Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies

Yoshiaki Nakamura, Hiroya Taniguchi, Masafumi Ikeda, Hideaki Bando, Ken Kato, Chigusa Morizane, Taito Esaki, Yoshito Komatsu, Yasuyuki Kawamoto, Naoki Takahashi, Makoto Ueno, Yoshinori Kagawa, Tomohiro Nishina, Takeshi Kato, Yoshiyuki Yamamoto, Junji Furuse, Tadamichi Denda, Hisato Kawakami, Eiji Oki, Takako NakajimaNaohiro Nishida, Kensei Yamaguchi, Hisateru Yasui, Masahiro Goto, Nobuhisa Matsuhashi, Koushiro Ohtsubo, Kentaro Yamazaki, Akihito Tsuji, Wataru Okamoto, Katsuya Tsuchihara, Takeharu Yamanaka, Izumi Miki, Yasutoshi Sakamoto, Hiroko Ichiki, Masayuki Hata, Riu Yamashita, Atsushi Ohtsu, Justin I. Odegaard, Takayuki Yoshino

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Comprehensive genomic profiling enables genomic biomarker detection in advanced solid tumors. Here, to evaluate the utility of circulating tumor DNA (ctDNA) genotyping, we compare trial enrollment using ctDNA sequencing in 1,687 patients with advanced gastrointestinal (GI) cancer in SCRUM-Japan GOZILA (no. UMIN000016343), an observational ctDNA-based screening study, to enrollment using tumor tissue sequencing in the same centers and network (GI-SCREEN, 5,621 patients). ctDNA genotyping significantly shortened the screening duration (11 versus 33 days, P < 0.0001) and improved the trial enrollment rate (9.5 versus 4.1%, P < 0.0001) without compromising treatment efficacy compared to tissue genotyping. We also describe the clonal architecture of ctDNA profiles in ~2,000 patients with advanced GI cancer, which reinforces the relevance of many targetable oncogenic drivers and highlights multiple new drivers as candidates for clinical development. ctDNA genotyping has the potential to accelerate innovation in precision medicine and its delivery to individual patients.

Original languageEnglish
JournalNature medicine
DOIs
Publication statusAccepted/In press - 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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