Discrepancy Between Liquid Biopsy and Tumor Next-Generation Sequencing Due to Low Tumor Fraction in a Patient With...

Tumor next-generation sequencing (NGS) is the gold standard molecular testing for driver genomic alterations in patients with advanced non-small cell lung cancer (NSCLC). However, it requires a biopsy, which is an invasive procedure. In contrast, a liquid biopsy is a minimally invasive test that measures circulating tumor DNA (ctDNA) in the plasma and can be also used for molecular profiling. We report a case of a patient with stage IV metastatic lung adenocarcinoma with a negative liquid biopsy for tumor-derived genomic alterations but positive tissue NGS for mutations, including a driver KRAS mutation. The discrepancy between the two results can be attributed to low levels of ctDNA determined by tumor fraction below 1%, which prevents the liquid biopsy assay from detecting genomic alterations when the tumor shedding into the blood is below the detection threshold. It is well known in the literature that false negative liquid biopsies are possible, but a significant finding this case highlights is the clinical importance of tumor fraction in a liquid biopsy report. We conclude that patients with a liquid biopsy with low tumor fraction need further testing with tumor NGS to determine the presence of driver genomic alterations.