J Natl Cancer I:非甾体抗炎药给子宫内膜癌预后“会心一击”?

2017-05-26 吴刚 环球医学

来自几项近期研究的一致数据均表明了结直肠癌患者中,阿司匹林和其他非甾体抗炎药(NSAIDs)的治疗获益。2017年5月,发表在《J Natl Cancer Inst》的一项由美国科学家进行的研究考察了NSAID与子宫内膜癌死亡和复发的相关性。请看本期多学科讨论组临床药师各抒己见为您梳理本文看点——背景:近期数据表明,使用NSAID与子宫内膜癌风险降低相关,然而非常少的研究考察了子宫内膜癌患者使用N

来自几项近期研究的一致数据均表明了结直肠癌患者中,阿司匹林和其他非甾体抗炎药(NSAIDs)的治疗获益。2017年5月,发表在《J Natl Cancer Inst》的一项由美国科学家进行的研究考察了NSAID与子宫内膜癌死亡和复发的相关性。请看本期多学科讨论组临床药师各抒己见为您梳理本文看点——

背景:近期数据表明,使用NSAID与子宫内膜癌风险降低相关,然而非常少的研究考察了子宫内膜癌患者使用NSAID是否与预后相关。

方法:研究对象由4374名NRG肿瘤/妇科肿瘤组210研究的子宫内膜癌参与者组成,这些参与者完成了术前调查问卷。该调查问卷评估了诊断前NSAID常规使用史和子宫内膜癌的风险因素。从病历记录和癌症注册中获取复发率、生命体征状态、死因等信息。Fine-Gray半成比例风险回归评估了NSAID使用与子宫内膜癌特异性死亡率和复发率之间相关性的调整亚风险比(HR)及其95%置信区间(CI)。根据子宫内膜癌类型[即1型(子宫内膜样)vs 2型(浆液性、透明细胞或癌肉瘤)]和组织学对模型进行分层。

结果:中位5年随访期共发生550例子宫内膜癌特异性死亡和737例复发。1型癌症者中,NSAID的使用与子宫内膜癌特异性死亡率增加66%相关(HR,1.66;95% CI,1.21~2.30)。之前和当前使用者中,该相关性具有统计学显着性,在使用了10年或更长时间NSAID的之前使用者中,该相关性最强烈(HR,2.23;95% CI,1.19~4.18;双侧P=0.01)。NSAID的使用与2型肿瘤患者子宫内膜癌特异性死亡或复发不相关。

结论:本研究中,NSAID的使用与子宫内膜癌特异性死亡率增加相关,尤其在1型肿瘤的患者中。除非有明确的NSAID增加原因特异性死亡风险的生物学机制,否则就需要谨慎理解。

多学科讨论记实:

在本项针对子宫内膜癌女性的前瞻性研究中,研究人员观察到,NSAID使用与癌症特定死亡风险增加相关,以及与较小程度的复发风险增加相关,尤其在子宫内膜样组织确诊的女性中。体外实验性研究已经显示,COX酶抑制导致前列腺素E2、芳香酶和雌激素合成的减少,尤其因为非对抗性雌激素在子宫内膜增生中起重要作用。实验性发现进一步支持了子宫内膜癌组织中COX-2表达与芳香酶之间的正相关性,以及NSAID使用与血液雌激素浓度之间的负相关性。鉴于这些活动机制,我们对于为什么NSAID使用与子宫内膜癌患者死亡或复发风险增加相关所知甚少。近期数据已经表明,子宫内膜癌是免疫原性,导致重要的治疗和预后意义(尤其与PD-1/PD-L1抑制剂应答相关)。以下观点似乎合理——NSAIDs的抗炎作用能通过可负面影响死亡的不同因子复原,来改变子宫内膜癌的免疫环境。

也应考虑局限性。报告的NSAID使用未经确认,未收集NSAIDs频率和剂量的数据,可能导致无差别的测量错误。

评估NSAID使用的一些指征的可能性(例如,患心血管疾病、关节炎)的能力受限,或混淆相关性。

此外,由于组织学分层模型中,NSAID使用者中事件的数量相对较小,研究人员无法共同考察NSAIDs新近使用和持续使用的相关性。

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    2017-09-05 liye789132251
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    2017-08-16 qidongfanjian
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    2017-05-26 尹玉伟

    厉害厉害……学习了

    0

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