Comprehensive Genome Profiling-Initiated Tumor-Informed Circulating Tumor DNA Monitoring for Patients With Advanced...

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Comprehensive genome profiling (CGP) as a companion diagnostic (CDx) is publicly insured in Japan since June 2019.
• However, the utilization of CGP data for guiding cancer drug therapy remains low.
• There is a need to maximize the utility of CGP data beyond initial treatment recommendations.

Purpose of the Study:

• To investigate the potential of using comprehensive genome profiling (CGP) as a foundation for tumor-informed circulating tumor DNA (ctDNA) monitoring.
• To retrospectively analyze the clinical utility of CGP-guided ctDNA monitoring in patients with malignant tumors.
• To assess the effectiveness of ctDNA monitoring for early relapse prediction and treatment response evaluation.

Main Methods:

• Retrospective validation of 219 patients with malignant tumors who underwent CGP.
• Analysis of patient demographics, genetic alterations, recommended drug therapies, and drug administration rates.
• Implementation of tumor-informed ctDNA monitoring based on somatic mutations identified by CGP in a subset of patients.

Main Results:

• Only 6.4% of patients received recommended actions post-CGP.
• In patients undergoing ctDNA monitoring (n=11), clinical validity was confirmed for early relapse prediction (45.5%) and treatment response evaluation (90.9%).
• 90.9% of patients in the ctDNA monitoring group received valuable clinical information.

Conclusions:

• Despite a low current rate of CGP directly leading to drug recommendations, CGP serves as a valuable resource for initiating longitudinal ctDNA monitoring.
• Tumor-informed ctDNA monitoring can provide crucial information for early relapse prediction and treatment response assessment.
• CGP data can be repurposed for ctDNA monitoring, enhancing its clinical utility in cancer care.