TY - JOUR
T1 - Yttrium-90 radioembolization for colorectal cancer liver metastases
T2 - a prospective cohort study on circulating angiogenic factors and treatment response
AU - Rosenbaum, C E N M
AU - van den Hoven, A F
AU - Braat, M N G J A
AU - Koopman, M
AU - Lam, M G E H
AU - Zonnenberg, B A
AU - Verkooijen, H M
AU - van den Bosch, Maurice
PY - 2016/12
Y1 - 2016/12
N2 - BACKGROUND: Yttrium-90 radioembolization ((90)Y-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 (90)Y-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 (90)Y-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 (90)Y-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 (90)Y-RE. Combination of (90)Y-RE with anti-angiogenic therapy may reduce these effects and result in better response.
AB - BACKGROUND: Yttrium-90 radioembolization ((90)Y-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 (90)Y-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 (90)Y-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 (90)Y-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 (90)Y-RE. Combination of (90)Y-RE with anti-angiogenic therapy may reduce these effects and result in better response.
KW - Yttrium-90 radioembolization
KW - Colorectal cancer liver metastases
KW - Angiogenesis
U2 - 10.1186/s13550-016-0236-1
DO - 10.1186/s13550-016-0236-1
M3 - Article
C2 - 28004357
SN - 2197-7364
VL - 6
JO - EJNMMI physics
JF - EJNMMI physics
M1 - 6:92
ER -