利用模拟试验研究含氮双膦酸盐的使用与上皮性卵巢癌风险之间的关联。

Use of an emulated trial to investigate the association between use of nitrogen-based bisphosphonates and risk of epithelial ovarian cancer.

机构信息

School of Public Health, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.

Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

出版信息

Int J Epidemiol. 2024 Jun 12;53(4). doi: 10.1093/ije/dyae108.

DOI:10.1093/ije/dyae108

PMID:39133937

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11319644/

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.

摘要

背景

上皮性卵巢癌（EOC）是女性第八大常见癌症，预后较差。观察性证据表明，含氮双膦酸盐（NBB）的使用可能与降低 EOC 风险相关，特别是子宫内膜样和浆液性组织类型；然而，指示性混杂是一个关注点。另一种研究 NBB 化学预防潜力的方法是通过识别所有开始使用 NBB 的女性，并研究持续使用者与停止使用者相比 EOC 的风险，来模拟目标试验。

方法

我们使用基于人群的链接数据，确定了所有 2004-12 年间首次使用 NBB 的 50 岁以上澳大利亚女性。我们使用首次使用后的年份来定义每位女性的治疗，要么是持续治疗，要么是停止治疗。我们使用稳定的逆概率权重进行随机化模拟，使用年龄、合并症和社会经济地位等协变量来平衡治疗组。我们从治疗分配开始随访女性，直到 EOC 诊断、死亡或 2013 年 12 月 31 日。我们使用灵活的参数时间事件模型评估 EOC（整体和组织类型）的风险，并生成时间变化系数。

结果

在研究的 313383 名女性中，472 人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。与停止治疗相比，持续使用 NBB 与整体 EOC（HR=0.87，95%CI：0.69，1.10）和浆液性 EOC（HR=0.71，95%CI：0.53，0.96）的风险降低相关，在 9 年的随访期间，估计值保持不变。