The 16 studies [12C17, 22C31] were published between 2007 and 2020, as well as the sample size of ctDNA prognosis analyses ranged from 20 to 551, with an overall total of 1 1,781

The 16 studies [12C17, 22C31] were published between 2007 and 2020, as well as the sample size of ctDNA prognosis analyses ranged from 20 to 551, with an overall total of 1 1,781. CI?=?1.30C4.28, 0.00001). The baseline BRAFV600 ctDNA mutation-positive group was significantly associated with adverse OS compared with the baseline ctDNA-negative group (pooled HR?=?1.90, 95% CI?=?1.58C2.29, 0.00001). There were no significant differences in PFS between the baseline BRAFV600 ctDNA mutation-detectable group and the undetectable group (pooled HR?=?1.02, 95% CI?=?0.72C1.44, 0.05 were considered significant for heterogeneity. For forest plots with more than 10 included studies or results, we evaluated publication bias using funnel plots for visual Setiptiline inspection and conducted quantitative estimations using Egger’s test. Sensitivity analysis was performed by excluding each study in turn to assess the stability of the results. All analyses were carried out using Review Manager version 5.3 (The Cochrane Collaboration, Copenhagen: The Nordic Cochrane Center, 2012) and STATA version 12.0 (STATA Corporation, College Station, TX, USA). 3. Results 3.1. Search Results A total of 2,365 articles were identified after removing duplicates. By reviewing titles and abstracts, 2,305 articles were excluded, of which 2,114 were not related to the disease or subject of our meta-analysis, 86 were reviews or systematic evaluations, and 105 were abstracts, conference papers, or case reports. After detailed reading and evaluation of 60 articles, we excluded eight articles because the number of patients analyzed for prognosis was less than 15. Twelve articles were excluded for lack of prognostic information. Twenty-one articles were excluded because they did not provide sufficient data to extract HRs for PFS or OS. Further three articles with or suspected to have overlapping study populations were excluded. Finally, 16 articles [12C17, 22C31] proved eligible for inclusion and were Setiptiline analyzed (Figure 1). Open in a separate window Figure 1 Study selection strategy and flow diagram. 3.2. Literature Characteristics and Quality The characteristics and quality of studies included in the meta-analysis are described in Table 1. The 16 studies [12C17, 22C31] were published between 2007 and 2020, and the sample size of ctDNA prognosis analyses ranged from 20 to 551, with an overall total of 1 1,781. Among the studies, four [12, 13, 25, 29] were from Australia, and one study each was from the UK [14], Poland [22], Spain [28], Norway [16], Italy [24], Belgium [15], France [27], and USA [31]. In addition, one study [23] was from Belgium and Germany. The samples from one study [17] were obtained from the participants of a phase 2 clinical trial in which the patients were from 10 countries. The samples from one study [26] were obtained from the participants of a phase 3 clinical trial in which the patients were from 12 countries. One study [30] included samples from the participants of four clinical trials, each involving patients from more than one country. Since two of the clinical trials enrolled the same patient populations, we chose the one with larger sample size for meta-analysis. In addition to the study [30] from three clinical trials, another three studies [12, 23, 26] were grouped by cohort or drug therapy. Therefore, we considered them as independent studies. All the patients in 15 studies had advanced melanoma, while the patients in one study [14] were at stage II-III. Plasma ctDNA levels were assessed in 12 studies [12C16, 22, 23, 25C27, 29, 30], serum ctDNA levels were assessed in three studies [17, 24, 31], and ctDNA was extracted from serum and plasma samples in one study [28]. Twelve studies [12, 13, 15, 16, 22C24, 26C29, 31] analyzed ctDNA from blood samples before and after treatment, and four studies [14, 17, 25, 30] analyzed ctDNA before treatment. However, among Setiptiline these 12 studies [12, 13, 15, 16, 22C24, 26C29, 31], PFS or OS analysis was not performed in eight studies [12, 15, 22, 24, 26C29] using posttreatment data, and pretreatment data was not performed in one study [31]. Droplet digital PCR (ddPCR) was used to detect ctDNA in blood samples in 11 studies [12C16, 22C26, 29]. Only the BRAFV600 ctDNA mutation was detected in seven studies [17, 22, 24, 26, 28, 30, 31], and multiple genes were detected in another study [23], although PFS or OS analysis of the BRAFV600 mutation was available. The other studies [12C16, 25, 27, 29] Tlr4 all detected the mutations in multiple genes. The quality of studies included was evaluated by NOS, and all the studies received.