TY - JOUR

T1 - Correlation between circulating mutant DNA and metabolic tumour burden in advanced non-small cell lung cancer patients

AU - Winther-Larsen, Anne

AU - Demuth, Christina

AU - Fledelius, Joan

AU - Madsen, Anne Tranberg

AU - Hjorthaug, Karin

AU - Meldgaard, Peter

AU - Sorensen, Boe Sandahl

PY - 2017/8/22

Y1 - 2017/8/22

N2 - BACKGROUND: Mutated circulating cell-free DNA (cfDNA) has been suggested as a surrogate marker of tumour burden and aggressiveness of disease. We examined the association between the level of plasma mutant cfDNA and metabolic tumour burden (MTB) measured by (18)F-fluoro-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). Furthermore, the presence of mutant cfDNA was correlated with patient survival.METHODS: Forty-six advanced non-small cell lung cancer (NSCLC) patients were included. At the time of inclusion, blood sampling and a PET/CT scan were performed. cfDNA was isolated and next-generation sequencing (NGS) was performed (Ion AmpliSeq Colon and Lung Cancer panel v2). MTB was defined by a volumetric PET parameter.RESULTS: NGS succeeded in 41 patients. Mutations were detected in the blood of 24 patients. A significant correlation between the allele frequency of the most frequent mutation and MTB was found (P=0.001). Patients with detectable mutated cfDNA had a significantly shorter median overall survival compared with patients without (3.7 versus 10.6 months, P=0.019). This impact on survival was independent of the MTB.CONCLUSIONS: Level of mutated cfDNA tends to correlate with MTB in advanced-stage NSCLC patients. Patients with detectable mutant DNA in plasma had an inferior survival, indicating that this could be an important predictor of survival.

AB - BACKGROUND: Mutated circulating cell-free DNA (cfDNA) has been suggested as a surrogate marker of tumour burden and aggressiveness of disease. We examined the association between the level of plasma mutant cfDNA and metabolic tumour burden (MTB) measured by (18)F-fluoro-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). Furthermore, the presence of mutant cfDNA was correlated with patient survival.METHODS: Forty-six advanced non-small cell lung cancer (NSCLC) patients were included. At the time of inclusion, blood sampling and a PET/CT scan were performed. cfDNA was isolated and next-generation sequencing (NGS) was performed (Ion AmpliSeq Colon and Lung Cancer panel v2). MTB was defined by a volumetric PET parameter.RESULTS: NGS succeeded in 41 patients. Mutations were detected in the blood of 24 patients. A significant correlation between the allele frequency of the most frequent mutation and MTB was found (P=0.001). Patients with detectable mutated cfDNA had a significantly shorter median overall survival compared with patients without (3.7 versus 10.6 months, P=0.019). This impact on survival was independent of the MTB.CONCLUSIONS: Level of mutated cfDNA tends to correlate with MTB in advanced-stage NSCLC patients. Patients with detectable mutant DNA in plasma had an inferior survival, indicating that this could be an important predictor of survival.

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers, Tumor

KW - Carcinoma, Non-Small-Cell Lung

KW - DNA, Neoplasm

KW - Female

KW - Fluorodeoxyglucose F18

KW - Gene Frequency

KW - Glycolysis

KW - Humans

KW - Lung Neoplasms

KW - Male

KW - Middle Aged

KW - Mutation

KW - Positron Emission Tomography Computed Tomography

KW - Radiopharmaceuticals

KW - Retrospective Studies

KW - Survival Rate

KW - Journal Article

U2 - 10.1038/bjc.2017.215

DO - 10.1038/bjc.2017.215

M3 - Journal article

C2 - 28683468

VL - 117

SP - 704

EP - 709

JO - B J C

JF - B J C

SN - 0007-0920

IS - 5

ER -