Division of Hematology Oncology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
Harvard Medical School, Boston, Massachusetts; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
J Thorac Oncol. 2020 Sep;15(9):1497-1506. doi: 10.1016/j.jtho.2020.04.033. Epub 2020 May 11.
Clinical venous thromboembolism (VTE) risk prediction scores, such as the Khorana Risk Score, perform poorly in NSCLC, possibly because the tumor molecular subtype is omitted. Previous studies suggest a possible increased VTE risk in ALK-rearranged NSCLC, but data are conflicting.
We performed a retrospective cohort study of patients with advanced-stage NSCLC diagnosed between 2009 and 2019. Multivariable, time-to-event analyses modeling the risk of first venous or arterial thrombosis in ALK and non-ALK NSCLC groups, controlling for covariates known to impact thrombosis risk (15 in VTE model and 17 in arterial thrombosis model), were performed using Cox proportional hazards regression and competing-risks regression. Multivariable negative binomial regression modeled the total VTE rate.
A total of 422 patients with ALK-rearranged and 385 patients with non-ALK-rearranged NSCLC were included. Patients with an ALK rearrangement were younger, had better performance status, and had lower rates of most thrombotic risk factors but had significantly higher rates of initial VTE (42.7% versus 28.6%, p < 0.0001), recurrent VTE (13.5% versus 3.1%, p < 0.0001), and similar rates of arterial thrombosis (5.0% versus 4.4%, p = 0.71) compared with non-ALK NSCLC. VTE risk attributable to ALK was significant (Cox model: hazard ratio 3.70, [95% confidence interval [CI]: 2.51-5.44, p < 0.001], competing risks: subhazard ratio 3.91 [95% CI: 2.55-5.99, p < 0.001]). Negative binomial modeling revealed higher VTE rates in patients with an ALK rearrangement (incidence rate ratio 2.47 [95% CI: 1.72-3.55, p < 0.001]). The OR for recurrent VTE was 4.85 (95% CI: 2.60-9.52, p < 0.001). Arterial thrombosis risk attributable to ALK was significant (Cox model: hazard ratio 3.15 [95% CI: 1.18-8.37, p = 0.021], competing risks: subhazard ratio 2.80 [95% CI: 1.06-7.43, p = 0.038]).
In time-to-event analyses controlling for thrombosis risk factors, the ALK rearrangement conferred a fourfold increase in VTE risk and a threefold increase in arterial thrombosis risk in NSCLC. These patients may benefit from pharmacologic thromboprophylaxis.
临床静脉血栓栓塞症 (VTE) 风险预测评分，如 Khorana 风险评分，在 NSCLC 中的表现不佳，可能是因为肿瘤分子亚型被忽略了。先前的研究表明，ALK 重排的 NSCLC 可能存在更高的 VTE 风险，但数据存在矛盾。
我们对 2009 年至 2019 年间诊断为晚期 NSCLC 的患者进行了回顾性队列研究。使用 Cox 比例风险回归和竞争风险回归，对多变量、时间事件分析模型进行了分析，该模型对 ALK 和非 ALK NSCLC 组中首次静脉或动脉血栓形成的风险进行建模，控制了已知影响血栓形成风险的协变量（VTE 模型中 15 个，动脉血栓形成模型中 17 个）。多变量负二项回归模型用于模拟总 VTE 率。
共纳入 422 例 ALK 重排和 385 例非 ALK 重排 NSCLC 患者。ALK 重排患者年龄较小，表现状态较好，大多数血栓形成危险因素的发生率较低，但初始 VTE（42.7%比 28.6%，p<0.0001）、复发性 VTE（13.5%比 3.1%，p<0.0001）的发生率显著更高，且动脉血栓形成的发生率相似（5.0%比 4.4%，p=0.71）。与非 ALK NSCLC 相比，ALK 导致的 VTE 风险具有显著意义（Cox 模型：风险比 3.70 [95%置信区间 [CI]：2.51-5.44，p<0.001]，竞争风险：亚风险比 3.91 [95% CI：2.55-5.99，p<0.001]）。负二项模型显示，ALK 重排患者的 VTE 发生率更高（发病率比 2.47 [95% CI：1.72-3.55，p<0.001]）。复发性 VTE 的 OR 为 4.85（95% CI：2.60-9.52，p<0.001）。ALK 导致的动脉血栓形成风险具有显著意义（Cox 模型：风险比 3.15 [95% CI：1.18-8.37，p=0.021]，竞争风险：亚风险比 2.80 [95% CI：1.06-7.43，p=0.038]）。
在控制血栓形成风险因素的时间事件分析中，ALK 重排使 NSCLC 患者的 VTE 风险增加了四倍，动脉血栓形成风险增加了三倍。这些患者可能受益于药物预防血栓形成。
