Mistletoe Therapy Research Articles

Systematic assessment of the influence of quality of studies on mistletoe in cancer care on the results of a meta-analysis on overall survival

PurposeMistletoe treatment in cancer patients is controversial, and a Cochrane review concluded that due to heterogeneity, performing a meta-analysis was not suitable. However, several systematic reviews included meta-analyses in favor of mistletoe. The aim of this work was to assess the influence of the methodological quality of controlled studies on the results of a meta-analysis regarding overall survival.MethodsBetween April and August 2022, Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL and Web of Science were systematically searched. In addition, reference lists of previously published meta-analyses were checked for relevant publications. A random effects meta-analysis with clustering was performed. The risk of bias within the studies was assessed using ROB 2.0 and ROBINS-I.ResultsThe search identified 4685 hits, and 28 publications reporting on 28 298 patients were included in the quantitative analysis. Overall, the analysis led to a significant result in favor of mistletoe therapy (overall HR = 0.61 with 95% CI [0.53;0.7]). According to our subgroup analysis of randomized studies, studies of higher quality (lower risk of bias) did not lead to a significant result in favor of mistletoe therapy (HR = 0.78; CI = [0.30; 2.00]).ConclusionsIn the case of mistletoe therapy, the results of the meta-analysis strongly depended on the methodological quality of the included studies. Calculating meta-analyses that include low-quality studies may lead to severe misinterpretation of the data.

Clinical characteristics and therapeutic behavior of breast cancer patients using mistletoe therapy consulting a clinic offering integrative oncology: a registry data analysis

MotivationCancer patients often use complementary and/or alternative medicine, such as mistletoe therapy, alongside conventional cancer therapies. In Switzerland, so far not much is known about treatment patterns of breast cancer patients using integrative oncology. Solid knowledge on complementary care utilization may help to enhance integrative oncology care in Switzerland.MethodsIn this exploratory, descriptive database study, we investigated the treatment pathways of a cohort of breast cancer patients who received mistletoe therapy and were documented in the cancer registry of an anthroposophic Swiss hospital offering integrative oncology treatments.ResultsPatients treated with mistletoe in this cohort are in median 10 years younger than Swiss breast cancer patients as a whole. Only 5.8% of these patients were treated with mistletoe alone, while 60.5% of them supplemented chemotherapy and/or hormone therapy and/or surgery and/or radiation with mistletoe therapy. Nearly 80% of patients started conventional therapy followed by additional mistletoe therapy or started mono mistletoe therapy after completion of conventional therapies. The median time from initial diagnosis to hospital admission (inpatient and/or outpatient) was less than one year. Almost ¾ of the patients were treated in an outpatient setting only.ConclusionFrom our data, it appears that younger breast cancer patients are more likely to use mistletoe therapy simultaneously with or following their conventional medical therapies. The extent to which these patients discuss their mistletoe therapy and eventually other complementary and/or alternative therapies with their primary oncologists is not clear from the data. We therefore recommend that (Swiss) oncologists should openly discuss the desire for integrative oncology therapies, especially with their younger breast cancer patients, in order to find the best holistic care pattern for these patients.

Patients with Advanced Pancreatic Cancer Treated with Mistletoe and Hyperthermia in Addition to Palliative Chemotherapy: A Retrospective Single-Center Analysis.

This retrospective analysis investigated the influence of integrative therapies in addition to palliative chemotherapy in patients with advanced pancreatic cancer, treated at a single institution specialized in integrative oncology between January 2015 and December 2019. In total, 206 consecutive patients were included in the study, whereof 142 patients (68.9%) received palliative chemotherapy (gemcitabine/nab-paclitaxel 33.8%; FOLFIRINOX 35.9%; gemcitabine 30.3%) while the remainder were treated with best supportive and integrative care. Integrative therapies were used in 117 of 142 patients (82.4%) in addition to conventional chemotherapy, whereby mistletoe was used in 117 patients (82.4%) and hyperthermia in 74 patients (52.1%). A total of 107/142 patients (86.3%) died during the observation period, whereby survival times differed significantly depending on the additional use of integrative mistletoe or hyperthermia: chemotherapy alone 8.6 months (95% CI 4.7-15.4), chemotherapy and only mistletoe therapy 11.2 months (95% CI 7.1-14.2), or a combination of chemotherapy with mistletoe and hyperthermia 18.9 months (95% CI 15.2-24.5). While the survival times observed for patients with advanced pancreatic cancer receiving chemotherapy alone are consistent with pivotal phase-III studies and German registry data, we found significantly improved survival using additional mistletoe and/or hyperthermia.

Patient' and social aspects related to complementary mistletoe therapy in patients with breast cancer: A systematic review commissioned by the German agency for Health Technology Assessment.

To mitigate side effects of conventional cancer care and improve quality of life, many patients with breast cancer in German-speaking countries opt for mistletoe therapy in addition to standard treatment. To understand the value for users, we evaluated the domain "Patient and Social aspects" in a health technology assessment on complementary mistletoe therapy in patients with breast cancer. A systematic review was conducted according to PRISMA guidelines. Fifteen electronic databases and the internet were searched. Qualitative studies were analyzed using qualitative content analysis; quantitative studies were systematically summarized in evidence tables. Seventeen studies out of 1203 screened publications with 4765 patients and 869 healthcare professionals were included in the review. The median proportion of patients using mistletoe therapy was 26.7% (range: 7.3-46.3%). Predictors for use were younger age and higher educational level. Main reasons for patients' use of mistletoe therapy were to leave nothing untried and to be actively involved in the treatment process. Reasons against use were related to a lack of knowledge or uncertainty regarding effectiveness and safety. Physicians mainly aimed to support the patient's physical condition as main reason for use and a lack of resources and knowledge as main reason against use. Mistletoe therapy was commonly used in the treatment of breast cancer despite a lack of scientific knowledge among patients and physicians. Transparent communication on motivation for use and its potential effect enables realistic expectations. Relatively small samples of mistletoe therapy users limit the representativeness and validity of our results.

The Introspective Patient Experience of Mistletoe Therapy in Cancer: A Qualitative Study.

The introspective experience of cancer patients using mistletoe therapy has received little scientific interest, although it is crucial for a holistic understanding of this therapy. This study contributes to patient-centered research and treatment by documenting the subjective experiences of individuals undergoing mistletoe therapy. In this qualitative, explorative study, 20 outpatients with a history of various cancer types were recruited from Arlesheim Hospital (Arlesheim, Switzerland). All patients received subcutaneous mistletoe therapy for at least 2 years (median 7.5 years). Data was collected through 2 semi-structured, in-depth interviews per patient. Qualitative content analysis was applied to examine the data. The individual experience of mistletoe therapy was analyzed in relation to 6 predefined levels of human experience: physical, vital, emotional, mental, spiritual and social. In addition, 3 further aspects, considered as cross-dimensional perspectives, emerged out of the material: warmth, immune strengthening, and general wellbeing. Data analysis revealed considerable heterogeneity among patients' experiences with mistletoe therapy. The importance of specific aspects became apparent, such as increased vitality to manage daily life, greater emotional and mental stability, warmth as a multidimensional phenomenon, feelings of safety and protection through mistletoe therapy, heightened self-awareness and improved self-care, as well as sensations of spiritual connectedness. Prior to this study it had not been shown that cancer patients using mistletoe therapy do have observations on different levels of experience. These results may lead to a deeper understanding of patients receiving mistletoe therapy, enabling them to be supported in a more holistic way both during mistletoe treatment and on their life path. Further investigations into the effects of mistletoe therapy on the emotional, mental, and spiritual level are warranted.

Systematic analysis of mistletoe prescriptions in clinical studies

PurposeMistletoe treatment is discussed controversial as a complementary treatment for cancer patients. Aim of this systematic analysis is to assess the concept of mistletoe treatment in the clinical studies with respect to indication, type of mistletoe preparation, treatment schedule, aim of treatment, and assessment of treatment results.MethodsIn the period from August to December 2020, the following databases were systematically searched: Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL, and “Science Citation Index Expanded” (Web of Science). We assessed all studies for study types, methods, endpoints and mistletoe preparations including their ways of application, host trees and dosage schedules.ResultsThe search concerning mistletoe therapy revealed 3296 hits. Of these, 102 publications and at total of 19.441 patients were included. We included several study types investigating the application of mistletoe in different groups of participants (cancer patients of any type of cancer were included as well as studies conducted with healthy volunteers and pediatric patients). The most common types of cancer were breast cancer, pancreatic cancer, colorectal cancer and malignant melanoma. Randomized controlled studies, cohort studies and case reports make up most of the included studies. A huge variety was observed concerning type and composition of mistletoe extracts (differing pharmaceutical companies and host trees), ways of applications and dosage schedules. Administration varied e. g. between using mistletoe extract as sole treatment and as concomitant therapy to cancer treatment. As the analysis of all studies shows, there is no relationship between mistletoe preparation used, host tree and dosage, and cancer type.ConclusionsOur research was not able to deviate transparent rules or guidelines with respect to mistletoe treatment in cancer care.

Additional treatment with mistletoe extracts for patients with breast cancer compared to conventional cancer therapy alone - efficacy and safety, costs and cost-effectiveness, patients and social aspects, and ethical assessment.

Background: Chemotherapy is often used in the treatment of breast cancer in women. Side effects such as diarrhea, fatigue, hair loss, fever or disturbances in blood formation impair the women’s quality of life. An essential treatment goal of the accompanying mistletoe therapy (MT) used in complementary medicine is to improve the health-related quality of life during cancer therapy.Aim and methods: The HTA report on which this article is based examines the medical efficacy and safety, costs and cost-effectiveness, patient and social aspects, and ethical aspects of MT in women with breast cancer. Systematic reviews were conducted for this purpose. The search period of the literature search ranged from 2004 to October 2020.Results: A total of 2 evidence-based medical guidelines, 3 randomized trials assessing efficacy and 1 additional non-randomized intervention trial, as well as 3 observational studies assessing safety, a cost analysis, 12 cross-sectional studies on patient aspects and 17 articles on ethical evaluation were included. Improvements in health-related quality of life compared to the control group were small to moderate. Due to the high risk of bias in the studies, it is possible that the difference is not caused by MT. One study with a small sample size showed no effect on progression-free survival after 5 years. Studies on the effect of MT on overall survival are lacking. In seven studies, local skin reactions of low and moderate severity were reported in a median of 25% (range 5 to 94%) of patients, and mild to moderate systemic reactions in a median of 2% (range 0 to 8%) of patients. A comparative cost analysis from Germany reported significantly lower medical costs within 5 years after surgery for patients with MT than for patients without MT, but the underlying observational study did not control for systematic bias. With regard to patient aspects, the frequency of use and the reasons for use from the patient’s or practitioner’s point of view were mainly investigated. A median of 25% (range 7 to 46%) of patients with breast cancer and 29% (range 29 to 79%) of treatment providers use MT. The main motivations of patients for use were to reduce side effects, strengthen the immune system and take an active role in the treatment process. Patients felt insufficiently advised. Studies on other aspects are lacking. The ethical evaluation was able to identify 6 overarching themes; the central challenge is the insufficient evidence on efficacy and safety.

A pilot study of the mistletoe and breast cancer (MAB) trial: a protocol for a randomised double-blind controlled trial

BackgroundA Cochrane review of mistletoe therapy concludes that there is some evidence that mistletoe extracts may offer benefits on measures of quality of life during chemotherapy for breast cancer, but these results need replication. Our aim is to add to this evidence base by initially testing the feasibility of a UK pilot placebo-controlled, double-blind randomised controlled trial of mistletoe therapy in patients with breast cancer undergoing chemotherapy with or without radiotherapy.Methods/designA mixed phase pilot placebo-controlled, double-blind randomised controlled trial of mistletoe therapy in patients with breast cancer (EudraCT number: 2018-000279-34). There will be three arms (groups) in the trial: Iscador M, Iscador P, with physiological saline as the placebo. The aim is to recruit 45 adult patients with a new diagnosis of early or locally advanced breast cancer, up to 12 weeks following definitive breast surgery whose standard treatment plan includes chemotherapy with or without radiotherapy. They will be taught to administer the mistletoe and breast cancer (MAB) therapies subcutaneously. MAB therapy will continue throughout their standard chemotherapy and radiotherapy and 1 month beyond. The main outcome of the MAB study is the feasibility of conducting such a trial within the NHS in order to inform a future fully powered investigative trial. Feasibility will be measured through recruitment, retention and patient experience using clinical research forms, patient diaries, cancer-related questionnaires and qualitative interviews conducted with both patients and oncology staff.DiscussionThis trial is the first of its kind in the UK. Currently, mistletoe therapy is mostly available through private practice in the UK. Completion of this feasibility study will support applications for further funding for a fully powered randomised controlled trial which will measure effectiveness and cost-effectiveness of this herbal therapy.

Profiling mistletoe therapy research and identifying evidence gaps: A systematic review of conditions treated, mode of application and outcomes

Mistletoe has been used as a medicine since prehistoric times. Modern Western herbal practice continues to use mistletoe. This systematic review aimed to profile mistletoe therapy in research studies and to understand the gaps in the evidence to inform future research. We used standard systematic review methodology, searching three databases (Medline, Central and Anthromed) from inception to June 2020. The search identified 31 relevant trials, and 10 systematic reviews published between 1996 -2020. These trials comprised 14 randomised controlled trials, 15 controlled trials and 2 cohort studies. The most common country for monocentric trials was Germany. Most of the trials declared direct or indirect financial support from companies that produce mistletoe products. All the included trials involved cancer patients, with breast cancer being the most common condition treated (n = 10). Subcutaneous injections were the most common route of administration (27/31). Quality of life was the most reported outcome. Quality appraisal of the individual trials shows that there was a lack of reporting on blinding of participants and blinding of assessors. A third of the trials did not adequately describe how they dealt with incomplete data. Recent published systematic reviews do not concur on the efficacy of mistletoe and patients’ quality of life; with the risk of bias of these publications being rated as ‘unclear’ overall. There were insufficient data to conduct a novel meta-analysis on mistletoe therapy efficacy. This systematic review identified gaps in mistletoe research for improving the evidence base for mistletoe therapy in supportive cancer care.

Thermoresponsive Hydrogel Containing Viscum album Extract for Topic and Transdermal Use: Development, Stability and Cytotoxicity Activity

Viscum album L. (Santalaceae), also known as European mistletoe, is a semi-parasitic plant that grows on different host trees. Our group recently demonstrated the antitumoral activity of ethanolic V. album extracts in vitro, depending on the dose and the host tree, V. album ssp abietis from Abies alba being the most active extract. The goal of this work focused on the development of a new topical formulation containing V. album extracts, evaluation of in vitro toxicity and ex vivo skin permeation assays. The Poloxamer 407 hydrogel containing 5% of dry (VA_DEH) or aqueous (VA_AEH) extract presented dermal compatible pH and microbiological stability for 180 days. The hydrogels flow curve presented a non-linear relation, characteristic of non-Newtonian fluids, and the mean viscosity for the VA_DEH and VA_AEH was 372.5 ± 7.78 and 331.0 ± 2.83 Pa.s, respectively, being statistically different (Welch’s t test; p < 0.01). Additionally, WST-1 in vitro assays revealed a dose-dependent toxicity for both formulations and VA_DEH presented a higher activity than the VA_AEH. The promising cytotoxic potential of VA_DEH lead to the ex vivo skin permeation assay with 2.73 ± 0.19 µg/cm2 of chlorogenic acid, which permeated at 8 h, showing a transdermal potential. These in vitro results support the idea that VA_DEH is a novel promising candidate for mistletoe therapy. Therefore, further in vivo and pre-clinical experiments should be performed to evaluate the safety and efficacy of this new dermic delivery system.

The introspective patient perception on mistletoe therapy and cancer: A qualitative study

The introspective patient perception on mistletoe therapy and cancer: A qualitative study

Profiling mistletoe therapy research: a systematic review of conditions treated, mode of application

Profiling mistletoe therapy research: a systematic review of conditions treated, mode of application

Complementary medicine in uro-oncology

Complementary and alternative medicine (CAM) is widespread in oncology patients with auser rate of approximately 40-50%. An accompanying supportive effect can arise through improved adherence, especially in long-term (e.g.endocrine) therapies through active patient involvement. When assessing the evidence on frequently requested methods, there is no high-quality evidence that homeopathy or anthroposophy leads to an improved prognosis. Mistletoe therapy can be considered to improve the quality of life, although the data quality is weak. In prostate cancer, pomegranate has an influence on the prostate-specific antigen. It is currently unclear whether this will also result in an improved prognosis. In contrast the evidence on selenium and vitaminD speaks in favor of integration into the aftercare concept. Supplementation is recommended after the serum level has been determined.

Integrative Oncology for Women with Breast Cancer

Integrative Oncology for Women with Breast Cancer Abstract. Integrative oncology is a patient-centered, evidence-informed field of cancer care, used worldwide to complement standard cancer care and is actively sought by patients. It is also well established in Switzerland. A wide range of procedures are used, such as mind body medicine, art therapies, exercise, nutrition, herbal medicines, nursing measures and specific complementary medical procedures. They support patients to regain health, improve their quality of life and enable them to take an active role in their health care management. An evidence-based guideline for integrative breast cancer treatment has been published by the Society of Integrative Oncology and implemented by the American Society of Clinical Oncology. Mistletoe therapy is a widely used herbal remedy to support cancer treatment and to improve quality of life. Its mode of action, safety and efficacy are being intensively investigated. The central focus of integrative oncology is a trusting and appreciative consultation on eye-level, so that a patient-centered and safe treatment concept can be designed.

Präklinische Untersuchungen von Wechselwirkungen zwischen Mistel und Radio- oder Chemotherapie auf pädiatrische Tumorzellen

Hintergrund: Mistelanwendungen werden als komplementäre Therapien häufig in der pädiatrischen Onkologie zusammen mit einer Radio- oder Chemotherapie verabreicht. Wechselwirkungen bei simultaner Applikation sind gerade in der Pädiatrie von großer Bedeutung, sie sind allerdings nach wie vor unzureichend untersucht. Material und Methoden: Zytotoxische Effekte des Mistelextraktes abnobaVISCUM Fraxini (aVF) auf LAN-1 Neuroblastomzellen und deren Etoposid- bzw. Cisplatin-resistente Subzelllinien wurden mittels Viabilitätstest untersucht, sowie mögliche Synergieeffekte zwischen aVF und den Chemotherapeutika durch die Softwareprodukte Combenefit und CompuSyn analysiert. Effekte einer Kombinationstherapie aus aVF und Bestrahlung auf SH-SY5Y Zellen wurden mittels Koloniebildungstest untersucht und Auswirkungen auf die Reparatureffizienz strahleninduzierter Doppelstrangbrüche mit Hilfe durchflusszytometrischer Quantifizierungen von γ-H2AX-Foci nach PI/FITC Doppelfärbung analysiert. Ergebnisse: Die Chemotherapie-resistenten LAN-1 Subzelllinien erwiesen sich als resistenter gegenüber der Mistelbehandlung als die Ursprungszelllinie. Auf Basis vier verschiedener Referenz­modelle konnten vor allem synergistisch/additive Effekte zwischen aVF und den Zytostatika Etoposid und Cisplatin berechnet werden. Die Kombination aus Mistelbehandlung und Bestrahlung führte zu einer Verringerung der Koloniebildung und zu einer Verzögerung der Reparaturgeschwindigkeit von strahleninduzierten Doppelstrangbrüchen. Schlussfolgerung: Die präklinischen Daten könnten darauf hinweisen, dass die Verwendung des Mistelextraktes, aVF, eine unterstützende Wirkung auf Radio- und Chemotherapien hat.

Gynecologists\u2019 attitudes toward and use of complementary and integrative medicine approaches: results of a national survey in Germany

PurposeDespite patients’ widespread use and acceptance of complementary and integrative medicine (IM), few data are available regarding health-care professionals’ current implementation of it in clinical routine. A national survey was conducted to assess gynecologists’ attitudes to and implementation of complementary and integrative treatment approaches.MethodsThe Working Group on Integrative Medicine of the German Society of Gynecological Oncology conducted an online survey in collaboration with the German Society of Gynecology and Obstetrics (DGGG) in July 2019. A 29-item survey was sent to all DGGG members by email.ResultsQuestionnaires from 180 gynecologists were analyzed, of whom 61 were working office-based in private practice and 95 were employed in hospitals. Seventy percent stated that IM concepts are implemented in their routine clinical work. Most physicians reported using IM methods in gynecological oncology. The main indications for IM therapies were fatigue (n = 98), nausea and vomiting (n = 89), climacteric symptoms (n = 87), and sleep disturbances (n = 86). The most commonly recommended methods were exercise therapy (n = 86), mistletoe therapy (n = 78), and phytotherapy (n = 74). Gynecologists offering IM were more often female (P = 0.001), more often had qualifications in anthroposophic medicine (P = 0.005) or naturopathy (P = 0.019), and were more often based in large cities (P = 0.016).ConclusionsThere is strong interest in IM among gynecologists. The availability of evidence-based training in IM is increasing. Integrative therapy approaches are being implemented in clinical routine more and more, and integrative counseling services are present all over Germany. Efforts should focus on extending evidence-based knowledge of IM in both gynecology and gynecological oncology.

Anticancer Effects of Viscum album Fraxini Extract on Medulloblastoma Cells in vitro

Background: Mistletoe therapy is frequently administered as a supportive treatment in diverse pediatric cancer entities including brain tumors. Medulloblastoma is the most common brain tumor in childhood. Its high risk to metastasize and its long-term sequelae caused by aggressive chemo- or radiotherapies are still challenging. Material and Methods: Effects of a lectin-rich mistletoe extract, abnobaVISCUM Fraxini, were investigated in two medulloblastoma cell lines (Daoy and ONS-76). Responsiveness of tumor cells was assessed by cell viability assays and xCELLigence real-time analyses. Moreover, impacts on proliferation, cell cycle and apoptosis were investigated. Apoptosis was studied by staining of vital mitochondria and assessing the involvement of caspases. In addition, effects on migration and invasion were analyzed. Results: Both medulloblastoma cell lines were more susceptible to treatment with the mistletoe extract than a nontumorigenic fibroblast cell line. In mistletoe-sensitive Daoy cells, reduction of proliferation and induction of caspase-mediated apoptosis were observed upon administration of 0.05 and 0.5 mg/mL abnobaVISCUM Fraxini treatment, respectively. Furthermore, mistletoe extract inhibited migration and invasion properties in Daoy and significantly impaired invasive capabilities of ONS-76 cells. Conclusion: AbnobaVISCUM Fraxini has cell line dependent antitumoral effects in medulloblastoma models. These results call for further investigations, to reveal mechanistic insights into antitumorigenic properties of mistletoe extracts.

Phytochemical analysis and in vitro anti-proliferative activity of Viscum album ethanolic extracts

BackgroundViscum album L. (Santalaceae), commonly known as mistletoe, is a hemiparasitic plant traditionally used in complementary cancer treatment. Its antitumor potential is mostly attributed to the presence of aqueous soluble metabolites; however, the use of ethanol as solvent also permits the extraction of pharmacological compounds with antitumor potential. The clinical efficacy of mistletoe therapy inspired the present work, which focuses on ethanolic extracts (V. album “mother tinctures”, MT) prepared from different host trees.MethodsSamples from three European subspecies (album, austriacum, and abietis) were harvested, and five different V. album-MT strains were prepared. The following phytochemical analyses were performed: thin layer chromatography (TLC), high-performance liquid chromatography (HPLC) and liquid chromatography-high resolution mass spectrometry (LC-HRMS). The proliferation assay was performed with WST-1 after incubation of tumor (Yoshida and Molt-4) and fibroblast cell lines (NIH/3 T3) with different MT concentrations (0.5 to 0.05% v/v). The cell death mechanism was investigated by flow cytometry (FACS) using Annexin V-7AAD.ResultsChemical analyses of MT showed the presence of phenolic acids, flavonoids and lignans. The MT flavonoid and viscotoxin contents (mg/g fresh weight) were highest in Quercus robur (9.67 ± 0.85 mg/g) and Malus domestica (3.95 ± 0.58 mg/mg), respectively. The viscotoxin isoform proportions (% total) were also different among the VA subspecies with a higher content of A3 in V. album growing on Abies alba (60.57 ± 2.13). The phytochemical compounds as well as the viscotoxin contents are probably related to the antitumor effects of MT. The cell death mechanisms evaluated by colorimetric and FACS methodologies involved necrotic damage, which was host tree-, time- and dose- dependent, with different selectivity to tumor cells. Mother tincture from V. album ssp. abietis was the most effective at inducing in vitro cellular effects, even when incubated at the smallest concentration tested, probably because of the higher content of VT A3.ConclusionOur results indicate the promising antitumor potential of Viscum album ethanolic extracts and the importance of botanical and phytochemical characterization for in vitro anti-proliferative effects.

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.

Preclinical Evaluation of Antitumoral and Cytotoxic Properties of Viscum album Fraxini Extract on Pediatric Tumor Cells.

In Europe, especially in German-speaking countries, administration of mistletoe extracts is the most common and popular complementary and alternative therapy approach reported in oncology. Mistletoe therapy is applied to children with cancer for curative and palliative therapeutic regimes with increasing frequency, but at the same time, there are only a few studies on the effectiveness of this therapy. Therefore, we have investigated the response of various pediatric cell lines (acute myeloid leukemia, Ewing's sarcoma, hepatocellular carcinoma, medulloblastoma, neuroblastoma, and osteosarcoma) to mistletoe extract, abnobaVISCUM Fraxini. Effects on cell proliferation, cell cycle distribution as well as on mitochondrial integrity and caspase-mediated apoptosis were investigated in neuroblastoma cell lines, SH-SY5Y and Kelly. Additionally, in vitro tumor cell migration and invasion were studied. In vivo effects of the mistletoe extract were investigated in a syngeneic neuroblastoma mouse model. We could show that tumor cell lines were from 5- to 640-fold more sensitive to abnobaVISCUM Fraxini treatment than non-tumorigenic fibroblasts, whereby neuroblastoma cell lines were the most sensitive. For two neuroblastoma cell lines, SH-SY5Y and Kelly, induction of caspase-9-mediated apoptosis, a decrease of mitochondrial integrity as well as attenuation of migration and invasion were observed. In vivo experiments revealed a reduction of tumor growth and a prolonged survival of tumor-bearing animals. In summary, we can state that these results provide the first preclinical data for cytotoxic activities of abnobaVISCUM Fraxini for a broad panel of pediatric tumor cell lines, in particular, neuroblastoma cells. Thus, it might be a potential remedy for the supportive treatment of neuroblastoma.