Liquid Biopsies in a Veteran Patient Population With Advanced Prostate and Lung Non-Small Cell Carcinomas: A New Paradigm and Unique Challenge in Personalized Medicine.

Abstract

Liquid biopsy in solid tumors is a major milestone in the field of precision oncology by analyzing circulating tumor cells in peripheral blood and genomic alterations. DNA damage repair gene (DDR) mutations have been reported in 25 to 40% of prostatic cancers and > 50% of non-small cell lung cancers (NSCLC). Tp53 mutation has been found to be associated with a poor prognosis and increased germline mutations. We herein present a quality assurance study for the utility of liquid biopsies with frequency of DDR, Tp53, and androgen receptor (AR) mutations and the clinical impact in advanced lung and prostate cancers in the veteran patient population; these quality assurance observations are the study endpoints. We reviewed documentation from advanced cancer biomarker tests on liquid biopsies performed at the Corporal Michael J. Crescenz Veteran Affairs Medical Center in Philadelphia, Pennsylvania, from May 2019 to April 15, 2020. Mutations were detected in 29 of 31 (93.5%) liquid biopsies, hence, 29 liquid biopsies had sufficient ctDNA for analysis. Notable mutations were found in 23 cases (79.3%), irrespective of the cancer type showed. Of 21 prostate cancers biopsies 4 (19.0%) biomarker test directed the targeted therapy to driver mutations of the AR gene. Gene mutations from the DDR gene family were detected in 8 of 23 (34.7%) advanced prostate and lung cancer liquid biopsies, and in 6 of 21 (28.5%) prostate cancer cases indicating poor outcome and possible resistance to the current therapy. Irrespective of the cancer type, 15 of 23 (65.2%) patients harbored Tp53 mutations, which is much more frequent than is documented in the literature. Of 31 patients, 15 (48.4%) were Vietnam era veterans with the potential of Agent Orange exposure and, 20 of 31 (64.5%) had a smoking history. Seven (46.6%) of the Vietnam era veterans with potential exposure to Agent Orange were positive for Tp53 mutations irrespective of the cancer type. The minimally invasive liquid biopsy shows a great promise as a diagnostic and prognostic tool in the personalized clinical management of advanced prostate and NSCLC in veteran patient population with unique demographic characteristics. Difference in frequency of the genetic mutations (DDR, TP53, AR) in this cohort provides valuable information for disease progression, lack of response, mechanism of resistance to the implemented therapy and clinical decision making. Precision oncology can be further tailored for this cohort by focusing on DNA repair genes and Tp53 mutations in future for personalized targeted therapy.