Does the Argentine Tango Sustainably Improve Cancer-Associated Fatigue and Quality of Life in Breast Cancer Survivors?

BACKGROUND: Chronic cancer-related fatigue is difficult to manage in breast cancer survivors. The tango trial showed that a six-week tango Argentino program was effective in reducing fatigue and improving quality of life, and here we investigated the sustainability of this tango program for breast cancer survivors. METHODS: Stage I-III breast cancer survivors with increased fatigue symptoms were analyzed. The fifty participants in the tango trial were compared with a control cohort (n = 108) who did not participate in the tango program. Using the European Organization for Research and Treatment of Cancer Questionnaire C30 (EORTC-QLQ-C30) and the German version of the cancer fatigue scale (CFS-D) self-reported quality of life parameters were assessed and longitudinal changes, correlations, and association factors were calculated. RESULTS: Significant improvements in fatigue (p = 0.006), physical functioning (p = 0.01), and diarrhea (p = 0.04) persisted in the 50 Tango participants at 6 months, but not in the control cohort. Twelve months after joining the tango program, increased fatigue was associated with reduced sporting activities (p = 0.0005), but this was not the case for tango dancing. CONCLUSIONS: The present results suggest that tango may be appropriate as a component of early supportive and follow-up care programs, to promote health-related quality of life and physical activity and also eventually to improve long-term clinical outcomes of breast cancer survivors. TRIAL REGISTRATION: Trial registration numbers DRKS00013335 on 27 November 2017 and DRKS00021601 on 21 August 2020 retrospectively registered.

Efficacy of Tango Argentino for Cancer-Associated Fatigue and Quality of Life in Breast Cancer Survivors: A Randomized Controlled Trial.

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.

Evaluation of quality of life in lung cancer patients receiving radiation and Viscum album L.: a real-world data study.

BACKGROUND: Lung cancer (LC) is associated with high mortality and poor quality of life (QoL). The disease as well as oncological treatments such as radiation and chemotherapy with adverse effects can impair the QoL of patients. Add-on treatment with extracts of Viscum album L. (white-berry European mistletoe, VA) has been shown to be feasible and safe and to improve the QoL of cancer patients. The aim of this study was to analyze the changes in QoL of LC patients being treated with radiation according to oncological guidelines and add-on VA treatment in a real-world setting. METHODS: A real-world data study was conducted using registry data. Self-reported QoL was assessed by the evaluation of the European Organization of Research and Treatment Health-Related Quality of Life Core Questionnaire scale (EORTC QLQ-C30). Adjusted multivariate linear regression analyses were performed to analyze factors associated with changes in QoL at 12 months. RESULTS: A total of 112 primary LC patients (all stages, 92% non-small-cell lung cancer, median age 70 (ICR: 63-75)), answered the questionnaires at first diagnosis and 12 months later. Assessment of 12 months changes in QoL revealed significant improvement of 27 points for pain (p = 0.006) and 17 points for nausea/vomiting (p = 0.005) in patients who received combined radiation and VA. In addition, significant improvements of 15 to 21 points for role (p = 0.03), physical (p = 0.02), cognitive (p = 0.04), and social functioning (p = 0.04) were observed in guideline treated patients receiving no radiation but add-on VA. CONCLUSIONS: Add-on VA therapy reveals supportive effects for the QoL of LC patients. Particularly in combination with radiation a significant reduction in pain and nausea/ vomiting has been observed. Trial registration The study received ethics approval and was retrospectively registered (DRKS00013335 on 27/11/2017).

Are Aspects of Integrative Concepts Helpful to Improve Pancreatic Cancer Therapy?

Numerous clinical studies have been conducted to improve the outcomes of patients suffering from pancreatic cancer. Different approaches using targeted therapeutic strategies and precision medicine methods have been investigated, and synergies and further therapeutic advances may be achieved through combinations with integrative methods. For pancreatic tumors, a particular challenge is the presence of a microenvironment and a dense stroma, which is both a physical barrier to drug penetration and a complex entity being controlled by the immune system. Therefore, the state of immunological tolerance in the tumor microenvironment must be overcome, which is a considerable challenge. Integrative approaches, such as hyperthermia, percutaneous irreversible electroporation, intra-tumoral injections, phytotherapeutics, or vitamins, in combination with standard-oncological therapies, may potentially contribute to the control of pancreatic cancer. The combined application of standard-oncological and integrative methods is currently being studied in ongoing clinical trials. An actual overview is given here.

Safety of Combined Targeted and Helixor®Viscum album L. Therapy in Breast and Gynecological Cancer Patients, a Real-World Data Study.

BACKGROUND: Newer personalized medicines including targeted therapies such as PARP inhibitors and CDK 4/6 inhibitors have been shown to improve the survival of breast and gynaecological cancer patients. However, efficacy outcomes may be ham5pered by treatment discontinuation due to targeted therapy-related adverse drug reactions or resistance. Studies have suggested that add-on mistletoe (Viscum album L., VA) improves the quality of life and ameliorates the cytotoxic side effects of standard oncological therapy in cancer patients. The primary objective of this real-world data study was to determine the safety profile of targeted therapy in combination with add-on Helixor® VA therapy compared to targeted therapy alone in breast and gynecological cancer patients. METHODS: The present study is a real-world data observational cohort study utilizing demographic and treatment data from the accredited national Network Oncology (NO) registry. The study has received ethics approval. The safety profile of targeted therapies with or without Helixor® VA therapy and safety-associated variables were evaluated by univariate and adjusted multivariable regression analyses. RESULTS: All stages of breast and gynecological cancer patients (n = 242) were on average 54.5 ± 14.2 years old. One hundred and sixty patients (66.1%) were in the control (CTRL, targeted therapy) and 82 patients (33.9%) were in the combinational (COMB, targeted plus Helixor® VA therapy) group. The addition of Helixor® VA did not hamper the safety profile (χ2 = 0.107, p-value = 0.99) of targeted therapy. Furthermore, no adverse events and a trend towards an improved targeted therapy adherence were observed in the COMB group. CONCLUSIONS: The present study is the first of its kind showing the applicability of Helixor® VA in combination with targeted therapies. The results indicate that add-on Helixor® VA does not negatively alter the safety profile of targeted therapies in breast and gynaecological cancer patients.

Viscum album L. Therapy in Oncology: An Update on Current Evidence.

BACKGROUND: A majority of oncological patients apply add-on white-berry European mistletoe (Viscum album L., VA) extracts to reduce disease- and treatment-related symptoms and to improve health-related quality of life (HRQL). VA extracts exert various antitumor, pro-apoptotic, anti-proliferative, and immunomodulatory effects. Two current meta-analyses attribute life-prolonging and HRQL-improving properties to additive VA therapy. The aim of the present update was to review the current knowledge on VA extracts in clinical oncology. Hereby, we concentrated on studies with the highest clinical relevance in the field of lung, gastric, colorectal and pancreatic, gynaecological, as well as breast cancer applying the anthroposophical mistletoe preparations. SUMMARY: The present update provides a brief overview regarding the use of VA preparations in clinical oncology reviewing current guidelines, systematic reviews, randomized controlled and real-world data studies. We have searched the pubmed.gov database of the National Library of Medicine with the search terms "mistletoe" and "cancer." We found good evidence of add-on VA therapy to improve the HRQL of patients with breast cancer (American Society of Clinical Oncology - endorsed Society for Integrative Oncology guideline) and of HRQL-improving and survival-prolonging properties of VA therapy in pancreatic cancer. In the field of gastrointestinal, gynaecological, and lung cancer, new or updating integrative and/or oncological guidelines should consider clear recommendations on integrative therapies including VA therapy. Nevertheless, further clinical and real-world data trials need to be performed in this field. KEY MESSAGES: Evidence for add-on VA treatment for the improved management of cancer and cancer-related side effects is accumulating. Patients with breast cancer: good evidence for add-on VA therapy to improve the HRQL of oncological patients. Patients with pancreatic cancer: good evidence for add-on VA to improve HRQL and prolong survival. Patients with gastrointestinal, gynaecological, and lung cancer: update of guidelines is recommended with regards to integrative oncological therapies including add-on VA.

TANGO: effect of tango Argentino on cancer-associated fatigue in breast cancer patients-study protocol for a randomized controlled trial.

BACKGROUND: The majority of breast cancer patients suffer from persistent impairments after completion of their primary oncological therapy. Cancer-related fatigue (CRF) in particular is a multidimensional syndrome having a profound negative impact on the quality of life. To counter CRF symptoms, physical activities are suggested as first-line interventions, mind-body therapies have been shown to be effective, and music therapy can also reduce anxiety and stress in breast cancer patients. Tango therapy that combines various elements can have an impact on physical, psychological, and cognitive abilities and could therefore have a beneficial effect on breast cancer patients. The purpose of this study is to investigate whether a 6-week tango module is suited as a therapeutic approach for people after primary breast cancer therapy to favorably influence their quality of life, especially CRF levels. METHODS: Sixty patients with a diagnosis for stage I-III breast cancer 12-48 months before enrollment and with CRF (age > 18) will be recruited and randomized 1:1 to a tango or a waiting-list group. Movement concepts using elements of Argentine tango (self-awareness, musical and spatial perception, self-perception, playfulness, shared experience) will be examined with the participants during six consecutive weekly 1-h tango sessions. The primary outcome will be the improvement of CRF (German version of the Cancer Fatigue Scale), and the secondary outcomes will be the improvement in sleep quality (Pittsburgh Sleep Quality Index) and quality of life (EORTC-QLQ-C30). Patient-reported outcomes will be measured at baseline and 6 weeks later; follow-up will be performed 6, 12, and 24 months after baseline. An evaluation will be performed by means of descriptive data analyses. DISCUSSION: Argentine tango, as a music-based movement therapy, can influence different skills and may improve several outcomes. The therapeutic use of Argentine tango in the care of breast cancer patients has not yet been reported. It is anticipated that participants receiving the tango module will have improved CRF, sleep, and quality of life scores compared to a waitlist control. TRIAL REGISTRATION: German Clinical Trials Registry (DRKS) DRKS00021601 . Retrospectively registered on 21 August 2020.

Integrative Medicine and Plastic Surgery: A Synergy-Not an Antonym.

BACKGROUND: Integrative medicine focuses on the human being as a whole-on the body, mind, and spirit-to achieve optimal health and healing. As a synthesis of conventional and complementary treatment options, integrative medicine combines the pathological with the salutogenetic approach of therapy. The aim is to create a holistic system of medicine for the individual. So far, little is known about its role in plastic surgery. HYPOTHESIS: We hypothesize that integrative medicine based on a conventional therapy with additional anthroposophic therapies is very potent and beneficial for plastic surgery patients. Evaluation and consequence of the hypothesis: Additional anthroposophic pharmacological and non-pharmacological treatments are promising for all areas of plastic surgery. We are convinced that our specific approach will induce further clinical trials to underline its therapeutic potential.

Assessment of integrative non-pharmacological interventions and quality of life in breast cancer patients using real-world data.

BACKGROUND: Treatments with non-pharmacological interventions (NPIs), comprising art and exercise therapies, nursing interventions, and educational components, are considered to improve quality of life of cancer patients. The aim of this study was to assess the longitudinal changes in self-reported quality of life of breast cancer patients receiving an integrative medicine program consisting of hospital-based NPIs and standard oncological treatments. METHODS: This real-world data study was conducted using data from the Network Oncology clinical registry of the Gemeinschaftskrankenhaus Havelhöhe. Primary breast cancer patients of all tumor stages, who answered the European Organization of Research and Treatment Health-Related Quality of Life Core Questionnaire scale (EORTC QLQ-C30) at first diagnosis and 12 months later, were included. Association factors between received NPIs and longitudinal EORTC QLQ-C30-changes were analyzed with additive non-parametric regression tests, considering treatment regimens and demographic variables, using the software R. RESULTS: A total of 231 primary breast cancer patients were enrolled and separate regression analyses were carried out. Significant associations between the received NPIs elaborate consultations and life review, nursing compresses, music and eurythmy therapy and improvements of 8-13 points for global health, all five functional EORTC-scales, and symptoms fatigue, dyspnea, insomnia, and financial difficulties were observed. CONCLUSION: Our findings support the beneficial impact of NPIs for breast cancer patients. Further research could be directed towards synergistic effects of multimodal applied NPIs. TRIAL REGISTRATION: Trial registration number DRKS00013335 on 27/11/2017 retrospectively registered.

Evaluation of the effects of integrative non-pharmacological interventions on the internal coherence and resilience of breast cancer patients.

PURPOSE: In the breast cancer center at the Gemeinschaftskrankenhaus Havelhöhe (GKH), integrative strategies are implemented in the routine care of breast cancer patients. The aim of this breast cancer real-world study was to systematically evaluate changes in patients' internal coherence and resilience, associated with the use of non-pharmacological interventions (NPIs). METHODS: This study included 231 primary breast cancer patients treated with standard oncological therapy and NPIs, which comprise art and movement therapies, nursing interventions, and educational components, and had answered the internal coherence scale (ICS) questionnaire at first diagnosis and 12 months later. Data were collected from the Network Oncology clinical registry of the GKH, and effects of NPIs on ICS changes were analyzed with adjusted linear multivariable regression analyses, using the software R. RESULTS: Two hundred twenty breast cancer patients of all tumor stages were eligible for a total of 27 separate adjusted multivariable linear regression analyses. The NPIs elaborate consultations and life review (ECLR); nursing compresses, music therapy, and rhythmic massages were significantly associated with increases of about 2-point changes in inner resilience and coherence (p < 0.05). Furthermore, a significant association with an elevation of the thermo coherence was observed for the application of nursing compresses. CONCLUSIONS: The evaluation of real-world data carried out here shows that the application of the multimodal treatment concept can lead to an enhancement of the internal coherence and resilience in breast cancer patients. To improve the care of cancer patients, this multimodal program should be further expanded into routine clinical practices. TRIAL REGISTRATION: Trial registration number DRKS00013335 on 27/11/2017 retrospectively registered.

Analysis of Changes in Cancer-Related Fatigue of Breast Cancer Patients Receiving an Integrative Medicine Program.

INTRODUCTION: Cancer-related fatigue (CRF) occurs frequently in breast cancer patients. The aim of this real-world study was to analyze the longitudinal changes of CRF in breast cancer patients receiving an integrative medicine program, which includes the application of non-pharmacological interventions (NPIs) and Viscum album L. (VA) extracts. METHODS: All data were collected from the clinical register of the Network Oncology of a German certified breast cancer center of the Gemeinschaftskrankenhaus Havelhöhe (GKH). Primary breast cancer patients, treated upon initial diagnosis with integrated NPIs, comprising art and exercise therapy, nursing interventions, and educational components, during their hospital stay, and who had answered the German Cancer-Fatigue Scale (CFS-D) questionnaire at first diagnosis and 12 months later, were included. The associations between NPIs and CFS-D changes were analyzed with adjusted multivariable regression analyses, considering received treatment regimens and demographic variables, using the software R. RESULTS: 231 female breast cancer patients of all tumor stages were evaluated. While chemotherapy exhibited significant severe deterioration, add-on VA applications seem to partially mitigate this impairment on CRF. 36 separate multivariable regression analyses for all NPIs showed that in particular significant associations between CFS-D improvements and the interventions nursing compresses (6 point change; P = .0002; R² = 28%) or elaborate consultations and life review (ECLR) (4 point change; P = .0002; R² = 25%) were observed. CONCLUSIONS: Breast cancer patients benefit from a hospital-based integrative medicine program. To alleviate fatigue symptoms during oncological therapy, an expansion of this concept should be developed in the future.

Overall Survival of Nonmetastasized NSCLC Patients Treated With Add-On Viscum album L: A Multicenter Real-World Study.

BACKGROUND: Recent data suggest a beneficial effect of add-on treatment with Viscum album L (VA) on the survival in cancer patients. The objective of this study was to compare the impact of standard oncological therapy plus add-on VA treatment (S+VA) versus standard oncological therapy alone (S) on the overall survival (OS) of patients with nonmetastasized non-small cell lung carcinoma (NSCLC). METHODS: The multicenter real-world data study was conducted using data from the Network Oncology Clinical Registry. The primary end point was OS. OS and impact on hazard in both treatment groups were compared. RESULTS: A total of 275 patients with stages I to IIIA NSCLC were enrolled (mean age = 67.6 years, 57.2% male patients). No significant difference of OS was observed between both groups. Even though not significant, for a subgroup of unresected patients with stage I NSCLC, adenocarcinoma or squamous cell carcinoma, a medium effect size OS improvement was observed for S+VA compared to S. CONCLUSIONS: Our findings support the importance of surgery as the most effective intervention in nonmetastasized NSCLC patients. Add-on VA therapy shows here no additional effect in resected patients. However, a small subgroup analysis suggests a possible role of add-on VA for nonresected subgroups. Our results complement existing knowledge on the clinical impact of add-on VA therapy in NSCLC patients and may serve as hypothesis-generating data for further examinations in this cohort. Further research could be directed towards the role of combined therapy for nonresected early-stage NSCLC.

Cost-effectiveness of real-world administration of chemotherapy and add-on Viscum album L. therapy compared to chemotherapy in the treatment of stage IV NSCLC patients.

BACKGROUND: For stage IV lung cancer patients receiving add-on Viscum album L. (VA) treatment an improved overall survival was detected. Information regarding cost-effectiveness (CE) for comparisons between chemotherapy (CTx) and CTx plus additive VA in stage IV lung cancer treatment is limited. The present study assessed the costs and cost-effectiveness of CTx plus VA (V) compared to CTx alone (C) for stage IV non-small cell lung cancer (NSCLC) patients treatment in a hospital in Germany. METHODS: In the observational real-world data study, data from the Network Oncology clinical registry were utilized. Enrolled stage IV lung cancer patients received the respective therapy (C or V) in a certified German Cancer Center. Cost and cost-effectiveness analyses from the hospital's perspective were investigated on the basis of overall survival (OS) and routine financial controlling data. In addition, the incremental cost-effectiveness ratio (ICER) was calculated. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. RESULTS: 118 patients (C: n = 86, V: n = 32) were included in the analysis, mean age 63.8 years, the proportion of male patients was 55.1%. Adjusted hospital's total mean costs for patients from the C and V group were €16,289, 95%CI: 13,834€-18,744€ (over an adjusted mean OS time of 13.4 months) and €17,992, 95%CI: 13,658-22,326 (over an adjusted mean OS time of 19.1 months), respectively. The costs per additional OS year gained (ICER) with the V-therapy compared to C therapy were €3,586. CONCLUSION: The findings of the present study suggest that the combined use of chemotherapy and VA was clinically effective and comparably cost-effective to chemotherapy alone in our analysed patient sample from the hospital's perspective. Further randomized and prospective cost-effectiveness studies are necessary to complement our findings.

Impact of Oncological Therapy and Viscum album L Treatment on Cancer-Related Fatigue and Internal Coherence in Nonmetastasized Breast Cancer Patients.

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.

Health-Related Quality of Life in Patients with Lung Cancer Applying Integrative Oncology Concepts in a Certified Cancer Centre.

BACKGROUND: Pretreatment health-related quality of life (HRQOL) is associated with survival outcome in lung cancer patients. There is a lack of systematic research on pretreatment HRQOL in lung cancer patients who receive integrative oncology (IO). We evaluated patient-reported outcomes in these patients at time of diagnosis at a certified oncology and lung cancer centre. METHODS: The present analysis is a prospective real-world data study. Clinical and demographic data were obtained from the accredited Network Oncology cancer registry. Pretreatment HRQOL was evaluated (international standardized questionnaires) for people with all-stage lung cancer at first diagnosis that received IO consisting of standard therapy and multimodal add-on complementary concepts. Univariate and adjusted multivariate regression analyses were performed with R. Results. Eighty seven patients with all-stage lung cancer were eligible for the questionnaire analysis (median age 68.0 years, IQR 59.0-74.4). Thirty percent of the total cohort reported financial difficulties. Self-reported pretreatment financial difficulty was associated with younger age (p=0.007), pretreatment pain (p=0.006), anxiety (p=0.04), and low mood (p=0.03). Pain (p=0.03) and young age (p=0.02) in the early- and late-stage lung cancer were associated with financial difficulties. CONCLUSION: We suggest physicians screen lung cancer patients at working age (broadly aged ≤65 years) and/or who report increased pain at the time of diagnosis as they might be at particular risk for emotional, physical, and financial problems. Our results emphasize to address emotional and physical needs before and during early treatment in lung cancer patients as suggested in integrative and supportive cancer concepts.

Cost-Effectiveness of Real-World Administration of Concomitant Viscum album L. Therapy for the Treatment of Stage IV Pancreatic Cancer.

BACKGROUND: For patients receiving add-on Viscum album L. (VA) treatments for late-stage pancreatic cancer, an improved overall survival (OS) was observed. Only limited information regarding cost-effectiveness (CE) for comparisons between standard of care and standard of care plus add-on VA in stage IV pancreatic cancer treatment is available. The present study assessed the costs and cost-effectiveness of standard of care plus VA (V) compared to standard of care alone (C) for a hospital in Germany. METHODS: An observational study was conducted using data from the Network Oncology clinical registry. Patients included had stage IV pancreatic cancer at diagnosis and received C or V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. RESULTS: 88 patients (C or n = 34; V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. n = 34; C or V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. C or V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. C or V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. C or. CONCLUSION: Based on this CEA analysis, from the hospital's point of view, the costs per mean month of OS and per mean hospital stay were lower for patients under combinational standard of care plus VA compared to patients receiving standard of care alone for the treatment of stage IV pancreatic cancer. Further prospective cost-effectiveness studies are mandatory to reevaluate our findings.

Statement to an Insufficient Systematic Review on Viscum album L. Therapy.

BACKGROUND: Up to 88% of oncological patients apply complementary therapies and up to 77% apply complementary mistletoe therapy in the context of integrative oncological approaches. An evidence-based consultation of oncological health professionals regarding complementary therapies used in Germany is missing. Therefore, a new S3-Guideline for Complementary Medicine in the Treatment of Oncological Patients is under development and is anticipated to be finalized in November 2020. It will be based on evidence-based publications and systematic reviews on complementary therapies in oncology. A recently published two-part systematic review on mistletoe treatment in oncology has been reevaluated. METHODS: The latest published systematic two-part review on mistletoe has been systematically proofread and checked in compliance with the Cochrane Handbook for Systematic Reviews of Intervention and the AMSTAR 2 (A MeaSurement Tool to Assess Systematic Reviews) tool. RESULTS: The here discussed two-part review is incomplete, lacks sound accuracy including insufficient assessment of the risk of bias, and contains imprecise statements. In addition, it does not sufficiently comply with the Cochrane Handbook for Systematic Reviews of Intervention and the AMSTAR 2 tool. CONCLUSION: In view of the approaching release of a new guideline in the field of complementary therapies in oncology, the present statement draws attention to a lack of profound methodology of conductance of a recently released systematic review on mistletoe. In consequence, a comprehensive overview of published mistletoe studies, i.e., a meta-analysis with a sound methodology of conductance, is necessary.

Mistletoe and Immunomodulation: Insights and Implications for Anticancer Therapies.

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.

Use and Safety of Viscum album L Applications in Cancer Patients With Preexisting Autoimmune Diseases: Findings From the Network Oncology Study.

BACKGROUND: Viscum album L (VA, mistletoe) extracts are commonly used in integrative oncology. Here the clinical safety profile of additional VA-treatments to standard care in cancer patients with preexisting autoimmune diseases was analyzed. METHODS: In this observational cohort study medical data and recorded adverse events (AEs) of treated patients were retrieved from the Network Oncology registry and a safety analysis was performed. RESULTS: A total of 106 patients (median age 63 years) treated with add-on VA-extracts were analyzed. Most frequent autoimmune diseases were Hashimoto's thyroiditis (27%), psoriasis (19%), and ulcerative colitis (15%). Seventeen patients (16%) experienced VA-related AEs, but neither long-term side effects nor VA-therapy discontinuations were recorded. In a subgroup of 30 patients receiving long-term VA-therapy no exacerbations or flares of underlying autoimmune diseases were recorded. Additionally, a significant halving of overall AE-rates was observed during VA-treatment periods (p= 0.019). CONCLUSIONS: Our findings suggest that add-on VA-therapy in cancer patients with preexisting autoimmune diseases as Hashimoto's thyroiditis, psoriasis, ulcerative colitis, Grave's disease, and some rheumatic diseases is safe. No higher rates of VA-associated AEs were observed and the overall AE-rates were significantly lowered in VA-therapy periods. However, results should be interpreted with caution in light of the study's observational character.

The Internal Coherence of Breast Cancer Patients Is Associated with the Decision-Making for Chemotherapy and Viscum album L. Treatment.

OBJECTIVE: In the present observational study, the influence of internal coherence on shared decision-making for chemotherapy (CTX) and Viscum album L. extracts (VA) treatment in breast cancer patients was evaluated. METHODS: Breast cancer patients with a guideline-oriented advice from the tumor board for CTX were included in the study. At first diagnosis (T0) and 6 months later (T1), a questionnaire, the internal coherence scale (ICS), was administered and evaluated. Prior to analysis, patients were classified retrospectively depending on their treatment decision. RESULTS: 64 primary nonmetastasized breast cancer patients (median age 54.8 years, IQR: 46.3-65.3) were analyzed in this study. At T0, adjusted multivariable linear regression analyses revealed significant low ICS scores in patients rejecting CTX, especially in the ICS subscale "thermo coherence" (p = 0.006). The decision for add-on VA-therapy was associated with low scores for the ICS subscale "inner resilience coherence", in particular low for the item "courage". At T1, in the CTX+VA-group the thermo coherence increased significantly (p(d) < 0.01), while in contrast, in the CTX-only group the thermo coherence decreased significantly (p(d) = 0.02). CONCLUSION: Add-on VA-applications in CTX treatment support the thermo coherence of breast cancer patients, revealing a decision option to encourage patients to undergo CTX in combination with additional VA-treatments.