{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:05:30Z","timestamp":1790762730476,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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":["Journal of Surgical Oncology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The interval from radiotherapy completion to surgery may affect pelvic fibrosis, operative difficulty, postoperative morbidity, and quality of rectal cancer resection. In total neoadjuvant therapy (TNT), however, this interval has different clinical content according to treatment sequence. We evaluated whether radiotherapy\u2010to\u2010surgery timing after induction TNT was associated primarily with perioperative morbidity and surgical oncologic quality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a retrospective cohort study of patients with locally advanced rectal adenocarcinoma treated at a tertiary cancer center from January 2020 through December 2024. The primary analysis included 94 patients receiving induction TNT, in whom systemic chemotherapy preceded radiotherapy. The radiotherapy\u2010to\u2010surgery interval was modeled continuously per 4\u2010week increase; categories of \u2264\u20098, &gt;\u20098\u201312, and &gt;\u200912 weeks were retained for descriptive reporting only because the early strata were sparse. The primary endpoint was Clavien\u2010Dindo grade \u2265\u2009III morbidity within 30 days. Secondary endpoints included reoperation, readmission, anastomotic leak, conversion, operative time, blood loss, length of stay, mesorectal quality, resection margins, and lymph\u2010node yield. Pathological complete response (pCR) and recurrence\u2010free survival were exploratory oncologic endpoints. Consolidation TNT was examined separately because its measured interval contains post\u2010radiotherapy chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 94 patients treated with induction TNT, the median radiotherapy\u2010to\u2010surgery interval was 143.5 days (IQR 104.8\u2013259.3). Major morbidity occurred in 17\/94 (18.1%), reoperation in 12\/93 (12.9%), and readmission in 9\/94 (9.6%). Median operative time was 279.5\u2009min, blood loss 100\u2009mL, and length of stay 4 days. Complete or near\u2010complete mesorectal quality was documented in 73\/91 (80.2%), R0 resection in 88\/94 (93.6%), and median lymph\u2010node yield was 9 (IQR 6\u201315). Each additional 4 weeks was not associated with major morbidity (adjusted OR 0.886, 95% CI 0.748\u20131.050;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.164), reoperation (OR 0.910, 95% CI 0.755\u20131.096;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.320), incomplete mesorectal excision (OR 1.113, 95% CI 0.971\u20131.275;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.125), operative time (adjusted\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009\u2212\u20090.4\u2009min, 95% CI \u22125.5 to 4.8;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.893), blood loss (1.4% change, 95% CI \u22124.8% to 7.9%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.668), or length of stay (\u22120.1% change, 95% CI \u22123.0% to 2.9%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.958). Exploratory analyses found no association with pCR or recurrence\u2010free survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>After adjustment for radiotherapy course, variation in radiotherapy\u2010to\u2010surgery timing was not associated with major postoperative morbidity, operative burden, or incomplete mesorectal excision. R0 resection was achieved in 93.6% of patients, while margin events were too infrequent for stable adjusted modeling. Lymph\u2010node yield showed no statistically significant association with interval duration. pCR and recurrence analyses were exploratory and did not show an interval association. Timing should be interpreted according to TNT sequence because consolidation therapy structurally prolongs the radiotherapy\u2010to\u2010surgery interval.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jso.70413","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:47:29Z","timestamp":1790761649000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Radiotherapy\u2010to\u2010Surgery Interval After Induction Total Neoadjuvant Therapy for Rectal Cancer: Perioperative Outcomes and Oncologic Quality of Total Mesorectal Excision"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3955-8198","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Aguilar\u2010Romero","sequence":"first","affiliation":[{"name":"Surgical Oncology Department Instituto Nacional de Cancerolog\u00eda Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6516-4212","authenticated-orcid":false,"given":"Itzel","family":"Vela\u2010Sarmiento","sequence":"additional","affiliation":[{"name":"Surgical Oncology Department Instituto Nacional de Cancerolog\u00eda Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7394-5123","authenticated-orcid":false,"given":"Leonardo S.","family":"Lino\u2010Silva","sequence":"additional","affiliation":[{"name":"Surgical Pathology Department Instituto Nacional de Cancerolog\u00eda Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7278-2808","authenticated-orcid":false,"given":"Estefan\u00eda","family":"Aguilar\u2010Romero","sequence":"additional","affiliation":[{"name":"Medical Oncology Department Instituto Nacional de Cancerolog\u00eda Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5915-2103","authenticated-orcid":false,"given":"Javier","family":"Melchor\u2010Ruan","sequence":"additional","affiliation":[{"name":"Surgical Oncology Department Instituto Nacional de Cancerolog\u00eda Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5314-2887","authenticated-orcid":false,"given":"Jorge L.","family":"Aguilar\u2010Frasco","sequence":"additional","affiliation":[{"name":"Surgical Oncology Department Instituto Nacional de Cancerolog\u00eda Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4537-8034","authenticated-orcid":false,"given":"Rosa A.","family":"Salcedo\u2010Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Surgical Oncology Department Instituto Nacional de Cancerolog\u00eda Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S1470-2045(20)30555-6","article-title":"Short\u2010Course Radiotherapy Followed by Chemotherapy before Total Mesorectal Excision (TME) Versus Preoperative Chemoradiotherapy, TME, and Optional Adjuvant Chemotherapy in Locally Advanced Rectal Cancer (RAPIDO): A Randomised, Open\u2010Label, Phase 3 Trial","volume":"22","author":"Bahadoer R. R.","year":"2021","journal-title":"Lancet Oncology"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/S1470-2045(21)00079-6","article-title":"Neoadjuvant Chemotherapy with FOLFIRINOX and Preoperative Chemoradiotherapy for Patients with Locally Advanced Rectal Cancer (UNICANCER\u2010PRODIGE 23): A Multicentre, Randomised, Open\u2010Label, Phase 3 Trial","volume":"22","author":"Conroy T.","year":"2021","journal-title":"Lancet Oncology"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1200\/JCO.22.00032","article-title":"Organ Preservation in Patients with Rectal Adenocarcinoma Treated with Total Neoadjuvant Therapy","volume":"40","author":"Garcia\u2010Aguilar J.","year":"2022","journal-title":"Journal of Clinical Oncology"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01208"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1200\/JCO.19.00308","article-title":"Randomized Phase II Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: CAO\/ARO\/AIO\u201012","volume":"37","author":"Fokas E.","year":"2019","journal-title":"Journal of Clinical Oncology"},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","DOI":"10.1001\/jamaoncol.2021.5445","article-title":"Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer: Long\u2010Term Results of the CAO\/ARO\/AIO\u201012 Randomized Clinical Trial","volume":"8","author":"Fokas E.","year":"2022","journal-title":"JAMA Oncology"},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"366","DOI":"10.6004\/jnccn.2024.0041","article-title":"NCCN Guidelines\u00ae Insights: Rectal Cancer, Version 3.2024: Featured Updates to the NCCN Guidelines","volume":"22","author":"Benson A. B.","year":"2024","journal-title":"Journal of the National Comprehensive Cancer Network"},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/s41571-021-00538-5","article-title":"International Consensus Recommendations on Key Outcome Measures for Organ Preservation After (Chemo)Radiotherapy in Patients With Rectal Cancer","volume":"18","author":"Fokas E.","year":"2021","journal-title":"Nature Reviews Clinical Oncology"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.05.528"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.24.01160"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prro.2024.11.003"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1200\/JCO.2016.67.6049","article-title":"Effect of Interval (7 or 11 Weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR\u20106)","volume":"34","author":"Lefevre J. H.","year":"2016","journal-title":"Journal of Clinical Oncology"},{"issue":"3","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/S1470-2045(17)30086-4","article-title":"Optimal Fractionation of Preoperative Radiotherapy and Timing to Surgery for Rectal Cancer (Stockholm III): A Multicentre, Randomised, Non\u2010Blinded, Phase 3, Non\u2010Inferiority Trial","volume":"18","author":"Erlandsson J.","year":"2017","journal-title":"Lancet Oncology"},{"key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1097\/SLA.0000000000000368","article-title":"Increasing the Interval Between Neoadjuvant Chemoradiotherapy and Surgery in Rectal Cancer: A Meta\u2010Analysis of Published Studies","volume":"263","author":"Petrelli F.","year":"2016","journal-title":"Annals of Surgery"},{"key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/bjs.9112","article-title":"Optimal Time Interval Between Neoadjuvant Chemoradiotherapy and Surgery for Rectal Cancer","volume":"100","author":"Sloothaak D. 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M.","year":"2013","journal-title":"British Journal of Surgery"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surge.2024.03.001"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-023-05601-3"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000003885"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/DCR.0000000000002555"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.4582"},{"key":"e_1_2_11_22_1","first-page":"205","article-title":"Classification of Surgical Complications: A New Proposal With Evaluation in a Cohort of 6,336 Patients","volume":"240","author":"Dindo D.","year":"2004","journal-title":"Annals of Surgery"},{"issue":"3","key":"e_1_2_11_23_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.surg.2009.10.012","article-title":"Definition and Grading of Anastomotic Leakage Following Anterior Resection of the Rectum: A Proposal by the International Study Group of Rectal Cancer","volume":"147","author":"Rahbari N. N.","year":"2010","journal-title":"Surgery"},{"key":"e_1_2_11_24_1","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1200\/JCO.2002.07.010","article-title":"Macroscopic Evaluation of Rectal Cancer Resection Specimen: Clinical Significance of the Pathologist in Quality Control","volume":"20","author":"Nagtegaal I. D.","year":"2002","journal-title":"Journal of Clinical Oncology"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00493-9"}],"container-title":["Journal of Surgical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jso.70413","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jso.70413","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jso.70413","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:47:32Z","timestamp":1790761652000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jso.70413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":24,"alternative-id":["10.1002\/jso.70413"],"URL":"https:\/\/doi.org\/10.1002\/jso.70413","archive":["Portico"],"relation":{},"ISSN":["0022-4790","1096-9098"],"issn-type":[{"value":"0022-4790","type":"print"},{"value":"1096-9098","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"assertion":[{"value":"2026-07-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jso.70413"}}