PDF(Pubmed)
Abstract：
Presence of circulating tumor DNA (ctDNA) is prognostic in solid tumors treated with curative intent. Studies have evaluated ctDNA at specific \"landmark\" or multiple \"surveillance\" time points. However, variable results have led to uncertainty about its clinical validity.
A PubMed search identified relevant studies evaluating ctDNA monitoring in solid tumors after curative intent therapy. Odds ratios for recurrence at both landmark and surveillance time points for each study were calculated and pooled in a meta-analysis using the Peto method. Pooled sensitivity and specificity weighted by individual study inverse variance were estimated and meta-regression using linear regression weighted by inverse variance was performed to explore associations between patient and tumor characteristics and the odds ratio for disease recurrence.
Of 39 studies identified, 30 (1924 patients) and 24 studies (1516 patients) reported on landmark and surveillance time points, respectively. The pooled odds ratio for recurrence at landmark was 15.47 (95% confidence interval = 11.84 to 20.22) and at surveillance was 31.0 (95% confidence interval = 23.9 to 40.2). The pooled sensitivity for ctDNA at landmark and surveillance analyses was 58.3% and 82.2%, respectively. The corresponding specificities were 92% and 94.1%, respectively. Prognostic accuracy was lower with tumor agnostic panels and higher with longer time to landmark analysis, number of surveillance draws, and smoking history. Adjuvant chemotherapy negatively affected landmark specificity.
Although prognostic accuracy of ctDNA is high, it has low sensitivity, borderline high specificity, and therefore modest discriminatory accuracy, especially for landmark analyses. Adequately designed clinical trials with appropriate testing strategies and assay parameters are required to demonstrate clinical utility.
A PubMed search identified relevant studies evaluating ctDNA monitoring in solid tumors after curative intent therapy. Odds ratios for recurrence at both landmark and surveillance time points for each study were calculated and pooled in a meta-analysis using the Peto method. Pooled sensitivity and specificity weighted by individual study inverse variance were estimated and meta-regression using linear regression weighted by inverse variance was performed to explore associations between patient and tumor characteristics and the odds ratio for disease recurrence.
Of 39 studies identified, 30 (1924 patients) and 24 studies (1516 patients) reported on landmark and surveillance time points, respectively. The pooled odds ratio for recurrence at landmark was 15.47 (95% confidence interval = 11.84 to 20.22) and at surveillance was 31.0 (95% confidence interval = 23.9 to 40.2). The pooled sensitivity for ctDNA at landmark and surveillance analyses was 58.3% and 82.2%, respectively. The corresponding specificities were 92% and 94.1%, respectively. Prognostic accuracy was lower with tumor agnostic panels and higher with longer time to landmark analysis, number of surveillance draws, and smoking history. Adjuvant chemotherapy negatively affected landmark specificity.
Although prognostic accuracy of ctDNA is high, it has low sensitivity, borderline high specificity, and therefore modest discriminatory accuracy, especially for landmark analyses. Adequately designed clinical trials with appropriate testing strategies and assay parameters are required to demonstrate clinical utility.
摘要：
背景：循环肿瘤DNA（ctDNA）的存在是治疗性实体瘤的预后。研究已经在特定的“地标”或多个“监测”时间点评估了ctDNA。然而,可变的结果导致其临床有效性的不确定性。
方法：PubMed搜索确定了相关研究，评估在根治性治疗后实体瘤的ctDNA监测。使用Peto方法计算每个研究的地标和监测时间点的复发几率（OR），并在荟萃分析中汇总。估计通过个体研究逆方差加权的集合敏感性和特异性，并利用逆方差加权的线性回归进行meta回归，以探索患者和肿瘤特征与疾病复发的OR之间的关联。
结果：在确定的39项研究中，30项（1924例）和24项研究（1516例）分别报道了界标和监测时间点。地标复发的合并OR为15.47（95％CI11.84-20.22），监测时为31.0（95％CI23.9-40.2）。地标和监测分析对ctDNA的合并敏感性为58.3％和82.2％。相应的特异性为92%和94.1%。肿瘤不可知组的预后准确性较低，而界标分析的时间较长，预后准确性较高。监测抽奖次数和吸烟史。辅助化疗对标志特异性产生负面影响。
结论：尽管ctDNA的预后准确性很高，灵敏度低,边界高特异性，因此，适度的辨别准确性，特别是对于具有里程碑意义的分析。需要具有适当的测试策略和测定参数的适当设计的临床试验来证明临床实用性。
方法：PubMed搜索确定了相关研究，评估在根治性治疗后实体瘤的ctDNA监测。使用Peto方法计算每个研究的地标和监测时间点的复发几率（OR），并在荟萃分析中汇总。估计通过个体研究逆方差加权的集合敏感性和特异性，并利用逆方差加权的线性回归进行meta回归，以探索患者和肿瘤特征与疾病复发的OR之间的关联。
结果：在确定的39项研究中，30项（1924例）和24项研究（1516例）分别报道了界标和监测时间点。地标复发的合并OR为15.47（95％CI11.84-20.22），监测时为31.0（95％CI23.9-40.2）。地标和监测分析对ctDNA的合并敏感性为58.3％和82.2％。相应的特异性为92%和94.1%。肿瘤不可知组的预后准确性较低，而界标分析的时间较长，预后准确性较高。监测抽奖次数和吸烟史。辅助化疗对标志特异性产生负面影响。
结论：尽管ctDNA的预后准确性很高，灵敏度低,边界高特异性，因此，适度的辨别准确性，特别是对于具有里程碑意义的分析。需要具有适当的测试策略和测定参数的适当设计的临床试验来证明临床实用性。
