Targeted therapy guided by circulating tumor DNA analysis in advanced gastrointestinal tumors

Although comprehensive genomic profiling has become standard in oncology for advanced solid tumors, the full potential of circulating tumor DNA (ctDNA)-based profiling in capturing tumor heterogeneity and guiding therapy selection remains underexploited, marked by a scarcity of evidence on its clinical impact and the assessment of intratumoral heterogeneity. The GOZILA study, a nationwide, prospective observational ctDNA profiling study, previously demonstrated higher clinical trial enrollment rates using liquid biopsy compared with tissue screening. This updated analysis of 4,037 patients further delineates the clinical utility of ctDNA profiling in advanced solid tumors, showcasing a significant enhancement in patient outcomes with a 24% match rate for targeted therapy. Patients treated with matched targeted therapy based on ctDNA profiling demonstrated significantly improved overall survival compared with those receiving unmatched therapy (hazard ratio, 0.54). Notably, biomarker clonality and adjusted plasma copy number were identified as predictors of therapeutic efficacy, reinforcing the value of ctDNA in reflecting tumor heterogeneity for precise treatment decisions. These new insights into the relationship between ctDNA characteristics and treatment outcomes advance our understanding beyond the initial enrollment benefits. Our findings advocate for the broader adoption of ctDNA-guided treatment, signifying an advancement in precision oncology and improving survival outcomes in advanced solid tumors.

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Publication Details

Journal
Nature Medicine
Published
2024-09-16
DOI
https://doi.org/10.1038/s41591-024-03244-8
Citations
42
Primary Topic
Cancer Genomics and Diagnostics
Type
article
Field-Weighted Citation Impact
11.98

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article

Targeted therapy guided by circulating tumor DNA analysis in advanced gastrointestinal tumors

Taito Esaki, Taroh Satoh, Mihoko Yuasa, Hiroya Taniguchi et al.
42 citations
Nature Medicine
Cancer Genomics and Diagnostics
11.98
article

Targeted therapy guided by circulating tumor DNA analysis in advanced gastrointestinal tumors

Taito Esaki, Taroh Satoh, Mihoko Yuasa, Hiroya Taniguchi, Yu Sunakawa, Yoshiaki Nakamura, Takeshi Kato, Masahiro Goto, Kentaro Yamazaki, Takashi Ohta, Hideaki Bando, Hironaga Satake, Hiroshi Ozaki, Tadamichi Denda, Yoshito Komatsu, Takayuki Yoshino, Eiji Oki, Koushiro Ohtsubo, Naoko Iida, Hisateru Yasui, Naoki Takahashi, Naohiro Okano, Satoshi Yuki, Ken Kato, Kensei Yamaguchi, Riu Yamashita, Nobuhisa Matsuhashi, Makoto Ueno, Tomohiro Nishina
article en
42 citations

Abstract

Although comprehensive genomic profiling has become standard in oncology for advanced solid tumors, the full potential of circulating tumor DNA (ctDNA)-based profiling in capturing tumor heterogeneity and guiding therapy selection remains underexploited, marked by a scarcity of evidence on its clinical impact and the assessment of intratumoral heterogeneity. The GOZILA study, a nationwide, prospective observational ctDNA profiling study, previously demonstrated higher clinical trial enrollment rates using liquid biopsy compared with tissue screening. This updated analysis of 4,037 patients further delineates the clinical utility of ctDNA profiling in advanced solid tumors, showcasing a significant enhancement in patient outcomes with a 24% match rate for targeted therapy. Patients treated with matched targeted therapy based on ctDNA profiling demonstrated significantly improved overall survival compared with those receiving unmatched therapy (hazard ratio, 0.54). Notably, biomarker clonality and adjusted plasma copy number were identified as predictors of therapeutic efficacy, reinforcing the value of ctDNA in reflecting tumor heterogeneity for precise treatment decisions. These new insights into the relationship between ctDNA characteristics and treatment outcomes advance our understanding beyond the initial enrollment benefits. Our findings advocate for the broader adoption of ctDNA-guided treatment, signifying an advancement in precision oncology and improving survival outcomes in advanced solid tumors.

Nature MedicineVol. 31(1)
Kansai Medical University (JP), Kyushu University (JP), St. Marianna University School of Medicine (JP), Kyorin University (JP), Kanagawa Prefectural Hospital Organization (JP), Shizuoka Cancer Center (JP), Kochi Medical School Hospital (JP), Osaka National Hospital (JP), National Hospital Organization Kyushu Cancer Center (JP), Kanazawa University Hospital (JP), Kansai Rosai Hospital (JP), Chiba Cancer Center (JP), Saitama Cancer Center (JP), Kanazawa Medical University Hospital (JP), Aichi Cancer Center (JP), Shikoku Cancer Center (JP), Hokkaido University Hospital (JP), National Cancer Center Hospital East (JP), Osaka University Hospital (JP), Kobe City Medical Center General Hospital (JP), Gifu University (JP), Japanese Foundation For Cancer Research (JP), Kanagawa Cancer Center, Osaka University of Pharmaceutical Sciences (JP), Kindai University (JP)
Japan Agency for Medical Research and Development
Good health and well-being
Openalex Percentile: Top 1%
Cancer Genomics and Diagnostics
11.98
DOIOpen Access PDFOpenAlex
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