Circulating Cell Free DNA Quantification for Survival and Tumor Response by CT Monitoring in Non-Small Cell Lung Cancer Patients: A Correlative Biomarker Study
폐암 환자에 대한 Cell Free DNA 정량 측정의 예후적 가치 및 CT 기반의 종양 반응에 대한 진단적 가치에 대한 Biomarker 연구
- 주제(키워드) cell free DNA quantification , prognosis , non-small cell lung cancer
- 발행기관 고려대학교 대학원
- 지도교수 김열홍
- 발행년도 2017
- 학위수여년월 2017. 8
- 학위구분 석사
- 학과 대학원 의학과(일반대학원)
- 세부전공 내과학 전공
- 원문페이지 60 p
- 실제URI http://www.dcollection.net/handler/korea/000000077004
- 본문언어 영어
- 제출원본 000045920324
초록/요약
Background: The aim of this study was to explore prognostic value for the quantification of cell-free deoxyribonucleic acid (cfDNA) and the predictive efficacy over time on tumor response by computed tomography (CT) scan after chemotherapy in non-small cell lung cancer (NSCLC). Patients and methods: A total of 177 NSCLC patients (including 112 chemo-naive stage IV adenocarcinoma (ADC)) were finally enrolled into a prospective biomarker trial to evaluate prognostic value of cfDNA. Among them, 43 patients (25 disease progression, 18 non-progression) were available for the cfDNA kinetics analysis. The quantitative analysis for cfDNA was performed with Agilent High Sensitivity DNA kit. All consecutive paired blood collections and CT scan assessment by RECIST v1.1 were done. The best cutoff for cfDNA to predict progression free survival (PFS) and overall survival (OS) was determined using X-tile analysis. cfDNA Kinetics analysis was done at different time point (at first follow up, at best response, at progression) Results: Data revealed that cfDNA concentration is not correlated to baseline demographic except for clinical stage (p value = 0.003). In total population, multivariate cox regression model identified cfDNA concentration is independent progsnostic parameter on PFS (hazard ratio (HR) = 2.60, 95% confidential interval (CI) = 1.65 – 4.10, p value = 0.008) and OS (HR = 2.63, 95% CI = 1.66 – 4.17, p value < 0.001). In addition, the cfDNA concentration in chemo-naive stage IV ADC only patients also showed independent progsnostic actor on PFS (HR = 2.21, 95% CI = 1.37 – 3.55, p value = 0.001) and OS (HR = 3.50, 95% CI = 1.90 – 6.45, p value < 0.001). In cfDNA kinetics analysis, there is no detectable pattern in percent changes of cfDNA concentration at first follow up, at best response, and at progression comparing to baseline as classified by radiologic best response. Conclusions: Our findings suggest that cfDNA concentration from plasma may be useful non-invasive technique for predict prognosis for NSCLC survival. However, its clinical validity to use predictive marker for tumor response is not supported.
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Contents
Abstract P4
Introduction P6
Methods P8
Results P13
Discussion P19
References P25
Tables P31
Figures P40
