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

• Published in: British journal of cancer 2017-08, Vol.117 (5), p.704-709
• Main Authors: Winther-Larsen, Anne, Demuth, Christina, Fledelius, Joan, Madsen, Anne Tranberg, Hjorthaug, Karin, Meldgaard, Peter, Sorensen, Boe Sandahl
• Format: Article
• Language: English
• Subjects: 692/4017; 692/4028/67/1612/1350; Aged; Aged, 80 and over; Biomarkers, Tumor - blood; Biomedical and Life Sciences; Biomedicine; Blood; Cancer Research; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - diagnostic imaging; Carcinoma, Non-Small-Cell Lung - genetics; Colon; Colon cancer; Computed tomography; Deoxyribonucleic acid; DNA; DNA, Neoplasm - blood; Drug Resistance; Epidemiology; Female; Fluorodeoxyglucose F18; Gene Frequency; Glucose; Glycolysis; Humans; Lung cancer; Lung Neoplasms - blood; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - genetics; Male; Metabolism; Middle Aged; Molecular Diagnostics; Molecular Medicine; Mutation; Non-small cell lung carcinoma; Oncology; Positron emission tomography; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Retrospective Studies; Survival; Survival Rate; Tomography; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2017.215

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.