Correlation of high levels of immature blood vessels in colorectal tumors with longer survival following bevacizumab treatment.

Abstract

10586 Background: Bevacizumab improves overall survival in metastatic colorectal cancer patients. Bevacizumab is a first line treatment in all metastatic colorectal cancer patients, however only 38-44% respond. Currently, there is no good marker to depict treatment response. Tumour microvascular density has been shown be a prognostic factor in late stage colorectal cancer patients, however, it does not predict response. Blood vessels mature by the recruitment of pericytes. We hypothesise blood vessels that lack pericytes will be more susceptible to regression and these tumours may benefit from targeting with bevacizumab. Methods: 80 patients had a primary colorectal cancer resection and were subsequently treated with bevacizumab in our tertiary referral centre of excellence. Tumours were stained using dual immunofluorescence staining for factor VIII (an endothelial marker) and α-smooth muscle actin (a pericyte marker). Levels of immature and mature blood vessels were screened using fluorescent microscopy, scoring multiple fields of view. The mean levels of immature and mature blood vessels were scored and correlated with overall and progression free survival using Spearman correlations and multivariate analyses. Results: 37 patients were metastatic at diagnosis and 43 were initially Duke’s A, B or C at diagnosis (early stage) and subsequently developed metastases. Mean duration on bevacizumab was 10.6 months. Mean overall survival was 38.6 months. Interestingly, there was no difference between levels of immature and mature vessels in tumours of early stage patients and metastatic patients. Patients with higher levels of immature blood vessels had longer survival following treatment (p value = 0.026). This remained significant following multivariate analyses correcting for gender, stage at diagnosis, whether patients received chemotherapy before or after treatment with bevacizumab and whether or not bevacizumab was first line or not. Conclusions: We have shown for the first time that the maturity levels of blood vessels in tumours significantly correlates to survival following treatment with bevacizumab.