Next generation sequencing of circulating tumor DNA to monitor treatment response to nivolumab in advanced gastric cancer

2022 Fiscal Year Annual Research Report

• Project/Area Number: 20K07709
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: LOW SIEWKEE 公益財団法人がん研究会, がんプレシジョン医療研究センター 免疫ゲノム医療開発プロジェクト, 研究員 (40634720)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ctDNA / liquid biopsy / NGS / solid tumors

Outline of Annual Research Achievements

Immune checkpoint inhibitor (ICI) is an effective treatment for various solid tumors, however, a significant proportion of patients do not respond to ICI. The current proposal aims to evaluate the usefulness of circulating tumor DNA (ctDNA) to identify patients who are most likely to respond to ICI. Several biomarkers and tumor mutational burden (TMB) were reported to correlate with better ICI outcome.
Hybrid capture ultradeep targeted sequencing was conducted with ctDNA extracted from advanced non-small cell lung cancer (NSCLC) using a panel that consist of >500 genes for blood TMB evaluation. The mean coverage is about 1800X. More than 500 SNV, MNV and indels were detected in 250 genes. About 65% of patients were categorized as bTMB-high by using the threshold value of >=10mut/Mb.
In addition, ultra-low pass whole genome sequencing was conducted to assess the tumor fraction from liquid biopsy. Whole exome sequencing of liquid biopsy with high tumor fraction was established and conducted to assess the potential clinical utilities of liquid biopsy, especially from patients who receive ICI.

Research Products

• [Journal Article] Tumor-informed or tumor-agnostic circulating tumor DNA as a biomarker for risk of recurrence in resected colorectal cancer patients (2023)
  • Author(s): Chan Hiu Ting、Nagayama Satoshi、Otaki Masumi、Chin Yoon Ming、Fukunaga Yosuke、Ueno Masashi、Nakamura Yusuke、Low Siew-Kee
  • Journal Title: Frontiers in Oncology Volume: 12 Pages: 1055968(1)~(14)
  • DOI: 10.3389/fonc.2022.1055968
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tumor-Informed Approach Improved ctDNA Detection Rate in Resected Pancreatic Cancer (2022)
  • Author(s): Watanabe Kazunori、Nakamura Toru、Kimura Yasutoshi、Motoya Masayo、Kojima Shigeyuki、Kuraya Tomotaka、Murakami Takeshi、Kaneko Tsukasa、Shinohara Yoshihito、Kitayama Yosuke、Fukuda Keito、Hatanaka Kanako C.、Mitsuhashi Tomoko、Pittella-Silva Fabio、Yamaguchi Toshikazu、Hirano Satoshi、Nakamura Yusuke、Low Siew-Kee
  • Journal Title: International Journal of Molecular Sciences Volume: 23 Pages: 11521～11521
  • DOI: 10.3390/ijms231911521
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Circulating Tumor DNA-Based Genomic Profiling Assays in Adult Solid Tumors for Precision Oncology: Recent Advancements and Future Challenges (2022)
  • Author(s): Chan Hiu Ting、Chin Yoon Ming、Low Siew-Kee
  • Journal Title: Cancers Volume: 14 Pages: 3275～3275
  • DOI: 10.3390/cancers14133275
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Rapid genomic profiling of circulating tumor DNA in non-small cell lung cancer using Oncomine Precision Assay with GenexusTM integrated sequencer (2022)
  • Author(s): Low Siew-Kee、Ariyasu Ryo、Uchibori Ken、Hayashi Rie、Chan Hiu Ting、Chin Yoon Ming、Akita Takahiro、Harutani Yuhei、Kiritani Ayu、Tsugitomi Ryosuke、Manabe Ryo、Ogusu Shinsuke、Amino Yoshiaki、Kitazono Satoru、Yanagitani Noriko、Nakamura Yusuke、Nishio Makoto
  • Journal Title: Translational Lung Cancer Research Volume: 11 Pages: 711～721
  • DOI: 10.21037/tlcr-21-981
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serial circulating tumor DNA monitoring of CDK4/6 inhibitors response in metastatic breast cancer (2022)
  • Author(s): Chin Yoon Ming、Shibayama Tomoko、Chan Hiu Ting、Otaki Masumi、Hara Fumikata、Kobayashi Takayuki、Kobayashi Kokoro、Hosonaga Mari、Fukada Ippei、Inagaki Lina、Ono Makiko、Ito Yoshinori、Takahashi Shunji、Ohno Shinji、Ueno Takayuki、Nakamura Yusuke、Low Siew‐Kee
  • Journal Title: Cancer Science Volume: 113 Pages: 1808～1820
  • DOI: 10.1111/cas.15304
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Clinical implications and translational oncology of liquid biopsy (2022)
  • Author(s): SK Low, Y Nakamura
  • Organizer: 第６回Liquid Biopsy研究会
  • Invited
• [Presentation] Clinical utility and translational oncology of liquid biopsy in breast cancer management (2022)
  • Author(s): SK Low
  • Organizer: The 30th Annual Meeting of the Japanese Breast Cancer Society
  • Int'l Joint Research / Invited
• [Presentation] PRECIOUS Phase III trial of HER2 inhibitor re-treatment in HER2-positive breast cancer: liquid biopsy biomarker study (2022)
  • Author(s): YM Chin, HT Chan, R Ikegami, M Otaki, Y Nakamura, T Ueno, SK Low
  • Organizer: The 81st Annual Meeting of the Japanese Cancer Association
  • Int'l Joint Research
• [Presentation] Is liquid biopsy genomic profiling more than just a complement to tissue testing for advanced cancer patients? (2022)
  • Author(s): HT Chan, M Otaki, N Hayashi, YM Chin, I Fukada, N Fukuda, S Takahashi, Y Nakamura, SK Low
  • Organizer: The 81st Annual Meeting of the Japanese Cancer Association
  • Int'l Joint Research