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癌症合并 COVID-19 住院患者的全身性抗癌治疗与血栓栓塞结局。

Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19.

机构信息

University of California Davis Comprehensive Cancer Center, Sacramento.

University of Cincinnati Cancer Center, Cincinnati, Ohio.

出版信息

JAMA Oncol. 2023 Oct 1;9(10):1390-1400. doi: 10.1001/jamaoncol.2023.2934.

Abstract

IMPORTANCE

Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.

OBJECTIVE

To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.

DESIGN, SETTING, AND PARTICIPANTS: This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.

EXPOSURE

Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.

MAIN OUTCOMES AND MEASURES

Main outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.

RESULTS

Of 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).

CONCLUSIONS AND RELEVANCE

In this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19-related thromboembolism in patients with cancer.

摘要

重要性

目前缺乏关于癌症患者 COVID-19 前后癌症治疗与血栓栓塞事件(TEEs)之间关联的系统数据。

目的

评估癌症患者 COVID-19 诊断后 3 个月内接受抗癌治疗与 TEEs 之间的关联。

设计、设置和参与者:本基于登记的回顾性队列研究纳入了住院且患有活动性癌症和实验室确诊 SARS-CoV-2 感染的患者。数据收集于 2020 年 3 月至 2021 年 12 月,分析于 2021 年 12 月至 2022 年 10 月进行。

暴露

有兴趣的治疗(TOIs)(内分泌治疗、血管内皮生长因子抑制剂/酪氨酸激酶抑制剂[VEGFis/TKIs]、免疫调节剂[IMiDs]、免疫检查点抑制剂[ICIs]、化疗)与 COVID-19 前 3 个月的参考(无全身治疗)。

主要结局和测量

主要结局为(1)静脉血栓栓塞(VTE)和(2)动脉血栓栓塞(ATE)。次要结局为 COVID-19 的严重程度(TOI 组与参考组在 30 天随访时接受 TEEs 的 ICU 入院率、机械通气率和 30 天全因死亡率)。

结果

在 4988 名患有癌症的住院患者中(中位数[IQR]年龄,69[59-78]岁;2608[52%]男性),1869 人接受了 1 种或多种 TOIs。所有 TOI 组的 VTE 发生率均较高:内分泌治疗为 7%,VEGFis/TKIs 为 10%,IMiDs 为 8%,ICIs 为 12%,化疗为 10%,而未接受全身治疗的患者为 6%。在多变量二项式回归分析中,与无暴露相比,所有 TOIs 合并暴露的 VTE(调整后的风险比[aRR],1.33;95%CI,1.04-1.69)而不是 ATE(aRR,0.81;95%CI,0.56-1.16)的相对风险显著更高。在个别药物中,ICIs 与 VTE 显著相关(aRR,1.45;95%CI,1.01-2.07)。还注意到 VTE 与活动性和进展性癌症(aRR,1.43;95%CI,1.01-2.03)、VTE 病史(aRR,3.10;95%CI,2.38-4.04)和癌症高危部位(aRR,1.42;95%CI,1.14-1.75)之间存在显著关联。黑人患者比白人患者发生 TEEs 的风险更高(aRR,1.24;95%CI,1.03-1.50)。发生 TEEs 的患者 ICU 入院率(46%)和机械通气率(31%)较高。发生 TEEs 的患者的死亡率相对风险在接受 TOIs 治疗的患者中高于未接受治疗的患者(aRR,1.12;95%CI,0.91-1.38),并且与较差的表现状态(aRR,1.77;95%CI,1.30-2.40)和活动性/进展性癌症(aRR,1.55;95%CI,1.13-2.13)显著相关。

结论和相关性

在本队列研究中,接受 TOIs 治疗的患者发生 VTE 的相对风险较高,且风险因治疗类型、潜在风险因素和种族和民族等人口统计学特征而有所不同。这些发现强调了需要密切监测并可能进行个体化的血栓预防,以预防癌症患者 COVID-19 相关血栓栓塞的发病率和死亡率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da3c/10436185/7b0324820e0e/jamaoncol-e232934-g001.jpg

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