Citations 1
Real-world Monitoring of ctDNA Reliably Predicts Cancer Recurrence and Treatment Efficacy in Patients with Resected Stages I-III Colon Cancer
Cohen, Stacey A. , Aushev, Vasily N. , Nagarajan, Arun , Wang, Chongkai , Alyunis, Fadhel, Tejani, Mohamedtaki Abdulaziz, Alqahtani, Ali , Marshall, John C., Chang, Jeremy , Manage, Kevin, George, Giby V., Malhotra, Meenakshi , Chandana, Sreenivasa R , Mehler, Shoshana , Somer, Bradley G. , Babadi, Ellie, Hanna, Diana L. , Chidharla, Anusha , Kasi, Anup , Vosoughi, Elham , Briski, Robert , Azzi, Georges, Katiyar, Vatsala , Sharma, Vivek R. , Shreenivas, Aditya , Fuqua, Jacob , Malla, Midhun , Polite, Blasé N. , Bent, Alisha H., Liu, Minetta C. , Aleshin, Alexey , Cohen, Stacey A , Laliotis, George , Jabbal, Iktej Singh , Fakih, Marwan , Sharif, Saima , Botta, Gregory P. , George, Giby V., Sharma, Shruti , Wu, Christina N. , Dayyani, Farshid , Pedersen, Katrina S. , Chan, Abigail Sy , Chakrabarti, Sakti , Bent, Alisha , Rabinowitz, Matthew , Jurdi, Adham Adel , Kopetz, Scott
Annals of Surgery | August 7, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available
Objective: In this study, we evaluate the utility of ctDNA analysis in a large cohort of patients for whom ctDNA testing was ordered commercially with real-world application. Summary Background Data: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for assessing post-surgical molecular residual disease (MRD) and response to treatment. Methods: A real-world data analysis was performed using commercial ctDNA testing (SignateraTM) from patients (N=795, n=5,971 plasma samples) with stage I-III colon cancer treated at multiple US institutions. The association of ctDNA detection within the MRD window, during surveillance, and the impact of ACT was correlated with patient outcomes. Results: ctDNA-positive patients during the MRD window and surveillance showed significantly shorter DFS compared to ctDNA-negative patients (hazard ratio (HR): 9.85, P<0.0001; HR: 26.91, P<0.0001). Multivariate analysis of the MRD window revealed ctDNA-positivity as the most significant factor associated with inferior DFS (adjHR: 7.7, P<0.001). MRD-positive patients who received ACT showed improved DFS compared to patients observed post-surgery (adjHR: 6.1, FDR adj P=0.0007). No ACT benefit was observed in MRD-negative patients (adj HR: 1.20, FDR adj P=0.768). On evaluating ctDNA dynamics from MRD to surveillance, patients who remained ctDNA-positive or converted from negative to positive showed a significantly inferior DFS (HR: 34.40, P<0.0001; HR: 13.65, P<0.0001) compared to persistently ctDNA-negative patients. Conclusions: Postsurgical ctDNA detection is prognostic of relapse and potentially predictive of ACT benefit in patients with resectable colon cancer, which may enable personalized surveillance, intervention, and/or trial options, ultimately improving patient outcomes.