Abstract 512: KRAS mutation in cell-free DNA was correlated with treatment response to gemcitabine/cisplatin chemotherapy in patients with pancreatic cancer

Abstract Cell-free DNA (cfDNA) of cancer patients has been known to be a useful marker for minimal residual disease detection and treatment monitoring. However, there are a few studies which showed correlation of cfDNA with pancreatic cancer treatment. Here we investigated applicability of cfDNA as a response and prognosis biomarker through comparing the qualitative and quantitative changes of the KRAS mutant in the patients with pancreatic cancer before and after treatment. Total of 44 pancreatic cancer patients who treated by gemcitabine and cisplatin included in the study. Serum from the blood samples was separated by centrifugation through the method established. cfDNA was extracted through the QIAamp Circulating Nucleic Acid Kit (Qiagen, Germany) from 0.8 ml of serum. Extracted cfDNA was quantified using the Qubit dsDNA HS Assay Kit (Thermo Fisher Scientific, USA). QX200 Droplet Digital PCR System (Biorad, USA) was applied to measure frequency of KRAS mutation. We performed digital PCR with KRAS screening multiplex droplet digital PCR kit which covers G12A, G12C, G12D, G12R, G12S, G12V and G13D sites (Biorad, USA). Mutant concentration and fractional abundance were analyzed by QuantaSoft software (Biorad, USA). The positive rate of KRAS mutation was 61% (27/44) and 47% (16/34) in before and after treatment. When we analyzed the treatment response according to the positive presence of KRAS mutation before treatment, 50% and 61% of KRAS mutations were observed in patients who showed either partial response (PR) or stable disease (SD) after chemotherapy, respectively. However, all the 5 patients (100%) with progressive disease (PD) showed KRAS mutation implicating significant correlation (p = 0.046) with treatment response. The fraction change of KRAS mutation was showed decrease in 18 (58.1%) patients and increase in 13 (41.9%) patients comparing before and after treatment status. When we observed the association the fraction change direction (decrease vs. increase) with the survival, there was no significant difference. These results implicate that KRAS mutation in cell-free DNA might be associated with treatment response to gemcitabine/cisplatin chemotherapy. In further studies, we will conduct in prospective study for pancreatic cancer patients. (This study was supported by National cancer center, Korea, Grant no. 1510203-1) Citation Format: Min Kyeong Kim, Yoon Kyong-Ah, Woo Sang Myung, Kim Yun Hee, Park Sang Jae, Kong Sun-Young. KRAS mutation in cell-free DNA was correlated with treatment response to gemcitabine/cisplatin chemotherapy in patients with pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 512.