JAMA Oncology最新文献

{"title":"How Can Guidelines Give Clearer Guidance on Prostate Cancer Screening?","authors":"Sigrid V Carlsson,William K Oh","doi":"10.1001/jamaoncol.2024.3909","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3909","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"1 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325297","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":"Meta-Analysis Methods for Neoadjuvant Chemoimmunotherapy for Non-Small Cell Lung Cancer.","authors":"Leisheng Zhang,Jing Li,Liang Guo","doi":"10.1001/jamaoncol.2024.4211","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.4211","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"11 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325294","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":"Complete Response to Locoregional Therapy Plus Immunotherapy for Hepatocellular Carcinoma.","authors":"Chi Leung Chiang,Kenneth Sik Kwan Chan,Keith Wan Hang Chiu,Francis Ann Shing Lee,Wenqi Chen,Natalie Sean Man Wong,Ryan Lok Man Ho,Venus Wan Yan Lee,Kwan Man,Feng Ming Spring Kong,Albert Chi Yan Chan","doi":"10.1001/jamaoncol.2024.4085","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.4085","url":null,"abstract":"ImportancePrevious studies showed that 42% to 50% of patients with locally advanced hepatocellular carcinoma (HCC) achieved complete remission (CR) after combined locoregional therapy (LRT) plus immunotherapy (IO). However, data on predictors of CR and long-term clinical outcomes without surgery and after discontinuation of IO are lacking.ObjectiveTo assess the long-term clinical outcomes among patients with unresectable HCC who achieved CR after LRT-IO and were placed on a watch-and-wait protocol.Design, Setting, and ParticipantsThis cohort study included patients with unresectable HCC who achieved CR after LRT-IO in 2 prospective studies between January 2018 and December 2022. The time of data cutoff was June 2023. Radiologic CR was defined per modified Response Evaluation Criteria in Solid Tumors. All patients underwent close surveillance after CR without surgical interventions, and IO was discontinued.ExposureAll patients had received stereotactic body radiotherapy followed by anti-programmed cell death protein 1 or anti-programmed death ligand 1 therapy. Forty-nine patients had received a dose of transarterial chemoembolization before stereotactic body radiotherapy.Main Outcomes and MeasuresThe primary outcome was the 3-year overall survival (OS) rate. Secondary outcomes included the 3-year time-to-progression rate, 3-year local control rate, and relapse pattern. Factors associated with CR were analyzed using multivariate analyses.ResultsA total of 63 patients were enrolled (58 male [92.1%]; median age, 69 years [range, 18-90 years]); 38 patients (60.3%) had macrovascular invasion, and the median tumor diameter was 10 cm (range, 3.8-31.1 cm). The median follow-up time was 34.7 months (95% CI, 6.5-64.6 months). Twenty-nine patients (46.0%) achieved CR. The patients achieving CR had a significantly better 3-year OS rate than patients not achieving CR (75.5% [95% CI, 58.2%-98.3%] vs 28.1% [95% CI, 7.4%-29.4%]; P < .001). Among the 29 patients with CR, the 3-year time-to-progression rate was 58.7% (95% CI, 38.7%-79.1%) and the 3-year local control rate was 90.5% (95% CI, 78.2%-100%). Ten patients (34.5%) developed recurrence; among them, 6 (60.0%) with solitary intrahepatic disease relapse underwent curative surgical treatment. The absence of tumor vascular invasion (odds ratio, 0.30; 95% CI, 0.10-0.89) and the sum of the largest lesion diameters of 8 cm or less (odds ratio, 0.26; 95% CI, 0.07-0.98) were associated with CR.Conclusions and RelevanceThis cohort study of LRT-IO with long-term follow-up data found a durable response in patients with locally advanced unresectable HCC. Long-term survival was attainable in patients with radiologic CR. Further randomized clinical trials are warranted.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"9 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325296","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":"Recurrent Fevers in a Patient With Splenomegaly.","authors":"Darren D'Souza,Braulio Cuesta,Jennie Y Law","doi":"10.1001/jamaoncol.2024.4029","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.4029","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"55 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325299","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":"Meta-Analysis Methods for Neoadjuvant Chemoimmunotherapy for Non-Small Cell Lung Cancer-Reply.","authors":"Mark Sorin,Connor Prosty,Jonathan D Spicer","doi":"10.1001/jamaoncol.2024.4214","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.4214","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"201 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325295","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":"Rogaratinib Plus Atezolizumab in Cisplatin-Ineligible Patients With FGFR RNA-Overexpressing Urothelial Cancer","authors":"Randy F. Sweis, Pablo Gajate, Rafael Morales-Barrera, Jae-Lyun Lee, Andrea Necchi, Filippo de Braud, Nicolas Penel, Viktor Grünwald, Marco Maruzzo, Johannes Meran, Tatiane Cristine Ishida, Weichao Bao, Yinghui Zhou, Peter Ellinghaus, Jonathan E. Rosenberg","doi":"10.1001/jamaoncol.2024.3900","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3900","url":null,"abstract":"ImportanceThe oral pan–fibroblast growth factor receptor inhibitor rogaratinib previously demonstrated encouraging safety and efficacy in a phase 1 study of patients with urothelial cancer (UC) overexpressing <jats:italic>FGFR</jats:italic> messenger RNA (mRNA).ObjectiveTo evaluate the safety, pharmacokinetics, and preliminary efficacy of rogaratinib in combination with the programmed cell death 1 ligand 1 (PD-L1) inhibitor atezolizumab in cisplatin-ineligible patients with <jats:italic>FGFR</jats:italic> mRNA-positive, locally advanced/metastatic UC.Design, Setting, and ParticipantsThe FORT-2 nonrandomized clinical trial was an open-label, single-arm, multicenter study conducted between May 15, 2018, and July 16, 2021, in 30 centers across Asia, Europe, and North America. Eligible patients had locally advanced/metastatic UC with <jats:italic>FGFR1</jats:italic>/<jats:italic>3</jats:italic> mRNA overexpression and were ineligible for cisplatin-based chemotherapy. The data analysis was completed from July 2022 to September 2022.InterventionsPatients received rogaratinib 600 mg or rogaratinib 800 mg twice daily in combination with intravenous atezolizumab 1200 mg every 21 days.Main Outcomes and MeasuresPrimary end points included safety, tolerability, and the recommended phase 2 dose (RP2D) of rogaratinib in combination with atezolizumab.ResultsAmong 153 patients screened, 73 (48%) had tumors with <jats:italic>FGFR1/3</jats:italic> mRNA overexpression, and 37 patients were enrolled and treated (median [range] age, 75.0 [47.0-85.0] years; 32 [87%] male). The most common treatment-emergent adverse events (TEAEs) included diarrhea in 23 patients (62%), hyperphosphatemia in 19 (51%), and fatigue in 15 (41%). Grade 3 or higher TEAEs were reported in 27 patients (73%), and 4 grade 5 TEAEs were reported, though unrelated to treatment. The RP2D was rogaratinib 600 mg in combination with atezolizumab 1200 mg. At the RP2D, the overall response rate was 53.8% in the rogaratinib 600 mg group, including 4 patients (15%) with complete responses; 12 responders (86%) did not have an <jats:italic>FGFR3</jats:italic> gene alteration, and 11 (79%) had low PD-L1 expression.Conclusions and RelevanceIn this phase 1b nonrandomized clinical trial, rogaratinib plus atezolizumab demonstrated a manageable safety profile, with no unexpected safety signals. Efficacy for this combination at the RP2D was observed in tumors with low PD-L1 and was not dependent on <jats:italic>FGFR3</jats:italic> gene alterations, suggesting broad potential benefit for patients with locally advanced/metastatic UC and <jats:italic>FGFR</jats:italic> mRNA overexpression.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/NCT03473756\">NCT03473756</jats:ext-link>","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"21 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275561","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":"Standardized Definitions for Efficacy End Points for Adjuvant Trials—The Updated STEEP Criteria","authors":"Dominik Hlauschek, Christian Fesl, Michael Gnant","doi":"10.1001/jamaoncol.2024.3888","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3888","url":null,"abstract":"This Viewpoint discusses how the inclusion or exclusion of certain events in the standardization of clinical trial end points can affect the interpretation of results.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"21 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275563","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":"Chimeric Antigen Receptor T Cells Targeting CD19 and GCC in Metastatic Colorectal Cancer","authors":"Naifei Chen, Chengfei Pu, Lingling Zhao, Wei Li, Chang Wang, Ruihong Zhu, Tingting Liang, Chao Niu, Xi Huang, Haiyang Tang, Yizhuo Wang, Hang Yang, Beibei Jia, Xianyang Jiang, Guiting Han, Wensheng Wang, Dongqi Chen, Yiming Wang, Eric K. Rowinsky, Eugene Kennedy, Victor X. Lu, Guozhen Cui, Zhao Wu, Lei Xiao, Jiuwei Cui","doi":"10.1001/jamaoncol.2024.3891","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3891","url":null,"abstract":"ImportanceChimeric antigen receptor (CAR) T-cell therapy (CART) has transformed the treatment landscape of hematologic cancer, but has negligible effects for adult solid cancers. In this trial, an autologous CAR T-cell product demonstrated antitumor activity in heavily pretreated patients with metastatic colorectal cancer (mCRC).ObjectiveTo evaluate the safety and efficacy of guanylate cyclase-C (GCC19) CART in participants with metastatic colorectal cancer (mCRC).Design, Setting, and ParticipantsThis single-arm, nonrandomized, phase 1 trial was conducted at the First Hospital of Jilin University from December 3, 2020, to April 13, 2022. Data analysis was conducted from May 2022 to April 2024. Adults with relapsed and refractory mCRC expressing GCC were treated with GCC19CART, a mixture of autologous CAR T cells transduced with lentiviral vectors expressing genes that encode either CD-19 CAR or GCC CAR.Main Outcomes and MeasuresSafety and tolerability of CAR T-cell therapy targeting GCC in patients with mCRC without therapeutic options is capable of conferring a reasonable likeliness of clinical benefit. Other outcomes included objective response rate, progression-free survival, overall survival, and immune activation.ResultsOf 15 patients 9 (60%) were women, and the median (range) age was 44 (33-61) years. Treatment with GCC19CART was associated with the development of cytokine release syndrome and diarrhea in most patients, all of which were self-limited and manageable. The objective response rate was 40%, with a partial response in 2 of 8 and 4 of 7 patients treated with either 1 × 10<jats:sup>6</jats:sup> cells/kg or 2 × 10<jats:sup>6</jats:sup> cells/kg. Median overall survival was 22.8 months (95% CI, 13.4-26.1) at data cutoff; the median progress-free survival was 6.0 months in the high dose level group (95% CI, 3.0 to not available).Conclusions and RelevanceThe results of this nonrandomized clinical trial suggest that GCC19CART was safe and tolerable in heavily pretreated patients with mCRC and is the first CAR T-cell therapy known to produce objective clinical activity in refractory cancer. Given the paucity of effective therapeutics developed for colorectal cancer in recent decades, the observation that CD-19 CART target engagement can robustly induce GCC19CART target engagement sufficient to produce objective activity may serve as a foundation to develop effective cellular therapy in mCRC and other solid cancers.Trial RegistrationChinese Clinical Trial Registry: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://www.chictr.org.cn/regstatusprojEN.html\">ChiCTR2000040645</jats:ext-link>","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"122 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275564","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":"Stereotactic vs Hypofractionated Radiotherapy for Inoperable Stage I Non–Small Cell Lung Cancer","authors":"Anand Swaminath, Sameer Parpia, Marcin Wierzbicki, Vijayananda Kundapur, Sergio Faria, Gordon S. Okawara, Theodoros K. Tsakiridis, Naseer Ahmed, Alexis Bujold, Khalid Hirmiz, Timothy Owen, Nelson Leong, Kevin Ramchandar, Edith Filion, Harold Lau, Zsolt Gabos, Robert Thompson, Brian Yaremko, Selma Mehiri, Alexander V. Louie, Kimmen Quan, Mark N. Levine, James R. Wright, Timothy J. Whelan","doi":"10.1001/jamaoncol.2024.3089","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3089","url":null,"abstract":"ImportanceStereotactic body radiotherapy (SBRT) is widely used for stage I medically inoperable non–small cell lung cancer (NSCLC), yet varied results from randomized clinical trials (RCTs) and concerns in treating centrally located tumors persist.ObjectiveTo examine whether SBRT would improve local control (LC) compared with hypofractionated conventional radiotherapy (CRT).Design, Setting, and ParticipantsThis phase 3 RCT was conducted in 16 Canadian centers. Patients with medically inoperable stage I (≤5 cm) NSCLC were randomized 2:1 to SBRT of 48 Gy in 4 fractions (peripheral NSCLC) or 60 Gy in 8 fractions (central NSCLC) vs CRT of 60 Gy in 15 fractions. Data were collected from May 2014 to January 2020, and data were analyzed from July 2022 to July 2023.InterventionsSBRT or CRT.Main Outcomes and MeasuresThe primary objective was to determine the effectiveness of SBRT compared with CRT based on LC at 3 years. Secondary outcomes included event-free survival, overall survival, and toxic effects. All radiation plans were subject to real-time/final review. Local failures were centrally adjudicated. The study was designed to detect a 3-year LC improvement of SBRT from 75% to 87.5%. The target sample size was 324 patients.ResultsOf 233 included patients, 119 (51.1%) were male, and the mean (SD) age was 75.4 (7.7) years; the median (IQR) follow-up was 36.1 (26.4-52.8) months. A total of 154 patients received SBRT and 79 received CRT. The 3-year LC was 87.6% (95% CI, 81.9%-93.4%) for SBRT and 81.2% (95% CI, 71.9%-90.5%) for CRT (hazard ratio [HR], 0.61; 95% CI, 0.31-1.20; <jats:italic>P</jats:italic> = .15). The HR was 1.02 (95% CI, 0.72-1.45; <jats:italic>P</jats:italic> = .87) for event-free survival and 1.18 (95% CI, 0.80-1.76; <jats:italic>P</jats:italic> = .40) for overall survival. Minimal acute toxic effects were observed. Among those randomized to SBRT, late grade 3 or 4 toxic effects occurred in 5 of 45 (11%) with central NSCLC and 2 of 109 (1.8%) with peripheral NSCLC; among those randomized to CRT, in 1 of 19 (5%) with central NSCLC and 1 of 60 (2%) with peripheral NSCLC. One patient who received SBRT for an ultracentral lesion (target overlapping proximal bronchus) experienced a possible treatment-related grade 5 event (hemoptysis).Conclusions and RelevanceThis RCT compared lung SBRT with hypofractionated CRT that included central/ultracentral tumors. No difference was detected in LC between groups. Severe toxic effects were limited, including patients with central tumors. The trial provides important prospective data evaluating SBRT; however, further research is necessary to determine if SBRT is more effective than CRT for peripheral and central NSCLC.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/NCT03924869\">NCT03924869</jats:ext-link>","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"36 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275593","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":"Molecular, Socioeconomic, and Clinical Factors Affecting Racial and Ethnic Disparities in Colorectal Cancer Survival.","authors":"Mahmoud Yousef,Abdelrahman Yousef,Saikat Chowdhury,Mohammad M Fanaeian,Mark Knafl,Jennifer Peterson,Mohammad Zeineddine,Kristin Alfaro,Fadl Zeineddine,Drew Goldstein,Nicholas Hornstein,Arvind Dasari,Ryan Huey,Benny Johnson,Victoria Higbie,Alisha Bent,Bryan Kee,Michael Lee,Maria Pia Morelli,Van Karlyle Morris,Daniel Halperin,Michael J Overman,Christine Parseghian,Eduardo Vilar,Robert Wolff,Kanwal P Raghav,Michael G White,Abhineet Uppal,Ryan Sun,Wenyi Wang,Scott Kopetz,Jason Willis,John Paul Shen","doi":"10.1001/jamaoncol.2024.3666","DOIUrl":"https://doi.org/10.1001/jamaoncol.2024.3666","url":null,"abstract":"ImportanceDisparity in overall survival (OS) and differences in the frequency of driver gene variants by race and ethnicity have been separately observed in patients with colorectal cancer; however, how these differences contribute to survival disparity is unknown.ObjectiveTo quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in overall survival among patients with colorectal cancer.Design, Setting, and ParticipantsThis single-center cohort study was conducted at a tertiary-level cancer center using relevant data on all patients diagnosed with colorectal cancer from January 1, 1973, to March 1, 2023. The relative contribution of variables to the disparity was determined using mediation analysis with sequential multivariate Cox regression models.Main OutcomeOS, from diagnosis date and from start of first-line chemotherapy.ResultsThe study population of 47 178 patients (median [IQR] age, 57.0 [49-66] years; 20 465 [43.4%] females and 26 713 [56.6%] males; 3.0% Asian, 8.7% Black, 8.8% Hispanic, and 79.4% White individuals) had a median (IQR) follow-up from initial diagnosis of 124 (174) months and OS of 55 (145) months. Compared with White patients, Black patients had worse OS (hazard ratio [HR], 1.16; 95% CI, 1.09-1.24; P &lt;.001), whereas Asian and Hispanic patients had better OS (HR, 0.66; 95% CI, 0.59-0.74; P &lt;.001; and 0.86; 95% CI, 0.81-0.92; P &lt;.001, respectively). When restricted to patients with metastatic disease, the greatest disparity was between Black patients compared with White patients (HR, 1.2; 95% CI, 1.06-1.37; P &lt;.001). Evaluating changes in OS disparity over 20 years showed disparity decreasing among Asian, Hispanic, and White patients, but increasing between Black patients and White patients (HRs, 1.18; 95% CI, 1.07-1.31 for 2008-2012; 1.24, 95% CI, 1.08-1.42 for 2013-2017; and 1.50; 95% CI, 1.20-1.87 for 2018-2023). Survival outcomes for first-line chemotherapy were worse for Black patients compared with White patients (median OS, 18 vs 26 months; HR, 1.30; 95% CI, 1.01-1.70). Among 7628 patients who had clinical molecular testing, APC, KRAS, and PIK3CA showed higher variant frequency in Black patients (false discovery rate [FDR], 0.01; &lt; 0.001; and 0.01, respectively), whereas BRAF and KIT were higher among White patients (FDR, 0.001 and 0.01). Mediation analysis identified neighborhood socioeconomic status as the greatest contributor to OS disparity (29%), followed by molecular characteristics (microsatellite instability status, KRAS variation and BRAF variation, 10%), and tumor sidedness (9%).ConclusionsThis single-center cohort study identified substantial OS disparity and differing frequencies of driver gene variations by race and ethnicity. Socioeconomic status had the largest contribution but accounted for less than one-third of the disparity, with substantial contribution from tumor molecular features. Further study of the associations of genetic ancestry and ","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"69 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142174605","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}