Simultaneous Boost in Neoadjuvant Radiotherapy for Rectal Cancer

Overview

The goal of this clinical trial is to learn whether new adjuvant radiotherapy with gross tumor volume(GTV) escalated to 58.75 Gy can improve complete response (CR) rates compared with GTV dose of 50 Gy in adult patients (18-79 years) with locally advanced rectal adenocarcinoma (T3-T4/N+, M0) located ≤10 cm from the anal verge.The main questions it aims to answer are: 1. Does GTV simultaneously boost to 58.75 Gy/25f increase complete response (pCR or cCR) compared with 50 Gy/25f? 2. How do the two regimens differ in terms of progression-free survival (PFS), pelvic local control (LC), tumor regression grade (TRG), organ preservation, and treatment-related toxicity? Researchers will compare GTV 58.75 Gy/25f (experimental arm) versus GTV 50 Gy/25f (control arm) to see if dose escalation improves tumor response rate. Participants will: 1. Receive neoadjuvant radiotherapy with one of the two PGTV dose escalated regimens (with concurrent chemotherapy: oral capecitabine or XELOX). 2. Undergo restaging with imaging and clinical assessment before surgery or observation. 3. Proceed to total mesorectal excision (TME), local excision, or "watch-and-wait" strategy depending on treatment response and patient preference. 4. Be followed regularly with clinical exams, imaging, endoscopy, and laboratory tests to assess efficacy, safety, and long-term outcomes.

This study is a randomized controlled trial designed to evaluate the clinical efficacy and safety of simultaneous integrated boost (SIB) dose escalation in the neoadjuvant treatment of locally advanced rectal cancer (LARC).Standard neoadjuvant chemoradiotherapy (nCRT) typically utilizes a dose of 50 Gy to the gross tumor volume (GTV). This trial investigates whether escalating the radiation dose specifically to the GTV to 58.75 Gy, delivered in 25 fractions, can significantly enhance tumor downstaging and increase the rates of pathologic complete response (pCR) or sustained clinical complete response (cCR).Study Arms and Radiation Technique:Participants are randomized into two arms. Both arms receive intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) with concurrent fluoropyrimidine-based chemotherapy.Experimental Arm: The planned target volume of the GTV (PGTV) receives a total dose of 58.75 Gy in 25 fractions ($2.35 \\text{ Gy/fraction}$), while the elective lymphatic drainage areas (PTV) receive 45-50 Gy.Control Arm: The PGTV receives a total dose of 50 Gy in 25 fractions ($2.0 \\text{ Gy/fraction}$), consistent with standard-of-care protocols.Clinical Workflow:Following the completion of neoadjuvant therapy, patients will undergo a mandatory restaging assessment 6-12 weeks post-radiation. This evaluation includes digital rectal examination (DRE), pelvic multiparametric MRI (mpMRI), and endoscopy.Surgical Intervention and Organ Preservation:Patients achieving a cCR may be offered a "Watch-and-Wait" (W\&W) strategy with intensive surveillance, aiming for organ preservation.Patients with a good but incomplete response may undergo local excision (LE) or total mesorectal excision (TME).The primary endpoint is the combined complete response (CR) rate, defined as pCR for those undergoing surgery and cCR (sustained for at least 6 months) for those entering the W\&W protocol.Secondary Objectives:The study will also perform a comparative analysis of progression-free survival (PFS), local control (LC) rates, and the distribution of Tumor Regression Grade (TRG). Safety profiles will be rigorously monitored using the Common Terminology Criteria for Adverse Events (CTCAE), focusing on acute and late gastrointestinal and genitourinary toxicities.