KRAS mutation effects on the 2-[18F]FDG PET uptake of colorectal adenocarcinoma metastases in the liver

Abstract

Background: Deriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regards to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM). Methods : 2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of 37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in different commercially available software packages. PET standard uptake values (SUV) were corrected for: 1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter; and 2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak, and maximum SUV were investigated using Student ’ s t-test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis. These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SUR_mean, SUR_peak, and SUR_max , respectively. Results: Fifteen patients harbored KRAS missense mutations ( KRAS+ ) while another 3 harbored KRAS gene amplification. For 31 lesions the mutational status was derived from the PET/CT-guided biopsy. The Student ’ s-t p-values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SUR MAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve (AUC) = 0.77 and 0.75 for the two different segmentations respectively with a mean specificity of 0.69 and sensitivity of 0.85. Conclusions: The correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.