ESTIMATION OF PLASMA EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) MUTATION STATUS AND ITS CORRELATION WITH TUMOR TISSUE EGFR MUTATION STATUS IN ADVANCED NON–SMALL CELL LUNG CANCER PATIENTS

PRAVEENA VOONNA; T. KANNAN; Bhargavi D; P.V.G.K. SARMA; SHILPA KANDIPALLI; P. SANTOSH

Volume : VIII, Issue : VI, June - 2018

ESTIMATION OF PLASMA EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) MUTATION STATUS AND ITS CORRELATION WITH TUMOR TISSUE EGFR MUTATION STATUS IN ADVANCED NON–SMALL CELL LUNG CANCER PATIENTS

Praveena Voonna, T. Kannan, Bhargavi D, P. V. G. K. Sarma, Shilpa Kandipalli, P. Santosh

Abstract :

Background:Patients with non–small cell lung cancer (NSCLC) harboring activating EGFR mutations respond to treatment with EGFR tyrosine kinase inhibitors (TKIs). However, obtaining adequate tumor tissue from NSCLC patients can be difficult. The aim of this study was to determine whether tumor tissue EGFR analysis can be replaced with plasma EGFR analysis to assess mutation status and to evaluate the association of mutation status with survival outcomes.

Methods: We prospectively evaluated EGFR gene mutation status (exons 18,19,20 and 21) in paired tissue and plasma from 68 advanced NSCLC patients (before starting anticancer treatment) during the period, May 2016 to May 2017 using Real Time based Amplification Refractory Mutation System–Polymerase Chain Reaction (ARMS–PCR) assay and Allele specific PCR techniques respectively. Concordance and discordance rates were assessed and survival analysis was done.

Results: Among 68 NSCLC patients, biopsy tissue was not sufficient for analysis in 6 patients, hence 62 patients were included in final analysis. EGFR mutations were identified in 14/62 (23%) biopsy samples and 25/62 (40%) plasma samples. Most common mutation identified in both tissue and plasma was exon 19 deletion. The overall concordance of EGFR mutation status between tissue and plasma reached 66% (41/62) (Kappa coefficient: 0.24; P=0.038). The sensitivity, specificity, positive and negative predictive values of plasma EGFR detection were 64%, 67%, 36% and 87% respectively. Among biopsy EGFR mutant patients, progression free survival (PFS) of plasma EGFR mutation detected patients was less compared to that of undetected patients.

Conclusion: EGFR gene mutation analysis of plasma is feasible with allele specific PCR assays with a high negative predictive value. It can be considered in frail patients not suitable for biopsy. But further investigation is required to determine whether plasma sample can be considered for determining EGFR mutation status in future.