The tumor grade may help identify patients with cancer who are at high risk of VTE. The association of tumor grade with recently identified biomarkers indicates a link between tumor differentiation and pathogenesis of cancer-associated VTE.

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Comment on Ferroni et al.: "Impact of chemotherapy on venous thromboembolism.Comment to: Regional lymph node metastases are a strong risk factor for venous thromboembolism: results from the Vienna Cancer and Thrombosis Study" HAEMATOL/2012/073338 and HAEMATOL/2013/092528The notion of an increased venous thromboembolism (VTE) risk in patients with distant and regional stage cancer compared to those with local stage cancer can obviously be explained by the elevated tumor burden and an already systemic interaction of tumor cells via the lymph and blood system in regional and distant stage cancer. 1Ferroni et al. 2 presented data of a cohort of ambulatory cancer patients who underwent chemotherapy and attempted to compare their results with our findings concerning VTE in regional stage cancer patients. 1 Interestingly, there was a similar incidence of VTE between the cohorts: 7% in the cohort of Ferroni et al. 2 and 6.9% in ours. 1 Also similar to the results in our Vienna Cancer And Thrombosis Study (CATS), the authors found an association between tumor stage and the occurrence of VTE. The univariate hazard ratio (HR) of progressive tumor stage (from low to regional to distant stage) for VTE was 1.61 (95% confidence interval (95%CI) 1.02-2.54; P=0.042). However, in multivariate analyses, predictive value of progressive stage for VTE was completely lost in their study. Unfortunately, detailed results of multivariate analyses were not shown by Ferroni et al. 2 Conversely, in CATS, patients with both regional stage and distant stage cancer had a significantly higher risk of VTE compared to local stage cancer patients in univariate and multivariate analyses. In detail, the association between progressive tumor stage and occurrence of VTE was strong and highly statistically significant (HR=1.81, 95%CI: 1.27-2.56; P=0.001; separate HRs for regional and distant stage versus local stage were 3.5 (95%CI: 1.4-8.9) and 4.0 (95%CI: 1.8-9.0), respectively.In a cross-tabulation analysis, Ferroni et al. 2 found a higher administration of prothrombotic anti-cancer drugs in patients with regional and distant disease. They conclude that a more aggressive treatment with anti-cancer drugs may contribute to the high VTE incidence in patients with regional and distant disease. We completely agree with the authors that treatment with specific anti-cancer drugs is an important risk factor for the occurrence of VTE. However, we want to stress that treatment with anti-cancer drugs is only one of many risk factors for cancer-associated VTE. [2][3][4][5][6][7][8] Naturally, there are interactions between the risk factors for cancer-associated VTE and thus not all risk factors are independent predictors of cancer-associated VTE. In our study we adjusted for multiple risk factors, including the administration of anti-cancer drugs. Moreover, the administration of anti-cancer drugs was considered as a timedependent variable in the multivariable Cox regression analysis, to provide better weighting of the duration of treatment with anti-cancer drugs...