Comparison of the Clinical Response in Total Neoadjuvant Treatment With Long-Term or Short-Term Chemoradiotherapy Followed by Consolidation Chemotherapy in Patients With Locally Advanced Rectal Cancer (Tehran); the Protocol for a Randomized Controlled Clinical Trial Publisher Pubmed



Aghili M ; Ghalehtaki R ; Yaghootikhorasani M ; Yazdi SMM ; Kolahdouzan K
Source: Cancer Medicine Published:2025

Abstract

Background: Total neoadjuvant therapy (TNT) is a preferred method for the treatment of locally advanced rectal cancer (LARC). Two techniques of radiotherapy have been used in TNT trials so far, including long-course chemoradiotherapy (LCRT) and short-course radiotherapy (SCRT). However, to date, no study compares these techniques in a head-to-head fashion. Our objective is to compare the complete clinical response among patients with LARC who receive long or short-course radiation therapy in combination with the same chemotherapy regimen. Methods: 158 patients (18–80 years old) with standard or high-risk LARC (T3/T4 tumor or lymph node positive) located at least 5 cm from the anal verge will be randomized into two groups: LCRT (with a dose of 50.4 Gy in 28 sessions) or SCRT (with a dose of 25 Gy in five sessions). Both of these groups will receive concurrent chemotherapy (capecitabine 825 mg/m2 twice daily) followed by consolidation chemotherapy with the CAPEOX regimen for 6 cycles or mFOLFOX7 for 9 cycles. We will compare the complete clinical response (initially 12–16 weeks after the last RT fraction and eventually 2 weeks after the last chemotherapy cycle) by MRI as the primary endpoint. Overall survival (OS), metastasis-free survival (MFS), local control, and toxicities will be evaluated after 3–5 years as the secondary endpoints. Discussion: Advances in the treatment of rectal cancer focus on metastasis control, besides local control by using neoadjuvant therapy. Determining the complete clinical response, OS, and MFS of short-course versus long-course chemoradiation will assist in choosing the best LARC treatment protocol. Trial Registration: ClinicalTrials.gov: NCT05920928, 2023.06.27. © 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.