3566 - Hypofractionated Radiotherapy Combined with Immunotherapy and Chemotherapy for Locally Recurrent Rectal Cancer (TORCH-R): A Prospective, Single-Arm, Two-Cohort, Phase II Trial

02:30pm - 03:45pm PT

Hall F

Screen: 6

POSTER

Presenter(s)

Ruiyan Wu, MD, PhD - Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai,

R. Wu¹, J. Wan¹, L. Shen¹, F. Xia¹, H. Zhang¹, Y. Liu¹, Y. Wang¹, S. Zhou¹, X. Li², and Z. Zhang¹; ¹Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, ²Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

Purpose/Objective(s): To assess whether the integration of hypofractionated radiotherapy with PD-1 inhibitor and chemotherapy therapy can lead to an improvement in objective responses in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally recurrence rectal cancer (LRRC).

Materials/Methods: We did a prospective, single-arm, two-cohort, phase 2 trial in LRRC patients without or with oligometastases. Eligible patients with previously untreated (cohort A) or progressive disease after first line therapy (cohort B), were assigned received 25-40 Gy/5 Fx irradiation or 15–30 Gy/5 Fx reirradiation for pelvic recurrence, followed by 18 weeks of chemotherapy, toripalimab, and stereotactic ablative radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles. The primary endpoint was confirmed local recurrence objective response rate (ORR). The study is registered with ClinicalTrials.gov, NCT05628038.

Results: Between Jan 31, 2023, and Feb 13, 2025, we enrolled 77 patients: 44 in cohort A and 34 in cohort B. Median follow-up duration was 14.3 months (IQR 8.3-19.3 months). The local recurrence ORR was achieved at 79.5% (35 of 44 patients) in cohort A and 70.6% (24 of 34 patients) in cohort B. Ten patients (22.7%) underwent radical resections (R0) in cohort A and Five patients (14.7 %) in cohort B. The CR rate was 34.1% (12 cCR patients + 3 pCR patients) in cohort A and 20.6 % (6 cCR patients + 1 pCR patients) in cohort B. The most frequent grade 3-4 toxicities were neutropenia (6.8 % in cohort A and 23.5% in cohort B) and diarrhea (17.1 % in cohort A and 20.6% in cohort B).

Conclusion: The PD-1 inhibitor remarkably improved ORR in pMMR/MSS LRRC compared with historical benchmark with acceptable toxicity. Up-front hypofractionated radiotherapy combined with immunochemotherapy was selected for future definitive study.