JAMA Oncology最新文献

{"title":"Urinary DNA Methylation Test for Bladder Cancer Diagnosis","authors":"In Gab Jeong, Sung-Cheol Yun, Hong Koo Ha, Sung Gu Kang, Sangchul Lee, Sungchan Park, Hyun Hwan Sung, Sun Il Kim, Eu Chang Hwang, Kyung Cheol Moon, Cheol Kwak","doi":"10.1001/jamaoncol.2024.6160","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.6160","url":null,"abstract":"ImportanceAn accurate noninvasive biomarker test is needed for the early diagnosis of bladder cancer.ObjectiveTo evaluate the performance of a urinary DNA methylation test (<jats:italic>PENK</jats:italic> methylation) and compare its diagnostic accuracy with that of the nuclear matrix protein 22 (NMP22) test or urine cytology test.Design, Setting, and ParticipantsIn this prospective multicenter study at 10 sites in the Republic of Korea, individuals 40 years and older with hematuria undergoing cystoscopy within 3 months between March 11, 2022, and May 30, 2024, participated. The study participants were evaluated for bladder cancer using a urinary DNA methylation test.ExposureUrinary DNA methylation test, NMP22 test, and urine cytology test.Main Outcomes and MeasuresThe primary outcomes were the sensitivity and specificity of the urinary DNA methylation test for high-grade or invasive bladder cancer. Secondary objectives included the accuracy of the test for overall bladder cancer (all stages and grades) and the comparison of sensitivities and specificities for bladder cancer between the urinary DNA methylation test and the NMP22 test or urine cytology test.ResultsAmong the 1099 participants, 614 (55.9%) were male; participants had a mean (SD) age of 65 (10) years. Of the 1099 participants, 219 and 176 participants had bladder cancer and high-grade or invasive bladder cancer, respectively. The urinary DNA methylation test had sensitivity and specificity for high-grade or invasive bladder cancer of 89.2% (95% CI, 84.6%-93.8%) and 87.8% (95% CI, 85.6%-89.9%), respectively. Sensitivity and specificity for overall bladder cancer were 78.1% (95% CI, 72.6%-83.6%) and 88.8% (95% CI, 86.7%-90.8%), respectively. The positive predictive value for high-grade or invasive bladder cancer was 61.3% (95% CI, 55.4%-67.3%), and the negative predictive value was 97.6% (95% CI, 96.6%-98.7%). In comparison with the NMP22 test or urine cytology test, the urinary DNA methylation test showed significantly superior sensitivity for high-grade or invasive bladder cancer and overall bladder cancer.Conclusions and RelevanceIn this prospective multicenter study of individuals with hematuria, the urinary DNA methylation test showed 89% sensitivity for detecting high-grade or invasive bladder cancer, outperforming the NMP22 test or urine cytology test with high specificity. While this test had an excellent negative predictive value, its positive predictive value was suboptimal.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"28 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056772","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":"Intracranial Outcomes of Ipilimumab and Nivolumab in Melanoma Brain Metastases After Progression on Anti–PD-1 Therapy","authors":"Sarah E. Lochrin, Hannah L. Kalvin, James W. Smithy, Monica F. Chen, Parisa Momtaz, Alexander N. Shoushtari, Katherine S. Panageas, Michael A. Postow","doi":"10.1001/jamaoncol.2024.6168","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.6168","url":null,"abstract":"This cohort study examines the response and survival rates associated with ipilimumab-nivolumab therapy in patients with progressive melanoma brain metastases after anti–programmed cell death 1 (anti–PD-1) therapy.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"354 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056828","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":"Gastroenteropancreatic Neuroendocrine Tumor Incidence by Sex and Age in the US","authors":"Yazan Abboud, Anand Shah, Riya Sutariya, Vraj P. Shah, Ahmed Al-Khazraji, Paul J. Gaglio, Kaveh Hajifathalian","doi":"10.1001/jamaoncol.2024.5937","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5937","url":null,"abstract":"This observational study reports on a comprehensive nationwide evaluation of rising gastroenteropancreatic neuroendocrine tumor incidence in the US from 2001 to 2020.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"68 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986885","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":"Intratumoral Injection of mRNA-2752 and Pembrolizumab for High-Risk Ductal Carcinoma In Situ","authors":"Kirithiga Ramalingam, Rachel Woody, Alexa Glencer, Christopher J. Schwartz, Hidetoshi Mori, Jasmine Wong, Gillian Hirst, Jennifer Rosenbluth, Natsuko Onishi, Jessica Gibbs, Nola Hylton, Alexander D. Borowsky, Michael Campbell, Laura J. Esserman","doi":"10.1001/jamaoncol.2024.5927","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5927","url":null,"abstract":"ImportanceIntratumoral immunotherapy that leverages the biological characteristics of high-risk ductal carcinoma in situ (DCIS) may be able to reduce the extent of surgical treatment and provide an alternative approach to improve patient outcomes.ObjectiveTo determine if combination intratumoral immunotherapy can activate immune cells to shrink or eliminate high-risk DCIS.Design, Setting, and ParticipantsThis phase 1 open-label nonrandomized clinical trial at a single academic center tested the safety and efficacy of intratumoral immunotherapy in patients with high-risk DCIS, defined as at least 2 of the following present: younger than 45 years, tumor size greater than 5 cm, high-grade, palpable mass, hormone receptor (HR)–negative, or ERBB2-positive. Patients were enrolled between June 8, 2021, and December 13, 2022.InterventionPembrolizumab (anti–programmed cell death protein 1), dose ranging from 2 mg to 8 mg, and mRNA-2752 (a combination of interleukin [IL]-23, IL-36γ, and OX40L mRNAs), dose ranging from 1 mg to 4 mg, delivered intratumorally, with 2 to 4 doses given 2 to 3 weeks apart.Main Outcomes and MeasuresThe primary objective was to evaluate the safety and tolerability of intratumoral injections of pembrolizumab and mRNA-2752. The secondary objectives were to assess radiologic and pathological responses and immunological and histological differences in the posttreatment tumor microenvironment.ResultsTen female patients with high-risk DCIS (median [range] age, 46 [35-80] years) were enrolled. The median (range) tumor size was 5.3 (1.0-10.0) cm. Five tumors were HR-negative ERBB2-positive; 2 HR-negative ERBB2-negative; 2 HR-positive ERBB2-negative; and 1 HR-positive ERBB2-positive. Of all treated patients, 8 of 10 responded to treatment, and all 8 patients had ERBB2-positive or HR-negative DCIS. Three patients had complete responses. Three patients with negative posttreatment core biopsy results declined surgery and remained disease-free after 1 to 2 years. Multiplex immunofluorescence staining demonstrated that high baseline levels of tumor-infiltrating lymphocytes and programmed cell death ligand 1–positive cells (immune or tumor) were associated with a better treatment response. All patients experienced up to 1 week of fever, malaise, flulike symptoms, axillary adenopathy, erythema, injection site swelling, and swelling in the breast. One patient had intermittent urticaria for 3 months. The dose was serially reduced from 8 mg to 2 mg for pembrolizumab and 4 mg to 1 mg for mRNA-2752 to improve tolerability. The final recommended combination dose is pembrolizumab, 4 mg, with mRNA-2752, 1 mg.Conclusions and RelevanceIn this phase 1 nonrandomized clinical trial, the results suggest that intratumoral injections of pembrolizumab and mRNA-2752 are safe and may induce rapid regression of high-risk DCIS with high immune infiltrates. These findings warrant additional investigation, and studies are ongoing.Trial RegistrationClinicalTrials.gov Id","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"245 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986884","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":"Biomarker-Directed Radiotherapy in Breast Cancer: A Narrative Review.","authors":"Icro Meattini,Charlotte E Coles,Trine Tramm,Simona Borghesi,David Krug,Angel Montero,Valerio Nardone,Viola Salvestrini,Marianna Valzano,Vincenzo Valentini,Cynthia Aristei,Philip Poortmans,","doi":"10.1001/jamaoncol.2024.5780","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5780","url":null,"abstract":"ImportanceIntegration of molecular biomarker information into systemic therapy has become standard practice in breast cancer care. However, its implementation in guiding radiotherapy (RT) is slower. Although postoperative RT is recommended for most patients after breast-conserving surgery and, depending on risk factors, following mastectomy, emerging evidence has indicated that patients with low scores on gene expression signatures or selected clinical-pathological features may have very low local recurrence rates. This narrative review explored the potential of biomarker-directed personalized RT approaches, which may optimize treatment strategies and be associated with improved patient outcomes and experiences.ObservationsDistinctions between prognostic and predictive biomarkers were highlighted, emphasizing the importance of analytical and clinical validity in biomarker-based studies. Findings from studies investigating the prognostic and predictive value of various genomic signatures and immunohistochemical markers for guiding breast RT were presented. These included the Adjuvant Radiotherapy Intensification Classifier and the Profile for the Omission of Local Adjuvant Radiation, which have shown potential in predicting RT benefits. The genomic-adjusted radiation dose and role of tumor-infiltrating lymphocytes were also discussed. Ongoing clinical trials exploring the use of biomarkers in ductal carcinoma in situ and invasive breast cancer to refine RT decision-making were illustrated.Conclusions and RelevanceThe results of this narrative review suggest that evidence-based shared decision-making is crucial to optimize treatment according to the individual's predicted benefits and risks along with their personal preferences. Incorporation of biomarker-directed approaches in RT for breast cancer may hold promise for personalized treatment, potentially facilitating omission of RT for patients at low risk of recurrence, while identifying those who may benefit from intensified therapy. This personalized RT approach may be associated with improved clinical outcomes and quality of life and facilitate decision-making for people with breast cancer. However, there remains a need for robust clinical and analytical validation of biomarkers to ensure reliability and clinical utility for RT optimization.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"45 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988591","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":"Overcoming Barriers to Make Patient-Reported Outcome Collection the Standard of Care in Oncology.","authors":"James A Colbert,Louis Potters","doi":"10.1001/jamaoncol.2024.6157","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.6157","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"66 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988523","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":"Genetic Ancestry–Based Differences in Biomarker-Based Eligibility for Precision Oncology Therapies","authors":"Kanika Arora, Sarah P. Suehnholz, Hongxin Zhang, Irina Ostrovnaya, Ritika Kundra, Subhiksha Nandakumar, Moriah H. Nissan, A. Rose Brannon, Chaitanya Bandlamudi, Marc Ladanyi, Alexander Drilon, Carol L. Brown, David B. Solit, Nikolaus Schultz, Michael F. Berger, Debyani Chakravarty","doi":"10.1001/jamaoncol.2024.5794","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5794","url":null,"abstract":"ImportanceAlthough differences in the prevalence of key cancer-specific somatic mutations as a function of genetic ancestry among patients with cancer has been well-established, few studies have addressed the practical clinical implications of these differences for the growing number of biomarker-driven treatments.ObjectiveTo determine if the approval of precision oncology therapies has benefited patients with cancer from various ancestral backgrounds equally over time.Design, Setting, and ParticipantsA retrospective analysis of samples from patients with solid cancers who underwent clinical sequencing using the integrated mutation profiling of actionable cancer targets (MSK-IMPACT) assay between January 2014 and December 2022 was carried out. The annual fraction of patients per ancestral group with at least 1 level 1 biomarker was calculated for FDA drug approvals from January 1998 to December 2023. Analysis began in January 2024.Main Outcomes and MeasuresFor each patient, genetic ancestry was quantitatively inferred, and patients were grouped based on predominant reference ancestry. OncoKB was used to identify all Food and Drug Administration (FDA)–recognized somatic biomarkers associated with FDA-approved therapies (level 1 biomarkers) in each tumor sample.ResultsOverall, the study included 59 433 patients. The approval of the <jats:italic>EGFR</jats:italic>-tyrosine kinase inhibitor erlotinib for patients with <jats:italic>EGFR</jats:italic>-mutant lung cancers in 2013 disproportionately benefited patients of East Asian and South Asian ancestries, leading to higher patient fractions with level 1 biomarkers in these ancestral groups compared with other populations. Although the increase in precision oncology drug approvals from 2019 to 2020 had a notable positive impact on clinical actionability for patients of European ancestry, patients of African ancestry had the lowest fraction of level 1 biomarkers compared with other groups from 2019 onward.Conclusion and RelevanceThis study systematically assessed and compared temporal changes in genomic biomarker-based eligibility for precision oncology therapies as a function of inferred genetic ancestry derived from DNA sequencing data. Despite the accelerated rate of FDA approvals for precision oncology therapies over the past decade, measurable differences in biomarker-based drug eligibility among patient ancestral groups exist. These differences may exacerbate the systemic disparities in clinical outcomes in patients of African ancestry due to existing deficiencies in their access to cancer care.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"2 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939823","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":"What We Can Learn About Patient Safety While Driving to Work","authors":"Lawrence B. Marks, Caprice C. Greenberg, Lukasz M. Mazur","doi":"10.1001/jamaoncol.2024.6151","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.6151","url":null,"abstract":"This Viewpoint discusses strategies used with driving that can be applied to health care to promote consistent and predictable physician and patient actions.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"20 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939874","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":"Shared Local Oncology Care After Allogeneic Hematopoietic Cell Transplantation","authors":"Gregory A. Abel, Haesook T. Kim, Ira Zackon, Edwin T. Alyea, Alexandra S. Bailey, John P. Winters, Kenneth R. Meehan, John L. Reagan, Jeanna H. Walsh, Thomas P. Walsh, Alexandra Ivanov, Meredith A. Faggen, Sarah Sinclair, Amy C. Joyce, Sara D. Close, Amy Emmert, Jon Koreth, Joseph H. Antin, Corey S. Cutler, Vincent T. Ho, Robert J. Soiffer","doi":"10.1001/jamaoncol.2024.5786","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5786","url":null,"abstract":"ImportanceAlthough sharing care with local oncologists after allogeneic hematopoietic cell transplantation (HCT) has been proposed for patients living far from HCT centers, it is not known whether a shared strategy is safe or improves patient quality of life (QOL).ObjectiveTo determine the efficacy and safety of sharing follow-up care after HCT between the HCT specialty center and local oncologists.Design, Setting, and ParticipantsThis was a multicenter collaborative randomized clinical trial of patients undergoing HCT at Dana-Farber Cancer Institute (DFCI)—a high volume HCT center in Boston (Massachusetts)—and 8 local oncology practices. Eligible patients were enrolled from December 2017 to December 2021 and were randomized 1:1 to shared vs usual care after neutrophil engraftment, stratified by local sites in Massachusetts, Rhode Island, New Hampshire, New York, and Maine. Data analyses were performed in January 2024.InterventionShared care involved alternating post-HCT visits at DFCI and local oncology practices through day 100; for usual care, all post-HCT visits occurred only at DFCI.Main Outcomes and MeasuresCoprimary outcomes were nonrelapse mortality (NRM) at day 100, and QOL measured by the FACT-BMT (Functional Assessment of Cancer Therapy–Bone Marrow Transplantation) instrument and the QLQ-C30 (European Organization for Research and Treatment of Cancer’s Quality of Life Questionnaire) at day 180. Prespecified secondary outcomes included day 100 QOL and 1-year overall survival.ResultsA total of 302 participants (median [range] age, 63 [20-79] years; 117 [38.7%] females; 185 [61.3%] males) were included in the analysis; 152 were randomized to shared care and 150 to usual care. Day 100 NRM was noninferior for shared vs usual care (2.6% [95% CI, 0.7% to 6.6%] vs 2.7% [95% CI, 0.7% to 6.7%]; <jats:italic>P</jats:italic> = .98). There were no differences at day 180 for the FACT-BMT total score (mean difference, 3.8; 95% CI, −2.1 to 9.6; <jats:italic>P</jats:italic> = .20) or QLQ-C30 global score (1.9; 95% CI, −4.9 to 8.8; <jats:italic>P</jats:italic> = .58). At day 100, the FACT-BMT total score was better for shared care (mean difference, 6.6; 95% CI, 1.0 to 12.1; <jats:italic>P</jats:italic> = .02) as was the QLQ-C30 global score (8.8; 95% CI, 1.8 to 15.7; <jats:italic>P</jats:italic> = .02).Conclusions and RelevanceThis randomized clinical trial found that shared care resulted in noninferior NRM at day 100 but similar QOL at day 180, with improved QOL at day 100. These data suggest that shared care is safe, improves QOL early on, and has the potential to become a routine model for post-HCT care.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT03244826\">NCT03244826</jats:ext-link>","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"22 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939875","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":"Immunotherapy Benefit Over Best Supportive Care in Hepatocellular Cancer With Child-Pugh B Dysfunction.","authors":"Manuel David Gil-Sierra,María Del Pilar Briceño-Casado,Cristina Moreno-Ramos","doi":"10.1001/jamaoncol.2024.5816","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.5816","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"306 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887556","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}