Cell-free circulating tumor DNA(ctDNA) analysis by next generation sequencing(NGS) panel in non small cell lung cancer patients(NSCLC): implications in clinical practice. XX Congresso Nazionale AIOM 2018 (Poster D18)

Background:The treatment of NSCLC has evolved into precision medicine that needs the implementation of biomarkers testing.In the last years, the number of potentially actionable molecular alterations has rapidly increased. Diagnostic samples are frequently not sufficient for molecular definition of NSCLC but with NGS can be analyzed many genes simultaneously.So we evaluated the feasibility of using ctDNA NGS in clinical practice to better identify alterations that may predict response and toxicity to the therapies. Material and methods:We performed a retrospective study about adults patients with advanced non squamous NSCLC.A cohort of 45 non squamous NSCLC was profiled using a NGS panel targeting 56 actionable and cancer related genes.45 plasma samples obtained were subjected to manual cell-free circulating tumor DNA extraction with Helix Circulating Nucleic Acid Diatech pharmacogenetics kit,NGS with Illumina MiSeq-Myriapod NGS-IL 56G Onco panel kit.Relationships between gene mutations,tumor response and grade of toxicity were evaluated using standard Recist Criteria and Common Terminology Criteria for Adverse Events(CTCAE)version 4.02.We used a database and analyzed the data using nonparametric methods. Results:Of 45 enrolled non squamous NSCLC patients,18 (40%) patients showed gene alterations. Recurrent alterations were observed in KRAS,TP53,MET,KDR,KIT,SMAD4 and MET genes, whereas the remaining genes (ERBB4, CTNNB1, EGFR) were mutated in <5% of the cases.The overall treatment response was higher in patients with SMAD4 mutation.Instead for KIT mutated patients we showed a poor prognosis associated to an increased gastrointestinal(G3/4)and haematological toxicity(G3/G4),according to CTCAE v. 4.02. Conclusions:Despite the low sample size the results seem to confirm the importance of more accurate analysis of genomic alterations.We highlighted that NGS panel represent an effective diagnostic tool showing the interesting role of some genes alterations that may predict responsiveness and toxicity to standard NSCLC regimens.There is interest in literature for potential applications of NGS-based liquid biopsy in the treatment of NSCLC despite the gap between theoretical and practice medicine.Further studies are needed to monitor tumor evolution,response and resistance to targeted therapies and to facilitate translational medicine.