Background: Biliary tract cancer (BTC) is an aggressive malignancy often diagnosed at an advanced stage and is associated with a poor prognosis. Non-invasive approaches can facilitate the early detection and identification of biomarkers to inform treatment strategies. Liquid biopsy, particularly through the analysis of circulating tumor DNA (ctDNA), has recently emerged as a valuable clinical and prognostic tool for guiding BTC management. Methods: The PubMed, Cochrane Library, and Wiley databases were searched for terms related to BTC and ctDNA, aiming to include studies evaluating the value of ctDNA as a predictor of overall (OS), progression-free (PFS), disease (DFS), and recurrence-free survival (RFS). Results: Twelve studies encompassing 2374 patients were considered eligible. The detection of ctDNA was associated with higher mortality and progression risk (HR 2.61, 95%CI 2.19–3.11 and HR 2.69, 95%CI 1.82–3.98, respectively), regardless of the ctDNA sampling time. The variant allele frequency (VAF) emerged as a valuable predictive marker, with higher VAF values being associated with higher mortality and progression risk (HR 2.37, 95%CI 1.83–3.06, and HR 2.22, 95%CI 1.40–3.53, respectively) compared with low levels of VAF. This association was observed regardless of chemotherapy administration, suggesting that VAF may serve as a potential marker of treatment resistance. Conclusions: This review underscores the clinical relevance of ctDNA status and related markers, such as VAF, in the management and prognostic evaluation of BTC. The findings support the integration of liquid biopsy into clinical practice to improve risk stratification, enable the early detection of relapse, and inform personalized treatment strategies, ultimately contributing to more precise and effective patient care in BTC.
背景：胆道癌（BTC）是一种侵袭性恶性肿瘤，常于晚期确诊且预后不良。非侵入性方法有助于早期检测和识别生物标志物，从而指导治疗策略。液体活检，特别是通过分析循环肿瘤DNA（ctDNA），近年来已成为指导BTC临床管理的重要工具。 方法：检索PubMed、Cochrane Library和Wiley数据库中与BTC及ctDNA相关的术语，旨在纳入评估ctDNA作为总生存期（OS）、无进展生存期（PFS）、无病生存期（DFS）和无复发生存期（RFS）预测指标价值的研究。 结果：共纳入12项研究，涉及2374例患者。无论ctDNA采样时间如何，ctDNA的检出均与更高的死亡风险和疾病进展风险相关（风险比分别为2.61，95%置信区间2.19–3.11和2.69，95%置信区间1.82–3.98）。变异等位基因频率（VAF）显示出重要的预测价值，较高VAF值比较低水平VAF具有更高的死亡风险和疾病进展风险（风险比分别为2.37，95%置信区间1.83–3.06和2.22，95%置信区间1.40–3.53）。无论是否接受化疗，该关联均存在，提示VAF可能作为治疗耐药的潜在标志物。 结论：本综述强调了ctDNA状态及相关标志物（如VAF）在BTC管理和预后评估中的临床意义。研究结果支持将液体活检整合到临床实践中，以改善风险分层、实现早期复发检测并指导个体化治疗策略，最终为BTC患者提供更精准有效的诊疗。
Prognostic Role of Circulating DNA in Biliary Tract Cancers: A Systematic Review and Meta-Analysis
肿瘤(癌症)患者之家