Circulating tumor DNA monitoring in esophageal squamous cell carcinoma patients

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10605
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Iwate Medical University
• Principal Investigator: Takeshi Iwaya 岩手医科大学, 医学部, 特任准教授 (70405801)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 食道癌 / circulating tumor DNA / 変異

Outline of Final Research Achievements

Esophageal squamous cell carcinoma (ESCC) is a poor prognosis tumor. Analysis of circulating tumor DNA (ctDNA) has demonstrated promising results for cancer diagnosis. However, ctDNA test hasn’t yet been an established tool in daily practice of cancer patients. This study aimed to investigate whether frequent tumor burden monitoring with ctDNA of individual tumor-specific mutations using digital PCR (dPCR) provides clinically useful information for ESCC patients. Mutation screening of primary ESCCs was performed with amplicon sequencing using originally-designed SCC panel, targeting 31 genes. The level of ctDNAs were evaluated using dPCR with originally-designed primer/probe sets for individual mutations. 27). This study demonstrated clinical validities of tumor burden monitoring with patient-specific ctDNA using dPCR in standard-of-care for ESCC patients including: 1) relapse and growth prediction, 2) treatment efficacy evaluation, and 3) relapse-free confirmation.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

次世代シークエンサー (NGS)を用いたctDNA解析は、組織採取困難な症例の癌診断や薬剤の投薬根拠となる変異の検出などいわゆるLiquid biopsyに適した方法である。しかし、治療期間での頻回な検査や長期間のfollow upなど広く多数の癌患者で行うことは、コストや解析時間を要する。また微量なctDNAはいずれの手法を用いても、偽陽性・偽陰性は完全に避けられないため、異なる手法による検証も必要である。治療法決定に多くの情報が必要な場合のNGS解析と治療効果の頻回な判定、長期間の再発モニタリングにはdigital PCRと合わせた効率的システムを確立した。