ESTRO 2024 - Abstract Book

S1496

Clinical - Lower GI

ESTRO 2024

Yaqi Wang 1 , Fan Xia 1 , Lijun Shen 1 , Juefeng Wan 1 , Hui Zhang 1 , Yan Wang 1 , Ruiyan Wu 1 , Ye Xu 2 , Sanjun Cai 2 , Zhen Zhang 1 1 Fudan University Shanghai Cancer Center, Department of Radiation Oncology, Shanghai, China. 2 Fudan University Shanghai Cancer Center, Department of Colorectal Surgery, Shanghai, China

Purpose/Objective:

For locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT) increases the rates of complete response and organ preservation. Hypofractionated radiotherapy shows better synergistic effects in combination with PD-1 inhibitor. The combination of PD-1 inhibitor and short-course radiotherapy (SCRT) based TNT is likely to improve tumor response and prognosis.

Material/Methods:

TORCH is a prospective, multicentre, randomized phase II trial (NCT04518280). 130 LARC (T3-4/N+M0, distance from anal verge ≤10cm) patients will be treated with TNT and assigned to consolidation arm (A) and induction arm (B). Arm A receives SCRT (25Gy/5Fx) followed by 6 cycles of Toripalimab combined with CAPOX (ToriCAPOX). Arm B receives 2 cycles of ToriCAPOX followed by SCRT and 4 cycles of ToriCAPOX. TME surgery is scheduled 2 weeks after TNT while a watch and wait (W&W) option can be applied to patients achieving clinical complete response (cCR). The primary endpoint is complete response (CR, pathological complete response [pCR] plus cCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, 3-year DFS rate, etc.

Results:

Up to 2023/5/31, 130 patients were recruited and 104 patients have completed the treatment (Arm A 54, Arm B 50). The median age was 55 and 91 patients were stage III. 82.7% (86/104) of them showed one of the following features: lower location (≤5cm), cT4, cN2, MRF+ and EMVI+. 59 patients underwent TME, of which 29 cases achieved pCR (49.2%, 29/59), and the major pathologic response rate (TRG0-1) was 62.7% (37/59). 29 patients achieved cCR and adopted W&W. The total CR rate was 55.8% (58/104), with 57.4% (31/54) in Arm A and 54.0% (27/50) in Arm B. The remaining 16 non-cCR patients refused surgery and went on with close follow-up. Among 53 patients who were assessed N+ on baseline MR and underwent surgery, 48 were pathologically confirmed N0 (90.6%, 48/53). The main grade 3-4 AE was thrombocytopenia (42.3%, 44/104), with 4 cases of grade 4 thrombocytopenia.

Conclusion:

For LARC, PD-1 inhibitor combined with SCRT based TNT has achieved a high CR rate, which could provide new choice to achieve organ preservation for MSS and low rectal cancer patients and worth to be further validated in phase III trial.

Keywords: Immunotherapy based total neoadjuvant therapy