ESTRO 2025 - Abstract Book

S1252

Clinical – Lower GI

ESTRO 2025

Conclusion: In patients who do not reach a confirmed clinical complete response, surgery is an integral part of multimodality management of LARC which improves patients' survival. Every effort should be made to convince patients with a non-complete response to undergo surgery after CRT to have the best possible outcome.

Keywords: Rectal Cancer, Surgery, Neoadjuvant radiotherapy

3785

Mini-Oral Radiotherapy followed by CAPOX and Tislelizumab in MSS locally advanced rectal cancer with resectable metastases: Results of the MIRACLE-1 study Menglong Zhou 1,2 , Lijun Shen 1,2 , Zezhi Shan 3,2 , Hui Zhang 1,2 , Juefeng Wan 1,2 , Wang Yang 1,2 , Yajie Chen 1,2 , Shujuan Zhou 1,2 , Dakui Luo 3,2 , Zilan Ye 3,2 , Weijing He 3,2 , Yufei Yang 3,2 , Yikuan Chen 3,2 , Changming Zhou 4,2 , Qingguo Li 3,2 , Xinxiang Li 3,2 , Fan Xia 1,2 , Zhen Zhang 1,2 1 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. 2 Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China. 3 Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. 4 Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, China Purpose/Objective: MSS tumors account for 95% of metastatic colorectal cancer and are characterized by a low response rate to immunotherapy. Emerging evidence showed that radiotherapy combined with chemotherapy and PD-1 inhibitors led to promising tumor responses in patients (pts) with locally advanced rectal cancer (LARC). MIRACLE-1 aims to investigate the safety and efficacy of such approach as upfront treatment of MSS LARC with resectable metastases. Material/Methods: MIRALCE-1 was a prospective, single arm, phase 2 study. The main inclusion criteria include MSS LARC with a distance of ≤10 cm from the anus by MRI evaluation and a limited number of metastases in the liver and/or lungs that were eligible for curable resection. Eligible patients were treated with upfront radiotherapy including hypofractionated radiotherapy (HFRT) for primary lesions and HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions. Afterwards, six cycles of systemic therapy consisted of CAPOX and Tislelizumab were administered. Then, reassessment was performed within 4 weeks afterwards by radiological and serological evaluations. Surgical resection, local ablative therapies or active surveillance was applied based on tumor response. For patients attained no-evidence of disease (NED), Tislelizumab was maintained until one year after surgery. Otherwise, the subsequent treatment was determined by the investigators. The primary endpoint is the 1-year NED rate. The secondary endpoints include objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicities. Results: From March 2023 to November 2024, 38 pts were enrolled and 20 were evaluable. At baseline, 60.0% of pts were male, median age was 57 years (range 34-71), 55.0% had liver metastases (mets), 15.0% had lung mets, and 30.0% had both liver and lung mets. 80.0% primary tumors had RAS/BRAF mutations. Upon reassessment, 18 (90.0%) pts had partial response (PR) and 2 (10.0%) had stable disease (SD). No patients showed progressive disease (PD). The ORR was 90.0%. 65% (13/20) pts attained NED. Median PFS and OS have not yet reached. No grade 5 adverse events occurred. The most common treatment-related adverse events (TRAEs) in all grades were fatigue (85.0%), thrombocytopenia (65.0%), leukopenia (50.0%) and anemia (40.0%). The most frequent grade 3/4 TRAEs were thrombocytopenia (30.0%) and neutropenia (20.0%).