Liquid biopsies for the front line therapy decision in non-small cell lung cancer.
Authors: Brice Kayla , Raez Luis E. , Dumais Katerine , Wietecha Delia , Lopez-Cohen Alejandro , Izquierdo Paola , Drusbosky Leylah , Dada Hiba I. , Powery Herman W. 
Published: June 2021

e21103

Background: Current literature has demonstrated non-inferiority of liquid biopsies relative to tissue genotyping to identify detectable biomarkers in patients with metastatic non-small cell lung cancer (NSCLC). However, liquid biopsies have the ability to report next generation sequencing (NGS) results faster than tissue NGS. Tissue NGS has the disadvantage that depends on the amount of tumor available after the original pathology report is issued and it is not infrequent that there is an insufficient sample for NGS (QNS). Another major disadvantage is that the results of tissue NGS usually take longer than blood NGS due to the process of requesting and shipping tissue. This study aimed to illustrate that liquid biopsies can be the new standard in front line decision making for patients with stage IV NSCLC when compared with tissue NGS. Methods: This was a retrospective review of adult patients within the Memorial Cancer Institute who were diagnosed with stage IV NSCLC and received, at the same time, a tissue and liquid biopsy between July 1, 2015 and June 30, 2020. Patients were excluded if biopsies were not performed within one month apart or the treatment decision was not determined. Data collected utilizing the electronic medical record included: demographics, biopsy turnaround time, biopsy type used to make the final treatment decision, insufficient tissue samples, date of disease progression and death, and detection of genomic biomarkers. Descriptive statistics and logistic regression analysis were calculated for all demographic and clinical outcomes. Results: One hundred and thirty-one patients were evaluated. Of the evaluated patients, 53% were female, 47% were men, 74% had a smoking history and 26% never smoked. Non-Hispanic Whites were 56%, Hispanics 29%, and African Americans 8%. The average age at diagnosis was 66 ± 13 years of age. Of the 122 tumors where genomic biomarkers were detected by liquid NGS, 75% had actionable genetic aberrations (EGFR, ALK, ROS-1, NTRK 1-3, BRAFv600, RET, METexon14skipping). While only 53% had actionable genetic alterations out of 111 tumors with detectable mutations by tissue NGS. Final treatment decisions were made in 70% of the patients based on the results of the liquid NGS that generally arrived first and only 30% of the treatment decisions on the tissue NGS. The median time to start therapy was 9 days with liquid NGS vs 33.5 days with tissue NGS. More than 90% of the patients with an actionable mutation with liquid NGS were able to start therapy within 11 ± 5 days. Progression free survival was similar for patients in which the treatment decision was based on liquid NGS vs tissue NGS (p = 0.99). Conclusions: In patients with stage IV NSCLC, NGS done by liquid biopsies may be used as the standard of care to make the front line therapeutic decision in patients with NSCLC. A prospective study with a larger sample is probably needed to validate these results.