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Updated: Aug 12, 2025
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Clinical utility of circulating tumor DNA sequencing with a large panel: a National Center for Precision Medicine
Background:
Circulating tumor DNA (ctDNA) sequencing is a promising approach for tailoring therapy in patients with cancer. We report hereby the results from a prospective study where we investigated the impact of comprehensive molecular profiling of ctDNA in patients with advanced solid tumors.
Patients And Methods:
Genomic analysis was performed using the FoundationOne Liquid CDx Assay [324 genes, tumor mutational burden (TMB), microsatellite instability status]. Each individual genomic report was reviewed and discussed weekly by a multidisciplinary tumor board (MTB). Actionable targets were classified by ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) tier leading to molecular-based treatment suggestions wherever it was possible.
Results:
Between December 2020 and November 2021, 1772 patients with metastatic solid tumors underwent molecular profiling. Median time to assay results was 12 days. Results were contributive for 1658 patients (94%). At least one actionable target was detected in 1059 patients (64%) with a total of 1825 actionable alterations including alteration of the DNA damage repair response pathway (n = 336, 18%), high TMB (>16 mutations/Mb; n = 243, 13%), PIK3CA mutations (n = 150, 8%), ERBB family pathway alterations (n = 127, 7%), PTEN alterations (n = 95, 5%), FGFR alterations (n = 67, 4%) and MET activations (n = 13, 0.7%). The MTB recommended a matched therapy for 597 patients (56%) with a total of 819 therapeutic orientations: clinical trials (n = 639, 78%), off-label/compassionate use (n = 81, 10%), approved drug (n = 51, 6%), and early access program (n = 48, 6%). In total, 122 patients (21%) were treated. Among the assessable patients (n = 107), 4 (4%) had complete response, 35 (33%) had partial response, 27 (25%) had stable disease, and 41 (38%) a progressive disease as best response. The median progression-free survival and median overall survival were 4.7 months (95% confidence interval 2.7-6.7 months) and 8.3 months (95% confidence interval 4.7-11.9 months) respectively.
Conclusions:
ctDNA sequencing with a large panel is an efficient approach to match patients with advanced cancer with targeted therapies.
Insights
Comprehensive circulating tumor DNA (ctDNA) sequencing identified actionable targets in 64% of advanced cancer patients. This approach efficiently matches patients with targeted therapies, improving treatment strategies.
Area of Science:
- Oncology
- Genomics
- Personalized Medicine
Background:
- Circulating tumor DNA (ctDNA) sequencing offers a promising avenue for personalized cancer therapy.
- This prospective study investigated the utility of comprehensive molecular profiling of ctDNA in patients with advanced solid tumors.
Purpose of the Study:
- To assess the impact of ctDNA profiling on treatment selection for advanced cancer patients.
- To identify actionable genomic alterations and guide therapy recommendations through a multidisciplinary tumor board.
Main Methods:
- 1772 patients with advanced solid tumors underwent comprehensive genomic profiling using the FoundationOne Liquid CDx Assay.
- Results were reviewed by a multidisciplinary tumor board (MTB) to classify actionable targets (ESCAT tier) and suggest molecular-based treatments.
- Analysis included 324 genes, tumor mutational burden (TMB), and microsatellite instability (MSI) status.
Main Results:
- Actionable targets were identified in 1059 patients (64%), with 1825 alterations noted, including DNA damage repair pathway alterations (18%) and high TMB (13%).
- The MTB recommended matched therapies for 597 patients (56%), leading to treatment in 122 patients (21%).
- Among treated patients, 4% had a complete response, 33% a partial response, 25% stable disease, and 38% progressive disease.
Conclusions:
- Comprehensive ctDNA sequencing is an efficient method for identifying patients with advanced cancer who can benefit from targeted therapies.
- This approach facilitates the matching of patients to appropriate treatment strategies, including clinical trials and approved drugs.
