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Detection of Cell-Free DNA in Blood Plasma Samples of Cancer Patients
Published on: September 9, 2020
Clinical Liquid Biopsy Testing for Detection of Actionable Genomic Alterations in Children and Young Adults With
Holly J Roberts1, Hannah Comeau2, Kelly Klega2,3
1Boston Children's Hospital, Harvard Medical School, Boston, MA.
Purpose:
Given the paucity of data regarding circulating tumor DNA (ctDNA) as a modality to guide diagnosis and treatment for children with advanced solid tumors, we conducted a prospective study to characterize the frequency and clinical impact of diagnostic and targetable genomic variants identified by clinical ctDNA testing.
Methods:
Our study cohort included 36 children and young adults with advanced solid tumors enrolled in the prospective, multicenter molecular profiling GAIN study. Tumor samples underwent next-generation sequencing, and serial blood samples were analyzed by the FoundationOne Liquid Companion Diagnostic ctDNA test. We evaluated the prevalence of ctDNA in our cohort using ctDNA tumor fraction (TF), the prevalence of genomic variants in ctDNA compared with those in tumor tissue stratified by ctDNA TF, the association between ctDNA TF and radiographic disease response, and the clinical impact of ctDNA testing.
Results:
In our cohort, 67% of patients had at least one liquid biopsy sample with detectable ctDNA by TF. Most patients (72%) had detection of a clinically relevant genomic alteration in at least one ctDNA sample. Most (85%) short variants and translocations identified in tissue were present in ctDNA when TF ≥ 1%, with variation by tumor type. We demonstrated statistically significant differences in absolute ctDNA TF changes among patients with radiographic disease progression (mean, +12.2%, standard deviation, 18.7%) and response (mean, -23.4%, standard deviation, 30.6%), P < .001. ctDNA results affected the clinical care of 26% of patients.
Conclusion:
ctDNA is prevalent across a wide range of advanced pediatric solid tumors, identifies clinically important variants, changes with radiographic disease burden, and has a clinical impact.
Insights
Circulating tumor DNA (ctDNA) is prevalent in children with advanced solid tumors, detecting key genomic variants and influencing clinical care. This liquid biopsy approach shows promise for guiding diagnosis and treatment.
Area of Science:
- Pediatric Oncology
- Genomics
- Liquid Biopsy
Background:
- Limited data exists on circulating tumor DNA (ctDNA) for guiding diagnosis and treatment in pediatric advanced solid tumors.
- Molecular profiling is crucial for understanding tumor heterogeneity and identifying therapeutic targets.
Purpose of the Study:
- To characterize the frequency and clinical impact of diagnostic and targetable genomic variants identified by ctDNA testing in children with advanced solid tumors.
Main Methods:
- Prospective, multicenter study of 36 children and young adults with advanced solid tumors.
- Analysis of tumor samples via next-generation sequencing and serial blood samples using the FoundationOne Liquid Companion Diagnostic ctDNA test.
- Evaluation of ctDNA prevalence (tumor fraction), genomic variant detection, association with radiographic response, and clinical impact.
Main Results:
- 67% of patients had detectable ctDNA; 72% had clinically relevant genomic alterations detected.
- 85% of tissue variants were identified in ctDNA with tumor fraction ≥ 1%, varying by tumor type.
- ctDNA tumor fraction changes correlated significantly with radiographic disease progression and response (P < .001); 26% of patients had care altered by ctDNA results.
Conclusions:
- ctDNA is prevalent in diverse advanced pediatric solid tumors.
- ctDNA testing identifies clinically significant variants and correlates with disease burden.
- ctDNA has a demonstrable clinical impact on patient care in this population.
