P-235Prognostic biomarkers after colorectal liver metastasis resection: Exploratory study for VEGF, VEGFR and SPARC expression

Introduction: Patients with liver metastasis from colorectal cancer (CRLM) may achieve prolonged survival after complete resection, although many of these patients will relapse and die of their disease. The optimal systemic therapy in the peri-operative setting is still unknown. The identification of biomarkers to predict relapse and response to treatment is also an unmet need. Methods: We retrospectively analyzed 24 patients who underwent neoadjuvant chemotherapy plus bevacizumab followed by curative resection of CRLM at our institution from 2006 to 2015. We evaluated VEGF-A, VEGF-R1, VEGF-R2 and SPARC expression by immunohistochemical (IHC) staining in the liver metastasis specimen. Relapse-free survival (RFS) was analysed by Cox regression. Results: The following basal characteristics were found for the cohort: median age at the time of surgery was 62 years, 42% were male, ECOG was 0 or 1 in 96%, well-differentiated histology in 88%, right-sided primary site in 38%, mutant RAS in 58%. 81% of the patients received treatment with FOLFOX or XELOX as neoadjuvant regimen, and 35% of the patients continued bevacizumab in the adjuvant setting. After neoadjuvant treatment RECIST criteria for CR/PR/SD were met for 12/56/28% of the patients, R0 resection was achieved in 58%, and a level of pathological regression of < 10%, 11-50% and >50% was found in 26%, 37% and 37% of the cases. At the time of the analysis 69% of the patients had relapsed and 27% had deceased. Radiological response by RECIST (CR+PR) was not predictive for RFS (HR 0.77, p = 0.6, 95%CI 0.27-2.24). Pathological response >50% was associated with a non-significant better RFS (HR 0.53, p = 0.245, 95%CI 0.18-1.55). VEGF overexpression (32%) was associated with a significant worse RFS (HR 15.43, p = 0.001, 95%CI 2.95-80.85). VEGF-R1 overexpression (53%) was associated with a non-significant worse RFS (HR 1.16, p = 0.780, 95%CI 0.40-3.37). VEGF-R2 IHC staining failed. SPARC overexpression (58%) showed a trend towards a worse RFS (HR 3.01, p = 0.069, 95%CI 0.92-9.82). Kaplan-Meier curves are shown in figure 1. Conclusion: VEGF and SPARC overexpression in CRLM may predict a shorter RFS after liver surgery. We found no statistically significant impact in survival for VEGF-R1 expression. Overall survival and prospective recruitment is ongoing to confirm these exploratory results.