The quantification of DNA in the serum is a useful prognostic factor in advanced non-small cell lung cancer (NSCLC) patients

Abstract

7195 Background: Analysis of circulating DNA in blood is a promising non-invasive diagnostic tool. The purpose was to study the association between the quantity of free circulating DNA and clinical variables in advanced NSCLC patients. Methods: 100 stage IIIB and stage IV patients, homogeneously treated with gemcitabine/cisplatin, were examined. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the serum using commercial adsorption columns. The amount of free circulating DNA in the serum was assayed by means of the titration of the catalytic subunit of telomerase (hTERT), quantified using RT-PCR. Results: Median age was 61 years (35–82) and 91% were males. 86% had performance status 0–1. 71% were in stage IV and 29% in stage IIIB. The histological subtypes were: 38% squamous cell carcinoma, 37% adenocarcinoma, 5% anaplastic large cell, and 20% undifferentiated. Patients received a median of 6 cycles of chemotherapy (1–7). 4% achieved complete response (CR), 38% partial response (PR), 25% had stable disease (SD) and 30% progressive disease (PD). hTERT levels for patients in stage IIIB were 21.1 [4.9–152.02] versus 18.03 [2.9–848.8] in patients in stage IV (p=0.53). There was not association between hTERT values and therapy response, 17.8 (2.9–845.8) in the CR+PR group vs. 22.1 (5.2–534.7) in the SD+PD group (p=0.23). hTERT values were not related with the localization of the metastasis. In the multivariate analysis, hTERT was an independent predictive variable for time to progression (TTP) (HR 1.1, CI 95% 1.1–1.2, p=0.02) and overall survival (HR 1.1, CI 95% 1.1–1.2, p=0.004). Conclusions: The quantification of free circulating DNA in serum, by means of hTERT, is an affordable and accurate method due to the low intra-assay variability and its high specificity. In advanced NSCLC, high serum hTERT levels may be a poor prognostic indicator for TTP and survival. No significant financial relationships to disclose.