Quantification of circulating cell-free DNA to predict patient survival in non-small-cell lung cancer

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We used computed tomography (CT) to explore the prognostic value of cellfree (cf) DNA quantification and its predictive efficacy over time after chemotherapy in non-small-cell lung cancer (NSCLC) patients. In total, 177 NSCLC patients were enrolled in a prospective biomarker trial. Consecutive paired blood collection was performed to determine cfDNA concentrations at baseline CT and throughout serial follow-ups. The best cfDNA cut-off value to predict progression-free and overall survival was determined using X-tile analysis. Among 112 chemo-naive patients with stage IV adenocarcinoma, 43 were available for follow-up analysis. Cox regression multivariate analysis indicated that a high cfDNA concentration was an independent negative prognostic factor for progression-free survival (hazard ratio: 2.60; 95% confidence interval: 1.65-4.10; p = 0.008) and overall survival (hazard ratio: 2.63; 95% confidence interval: 1.66-4.17; p < 0.001). However, cfDNA concentration changes during treatment did not correlate with radiological CT responses at first follow-up or best response. No pattern was noted in the percent change in the cfDNA concentration from baseline or subsequently measured level to progression. The serum cfDNA concentration is thus associated with NSCLC patient prognosis, but does not appear to be a clinically valid marker for tumor responses.

Original languageEnglish
Pages (from-to)94417-94430
Number of pages14
JournalOncotarget
Volume8
Issue number55
DOIs
Publication statusPublished - 2017 Nov 1

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Non-Small Cell Lung Carcinoma
Survival
DNA
Tomography
Disease-Free Survival
Confidence Intervals
Tumor Biomarkers
Adenocarcinoma
Multivariate Analysis
Biomarkers
Regression Analysis
Drug Therapy
Serum
Therapeutics

Keywords

  • Cell-free DNA concentration
  • Non-small-cell lung cancer
  • Prognostic value

ASJC Scopus subject areas

  • Oncology

Cite this

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title = "Quantification of circulating cell-free DNA to predict patient survival in non-small-cell lung cancer",
abstract = "We used computed tomography (CT) to explore the prognostic value of cellfree (cf) DNA quantification and its predictive efficacy over time after chemotherapy in non-small-cell lung cancer (NSCLC) patients. In total, 177 NSCLC patients were enrolled in a prospective biomarker trial. Consecutive paired blood collection was performed to determine cfDNA concentrations at baseline CT and throughout serial follow-ups. The best cfDNA cut-off value to predict progression-free and overall survival was determined using X-tile analysis. Among 112 chemo-naive patients with stage IV adenocarcinoma, 43 were available for follow-up analysis. Cox regression multivariate analysis indicated that a high cfDNA concentration was an independent negative prognostic factor for progression-free survival (hazard ratio: 2.60; 95{\%} confidence interval: 1.65-4.10; p = 0.008) and overall survival (hazard ratio: 2.63; 95{\%} confidence interval: 1.66-4.17; p < 0.001). However, cfDNA concentration changes during treatment did not correlate with radiological CT responses at first follow-up or best response. No pattern was noted in the percent change in the cfDNA concentration from baseline or subsequently measured level to progression. The serum cfDNA concentration is thus associated with NSCLC patient prognosis, but does not appear to be a clinically valid marker for tumor responses.",
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author = "Hyun, {Myung Han} and Sung, {Jae Sook} and Kang, {Eun Joo} and Choi, {Yoon Ji} and Park, {Kyong Hwa} and Shin, {Sang Won} and Lee, {Sung Yong} and Kim, {Yeul Hong}",
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AU - Hyun, Myung Han

AU - Sung, Jae Sook

AU - Kang, Eun Joo

AU - Choi, Yoon Ji

AU - Park, Kyong Hwa

AU - Shin, Sang Won

AU - Lee, Sung Yong

AU - Kim, Yeul Hong

PY - 2017/11/1

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N2 - We used computed tomography (CT) to explore the prognostic value of cellfree (cf) DNA quantification and its predictive efficacy over time after chemotherapy in non-small-cell lung cancer (NSCLC) patients. In total, 177 NSCLC patients were enrolled in a prospective biomarker trial. Consecutive paired blood collection was performed to determine cfDNA concentrations at baseline CT and throughout serial follow-ups. The best cfDNA cut-off value to predict progression-free and overall survival was determined using X-tile analysis. Among 112 chemo-naive patients with stage IV adenocarcinoma, 43 were available for follow-up analysis. Cox regression multivariate analysis indicated that a high cfDNA concentration was an independent negative prognostic factor for progression-free survival (hazard ratio: 2.60; 95% confidence interval: 1.65-4.10; p = 0.008) and overall survival (hazard ratio: 2.63; 95% confidence interval: 1.66-4.17; p < 0.001). However, cfDNA concentration changes during treatment did not correlate with radiological CT responses at first follow-up or best response. No pattern was noted in the percent change in the cfDNA concentration from baseline or subsequently measured level to progression. The serum cfDNA concentration is thus associated with NSCLC patient prognosis, but does not appear to be a clinically valid marker for tumor responses.

AB - We used computed tomography (CT) to explore the prognostic value of cellfree (cf) DNA quantification and its predictive efficacy over time after chemotherapy in non-small-cell lung cancer (NSCLC) patients. In total, 177 NSCLC patients were enrolled in a prospective biomarker trial. Consecutive paired blood collection was performed to determine cfDNA concentrations at baseline CT and throughout serial follow-ups. The best cfDNA cut-off value to predict progression-free and overall survival was determined using X-tile analysis. Among 112 chemo-naive patients with stage IV adenocarcinoma, 43 were available for follow-up analysis. Cox regression multivariate analysis indicated that a high cfDNA concentration was an independent negative prognostic factor for progression-free survival (hazard ratio: 2.60; 95% confidence interval: 1.65-4.10; p = 0.008) and overall survival (hazard ratio: 2.63; 95% confidence interval: 1.66-4.17; p < 0.001). However, cfDNA concentration changes during treatment did not correlate with radiological CT responses at first follow-up or best response. No pattern was noted in the percent change in the cfDNA concentration from baseline or subsequently measured level to progression. The serum cfDNA concentration is thus associated with NSCLC patient prognosis, but does not appear to be a clinically valid marker for tumor responses.

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