背景:BRCA状态的知识为评估腹膜内途径在晚期卵巢癌原发性细胞减灭术后通过生物分子谱选择的患者中的作用提供了机会。
方法:我们进行了回顾性研究,多中心研究根据辅助治疗(腹膜内[IP]与静脉内[IV])和BRCA状态(BRCA1/2突变与BRCA野生型[WT])。主要终点是确定无进展生存期。次要目标是总生存期和毒性。
结果:共包括来自八个中心的288名女性:IP臂177名,IV臂111名,根据BRCA1/2状态分为四组。在接受IP化疗的BRCA1/2突变患者中观察到明显更好的PFS(HR:0.35;95%CI,0.16-0.75,p=0.007),在进行静脉化疗的BRCA1/2突变患者中不存在(HR:0.65;95%CI,0.37-1.12,p=0.14)。在IP化疗中也观察到显著更好的OS(HR:0.17;95%CI,0.06-043,p<0.0001),但与BRCA突变相关的静脉化疗中不存在(HR:0.52;95%CI,0.22-1.27,p=0.15).对于BRCAWT患者,无论使用何种佐剂途径,均观察到更差的生存率.与IV路线相比,IP路线毒性更大,但长期随访时毒性相当.
结论:这项回顾性研究表明,BRCA状态可以帮助提供个性化,晚期卵巢癌最佳初级手术后的系统治疗,但受到样本量小的限制。前瞻性试验对于证实这些结果至关重要。
BACKGROUND: The knowledge of BRCA status offers a chance to evaluate the role of the intraperitoneal route in patients selected by biomolecular profiles after primary cytoreduction surgery in advanced ovarian cancer.
METHODS: We performed a retrospective, multicenter study to assess oncological outcomes depending on adjuvant treatment (intraperitoneal [IP] vs intravenous [IV]) and BRCA status (BRCA1/2 mutated vs. BRCA wild type [WT]). The primary endpoint was to determine progression-free survival. The secondary objectives were overall survival and toxicity.
RESULTS: A total of 288 women from eight centers were included: 177 in the IP arm and 111 in the IV arm, grouped into four arms according to BRCA1/2 status. Significantly better PFS was observed in BRCA1/2-mutated patients with IP chemotherapy (HR: 0.35; 95% CI, 0.16-0.75, p = 0.007), which was not present in BRCA1/2-mutated patients with IV chemotherapy (HR: 0.65; 95% CI, 0.37-1.12, p = 0.14). Significantly better OS was also observed in IP chemotherapy (HR: 0.17; 95% CI, 0.06-043, p < 0.0001), but was not present in IV chemotherapy in relation with BRCA mutation (HR: 0.52; 95% CI, 0.22-1.27, p = 0.15). For BRCA WT patients, worse survival was observed regardless of the adjuvant route used. The IP route was more toxic compared to the IV route, but toxicity was equivalent at the long-term follow-up.
CONCLUSIONS: This retrospective study suggests that BRCA status can help to offer an individualized, systematic treatment after optimal primary surgery for advanced ovarian cancer, but is limited by the small sample size. Prospective trials are essential to confirm these results.