{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:00:49Z","timestamp":1788447649129,"version":"build-2803163510"},"reference-count":10,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Regorafenib and trifluridine\/tipiracil (FTD\/TPI) are standard later-line treatments for patients with refractory metastatic colorectal cancer. However, these drugs show limited efficacy in some patients, and inappropriate use may increase toxicity and reduce quality of life. This study aimed to identify clinical predictors of early mortality after regorafenib or FTD\/TPI initiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed patients enrolled in the multicenter REGOTAS study. Early mortality was defined as death within 12\u2009weeks of treatment initiation. Variables with P\u2009&amp;lt;\u2009.05 in univariate analysis were entered into a multivariable Cox model for overall survival (OS). Patients alive at 15\u2009weeks (a 3-week margin beyond 12\u2009weeks) were censored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We analyzed 523 patients (regorafenib, N\u2009=\u2009212; FTD\/TPI, N\u2009=\u2009311). Independent predictors of early mortality were Eastern Cooperative Oncology Group performance status (\u22651), low albumin level (&amp;lt;3.5\u2009g\/dL), high C-reactive protein level (\u22651.0\u2009mg\/dL), and short time from first-line chemotherapy initiation (&amp;lt;18\u2009months). The high-risk group (patients with all four factors, N\u2009=\u200935) showed higher mortality and shorter OS than the low-risk group (others, N\u2009=\u2009488): 12-week mortality rate 40% vs 14%, 14-week mortality rate 60% vs 18%, and median OS: 2.8\u2009months vs 7.8\u2009months (hazard ratio: 3.52; P-value &amp;lt; .0001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our predictive model may help identify patients at high risk of early mortality after regorafenib or trifluridine\/tipiracil initiation and support shared decision-making between clinicians and patients regarding further chemotherapy or best supportive care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag142","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T11:20:50Z","timestamp":1776079250000},"source":"Crossref","is-referenced-by-count":1,"title":["Predictive factors for early mortality after regorafenib or trifluridine\/tipiracil initiation in metastatic colorectal cancer"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7521-1596","authenticated-orcid":false,"given":"Toshiki","family":"Masuishi","sequence":"first","affiliation":[{"name":"Department of Clinical Oncology, Aichi Cancer Center Hospital , Aichi, 464-8681,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9460-4486","authenticated-orcid":false,"given":"Shota","family":"Fukuoka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Cancer Institute Hospital Gastroenterology Center , Tokyo, 135-8550,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8456-1248","authenticated-orcid":false,"given":"Atsuo","family":"Takashima","sequence":"additional","affiliation":[{"name":"Gastrointestinal Medical Oncology Division, National Cancer Center Hospital , Tokyo, 104-0045,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Kumekawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Saitama Cancer Center , Saitama, 362-0806,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Oncology, Shizuoka Cancer Center , Shizuoka, 411-8777,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Center for Integrated Medical Research, Hiroshima University Hospital, Hiroshima University , Hiroshima, 734-8551,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikazu","family":"Moriwaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Kurashiki Central Hospital , Okayama, 710-8602,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"2026060406342805800_oyag142-B1","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/S0140-6736(12)61900-X","article-title":"Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial","volume":"381","author":"Grothey","year":"2013","journal-title":"Lancet"},{"key":"2026060406342805800_oyag142-B2","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1056\/NEJMoa1414325","article-title":"Randomized trial of TAS-102 for refractory metastatic colorectal cancer","volume":"372","author":"Mayer","year":"2015","journal-title":"N Engl J Med"},{"key":"2026060406342805800_oyag142-B3","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1634\/theoncologist.2017-0275","article-title":"Propensity score analysis of regorafenib versus trifluridine\/tipiracil in patients with metastatic colorectal cancer refractory to standard chemotherapy (REGOTAS): a Japanese society for cancer of the Colon and rectum multicenter observational study","volume":"23","author":"Moriwaki","year":"2018","journal-title":"Oncologist"},{"key":"2026060406342805800_oyag142-B4","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1186\/s12885-015-1862-0","article-title":"Withdrawal of anticancer therapy in advanced disease: a systematic literature review","volume":"15","author":"Clarke","year":"2015","journal-title":"BMC Cancer"},{"key":"2026060406342805800_oyag142-B5","doi-asserted-by":"publisher","first-page":"4675","DOI":"10.1007\/s00520-022-06831-y","article-title":"Hope therapy in cancer patients: a systematic review","volume":"30","author":"Salimi","year":"2022","journal-title":"Support Care Cancer"},{"key":"2026060406342805800_oyag142-B6","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1245\/s10434-008-0267-6","article-title":"Blood neutrophil-to-lymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy","volume":"16","author":"Yoji","year":"2009","journal-title":"Ann Surg Oncol"},{"key":"2026060406342805800_oyag142-B7","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1002\/cncr.26413","article-title":"Validation of the Royal Marsden hospital prognostic score in patients treated in the phase I clinical trials program at the MD Anderson cancer center","volume":"118","author":"Ignacio","year":"2012","journal-title":"Cancer"},{"key":"2026060406342805800_oyag142-B8","doi-asserted-by":"publisher","first-page":"e000752","DOI":"10.1136\/esmoopen-2020-000752","article-title":"Effect of trifluridine\/tipiracil in patients treated in RECOURSE by prognostic factors at baseline: an exploratory analysis","volume":"5","author":"Tabernero","year":"2020","journal-title":"ESMO Open"},{"key":"2026060406342805800_oyag142-B9","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/S0140-6736(23)00772-9","article-title":"Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study","volume":"402","author":"Dasari","year":"2023","journal-title":"Lancet"},{"key":"2026060406342805800_oyag142-B10","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1056\/NEJMoa2214963","article-title":"Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer","volume":"388","author":"Prager","year":"2023","journal-title":"N Engl J Med"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article-pdf\/doi\/10.1093\/oncolo\/oyag142\/68099558\/oyag142.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/31\/6\/oyag142\/68099558\/oyag142.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/31\/6\/oyag142\/68099558\/oyag142.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:34:31Z","timestamp":1780569271000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/doi\/10.1093\/oncolo\/oyag142\/8657072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":10,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,5,8]]}},"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyag142","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6]]},"published":{"date-parts":[[2026,4,16]]},"article-number":"oyag142"}}