Multicenter study of concurrent tissue and ctDNA molecular profiling to detect targetable mutations in a multicancer cohort

Tissue-based next-generation sequencing (NGS) of solid tumors is the standard for identifying actionable mutations. NGS of circulating tumor DNA (ctDNA) can also identify tumor-derived mutations. A multicenter cohort study of 3209 patients with stage IV NSCLC, breast, prostate, or colorectal cancer evaluated concurrent tissue and ctDNA molecular profiling. An actionable variant was detected in 45.1% of patients. Of these patients, 9.3% had a clinically actionable variant detected by ctDNA profiling that was not detected by solid-tissue testing, and 24.2% had a variant detected by solid-tissue testing but not by ctDNA profiling. Among patients with breast cancer with actionable variants, 20.2% had a unique variant detected by ctDNA profiling; most (55%) of these unique ctDNA variants were in the ESR1 gene. The authors conclude that concurrent tumor tissue-based and ctDNA-based genomic profiling identified more patients with targetable variant than would have been discovered by tissue profiling alone.