Utility of a targeted NGS oncology assay for circulating tumor DNA in a multi-histology clinical setting

Genomic profiling of tumor tissue at diagnosis is the standard of care for various cancers. Profiling of circulating-tumor DNA (ctDNA) found in peripheral blood of cancer patients is an attractive alternative to invasive tissue biopsy. We describe the use of a comprehensive NGS sequencing assay of ctDNA in the clinical setting. The Resolution Bioscience ctCDx™ assay comprehensively targets actionable somatic SNVs, indels, fusions and copy number variants in 16 genes implicated in lung and other cancers, using a proprietary, high-efficiency hybrid capture system and NGS sequencing of ctDNA from plasma. 385 patients (335 from 42756493EDI1001 clinical trial screening, and 50 from a University of Washington study CC9372) were analyzed in the Resolution Bioscience CLIA laboratory. Patients had previously been diagnosed with one of ten histologies, including lung, breast, and ovarian cancer. The patient cohort was a clinically relevant sampling, of treatment-naïve patients, those on therapy, and those with refractory disease after >= 1 therapy course. Average turn-around-time (TAT) was 8.6 calendar days. The ctCDx™ assay detected >435 somatic mutations of all 4 types; SNVs, indels, fusions, and copy number variation. Somatic lesions were detected in 61% of patients. At least 25% of patients demonstrated canonical driver mutations, including KRAS SNVs, EGFR indels, ERBB2 amps., and EML4-ALK fusions. Resistance mutations such as EGFR T790M were detected in refractory patients. Detection rates of driver mutations in each indication closely mirrored the published detection rates in tumor tissue. At least 8% of patients from one clinic had complications that precluded a tissue biopsy, thus benefiting from access to a blood-based assay. Our comprehensive blood-based genomic ctCDx platform has the demonstrated capacity to improve access in a clinically relevant TAT for oncology patients in many indications. Variant detection frequencies in blood from a representative clinical cohort generally aligned with expected alteration frequencies identified in tissue from published literature.