Cell free tumor DNA ( CfTDNA) in cervical carcinoma as diagnostic and prognostic marker: Pilot study.

Abstract

e24100 Background: To study a non-invasive genetic panel for timely detection of cervical carcinoma and its prognostication by using cell-free circulating tumor DNA (cfTDNA). Methods: A total of 25 patients with locally advanced squamous cell carcinoma of cervix (Stage IB-IIIB) were tested prospectively with 50 tumor gene panel in a NABL accredited laboratory. Four ml serum was collected, CfTDNA was isolated and they were checked for single nucleotide variants (SNVs) / copy number variants (CNVs) by using Next Generation Sequencing (NGS).All Patients underwent EBRT and Brachytherapy according to the institutional protocol and were on regular follow up.And patients were followed upto 30 months - survival and local control were assessed. Results: In 21/25(84%) patients, CFTDNA was detected and sufficient to carry under NGS. Out of 50 genes, around 32 genetic alteration were detected. Mean genetic alteration was 4.08(2-14). Most common SNVs detected included were, , TP53 -11/21 (52.3%) patients, CDKN2A- 10/21(47.6%)patients, PTEN and STK11 -7/21 (33.3%)patients, BRAF and VHL -6/21 (28.5%)patients , EGFR and SMAD4 -4/21(19%). On combination of these genetic alterations - EGFR, KIT,PTEN, PIK3CA,TP 53, VHL are the main alterations and combination of these gene (Diagnostic GENETIC MODULE) , at least one genetic alteration among combination was found in 100% patients at any point of time. Further follow up data regarding correlation of this genetic alteration with prognosis will follows. On follow up data – median survival was 19 months. 12 out of 21 cases were alive and remaining 9 patients were dead at the end of the study. Patients with VHL; PTPN11; KIT; JAK3; HRAS; FLT3; EGFR; CSF1R; ATM; APC; BRAF; CDKN2A; PTEN; STK11 and TP53 genes will have a more aggressive disease. Patients with SMO; KRAS; NPM1; NOTCH1; FGFR3; FBXW7; ERBB4; CTNNB1 genes associated with good prognosis genes . Conclusions: CfTDNA can be easily demonstrable and can be used as a minimally invasive diagnostic and therapeutic response tool in cervical carcinoma. With available genetic panel showed good and bad prognostic modules on follow up data.