Association of KRAS mutations detected via liquid biopsy in metastatic non-small cell lung cancer patients with high levels of FDG-PET SUV.

Abstract

e20594 Background: We had previously evaluated the relationship between FDG-PET SUV with TP53 and KRAS mutations in formalin fixed paraffin embedded tissue (FFPE) in non-small cell lung cancers (NSCLC) in which genomic profiling had been performed. Considering FDG-PET SUV as a surrogate of glycolysis, we found TP53 and KRAS mutations were associated with increased glycolytic activity. The aim for this study was to evaluate KRAS and TP53 in circulating tumor DNA (ctDNA) in relation to FDG-PET SUV in a different cohort of NSCLCs in which genomic profiling was performed on peripheral blood. Methods: All stage IV NSCLC patients with genomic analysis from ctDNA and baseline FDG-PET scans between December 2014 and November 2016 were included. Associations between KRAS and TP53 mutations and maximal standard uptake value (SUVmax) were assessed using the Mann-Whitney and Kruskal-Wallis test. A subset analysis studying all KRAS positive patients from FFPE and ctDNA was performed based on the specific KRAS mutation. Results:122 patients had FDG-PET scans and genomic analyses of their circulating tumor cells. 62 (51%) patients had a TP53 mutation, 20 (17%) patients had a KRAS mutation, and 13 (11%) patients had both TP53 and KRAS mutations. Patients with a KRAS mutation had a higher SUVmax with a mean of 12.32 (p = 0.019). The presence of TP53 alone or concurrent TP53/KRAS was not significantly related to SUVmax. Analyzing 48 patients with KRAS mutation from FFPE and ctDNA assay, 16 patients had mutations of G12C and 9 patients had G12V. The presence of the G12C mutation was particularly highly correlated with higher SUVmax with a mean of 17.68 (p = 0.0006). Conclusions: In analyzing ctDNA, a larger cohort, mutations in KRAS had the strongest correlation with increased SUVmax. Targeting glycolysis and cellular metabolism could be a potential therapeutic strategy for patients with KRAS mutations. Although individual numbers are small, KRAS subtype analysis showed the presence of the G12C mutation might have the strongest relationship with SUV max and increased glycolysis.