Clinical implications of circulating cell-free DNA quantification and metabolic tumor burden in advanced non-small cell lung cancer

Myung Han Hyun, Eun Seong Lee, Jae Seon Eo, Sungeun Kim, Eun Joo Kang, Jae Sook Sung, Yoon Ji Choi, Kyong Hwa Park, Sang Won Shin, Sung Yong Lee, Yeul Hong Kim

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Objectives: This study unravels the significance of cell-free DNA (cfDNA) quantification as a promising measure of the biological behavior/aggressiveness of tumors. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured by positron emission tomography/computed tomography scan enable a precise assessment of metabolic tumor burden. However, their clinical implications in identifying patients who need more aggressive treatment in advanced non-small cell lung cancer (NSCLC) are not fully understood. Materials and methods: In the current prospective trial, we analyzed 101 newly diagnosed advanced NSCLC (stage III-IV) patients with measurable baseline MTV, TLG, and cfDNA quantification. The best cut-offs for cfDNA levels, MTV, and TLG to predict progression-free survival and overall survival were determined using X-tile analysis. Results: There were significant positive correlations between cfDNA and MTV (r = 0.488, p < 0.001) and between cfDNA and TLG (r = 0.554, p < 0.001). High-cfDNA levels and high-MTV/TLG negatively correlated with overall survival (OS) (all p < 0.001). Patients with high-MTV showed similar median OS irrespective of their cfDNA levels (low-cfDNA vs. high-cfDNA=9.2 vs 6.6 months; p > 0.05). However, patients with low-MTV and low-cfDNA levels showed longer OS than those with low-MTV and high-cfDNA levels (low-cfDNA vs. high-cfDNA=49.3 vs 11.5 months; p < 0.001). The patient group with low-TLG also showed similar trends. The cfDNA level was an independent prognostic factor for OS by Cox-proportional hazard analysis. Conclusion: Although the patients with high metabolic tumor burden had a poor prognosis, regardless of the biological behavior/aggressiveness of the tumor, patients with low metabolic tumor burden and high cfDNA levels showed a poor prognosis. Taken together, this study indicates a stronger prognostic value of baseline cfDNA levels in identifying patients with advanced NSCLC and personalizing their treatment strategies for better survival.

Original languageEnglish
Pages (from-to)158-166
Number of pages9
JournalLung Cancer
Publication statusPublished - 2019 Aug


  • Cell-free nucleic acids quantification
  • Metabolic tumor volume
  • Non-small-cell lung carcinoma
  • Prognosis
  • Total lesion glycolysis

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research


Dive into the research topics of 'Clinical implications of circulating cell-free DNA quantification and metabolic tumor burden in advanced non-small cell lung cancer'. Together they form a unique fingerprint.

Cite this