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Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies
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.
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“This highlights the possible utility of liquid biopsies for molecular genotyping, facilitating more rapid patient access to targeted therapy options in the future (30).”
From Efficacy and Safety of Adagrasib plus Cetuximab in Patients with KRAS G12C-Mutated Metastatic Colorectal Cancer (2024) · cites this paper as [30]
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Metadata
- Authors
- Nakamura, Y., Taniguchi, H., Ikeda, M., Bando, H., Kato, K., Morizane, C., Esaki, T., Komatsu, Y., Kawamoto, Y., Takahashi, N., Ueno, M., Kagawa, Y., Nishina, T., Kato, T., Yamamoto, Y., Furuse, J., Denda, T., Kawakami, H., Oki, E., Nakajima, T., Nishida, N., Yamaguchi, K., Yasui, H., Goto, M., Matsuhashi, N., Ohtsubo, K., Yamazaki, K., Tsuji, A., Okamoto, W., Tsuchihara, K., Yamanaka, T., Miki, I., Sakamoto, Y., Ichiki, H., Hata, M., Yamashita, R., Ohtsu, A., Odegaard, J. I., & Yoshino, T.
- Affiliations
- National Cancer Center Hospital East (JP)
- Aichi Cancer Center (JP)
- National Cancer Center Hospital (JP)
- National Hospital Organization Kyushu Cancer Center (JP)
- Hokkaido University Hospital (JP)
- Saitama Cancer Center (JP)
- Kanagawa Cancer Center (JP)
- Kansai Rosai Hospital (JP)
- Shikoku Cancer Center (JP)
- Osaka National Hospital (JP)
- University of Tsukuba Hospital (JP)
- Kyorin University Hospital (JP)
- Chiba Cancer Center (JP)
- Kindai University Hospital (JP)
- Kyushu University (JP)
- St. Marianna University School of Medicine (JP)
- The University of Osaka (JP)
- The Cancer Institute Hospital (JP)
- Kobe Medical Center (JP)
- Osaka Medical and Pharmaceutical University Hospital (JP)
- Gifu University (JP)
- Kanazawa University (JP)
- Shizuoka Cancer Center (JP)
- Kagawa University Hospital (JP)
- Hiroshima University Hospital (JP)
- Guardant (United States) (US)
- Corresponding author
- Yoshino, Takayuki
- ORCID
- Nakamura, Yoshiaki
- Taniguchi, Hiroya
- Ikeda, Masafumi
- Bando, Hideaki
- Kato, Ken
- Morizane, Chigusa
- Esaki, Taito
- Komatsu, Yoshito
- Kawamoto, Yasuyuki
- Takahashi, Naoki
- Ueno, Makoto
- Kagawa, Yoshinori
- Nishina, Tomohiro
- Kato, Takeshi
- Yamamoto, Yoshiyuki
- Furuse, Junji
- Denda, Tadamichi
- Kawakami, Hisato
- Oki, Eiji
- Nakajima, Takako
- Nishida, Naohiro
- Yamaguchi, Kensei
- Yasui, Hisateru
- Goto, Masahiro
- Matsuhashi, Nobuhisa
- Ohtsubo, Koushiro
- Yamazaki, Kentaro
- Tsuji, Akihito
- Okamoto, Wataru
- Tsuchihara, Katsuya
- Yamanaka, Takeharu
- Sakamoto, Yasutoshi
- Ichiki, Hiroko
- Yamashita, Riu
- Ohtsu, Atsushi
- Odegaard, Justin I.
- Yoshino, Takayuki
- Venue
- Nature Medicine
- Published
- 2020-10-05
- Volume
- 26
- Issue
- 12
- Pages
- 1859-1864
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W3089353724
- Cited by
- 373
- References
- 32
- Citations by year
- 2026: 41 · 2025: 57 · 2024: 60 · 2023: 71 · 2022: 73 · 2021: 67 · 2020: 3
- FWCI
- 18.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- circulating tumor DNA, liquid biopsy, advanced gastrointestinal cancer, clinical trial recruitment, clonal architecture, oncogenic drivers, precision medicine
- MeSH terms
- Circulating Tumor DNA, Adult, DNA, Neoplasm, Gastrointestinal Neoplasms, Genotype, Humans, Japan, Male, Middle Aged, Mutation, Biomarkers, Tumor, Precision Medicine, High-Throughput Nucleotide Sequencing
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