Independent validation of a prognostic genomic profile (ColoPrint) for stage II colon cancer (CC) patients.

Abstract

3513 Background: Adjuvant therapy is not routinely recommended for stage II CC patients but may be considered for high-risk patients. In this study we aim to independently validate a genomic profile that was developed to identify high risk patients and can assist in treatment decisions. Methods: An 18-gene profile had been developed using gene expression data from whole genome Agilent 44K oligonucleotide arrays and was validated in samples from an independent cohort of 178 stage II/III CC patients and in in silico datasets (Salazar et al. 2010 submitted). The profile was translated into a robust diagnostic test (ColoPrint) using the Agilent 8-pack arrays. For this study, 232 patients who underwent curative resection (R0) for colon cancer stages II or III at the Klinikum rechts der Isar from 1987 to 2003 were selected. Fresh frozen tissues, clinical parameters and follow-up data for all patients were available. The samples were hybridized to 8- pack arrays and the ColoPrint index was determined for all samples blinded from the clinical data. Results: Patients in this study had a median age of 64 years and median follow-up of 97 months. The median number of resected lymph nodes was 21, giving an indirect measure of the quality of surgery. In the 137 stage II patients, ColoPrint identified most patients (74%) as low risk. The 5-year distant-metastasis-free survival was 95% for low risk patients and 79.9% for high risk patients. In the univariate analysis, ColoPrint was the only significant parameter to predict the development of distant metastasis with a HR of 4.3 (95% CI 1.36-13.56, p = 0.007). Using clinical parameters from the ASCO recommendation (T4, perforation, less than 12 LN assessed and/ or high grade) for the identification of high-risk patients was not significant (HR 2.1; 95% CI 0.64-7.04, p = 0.2) and did not add power to the ColoPrint classification. Risk assessment by ColoPrint in mostly treated stage III patients (n = 97) classified 75% as low risk and 25% as high risk and was not significantly correlated. Conclusions: ColoPrint is able to predict the development of distant metastasis of stage II colon cancer patients and facilitates the identification of patients who may benefit from adjuvant chemotherapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Agendia Agendia