Dataset Information

Prognostic value of circulating tumor DNA in patients with colon cancer: Systematic review.

ABSTRACT: The application of circulating tumor DNA(ctDNA) represents a non-invasive method for tumor detection. Its prognostic significance in patients with colorectal cancer is controversial. We performed a systematic review of data from published studies to assess the prognostic values of ctDNA in patients with colorectal cancer. We searched Medline, Embase, Web of Science, the Cochrane Library, and Scopus databases to identify eligible studies reporting disease-free survival (DFS) and overall survival (OS) stratified by ctDNA prior to December 6, 2016. We evaluated the quality and design of these studies. A total of 22 studies were eligible for systematic review. Among them, 11 studies investigated the prognostic value of ctDNA on disease-free survival (DFS). Seven of 11 studies showed that ctDNA was an independent variable to estimate the probability of DFS by multivariate analyses. Thirteen studies assessed the relationship between ctDNA and overall survival (OS). Eight of 13 studies showed that ctDNA was an independent predictor of worse OS through the use of multivariate analyses. This analysis provides evidence that ctDNA may be a prognostic biomarker, negatively correlated with the survival of patients with colorectal cancer.

SUBMITTER: Fan G

PROVIDER: S-EPMC5302475 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Prognostic value of circulating tumor DNA in patients with colon cancer: Systematic review.

Fan Gaowei G Zhang Kuo K Yang Xin X Ding Jiansheng J Wang Zujian Z Li Jinming J

PloS one 20170210 2

The application of circulating tumor DNA(ctDNA) represents a non-invasive method for tumor detection. Its prognostic significance in patients with colorectal cancer is controversial. We performed a systematic review of data from published studies to assess the prognostic values of ctDNA in patients with colorectal cancer. We searched Medline, Embase, Web of Science, the Cochrane Library, and Scopus databases to identify eligible studies reporting disease-free survival (DFS) and overall survival ...[more]

PMID: 28187169

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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.

Project description:ObjectiveCirculating tumor DNA (ctDNA) is increasingly being used as a potential prognosis biomarker in patients of breast cancer. This review aims to assess the clinical value of ctDNA in outcome prediction in breast cancer patients throughout the whole treatment cycle.MethodsPubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov were searched from January 2016 to May 2022. Conference abstracts published in last three years were also included. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English languages were included. The following pre-specified criteria should be met for inclusion: (1) observational studies (prospective or retrospective), randomized control trials, case-control studies and case series studies; (2) patients with breast cancer; (3) ctDNA measurement; (4) clinical outcome data such as objective response rate (ORR), pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS), and so on. The random-effect model was preferred considering the potential heterogeneity across studies. The primary outcomes included postoperative short-term outcomes (ORR and pCR) and postoperative long-term outcomes (RFS, OS, and relapse). Secondary outcomes focused on ctDNA detection rate.ResultsA total of 30 studies, comprising of 19 cohort studies, 2 case-control studies and 9 case series studies were included. The baseline ctDNA was significantly negatively associated with ORR outcome (Relative Risk [RR] = 0.65, 95% confidence interval [CI]: 0.50-0.83), with lower ORR in the ctDNA-positive group than ctDNA-negative group. ctDNA during neoadjuvant therapy (NAT) treatment was significantly associated with pCR outcomes (Odds Ratio [OR] = 0.15, 95% CI: 0.04-0.54). The strong association between ctDNA and RFS or relapse outcome was significant across the whole treatment period, especially after the surgery (RFS: Hazard Ratio [HR] = 6.74, 95% CI: 3.73-12.17; relapse outcome: RR = 7.11, 95% CI: 3.05-16.53), although there was heterogeneity in these results. Pre-operative and post-operative ctDNA measurements were significantly associated with OS outcomes (pre-operative: HR = 2.03, 95% CI: 1.12-3.70; post-operative: HR = 6.03, 95% CI: 1.31-27.78).ConclusionsIn this review, ctDNA measurements at different timepoints are correlated with evaluation indexes at different periods after treatment. The ctDNA can be used as an early potential postoperative prognosis biomarker in breast cancer, and also as a reference index to evaluate the therapeutic effect at different stages.

Project description:BackgroundTP53 mutations are common in breast cancer. There is currently no large-scale cohort study to investigate the TP53 landscape in breast cancer patients from China. The predictive value of TP53 mutations for the efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy in breast cancer remains controversial. In the present study, we aimed to analyze the clinical spectrum and prognostic value of TP53 mutations in circulating tumor DNA (ctDNA) from breast cancer patients in China.MethodsWe retrospectively analyzed the clinical data and TP53 mutation features in ctDNA samples from 804 patients with metastatic breast cancer. TP53 mutations were detected by target region capture-based next-generation sequencing. The relationship between TP53 mutation status and disease-free survival (DFS) was analyzed in 444 patients with metastatic breast cancer. Moreover, the relationship between TP53 mutation status and progression-free survival (PFS) was analyzed in 55 HER2-positive patients treated with first-line trastuzumab-based therapy. Kaplan-Meier analysis was performed to estimate the survival curves of the different subgroups, and the log-rank test was used to compare the curves. A Cox regression model was used to estimate multivariable-adjusted hazard ratios and their 95% confidence intervals (CIs) associated with the DFS and PFS.ResultsAmong the 804 investigated patients, 431 (53.6%) patients harbored TP53 mutations. TP53 mutations were differentially distributed among different molecular subtypes of breast cancer (P < 0.05). Patients with TP53 mutations had a shorter DFS than those with wild-type TP53 (hazard ratio = 1.32, 95% CI = 1.09-1.61, P = 0.005). TP53 mutations in exons 5-8 were associated with worse outcome (hazard ratio = 1.50, 95% CI = 1.11-2.03, P = 0.009). However, TP53 mutation status was not significantly associated with PFS in HER2-positive patients who received first-line trastuzumab-based therapy (P = 0.966). Interestingly, in the taxane combination group, patients with TP53 mutations exhibited longer PFS than those without TP53 mutations (hazard ratio = 0.08, 95% CI = 0.02-0.30, P < 0.001). However, in the non-taxane combination group, patients with TP53 mutations displayed shorter PFS than those with wild-type TP53 (hazard ratio = 4.84, 95% CI = 1.60-14.66, P = 0.005).ConclusionsTP53 mutations in exons 5-8 may be an independent prognostic marker for short DFS in patients with metastatic breast cancer. TP53 mutations had opposite effects on trastuzumab-treated patients treated with and without taxanes.

Dataset Information

Prognostic value of circulating tumor DNA in patients with colon cancer: Systematic review.

Publications

Prognostic value of circulating tumor DNA in patients with colon cancer: Systematic review.

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