{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:34:00Z","timestamp":1787826840943,"version":"build-2784847793"},"reference-count":47,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Total neoadjuvant therapy (TNT) has emerged as a promising strategy for locally advanced rectal cancer (LARC). By administering both chemoradiotherapy (CRT) and systemic chemotherapy (CHT) pre-surgery, TNT is associated with improved disease-free survival (DFS), reduced distant metastases, and higher pathological complete response (pCR) rates. Materials and Methods: This study included patients with LARC who received various TNT schedules: induction chemotherapy (iCHT), consolidation chemotherapy (cCHT), or a combination of both (sandwichCHT). We analyzed treatment adherence, toxicity, and pathological response. Local and distant disease recurrence, as well as survival outcomes, were also evaluated. Results: Between May 2021 and January 2025, 70 patients received TNT. Treatment included iCHT (41%), sandwichCHT (49%), and cCHT (10%). Most patients (94%) received long-course radiotherapy (LCRT). Overall, TNT was well tolerated, with grade 2 gastrointestinal toxicity during CRT being the most common frequent adverse event (33%). Disease progression during TNT was noted in five patients (7%); three of these patients were receiving chemotherapy, while two underwent surgical resection of the primary tumor. A watch-and-wait strategy was adopted for five patients (7%) following TNT. Surgical procedures performed included anterior resection (92%), abdominoperineal resection (7%), and local excision (1%). Pathological assessment revealed an overall pCR rate of 30%. With a median follow-up of 17 months, no patients experienced local recurrence. Post-surgery, 10 patients (17%) developed disease progression. The median DFS was 14.7 months. Five patients (7%) died during the follow-up period, with only one death attributed to causes other than disease progression. Conclusions: In this cohort of LARC patients, TNT demonstrated favorable tolerability and encouraging short-term efficacy.<\/jats:p>","DOI":"10.3390\/cancers17152416","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T08:45:18Z","timestamp":1753173918000},"page":"2416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Evaluation of Sequencing, Response, and Toxicity in a Single-Institution Cohort"],"prefix":"10.3390","volume":"17","author":[{"given":"Maria Cristina","family":"Barba","sequence":"first","affiliation":[{"name":"Radiation Therapy Unit, Department of Onco Hematology, \u201dVito Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7332-9099","authenticated-orcid":false,"given":"Paola","family":"De Franco","sequence":"additional","affiliation":[{"name":"Radiation Therapy Unit, Department of Onco Hematology, \u201dVito Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9246-7981","authenticated-orcid":false,"given":"Donatella","family":"Russo","sequence":"additional","affiliation":[{"name":"Radiation Therapy Unit, Department of Onco Hematology, \u201dVito Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Cavalera","sequence":"additional","affiliation":[{"name":"Radiation Therapy Unit, Department of Onco Hematology, \u201dVito Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7423-3232","authenticated-orcid":false,"given":"Elisa","family":"Ciurlia","sequence":"additional","affiliation":[{"name":"Radiation Therapy Unit, Department of Onco Hematology, \u201dVito Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"De Matteis","sequence":"additional","affiliation":[{"name":"Radiation Therapy Unit, Department of Onco Hematology, \u201dVito Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Di Paola","sequence":"additional","affiliation":[{"name":"Radiation Therapy Unit, Department of Onco Hematology, \u201dVito Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corradino","family":"Federico","sequence":"additional","affiliation":[{"name":"Department of Palliative Care, ASL Lecce, 73016\u00a0San Cesario di Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Leone","sequence":"additional","affiliation":[{"name":"Radiation Therapy Unit, Department of Onco Hematology, \u201dVito Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Papaleo","sequence":"additional","affiliation":[{"name":"Radiation Therapy Unit, Department of Onco Hematology, \u201dVito Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Santo","sequence":"additional","affiliation":[{"name":"Radiation Therapy Unit, Department of Onco Hematology, \u201dVito Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3807-0752","authenticated-orcid":false,"given":"Dino","family":"Rubini","sequence":"additional","affiliation":[{"name":"Radiation Therapy Unit, Department of Precision Medicine, Universit\u00e0 degli Studi della Campania Luigi Vanvitelli, 80128 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1972-3308","authenticated-orcid":false,"given":"Giuseppe","family":"Rubini","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, Interdisciplinary Department of Medicine, University of Bari, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Sardaro","sequence":"additional","affiliation":[{"name":"Radiation Therapy Unit, Department of Onco Hematology, \u201dVito Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"ref_1","unstructured":"Del, N., and Dell, R.E. 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