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Circulating Tumor DNA as a Prognostic Biomarker in Localized Non-small Cell Lung Cancer.

ABSTRACT: Background:Routine clinical surveillance involves serial radiographic imaging following radical surgery in localized non-small cell lung cancer (NSCLC). However, such surveillance can detect only macroscopic disease recurrence and is frequently inconclusive. We investigated if detection of ctDNA before and after resection of NSCLC identifies the patients with risk of relapse, and furthermore, informs about response to management. Methods:We recruited a total of 77 NSCLC patients. A high-throughput 127 target-gene capture technology and a high-sensitivity circulating single-molecule amplification and resequencing technology (cSMART) assay were used to detect the somatic mutations in the tumor tissues as well as the plasma of NSCLC patients before and after surgery to monitor for minimal residual disease (MRD). Kaplan-Meier and Cox regression analysis were performed to evaluate the relapse-free survival (RFS) and overall survival (OS) of patients with predictor variables. Results:Patients with a higher stage (III/IV) and preoperative ctDNA-positive status demonstrated a significant 2.8-3.4-fold risk and 3.8-4.0-fold risk for recurrence and death, respectively. Preoperative ctDNA-positive patients associated with a lower RFS (HR = 3.812, p = 0.0005) and OS (HR = 5.004, p = 0.0009). Postoperative ctDNA-positive patients also associated with a lower RFS (HR = 3.076, p = 0.0015) and OS (HR = 3.195, p = 0.0053). Disease recurrence occurred among 63.3% (19/30) of postoperative ctDNA-positive patients. Most of these patients 89.5% (17/19) had detectable ctDNA within 2 weeks after surgery and was identified in advance of radiographic findings by a median of 12.6 months. Conclusion:Advanced stage and preoperative ctDNA-positive are strong predictors of RFS and OS in localized NSCLC patients undergoing complete resection. Postoperative detection of ctDNA increases chance to detect early relapse, thus can fulfill an important role in stratifying patients for immediate further treatment with adjuvant and neoadjuvant therapy.

SUBMITTER: Peng M

PROVIDER: S-EPMC7523087 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Circulating Tumor DNA as a Prognostic Biomarker in Localized Non-small Cell Lung Cancer.

Peng Muyun M Huang Qi Q Yin Wei W Tan Sichuang S Chen Chen C Liu Wenliang W Tang Jingqun J Wang Xiang X Zhang Bingyu B Zou Min M Li Jina J Su Wenhui W Wang Lientu L Chin Lihan L Yu Fenglei F

Frontiers in oncology 20200915

<h4>Background</h4>Routine clinical surveillance involves serial radiographic imaging following radical surgery in localized non-small cell lung cancer (NSCLC). However, such surveillance can detect only macroscopic disease recurrence and is frequently inconclusive. We investigated if detection of ctDNA before and after resection of NSCLC identifies the patients with risk of relapse, and furthermore, informs about response to management.<h4>Methods</h4>We recruited a total of 77 NSCLC patients. ...[more]

PMID: 33042842

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Project description:BackgroundSeveral recent studies have reported the increasing application of preoperative circulating tumor DNA (ctDNA) as a biomarker of tumor burden for guiding potential postoperative treatment strategies.MethodsA meta-analysis of prospective/retrospective cohort studies was conducted to compare the prognosis of preoperatively genetically positive and genetically negative NSCLC patients. The endpoints used in the included studies were overall survival (OS) and recurrence-free survival (RFS). The objective of the meta-analysis was to comprehensively explore the prognostic value of preoperative ctDNA for patients with non-small-cell lung cancer (NSCLC) and its significance in guiding postoperative adjuvant therapy (AT) in patients with NSCLC.ResultsThe preliminary analysis identified 1565 studies, among which only 11 studies fulfilled the eligibility criteria and were finally included in the present systematic review and meta-analysis. The statistical results revealed that the expression of preoperative ctDNA was associated with worse RFS (HR = 3.00; 95% CI 2.26-3.98; I2 = 0%) and OS (HR = 2.77; 95% CI 1.67-4.58; I2 = 0%), particularly in lung adenocarcinoma (LUAD) patients (RFS: HR = 3.46; 95% CI 2.37-5.05; I2 = 0%; OS: HR = 3.52; 95% CI 1.91-6.49; I2 = 0%) and patients with I-II stage of NSCLC (RFS: HR = 2.84; 95% CI 1.88-4.29; I2 = 0%; OS: HR = 2.60; 95% CI 1.43-4.74; I2 = 0%). Moreover, compared to patients with negative preoperative ctDNA, patients with positive preoperative ctDNA presented greater survival benefits (HR = 0.39; 95% CI 0.22-0.67; I2 = 2%) from postoperative AT.ConclusionThe evaluation of the prognostic value of preoperative ctDNA revealed that preoperative ctDNA might be used as a prognostic biomarker for patients with LUAD or those with stage I-II NSCLC. In addition, postoperative AT is recommended for NSCLC patients with positive preoperative ctDNA, regardless of the disease stage and subtype.

Dataset Information

Circulating Tumor DNA as a Prognostic Biomarker in Localized Non-small Cell Lung Cancer.

Publications

Circulating Tumor DNA as a Prognostic Biomarker in Localized Non-small Cell Lung Cancer.

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