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Updated: Dec 9, 2025
Detection of Cell-Free DNA in Blood Plasma Samples of Cancer Patients
Published on: September 9, 2020
Identification of Actionable Genomic Alterations Using Circulating Cell-Free DNA
Nora S Sánchez1, Michael P Kahle1, Ann Marie Bailey1
1The University of Texas MD Anderson Cancer Center, Houston, TX.
Purpose:
Cell-free DNA (cfDNA) next-generation sequencing is a noninvasive approach for genomic testing. We report the frequency of identifying alterations and their clinical actionability in patients with advanced/metastatic cancer.
Patients And Methods:
Prospectively consented patients had cfDNA testing performed. Alterations were assessed for therapeutic implications.
Results:
We enrolled 575 patients with 37 tumor types. Of these patients, 438 (76.2%) had at least one alteration detected, and 205 (35.7%) had one or more alterations of high potential for clinical action. In diseases with 10 or more patients enrolled, 50% or more had at least one alteration deemed of high potential for clinical action. Trials were identified in 80% of patients (286 of 357) with any alteration and in 92% of patients (188 of 205) with one or more alterations of high potential for clinical action of whom 57.6% (118 of 205) had 6 or more months of follow-up available. Of these patients, 10% (12 of 118) had received genomically matched therapy through enrollment in clinical trials (n = 8), off-label drug use (n = 3), or standard of care (n = 1). Although 88.6% of all patients had a performance status of 0 or 1 upon enrollment, the primary reason for not acting on alterations was poor performance status at next treatment change (28.1%; 27 of 96).
Conclusion:
cfDNA testing represents a readily accessible method for genomic testing and allows for detection of genomic alterations in most patients with advanced disease. Utility may be higher in patients interested in investigational therapeutics with adequate performance status. Additional study is needed to determine whether utility is enhanced by testing earlier in the treatment course.
Insights
Cell-free DNA (cfDNA) next-generation sequencing detects genomic alterations in most advanced cancer patients. Clinical actionability is high, but treatment is limited by performance status and trial availability.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Noninvasive genomic testing is crucial for advanced cancers.
- Cell-free DNA (cfDNA) sequencing offers a promising approach.
Purpose of the Study:
- To determine the frequency of detectable genomic alterations using cfDNA sequencing.
- To assess the clinical actionability of these alterations in advanced cancer patients.
Main Methods:
- Prospective enrollment of 575 patients with diverse advanced/metastatic cancers.
- cfDNA next-generation sequencing performed on all participants.
- Assessment of identified alterations for therapeutic implications and clinical actionability.
Main Results:
- 76.2% of patients had detectable alterations; 35.7% had high clinical actionability.
- In specific tumor types (≥10 patients), ≥50% showed actionable alterations.
- Genomically matched therapy was administered to 10% of eligible patients, often limited by performance status.
Conclusions:
- cfDNA sequencing is accessible and detects genomic alterations in most advanced cancer patients.
- Clinical utility is notable for patients pursuing investigational therapies with adequate performance status.
- Further research is needed to optimize cfDNA testing timing in treatment protocols.
