-year risks were 21% and 18% in UK men and women 70 years and older, respectively. Furthermore, absolute 5-year risks of cirrhosis and liver cancer were substantially increased in UK individuals with spleen volume of 400 mL or greater, with 5-year risks for cirrhosis reaching 10.8% in men and 9.3% in women 70 years and older with spleen volume of 500 mL or greater. Five-year risks for liver cancer were 3.2% in men and 1.2% i","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"81 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972244","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 : 2026-01-15DOI: 10.1001/jamaoncol.2025.5924
Renda Li, Pan Wang, Hao Zhang, Qingpeng Zeng, Chenran Wang, Ni Li, Wenjing Yang, Fengwei Tan, Jie He
Importance Lymph node dissection for early-stage lung adenocarcinoma is controversial. Histologic pattern subtyping reveals heterogeneity of lung adenocarcinoma, yet its association with lymph node involvement and dissection is understudied. Objective To assess the association between guideline-adherent lymph node dissection, histologic pattern subtyping, and overall survival in patients with clinical T1N0M0 lung adenocarcinoma. Design, Setting, and Participants This multicenter cohort study used data from the National Cancer Center LungReal database, a multicenter, electronic health records-based database for patients undergoing surgery for lung cancer, from January 2014 to December 2021, with the last follow-up in December 2022. Patients were categorized based on histologic pattern of adenocarcinoma into 2 groups: lepidic without high-grade pattern, and high-grade or no lepidic pattern. The data analysis was performed from April to November 2025. Exposure Lymph node dissection adherence or nonadherence with the 3 + 1 standard (3 N2 plus 1 N1 station) and the 6-station standard (the subcarinal plus 2 other N2 stations and 3 N1 stations). Main Outcome and Measure Overall survival. Results Of 35 265 patients screened, 27 191 participants (mean [SD] age, 58.3 [11.7] years; 16 280 female [59.9%] and 10 911 male [40.1%] individuals) from 19 centers were included; among them, 15 593 (57.3%) received lymph node dissection adherent with the 3 + 1 standard and 4023 (14.8%) with the 6-station standard. Among the group of 13 369 patients (49.2%) with adenocarcinoma of lepidic without high-grade pattern, no association was observed between survival and adherence with the 3 + 1 standard (hazard ratio [HR], 0.81; 95% CI, 0.57-1.15) or the 6-station standard (HR, 0.54; 95% CI, 0.26-1.13). Whereas, among the group of 13 822 patients (50.8%) with adenocarcinoma of high-grade or no lepidic pattern, adherence with the 3 + 1 standard (HR, 0.81; 95% CI, 0.69-0.95; absolute risk difference at 3-year, 1.2%; 95% CI, 0.2%-2.2%; E-value, 1.78) or the 6-station standard (HR, 0.61; 95% CI, 0.45-0.83; absolute risk difference at 3 years, 1.0%; 95% CI, 0.1%-1.9%; E-value, 2.67) was associated with a significant but small absolute survival benefit. Conclusion and Relevance In this cohort study, guideline-adherent nodal dissection was associated with small absolute survival benefit for patients with adenocarcinoma of high-grade or no lepidic pattern, but not for those with lepidic without high-grade pattern. These observational findings warrant prospective validation and should not be interpreted as causal.
{"title":"Lymph Node Dissection Guideline Adherence and Survival in Patients With T1N0M0 Lung Adenocarcinoma","authors":"Renda Li, Pan Wang, Hao Zhang, Qingpeng Zeng, Chenran Wang, Ni Li, Wenjing Yang, Fengwei Tan, Jie He","doi":"10.1001/jamaoncol.2025.5924","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.5924","url":null,"abstract":"Importance Lymph node dissection for early-stage lung adenocarcinoma is controversial. Histologic pattern subtyping reveals heterogeneity of lung adenocarcinoma, yet its association with lymph node involvement and dissection is understudied. Objective To assess the association between guideline-adherent lymph node dissection, histologic pattern subtyping, and overall survival in patients with clinical T1N0M0 lung adenocarcinoma. Design, Setting, and Participants This multicenter cohort study used data from the National Cancer Center LungReal database, a multicenter, electronic health records-based database for patients undergoing surgery for lung cancer, from January 2014 to December 2021, with the last follow-up in December 2022. Patients were categorized based on histologic pattern of adenocarcinoma into 2 groups: lepidic without high-grade pattern, and high-grade or no lepidic pattern. The data analysis was performed from April to November 2025. Exposure Lymph node dissection adherence or nonadherence with the 3 + 1 standard (3 N2 plus 1 N1 station) and the 6-station standard (the subcarinal plus 2 other N2 stations and 3 N1 stations). Main Outcome and Measure Overall survival. Results Of 35 265 patients screened, 27 191 participants (mean [SD] age, 58.3 [11.7] years; 16 280 female [59.9%] and 10 911 male [40.1%] individuals) from 19 centers were included; among them, 15 593 (57.3%) received lymph node dissection adherent with the 3 + 1 standard and 4023 (14.8%) with the 6-station standard. Among the group of 13 369 patients (49.2%) with adenocarcinoma of lepidic without high-grade pattern, no association was observed between survival and adherence with the 3 + 1 standard (hazard ratio [HR], 0.81; 95% CI, 0.57-1.15) or the 6-station standard (HR, 0.54; 95% CI, 0.26-1.13). Whereas, among the group of 13 822 patients (50.8%) with adenocarcinoma of high-grade or no lepidic pattern, adherence with the 3 + 1 standard (HR, 0.81; 95% CI, 0.69-0.95; absolute risk difference at 3-year, 1.2%; 95% CI, 0.2%-2.2%; E-value, 1.78) or the 6-station standard (HR, 0.61; 95% CI, 0.45-0.83; absolute risk difference at 3 years, 1.0%; 95% CI, 0.1%-1.9%; E-value, 2.67) was associated with a significant but small absolute survival benefit. Conclusion and Relevance In this cohort study, guideline-adherent nodal dissection was associated with small absolute survival benefit for patients with adenocarcinoma of high-grade or no lepidic pattern, but not for those with lepidic without high-grade pattern. These observational findings warrant prospective validation and should not be interpreted as causal.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"60 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972165","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 : 2026-01-08DOI: 10.1001/jamaoncol.2025.5869
Ruofan Shi, Yongle Zhan, Ruochen Ma, Salida Ali, Chi Yao, Tsun Tsun Stacia Chun, Ada Tsui-Lin Ng, Matthew Kin-Liang Chiu, Bryan Cho Wing Li, Rong Na
Importance While preliminary evidence suggests that sodium-glucose cotransporter 2 (SGLT2) inhibitors for diabetes may have antitumorigenic effects, their potential benefits in prostate cancer remain unexplored. Understanding their association with outcomes among patients undergoing hormone therapy could inform future adjunct treatment strategies. Objective To evaluate whether the use of SGLT2 inhibitors is associated with clinical outcomes in patients with prostate cancer receiving hormone therapy. Design, Setting, and Participants This population-based, sequential target trial emulation of monthly cohorts used territory-wide electronic health records (January 1, 1993, to April 30, 2025) from the Hong Kong Hospital Authority, covering a population of approximately 7.5 million. Adult men diagnosed with prostate cancer who initiated androgen deprivation therapy (ADT) were included. Follow-up extended through April 2025, and data were analyzed from June to October 2025. Exposures Use of SGLT2 inhibitors (primarily dapagliflozin and empagliflozin) initiated during hormone therapy and maintained for at least 1 month. Comparator groups included nonusers of SGLT2 inhibitors. Main Outcomes and Measures The primary outcome was time to ADT failure. Secondary outcomes include time to next-generation hormonal agent failure, disease-specific survival, and overall survival. Both intention-to-treat and per-protocol analyses were conducted using complementary log-log model regression to provide the hazard ratio (HR) estimate. Results Among 14 223 eligible patients (median [IQR] age at enrollment, 74 [68-80] years) with a median follow-up of 66 months (95% CI, 65-67 months), intention-to-treat SGLT2 inhibitor use was associated with reduced risk of ADT failure (HR, 0.63; 95% CI, 0.41-0.95; P = .03) and next-generation hormonal agent failure (HR, 0.44; 95% CI, 0.20-0.97; P = .04). Sensitivity analyses confirmed robustness of these findings across different comparator subgroups. Metformin monotherapy was not associated with disease progression but was associated with improved overall survival (HR, 0.59; 95% CI, 0.42-0.83; P = .002). No statistically significant outcome differences were observed between dapagliflozin and empagliflozin. Conclusions and Relevance In this cohort study with a target trial emulation design, SGLT2 inhibitor use was associated with delayed hormone therapy failure in patients with prostate cancer, suggesting a potential oncologic benefit beyond glucose lowering. These findings support the potential of SGLT2 inhibitors in treatment for prostate cancer.
虽然初步证据表明，钠-葡萄糖共转运蛋白2 （SGLT2）抑制剂治疗糖尿病可能具有抗肿瘤作用，但其对前列腺癌的潜在益处尚不清楚。了解它们与接受激素治疗的患者预后的关系可以为未来的辅助治疗策略提供信息。目的评价SGLT2抑制剂的使用是否与接受激素治疗的前列腺癌患者的临床结果相关。设计、设置和参与者这项以人群为基础的顺序目标试验模拟每月队列，使用香港医院管理局的全地区电子健康记录（1993年1月1日至2025年4月30日），涵盖约750万人口。被诊断为前列腺癌并开始雄激素剥夺治疗（ADT）的成年男性被纳入研究对象。随访至2025年4月，分析2025年6月至10月的数据。在激素治疗期间开始使用SGLT2抑制剂（主要是达格列净和恩格列净）并维持至少1个月。比较组包括未使用SGLT2抑制剂的患者。主要观察指标为ADT失效时间。次要结局包括到下一代激素药物失效的时间、疾病特异性生存期和总生存期。意向治疗和方案分析均使用互补对数-对数模型回归进行，以提供风险比（HR）估计。结果在14223例符合条件的患者中（入组时中位[IQR]年龄为74[68-80]岁），中位随访66个月（95% CI， 65-67个月），有意治疗SGLT2抑制剂的使用与ADT失败风险降低（HR, 0.63; 95% CI, 0.41-0.95; P = 0.03）和下一代激素药物失败风险降低（HR, 0.44; 95% CI, 0.20-0.97; P = 0.04）相关。敏感性分析证实了这些发现在不同比较物亚组中的稳健性。二甲双胍单药治疗与疾病进展无关，但与改善的总生存率相关（HR, 0.59; 95% CI, 0.42-0.83; P = 0.002）。在达格列净和恩格列净之间没有统计学上的显著差异。结论和相关性在这项目标试验模拟设计的队列研究中，SGLT2抑制剂的使用与前列腺癌患者延迟激素治疗失败相关，这表明除了降糖外，SGLT2抑制剂的潜在肿瘤益处。这些发现支持SGLT2抑制剂治疗前列腺癌的潜力。
{"title":"Sodium-Glucose Cotransporter 2 Inhibitors for Patients With Prostate Cancer Undergoing Hormone Therapy","authors":"Ruofan Shi, Yongle Zhan, Ruochen Ma, Salida Ali, Chi Yao, Tsun Tsun Stacia Chun, Ada Tsui-Lin Ng, Matthew Kin-Liang Chiu, Bryan Cho Wing Li, Rong Na","doi":"10.1001/jamaoncol.2025.5869","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.5869","url":null,"abstract":"Importance While preliminary evidence suggests that sodium-glucose cotransporter 2 (SGLT2) inhibitors for diabetes may have antitumorigenic effects, their potential benefits in prostate cancer remain unexplored. Understanding their association with outcomes among patients undergoing hormone therapy could inform future adjunct treatment strategies. Objective To evaluate whether the use of SGLT2 inhibitors is associated with clinical outcomes in patients with prostate cancer receiving hormone therapy. Design, Setting, and Participants This population-based, sequential target trial emulation of monthly cohorts used territory-wide electronic health records (January 1, 1993, to April 30, 2025) from the Hong Kong Hospital Authority, covering a population of approximately 7.5 million. Adult men diagnosed with prostate cancer who initiated androgen deprivation therapy (ADT) were included. Follow-up extended through April 2025, and data were analyzed from June to October 2025. Exposures Use of SGLT2 inhibitors (primarily dapagliflozin and empagliflozin) initiated during hormone therapy and maintained for at least 1 month. Comparator groups included nonusers of SGLT2 inhibitors. Main Outcomes and Measures The primary outcome was time to ADT failure. Secondary outcomes include time to next-generation hormonal agent failure, disease-specific survival, and overall survival. Both intention-to-treat and per-protocol analyses were conducted using complementary log-log model regression to provide the hazard ratio (HR) estimate. Results Among 14 223 eligible patients (median [IQR] age at enrollment, 74 [68-80] years) with a median follow-up of 66 months (95% CI, 65-67 months), intention-to-treat SGLT2 inhibitor use was associated with reduced risk of ADT failure (HR, 0.63; 95% CI, 0.41-0.95; <jats:italic toggle=\"yes\">P</jats:italic> = .03) and next-generation hormonal agent failure (HR, 0.44; 95% CI, 0.20-0.97; <jats:italic toggle=\"yes\">P</jats:italic> = .04). Sensitivity analyses confirmed robustness of these findings across different comparator subgroups. Metformin monotherapy was not associated with disease progression but was associated with improved overall survival (HR, 0.59; 95% CI, 0.42-0.83; <jats:italic toggle=\"yes\">P</jats:italic> = .002). No statistically significant outcome differences were observed between dapagliflozin and empagliflozin. Conclusions and Relevance In this cohort study with a target trial emulation design, SGLT2 inhibitor use was associated with delayed hormone therapy failure in patients with prostate cancer, suggesting a potential oncologic benefit beyond glucose lowering. These findings support the potential of SGLT2 inhibitors in treatment for prostate cancer.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"28 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919899","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 : 2026-01-08DOI: 10.1001/jamaoncol.2025.5774
Sarah P. Shubeck, Adrian Diaz
This decision analytical model evaluates projected changes in cancer screening and outcomes following changes to federal Medicaid funding and eligibility restrictions enacted with the 2025 Budget Reconciliation Bill.
{"title":"Projected Cancer Screening and Outcomes Under the 2025 Federal Medicaid Eligibility Restrictions","authors":"Sarah P. Shubeck, Adrian Diaz","doi":"10.1001/jamaoncol.2025.5774","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.5774","url":null,"abstract":"This decision analytical model evaluates projected changes in cancer screening and outcomes following changes to federal Medicaid funding and eligibility restrictions enacted with the 2025 Budget Reconciliation Bill.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"83 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919901","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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