{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:20:10Z","timestamp":1792153210092,"version":"4.4.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Traditional adverse event (AE) reporting in oncology trials focuses on the single worst CTCAE grade, which may underrepresent chronic or recurrent toxicity burden. We applied a longitudinal toxicity framework to compare toxicity profiles of chemotherapy with or without cetuximab in metastatic colorectal cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We pooled 2 randomized first-line trials in the ARCAD database. AEs examined were diarrhea, rash, hand-foot syndrome (HFS), fatigue, anorexia, and mucositis. Outcomes included grade \u22653 AEs, time to first occurrence of maximum grade, early onset (\u22646\u2009weeks), and adverse event load (AEL), a normalized measure of cumulative toxicity burden over treatment. Analyses were adjusted for chemotherapy backbone, ECOG performance score, sex, primary tumor location, dose reduction, and treatment duration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with chemotherapy alone (n\u2009=\u2009564), chemotherapy plus cetuximab (n\u2009=\u2009738) was associated with higher-grade \u22653 rash (21% vs 0.5%; adjusted odds ratio [OR] = 49.89, 95% CI\u2009=\u200915.8 to 157.4), higher rash AEL (0.257 vs 0.069; adjusted mean difference = 0.22, 95% CI\u2009=\u20090.21 to 0.23), and more frequent early-onset maximum rash (67% vs 34%; adjusted OR = 4.28, 95% CI\u2009=\u20092.72 to 6.74). Rash AEL remained higher with cetuximab within maximum-grade strata. HFS showed higher-grade \u22653 risk and overall AEL with cetuximab, but no within-grade AEL difference, indicating higher overall HFS burden reflected grade distribution rather than within-grade chronicity. No consistent differences were observed for other AEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Incorporating onset timing and AEL distinguished persistent toxicity burden from isolated peak events. This framework may support comparative tolerability assessment when chronic toxicity burden is central to decision-making.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djag287","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:46:06Z","timestamp":1787226366000},"source":"Crossref","is-referenced-by-count":1,"title":["Evaluating longitudinal toxicity and adverse events in cetuximab-treated metastatic colorectal cancer: a pooled analysis from 1302 patients in the ARCAD database"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3242-9664","authenticated-orcid":false,"given":"Jun","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Moffitt Cancer Center , Tampa, FL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine E","family":"Francis","sequence":"additional","affiliation":[{"name":"NHMRC Clinical Trials 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Levallois-Perret,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-6499","authenticated-orcid":false,"given":"Axel","family":"Grothey","sequence":"additional","affiliation":[{"name":"West Cancer Center and Research Institute, OneOncology , Germantown, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0489-4756","authenticated-orcid":false,"given":"Takayuki","family":"Yoshino","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology, National Cancer Center Hospital East ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7940-9877","authenticated-orcid":false,"given":"Aimery","family":"De Gramont","sequence":"additional","affiliation":[{"name":"Institut Hospitalier Franco-Britannique , Levallois-Perret,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4640-8832","authenticated-orcid":false,"given":"Qian","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic , Rochester, MN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Tournigand","sequence":"additional","affiliation":[{"name":"AP-HP, H\u00f4pital Henri Mondor, Service d\u2019oncologie m\u00e9dicale, Cr\u00e9teil, France; Univ Paris Est Cr\u00e9teil, INSERM , Cr\u00e9teil, F-94010, IMRB,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin M","family":"Sjoquist","sequence":"additional","affiliation":[{"name":"NHMRC Clinical Trials Centre, University of Sydney , 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