Cancer Patients' Experiences of Using Mistletoe ( Viscum album ): A Qualitative Systematic Review and Synthesis

Abstract

Objective:

Systematic reviews of mistletoe therapy (MT) trials in cancer show promising results in improvement of patients' quality of life during chemotherapy and reduction of fatigue. However, patients' experiences of side effects and the acceptability, tolerability, and perceived benefits of MT have not been systematically reviewed. The aim of this study was to systematically review and synthesise the results of qualitative studies of cancer patients' experiences of using MT.

Design:

A systematic search was conducted in MEDLINE, Embase, PsychLIT, CINAHL, and AMED to identify qualitative studies of MT. Articles were screened independently by two reviewers and critically appraised using the Critical Appraisal Skills Programme tool. A thematic synthesis of the findings was carried out.

Results:

One hundred and seventy-three papers were identified; 156 were excluded at initial screening. Seventeen papers were read in full, 14 of which were excluded. Three articles about patients' experiences of MT alongside conventional treatment were included in the synthesis, either as a monotherapy (two articles) or as part of a package of anthroposophic treatment (one article). Patients reported demonstrable changes to their physical, emotional, and psychosocial well-being following MT, as well as a reduction in chemotherapy side effects. Self-reported side effects from MT were few, and the studies suggest good adherence to the therapy. Self-injection gave patients a sense of empowerment through involvement in their own treatment.

Conclusions:

A systematic search revealed a small number of qualitative studies of MT in cancer. These were effectively combined to provide a detailed overview of patients' experiences in order to complement the developing evidence base from trials. Given the variation in context of MT delivery across the articles, it is not possible to ascribe changes in patients' quality of life specifically to MT. The results of this review will help in the design of outcome measures that more fully capture patients' experiences. It is essential to embed qualitative research of patients' experiences of MT and other CAM therapies within future trials.

Introduction

Mistletoe has long been used in the treatment of a variety of acute and chronic conditions and has been used in the treatment of cancer since the 1920s.¹ It is given to patients as the central component of a complex, broader treatment regimen in the practice of anthroposophic medicine,² mainly in Europe, or as a single herbal treatment agent outside the context of anthroposophic care. In the treatment of malignancies, it is most often used in conjunction with conventional treatments: surgery, radiotherapy, and chemotherapy. It is given before, with, and after these treatments to reduce adverse reactions and improve quality of life (QoL).

A Cochrane review of mistletoe in oncology included 21 randomized controlled trials.³ The recommendations of this review included replication of “two trials suggesting beneficial effects of mistletoe extracts on QoL of breast cancer patients during chemotherapy.”³ A further systematic review of mistletoe therapy (MT) for cancer treatment that focused on QoL outcomes included 26 randomized controlled trials (RCTs) and 10 controlled trials.⁴ The authors reported that 22 RCTs showed improvement in QoL measures, 3 showed no differences, and one did not report. In 2012, a systematic review focused on the mistletoe preparation Iscador^® (Weleda, Arlesheim, Switzerland).⁵ A random-effects meta-analysis of 13 controlled studies (9 of which were RCTs) estimated an overall short-term treatment standardized mean effect of 0.56 (95% confidence interval, 0.41–0.71; p < 0.0001) but emphasised that the methodologic quality of studies was poor. Some evidence suggests that mistletoe might be particularly valuable in combating cancer fatigue, a debilitating side effect of cancer, and its treatment, for which there are limited therapeutic strategies at present.⁶

A recent survey carried out in 11 European countries, including the United Kingdom, showed that 46% of women with breast cancer had used herbal medicine since diagnosis.⁷ In the United Kingdom, overall complementary and alternative medicine (CAM) use by patients with breast cancer was 38%, but the proportion using herbal medicine is unknown. A recent qualitative meta-ethnography of patients' experiences of using CAM after a diagnosis of cancer showed that improving well-being and QoL, dealing with symptoms, and finding relief from the side effects of treatment were important motivating factors toward CAM use.⁸

In light of the increasing interest by patients and health professionals in using CAM in supportive cancer care and the evidence from mistletoe trials, it is important to further explore patients' experience of MT. One limitation of previous studies is the reliance on validated QoL scales as outcome even though the consensus regarding the definition of QoL for cancer is by no means established.⁶ This highlights the need for qualitative studies to gauge the significance of the mistletoe treatment from the patient's point of view in terms of its benefit, acceptability, and tolerability. Therefore, this systematic review of qualitative studies aimed to articulate the experiences of patients with cancer when using mistletoe. The review was guided by the research question “What are cancer patients' views on and experiences of the use of MT?”

Materials and Methods

The review had four stages: (1) scoping the topic, (2) systematic literature search, (3) critical appraisal, and (4) synthesis of findings.

Scoping the topic

The SPIDER tool was used to scope the topic.⁹ This tool comprises five items: Sample, Phenomenon of Interest, Design, Evaluation, Research type. By using this tool, the inclusion and exclusion criteria were determined and in turn the search strategy written.

The inclusion criteria were as follows: (1) studies of adults with cancer regarding the use of anthroposophic mistletoe preparations by any administration route as monotherapy or as part of a complex intervention; (2) studies of qualitative design, such as focus groups, interviews, and questionnaires with free-text sections that describe views, experiences, or opinions of patients with cancer and health professionals; and (3) studies in all languages.

The exclusion criteria were the following: (1) studies of pediatric patients with cancer, (2) studies of anthroposophic therapies that did not involve mistletoe, and (3) studies that included questionnaires concerning QoL that yielded quantitative data only.

Systematic literature search

The parent search strategy was devised and run in MEDLINE and MEDLINE in Process (Appendix 1). Modified search strategies based on this parent search were run in Embase, PsychLIT, CINAHL, and AMED from database inception until November 21, 2012. The search was updated to April 17, 2015, and no new articles that met the inclusion criteria were found. The reference lists of papers that reached the full paper stage were screened for any extra studies. Authors that had at least three mistletoe publications in the search results were contacted in order to identify any publications that might have been missed and to provide information on any current studies. Proceedings from mistletoe conferences were screened for extra studies at www.mistelsymposium.de. The website anthromed.org was also screened. This site includes past issues of the Journal of Anthroposophical Medicine from 1982 to 1999.

References from the searches were screened independently by two of the authors and then collated. Any disagreements or queries were resolved by a third author. The references were first screened by title and abstract, and then those of interest were obtained as full papers. The second screening was conducted by reading the full text.

Critical appraisal

Papers that met the inclusion criteria were assessed for quality by using the Critical Appraisal Skills Programme screening tool.¹⁰

Synthesis of findings

Synthesis of qualitative studies involves a rigorous process of data extraction to identify the key concepts from each article.¹¹ There are many methods for synthesizing qualitative research.^12,13 Thematic synthesis was used here to combine the studies.¹⁴ Thematic synthesis has three stages: the coding of text line by line, the development of descriptive themes, and the generation of analytic themes. Descriptive themes are drawn directly from the primary studies, and analytic themes represent a stage of interpretation whereby the reviewers “go beyond” the primary studies and generate new interpretive constructs. Two authors (M.E. and S.B.) independently extracted data from the included papers using line-by-line coding to initially identify descriptive themes. These were drawn from verbatim quotations from participants describing their views, accounts and interpretations of their experiences of using MT and from themes identified by the authors of the articles, giving their views and interpretations of that data.

These data extraction sheets were compared between the two reviewers and consensus was reached. The descriptive themes were listed in an Excel spreadsheet (Microsoft Corp., Redmond, WA) and then synthesized to develop analytic themes. These comprise the authors' interpretations of concepts occurring across the articles. Table 1 lists the analytic themes and shows which descriptive themes in each of the articles contributed to them.

Table 1.

Development of Analytic Themes

Analytic theme	Description	Article
Treating the inner and outer worlds	Patients described inner healing and increased self-awareness during MT, which was enhanced by positive interactions with health professionals
	Homecoming	A
	Mirroring/being “seen”' by caregiver	A
	Intense personal contact with health professionals	B
	Absence of technology	A
	Return to mother's cradle	A
	Memories of childhood tastes	K
	Mistletoe is “sincere”	K
	Comforting environment	A, K
	Holistic care	A
	Renewed hope and renewed opportunities	A
	New priorities	A, B
	Let the mask fall and be sick	A
	Changing relationship with disease	B
	Acceptance of the disease	B
	Disease as a teacher	B
	More positive attitude	B
	Process past events	B
	Improved self-awareness	B, K
	Inner and outer atmospheres	A
	Stronger vitality	B
	Mistletoe as a “saviour”	K
	Restitution narrative	K
Moving from darkness into light	Patients graphically described their change in mood from dark to light following therapy, which is mirrored by imagery relating to the sun
	Light at the end of the tunnel	A
	Duty and survival to lightness	A
	MT associated with the sun	K
	Increased cheerfulness and joie de vivre	A, K
	Golden mistletoe	K
	Moving out of a “dreadful hole”	K
Taking control and increasing personal autonomy	MT injecting is seen to have ritual significance and the MT itself is redolent of healing energy
	Self-injection as a reminder of the disease	B
	Self-injection as a small ritual	K
	More autonomy, less affected by others	B
	Free from conventions	B
	Distinguishing important and less important things	B
	Changing conditions of subjective stress	B
	Getting personal needs met	B
	Drawing together family members	B
	Dealing with the disease better	A, B
	Active participation in multimodal treatment	B
Tangible outcomes	External, potentially measurable, changes reported after MT
	Tools for living a healthy lifestyle	A
	New personal achievements	B
	Increased motivation to deal with disease	B
	Increased emotional stability	B
	Reduction in pain	B
	Less depression	B
	Reduction in frequency of colds	B
	Stronger vitality	B, K
	Converting ideas into actions	B
	Cutting wood	B
	Distinguishing important and less important things	B
	Booking travel	B
	Staring new projects	B
	Increase in personal achievements	B
	On my legs again	K
	Improve personal relationships	B
	Liberation in personal relationships	B
	Solving/limiting professional stress	B
	Bringing together family members	B
Ambivalence about MT	Despite patients' commitment to MT, uncertainty is expressed in relation to its uptake, effectiveness, and side effects
	Overcoming prejudice for another paradigm	A
	Doubt about outcomes on disease and QoL	A, B
	Doubts about reduction of side effects of radiotherapy	B
	Experience of side effects of MT	B
	Mistletoe looks like cancer in the tree	K
	Decrease in QoL	B
Bridging the gap between conventional and integrative care	The perceived gap between conventional and integrative care is problematized, with patients having to function as a “bridge”
	Contrasting environments of care	A
	Overcoming prejudice for another paradigm	A
	Patients as a “bridge”	A
	Patients want more integration	A
	Patients taking “burden” and “risk”	A

A, Arman et al.; B, Brandenberger et al.; K, Konitzer et al.; MT, mistletoe therapy; QoL, quality of life.

Results

Screening of articles

From the searches, 173 papers were identified and no additional papers were gained from contacting authors. One hundred and fifty-six were excluded at the title and abstract screening stage. The remaining 17 papers were read in full, and further screening took place. Three articles relating to patients' experiences of mistletoe were included in the review0^15
–17 (see Preferred Reporting Items for Systematic Reviews and Meta-Analyses diagram in Appendix 2). One of these, written in German, was translated into English.¹⁵

Critical appraisal

The quality assessment of the included articles is summarized in Table 2. One paper relied on content analysis of interviews, which can lack depth of interpretation.¹⁷ Data for another article was drawn from a closed group undergoing psychotherapy, which may not reflect the views of typical patients.¹⁵ No authors reflected on the role of researcher-patient relationship. However, despite these limitations, in line with other qualitative syntheses the current authors were reluctant to exclude a paper on the basis of reporting quality alone because it might still be relevant to the synthesis. Each paper was evaluated on the approach of Dixon-Woods et al.¹⁸ Of the three included articles, one could be classified as a “key paper” in terms of its relevance to the overall research question despite some quality limitations, and two were “satisfactory.” All three articles provided a rich resource of primary data for the purpose of synthesis.

Table 2.

Summary of the Critical Appraisal Skills Programme Quality Assessment of Included Papers

Article, year	Was there a clear statement of the research aims?	Is a qualitative methodology appropriate?	Was the research design appropriate to address the aims of the research?	Was the recruitment strategy appropriate to the aims of the research?	Were the data collected in a way that addressed the research issue?	Has the relationship between researcher and participants been adequately considered?	Have ethical issues been taken into consideration?	Was the data analysis sufficiently rigorous?	Is there a clear statement of findings?	Is the research valuable?	Key paper or satisfactory paper
Arman et al, 2008¹⁶	Y	Y	Y	Y	Y	N	Y	Y	Y	Y	SAT
Brandenberger et al, 2012¹⁷	Y	Y	Y	Y	Y	N	Y	N	Y	Y	KP
Konitzer et al, 2001¹⁵	Y	Y	Y	Y	Y	N	N	Y	Y	Y	SAT

Modified from Critical Appraisal Skills Programme (CASP) Public Health Resource Unit. Oxford, United Kingdom, 2006. Final column uses Dixon-Woods appraisal criteria.

Y, yes; N, no; SAT, satisfactory paper (may provide less conceptual relevance to the synthesis); KP, key paper (conceptually rich and could potentially make an important contribution to the synthesis).

Study descriptions

The three included articles varied in methods and content. Study characteristics are given in Table 3. In Konitzer and colleagues' study, MT was provided as a monotherapy in general practice, supported by regular group therapy sessions.¹⁵ In Arman and colleagues' study, MT was embedded in an individually prescribed package of anthroposophic care at a specialist clinic.¹⁶ This included “natural remedies (herbs, plant extracts, essential oils, potentized natural substance).” This study included a mixed sample of patients, some of whom were being treated for cancer and some for burn-out syndrome, but the data analysis did not distinguish between the two groups. In Brandenberger and colleagues' study, MT was given as an outpatient monotherapy at a private integrative hospital.¹⁷

Table 3.

Study Description

Study, Year (Location)	Aim	Setting	Theoretical approach	Methods	Sample, age, and sex	Type of cancer	Types of therapy
Arman et al, 2008 (Sweden)¹⁶	(1) To deepen understanding of what constitutes good care from a patient's perspective to alleviate patient suffering and identify clinical markers for this(2) To explore what in anthroposophic care is experienced as being beneficial or difficult	12–21 d spent as inpatient at anthroposophic clinic	Clinical application research, participatory and action research	Narrative interviews in patients' homes 2–4 wk after stay in the clinic	n = 16Cancer: n = 9Age range: 50– 72 yMen: n = 5Women: n = 4Burnout syndrome: n = 7Age range: 32–58 yMen: n = 4Women: n = 3	Locally limited: n = 3Recurrent: n = 6Time since diagnosis: 1–3 y	Individually prescribed package of anthroposophic care, 1 element of which consisted of herbs and plants extracts, including Iscador (mistletoe)Mode of delivery of MT not statedNo reference to where and when patient received conventional treatment
Brandenberger et al., 2012 (Switzerland)¹⁷	What are patients' expectations and experiences of MT and its effects on QoL	MT given to hospital outpatients at an integrative hospital	Mixed methods: exploratory, prospective, before/after cohort study using standard QoL questionnaires and interviews. Content and theory generating analysis.	Patient interviews at start of MT and 3 mo later in hospital or other location of patient's choice	n = 17 (12 sets of repeat interviews included in the analysis)Wider cohort study: n = 25Mean age: 62 ± 11.1 yMen: n = 14Women: n = 11	Wider cohort study:colorectal cancer: n = 7Prostate cancer: n = 4Breast cancer: n = 4Lung cancer: n = 3Pancreatic cancer: n = 3Melanoma: n = 1Renal cancer: n = 1Myeloma: n = 1Multifocal basalioma: n = 1Time since diagnosis:Ranged 1.5 months to >5 years	Subcutaneous injections of anthroposophic mistletoe preparations 2–3 times per week, often performed by patient:Iscador^® (Weleda, Arlesheim, Switzerland): n = 13Abnoba viscum: n = 11Isorel^® (Novipharm, Pörtschach, Austria): n = 1Conventional treatment :Chemotherapy before: n = 9(of whom n = 6 continued chemotherapy during MT)Radiotherapy before: n = 3(of which n = 2 during MT)Hormone therapy: n = 4Other CAM therapies: n = 2Psychotherapy: n = 1No reference to whether conventional treatment and MT received at the same hospital
Konitzer et al., 2001 (Germany)¹⁵	To explore whether the term “mistletoe” is associated with images of “cancer” or a “counteragent against cancer” for patients treated with it	MT given in general practice over 1.5 years 1–3 times per week	Grounded theory; linguistic data triangulated with pictures; data triangulated with external theories on metaphor based in the work of Steiner, Seligman, and Frazer	Patients attending a weekly psychotherapy group session during MT were asked to draw pictures of their MT and talk about their experiences	n = 12Mean age: 51.6 ± 3.65Sex not stated	Breast cancer: n = 9Uterine cancer: n = 2 Hypernephroma: n = 1Time since diagnosis not stated	Infusions of mistletoe extracts: IsorelNo reference to whether, where, or when patient received conventional treatment

Mode of delivery of MT varied: One study used infusions,¹⁵ one used subcutaneous injections,¹⁷ and one did not report methods of administration.¹⁶ In two studies, data were collected by individual interview.^16,17 In the third, patients were asked to draw pictures of MT and talk about their experiences during an ongoing group therapy session.¹⁵ All articles provided data on aspects of patients' experience with MT, reporting directly on perceived changes in well-being;^16,17 one article related this symbolically to the nature of the mistletoe plant from which the extract is derived.¹⁵

Overview

Patients receiving MT reported improvements in their physical, emotional, and psychosocial well-being and felt able to construct meaning from the experience of the disease and its treatment.

Six analytic themes were identified that encompassed all the relevant data in the articles and provided a synthesis across all three. Table 1 shows the concepts that emerged from each paper and contributed to the themes. It is not possible to distinguish the effects of MT from those of other aspects of the holistic package in the study by Arman et al.¹⁶ However, patients' verbatim quotations were chosen where possible with specific reference to their experience with MT. The themes were treating the inner and outer worlds, moving from darkness into light, taking control and increasing personal autonomy, tangible outcomes, ambivalence about MT, and bridging the gap between conventional and integrative care.

Verbatim quotations from the articles are used to illustrate the themes. Most quotations directly report the patients' words. Where the authors' words are quoted, this is marked “[authors].”

Treating the inner and outer worlds

The experience of receiving MT appears to be intimately connected to a sense of both the outer and inner worlds of the patient being nurtured and treated in a “holistic” way. MT was perceived as an agent that works with body, mind, and spirit. Treatment involved intense personal contact with health professionals in a relatively low-tech environment so that patients felt they were fully “seen” by their carers. Staff provided holistic care and attention, which were then mirrored by the patients; in turn, patients became more self-reflective, focusing on their inner needs as a precursor to growth and change.¹⁶ This stimulated memories of childhood, such as a return to “mother's cradle,” a place where fear was diminished.^15,16 Patients felt able to rest in a comfortable place, exemplified by one patient who physically lay down after each mistletoe injection.¹⁵

MT was perceived as a powerful positive force underpinning many of the outcomes described by patients, as captured in one article with phrases such as “mistletoe is a sincere agent,” “like a small saviour out of the vicious circle.”¹⁵ The qualities of mistletoe in the wild supported its use as a treatment, and patients perceived MT to be redolent of healing energy: “The corresponding energy could only now be set free, so that I can finally come to my truth, to what I am.”¹⁷

Patients described MT as providing a turning point in their experience of disease and increasing their self-awareness: “Patients were able to return to their own inner path, returning to their inner sources and discovery of basic values of their own lives” [authors].”¹⁶ Brandenberger et al. refer to “internal changes” [authors] that helped patients to develop a greater sense of hope and ability to cope:

Mistletoe therapy was adopted by the study patients mostly with a supportive aim and seemed to offer a platform for an integrative coping with the disease, which in itself is likely to have helped the cancer patients, inasmuch as it gave them hope and probably increased their motivation to deal with this devastating disease. During MT, the patients often perceived an improvement of QoL which was associated with a higher vitality and autonomy and translated into clear-cut personal achievements [authors].

The interviewer noted that patients were more talkative, self-reflective, and positive at second interview, after MT.

Life and vitality were seen as returning through a process that involved first of all patients allowing themselves to “be sick’[authors] ¹⁶ and letting the disease then become their ‘teacher … who shows me what is happening with me at each moment.” The perceived transformative power of MT is emphasized by comments like “I have experienced this myself” as a way of vouching for the credibility of the patient's story.¹⁵

Moving from darkness into light

The changing inner world of patients with cancer receiving MT was conceptualized as moving from “darkness” or a “dreadful hole” into “light.”^15,16 In both these papers, MT is conceptualized as bright, warm, light, “golden,” a provider of energy akin to the sun. The experience was enhanced by injection as the mode of delivery, with patients describing a sense of the healing energy of mistletoe flowing into their body. Patients reported a reduction in “dark thoughts” and fear, with a lightening in their mood state to an increased sense of “joie de vivre”¹⁵ or cheerfulness and an ability to see “light at the end of the tunnel.”¹⁶ This contrasted with a previous focus on “duty” and “survival.” The metaphor of “lightness” encompassed their attitude to life more generally, “not taking things as seriously as before.”¹⁷ For some it led to improved personal relationships, an experience described as “liberation.”¹⁷ There was an effect on patients” attitude to life more generally: “Yes this is a whole new phase for me, it' like I've become a brand new person afterwards, in a way.”¹⁶ MT helped patients to make changes in their lives, convert ideas into actions, and reassess their priorities, such as spending more time with their partner or setting limits to their professional life and reducing stress: “I now feel in terms of close relationships that I don't always have to be everywhere … I can set boundaries for myself … it's a relief.”¹⁷

Taking control and increasing personal autonomy

The ritual of self-injection provided a sense of personal empowerment through active participation in the treatment process and gave patients a sense of control, particularly when conventional treatment ended. The injections functioned as a regular reminder of the disease and helped patients to become more accepting of its presence, also bringing them closer to family members: “In some cases, MT seemed to bring together family members, who until then had had different opinions on therapeutic choices or on disease perception, thereby fulfilling psychosocial functions … it is likely that MT might have played a role in improving quality of life … a chance to consider personal preferences, concepts and settings to integrate the help of their loved ones”[authors].¹⁷

After MT, patients reported feeling less vulnerable and more assertive about getting their personal needs met, such as ensuring that their own daily rhythms and coping mechanisms were respected by health professionals and employers. Patients felt less constrained by conventional ways of behaving and were able to establish personal priorities and boundaries more clearly, leading to “more genuine ways of living” [authors].¹⁶ This improved sense of personal autonomy enabled patients to start new projects in their lives and reduce their experience of subjective stress.

Tangible outcomes

After MT, patients in all three articles reported tangible, potentially measurable changes in their physical and psychological well-being and a reduction in side effects of cancer and its treatment: “The hair loss stopped! The side effects of the chemotherapy were less. I felt (feel) good!”¹⁵ Some patients reported almost no side effects when undergoing chemotherapy and MT simultaneously and “reported doing better after 3 months” of MT.[authors]¹⁷

Patients reported emerging from therapy with a “stronger vitality,” “new” view of life, with new priorities and “tools for living a healthy life,” such as a good diet, the importance of rest, and therapeutic exercises.¹⁶ MT was seen as a “health supporter” leading to pain reduction, and fewer colds, suggesting improved immune function. Increased emotional stability, less depression, and improved strength and energy led to new personal achievements and regaining of function: “I got the mistletoe one I was quickly back on my legs again … I can say, because I got nothing else [only mistletoe]. I really did feel it and I was in a terrible hole then, and I was absolutely not getting back up again and yet this has me completely back up.”¹⁵

Patients gave example of tangible changes, such as quitting a stressful job and accepting part-time employment, setting up a new horse stable, buying a computer in order to self-educate about cancer, chopping wood, booking tickets for travel, and seeking information from other patients with cancer: “I don't fear anything—absolutely nothing; I don't have dark thoughts … I feel fine and I have my projects … and I have a new computer.”¹⁷

Ambivalence about MT

Decisions to use MT were mixed, sometimes driven by a lack of viable alternatives and a feeling that “any therapy is better than none,” particularly if conventional medicine had not helped and patients were hoping for improved disease outcome. Anthroposophic medicine, including MT, was for some a mere “snatching at straws” and was challenging for those who had to “overcome prejudice for another paradigm” that lay outside conventional medicine.^16,17

In the context of mostly positive feedback, some patients expressed uncertainty about whether changes they experienced could be attributed solely to MT. These findings are unsurprising given the context of multimodal treatments. In Brandenberger and colleagues' article, only three patients at interview attributed their improvements explicitly to MT. It was difficult to tell whether, for example, chemotherapy side effects might have been worse without MT. Patients undergoing chemotherapy and MT simultaneously reported having almost no side effects and doing better after the 3-month period of MT. This improvement could be attributable to MT, successful chemotherapy, or diminishing side effects over time. Accounts of negative experience of MT were rare. One patient reported a decrease in QoL during MT and died shortly after interview because of disease progression. Nevertheless, this patient reported that he still had hope and his spouse—who participated in the interview—felt “that she and her husband had become closer to each other because of the process of choosing and doing MT together.”¹⁷

Symbolic reference in the Konitzer article to the nature of the mistletoe plant illustrates this ambivalence. The parasitic plant can be likened to a cancer itself, while it is also conceptualized as a bringer of light, energy, and health. There were some reported side effects of MT, such as redness and hardening at the injection site, particularly following a high concentration or repeated injection at the same site. Local reactions such as these are expected with MT. One patient reported a systemic reaction: tiredness, fever, muscle aches, sleeplessness, and problems with concentration. However, no patients in any of the three studies interrupted MT because of these reactions, although one patient reported feeling “relieved” when the treatment and the associated side effects ended.

Bridging the gap between conventional and integrative care

This theme is derived only from the Arman article but is relevant to the wider literature on integrative medicine. Arman points to a mutual skepticism between practitioners of conventional and anthroposophic healthcare, also evident among some patients. This is exemplified by one who expressed difficulty in “opening up” to the idea of MT and “overcoming prejudices.” In this article, patients were seen as having to do the work of being “bridge-builders” between the two systems, carrying “the burden and the risk which may cause stress” [authors]: “The gap implies a lack of knowledge and occasionally ignorance on both sides. Patients have to bridge the gap by themselves … they feel like they are standing with one foot on each side” [authors].

Discussion

This systematic review has revealed a small number of qualitative studies of MT, which is in sharp contrast to the number of clinical and laboratory-based studies. The initial searches also revealed a total absence of studies investigating health professionals' attitudes to the use of MT, a key question for the transferability of MT to other clinical and international settings where it is not currently used. The initial searches (November 2012) were updated in April 2015, generating no new articles. To maintain consistency and comparability for the synthesis, the articles included in the study were all qualitative studies of adults receiving MT.

This review does reveal a coherent narrative of patients' experience of MT despite diverse types of data drawn from the primary studies. All the articles were based in Northern Europe, and further studies may on the appropriateness of MT in other contexts may be needed.

Although these three studies on the use of MT are a rich source of patient-centered information, they are small-scale and exploratory. Synthesis of the findings gives added value by combining the insights gained in individual papers and thereby provides a stronger indication of the likely impact of MT on patients. MT was experienced in many ways, and benefits were mediated via the symbolic nature of the mistletoe plant itself, the ritual of self-injection, and the physiologic impact of the therapy. It is not possible to clearly distinguish the effects of MT from other aspects of the holistic package in Arman and colleagues' article.¹⁶

The data may reflect the particular context of MT delivery. Patients' descriptions of their experiences of MT in two of the articles were likely to have been influenced by the anthroposophic context of their treatment, in one case receiving a package of anthroposophic treatment¹⁶ and in the other receiving group analytic therapy.¹⁵ However, in Brandenberger and colleagues' article, patients received MT in an integrative medicine setting where MT was combined with conventional rather than anthroposophic medicine. Of note, all but two of the themes emerged from data across all three articles, suggesting a communality of experience.

There were many specific examples of a reduction in side effects of chemotherapy and improvements in well-being, such as improved mood and increased energy; these are consistent with findings in clinical trials and cohort studies. Patients' narratives went beyond the physical improvements into emotional and psychosocial benefits and the construction of meaning around their disease.

The fact that patients at interview were unwilling or unable to decisively ascribe these improvements to MT is not surprising given the multimodal treatments that they were receiving. However, despite some initial skepticism and some experience of side effects, the data suggest that patients' adherence to MT was impressive in these studies. This reinforces the importance that patients gave to the treatment. This review captures important insights into changes that were meaningful for patients and underlines the limitation of relying on quantitative measures of QoL alone.

The importance of MT as a means of gaining a sense of control is consistent with reports in the literature on the use of complementary and alternative therapies in cancer.¹⁹ Self-injection enhances the experience of patient participation in the patient's own treatment, and participation improves mood and psychological coping and may affect survival.²⁰

One of the articles highlights the mutual professional skepticism across disciplinary boundaries between conventional and integrative medicine, with patients feeling they have to form a “bridge.” Such institutional polarization has previously been reported as a barrier for patients in achieving a positive experience of complementary therapies in cancer care.⁴ This issue needs to be addressed through education for healthcare providers if MT use is to be extended to clinical settings outside of central Europe.

Limitations

Since the searches for this review were conducted, further, more recent archives of the Journal of Anthroposophical Medicine have become available online via a German website. The review would have been more comprehensive if we had screened these archives. However, any qualitative studies that met the inclusion criteria are most likely to have been published in the major databases searched. The authors also contacted anthroposophical researchers, who would have mentioned any of their relevant studies published in this journal.

The focus of two of the articles was indirectly rather than directly relevant to the research question, one reporting on symbolic understanding of mistletoe and the other on a package of anthroposophic care, not just MT. Some of the data sources were “nonstandard,” for example, material gathered from a therapy group, including the use of art therapy material.¹⁵

It is difficult to separate the experience of MT from the context in which it was delivered. In all three studies, MT was part of a multimodal approach to cancer treatment that included conventional care and other, unspecified complementary therapies.

The mode of delivery and dosage of mistletoe treatment were different in each article. Arman and colleagues' study included a mixed sample of patients, some of whom were being treated for cancer and some for “burn-out syndrome,” but the data analysis did not distinguish between the two groups.

Conclusions

The results of this review suggest that MT is well tolerated by patients, who reported good adherence to the therapy and articulated a range of important benefits in their physical and psychosocial well-being. In line with patients' comments, it is important to acknowledge that the benefits cannot necessarily be ascribed directly to MT in the context of other therapies being received, although references specifically to MT were frequent across articles. Patients also welcomed active participation in treatment through self-injection.

Further good-quality qualitative studies of MT need to be carried out, and it is essential to embed qualitative research of patients' experience within future trials of MT. A qualitative approach to health professionals' views of MT across a range of approaches within both anthroposophical and conventional medicine would also add an important dimension in identifying key questions and designing future research. A major goal for future research should be the disentangling of MT from the context of delivery. Given the high prevalence of cancer, the expanding range of treatment options, and increased survivorship, MT should be more widely assessed through well-designed trials as a potential adjunctive treatment in supportive cancer care, with high-quality focussed qualitative research as an essential element.

Footnotes

Acknowledgments

This article is part of a pilot study for a randomized controlled trial of mistletoe use in breast cancer, funded by the National School for Primary Care Research.

Authors' contributions: M.E., G.F., and A.H. were involved in the conception of the review. A.H. led on the written methods section and carried out the electronic searches. M.E., S.B., and A.H. screened the references. M.E. led the qualitative data extraction and drafted the results and discussions. S.B. and M.E. completed the data extraction and synthesis. G.F. made a substantial contribution to drafting the manuscript. All authors contributed to the final manuscript.

M.E. and A.H. are research fellows, S.B. a research associate, and G.F. a professor at the Centre for Academic Primary Care, University of Bristol. G.F. is also a general practitioner.

Author Disclosure Statement

No competing financial interests exist.

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