Genomic Tissue Analysis and Liquid Biopsy Profiles from Patients Diagnosed with Advanced Adenocarcinoma of the Lung

Edgardo S. Santos, Luis E. Raez, Lilibeth Del Carmen Castillero, Camila Marana and Brian Hunis

Department of Thoracic Oncology Program, Lynn Cancer Institute, USA
Department of Hematology/Oncology, Memorial Cancer Institute/Memorial Health Care System, USA
University of Panama School of Medicine, Panama

^*Correspondance to: Edgardo S. Santos 

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Abstract:

Background: Several genomic abnormalities have been discovered in adenocarcinoma of the lung in the last years; however, adequate quantity of tumor tissue for molecular analysis is a major handicap to offer most of the patients a personalized medicine. Reasons such as difficulty to perform tumor biopsy either because of tumor location or patient’s co-morbid conditions are among the common factors for lack of molecular profiling results. Hence, liquid biopsy has emerged as a potential alternative to detect these genomic alterations.Methods: We analyzed 81 consecutive patients to whom a liquid biopsy using Guardant 360 test was ordered in our thoracic oncology clinics at Lynn Cancer Institute, Boca Raton, Florida and Memorial Cancer Institute, Hollywood, Florida. Results from tissue genomic molecular profiling from each subject was obtained or recovered for comparison. Molecular genomic profiling results from this cohort were developed by different CLIA laboratories (e.g. Response Genetics, Caris Life Sciences, Foundation Medicine, BioTheranostics, and Genoptix). For liquid biopsy analysis, only Guardant 360 test was considered. The Guardant 360 test assays a panel of 70 genes. To identify genomic alterations in cancer-associated somatic variants with high sensitivity, cell-free DNA is extracted from plasma and genomic alterations are analyzed by massively parallel sequencing of amplified target genes.Results: The distribution by gender was: 56 female patients and 25 males; median age 71 (range, 27- 99). Eighty percent (65/81) of the patients had at least 1 genomic alteration by liquid biopsy (range, 1-10). Most common abnormalities found in liquid biopsy were: TP53 (49%), EGFR (42%), NF1 (25%), KRAS (17%), MET (15%). From this 65 pts with positive liquid biopsy results, 49 patients (75%) had tumor tissue molecular profiling results for comparison. Major reason for lack of tumor tissue molecular profiling results: insufficient tumor (18/81; 22%). For comparison between the 2 modalities, we considered all patients with available results in both tests; hence, sixty-three patients were used to compare tumor biopsy with liquid biopsy. Thirty-three patients out of 63 (52%) had at least 1 similar genomic abnormality or molecular profiling results found in both tumor and liquid biopsy. Most of the concordance was in EGFR alterations (17/22; 77%). Liquid biopsy caught 10 additional EGFR genomic aberrations not being identified by tumor biopsy (a total of 27 EGFR genomics aberrations were identified in liquid biopsy). Fourteen EGFR found in liquid biopsy were actionable; three out of 10 EGFR mutations found only in liquid biopsy were actionable.Conclusion: Liquid biopsy using Guardant 360 evaluation offers an alternative to identify genomic alterations including actionable mutations; still, insufficient tumor is the major reason for lacking of tumor molecular profiling results and more advances to obtain tumor biopsy are needed. Our cohort had 77% concordance between liquid and tumor biopsies for EGFR alterations despite multiple factors against discussed in this manuscript.

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Cite the Article:

Santos ES, Raez LE, Castillero LDC, Marana C, Hunis B. Genomic Tissue Analysis and Liquid Biopsy Profiles from Patients Diagnosed with Advanced Adenocarcinoma of the Lung. Clin Oncol. 2016; 1: 1099.