Abstract
BACKGROUND: Neoadjuvant radiochemotherapy followed by radical surgery is the standard treatment strategy for local advanced rectal cancer (LARC). However, the efficacy of neoadjuvant radiochemotherapy is limited, especially for patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer. Considering the amazing therapeutic effect of immune check point inhibitors for metastatic colorectal cancer, we conduct this multicenter, phase Ib study to investigate the safety and efficacy of anti-PD-1 antibody, sintilimab combined with hypofractionated radiotherapy in MSI-H/dMMR rectal cancer patients. METHODS: Patients with MSI-H/dMMR LARC will receive hypofractionated radiotherapy (5 Gy × 5) and three cycles of sintilimab 200 mg IV every 2 weeks. Radical surgery will be performed 6-8 weeks after radiotherapy. The primary endpoint is adverse reaction after neoadjuvant treatment and perioperative complications. Secondary endpoints include pathological response rate, complete resection rate, and quality of life. DISCUSSION: This is the first study to investigate the safety and effectiveness of neoadjuvant radiotherapy combined with immunotherapy for MSI-H/dMMR LARC. It is expected that this study will propose a brand new and effective treatment strategy for MSI-H/dMMR LARC.