Hypofractionated radiotherapy combined with chemotherapy and Toripalimab for locally recurrent rectal cancer: a single-arm, phase II trial (TORCH-R)

Abstract Background For patients with locally recurrent rectal cancer (LRRC), R0 resection of pelvic recurrent tumour is most important prognostic factor influencing survival. However, only approximately 40% of patients with recurrent rectal cancer can undergo R0 resection. Recent studies have shown promising synergistic effects of the combination of immunotherapy (PD-1/PD-L1 antibodies) and neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Thus, for LRRC patients, addition of immunotherapy to preoperative CRT is likely to further improve the rate R0 resection and prognosis. Methods TORCH-R is a prospective, single-center, single-arm phase II trial of preoperative hypofractionated radiotherapy, chemotherapy and immunotherapy in LRRC. A total of 75 locally recurrent rectal cancer (LRRC) patients will be recruited and receive 25-40Gy/5Fx irradiation or 15-25Gy/5Fx reirradiation, 6 cycles of CAPOX and toripalimab, followed by multidisciplinary team (MDT) for decision: radical surgery, sustained treatment until resectable or exit. The primary endpoint is the R0 resection rate of pelvic recurrent tumour. The secondary endpoints include the overall response rate (ORR), progression-free survival (PFS), overall survival (OS), safety and tolerability. Discussion TORCH-R will investigate whether hypofractionated radiotherapy combined with chemotherapy and Toripalimab can achieve better R0 resection rates, good tolerance and prognosis in LRRC patients. This is the first clinical trial to induce immunotherapy and consolidative chemoradiotherapy in LRRC patients. Trial registration: Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT05628038, November 17, 2022.