Mistletoe Extract in Patients With Advanced Pancreatic Cancer: a Double-Blind, Randomized, Placebo-Controlled Tial (MISTRAL)

BACKGROUND: Patients with advanced pancreatic cancer have limited survival and few treatment options. We studied whether mistletoe extract (ME), in addition to comprehensive oncological treatment and palliative care, prolongs overall survival (OS) and improves health-related quality of life (HRQoL). METHODS: The double-blind, placebo-controlled MISTRAL trial was conducted in Swedish oncology centers. The main inclusion criteria were advanced exocrine pancreatic cancer and Eastern Cooperative Oncology Group (ECOG) performance status 0-2. The subjects were randomly assigned to ME (n=143) or placebo (n=147) and were stratified by study site and by eligibility (yes/no) for palliative chemotherapy (June 2016-December 2021). ME or placebo was injected subcutaneously three times a week for nine months. The primary endpoint was overall survival (OS); one of the secondary endpoints was the HRQoL dimension global health/QoL (EORTC-QLQ-C30), as assessed at seven time points over nine months. Trial registration: EudraCT 2014-004552-64, NCT02948309. RESULTS: No statistically significant benefit of adding ME to standard treatment was seen with respect to either OS or global health/ QoL. The adjusted hazard ratio for OS was 1.13 [0.89; 1.44], with a median survival time of 7.8 and 8.3 months for ME and placebo, respectively. The figures for the HRQoL dimension "global health/QoL" were similar in the two groups (p=0.86). The number, severity, and outcome of the reported adverse events were similar as well, except for more common local skin reactions at ME injection sites (66% vs. 1%). CONCLUSION: ME is unlikely to have a clinically significant effect on OS or the HRQoL dimension global health/QoL when administered in patients with advanced pancreatic cancer in addition to comprehensive cancer care.

Acupuncture in cancer care: recommendations for safe practice (peer-reviewed expert opinion).

BACKGROUND: Up-to-date recommendations for the safe practice of acupuncture in integrative oncology are overdue with new cancer treatments and an increase in survivors with late effects of disease; 17 years have elapsed since Filshie and Hester's 2006 guidelines. During 2022/2023 an expert panel assembled to produce updated recommendations aiming to facilitate safe and appropriate care by acupuncturists working with people with cancer. METHODS: A core development team comprising three integrative oncology professionals comprehensively updated pre-existing unpublished recommendations. Twelve invited international experts (senior acupuncturists with and without experience of working in oncology settings, oncologists, physicians and nurses trained in integrative oncology, researchers, academics, and professional body representatives) reviewed the recommendations. In multiple iterations, the core team harmonised comments for final ratification. To aid dissemination and uptake the panel represents national and international integrative oncology associations and major cancer treatment centres in Europe, USA, Australia, and the Middle East. RESULTS: These recommendations facilitate safe care by articulating contra-indications, cautions, and risks for patients both on and off treatment (surgery, SACT, radiotherapy). Situations where acupuncture may be contra-indicated or practices need adapting are identified. "Red and Amber Flags" highlight where urgent referral is essential. CONCLUSION: These are the first international, multidisciplinary peer-reviewed recommendations for safe acupuncture practice in integrative oncology. Concerns about safety remain a significant barrier to appropriate referral from oncology teams, to use by acupuncturists and to uptake by patients. Disseminating trustworthy, widely accessible guidance should facilitate informed, confident practice of acupuncture in and outside of oncology healthcare settings.

Communication About Complementary and Alternative Medicine When Patients Decline Conventional Cancer Treatment: Patients' and Physicians' Experiences.

BACKGROUND: Complementary and alternative medicine (CAM) is a broad set of nonconventional practices used alongside or instead of conventional treatment: The latter poses obvious risks related to cancer prognosis. Patient-physician dialogue about CAM is crucial for patient safety and mutual trust. Little is known about communication in the rare situations when patients decline recommended cancer treatment and consider using CAM. The objective of this study was to explore patients' and physicians' experiences from situations when patients decline recommended cancer treatment and consider using CAM. MATERIALS AND METHODS: Semi-structured interviews were carried out with 7 CAM-using cancer patients who had declined some or all conventional treatment as well as 10 physicians from oncology and palliative care. Framework analysis was used. RESULTS: Regarding treatment choices, there was a dissonance between physicians' focus on medical reasoning and patients' expression of complex values. Physicians' difficulty in understanding patients' treatment decline was exacerbated when patients considered using CAM, impairing communication even further. Inequalities in roles resulting in power struggles risked pushing both parties toward extreme and inflexible standpoints. Despite these challenges regarding treatment choices and hierarchical roles, both parties considered open and respectful communication as crucial. CONCLUSIONS: This study highlights the difficulty of shared decision-making in practice when patients' and physicians' views on treatment decisions deviate in clinically challenging situations. Our results point to a need to address the complexity of these situations, pay attention to patients' values, and improve knowledge among physicians about CAM.

Use of CAM among cancer patients : Results of a regional survey in Sweden.

BACKGROUND: The use of complementary and alternative medicine (CAM) by patients is widespread. However, there is a lack of knowledge regarding the extent and details of patient CAM use in Sweden, especially in rural Sweden. The aim of this study was to estimate the extent and characteristics of CAM use among cancer patients in Region Gävleborg. METHODS: A total of 631 questionnaires were distributed to which 376 responses were registered, yielding a response rate of 59.6%. Questionnaires were distributed to oncology patients at their first visit for curative treatment at the Department of Oncology, Gävle Hospital. Palliative patients were recruited at their first visit and during enrollment in palliative outpatient care in their own homes. The characteristics of the respondents were presented with standard descriptive statistics. A multivariable logistic model was fitted to calculate odds ratios (ORs) and identify potential predictors (Age, Gender, Education, Diagnosis) of CAM use post-cancer diagnosis. RESULTS: 54% of all participants reported lifetime CAM use, 34% reported CAM use post-diagnosis. The most common CAM methods used after diagnosis are vitamins, health food preparations, herbal teas, prayer and dietary methods. The most common source of information reported is family and friends. Almost 70% of those who used CAM after their diagnosis stated that they did not discuss their use with healthcare professionals. Most patients reported that they would like some CAM modalities to be offered within conventional care regardless of their own CAM use. CONCLUSIONS: The use of CAM is common among patients with cancer in the region of Gävleborg, and previous studies show a similar use in Sweden in general. Based on the widespread use of CAM and patient interest in discussing CAM use with healthcare professionals, greater attention and focus should be placed on creating a basis for this dialogue. If we, as healthcare professionals, are to emphasise our commitment to providing patient-centred care, we must acknowledge that patients use CAM and are seeking a dialogue about CAM use in their care.

Consultations with health care providers and use of self-management strategies for prevention and treatment of COVID-19 related symptoms. A population based cross-sectional study in Norway, Sweden and the Netherlands.

OBJECTIVES: The present study was initiated to determine consultations with health care providers and use of self-management strategies for prevention or treatment of COVID-19 related symptoms in countries with a full lockdown (Norway), a partial lockdown (the Netherlands) and no lockdown (Sweden) during the first three months of the COVID-19 pandemic, and if such use correlates with worries of being infected by COVID-19 disease. DESIGN: Data were collected in collaboration with Ipsos A/S in April-June 2020. An adapted version of the International Questionnaire to measure use of Complementary and Alternative Medicine (I-CAM-Q) was used with the categories "for prevention of COVID-19" and "to treat COVID-19-related symptoms" added. Data were collected among a representative sample in Norway, Sweden and the Netherlands using data assisted telephone interviews (Norway, n=990 and Sweden, n=500), and an online survey (the Netherlands, n=1004). Total response rate was 30%. RESULTS: Very few consulted a health care provider with the intention to treat or prevent COVID-19 (1.2% and 1.0% respectively) with medical doctors mostly visited (1.0% and 0.9% respectively). Similarly, the use of self-management strategies to prevent or treat COVID-19 was low (3.4% and 0.2% respectively); most commonly used for prevention of COVID-19 were vitamins and minerals (2.8%). Consultations with health care providers and use of self-management strategies for prevention of COVID-19 were positively associated with worries of being infected with COVID-19. CONCLUSIONS: The COVID-19 pandemic does not seem to have evoked a large-scale difference in behavior related to consultations with health care providers or the use of self-management strategies in any of the three countries.

Efficacy of mistletoe extract as a complement to standard treatment in advanced pancreatic cancer: study protocol for a multicentre, parallel group, double-blind, randomised, placebo-controlled clinical trial (MISTRAL).

BACKGROUND: Most pancreatic cancer patients present with advanced stage at diagnosis with extremely short expected survival and few treatment options. A multimodal palliative approach is necessary for symptom relief and optimisation of health-related quality of life. In a recent open-label trial of mistletoe extract for advanced pancreatic cancer patients not eligible for chemotherapy, promising results on improved overall survival and better health-related quality of life were reported. The objective of the present study is to assess the value of mistletoe extract as a complement to standard treatment (palliative chemotherapy or best supportive care) in advanced pancreatic cancer patients with regard to overall survival and health-related quality of life. METHODS: The trial is prospective, randomised, double-blind, multicentre, parallel group and placebo-controlled. In total, 290 participants are randomly assigned to placebo or mistletoe extract given subcutaneously in increasing dosage from 0.01 to 20 mg three times per week for 9 months. Stratification is performed for site and palliative chemotherapy. Main inclusion criteria are advanced pancreatic cancer and Eastern Cooperative Oncology Group performance status 0 to 2; main exclusion criteria are life expectancy less than 4 weeks and neuroendocrine tumour of the pancreas. Two ancillary studies on sub-sets of participants are nested in the trial: a biomarker study collecting blood samples and a cross-sectional qualitative study with semi-structured face-to-face interviews. DISCUSSION: To our knowledge, this is the first placebo-controlled randomised trial assessing the impact of mistletoe extract as a complement to standard treatment on overall survival and health-related quality of life in patients with advanced pancreatic cancer. The presented trial with its two nested ancillary studies exploring biomarkers and patient experiences is expected to give new insights into the treatment of advanced pancreatic cancer. TRIAL REGISTRATION: EU Clinical Trial Register, EudraCT Number 2014-004552-64 . Registered on 19 January 2016. ClinicalTrials.gov NCT02948309 . Registered on 28 October 2016.

Cancer patients' use of complementary and alternative medicine in Sweden: a cross-sectional study.

BACKGROUND: Access to and advice on Complementary and Alternative Medicine (CAM) are uncommon within Swedish conventional cancer care and little is known about cancer patients' own use of CAM. The aim of this cross-sectional study was to explore Swedish cancer patients´ patterns of CAM use, their experiences and preferences. METHODS: Questionnaires were distributed consecutively to 1297 cancer patients at a university hospital's out-patient oncology units. The response rate was 58% (n = 755). Descriptive statistics were used to analyze the survey data. A logistic regression model was used to investigate the association between CAM use and gender, age and level of education. Open-ended responses were analyzed, using qualitative content analysis. RESULTS: Lifetime CAM use was reported by 34% (n = 256), and 26% (n = 198) used CAM after cancer diagnosis. Being female, younger and having higher education predicted CAM use. Most commonly used methods were natural products including vitamins and minerals and relaxation. Main reasons for CAM use were improvement of physical, general and emotional wellbeing and increasing the body's ability to fight cancer. Satisfaction with CAM usage was generally high. Reported adverse effects were few and mild; 54% of users spent < 50 Euro a month on CAM. One third had discussed their CAM use with cancer care providers. More than half of all participants thought that cancer care providers should be able to discuss (58%) and to consider (54%) use of CAM modalities in cancer care. CONCLUSIONS: Despite limited access and advice within conventional cancer care, one fourth of Swedish cancer patients use CAM. The insufficient patient-provider dialogue diverges with most patients' wish for professional guidance in their decisions and integration of CAM modalities in conventional cancer care. Concurrent and multimodal CAM use implies challenges and possibilities for cancer care that need to be considered.

Mistletoe treatment in cancer-related fatigue: a case report.

Cancer-related fatigue (CRF) is a major and very common disabling condition in cancer patients. Treatment options do exist but have limited therapeutic effects. Mistletoe extracts are widely-used complementary cancer treatments whose possible impact on CRF has not been investigated in detail. A 36-year-old Swedish woman with a 10-year history of recurrent breast cancer, suffering from severe CRF, started complementary cancer treatment with mistletoe extracts. Over two and a half years a correspondence was observed between the intensity of mistletoe therapy and the fatigue. Mistletoe extracts seemed to have a beneficial, dose-dependent effect on CRF. Although such effect has also been noted in clinical studies, it has never been the subject of detailed investigation. More research should clarify these observations.

Anthroposophic health care--different and home-like.

Anthroposophic health care is rooted in the work of Steiner and Wegman in Switzerland during the 1920s. The Swedish hospital in this study offers integrated conventional and anthroposophic health care therapies which are conceptualized as an extended and integrative variant of health care and not as CAM. In anthroposophic care, health is viewed as a matter of body, soul and spirit in balance. Therapeutic resources include nursing care, therapeutic conduct (art and body therapies) and medicines based on natural remedies. This study aims to deepen the understanding of what constitutes good care from a patient's perspective to alleviate patients' suffering and to identify clinical markers for good care. As anthroposophic care is associated with theory and holistic ideas, this study aims at exploring whether or not anthroposophic care has a beneficial effect. A qualitative method was used, and the analysis was conducted with a phenomenological hermeneutic approach. Sixteen former patients, of whom nine were diagnosed with various kinds of cancer and seven with burnout syndrome, were interviewed regarding their experience of anthroposophic care. Patients especially noted the benefits of the holistic caring environment; the empathetic approach and true caring offered, as well as the peaceful atmosphere and rest. A turning point or shift in perspectives, implying a home coming in relation to inner aspects was discussed as an outcome. Although patients in general were overwhelmingly impressed and positive they were also ambivalent. One interpretation is that there is a gap between the anthroposophic and conventional paradigm that affects patients negatively. As mutual scepticism still prevents any real integration between integrative and conventional care, the onus appears to be on the patient to take the risk and act as bridge-builder. From a caring science perspective, the study shows that appropriation of specific values and theory makes it possible to create a true caring culture.