Dynamic contrast-enhanced computed tomography as a potential biomarker in patients with metastatic colorectal cancer treated with regorafenib. (July 2019) - Andersen, Iben R
Background: RECIST 1.1 presents challenges when evaluating treatment response to angiogenesis inhibitors. The objective response rate, when evaluating the treatment effect of regorafenib, using RECIST 1.1, is < 2% and beneficial treatment could erroneously be terminated. Dynamic contrast-enhanced computed tomography (DCE-CT) has potential as a non-invasive functional imaging biomarker, by quantifying the treatment effect of this targeted therapy. Purpose: To evaluate three-dimensional (3D) tumor dynamic parameters representing tumor microcirculation assessed by DCE-CT during the treatment with regorafenib in a cohort of patients with treatment-refractory metastatic colorectal cancer. Material and Methods: Thirty-three patients with colorectal metastases (27 liver lesions, three abdominal lesions, and three pulmonary lesions) were treated with regorafenib and evaluated using DCE-CT. A total of 112 DCE-CT scans were analyzed using Advanced Perfusion and Permeability Application and correlated to standard contrast-enhanced computed tomography (CE-CT) evaluated using RECIST 1.1. Results: A significant decrease in most DCE-CT parameters, a simultaneous decrease in tumor attenuation and an increase in tumor volume were detected during treatment. However, no associations were found between the DCE-CT parameters and PFS or OS using simple COX proportional hazards regression. Conclusion: In this exploratory study, a significant decrease in most dynamic parameters suggests an overall treatment effect of regorafenib in tumor vasculature. DCE-CT may assist in an objective evaluation of these responses compared to RECIST. The anti-angiogenic changes could not be associated with treatment outcome in terms of PFS and OS, which might be due to the small cohort or a rather limited survival benefit in this pre-medicated treatment-refractory group of patients.