Circulating free DNA concentration is an independent prognostic biomarker in lung cancer.
Plasma circulating cell-free (cf)DNA is of interest in oncology because it has been shown to contain tumour DNA and may thus be used as liquid biopsy. In nonsmall cell lung cancer (NSCLC), cfDNA quantification has been proposed for the monitoring and follow-up of patients. However, available studies are limited and need to be confirmed by studies with larger sample sizes and including patients who receive more homogenous treatments. Our objective was to assess the predictive and prognostic value of plasma cfDNA concentration in a large series of patients with NSCLC and treated with a standard chemotherapy regimen.We included samples from lung cancer patients recruited into the Pharmacogenoscan study. The cfDNA of 218 patients was extracted and quantified by fluorometry before and after two or three cycles of platinum-based chemotherapy. The association between baseline and post-chemotherapy concentrations and treatment response, assessed by RECIST (response evaluation criteria in solid tumours) or patient survival was analysed.Patients with high cfDNA concentrations (highest tertile) at baseline had a significantly worse disease-free and overall survival than those with lower concentrations (lowest and middle tertiles) (median overall survival 10 months (95% CI 10.7-13.9) versus 14.2 months (95% CI 12.6-15.8), respectively; p=0.001). In multivariate analysis, increased baseline concentration of cfDNA was an independent prognostic factor. However, we did not find any association between cfDNA concentration and response to treatment.cfDNA may be a biomarker for the assessment of prognosis in NSCLC. However, total concentration of cfDNA does not appear to predict chemotherapy response.
Department of Acute Respiratory Medicine and Thoracic Oncology Department, Lyon Sud Hospital and Lyon University Cancer Institute, Lyon University Hospital, Pierre Bénite, France International Agency for Research on Cancer, Molecular Mechanisms and Biomarkers Group, Lyon, France.
Claire
C
Tissot
Université Grenoble 1, INSERM, U 823, Institut A Bonniot, Université J Fourier, La Tronche, France Thoracic Oncology Unit, Teaching Hospital A Michallon, Grenoble, France.
Anne-Claire
AC
Toffart
International Agency for Research on Cancer, Molecular Mechanisms and Biomarkers Group, Lyon, France.
Stéphanie
S
Villar
Department of Acute Respiratory Medicine and Thoracic Oncology Department, Lyon Sud Hospital and Lyon University Cancer Institute, Lyon University Hospital, Pierre Bénite, France.
Pierre-Jean
PJ
Souquet
Thoracic Oncology Unit, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.
Patrick
P
Merle
Université Grenoble 1, INSERM, U 823, Institut A Bonniot, Université J Fourier, La Tronche, France Thoracic Oncology Unit, Teaching Hospital A Michallon, Grenoble, France.
Denis
D
Moro-Sibilot
Thoracic Oncology Unit, Lyon Cancer Centre Léon Bérard, Lyon, France.
Maurice
M
Pérol
International Agency for Research on Cancer, Molecular Mechanisms and Biomarkers Group, Lyon, France.
Jiri
J
Zavadil
Université Grenoble 1, INSERM, U 823, Institut A Bonniot, Université J Fourier, La Tronche, France Thoracic Oncology Unit, Teaching Hospital A Michallon, Grenoble, France.
Christian
C
Brambilla
International Agency for Research on Cancer, Molecular Mechanisms and Biomarkers Group, Lyon, France.
Magali
M
Olivier
Department of Acute Respiratory Medicine and Thoracic Oncology Department, Lyon Sud Hospital and Lyon University Cancer Institute, Lyon University Hospital, Pierre Bénite, France EMR 3738 "Therapeutic Targeting in Oncology", Lyon Sud - Charles Mérieux Faculty of Medicine, Lyon 1 University, Oullins, France sebastien.couraud@chu-lyon.fr.
Sébastien
S
Couraud
D000230:Adenocarcinoma / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D018287:Carcinoma, Large Cell / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D004247:DNA / Q000097:blood*; D004273:DNA, Neoplasm / Q000097:blood; D005260:Female; D005470:Fluorometry; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis
D015415:Biomarkers; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004247:DNA