Jama Oncology最新文献

{"title":"Polygenic Risk Scores for Prostate Cancer: Informing Prevention or Therapy.","authors":"Konrad H Stopsack","doi":"10.1001/jamaoncol.2024.5203","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5203","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814770","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}

{"title":"Bilateral Mastectomy vs Lumpectomy and Breast Cancer Mortality Risk.","authors":"Thomas J O'Keefe, Michael D Alvarado, Laura J Esserman","doi":"10.1001/jamaoncol.2024.5655","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5655","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814745","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}

{"title":"Bilateral Mastectomy vs Lumpectomy and Breast Cancer Mortality Risk-Reply.","authors":"Steven A Narod, Vasily Giannakeas","doi":"10.1001/jamaoncol.2024.5658","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5658","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814748","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}

{"title":"Polygenic Risk Score and Upgrading in Patients With Prostate Cancer Receiving Active Surveillance.","authors":"Louisa B Goss, Menghan Liu, Yingye Zheng, Boya Guo, David V Conti, Christopher A Haiman, Linda Kachuri, William J Catalona, John S Witte, Daniel W Lin, Lisa F Newcomb, Burcu F Darst","doi":"10.1001/jamaoncol.2024.5398","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5398","url":null,"abstract":"<p><strong>Importance: </strong>Active surveillance is the preferred management strategy for patients with low- or favorable intermediate-risk prostate cancer (PCa); however, frequent health care visits can be costly and burdensome to patients. Identifying patients who may benefit from intensive vs passive surveillance could reduce these burdens.</p><p><strong>Objective: </strong>To investigate associations between a polygenic risk score (PRS) and risk of upgrading and other prostate tumor features in patients receiving active surveillance.</p><p><strong>Design, setting, and participants: </strong>This prospective multicenter cohort study across 10 US sites included 1220 patients from the Canary Prostate Active Surveillance Study (PASS) enrolled from July 2008 to November 2017, with follow-up (median, 5.3 years) through August 2022. Participants were those with clinically localized PCa (cT1-T2) receiving active surveillance. Analyses took place from January 2023 to April 2024.</p><p><strong>Exposure: </strong>Multi-ancestry PRS of 451 PCa risk variants (PRS-451) and 400 PCa risk variants (PRS-400) after excluding prostate-specific antigen (PSA)-associated variants.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was PCa upgrading (any Gleason grade increase) vs no upgrading. Secondary outcomes included prostate volume, PSA, PSA density, percentage of biopsy cores with cancer, and Gleason grade group at diagnosis.</p><p><strong>Results: </strong>The median (IQR) age at diagnosis of the 1220 patients receiving active surveillance was 63 (58-67) years. During follow-up, 470 patients upgraded; the 2- and 5-year risks of upgrading were 17.7% (95% CI, 15.5%-19.9%) and 33.3% (95% CI, 30.5%-36.3%), respectively. Each 1-SD unit increase in PRS-451 was associated with 23% increased hazard of upgrading (95% CI, 1.11-1.35; P < .001), whereas PRS-400 was associated with 27% increased hazard (95% CI, 1.15-1.39; P < .001) at any point in time during follow-up. Except for PSA, associations with remaining outcomes were similar or stronger using PRS-400. Higher PRS-400 was associated with smaller prostate volume, a higher percentage of biopsy cores with cancer, and higher PSA density. A model with clinical risk factors had a C-index of 0.64 (95% CI, 0.62-0.67); adding PRS-400 led to a C-index of 0.65 (95% CI, 0.63-0.68).</p><p><strong>Conclusions and relevance: </strong>In this cohort study, among patients receiving active surveillance, high PRS was associated with risk of upgrading and possibly tumor multifocality. Excluding PSA variants from the PRS revealed an association with smaller prostate size, which has been previously associated with more aggressive tumors. Although PRS may inform active surveillance, it is yet to be seen whether they improve clinical decisions.</p>","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814769","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}

{"title":"Second Primary Cancer After Chimeric Antigen Receptor-T-Cell Therapy: A Review.","authors":"Shyam A Patel, Jay Y Spiegel, Saurabh Dahiya","doi":"10.1001/jamaoncol.2024.5412","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5412","url":null,"abstract":"<p><strong>Importance: </strong>The commercialization of chimeric antigen receptor-T-cell (CAR-T) therapy has changed the landscape of treatment of hematological cancers. Numerous studies from the early 2000s paved the way for cell-based targeted therapeutics, which have been established as practice-changing therapies in lymphoma, leukemia, and multiple myeloma. However, there has been some recent concern about the risk for second primary cancers (SPCs).</p><p><strong>Observations: </strong>Multiple cases of SPCs arising after CAR-T therapy have been reported to the US Food and Drug Administration. Most SPCs have been negative for the chimeric antigen receptor transgene, with rare reports of transgene-positive cancers. This review summarizes the most salient literature on epidemiology and pathobiology of SPCs after CAR-T therapy. Additionally, a discussion is provided on potential mitigation strategies for SPCs after CAR-T therapies.</p><p><strong>Conclusions and relevance: </strong>The results of this review suggest that there are limited data to suggest that inadvertent transgene insertion is associated with SPCs in the post-CAR-T setting. Nonetheless, evidence-based practical solutions and scientific strategies for risk mitigation can be implemented. These include optimization of T-cell manufacturing, application of safer synthetic immunobiology, and implementation of high-fidelity genomic testing, including baseline screening for clonal hematopoiesis. These strategies may inform optimal design of the next generation of CAR-T products that confer minimal risk for SPCs such that the risk-benefit profile remains favorable to proceed with CAR-T administration for eligible patients.</p>","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814771","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}

{"title":"Oncological Safety of MRI-Informed Biopsy Decision-Making in Men With Suspected Prostate Cancer.","authors":"Charlie A Hamm, Patrick Asbach, Anna Pöhlmann, Ivo G Schoots, Veeru Kasivisvanathan, Thomas O Henkel, Manfred Johannsen, Thomas Speck, Alexander D J Baur, Matthias Haas, Federico Collettini, Tobias Penzkofer, Lynn J Savic, Frank Konietschke, Lothar Weißbach, Bernd Hamm, Frank König, Hannes Cash","doi":"10.1001/jamaoncol.2024.5497","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5497","url":null,"abstract":"<p><strong>Importance: </strong>The magnetic resonance imaging (MRI) pathway for diagnosing clinically significant prostate cancer (csPCa; defined as International Society of Urological Pathology grade group ≥2) uses multiparametric MRI (mpMRI) for prostate biopsy (PB) decision-making. However, the intermediate impact on patient outcomes in men with negative MRI results avoiding PB and men with positive MRI results without PCa remains unknown.</p><p><strong>Objective: </strong>To assess the feasibility and safety of a community-based MRI diagnostic strategy in men with suspected PCa using 3-year active monitoring.</p><p><strong>Design, setting, and participants: </strong>This multisite, longitudinal cohort trial took place across 54 community-based urology practices and 2 radiology imaging centers at a referral academic institution in Berlin, Germany. Eligible participants aged 18 to 75 years with clinically suspected PCa were enrolled between September 2016 and December 2017 and monitored for 3 years. Final analysis was reported on December 23, 2023.</p><p><strong>Exposures: </strong>Participants underwent 3-T mpMRI. Men with findings suspected to be PCa were recommended for targeted PB (diagnostic phase). Men with negative mpMRI results or positive mpMRI results with benign findings at PB were systematically monitored for 3 years (monitoring phase). Clinical visits were recommended every 6 months.</p><p><strong>Main outcomes and measures: </strong>The total proportion of men avoiding PB and those with csPCa.</p><p><strong>Results: </strong>A total of 593 men (median [IQR] age, 64 [58-70] years) underwent mpMRI, with 286 (48%) having negative MRI results, 261 (44%) avoiding PB initially, and 242 (41%) avoiding PB over 3 years. csPCa was detected in 161 (27%) men after immediate PB, increasing to 172 (29%) men after 3 years. Seven men with negative MRI results were diagnosed with PCa by immediate PB (including 4 cases of csPCa), while 279 entered monitoring. Three-year monitoring was completed by 233 (84%) men, with 7 diagnoses of csPCa. Of 307 men with positive MRI results, 58 (19%) showed no PCa after immediate PB, of which 41 (71%) completed monitoring and 4 (7%) were diagnosed with csPCa.</p><p><strong>Conclusions and relevance: </strong>In this cohort study, men with negative mpMRI results avoiding biopsy were not at elevated risk of csPCa. The study confirms the oncological safety of the prebiopsy MRI strategy of avoiding an immediate PB after negative MRI results when a programmatic safety net is in place.</p>","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814751","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}

{"title":"Patient-Reported Outcomes for Low-Risk Ductal Carcinoma In Situ: A Secondary Analysis of the COMET Randomized Clinical Trial.","authors":"Ann H Partridge, Terry Hyslop, Shoshana M Rosenberg, Antonia V Bennett, Sarah Drier, Mattias Jonsson, Ayako Shimada, Yutong Li, Yan Li, Thomas Lynch, Elizabeth Frank, Deborah Collyar, Desiree Basila, Donna Pinto, Anna Weiss, Anna Wolf, Kelsey Norris, Meredith Witten, Marc Boisvert, Armando Giuliano, Kelsey E Larson, Kathleen Yost, Priscilla F McAuliffe, Amy Krie, Nina Tamirisa, Sonja Darai, Lisa Carey, Alastair Thompson, E Shelley Hwang","doi":"10.1001/jamaoncol.2024.6556","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.6556","url":null,"abstract":"<p><strong>Importance: </strong>Active monitoring (AM) for low-risk ductal carcinoma in situ (DCIS) has been considered as a potential alternative to guideline-concordant care (GCC; inclusive of surgery with or without radiation). Reported data comparing patient-reported outcomes (PROs) between GCC and AM for DCIS are lacking.</p><p><strong>Objective: </strong>To compare PROs at baseline and over time in patients with low-risk DCIS randomized to receive either AM or GCC.</p><p><strong>Design, setting, and participants: </strong>This prespecified secondary outcome analysis used prospectively collected validated questionnaires at baseline, 6 months, 1 year, and 2 years from participants enrolled from June 2017 to January 2023 in the Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) study for low-risk DCIS, which randomized participants to receive GCC or AM.</p><p><strong>Intervention: </strong>Randomization to GCC or AM.</p><p><strong>Main outcomes and measures: </strong>Context-relevant PROs, including health-related quality of life, anxiety, depression, and symptoms measured by validated survey instruments. Mixed models, including sensitivity analyses, with group, point, and group-by-point effects were used to compare PROs between groups.</p><p><strong>Results: </strong>Of the 957 participants in COMET, 225 (24%) were younger than 55 years at enrollment, 325 (34%) were aged 55 to 65 years, and 403 (42%) were older than 65 years, and 953 (99.5%) completed questionnaires at some point within the first 2 years, with a completion rate of more than 83% at all points. Quality of life, anxiety, depression, worries about DCIS, and symptom trajectories were comparable between groups, with modest fluctuations over time of limited clinical significance. Physical functioning was the only specific Medical Outcomes Study 36-item short-form health survey (SF-36) domain for which changes in the score trajectory differed by group over time, with mean scores ranging from 50 (baseline) to 48 (6, 12, and 24 months) in the GCC group and 50 (baseline) to 47 (12 months) and 48 (6 and 24 months) in the AM group (pooled SD, 9.9; P = .01), although these were also of limited clinical significance.</p><p><strong>Conclusions and relevance: </strong>In this prespecified secondary analysis of the COMET prospective randomized trial, the overall lived experience of women randomized to undergo AM for low-risk DCIS was similar to that of women randomized to GCC during the 2 years following diagnosis.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT02926911.</p>","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814754","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}

{"title":"Neoadjuvant Exercise Therapy in Patients With Prostate Cancer-Reply.","authors":"Lee W Jones, Behfar Ehdaie, Paul C Boutros","doi":"10.1001/jamaoncol.2024.5569","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5569","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787436","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}

{"title":"Neoadjuvant Exercise Therapy in Patients With Prostate Cancer.","authors":"Fabian Falkenbach, Lars Budäus","doi":"10.1001/jamaoncol.2024.5566","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5566","url":null,"abstract":"","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787408","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}

{"title":"Biomarkers to Inform Prognosis and Treatment for Unresectable or Metastatic GEP-NENs.","authors":"Jonathan M Loree, David Chan, Jennifer Lim, Heather Stuart, Nicolas Fidelman, Jonathan Koea, Jason Posavad, Meredith Cummins, Sarah Doucette, Sten Myrehaug, Boris Naraev, Dale L Bailey, Andrew Bellizzi, David Laidley, Veronica Boyle, Rachel Goodwin, Jaydi Del Rivero, Michael Michael, Janice Pasieka, Simron Singh","doi":"10.1001/jamaoncol.2024.4330","DOIUrl":"10.1001/jamaoncol.2024.4330","url":null,"abstract":"<p><strong>Importance: </strong>Evidence-based treatment decisions for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) require individualized patient-centered decision-making that accounts for patient and cancer characteristics.</p><p><strong>Objective: </strong>To create an accessible guidance document to educate clinicians and patients on biomarkers informing prognosis and treatment in unresectable or metastatic GEP-NENs.</p><p><strong>Methods: </strong>A multidisciplinary panel in-person workshop was convened to define methods. English language articles published from January 2016 to January 2023 in PubMed (MEDLINE) and relevant conference abstracts were reviewed to investigate prognostic and treatment-informing features in unresectable or metastatic GEP-NENs. Data from included studies were used to form evidence-based recommendations. Quality of evidence and strength of recommendations were determined using the Grading of Recommendations, Assessment, Development and Evaluations framework. Consensus was reached via electronic survey following a modified Delphi method.</p><p><strong>Findings: </strong>A total of 131 publications were identified, including 8 systematic reviews and meta-analyses, 6 randomized clinical trials, 29 prospective studies, and 88 retrospective cohort studies. After 2 rounds of surveys, 24 recommendations and 5 good clinical practice statements were developed, with full consensus among panelists. Recommendations focused on tumor and functional imaging characteristics, blood-based biomarkers, and carcinoid heart disease. A single strong recommendation was made for symptomatic carcinoid syndrome informing treatment in midgut neuroendocrine tumors. Conditional recommendations were made to use grade, morphology, primary site, and urinary 5-hydroxyindoleacetic levels to inform treatment. The guidance document was endorsed by the Commonwealth Neuroendocrine Tumour Collaboration and the North American Neuroendocrine Tumor Society.</p><p><strong>Conclusions and relevance: </strong>The study results suggest that select factors have sufficient evidence to inform care in GEP-NENs, but the evidence for most biomarkers is weak. This article may help guide management and identify gaps for future research to advance personalized medicine and improve outcomes for patients with GEP-NENs.</p>","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":" ","pages":"1707-1720"},"PeriodicalIF":28.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367078","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}