Abstract 5682: Circulating tumour DNA following decompression using selfexpandable metallic stent

Abstract Background: Decompression using selfexpandable metallic stent (SEMS) has been reported to improve short-term outcomes in patients with malignant large bowel obstruction (MLBO). However, some reports suggest that SEMS worsen long-term survival. Conversely, trans-anal drainage tubes (TDT), which are similar to the ileus tubes widely used in Japan for MLBO, have had no reports suggesting reduced survival. SEMS worsen long-term survival by compressing tumor continuously and induce tumor cell death which can lead production of various types of mediator which could negatively affect prognosis. In this study, we investigated tumor cell death induced by decompression procedure by using circulating tumour DNA (ctDNA). Methods: Plasma samples were obtained before and 1, 3 and 7 days after decompression. First, we purified circulating cell free DNA (ccfDNA) from 1 mL of plasma and measured the concentration using fluorometer. Second, we measured mutated fragment of ccfDNA (circulating tumour DNA) which is derived from tumor cell. Mutational analysis from the main tumour was performed using Ion PGM™ Sequencer following library preparation with Ampliseq CHPver.2 (Thermo Fisher Scientific). Each mutant fragment in ccfDNA was quantified using digital PCR (QuantStudio 3D® digital PCR system). Results: We enrolled 30 patients (22 SEMS and 8 TDT). CcfDNA levels on day7 was significantly increased in the SEMS group (before; 623ng/ml, day7; 1455ng/ml, p=0.006) but TDT group. Sequencing result revealed that the average number of mutation per tumor was 3.7 (e.g. APC, TP53, and KRAS) out of 50 genes. Mutant fragments (ctDNA) were detected in the ccfDNA in all cases. Mutant fragment also increased after decompression in SEMS group(before; 6.2copies/μl, day3; 22.6copies/μl, p=0.03)but in TDT group. Conclusion: SEMS insertions increased plasma levels of not only ccfDNA but also ctDNA in patients with MLBO. This indicated that SEMS would induce massive cancer cell death. This tumor cell death can drain various mediators, including DAMPs, into blood flow and may worsen prognosis of patients with MLBO. Conversely, TDT may not induce massive tumor cell death. Citation Format: Goro Takahashi, Takeshi Yamada, Takuma Iwai, Kohki Takeda, Michihiro Koizumi, Seiichi Shinji, Yasuyuki Yokoyama, Keisuke Hara, Hiroyasu Furuki, Atsushi Watanabe, Keiichro Ohta, Eiji Uchida. Circulating tumour DNA following decompression using selfexpandable metallic stent [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 5682. doi:10.1158/1538-7445.AM2017-5682