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M. Dancewicz



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    ORAL 16 - Clinical Care of Lung Cancer and Advanced Biopsies (ID 115)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      ORAL16.02 - Thromboembolic and Bleeding Risk with Adjuntctive LMWHs Anticoagulation in Lung Cancer Patients. Meta-Analysis of Randomized Trials (ID 2157)

      10:45 - 12:15  |  Author(s): M. Dancewicz

      • Abstract
      • Presentation
      • Slides

      Background:
      Venous thromboembolism (VTE) has been demonstrated one of the leading causes of mortality in lung cancer patients. While incidence of VTE in cancer patients varies from 4-20%, at autopsy VTE accounts for as high as 50%. Various strategies of VTE prophylaxis have been proposed, among them low-molecular weight heparins (LMWHs). While different randomized controlled trials (RCTs) showed benefit with LMWHs in regard to VTE, none single RCT was adequately powered for major bleeding. In a meta-analysis of RCTs we aimed to investigate the relation between thromboembolic and bleeding risk associated with LMWHs anticoagulation in lung cancer patients.

      Methods:
      Established methods were used in compliance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement in healthcare interventions. PubMed, EMBASE, CINAHL, Cochrane, Scopus databases as well as major congress proceedings until April 2015 were screened for RCTs comparing LMWHs with control/placebo. Outcomes assessed were VTE and major bleeding. Odds ratios (OR) and 95% confidence intervals were used as summary statistics. Data were analysed according to Intention-to-treat principle.

      Results:
      Four RCTs (N=3097) were included in the meta-analysis (Table 1). Average follow-up was 237 days. In a fixed effects model, LMWHs were associated with a significant 50% reduction of the odds of VTE as compared to controls: OR (95% CI): 0.50 (0.35-0.71); p<0.0001; I[2]=0%; (Figure 1A); the number needed to treat =33. A significant, over 2-fold increase in the odds of major bleeding was observed with LMWHs: OR (95% CI): 2.16 (1.16-4.05); p=0.02; I[2]=0%; (Figure 1B); the number needed to harm was 104.

      Table 1. Characteristics of included studies
      Study N of pts LMWH Dose NSCLC/SCLC Follow-up (d)
      Agnelli et al. 2009 279 Nadroparin 3800 IU qd 79.9%-20.1% 112
      Altinbas et al. 1-2, 2004 84 Dalteparin 5000 IU qd 0%-100% 301
      Haas et al. 2012 546 Certoparin 3000 IU qd 100%-0% 168
      Woodruff et al. 2013 2202 Dalteparin 5000 IU qd 82.2%-18.8% 365
      Figure 1



      Conclusion:
      Low-molecular weight heparins significantly reduce the risk of venous thromboembolism at a price of increased major bleeding in patients with lung cancer. One episode of major bleeding occurred at every 3 VTEs prevented with LMWHs. Dose-escalation studies are certainly warranted to identify patients who would benefit most from LMWHs.

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    P2.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 210)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      P2.02-011 - Optimal Strategy to Prevent Atrial Fibrillation in Patients Undergoing Pulmonary Resection for Lung Cancer. Network Meta-Analysis (ID 2383)

      09:30 - 17:00  |  Author(s): M. Dancewicz

      • Abstract
      • Slides

      Background:
      Atrial fibrillation (AF) after pulmonary resections for lung cancer, although transient in most cases, occurs in up to 30% following lobectomy and up to 65% after pneumonectomy and might, in turn, lead to serious adverse events including stroke, myocardial infarction and death. Different preventive measures have been investigated, however because of paucity of evidence from randomized studies, straightforward recommendations are still uncertain. We aimed to perform a Bayesian-framework mixed treatments comparison (network) meta-analysis of both randomized controlled- (RCTs) and observational studies, to investigate the net-relative benefit of diverse drugs in prevention of atrial fibrillation following pulmonary resections for lung cancer.

      Methods:
      We screened Medline, Google Scholar, EMBASE and Cochrane CENTRAL registries for randomized and observational studies comparing drugs to each other and/or to placebo. Studies with post-operative AF as prespecified end-point were retrieved for detailed abstraction. Primary outcome was assessed at longest available follow-up.

      Results:
      Overall 15 studies (13 RCTs) were identified, enrolling N=1753 patients. Beta-blockers, Atrial Natriuretic Peptide and Flecainide were associated with significant relative reduction in odds of postoperative AF, OR (2.5-97.5% CrI) of 0.34 (0.02-0.92); 0.35 (0.00-0.94) and 0.11 (0.00-0.46) respectively; Digoxin was found to increase these odds. Addition of observational data allowed for identification of Amiodarone as another potentially preventive treatment OR (2.5-97.5% CrI) 0.28 (0.03-0.69). Bayesian posterior probability curves revealed the ranking among treatments with Flecainide, beta-blockers, ANP and Amiodarone being associated with the highest probability to reduce the odds of AF, magnesium and calcium blockers with virtually no effect and digoxin found inferior to placebo. Figure 1



      Conclusion:
      Beta-blockers and Flecainide are effective in reducing the incidence of postoperative AF in patients after pulmonary resections which is not the case with digoxin; data on remaining treatments are sparse and preclude drawing definite conclusions.

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