Yttrium-90 radioembolization for colorectal cancer liver metastases: a prospective cohort study on circulating angiogenic factors and treatment response

Background: Yttrium-90 radioembolization (Y-90-RE) as a treatment for liver tumours induces radiation damage and hypoxia in liver tissue, which is also a trigger for systemic release of angiogenic factors, potentially stimulating tumour growth. We examined changes in circulating angiogenic factors following Y-90-RE and investigated the association between response and angiogenic factors. In this prospective study, 42 patients with unresectable, chemorefractory metastatic colorectal cancer (CRCLM) were treated with Y-90-RE. Blood samples were collected pre-treatment and at 0, 1, 3, 7 and 30 days of follow-up. Response was measured with MRI according to RECIST 1.1 at 1 month and subsequently 3-month interval until progressive disease (PD) occurred. Associations between circulating angiogenic factors and response were examined with linear mixed model analysis. Results: Following Y-90-RE, three angiogenic factors demonstrated an increase in plasma levels, i.e., vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and angiopoietin-2 (Ang-2). Non-responders (= PD at 1-month follow-up, n = 10) had a significant increase of Ang-2 and HGF at 3 and 7 days post treatment compared to responders (= stable disease or better, n = 32), who showed little to no changes in plasma levels (respectively p = 0.01 and p = 0.007). Median overall survival was 9.2 months (95% confidence interval 6.1-12.4). Conclusions: Significant increases in plasma levels of Ang-2 and HGF in the first week after treatment were associated with rapid progressive disease of liver lesions at 1 month after Y-90-RE. Combination of Y-90-RE with anti-angiogenic therapy may reduce these effects and result in better response.