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 206 CC patients and in in-silico datasets (Salazar et al. JCO 2010 in press). The profile was translated into a robust diagnostic test (ColoPrint) using customized 8-pack arrays. For this study, 233 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 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 135 stage II patients, ColoPrint identified most patients (73%) as low risk. The 5-year distant-metastasis free survival was 95% for low-risk patients and 80% 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 4.1 (95% CI 1.31-13.01, p=0.009). 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 2.3; 95% CI 0.68-7.53, p=0.18) and did not add power to the ColoPrint classification. These results are in good agreement with results from the first independent validation. 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 be safely managed without chemotherapy.
Publication Name: ASCO GI 2011