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

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/m 2 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