Chemotherapy Treatment Response of Colorectal Cancer Liver Metastases: A Prospective Multicenter Follow-up Study with MRI, DWI and 1H-MRS Compared with Histology

Figure legend: A gadolinium enhanced T1 VIBE MRI of a liver metastasis before (A) and after (B) chemotherapy. The corresponding apparent diffusion coefficient (ADC) maps calculated from diffusion weighted images (DWI) of the same tumor before (C) and after systemic therapy (D). The C-formed rim between the yellow and red linings was the postulated active tumor area. Purpose: Liver metastases in colorectal cancer respond to chemotherapy and targeted agents not only by shrinking, but also by morphological and metabolic changes. The aim of this study was to explore how these changes can be detected with advanced MRI imaging. Methods: We investigated contrast-enhanced magnetic resonance imaging (MRI), apparent diffusion coefficient (ADC) in diffusion weighted imaging, and 1H-magnetic resonance spectroscopy (1H-MRS) in detecting early morphological and metabolic changes in borderline or resectable liver metastases, as a response to first line neoadjuvant or conversion therapy in a prospective substudy of the RAXO (NCT01531621). MRI findings were compared with histology of resected liver metastases and outcome as overall survival (OS). Results: In 2012–2018, 52 patients at four Finnish University Hospitals were recruited and 47 received neoadjuvant or conversion chemotherapy. Liver resection was performed in 40. Low ADC values (below median), of the representative liver metastases, at baseline and after systemic therapy associated with partial response according to RECIST criteria, but not with morphological MRI changes or histology. Decreasing ADC values with systemic therapy were associated with improved OS versus increasing values, both after liver resection (5-year OS-rate 100% and 34%, respectively, p=0.022) and with systemic therapy (5-year OS-rate 62% and 23%, p=0.049). 1H-MRS associated with steatohepatosis induced by systemic therapy. Conclusion: Lower ADC values at baseline or during systemic therapy are not associated with morphological or metabolic changes, but predict better response to oncological treatment. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.