Department of Pharmacy, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
Bill Walsh Translational Research Laboratory, Kolling Institute Medical Institute of Research, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Northern Clinical School, University of Sydney, St Leonards, New South Wales, Australia; Northern Cancer Institute, St Leonards, New South Wales, Australia; Department of Medical Oncology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Lung Cancer. 2020 Apr;142:34-40. doi: 10.1016/j.lungcan.2020.01.017. Epub 2020 Jan 22.
This study aimed to describe the longitudinal thromboembolism (TE) risk relative to the natural history of disease and clinical course of ROS1 rearranged non-small cell lung cancer (NSCLC).
Cases of ROS1-rearranged NSCLC from six Australian hospitals were pooled and evaluated for incidence, timing, predictors and outcomes of venous or arterial TE, as well as objective response rate (ORR) to active therapy and overall survival (OS).
Of 42 patients recruited, 20 (48%) experienced TE; one (2%) arterial, 13 (31%) a pulmonary emboli (PE), and 12 (29%) a deep vein thrombosis. Among those with TE, six (30%) experienced multiple events, three as concurrent and three as recurrent diagnoses. The cumulative incidence of TE over time, adjusted for death as a competing risk factor, approached 50%. TE occurred prior to, during and post the peri-diagnostic period and occurred irrespective of treatment strategy. A thrombophilia was identified in n = 3/10 (30%) cases screened: in two factor V Leiden and in one anti-thrombin III (ATIII) deficiency. Median OS was 21.3 months in those with TE vs. 28.8 months in those without; hazard ratio 1.16 (95%CI 0.43-3.15). Respective ORR to first-line therapy with TE was 50% vs. 44% without TE in the chemotherapy arm and 67% vs. 50% in the targeted therapy arm.
In the rare cancer subtype, ROS1, these real-world data demonstrate sustained TE risk beyond the diagnostic period irrespective of therapeutic strategy. High incidence of PE, concurrent TE, and recurrent TE warrant validation in larger cohorts. Consideration of primary thromboprophylaxis in ROS1 populations is recommended.
本研究旨在描述 ROS1 重排非小细胞肺癌（NSCLC）的疾病自然史和临床过程中与纵向血栓栓塞（TE）风险的关系。
汇集了来自澳大利亚六家医院的 ROS1 重排 NSCLC 病例，并评估了静脉或动脉 TE 的发生率、时间、预测因素和结果，以及对活性治疗的客观缓解率（ORR）和总生存率（OS）。
在招募的 42 名患者中，有 20 名（48%）发生了 TE；1 名（2%）动脉，13 名（31%）肺栓塞（PE），12 名（29%）深静脉血栓形成。在有 TE 的患者中，有 6 名（30%）经历了多次事件，3 次为同时诊断，3 次为复发诊断。调整死亡作为竞争风险因素后，TE 的累积发生率随时间接近 50%。TE 发生在诊断前、诊断期间和诊断后，且与治疗策略无关。在筛选的 10 例中，有 3 例（30%）发现存在血栓形成倾向：2 例为因子 V Leiden，1 例为抗凝血酶 III（ATIII）缺乏症。有 TE 的患者中位 OS 为 21.3 个月，无 TE 的患者为 28.8 个月；风险比为 1.16（95%CI 0.43-3.15）。在化疗组中，有 TE 的患者的一线治疗的 ORR 为 50%，无 TE 的患者为 44%；在靶向治疗组中，有 TE 的患者为 67%，无 TE 的患者为 50%。
在罕见的癌症亚型 ROS1 中，这些真实世界的数据表明，无论治疗策略如何，诊断后仍存在持续的 TE 风险。PE 发生率高、同时发生的 TE 和复发性 TE 需要在更大的队列中验证。建议在 ROS1 人群中考虑进行原发性血栓预防。
