Alexander Marliese, Ball David, Solomon Benjamin, MacManus Michael, Manser Renee, Riedel Bernhard, Westerman David, Evans Sue M, Wolfe Rory, Burbury Kate
Department of Epidemiology and Preventive Medicine Monash University, 99 Commercial Road, Melbourne, VIC 3004, Australia.
Pharmacy Department, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, VIC 3000, Australia.
Cancers (Basel). 2019 Jan 8;11(1):50. doi: 10.3390/cancers11010050.
Prevention of cancer-associated thromboembolism (TE) remains a significant clinical challenge and priority world-wide safety initiative. In this prospective non-small cell lung cancer (NSCLC) cohort, longitudinal TE risk profiling (clinical and biomarker) was undertaken to develop risk stratification models for targeted TE prevention. These were compared with published models from Khorana, CATS, PROTECHT, CONKO, and CATS/MICA. The NSCLC cohort of 129 patients, median follow-up 22.0 months (range 5.6-31.3), demonstrated a hypercoagulable profile in >75% patients and TE incidence of 19%. High TE risk patients were those receiving chemotherapy with baseline fibrinogen ≥ 4 g/L and d-dimer ≥ 0.5 mg/L; or baseline d-dimer ≥ 1.5 mg/L; or month 1 d-dimer ≥ 1.5 mg/L. The model predicted TE with 100% sensitivity and 34% specificity (c-index 0.67), with TE incidence 27% vs. 0% for high vs. low-risk. A comparison using the Khorana, PROTECHT, and CONKO methods were not discriminatory; TE incidence 17⁻25% vs. 14⁻19% for high vs. low-risk (c-index 0.51⁻0.59). Continuous d-dimer (CATS/MICA model) was also not predictive of TE. Independent of tumour stage, high TE risk was associated with cancer progression (HR 1.9, = 0.01) and mortality (HR 2.2, = 0.02). The model was tested for scalability in a prospective gastrointestinal cancer cohort with equipotency demonstrated; 80% sensitivity and 39% specificity. This proposed TE risk prediction model is simple, practical, potent and can be used in the clinic for real-time, decision-making for targeted thromboprophylaxis. Validation in a multicentre randomised interventional study is underway (ACTRN12618000811202).
预防癌症相关血栓栓塞（TE）仍然是一项重大的临床挑战，也是全球安全倡议的重点。在这个前瞻性非小细胞肺癌（NSCLC）队列中，进行了纵向TE风险分析（临床和生物标志物），以开发针对性TE预防的风险分层模型。将这些模型与来自Khorana、CATS、PROTECHT、CONKO和CATS/MICA的已发表模型进行比较。129例NSCLC患者的队列，中位随访时间22.0个月（范围5.6 - 31.3个月），超过75%的患者表现出高凝状态，TE发生率为19%。高TE风险患者是那些接受化疗且基线纤维蛋白原≥4 g/L和D - 二聚体≥0.5 mg/L的患者；或基线D - 二聚体≥1.5 mg/L的患者；或第1个月D - 二聚体≥1.5 mg/L的患者。该模型预测TE的敏感性为100%，特异性为34%（c指数0.67），高风险组与低风险组的TE发生率分别为27%和0%。使用Khorana、PROTECHT和CONKO方法进行的比较没有鉴别力；高风险组与低风险组的TE发生率分别为17⁻25%和14⁻19%（c指数0.51⁻0.59）。连续D - 二聚体（CATS/MICA模型）也不能预测TE。与肿瘤分期无关，高TE风险与癌症进展（HR 1.9，P = 0.01）和死亡率（HR 2.2，P = 0.02）相关。该模型在前瞻性胃肠道癌队列中进行了可扩展性测试，并证明了等效性；敏感性为80%，特异性为39%。这个提出的TE风险预测模型简单、实用、有效，可用于临床进行实时针对性血栓预防的决策。一项多中心随机干预研究的验证正在进行中（ACTRN12618000811202）。
