PDF(Pubmed)
Abstract：
BACKGROUND: Epithelial ovarian cancer (EOC) is the eighth most common cancer in women, with poor survival outcomes. Observational evidence suggests that nitrogen-based bisphosphonate (NBB) use may be associated with reduced risk of EOC, particularly the endometrioid and serous histotypes; however, confounding by indication is a concern. An alternative approach to investigate the chemo-preventive potential of NBBs is to emulate a target trial by identifying all women who initiate use of NBBs and investigate the risk of EOC for continued users compared with discontinued users.
METHODS: Using population-based linked data, we identified all Australian women aged over 50 years who first used NBBs over 2004-12. We used the year after first use to define treatment for each woman as either continued or discontinued use. We emulated randomization using stabilized inverse probability weights to balance the treatment groups using covariates including age, comorbidities and socioeconomic status. We followed women from treatment assignment until EOC diagnosis, death or 31 December 2013. We assessed the risk of EOC (overall and by histotype) using flexible parametric time-to-event models allowing for time-varying effects, and produced time-varying coefficients.
RESULTS: Of the 313 383 women in the study, 472 were diagnosed with EOC during follow-up (261 serous EOC), with an average age at diagnosis of 72 years. Continued use of NBBs was associated with reduced risk of EOC overall (HR = 0.87, 95% CI: 0.69, 1.10), and serous EOC (HR = 0.71, 95% CI: 0.53, 0.96), compared with discontinued treatment, with estimates remaining constant over the 9-year follow-up.
CONCLUSIONS: Results from our emulated trial suggest that in women who initiated NBB treatment, those who continued use had 13% and 29% lower hazards of being diagnosed with EOC overall and serous EOC, respectively, compared with women who discontinued use.
METHODS: Using population-based linked data, we identified all Australian women aged over 50 years who first used NBBs over 2004-12. We used the year after first use to define treatment for each woman as either continued or discontinued use. We emulated randomization using stabilized inverse probability weights to balance the treatment groups using covariates including age, comorbidities and socioeconomic status. We followed women from treatment assignment until EOC diagnosis, death or 31 December 2013. We assessed the risk of EOC (overall and by histotype) using flexible parametric time-to-event models allowing for time-varying effects, and produced time-varying coefficients.
RESULTS: Of the 313 383 women in the study, 472 were diagnosed with EOC during follow-up (261 serous EOC), with an average age at diagnosis of 72 years. Continued use of NBBs was associated with reduced risk of EOC overall (HR = 0.87, 95% CI: 0.69, 1.10), and serous EOC (HR = 0.71, 95% CI: 0.53, 0.96), compared with discontinued treatment, with estimates remaining constant over the 9-year follow-up.
CONCLUSIONS: Results from our emulated trial suggest that in women who initiated NBB treatment, those who continued use had 13% and 29% lower hazards of being diagnosed with EOC overall and serous EOC, respectively, compared with women who discontinued use.
摘要：
背景：上皮性卵巢癌（EOC）是女性第八常见的癌症，生存结果不佳。观察证据表明，使用氮基双膦酸盐（NBB）可能与降低EOC风险有关。特别是子宫内膜样和浆液性组织型；然而，由指示混淆是一个问题。调查NBBs的化学预防潜力的另一种方法是通过识别所有开始使用NBBs的女性来模拟目标试验，并调查持续使用者与停止使用者相比的EOC风险。
方法：使用基于人群的关联数据，我们确定了所有在2004-12年首次使用NBBs的50岁以上的澳大利亚女性.我们在首次使用后的一年将每位女性的治疗定义为继续使用或停止使用。我们使用稳定的逆概率权重来模拟随机化，以使用包括年龄在内的协变量来平衡治疗组，合并症和社会经济地位。我们跟踪女性从治疗分配到EOC诊断，死亡或2013年12月31日。我们使用灵活的参数时间到事件模型评估EOC的风险（总体和组织型），允许随时间变化的影响，并产生时变系数。
结果：在研究中的313383名女性中，472例患者在随访期间被诊断为EOC（261例浆液性EOC），诊断时的平均年龄为72岁。继续使用NBBs与整体EOC风险降低相关(HR=0.87,95%CI:0.69,1.10),和浆液性EOC（HR=0.71，95%CI：0.53，0.96），与停止治疗相比，在9年的随访中，估计保持不变。
结论：我们的模拟试验结果表明，在开始NBB治疗的女性中，那些继续使用EOC的患者被诊断为整体EOC和浆液性EOC的风险分别降低了13％和29％，分别,与停止使用的女性相比。
方法：使用基于人群的关联数据，我们确定了所有在2004-12年首次使用NBBs的50岁以上的澳大利亚女性.我们在首次使用后的一年将每位女性的治疗定义为继续使用或停止使用。我们使用稳定的逆概率权重来模拟随机化，以使用包括年龄在内的协变量来平衡治疗组，合并症和社会经济地位。我们跟踪女性从治疗分配到EOC诊断，死亡或2013年12月31日。我们使用灵活的参数时间到事件模型评估EOC的风险（总体和组织型），允许随时间变化的影响，并产生时变系数。
结果：在研究中的313383名女性中，472例患者在随访期间被诊断为EOC（261例浆液性EOC），诊断时的平均年龄为72岁。继续使用NBBs与整体EOC风险降低相关(HR=0.87,95%CI:0.69,1.10),和浆液性EOC（HR=0.71，95%CI：0.53，0.96），与停止治疗相比，在9年的随访中，估计保持不变。
结论：我们的模拟试验结果表明，在开始NBB治疗的女性中，那些继续使用EOC的患者被诊断为整体EOC和浆液性EOC的风险分别降低了13％和29％，分别,与停止使用的女性相比。
