TY - JOUR
T1 - Analysis of Survival among Adults with Early-Onset Colorectal Cancer in the National Cancer Database
AU - Cheng, En
AU - Blackburn, Holly N.
AU - Ng, Kimmie
AU - Spiegelman, Donna
AU - Irwin, Melinda L.
AU - Ma, Xiaomei
AU - Gross, Cary P.
AU - Tabung, Fred K.
AU - Giovannucci, Edward L.
AU - Kunz, Pamela L.
AU - Llor, Xavier
AU - Billingsley, Kevin
AU - Meyerhardt, Jeffrey A.
AU - Ahuja, Nita
AU - Fuchs, Charles S.
N1 - Funding Information:
Funding/Support: This study was supported by, in part, by grants P30CA016359, R01CA169141, and R01CA118553 from the National Institutes of Health and Cancer Dream Team Translational Research Grant SU2C-AACR-DT22-17 from Stand Up To Cancer, which is a division of the Entertainment Industry Foundation and whose scientific partner, the American Association for Cancer Research, administers the grant.
Funding Information:
Acquisition, analysis, or interpretation of data: Cheng, Ng, Irwin, Ma, Tabung, Kunz, Llor, Billingsley, Meyerhardt, Ahuja, Fuchs. Drafting of the manuscript: Cheng, Blackburn. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Cheng, Spiegelman, Giovannucci. Obtained funding: Fuchs. Administrative, technical, or material support: Cheng, Blackburn, Fuchs. Supervision: Cheng, Spiegelman, Irwin, Gross, Giovannucci, Kunz, Ahuja, Fuchs. Clinical input: Kunz. Conflict of Interest Disclosures: Dr Ng reported receiving grants from Evergrande Group, Janssen, Revolution Medicines, Genentech, and Gilead Sciences; a drug for clinical trial from Pharmavite; and personal fees from Seagen, Array BioPharma, BiomX, and X-Biotix Therapeutics outside the submitted work. Dr Gross reported receiving grants from the National Comprehensive Cancer Network (NCCN) Foundation (via Pfizer and AstraZeneca), Johnson & Johnson, and Genentech and speaking fees from Flatiron Health outside the submitted work. Dr Kunz reported receiving grants from Advanced Accelerator Applications (a subsidiary of Novartis), Brahms (a subsidiary of Thermo Fisher Scientific), Ipsen, Lexicon, and Xencor and personal fees from Advanced Accelerator Applications, Ipsen, Lexicon, Sun Pharmaceutical Industries, and Acrotech outside the submitted work. Dr Meyerhardt reported receiving institutional research funding from Boston Biomedical and personal fees from Ignyta, Taiho Pharmaceutical Group, and Cota Healthcare outside the submitted work. Dr Ahuja reported serving as a consultant for Cepheid and Johnson & Johnson, a member of the Yale New Haven Health Board and scientific advisory council to No Stomach for Cancer, and an advisor to Celgene; licensing a biomarker for early detection of pancreas cancer to Cepheid; and receiving a grant from Astex Pharmaceuticals and book fees from Elsevier outside the submitted work. Dr Fuchs reported receiving personal fees from Agios Pharmaceuticals, Amylin Pharmaceuticals, AstraZeneca, Bain Capital, CytomX Therapeutics, Daiichi Sankyo, Eli Lilly, Entrinsic Health, Evolveimmune Therapeutics, Genentech, Merck, Taiho Pharmaceutical Group, and Cogent Biosciences outside the submitted work; serving as a director for CytomX Therapeutics; owning unexercised stock options for CytomX Therapeutics and Entrinsic Health; cofounding and owning equity in Evolveimmune Therapeutics; providing expert testimony for Amylin Pharmaceuticals and Eli Lilly; and now serving as an employee of Genentech, part of the Roche Group. Dr Spiegelman reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study and grants from NIH outside the submitted work. Dr Ma reported receiving grants from Celgene/Bristol Myers Squibb and personal fees from Bristol Myers Squibb outside the submitted work. No other disclosures were reported.
Publisher Copyright:
© 2021 Annual Reviews Inc.. All rights reserved.
PY - 2021/6/16
Y1 - 2021/6/16
N2 - ImportanceWhile increased adherence to colorectal cancer (CRC) screening guidelines in the US has been associated with significant reductions in cancer incidence in US individuals aged 50 years and older, the incidence of CRC among those aged younger than 50 years has been steadily increasing. Understanding the survival among individuals with early-onset CRC compared with those aged 50 years and older is fundamental to informing treatment approaches and understanding the unique biological distinctiveness within early-onset CRC. ObjectiveTo characterize the overall survival for individuals with early-onset CRC. Design, Setting, and ParticipantsThis cohort study used data from the National Cancer Database. Included individuals were ages 0 to 90 years and diagnosed with primary CRC from January 1, 2004, through December 31, 2015. Individuals diagnosed at ages 51 through 55 years were selected as the reference group and defined as later-onset CRC for this study. Individuals diagnosed at age 50 years were excluded to minimize an apparent screening detection bias at that age in our population, given that these individuals disproportionately presented with earlier stage. All statistical analyses were conducted from January 4, 2020, through December 26, 2020. ExposuresEarly-onset CRC was defined as age younger than 50 years at diagnosis. Main Outcomes and MeasuresOverall survival was assessed by Kaplan-Meier analysis and Cox proportional hazards regression. ResultsAmong 769 #8239 871 individuals with CRC (377 #8239 890 [49.1%] women; 636 #8239 791 White individuals [82.7%]), 353 #8239 989 individuals (46.0%) died (median [range] follow-up: 2.9 [0-14.0] years), 102 #8239 168 individuals (13.3%) had early-onset CRC, and 78 #8239 812 individuals (10.2%) had later-onset CRC. Individuals with early-onset CRC, compared with those diagnosed with CRC at ages 51 through 55 years, had a lower 10-year survival rate (53.6% [95% CI, 53.2%-54.0%] vs 54.3% [95% CI, 53.8%-54.8%]; P lt .001) in unadjusted analysis. However, after adjustment for other factors associated with mortality, most notably stage, individuals with early-onset CRC had a lower risk of death compared with individuals diagnosed from ages 51 through 55 years (adjusted hazard ratio [HR], 0.95 [95% CI, 0.93-0.96]; P lt .001). In the model adjusted for stage, the HR for individuals with early-onset CRC was 0.89 (95% CI, 0.88-0.90; P lt .001). The survival advantage was greatest for individuals diagnosed at ages 35 through 39 years (adjusted HR, 0.88 [95% CI, 0.84-0.92]; P lt .001) and stages I (adjusted HR, 0.87 [95% CI, 0.81-0.93]; P lt .001) and II (adjusted HR, 0.86 [95% CI, 0.82-0.90]; P lt .001) and was absent among those diagnosed at ages 25 years or younger and stages III through IV. Conclusions and RelevanceThese findings suggest that there is a survival benefit for individuals with early-onset CRC compared with those diagnosed with CRC at later ages. Further study is needed to understand the underlying heterogeneity of survival among individuals with early-onset CRC by age and stage.
AB - ImportanceWhile increased adherence to colorectal cancer (CRC) screening guidelines in the US has been associated with significant reductions in cancer incidence in US individuals aged 50 years and older, the incidence of CRC among those aged younger than 50 years has been steadily increasing. Understanding the survival among individuals with early-onset CRC compared with those aged 50 years and older is fundamental to informing treatment approaches and understanding the unique biological distinctiveness within early-onset CRC. ObjectiveTo characterize the overall survival for individuals with early-onset CRC. Design, Setting, and ParticipantsThis cohort study used data from the National Cancer Database. Included individuals were ages 0 to 90 years and diagnosed with primary CRC from January 1, 2004, through December 31, 2015. Individuals diagnosed at ages 51 through 55 years were selected as the reference group and defined as later-onset CRC for this study. Individuals diagnosed at age 50 years were excluded to minimize an apparent screening detection bias at that age in our population, given that these individuals disproportionately presented with earlier stage. All statistical analyses were conducted from January 4, 2020, through December 26, 2020. ExposuresEarly-onset CRC was defined as age younger than 50 years at diagnosis. Main Outcomes and MeasuresOverall survival was assessed by Kaplan-Meier analysis and Cox proportional hazards regression. ResultsAmong 769 #8239 871 individuals with CRC (377 #8239 890 [49.1%] women; 636 #8239 791 White individuals [82.7%]), 353 #8239 989 individuals (46.0%) died (median [range] follow-up: 2.9 [0-14.0] years), 102 #8239 168 individuals (13.3%) had early-onset CRC, and 78 #8239 812 individuals (10.2%) had later-onset CRC. Individuals with early-onset CRC, compared with those diagnosed with CRC at ages 51 through 55 years, had a lower 10-year survival rate (53.6% [95% CI, 53.2%-54.0%] vs 54.3% [95% CI, 53.8%-54.8%]; P lt .001) in unadjusted analysis. However, after adjustment for other factors associated with mortality, most notably stage, individuals with early-onset CRC had a lower risk of death compared with individuals diagnosed from ages 51 through 55 years (adjusted hazard ratio [HR], 0.95 [95% CI, 0.93-0.96]; P lt .001). In the model adjusted for stage, the HR for individuals with early-onset CRC was 0.89 (95% CI, 0.88-0.90; P lt .001). The survival advantage was greatest for individuals diagnosed at ages 35 through 39 years (adjusted HR, 0.88 [95% CI, 0.84-0.92]; P lt .001) and stages I (adjusted HR, 0.87 [95% CI, 0.81-0.93]; P lt .001) and II (adjusted HR, 0.86 [95% CI, 0.82-0.90]; P lt .001) and was absent among those diagnosed at ages 25 years or younger and stages III through IV. Conclusions and RelevanceThese findings suggest that there is a survival benefit for individuals with early-onset CRC compared with those diagnosed with CRC at later ages. Further study is needed to understand the underlying heterogeneity of survival among individuals with early-onset CRC by age and stage.
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U2 - 10.1001/jamanetworkopen.2021.12539
DO - 10.1001/jamanetworkopen.2021.12539
M3 - Article
C2 - 34132794
AN - SCOPUS:85108332444
SN - 1543-5008
VL - 4
JO - Annual Review of Plant Biology
JF - Annual Review of Plant Biology
IS - 6
M1 - e2112539
ER -