Medical Oncology Department, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain; Facultad de Medicina, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Madrid, Spain.
Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Thromb Res. 2023 Dec;232:133-137. doi: 10.1016/j.thromres.2023.11.007. Epub 2023 Nov 12.
We aimed to determine if advanced BRAF-mutant NSCLC has a higher thromboembolic events (TEE) rate than the expected.
Between 2008 and 2021, 182 patients with BRAF-mutant advanced NSCLC (BRAF V600E, n = 70; BRAF non-V600E, n = 112) were retrospectively identified from 18 centers in Spain. Patients received chemotherapy (n = 147), immunotherapy (n = 69), targeted therapy (n = 42), and immunotherapy + chemotherapy (n = 26).
Incidence rate of TEE was 26.4 % (95%CI: 19.9 %-32.9 %). A total of 72 TEE were documented among 48 patients, as 18 patients (37.5 %) developed more than one event. Median time to TEE onset was 2 months, 69 % of TEE occurred in the peridiagnostic period (+/- 90 days from cancer diagnosis), and in 16 pts. (33 %) TEE was the form of lung cancer presentation. Although most TEE were only venous (82 %; PE, n = 33; DVT, n = 16), arterial events were reported in 31 % and occurred earlier, or TEE presented in atypical locations (13.9 %). TEE were related to high hospitalization rate (59 %), recurrence (23 %), and mortality (10.4 %) despite appropriate anticoagulant/antiaggregant treatment. Median OS in patients without-TEE was 19.4 months (95%CI: 4.6-34.1), and significantly shorter in patients with arterial-TEE vs venous-TEE vs both of them: 9.9 months (95%CI: 0-23.5) vs 41.7 months (95%CI: 11.3-72.2 m) vs 2.7 months (95%CI: 2.1-3.3), p = 0.001. Neither clinical or molecular features (BRAF V600E/non-V600E), nor cancer treatment was associated to TEE occurrence. Khorana score underperformed to predict thrombosis at cancer diagnosis, as only 19.2 % of patients were classified as high-risk.
Thrombotic events represent a new clinical feature of BRAF-mutant lung cancer. Patients with almost a 30 % incidence of TEE should be offered systematic anticoagulation.
我们旨在确定 BRAF 突变型非小细胞肺癌（NSCLC）的血栓栓塞事件（TEE）发生率是否高于预期。
在 2008 年至 2021 年期间，从西班牙的 18 个中心回顾性地确定了 182 名 BRAF 突变型晚期 NSCLC 患者（BRAF V600E，n=70；非 BRAF V600E，n=112）。患者接受了化疗（n=147）、免疫治疗（n=69）、靶向治疗（n=42）和免疫治疗+化疗（n=26）。
TEE 的发生率为 26.4%（95%CI：19.9%-32.9%）。48 名患者中有 72 例记录到 TEE，其中 18 名患者（37.5%）发生了不止一次事件。TEE 的中位发病时间为 2 个月，69%的 TEE 发生在诊断前的时期（癌症诊断前后 90 天），16 名患者（33%）的 TEE 是肺癌的表现形式。尽管大多数 TEE 仅是静脉性的（82%；PE，n=33；DVT，n=16），但报告了 31%的动脉性事件，且这些事件更早发生，或者 TEE 发生在非典型部位（13.9%）。尽管进行了适当的抗凝/抗聚集治疗，但 TEE 与高住院率（59%）、复发（23%）和死亡率（10.4%）相关。无 TEE 的患者的中位 OS 为 19.4 个月（95%CI：4.6-34.1），有动脉性 TEE 的患者明显短于有静脉性 TEE 的患者和同时有两种 TEE 的患者：9.9 个月（95%CI：0-23.5）vs.41.7 个月（95%CI：11.3-72.2m）vs.2.7 个月（95%CI：2.1-3.3），p=0.001。临床或分子特征（BRAF V600E/非-V600E）或癌症治疗均与 TEE 的发生无关。Khorana 评分在癌症诊断时预测血栓形成的效果不佳，因为只有 19.2%的患者被归类为高危。
血栓栓塞事件是 BRAF 突变型肺癌的一种新的临床特征。近 30%的 TEE 发生率的患者应接受系统抗凝治疗。
