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BRCA1/2 基因突变对二次细胞减灭术疗效的影响。

Impact of BRCA1/2 Mutations on the Efficacy of Secondary Cytoreductive Surgery.

机构信息

Department of Medical Oncology, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.

Department of Oncogenetics, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.

出版信息

Ann Surg Oncol. 2021 Jul;28(7):3637-3645. doi: 10.1245/s10434-020-09366-w. Epub 2020 Nov 21.

Abstract

BACKGROUND

Phase III trials evaluating the role of secondary cytoreductive surgery (SCS) in recurrent ovarian cancer have pointed to the importance of patient selection. Two studies showed conflicting results regarding the benefit of SCS in BRCA1/2 mutation carriers. Our aim was to evaluate the impact of SCS on recurrent ovarian cancer according to BRCA1/2 status.

METHODS

All patients with ovarian carcinoma with platinum-sensitive recurrent disease and tested for BRCA1/2 germline mutations were included. Cox regression and log rank test were used to evaluate the impact of SCS on progression-free survival (PFS) and the influence of BRCA1/2 mutations on the effect of SCS.

RESULTS

127 patients were included, 45.6% were treated with SCS and chemotherapy and 54.3% treated with chemotherapy only. Patients treated with SCS were younger, presented better performance status, had lower CA125, and had a longer platinum-free interval. In multivariate analysis SCS was associated with longer PFS (HR 0.42, 95% CI 0.25-0.72, p = 0.002). BRCA1/2 mutations were found in 35 patients (27.5%), and 11.8% of patients were treated with PARP inhibitors. Although not statistically significant, both BRCA1/2 wild type patients (PFS: 21.6 vs 18.4 months; p = 0.114) and BRCA1/2 mutation carriers (PFS: 23.1 vs 18.2 months, p = 0.193) appeared to derive benefit from SCS.

DISCUSSION

The present study suggests a benefit of SCS irrespective of BRCA1/2 status among patients mostly not treated with PARP inhibitor. Further data on post hoc analysis from the phase III trials are warranted to confirm whether BRCA1/2 mutated patients should be selected for SCS.

摘要

背景

评估辅助细胞减灭术(SCS)在复发性卵巢癌中的作用的 III 期临床试验表明了患者选择的重要性。两项研究显示 SCS 对 BRCA1/2 突变携带者的益处存在矛盾的结果。我们的目的是根据 BRCA1/2 状态评估 SCS 对复发性卵巢癌的影响。

方法

所有铂类敏感复发性疾病且检测到 BRCA1/2 种系突变的卵巢癌患者均被纳入研究。Cox 回归和对数秩检验用于评估 SCS 对无进展生存期(PFS)的影响,以及 BRCA1/2 突变对 SCS 效果的影响。

结果

共纳入 127 例患者,45.6%接受 SCS 和化疗治疗,54.3%仅接受化疗治疗。接受 SCS 治疗的患者年龄较小,表现状态较好,CA125 水平较低,且铂类无进展间期较长。多变量分析显示 SCS 与较长的 PFS 相关(HR 0.42,95%CI 0.25-0.72,p=0.002)。35 例患者(27.5%)发现 BRCA1/2 突变,11.8%的患者接受 PARP 抑制剂治疗。虽然没有统计学意义,但 BRCA1/2 野生型患者(PFS:21.6 与 18.4 个月;p=0.114)和 BRCA1/2 突变携带者(PFS:23.1 与 18.2 个月,p=0.193)似乎都从 SCS 中获益。

讨论

本研究表明,在未接受 PARP 抑制剂治疗的患者中,SCS 不论 BRCA1/2 状态如何均有益。需要进一步的 III 期临床试验事后分析数据来证实 BRCA1/2 突变患者是否应选择 SCS。

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