Table 2_Association of COX-inhibitors with cancer patients’ survival under chemotherapy and radiotherapy regimens: a real-world data retrospective cohort analysis.xlsx

IntroductionWe conducted an extensive, sex-oriented real-world data analysis to explore the impact and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (coxibs) on cancer treatment outcomes. This is particularly relevant given the role of the COX-2/PGE2 pathway in tumor cell resistance to chemotherapy and radiotherapy.
MethodsThe study applied a retrospective cohort design utilizing the TriNetX research database consisting of patients receiving cancer treatment in 2008-2022. The treated cohorts included patients who were prescribed with coxibs, aspirin or ibuprofen, while individuals in the control cohort did not receive these medicines during their cancer treatment. A 1:1 propensity score matching technique was used to balance the baseline characteristics in the treated and control cohorts. Then, Cox proportional hazards regression and logistic regression were applied to assess the mortality and morbidity risks among patient cohorts in a 5-year follow-up period.
ResultsUse of coxibs (HR, 0.825; 95% CI 0.792-0.859 in females and HR, 0.884; 95% CI 0.848-0.921 in males) and ibuprofen (HR, 0.924; 95% CI 0.903-0.945 in females and HR, 0.940; 95% CI 0.917-0.963 in males) were associated with improved survival. Female cancer patients receiving aspirin presented increased mortality (HR, 1.078; 95% CI 1.060-1.097), while male cancer patients also had improved survival when receiving aspirin (HR, 0.966; 95% CI 0.951-0.980). Cancer subtype specific analysis suggests coxibs and ibuprofen correlated with survival, though ibuprofen and aspirin increased emergency department visits’ risk. Secondary analyses, despite limited by small cohort sizes, suggest that COX inhibition post-cancer diagnosis may benefit patients with specific cancer subtypes.
DiscussionSelective COX-2 inhibition significantly reduced mortality and emergency department visit rates. Further clinical trials are needed to determine the optimal conditions for indication of coxibs as anti-inflammatory adjuvants in cancer treatment.

引言：本研究开展了一项大规模、按性别分层的真实世界数据分析，旨在探讨非甾体类抗炎药（non-steroidal anti-inflammatory drugs, NSAIDs）与选择性环氧合酶-2抑制剂（selective COX-2 inhibitors, coxibs）对癌症治疗结局的影响及安全性。鉴于环氧合酶-2/前列腺素E2通路（COX-2/PGE2 pathway）在肿瘤细胞对化疗与放疗产生耐药性中的作用，本研究的开展具有重要的现实意义。

方法：本研究采用回顾性队列研究设计（retrospective cohort design），使用TriNetX研究数据库中2008年至2022年接受癌症治疗的患者数据。干预队列纳入在癌症治疗期间服用coxibs、阿司匹林或布洛芬的患者，对照队列则纳入同期未接受上述药物治疗的患者。本研究采用1:1倾向得分匹配法对干预队列与对照队列的基线特征进行均衡性校正。随后，通过Cox比例风险回归（Cox proportional hazards regression）与logistic回归（logistic regression），对5年随访期内各患者队列的死亡风险与并发症风险进行评估。

结果：使用coxibs（女性患者的风险比（Hazard Ratio, HR）=0.825，95%置信区间（Confidence Interval, CI）：0.792~0.859；男性患者HR=0.884，95%CI：0.848~0.921）与布洛芬（女性患者HR=0.924，95%CI：0.903~0.945；男性患者HR=0.940，95%CI：0.917~0.963）均与患者生存获益相关。服用阿司匹林的女性癌症患者死亡率升高（HR=1.078，95%CI：1.060~1.097），而服用阿司匹林的男性癌症患者则表现出生存获益（HR=0.966，95%CI：0.951~0.980）。癌症亚型特异性分析显示，coxibs与布洛芬与患者生存相关，但布洛芬与阿司匹林会增加急诊就诊风险。亚组分析虽受限于队列样本量较小，但结果提示癌症确诊后进行环氧合酶抑制治疗可能使特定癌症亚型患者获益。

讨论：选择性环氧合酶-2抑制治疗可显著降低患者死亡率与急诊就诊率。未来仍需开展进一步的临床试验，以明确coxibs作为癌症治疗抗炎辅助剂的最佳适用条件。