{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:03:22Z","timestamp":1784199802930,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Total neoadjuvant therapy (TNT) is the standard treatment for locally advanced rectal cancer (LARC). Few studies have focused on the toxicity of TNT. Moreover, the differences in safety and tolerability between radiotherapy\u2010first and chemotherapy\u2010first strategies remain unclear. This study aimed to evaluate the differences in treatment\u2010related toxicities between radiotherapy\u2010first and chemotherapy\u2010first strategies for TNT in patients with LARC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with LARC who were treated with TNT at a single cancer center between June 2020 and July 2023 were retrospectively included. TNT consisted of induction chemotherapy followed by long\u2010course chemoradiotherapy (INCT\u2010LC\u2010CRT) or long\u2010course chemoradiotherapy\/short\u2010course radiotherapy followed by consolidation chemotherapy (LC\u2010CRT\u2010CNCT\/SC\u2010RT\u2010CNCT). Adverse events (AEs) and treatment exposure were compared between the groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, 93 patients were included. Patients in the INCT\u2010LC\u2010CRT and LC\u2010CRT\u2010CNCT\/SC\u2010RT\u2010CNCT groups were 28 (30.1%) and 45 (48.4%) \/ 20 (21.5%), respectively. Chemotherapy\u2010related grade 3 or 4 AEs were significantly more frequent in the LC\u2010CRT\u2010CNCT\/SC\u2010RT\u2010CNCT group than in the INCT\u2010LC\u2010CRT group (50.8% vs. 17.9%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) but were not significantly different between the LC\u2010CRT\u2010CNCT and SC\u2010RT\u2010CNCT groups (53.3% vs. 40.0%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.42). The proportion of patients who received a full dose of chemotherapy was higher in the INCT\u2010LC\u2010CRT group than in the LC\u2010CRT\u2010CNCT\/SC\u2010RT\u2010CNCT group (53.6% vs. 24.6%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). One (3.6%) and six (9.2%) patients discontinued chemotherapy owing to AEs in the INCT\u2010LC\u2010CRT and LC\u2010CRT\u2010CNCT\/SC\u2010RT\u2010CNCT groups, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Grade 3 or 4 AEs during chemotherapy were more frequent and required dose modification in the LC\u2010CRT\u2010CNCT\/SC\u2010RT\u2010CNCT group than in the INCT\u2010LC\u2010CRT group.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72011","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:31:15Z","timestamp":1782189075000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and Tolerability of Different Total Neoadjuvant Therapies in Patients With Locally Advanced Rectal Cancer"],"prefix":"10.1002","volume":"15","author":[{"given":"Shohei","family":"Udagawa","sequence":"first","affiliation":[{"name":"Department of Gastroenterological Chemotherapy Cancer Institute Hospital of the Japanese Foundation for Cancer Research  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Osumi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Chemotherapy Cancer Institute Hospital of the Japanese Foundation for Cancer Research  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3932-8084","authenticated-orcid":false,"given":"Senzo","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Cancer Institute Hospital of the Japanese Foundation for Cancer Research  Tokyo 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