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- Title
Dynamic Thromboembolic Risk Modelling to Target Appropriate Preventative Strategies for Patients with Non-Small Cell Lung Cancer.
- Authors
Alexander, Marliese; Ball, David; Solomon, Benjamin; MacManus, Michael; Manser, Renee; Riedel, Bernhard; Westerman, David; Evans, Sue M.; Wolfe, Rory; Burbury, Kate
- Abstract
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, p = 0.01) and mortality (HR 2.2, p = 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).
- Subjects
LUNG cancer complications; LUNG cancer prevention; LUNG cancer treatment; THROMBOEMBOLISM prevention; THROMBOEMBOLISM risk factors; FIBRINOGEN; BIOMARKERS; CANCER chemotherapy; LONGITUDINAL method; TUMOR classification; GASTROINTESTINAL tumors; ODDS ratio; THERAPEUTICS
- Publication
Cancers, 2019, Vol 11, Issue 1, p50
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers11010050