Chemotherapy and targeted therapy for advanced biliary tract cancers: an umbrella review.
Chemotherapy and targeted therapy for advanced biliary tract cancers: an umbrella review.
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DOI：
10.1186/s12885-023-10679-8
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发表时间：
2023-04-25
期刊：
影响因子：
3.8
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中科院分区：
文献类型：
--
作者：
胆道系统恶性肿瘤的特点是恶性程度高、侵袭性强，诊断往往较晚，预后差。对于晚期胆道癌患者，化疗和靶向治疗是改善预后和延缓肿瘤进展的两种选择。本研究旨在通过已发表的系统评价和荟萃分析（SRoMA），全面评价各种化疗方案治疗晚期胆道癌的安全性和有效性。采用了一种伞式综述方法，旨在总结围绕一个研究主题的多项研究的现有证据。使用PubMed、Web of Science、科克伦数据库和手动筛选确定截至2022年4月9日的SRoMA。根据纳入和排除标准筛选合格的研究。本研究已在PROSPERO注册（CRD 42022324548）。对于每个合格的研究，我们提取了一般特征和主要发现的数据。纳入研究的方法学质量采用AMSTAR 2量表进行评估，证据质量采用GRADE工具进行评价。共检索了1833篇文章;根据合格性标准识别出14篇独特的文章，涉及94个结局。接受吉西他滨化疗加靶向治疗的患者中皮疹（RR = 18.11，95% CI 5.13-63.91，等级：中度）和腹泻（RR = 2.48，95% CI 1.2-5.10，等级：中度）的发生率高于接受吉西他滨单药治疗的患者。接受基于吉西他滨的化疗后发生白细胞减少症的患者数量（OR = 7.17，95% CI 1.43-36.08，等级：中度），贫血（OR = 7.04，95% CI 2.59-19.12，等级：高），血小板减少症（RR = 2.45，95% CI 1.39-4.32，等级：中度）和中性粒细胞减少（RR = 3.30，95% CI 1.04-10.50，等级：中度）显著高于接受无吉西他滨方案的患者。此外，接受S-1单药治疗的患者的ORR（RR = 2.46，95% CI 1.27-4.57，等级：中度）显著优于接受S-1 +吉西他滨治疗的患者。接受含氟嘧啶化疗的患者OS较长（HR = 0.83，95% CI 0.7-0.99，等级：中度），DCR较高（0 R = 5.18，95% CI 3.3-10.23，等级：中度），ORR较高（0 R = 3.24，95% CI 1.18-8.92，等级：中度）与接受5-FU/LV单药治疗或支持性治疗的患者相比。令人惊讶的是，我们发现与最佳支持治疗相比，基于吉西他滨的化疗没有改善术后患者的OS（HR = 0.91，95% CI 0.74-1.12，等级：中度）。本研究全面评价了晚期胆道癌化疗或靶向治疗方案的安全性和有效性，发现11项结局为“中度”或“高”水平;但大多数结局仍为“低”或“极低”水平。未来需要更多的随机对照研究来进一步总结高水平的证据。在线版本包含补充材料，可通过10.1186/s12885-023-10679-8获得。
Malignant tumors of the biliary system are characterized by a high degree of malignancy and strong invasiveness, and they are usually diagnosed at late stages with poor prognosis. For patients with advanced biliary tract cancer, chemotherapy and targeted therapy are two of the options available to improve prognosis and delay tumor progression. This study aimed to comprehensively evaluate the safety and effectiveness of various chemotherapy schemes for the treatment of advanced biliary tract cancer in published systematic reviews and meta-analyses (SRoMAs). An umbrella review method was adopted, which aims to summarize the existing evidence from multiple studies around a research topic. SRoMAs up to April 9, 2022, were identified using PubMed, Web of Science, the Cochrane database, and manual screening. Eligible studies were screened according to inclusion and exclusion criteria. This study had been registered at PROSPERO (CRD42022324548). For each eligible study, we extracted the data of general characteristics and the main findings. The methodological quality of the included studies were assessed by the AMSTAR2 scale, and the quality of evidence was evaluated by the GRADE tools. A total of 1833 articles were searched; 14 unique articles with 94 outcomes were identified by eligibility criteria. The incidence of skin rash (RR = 18.11, 95% CI 5.13–63.91, GRADE: Moderate) and diarrhea (RR = 2.48, 95% CI 1.2–5.10, GRADE: Moderate) was higher in patients receiving gemcitabine-based chemotherapy plus targeted therapy than in patients receiving gemcitabine monotherapy. The number of patients receiving gemcitabine-based chemotherapy who developed leukopenia (OR = 7.17, 95% CI 1.43–36.08, GRADE: Moderate), anemia (OR = 7.04, 95% CI 2.59–19.12, GRADE: High), thrombocytopenia (RR = 2.45, 95% CI 1.39–4.32, GRADE: Moderate), and neutropenia (RR = 3.30, 95% CI 1.04–10.50, GRADE: Moderate) was significantly higher than that of patients who received gemcitabine-free regimens. In addition, patients receiving S-1 monotherapy had significantly better ORR (RR = 2.46, 95% CI 1.27–4.57, GRADE: Moderate) than patients receiving S-1 + gemcitabine. Patients receiving fluoropyrimidine-based chemotherapy had longer OS (HR = 0.83, 95% CI 0.7–0.99, GRADE: Moderate), higher DCR (0R = 5.18, 95% CI 3.3–10.23, GRADE: Moderate), and higher ORR (0R = 3.24, 95% CI 1.18–8.92, GRADE: Moderate) compared with patients who received 5-FU/LV monotherapy or supportive therapy. Surprisingly, we found evidence that gemcitabine-based chemotherapy did not improve postoperative patients’ OS (HR = 0.91, 95% CI 0.74–1.12, GRADE: Moderate) when compared with best supportive care. This study comprehensively evaluated the safety and efficacy of chemotherapy or targeted therapy regimens for advanced biliary tract cancer and found 11 outcomes with “Moderate” or “High” levels; however, most of the outcomes were still at “low” or “very low” levels. More randomized controlled studies are needed in the future to further summarize high levels of evidence. The online version contains supplementary material available at 10.1186/s12885-023-10679-8.
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7.2
作者：
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