P1.02-039 Assessment of KRAS mutations (by Digital PCR) in Circulating Tumoral DNA from Lung Adenocarcinoma Patients

Abstract

KRAS mutations are detected in approximately 25% of lung adenocarcinomas (LA). Targeted therapies against KRAS are under investigation. The use of tumor biopsy for molecular testing may be challenging due to the invasiveness of the procedure, the limited material for multiple biomarker analyses and tumor heterogeneity. Mutation detection in circulating cell-free tumor DNA (ctDNA) can overcome these caveats and also be used for tracking tumor dynamics. The aim of this study was to evaluate KRAS mutation detection in plasma samples from LA. Plasma samples from 35 patients with histologically confirmed KRAS mutant LA were collected at initiation of chemotherapy. KRAS mutations were assessed using digital PCR technology (QuantStudio3D Digital PCR System, Thermofisher Scientific). Correlation between ctDNA and tumor biopsies in terms of mutation detection was analyzed. In 5 cases plasma samples were obtained during the course of the disease to monitor clonal dynamics. Most cases were male (71%), with stage IV disease (83%), and showed KRAS mutation on codon12 (94%). KRAS mutation was found in plasma samples in 28/35 cases, showing a concordance with the tumor of 80%. In patients whose disease was limited to thorax (stages II, III, and IVa) KRAS mutation was detected in 7/10 (70%) plasma samples. Plasma/tumor biopsy concordance in cases with extra-thoracic metastases was 84% (21/25). The 4 false negative cases had low burden of extra-thoracic disease, with bone (2 cases), brain (1 case), and abdominal lymph node (1 case) as the only metastatic location outside the thorax. KRAS clonal dynamics in plasma showed a good correlation with treatment responses in some cases (figure 1). High concordance in the detection of KRAS mutations was found between plasma and tumor tissue using digital PCR technology, particularly in cases with extra-thoracic disease. Digital PCR allows for tracking clonal dynamics in KRAS mutant LA.