LAUSR

Cancer patients frequently use extracts from European mistletoe (Viscum album L.) as a complementary treatment (Zänker and Kaveri 2015). Freuding et al. aimed at reviewing the effects of mistletoe extracts in cancer therapy on overall survival and safety and giving an overview about current research (Freuding et al. 2019). Risk of bias was declared to have been assessed by means of the Cochrane Risk of Bias Tool (Higgins et al. 2017). The authors conclude that “most studies did not show any effect of mistletoe on survival”, and that “with respect to survival, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients with cancer.” We argue in the following that both these statements of Freuding et al. are not supported by their own analysis. In their analysis, 14 out of the 26 reviewed publications reported on survival time. Mistletoe extracts numerically prolonged survival in 11 of these 14 studies (79%), with five studies (36%) demonstrating statistically significant prolongation of survival. Freuding et al. did not perform a meta-analysis in their review. The Cochrane Handbook for Systematic Reviews of Interventions states that “Potential advantages of metaanalyses include an increase in power, an improvement in precision, the ability to answer questions not posed by individual studies, and the opportunity to settle controversies arising from conflicting claims” (Deeks et al. 2017). Given the fact that 5 out of 14 studies yielded significant survival benefits and further 6 out of the 14 studies showed a favorable trend, a meta-analysis seems indicated to increase power to detect any real differences in survival. The meta-analysis conducted by Ostermann et al. in 2009 on the effects of fermented mistletoe extracts correspondingly came to the conclusion “A random effect meta-analysis estimated the overall hazard ratio at HR = 0.59 (CI 0.53 to 0.66, p < 0.0001)”. As a scientific community we should be committed to avoiding communication of false-positive as well as false-negative results. Therefore, the statement that “most studies did not show any effect of mistletoe on survival” seems not justified to us, in view of the available data. Furthermore, risk of bias assessment is largely faulty and was only insufficiently conducted according to the declared methods (Cochrane Risk of Bias Tool (Higgins et al. 2017)). In the following, we refer mainly to Table 3 of the publication and the corresponding parts of the text.