2287 - Neoadjuvant Short-Course Radiotherapy Combined with Immunochemotherapy vs. Chemotherapy Alone in pMMR Colon Cancers: The TORCH-C Randomized Phase 2 Clinical Trial
Presenter(s)
H. Zhang1, F. Xia1, Y. Li2, W. Yang1, Y. Chen1, Y. Wang1, L. He1, M. Zhou1, L. Shen1, Y. Wang3, J. Wan1, J. Wang1, R. Wu1, S. Zhou1, J. Zhang1, F. Liu2, S. Cai3, and Z. Zhang4; 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, 2Fudan University Shanghai Cancer Center, Shanghai, China, 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China, 4Department of Radiation Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University; Shanghai Clinical Research Center for Radiation Oncology; Shanghai Key Laboratory of Radiation Oncology, Shanghai, China
Purpose/Objective(s):
The prognosis for locally advanced colon cancer (LACC) with bulky nodal disease and/or clinically T4 stage remains poor, with high rate of recurrence and metastasis. Short-course radiotherapy (SCRT) has demonstrated enhanced synergistic effects when combined with PD-1 inhibitors and chemotherapy in rectal cancer. However, there has been little progress in colon cancer. For locally advanced colon cancer with T4b stage or bulky lymph nodes, neoadjuvant chemotherapy is currently widely used. Whether combining it with immunotherapy and radiotherapy can improve efficacy is worthy of exploration. TORCH-C is the first study to evaluate this combination.Materials/Methods:
TORCH-C is a prospective, multicenter, randomized phase 2 study enrolled patients from April 3, 2023, through September 9, 2025. A total of 120 high-risk LACC (T4/bulky N+M0,pMMR/MSS) patients were 1:1 randomized to either a SCRT combined with immunotherapy and CAPOX chemotherapy group (group A) or a chemotherapy alone group (group B). Patients in the group B received 4 cycles of CAPOX (oxaliplatin 130 mg/m2 intravenously day 1 and capecitabine 1000 mg/m2 orally days 1-14). Patients in the group A received SCRT(25Gy in 5 fraction)and 4 cycles of the PD-1 inhibitor (serplulimab, 300mg intravenously day 1) combined with CAPOX. The radiotherapy target volume includes only the primary colon tumor and enlarged lymph nodes, without elective nodal irradiation. Radiotherapy was delivered on a CT-linac using an online adaptive radiotherapy (ART) guided by daily diagnostic CT imaging. After neoadjuvant therapy, patients will be evaluated for radical colon resection. All patients will receive adjuvant chemotherapy of four cycles of CAPOX. The primary outcome was pathological complete response (pCR) rate. The secondary outcomes included tumor downstaging, R0 resection, 3-year disease free survival (DFS), 3-year overall survival (OS), 3-year local recurrence-free survival and treatment-related toxicity.Results: 120 patients have been enrolled and randomized. 107 patients were included in the mITT analysis (54 in group A and 53 in group B). 103 have received surgery (50 in the chemotherapy group, 53 in the radiotherapy group). The pCR rate was 10% (5/50) in chemotherapy group (group B) and 45.3% (24/53) in the radiotherapy group (group A) (P<0.05). The most common grade 3-4 adverse event (AE) among patients was thrombocytopenia, (22.2%, 12/54) in the group A and (18.9%, 10/53) in the group B. Radiotherapy was safely delivered, the most common AE was grade 1-2 diarrhea and Abdominal pain.
Conclusion: The combination of SCRT, PD-1 inhibitor, and chemotherapy shows promising efficacy and significantly improve pCR rates in patients with MSS/pMMR high-risk LACC. SCRT could be safely delivered by high-resolution CT image-guided ART.