Short-course radiotherapy followed by sintilimab and CAPOX as total neoadjuvant treatment in locally advanced rectal cancer: A prospective, randomized controlled trial (SPRING-01).

3519 Background: Neoadjuvant short-course radiotherapy (SCRT) combined with chemotherapy as total neoadjuvant therapy (TNT) increases the pathological complete response (pCR) rate for locally advanced rectal cancer (LARC). The potential synergistic effects of combining radiotherapy and immunotherapy might benefit patients with LARC. This study aimed to compare the efficacy and safety of SCRT followed by 6 cycles of CAPOX chemotherapy with or without immunotherapy as TNT in LARC patients. Methods: In this randomized controlled trial, patients with T3-4, N+, EMVI(+), MRF(+) or lateral lymph node(+) rectal adenocarcinoma were randomly assigned to receive SCRT followed by 6 cycles of CAPOX chemotherapy with or without sintilimab. Total mesorectal excision (TME) was performed 2-3 weeks after the completion of TNT. The primary study endpoint was the pCR rate. Results: In this randomized controlled trial, patients with T3-4, N+, EMVI(+), MRF(+) or lateral lymph node(+) rectal adenocarcinoma were randomly assigned to receive SCRT followed by 6 cycles of CAPOX chemotherapy with or without sintilimab. Total mesorectal excision (TME) was performed 2-3 weeks after the completion of TNT. The primary study endpoint was the pCR rate. Conclusions: In LARC patients, SCRT combined with sintilimab and CAPOX as a TNT significantly increases the pCR rate while maintaining manageable safety in patients with LARC. SCRT followed by sintilimab and CAPOX can be recommended as a superior neoadjuvant treatment option for these patients. Clinical trial information: ChiCTR2100052288 . The efficacy of SIN+CAPOX and surgical and pathological results. Intention-to-treat (ITT) population SIN+CAPOX (N = 49) CAPOX (N = 49) Pathological complete response (ypT0N0, ITT population) — no. (%) 29（59.2） 16（32.7） (% [95% CI]) (45.4, 72.9) (19.5, 45.8) Complete response 30（61.2） 16（32.7） Surgical population SIN+CAPOX (N = 45) CAPOX (N = 44) Tumor regression grading (AJCC 8th edition) — no. (%) 0 29（64.4） 16（36.4） 1 7（15.6） 7（15.9） 2 5（11.1） 13（29.5） 3 4（8.9） 8（18.2） Abbreviations: IQR, interquartile range; N, regional nodal category; T, primary tumor category; yp, pathologic.