Circulating Tumor DNA Reflects Tumor Metabolism Rather Than Tumor Burden in Chemotherapy-Naive Patients with Advanced Non-Small Cell Lung Cancer: 18 F-FDG PET/CT Study

J Nucl Med. 2017 Nov;58(11):1764-1769. doi: 10.2967/jnumed.117.193201. Epub 2017 Apr 27.


We aimed to evaluate the relationships between circulating tumor cells (CTCs) or plasma cell-free DNA (cfDNA) on one side and a comprehensive range of 18F-FDG PET/CT-derived parameters on the other side in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC). Methods: From a group of 79 patients included in a trial evaluating the role of pretreatment circulating tumor markers as predictors of prognosis in chemotherapy-naive patients with advanced NSCLC, we recruited all those who underwent 18F-FDG PET/CT for clinical reasons at our institution before inclusion in the trial (and thus just before chemotherapy). For each patient, a peripheral blood sample was collected at baseline for the evaluation of CTCs and cfDNA. CTCs were isolated by size using a filtration-based device and then morphologically identified and enumerated; cfDNA was isolated from plasma and quantified by a quantitative polymerase chain reaction using human telomerase reverse transcriptase. The following 18F-FDG PET/CT-derived parameters were computed: maximum diameter of the primary lesion (T), of the largest lymph node (N), and of the largest metastatic lesion (M); SUVmax; SUVmean; size-incorporated SUVmax; metabolic tumor volume; and total lesion glycolysis. All parameters were independently measured for T, N, and M. The associations among CTCs, cfDNA, and 18F-FDG PET/CT-derived parameters were evaluated by multivariate-analysis. Patients were divided into 2 groups according to the presence of either limited metastatic involvement (M1a or M1b due to extrathoracic lymph nodes only) or disseminated metastatic disease. The presence or absence of metabolically active bone lesions was also recorded for each patient, and patient subgroups were compared. Results: Thirty-seven patients recruited in the trial matched our PET-based criteria (24 men; age, 64.5 ± 8.1 y). SUVmax for the largest metastatic lesion was the only variable independently associated with baseline cfDNA levels (P = 0.016). Higher levels of cfDNA were detected in the subgroup of patients with metabolically active bone lesions (P = 0.02), but no difference was highlighted when patients with more limited metastatic disease were compared with patients with disseminated metastatic disease. Conclusion: The correlation of cfDNA levels with tumor metabolism, but not with metabolic tumor volume at regional or distant levels, suggests that cfDNA may better reflect tumor biologic behavior or aggressiveness rather than tumor burden in metastatic NSCLC.

Trial registration: NCT02055144.

Keywords: PET; SUVmax; circulating tumor markers; metabolic tumor volume; non–small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • DNA, Neoplasm / blood*
  • Female
  • Fluorodeoxyglucose F18
  • Glycolysis
  • Humans
  • Image Processing, Computer-Assisted
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Multimodal Imaging
  • Neoplasm Metastasis / pathology
  • Positron Emission Tomography Computed Tomography
  • Radiopharmaceuticals
  • Tumor Burden*


  • DNA, Neoplasm
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18

Associated data