Health-related quality of life (HRQL) refers to various aspects of "the patients' experience or suffering, their ability to participate actively or with limitations in everyday, social and professional life and to manage difficulties independently" . Mistletoe therapy is often the method of choice for improving quality of life. This can be seen in many studies published on the subject [24, 25].
A systematic review showed that 22 of 26 randomised controlled trials (RCTs) showed an advantage for mistletoe therapy with respect to HRQL . A Health Technology Assessment Report concluded that mistletoe therapy administered in addition to chemotherapy has a positive effect on the HRQL of breast cancer patients . A systematic Cochrane review and a recent systematic review come to the same conclusion [6,279].
The current recommendation (grade C) of the SIO (Society for Integrative Oncology) guideline from 2017  considers the use of subcutaneous mistletoe therapy for quality of life improvement in breast cancer patients. These have been recognised by the American Cancer Society (ASCO) in 2018 . This means that since then, an international evaluation of mistletoe therapy has been available from the largest American oncological society.
Some studies on mistletoe therapy have investigated its impact on self-regulation, i.e. the patients' own activity which enables them to achieve their inner balance and a feeling of competence and safety in stressful situations [73, 74]. Self-regulation has been shown to increase significantly under add-on mistletoe therapy [6, 75, 76, 77]. Furthermore, there is evidence that good self-regulation in turn improves the response to mistletoe therapy  and can lead to a survival advantage . In a prospective study involving 25 cancer patients, it was shown that after three months of mistletoe therapy there was an improvement of acceptance and adaption to the situation, a stabilization of vitality, an improvement of autonomy as well as social, professional and personal performance .
The therapy- or disease-related fatigue syndrome (state of exhaustion) has a major impact on cancer patients. Additional mistletoe therapy frequently improves fatigue syndrome to a relevant extent [44, 47, 79, 80, 81,284].
One review stated that mistletoe therapy significantly improved fatigue/fatigue-associated symptoms in 60 percent of the studies analysed. In 67 percent of the studies this also applied to symptoms of insomnia .
As part of a validation study, the Cancer Fatigue Scale (CFS-D, 15 questions) was used to verify a sensitive and validated questionnaire . It is suitable for the assessment of cancer-related fatigue (CRF) in cancer patients treated with mistletoe therapy. A reduction of global and cognitive CRF-related deficits could be observed in breast cancer patients treated continuously with mistletoe therapy compared to patients who received mistletoe therapy only after the third chemotherapy cycle. This indicates the importance of additive mistletoe therapy given simultaneously with chemotherapy .
Furthermore, improvement of reduced internal coherence (resilience) in patients with breast and colorectal cancer undergoing chemotherapy can be achieved with additional continuous mistletoe therapy, being effective by the beginning of the third chemotherapy cycle [85, 86].
Add-on mistletoe therapy can improve symptoms such as nausea and vomiting [27, 31, 44, 47], pain [31, 44, 47, 53, 79, 80, 81], loss of appetite [44, 47, 53, 79, 80, 81], diarrhoea or constipation [44, 47, 87], and stabilize emotional well-being [44, 47, 79], role [44, 47, 53], social [44, 47] and cognitive performances .
In the context of a qualitative study, experienced doctors also reported an improvement in patient’s vitality and well-being , nutritional status and body weight, digestion and temperature regulation (feeling of warmth) [79, 80]. Some of the studies on HRQL are described in more detail below.
A RCT of 224 patients with breast (n=68), ovarian (n=71) and non-small-cell lung cancer treated with the mistletoe extract Helixor A showed significant improvements in quality of life (Functional Living Index-Cancer questionnaire), particularly for nausea and pain, compared to patients who had been administered lentinan (an immomodulating glucan from the shiitake mushroom) .
In a randomised study, the HRQL of 123 patients with breast cancer (stage I-IIIA) receiving chemotherapy alone or in combination with Iscador M or Helixor A was investigated. It was shown that in the combination arm 8-9 of 15 scores of the EORTC-QLQ-C30 questionnaire were improved significantly and to a clinically relevant extent, including pain, nausea and vomiting as well as insomnia – factors resembling important challenges during chemotherapy [44, 47]. In addition, role, emotional and social function, appetite and diarrhoea improved in the combination arm.
A prospective longitudinal study demonstrated that mistletoe therapy with abnobaVISCUM Mali in addition to adjuvant chemotherapy significantly stabilises the HRQL of breast cancer patients and improves the tolerability of chemotherapy by reducing its side effects .
In a Phase III RCT study, the quality of life of 220 patients with locally advanced or metastasized pancreatic cancer receiving best supportive care (BSC) or BSC plus mistletoe was investigated. In the combination group, 13 of 15 EORTC-QLQ-C30 scores improved significantly, including global quality of life, appetite, fatigue syndrome, insomnia, pain and nausea .
Patients with pancreatic carcinoma (n = 396) receiving additional mistletoe therapy with Iscador as part of their supportive therapy experienced fewer side effects caused by conventional therapy (mostly with gemcitabine) and fewer cancer-related symptoms than patients without mistletoe therapy .
In a randomised study, a significantly improved quality of life including less diarrhoea was observed in stage IB/II gastric cancer patients who received the mistletoe preparation abnobaVISCUM Quercus in addition to oral chemotherapy with doxifluridine . Furthermore, the safety of add-on mistletoe therapy was confirmed in this study.
It was also demonstrated that symptom burden in patients with non-metastatic colorectal cancer treated with the mistletoe preparation Iscador in addition to conventional therapy or during passive aftercare were significantly reduced compared to patients without mistletoe therapy . Moreover, a survival advantage of the mistletoe group was described in this multicentre controlled observational study with 804 patients from 26 study centres.
Last update: December 15th, 2020/AT1