Dynamic contrast-enhanced computed tomography as a potential biomarker in patients with metastatic colorectal cancer treated with regorafenib

摘要

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.