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B. Riedel

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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.01-033 - Thrombogenic Biomarkers in Patients with NSCLC – Associations with Thrombosis, Progression, and Survival (ID 8852)

      09:30 - 16:00  |  Author(s): B. Riedel

      • Abstract
      • Slides

      For patients with NSCLC, the risk of thromboembolism (TE) is high but heterogeneous. We aimed to profile biomarkers among NSCLC patients receiving anticancer therapy to identify patients and time periods of high TE risk where intervention with proven preventative strategies is likely to achieve maximal benefit.

      We assessed the association between baseline biomarker levels and longitudinal biomarker changes, with subsequent incidence of TE (venous (VTE) or arterial (ATE)), disease progression and overall survival. Biomarkers (thromboelastography, d-dimer, fibrinogen, haemoglobin, white cell count, platelet count, neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR)) were sequentially assessed at commencement of anticancer therapy (baseline), weeks 1, 4 and 12, and 3-monthly until 12 months.

      During study follow-up (median 22 months, range 6-31), 129 patients were sequentially assessed over median 5 time points (range 1-9). Patients underwent surgery (n=12), chemo-radiotherapy (CRT, n=47), palliative chemotherapy (CHT, n=36), and single modality radiotherapy (RT, n=34) – only surgical patients received thromboprophylaxis. 24 patients (19%) had documented TE, 19 (15%) VTE and 5 (4%) ATE; 79% occurred within the first 6 months with median time to TE 48 days (range 1-151). Among ambulatory patients (CHT/CRT/RT), an initial model identified as high TE risk those patients with baseline fibrinogen ≥4g/L and d-dimer ≥0.5mg/L, or d-dimer ≥1.5mg/L. Hazard ratio (HR) for TE was 8.0 (p=0.04) for high versus low risk CHT/CRT patients and 6.5 (p=0.07) for high versus low risk for CHT/CRT/RT patients. Comparatively, using an established risk score, HR for TE with Khorana score ≥3 vs. <3 was 1.3 (p=0.68) for CHT/CRT and 1.1 (p=0.91) for CHT/CRT/RT. Considering temporal changes (d-dimer ≥1.5mg/L at week 4), risk assessment was enhanced with 100% sensitivity and 34% specificity for CHT/CRT. Specificity reduced to 27% when including RT patients. NLR, PLR and platelet count were not associated with TE. High TE risk patients (Fib≥4 + d-dimer ≥0.5, d-dimer ≥1.5) also had increased risk of cancer progression (HR 2.3, p<0.01) and mortality (HR 2.5, p<0.01). Baseline NLR≥2.5 and platelet count ≥350 were associated with progression (HR 2.0, p=0.01 and HR 2.0, p<0.01 respectively) and mortality (HR 2.6, p=0.01 and HR 1.9, p=0.01 respectively); PLR was not.

      For ambulatory patients with NSCLC, d-dimer and fibrinogen were associated with TE, cancer progression, and prognosis and could easily be applied in a simple algorithm, for real-time decision-making. In spite of low specificity, consideration of thromboprophylaxis is warranted for high risk patients given substantial TE-associated adverse clinical and economic consequences.

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