In early tumor development, cancer cells develop a plethora of strategies to escape surveillance from the adaptive and innate immune system. Cancer immunotherapies, in particular immune checkpoint inhibitors, are becoming a highly promising cancer therapeutic approach that has remarkable increased progress in combating various cancer types. Unfortunately, their mechanisms of action induce some complications, such as inflammatory reactions and immune-related adverse events. In the management of side effects during anticancer therapy, complementary and integrative therapy approaches are becoming of growing interest. Particularly, mistletoe, Viscum album L. (VA), has a long traditional history of about 100 years as an add-on therapy of cancer treatment in German-speaking countries. Besides antitumoral and quality of life-promoting activities, VA applications reduce side effects of modern conventional anticancer therapies and exert immunomodulatory characteristics. As these properties may provide a good basis for a combination with modern oncological therapies, the biological activities of VA applications and mechanisms involved have to be understood. In this review, the impact of VA compounds on different cellular pathways and immunological reactions in the fight against cancerous cells is discussed.

Background: Persistent impairments of quality of life—in particular, cancer-associated fatigue—are a major limitation for breast cancer survivors. As physical activity and mindfulness interventions have been shown to be effective in reducing fatigue symptoms, we investigated the efficacy of a six-week Argentine tango program. Methods: A randomized controlled trial was conducted with 60 breast cancer survivors diagnosed with stage I-III tumors 12–48 months prior to study enrollment and who had increased symptoms of fatigue. The participants were randomly assigned with a 1:1 allocation to either the tango or the waiting group. The treatment consisted of six weeks of supervised weekly one-hour tango group-sessions. Self-reported fatigue and further quality of life parameters were assessed at baseline and six weeks post-baseline. Longitudinal changes, correlations, Cohen’s D (d) effect sizes, and association factors were also calculated. Results: Superiority of the tango intervention over the waiting list control was found in terms of improvement in fatigue (d = −0.64; 95%CI, −1.2 to −0.08; p = 0.03), especially cognitive fatigue. In addition, a superiority of the tango intervention over the waiting list was found in the improvement of diarrhea (d = −0.69; 95%CI, −1.25 to −0.13; p = 0.02). A pooled pre-post analysis of the 50 participants completing the six-week tango program revealed a close to 10% improvement of fatigue (p = 0.0003), insomnia (p = 0.008) and further quality of life outcomes. Adjusted multivariate linear regression analyses revealed the greatest improvements for participants who were more active in sports. In particular, survivors who received endocrine therapies, were obese, or had no prior dance experience seemed to especially benefit from the tango program. Conclusions: This randomized controlled trial demonstrated that a six-week Argentine tango program improves fatigue in breast cancer survivors. Further trials are warranted to determine whether such improvements lead to better long-term clinical outcomes. Trial registration: trial registration number DRKS00021601. Retrospectively registered on 21 August 2020.

Background: Despite improvement of tumor response rates, targeted therapy may induce toxicities in cancer patients. Recent studies indicate amelioration of adverse events (AEs) by add-on mistletoe (Viscum album L., VA) in standard oncological treatment. The primary objective of this multicenter observational study was to determine the safety profile of targeted and add-on VA therapy compared to targeted therapy alone. Methods: Demographic and medical data were retrieved from the Network Oncology registry. Allocation to either control (targeted therapy) or combinational group (targeted/add-on VA) was performed. Safety-associated variables were evaluated by adjusted multivariable analyses. Results: The median age of the study population (n = 310) at first diagnosis was 59 years; 67.4% were female. In total, 126 patients (40.6%) were in the control and 184 patients (59.4%) in the combination group. Significant differences were observed between both groups with respect to overall AE frequency (χ² = 4.1, p = 0.04) and to discontinuation of standard oncological treatment (χ² = 4.8, p = 0.03) with lower rates in the combinational group (20.1%, 35% respectively) compared to control (30.2%, 60.5%, respectively). Addition of VA to targeted therapy significantly reduced the probability of oncological treatment discontinuation by 70% (Odds ratio (OR) 0.30, p = 0.02). Conclusions: Our results indicate a highly significant reduction of AE-induced treatment discontinuation in all-stage cancer patients when treated with VA in addition to targeted therapy.

Introduction: Viscum album L extracts (VA) are frequently used in integrative oncology. Aim of this study was to evaluate the impact of add-on VA applications on various patient-reported outcome measures. Methods: A longitudinal real-world study was conducted, using data from the Network Oncology clinical registry. Primary, nonmetastasized breast cancer patients treated with oncological standard therapy partly combined with VA applications were included. Internal Coherence Cancer-related Fatigue, and EORTC QLQ-C30 questionnaires were assessed at baseline and 6, 12, and 24 months later. Results: A total of 319 patients received standard oncological therapy and 40% of them additionally VA applications. After 6 and 12 months for patients treated with chemotherapy (Ctx) only a significant decline of the thermo-coherence, and worsening of fatigue was observed. For patients receiving VA applications but no Ctx, significant beneficial effects on thermo-coherence, fatigue, and seven EORTC QLQ-C30 scales were observed 24 months later. Adjusted multivariable long-term subgroup (n = 106) regression analysis revealed that Ctx, immuno-, and endocrine therapies had a worsening of 17, 17, and 6 point changes, respectively, for EORTC QLQ-C30 fatigue (P = .0004), while VA applications showed an improvement of 12 point change. A similar impact of improvement (add-on VA) and worsening (standard oncological treatment regimens) on EORTC QLQ-C30 insomnia (P = .009) and physical functioning (P = .005) were observed. Conclusions: In the present real-world study, add-on VA applications had a supportive effect on cancer-related fatigue, insomnia, physical functioning, and thermo-coherence. Thus, VA applications might be suited to alleviate symptom burden during anticancer therapy in breast cancer patients.

Objective: The concept of integrative oncology (IO) comprising guideline-oriented standard and add-on complementary medicine has gained growing importance. The Anthroposophic-integrative Cancer Centre (CC) at the hospital Gemeinschaftskrankenhaus (GKH) in Berlin has been implementing IO concepts during recent years. Furthermore, it is a certified CC and has been annually audited by national cancer authorities since 2012. The objective of the present study was to evaluate IO concepts of the certified CC GKH. Methods: Clinical, demographic, integrative treatment and follow-up data were analyzed between 2011 and 2016. In addition, CC GKH quality measures were compared with those of nationwide benchmarking CCs. Results: Between 2011 and 2016, 2.382 primary cancer patients, median age 66 years, were treated at the CC GKH. 70.1% of the patients showed either Union for International Cancer Control (UICC) stage 0, I, II or III and 25.6% were in UICC stage IV. IO therapies included surgery (64.4% of patients), radiation (41.2%), and application of cytostatic drugs (53.9%), add-on mistletoe therapy (30.5%), and non-pharmacological interventions (87.3%). Regarding psycho-oncological support and quota of patient’s enrollment in studies the CC GKH performs above nationwide benchmarks. Research outcomes including safety issues, clinical impact as well as patient’s health-related quality of life are continuously evaluated and integrated into hospital’s decision-management. Conclusion: This analysis reveals that IO concepts are applied to a high proportion of male and female primary cancer patients of all age groups, indicating a successful implementation at the certified CC GKH. Ongoing clinical evaluations have been initiated and cost-effectiveness comparisons are under analyses.