Cell-Free Circulating Tumor DNA Improves Standard Genotyping of Non-Small-Cell Lung Cancer and Increases Detection of Targetable Alterations in a Selected Hispanic Cohort

Abstract

<b><i>Background:</i></b> Several studies have shown that the non-small-cell lung cancer (NSCLC) genomic background among Hispanics differs from other populations. The finding of low-frequency genomic alterations in cell-free DNA (cfDNA) can increase diagnostic accuracy and could improve treatment in NSCLC. <b><i>Methods:</i></b> Data from 54 Hispanic patients with advanced NSCLC with high clinical suspicion for <i>ALK</i>, <i>EGFR</i>, and <i>ROS1</i> mutations were collected (including young age, female sex, and non-smokers). cfDNA was extracted from plasma and analyzed using a commercial next-generation sequencing test (Guardant360) which detects genomic alterations in 74 genes. <b><i>Results:</i></b> The median age was 56 years (range 31–83). Most patients were female (661.1%) and never smokers (72.3%). Among the patients included, 96% (52/54) had cfDNA detectable alterations with a mean number of 3.37 cfDNA alterations per test (range 1–10). cfDNA was able to detect some genomic alterations previously undetected by tissue biopsy. Among patients with insufficient or unavailable tissue to perform testing, mutations in <i>EGFR</i> and <i>ALK</i> which led to a change in therapy were determined using cfDNA in 28.8 and 3.8% of cases, respectively. Among patients with cfDNA alterations, 46.1% (<i>n</i> = 24) were switched to a targeted therapy with a median progression-free survival of 11.1 months (95% CI 7.6–14.6) and an overall survival of 40.3 months (95% CI 27.1–53.6). Concurrent genetic mutations with <i>TP53</i> and <i>KRAS</i> negatively impacted the prognosis. <b><i>Conclusions:</i></b> In a selected population of NSCLC Hispanic patients, comprehensive cfDNA analysis allowed a treatment change in 46.1% of the cases. Guardant360 allows the identification of genomic alterations to improve treatment selection and increase prognosis.

Impact of Simultaneous Circulating Tumor DNA and Tissue Genotyping in the Workup of Stage IV Lung Adenocarcinoma on Quality of Care in an Academic Community Medical Center

“…Clinically actionable GAs can also be identified by testing blood for circulating tumor DNA (ctDNA), colloquially known as liquid biopsy. 5 Liquid biopsy may identify GAs missed by tissue biopsy [6][7][8][9] and patients benefit similarly from therapies that target GAs identified by either method. 7,[10][11][12] Liquid biopsy has been endorsed by European Society for Medical Oncology and International Association for the Study of Lung Cancer 1,2,13 and is clearly indicated when tissue genotyping fails.…”