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

Research output: Contribution to journalArticle

Abstract

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
Volume134
DOIs
Publication statusPublished - 2019 Aug 1

Fingerprint

Tumor Burden
Non-Small Cell Lung Carcinoma
DNA
Glycolysis
Survival
Disease-Free Survival
Neoplasms

Keywords

  • 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

Cite this

@article{4b4639dd25fc462e9141205b961950e9,
title = "Clinical implications of circulating cell-free DNA quantification and metabolic tumor burden in advanced non-small cell lung cancer",
abstract = "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.",
keywords = "Cell-free nucleic acids quantification, Metabolic tumor volume, Non-small-cell lung carcinoma, Prognosis, Total lesion glycolysis",
author = "Hyun, {Myung Han} and Lee, {Eun Seong} and Eo, {Jae Seon} and Sungeun Kim and Kang, {Eun Joo} and Sung, {Jae Sook} and Choi, {Yoon Ji} and Park, {Kyong Hwa} and Shin, {Sang Won} and Lee, {Sung Yong} and Kim, {Yeul Hong}",
year = "2019",
month = "8",
day = "1",
doi = "10.1016/j.lungcan.2019.06.014",
language = "English",
volume = "134",
pages = "158--166",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Clinical implications of circulating cell-free DNA quantification and metabolic tumor burden in advanced non-small cell lung cancer

AU - Hyun, Myung Han

AU - Lee, Eun Seong

AU - Eo, Jae Seon

AU - Kim, Sungeun

AU - Kang, Eun Joo

AU - Sung, Jae Sook

AU - Choi, Yoon Ji

AU - Park, Kyong Hwa

AU - Shin, Sang Won

AU - Lee, Sung Yong

AU - Kim, Yeul Hong

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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.

AB - 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.

KW - Cell-free nucleic acids quantification

KW - Metabolic tumor volume

KW - Non-small-cell lung carcinoma

KW - Prognosis

KW - Total lesion glycolysis

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U2 - 10.1016/j.lungcan.2019.06.014

DO - 10.1016/j.lungcan.2019.06.014

M3 - Article

VL - 134

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EP - 166

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

ER -