Adaptive Boost Radiotherapy to Primary Lesions and Positive Nodes in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer

This prospective, single-center, randomized controlled trial evaluates whether online adaptive radiotherapy (ART) with a sequential boost to both the primary rectal tumor and clinically involved lymph nodes improves pathologic complete response in patients with high-risk, node-positive locally advanced rectal cancer. Participants were randomly assigned 1:1 to online ART with a sequential boost or conventional non-adaptive intensity-modulated radiotherapy (IMRT). Both groups received concurrent capecitabine during long-course chemoradiotherapy, followed by 3-4 cycles of CAPEOX consolidation chemotherapy and planned total mesorectal excision. The planned sample size was 128 participants. Enrollment was discontinued after an interim review after 76 participants had been randomized; long-term follow-up of enrolled participants is ongoing.

Inclusion Criteria 1. Age 18 years or older. 2. ECOG performance status of 0 or 1. 3. Histologically confirmed rectal adenocarcinoma. 4. Primary tumor located within 10 cm of the anal verge by pelvic MRI and/or rigid sigmoidoscopy. 5. Clinically involved regional lymph nodes (cN1-2) according to the AJCC 8th edition. 6. At least one additional high-risk feature: cT4 disease, cN2 disease, extramural vascular invasion, mesorectal fascia involvement, lateral pelvic lymph-node involvement, tumor deposits, or low rectal cancer (≤5 cm from the anal verge). 7. Baseline locoregional staging with contrast-enhanced pelvic MRI and chest/abdominal imaging excluding distant metastases. 8. Treatment-naïve with respect to systemic therapy and pelvic radiotherapy for the index rectal cancer and suitable for total mesorectal excision. 9. Adequate organ function and no medical contraindication to chemoradiotherapy. 10. Written informed consent before study-specific procedures. Exclusion Criteria 1. Prior pelvic radiotherapy. 2. Prior rectal surgery for the index cancer, including local excision or transanal procedures. 3. Radiologically or pathologically confirmed distant metastasis. 4. Locally recurrent rectal cancer. 5. Active inflammatory bowel disease. 6. History of another primary malignancy within the preceding 5 years, except adequately treated non-melanoma skin cancer or carcinoma in situ. 7. Pregnancy or lactation. 8. Severe or uncontrolled medical condition contraindicating chemoradiotherapy or surgery. 9. Clinically significant hypersensitivity to protocol systemic therapy that precludes treatment.