JAMA Oncology最新文献

{"title":"Pembrolizumab in Patients With Advanced Clear Cell Gynecological Cancer","authors":"Rebecca Kristeleit, Michael-John Devlin, Andrew Clamp, Charlie Gourley, René Roux, Marcia Hall, Rachel Nirsimloo, Valentinos Kounnis, Lesley Sage, Priya Narayanan, C. Simon Herrington, Rupali Arora, Laura Farrelly, Laura Hughes, Nicholas Counsell, Rowan E. Miller","doi":"10.1001/jamaoncol.2024.6797","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.6797","url":null,"abstract":"ImportanceAdvanced clear cell gynecological cancers (CCGCs) have a poor prognosis, with response rates to second-line chemotherapy less than 8%. Preliminary clinical activity with programmed cell death 1 protein (PD-1) inhibitors reported in CCGC merits further investigation.ObjectiveTo assess the clinical benefit of pembrolizumab in patients with previously treated advanced CCGC.Design, Setting, and ParticipantsThe PEACOCC trial is a single-arm multicenter phase 2 trial conducted at 5 UK centers investigating the clinical benefit and safety of pembrolizumab. PD-1 inhibitor–naive patients with histologically confirmed advanced CCGC, radiological disease progression following 1 or more prior courses of chemotherapy, and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 to 1 were included. Patients were enrolled from March 2019 to October 2021, with data collected until July 2024.InterventionsPembrolizumab, 200 mg, intravenously every 21 days up to 2 years until progression, discontinuation due to toxic effects, or patient/clinician decision. Up to 1 year of retreatment on diseases progression, if stable disease, partial response, or complete response at 2 years.Main Outcomes and MeasuresThe primary end point was progression-free survival (PFS) rate at 12 weeks using Response Evaluation Criteria in Solid Tumors version 1.1 to detect a 12-week PFS rate of 33% or greater and exclude a PFS rate of less than 15%, with 90% power and 1-sided 5% significance level. Secondary end points included objective response rate, duration of response, PFS, overall survival, safety, and quality of life.ResultsA total of 48 patients were eligible. The median (range) age was 58.5 (32-77) years, and 26 (54%) had an ECOG PS score of 0 and 22 (46%) had an ECOG PS score of 1; 41 (85%) had ovarian, 6 (13%) had endometrial, and 1 (2%) had cervical advanced CCGC. The median (range) courses prior therapy was 3 (1-6); 19 patients (40%) received prior anti-angiogenic therapy, and 19 (40%) had a platinum-free interval of more than 12 months. Grade 3 treatment-related adverse events were observed in 9 patients (19%), and no patients had grade 4 or 5 adverse events. A total of 45 of 46 patients (98%) had mismatch repair–proficient tumors. The 12-week PFS rate was 42% (95% CI, 28-57), and the best objective response rate was 25% (95% CI, 14-40), with 12 partial responses. After a median follow-up of 46.9 months (95% CI, 43.4-55.0), the median PFS was 2.7 months (95% CI, 1.3-5.4), and the median overall survival was 14.8 months (95% CI, 6.7-28.2).Conclusions and RelevanceThe PEACOCC trial showed clinical benefit with pembrolizumab in patients with previously treated advanced CCGC, of whom all except 1 had MMR-proficient disease. Clinical outcomes were durable with an overall tolerable safety profile, justifying further evaluation of pembrolizumab monotherapy for advanced CCGC in a randomized clinical trial.Trial RegistrationClinicalTrials.gov Identifier:","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"8 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191922","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":"Circulating Tumor DNA as Measurable Residual Disease in Aggressive B-Cell Lymphoma","authors":"Mark Roschewski, Dan L. Longo, James O. Armitage","doi":"10.1001/jamaoncol.2024.6144","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.6144","url":null,"abstract":"ImportanceAchieving remission is the first step toward a cure in treating aggressive B-cell lymphomas. Radiographic imaging, such as fluorodeoxyglucose–positron emission tomography/computed tomography scans are the current standard to define remission at the end of therapy but lack specificity for lymphoma and cannot detect disease at the molecular level. Identifying measurable residual disease with ultrasensitive detection of circulating tumor DNA potentially offers the possibility of improving clinical outcomes.ObservationsEarly studies of circulating tumor DNA in aggressive B-cell lymphomas showed a strong association with overall tumor burden, and baseline quantitative levels are associated with clinical outcomes after frontline chemotherapy. Next-generation sequencing methods that detect lymphoma-relevant genetic aberrations in circulating tumor DNA can also be used for noninvasive genotyping that strongly mirror tissue biopsies. Rapid changes in circulating tumor DNA dynamics after 1 or 2 cycles of frontline chemotherapy or within weeks of treatment with chimeric antigen receptor T-cell salvage therapy are also highly prognostic. Although serial monitoring of circulating tumor DNA can detect molecular relapse 3 to 6 months before clinical relapse, improved analytical thresholds are required to detect measurable residual disease at a singular point at the end of therapy. Modern advances in circulating tumor DNA methods now allow for the reliable detection of measurable residual disease, with an analytical detection threshold of 1 in 1 million cell-free DNA molecules.Conclusions and RelevanceThe results of this review suggest that modern ultrasensitive methods of detecting circulating tumor DNA may improve the current definition of remission in aggressive B-cell lymphomas. Incorporating circulating tumor DNA at the end of therapy assessment identifies patients who do not require surveillance monitoring and introduces paradigms of treating measurable residual disease within clinical trials. Practical barriers, including standardization of collection, availability, turnaround times, and cost, remain hurdles preventing widespread implementation into clinical practice.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"136 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191923","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":"Concerns in Interpretation of Results in the Identification of Immune Checkpoint Inhibitor-Induced Diabetes.","authors":"Halis K Akturk,Aaron W Michels","doi":"10.1001/jamaoncol.2024.6473","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.6473","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"39 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062064","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":"Making Time—A Meta-Static Journey","authors":"Michael S. Avidan","doi":"10.1001/jamaoncol.2024.6470","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.6470","url":null,"abstract":"This essay describes the author’s experience with an unexpected diagnosis of stage IV cancer and the valuable perspectives gained from unexpected additional quality time.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"84 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056764","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":"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}