A prospective randomized controlled trial of FAPI PET/CT-guided radiotherapy combined with second-line standard systemic treatment and cadonilimab versus second-line standard systemic treatment alone in patients with peritoneal metastasis from colore

3545 Background: This study evaluates the efficacy and safety of FAPI PET/CT-guided radiotherapy combined with second-line systemic treatment and cadonilimab compared to second-line systemic treatment alone in patients with peritoneal metastasis from colorectal cancer. Methods: In this prospective randomized controlled trial, we enrolled patients with peritoneal metastasis from colorectal cancer who progressed after first-line systemic therapy. Patients were randomly assigned to the control group, receiving second-line standard systemic treatment (n = 20), or the study group, which received hyopfractionated radiotherapy (20-25 Gy in 5 fractions) combined with second-line systemic treatment and cadonilimab (n = 20). The primary endpoint was overall response rate (ORR). A total of 40 patients were enrolled, with 19 evaluable patients in each group following loss to follow-up. Results: The ORR was significantly higher in the study group at 63.2% (12/19) compared to 15.8% (3/19) in the control group (p = 0.003). Adverse events (AEs) of grade 3-4 in the study group included neutropenia (26.3%, 5/19), nausea (15.8%, 3/19), vomiting (15.8%, 3/19), and diarrhea (15.8%, 3/19). In the control group, the most common grade 3-4 AE was neutropenia (21.1%, 4/19) and vomiting (10.5%, 2/19). Immune-related AEs of grades 1-2 in the study group included skin reactions (15.8%, 3/19), hypothyroidism (5.3%, 1/19), hepatitis (5.3%, 1/19), and myocarditis (15.8%, 3/19). One case of grade 3-4 skin reaction (5.3%) was observed in the study group. Conclusions: FAPI PET/CT-guided radiotherapy combined with second-line systemic treatment and cadonilimab significantly improves ORR in patients with peritoneal metastasis from colorectal cancer compared to standard second-line treatment alone, with manageable toxicity profiles. These findings support a promising therapeutic strategy for this challenging patient population. Clinical trial information: NCT07079462 .