Background & Aims: Next-generation sequencing (NGS) that enables the analyses of massively parallel sequences of DNA can advance the understanding of the underlying molecular pathophysiologies of cancer. Such recent genomic analyses have revealed a complex mutational landscape for PDACs. The aims of this study were to investigate the genomic profile to predict the chemotherapy response in unresectable PDACs.

Methods: The total of 80 pathologically confirmed PDACs were enrolled and genomic DNA was extracted and quality control metrics of DNA analytes were measured. The specimens that passed a quality control test underwent targeted deep sequencing using a customized cancer panel (CancerSCAN) enriched in the exons of 83 genes.

Results: Clinical prognostic factors associated with survival in PDAC were gender, tumor mass size, stage and chemotherapy response rate. (P=0.078, 0.009, 0.052 and <0.001, respectively). Multivariate Cox proportional-hazards analysis revealed chemotherapy response rate (P < 0.001, hazard ratio (HR) = 1.908, 95% CI, 1.281 to 2.840) is an independent prognostic factor. There were 56 (71%) and 9 (11%) study patients who underwent gemcitabine based chemotherapy and FOLFIRINOX respectively. Response rate of study patients were as follows; CR+PR 14 (20%), SD (27%) and PD 28 (41%). There were only 9 (16%) and 4 (50%) patients who had CR+PR response gemcitabine based chemotherapy and FOLFIRINOX respectively.

Conclusion: Targeted sequencing using EUS-FNA specimens in PDAC showed excellent compatibilities to analyze genomic profiles of PDACs. Furthermore, novel genes associated with survival, metastasis and chemotherapy response in PDAC were identified.

Citation Format: Joo Kyung Park, Kwang Hyuck Lee, Donghyun Park, Woong-Yang Park, Dae-Soon Son, Jong Kyun Lee, Kyu Taek Lee. Detection of genetic alterations to predict the chemotherapeutic responses in unresectable pancreatic ductal adenocarcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 423. doi:10.1158/1538-7445.AM2017-423