Journal Article

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

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

2025

Overview

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. In the observational SCRUM-Japan GOZILA study, after a median follow-up of 11 months, patients with metastatic gastrointestinal tumors who received biomarker-matched therapies based on circulating tumor DNA profiling showed a greater clinical benefit than those receiving unmatched therapy.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/67/1857 / 631/67/69 / Adult / Aged / Biomarkers / Biomarkers, Tumor - blood / Biomarkers, Tumor - genetics / Biomedical and Life Sciences / Biomedicine / Biopsy / Cancer Research / Circulating Tumor DNA - blood / Circulating Tumor DNA - genetics / Circulation / Copy number / Deoxyribonucleic acid / DNA / DNA fingerprinting / Female / Gastrointestinal Neoplasms - blood / Gastrointestinal Neoplasms - drug therapy / Gastrointestinal Neoplasms - genetics / Gastrointestinal Neoplasms - pathology / Genomic analysis / Heterogeneity / Humans / Infectious Diseases / Liquid Biopsy / Male / Metabolic Diseases / Metastases / Middle Aged / Molecular Medicine / Molecular Targeted Therapy / Neurosciences / Oncology / Patients / Precision Medicine / Prospective Studies / Solid tumors / Survival / Therapy / Treatment Outcome / Tumors