Relationship between FDG-PET/CT scans and KRAS Mutations in Metastatic Colorectal Cancer

Abstract

A number of studies have shown that KRAS mutations in colorectal cancer (CRC) result in the lack of response to anti-epidermal growth factor receptor (EGFR)-based therapy; thus, KRAS mutational testing has been incorporated into routine clinical practice. However, one limitation of this test is the heterogeneity of KRAS status, which can either be intratumoral heterogeneity within an individual primary CRC, or discordant KRAS status between a primary CRC and its corresponding metastases. We previously reported that fluorodeoxyglucose (FDG) accumulation was significantly higher in primary CRCs with mutated KRAS than in those with wild-type KRAS. However, the clinical utility of the previous report has been limited because endoscopic biopsy for testing KRAS status is safe and feasible only in primary CRC. The purpose of this study was to investigate whether KRAS status is associated with FDG accumulation in metastatic CRC, and whether FDG-Positron emission tomography/computed tomography (PET/CT) scans can be used to predict the KRAS status of metastatic CRC. Methods: A retrospective analysis was performed on 55 metastatic CRC tumors that were identified by FDG-PET/CT before surgical resection. Maximum standardized uptake value (SUV_max) of the respective metastatic tumor was calculated from FDG accumulation. Results: From the analysis with the 55 tumors, no significant correlation was found between SUV_max and KRAS status. We next analyzed only tumors larger than 10mm to minimize the bias of partial volume effect, and found that SUV_max was significantly higher in the KRAS mutated group than in the wild-type group (8.3 ± 4.1 vs. 5.7 ± 2.4, respectively; P = 0.03). Multivariate analysis indicated that SUV_max remained significantly associated with KRAS mutations (P = 0.04). KRAS status could be predicted with an accuracy of 71.4% when SUV_max cutoff value of 6.0 was used. Conclusion: FDG accumulation into metastatic CRC was associated with KRAS status. FDG-PET/CT scans may be useful for predicting the KRAS status of metastatic CRC, and help in determining the therapeutic strategies against metastatic CRC.