TITLE:
The Prognostic Value of Cell-Free DNA in Advanced Non-Small-Cell Lung Cancer
AUTHORS:
Anneli Dowler Nygaard, Karen-Lise Garm Spindler, Niels Pallisgaard, Rikke Fredslund Andersen, Anders Jakobsen
KEYWORDS:
Cell-Free DNA; Prognostic; NSCLC; Circulating DNA
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.8A,
August
13,
2013
ABSTRACT: Background: Cell-free DNA (cfDNA) holds promise as a tumor marker of clinical importance.
We aimed to investigate
the prognostic value of baseline cfDNA in non small-cell lung cancer (NSCLC). Material and Methods: During a
three-year period, patients with newly diagnosed, previously untreated advanced
NSCLC were included in a consecutive, prospective marker-trial. Plasma was isolated from a pre-treatment
peripheral blood sample and the level of total cfDNA was measured by an
in-house assay qPCR-method. The treatment comprised carboplatin (AUC 5) intravenously
day 1), and vinorelbine (30 mg/m2 intravenously day 1 and 60 mg/m2 perorally day 8) q3w
for a maximum of six cycles. The primary end-point was overall survival (OS).
Secondary end-points were progression free survival (PFS) and overall response rate (ORR). Results: 245 patients were included and
received a minimum of 1 cycle of chemotherapy (median 4). The median OS was 8.9 months,
the median PFS by intention to treat 5.4 months and the ORR was 25%. The
patients were divided into four groups based on quartiles of cfDNA and
subsequently dichotomized by the 75th percentile revealing a significantly worse
prognosis for patients in the upper 75th percentile (median OS 4.9 months) compared to patients with lower levels
(10.0 months) (HR 2.1, 95%CI 1.4 - 3.1, p 0.0001). A multivariate analysis confirmed the independent prognostic
value of cfDNA. A subgroup analysis of patients with high cfDNA and poor performance status (PS = 2) identified a group of patients with
even worse prognosis (median OS 2.0 versus 9.1 months, HR 3.6, 95%CI 1.4 - 9.2, p 0.0001). Similar and significant
results were found when comparing level of cfDNA and PFS. Conclusions: High pre-treatment level of cfDNA seems to have a
strong prognostic impact in patients with newly diagnosed advanced NSCLC.
Combined with PS it identifies a patient group with minimal or no benefit of
chemotherapy.