{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T14:49:53Z","timestamp":1774795793963,"version":"3.50.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japanese Foundation for Multidisciplinary Treatment of Cancer"},{"name":"Gastrointestinal Medical Oncology Division, National Cancer Center Hospital"},{"name":"One2Treat, Louvain-la-Neuve"},{"name":"IDDI"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Given the superior relapse-free survival (RFS) and different safety profiles of 1\u2009year of adjuvant S-1 or uracil\/tegafur (UFT) for stage II\/III rectal cancer, the benefit-risk of these 2 regimens was formally assessed using the net treatment benefit (NTB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>Individual patient data from the Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC) 35-C1 trial were used. S-1 and UFT were compared regarding RFS, incidence of grade \u22653 symptoms, and incidence of grade \u22653 laboratory abnormalities reported as adverse events (AEs). Laboratory abnormalities and symptoms were analyzed as binary variables and as counts. Univariate and multivariate NTBs were computed for various ways of prioritizing the outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The univariate NTB for RFS was 9.2% (95% CI, 3.4%-15.2%, P\u2009=\u2009.005) in favor of S-1. The univariate NTB was not statistically significant for any symptom. For grade \u22653 laboratory AEs, only thrombocytopenia was statistically significant in favor of UFT (NTB = \u22120.8%; 95% CI, \u22121.6% to \u22120.02%; P\u2009=\u2009.044). In the multivariate analysis considering RFS as the outcome of first priority, the incidence of grade \u22653 symptoms as second, and the incidence of grade \u22653 laboratory abnormalities as third, the multivariate NTB was 8.8% (95% CI, 2.7%-14.9%, P\u2009=\u2009.014) in favor of S-1. In sensitivity analyses according to age group, the NTB was generally positive for patients &amp;lt;70\u2009years but nonsignificant for those \u226570\u2009years old.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The reanalysis of the JFMC 35-C1 trial suggests that S-1 has a superior benefit-risk to UFT when RFS is considered as the outcome of first priority, followed by the incidence of grade \u22653 symptoms and of grade \u22653 laboratory abnormalities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag081","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T12:39:55Z","timestamp":1773146395000},"source":"Crossref","is-referenced-by-count":0,"title":["Benefit-risk balance of S-1 versus UFT as adjuvant chemotherapy for stage II\/III rectal cancer (JFMC35-C1: ACTS-RC)"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7346-5843","authenticated-orcid":false,"given":"Jean-Christophe","family":"Chiem","sequence":"first","affiliation":[{"name":"One2Treat , Louvain-la-Neuve, 1348,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hatem","family":"Alharazin","sequence":"additional","affiliation":[{"name":"One2Treat , Louvain-la-Neuve, 1348,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4039-588X","authenticated-orcid":false,"given":"Everardo D","family":"Saad","sequence":"additional","affiliation":[{"name":"IDDI (International Drug Development Institute) , Louvain-la-Neuve, 1341,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5468-8988","authenticated-orcid":false,"given":"Koji","family":"Oba","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo , Tokyo 113-0033,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaru","family":"Muto","sequence":"additional","affiliation":[{"name":"Japanese Foundation for Multidisciplinary Treatment of Cancer , Tokyo 136-0071,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisakazu","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Japanese Foundation for Multidisciplinary Treatment of Cancer , Tokyo 136-0071,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4316-0763","authenticated-orcid":false,"given":"Junichi","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Japanese Foundation for Multidisciplinary Treatment of Cancer , Tokyo 136-0071,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1936-9484","authenticated-orcid":false,"given":"Takaki","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Gastrointestinal Medical Oncology Division, National Cancer Center Hospital , Tokyo 104\u20110045,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4559-0994","authenticated-orcid":false,"given":"Marc","family":"Buyse","sequence":"additional","affiliation":[{"name":"One2Treat , Louvain-la-Neuve, 1348,","place":["Belgium"]},{"name":"IDDI (International Drug 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