Node-sparing modified short-course radiotherapy combined with CAPOX and tislelizumab for locally advanced MSS of middle and low rectal cancer (mRCAT): An open-label, single-arm, prospective, multicentre clinical trial.

Abstract

TPS233 Background: Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer was highly sensitive to PD-1 blockade. However, most rectal cancers are mismatch repair-proficient or microsatellite stable subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8+ T cells, further enhancing the responses of microsatellite stable rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with microsatellite stable locally advanced rectal cancer. Methods: Our clinical trial investigates the safety and efficacy of node-sparing modified short-course radiotherapy combined with CAPOX and tislelizumab for microsatellite stable locally advanced middle and low rectal cancer. This phase II study will recruit 32 patients to receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. 2 of planned 32 patients have been enrolled. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m2 intravenous infusion, day 1; capecitabine 1000 mg/m2 oral administration, days 1-14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be three 21-day cycles. TME will be performed at weeks 11-12. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed. Clinical trial information: NCT05972655 .