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Updated: Jun 13, 2025
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Targeted therapy guided by circulating tumor DNA analysis in advanced gastrointestinal tumors
Yoshiaki Nakamura1,2,3, Hiroshi Ozaki2, Makoto Ueno4
1International Research Promotion Office, National Cancer Center Hospital East, Kashiwa, Japan.
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.
Insights
Circulating tumor DNA (ctDNA) profiling in advanced solid tumors significantly improves outcomes. Matched targeted therapy based on ctDNA analysis led to better overall survival, highlighting its clinical utility in precision oncology.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Comprehensive genomic profiling is standard for advanced solid tumors, but the clinical impact of circulating tumor DNA (ctDNA)-based profiling is underexploited.
- Previous GOZILA study showed higher clinical trial enrollment with liquid biopsy versus tissue screening.
- Intratumoral heterogeneity assessment and ctDNA's role in guiding therapy selection require further evidence.
Purpose of the Study:
- To delineate the clinical utility of ctDNA profiling in advanced solid tumors.
- To assess the impact of ctDNA-guided targeted therapy on patient outcomes.
- To identify predictors of therapeutic efficacy using ctDNA characteristics.
Main Methods:
- Nationwide, prospective observational study (GOZILA) analyzing 4,037 patients with advanced solid tumors.
- ctDNA profiling for targeted therapy matching.
- Analysis of overall survival in patients receiving matched versus unmatched therapy.
- Evaluation of biomarker clonality and adjusted plasma copy number as efficacy predictors.
Main Results:
- A 24% match rate for targeted therapy was achieved using ctDNA profiling.
- Patients receiving ctDNA-matched targeted therapy showed significantly improved overall survival (hazard ratio, 0.54) compared to unmatched therapy.
- Biomarker clonality and adjusted plasma copy number predicted therapeutic efficacy.
Conclusions:
- ctDNA profiling enhances patient outcomes in advanced solid tumors beyond initial enrollment benefits.
- ctDNA analysis effectively captures tumor heterogeneity, supporting precise treatment decisions.
- Broader adoption of ctDNA-guided treatment is advocated to improve survival in precision oncology.
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