Department of Medical Oncology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
National Institute for Heath Technology Assessment, Postgraduate Program in Epidemiology, Porto Alegre, Brazil.
Cancer Treat Rev. 2019 Nov;80:101895. doi: 10.1016/j.ctrv.2019.101895. Epub 2019 Sep 6.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Recent studies have shown that 4-20% of patients with PDAC have a germline BReast CAncer (gBRCA) genes 1 and 2 mutation (m). Because homologous recombination is impaired in patients with gBRCAm, some reports suggested that these tumors may be more sensitive to platinum compounds. Therefore, this systematic review and meta-analysis focused on benefit of patients with gBRCAm receiving a platinum-based chemotherapy (PtCh) compared with those treated with a non-platinum-based chemotherapy (NPtCh).
The following electronic databases were searched from inception to May 12, 2018: PubMed (MEDLINE), EMBASE, and Cochrane Library. Abstracts from conferences were also reviewed for inclusion. Cohort, case-control and randomized studies of patients with PDAC and gBRCAm were eligible for inclusion if they provided data to compare patients receiving PtCh vs NPtCh. The primary endpoint was overall survival (OS) in the PtCh group vs the NPtCh group in patients with clinical stage III (locally advanced) or IV (metastatic) (CS III-IV) PDAC.
Of 112 studies identified, 6 were included (total of 108 patients); of these, 4 provided sufficient data for meta-analysis. Half of the patients were males, with a mean age ranging from 58 to 63 years. The OS in the 85 patients with CS III-IV PDAC was higher in the PtCh group (23.7 vs 12.2 months; mean difference of 10.21 months, 95% confidence interval [CI] 5.05-15.37; P < 0.001; very low quality of evidence). PtCh was associated with a lower mortality (62.3 vs 87.5%; relative risk of 0.80, 95%CI 0.66-0.97; P = 0.021; very low quality of evidence).
Our study confirmed the hypothesis that patients with CS III-IV gBRCAm preferably benefit from a PtCh compared with NPtCh. However the very low quality of evidence should induce to be careful about the risk of potential biases. The generated hypothesis should be prospectively investigated in homogenous clinical settings.
胰腺导管腺癌（PDAC）是全球最致命的癌症之一。最近的研究表明，4-20%的 PDAC 患者存在种系 BReast CAncer（gBRCA）基因 1 和 2 突变（m）。由于同源重组在 gBRCAm 患者中受损，一些报告表明这些肿瘤可能对铂类化合物更敏感。因此，本系统评价和荟萃分析主要关注 gBRCAm 患者接受铂类化疗（PtCh）与非铂类化疗（NPtCh）相比的获益。
从成立到 2018 年 5 月 12 日，检索了以下电子数据库：PubMed（MEDLINE）、EMBASE 和 Cochrane 图书馆。还对会议摘要进行了审查以纳入研究。如果提供的数据可用于比较接受 PtCh 与 NPtCh 的患者，则合格的研究为患有 PDAC 和 gBRCAm 的患者的队列、病例对照和随机研究，且这些患者提供了临床分期 III（局部晚期）或 IV（转移性）（CS III-IV）PDAC 患者的总体生存（OS）数据。
在 112 项研究中，有 6 项符合纳入标准（共 108 例患者）；其中 4 项提供了足够的数据进行荟萃分析。一半的患者为男性，平均年龄为 58-63 岁。在 85 例 CS III-IV PDAC 患者中，PtCh 组的 OS 更高（23.7 与 12.2 个月；平均差异为 10.21 个月，95%置信区间[CI]为 5.05-15.37；P<0.001；极低质量证据）。PtCh 与较低的死亡率相关（62.3%与 87.5%；相对风险为 0.80，95%CI 为 0.66-0.97；P=0.021；极低质量证据）。
本研究证实了假设，即 CS III-IV gBRCAm 患者从 PtCh 中获益优于 NPtCh。然而，极低的证据质量应引起对潜在偏倚风险的注意。应在同质临床环境中前瞻性地研究提出的假设。
