{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:23:56Z","timestamp":1787869436610,"version":"build-2784847793"},"reference-count":49,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"25","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>High-risk locally advanced rectal cancer (LARC) carries a substantial risk of distant recurrence, which limits disease-free survival (DFS). We compared total neoadjuvant therapy (TNT) integrating long-course radiotherapy (LCRT) with uninterrupted doublet chemotherapy (doublet-LC TNT) versus conventional neoadjuvant chemoradiotherapy (nCRT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      In this multicenter, randomized, phase III trial, patients with stage II\/III LARC and at least 1 high-risk feature (cT4a-b, cN2, mesorectal fascia involvement, or cT3c-d with extramural vascular invasion) were enrolled. Patients were assigned to doublet-LC TNT (induction, concurrent, and consolidation capecitabine plus oxaliplatin with LCRT) before surgery or nCRT (capecitabine with LCRT) followed by surgery and adjuvant chemotherapy. The primary end point was DFS (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03177382\">NCT03177382<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Between June 6, 2017, and December 27, 2023, 458 patients were randomly assigned to doublet-LC TNT (n = 232) or nCRT (n = 226). At a median follow-up of 51 months, doublet-LC TNT improved 3-year DFS (74.8%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      66.0%; hazard ratio [HR], 0.674 [95% CI, 0.489 to 0.929];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .016). Metastasis-free survival (MFS; 77.7%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      67.6%; HR, 0.655 [95% CI, 0.469 to 0.915]) and pathologic complete response rates (pCR; 26.37%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      9.80%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001) were higher with doublet-LC TNT, whereas locoregional failure remained low and comparable (6.03%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      6.19%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .943). Although grade \u22653 adverse events during the neoadjuvant phase were more frequent with doublet-LC TNT (27.59%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      8.56%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001), severe toxicities during the entire treatment course (28.02%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      24.32%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .371) and major postoperative complications (3.98%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      2.94%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .567) were comparable.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Compared with conventional nCRT, doublet-LC TNT improved DFS, MFS, and pCR rates with manageable toxicity. These findings support this intensified, doublet-based regimen as a standard option within the modern TNT paradigm. Further comparative studies are warranted to evaluate these results against other short-course radiotherapy\u2011based or nondoublet-concurrent TNT regimens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-03110","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T19:59:16Z","timestamp":1784836756000},"page":"2409-2421","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Total Neoadjuvant Therapy With Long-Course Radiotherapy Versus Chemoradiotherapy in High-Risk Locally Advanced Rectal Cancer (TNTCRT): A Multicenter, Randomized, Phase III Trial"],"prefix":"10.1200","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct03177382","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Abdominal Tumor Multimodality Treatment, Department of Radiation Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9240-2112","authenticated-orcid":false,"given":"Yuanling","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Abdominal Tumor Multimodality Treatment, Department of Radiation Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0206-621X","authenticated-orcid":false,"given":"Junyang","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 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