Influence of Multimodal Treatment on Rest/Activity and Autonomic Regulation in Breast Cancer Patients with Cancer-Related Fatigue: Results of a Tri-Centre Trial with a Comprehensive Cohort Design.

INTRODUCTION: Breast cancer patients with cancer-related fatigue (BC-CRF) often have lower physical activity. To investigate how this could be improved, we evaluated a multimodal treatment (MT) and a combination of MT with aerobic training (CT) and compared these with aerobic training (AT) regarding rest/activity rhythm and state autonomic regulation (State aR). METHODS: In this pragmatic comprehensive cohort design study, the explorative analysis focused on actigraphy and State aR including the rest/activity regulation subscale (State aR-R/A) which were assessed at baseline (T0), after 10 weeks of intervention (T1), and State aR additionally 6 months later (T2). STATISTICS: General linear modelling including propensity scores. RESULTS: 65 BC-CRF were randomized, and 61 were allocated by preference to the treatment arms. 105 patients started the intervention. At T1, State aR-R/A improved the most in MT (+3.49, CI [2.42; 4.55]) compared to AT (+1.59, CI [0.13; 3.06]) and CT (+1.68, CI [0.83; 2.52]), showing superiority of MT to AT (p = 0.048). At T2 MT was sustainably superior to AT regarding State aR-R/A (+3.61, CI [2.38; 4.83] p < 0.01) and State aR also showed superiority of MT to AT (p = 0.006). AT T1 24-h activity was higher in MT compared to AT (p = 0.029). CONCLUSIONS: MT was superior to AT regarding State aR total score after 6 months, State aR-R/A after 10 weeks, and after 6 months. Actigraphically measured total activity also improved after 10 weeks.

Feasibility and Possible Effects of Mindful Walking and Moderate Walking in Breast Cancer Survivors: A Randomized Controlled Pilot Study With a Nested Qualitative Study Part.

INTRODUCTION: Breast cancer (BC) survivors often suffer from disease- and therapy-related long-term side-effects. The study aim was to explore the feasibility, adherence, and individual experiences as well as possible effects of 2 different walking interventions in BC patients. METHODS: This randomized controlled, pragmatic pilot trial included a qualitative study component. BC patients were randomized to either mindful walking (MFW) with mindfulness exercises and walking or moderate walking (MW) alone in weekly group sessions over 8 weeks. After 8 and 16 weeks, satisfaction, and self-perceived effectiveness as well as different health-related outcomes including health-related (WHOQOL-BREF) and disease-specific quality of life (FACT-G), perceived stress (PSQ) and cancer-related fatigue (CFS-D) were assessed. ANCOVA was used to evaluate differences in study outcomes. Qualitative data included 4 focus group interviews including 20 patients and were analyzed using a directed qualitative content analysis approach. RESULTS: Altogether, 51 women (mean age 55.8 years (SD 10.9)) were randomized (n = 24 MFW; n = 27 MW). Both groups would recommend the course to other BC patients (MFW 88.9%; MW 95.2%) and showed possible improvements from baseline to week 8, without statistically significant difference between groups: WHOQOL-BREF (MFW: adjusted mean 65.4 (95% confidence interval (CI), 57.1-73.7); MW: 61.6 (53.6-69.6)); FACT-G (MFW: 76.0 (71.5-80.5); MW: 73.0 (68.5-77.4)); PSQ (MFW: 45.3 (40.5-50.1); MW: 45.4 (40.8-50.0)); CFS-D (MFW: 24.3 (20.8-27.8); MW: 25.5 (22.1-28.8)). Improvements lasted until the 16-weeks follow-up. The qualitative analysis suggested that MFW primarily promoted mindfulness, self-care, and acceptability in BC patients, whereas MW activated and empowered the patients as a result of the physical exercise. CONCLUSION: Both study interventions were positively evaluated by patients and showed possible pre-post effects in disease-specific health-related outcomes without differences between groups. The qualitative analysis results indicate that different resources and coping strategies were addressed by the 2 study interventions. TRIAL REGISTRATION: DKRS00011521; prospectively registered 21.12.2016; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011521.

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

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

Yoga, Eurythmy Therapy and Standard Physiotherapy (YES-Trial) for Patients With Chronic Non-specific Low Back Pain: A Three-Armed Randomized Controlled Trial.

We aimed to evaluate the effects of yoga and eurythmy therapy compared to conventional physiotherapy exercises in patients with chronic low back pain. In a three-armed, multicentre, randomized controlled trial, patients with chronic low back pain were treated for 8 weeks in group sessions (75 minutes once per week). Primary outcome was patients' physical disability (measured by RMDQ) from baseline to week 8. Secondary outcome variables were pain intensity and pain-related bothersomeness (VAS), health-related quality of life (SF-12) and life satisfaction (BMLSS). Outcomes were assessed at baseline, after the intervention at 8 weeks and at a 16-week follow up. Data of 274 participants were used for statistical analyses. There were no significant differences between the three groups for the primary and all secondary outcomes. In all groups, RMDQ decreased comparably at 8 weeks, but did not reach clinical meaningfulness. Pain intensity and pain-related bothersomeness decreased, while quality of life increased in all 3 groups. In explorative general linear models for the SF-12's mental health component participants in the eurythmy arm benefitted significantly more compared to physiotherapy and yoga. Furthermore, within-group analyses showed improvements of SF-12 mental score for yoga and eurythmy therapy only. All interventions were safe. Clinical Trials Register: DRKS-ID: DRKS00004651 Perspective: This article presents the results of a multicentre three-armed randomized controlled trial on the clinical effects of three 8-week programs in patients with chronic low back pain. Compared to the 'gold standard' of conventional physiotherapeutic exercises, eurythmy therapy and yoga therapy lead to comparable symptomatic improvements in patients with chronic low back pain. However, the within-group effect sizes were small to moderate and did not reach clinical meaningfulness on patients' physical disability (RMDQ).

Correction to: Impact of a combined multimodal-aerobic and multimodal intervention compared to standard aerobic treatment in breast cancer survivors with chronic cancer-related fatigue - results of a three-armed pragmatic trial in a comprehensive cohort design.

An amendment to this paper has been published and can be accessed via the original article.

Impact of a Multimodal and Combination Therapy on Self-Regulation and Internal Coherence in German Breast Cancer Survivors With Chronic Cancer-Related Fatigue: A Mixed-Method Comprehensive Cohort Design Study.

Background: Recent studies have proved the relevance of salutogenetic variables for fatigue management in breast cancer survivors with cancer-related fatigue (CRF). This comprehensive cohort design study is the first to examine the impact of 2 multimodal therapies, multimodal therapy (MT) and combined therapy (CT), compared with standard aerobic training (AT) on salutogenetic variables (self-regulation and internal coherence) and distress in breast cancer survivors with CRF. Methods: A total of 105 patients started the therapies and n = 84 completed the Self-regulation Scale, the Internal Coherence Scale, the Cancer Fatigue Scale, and the Hospital Anxiety and Depression Scale at baseline, 10 weeks after treatment (T1) and n = 81 after 6 months (T2). Patient satisfaction and qualitative feedback regarding therapy quality was assessed at T1. A general linear model including allocation type, therapy arm (MT/CT/AT), and bias-adjusting propensity scores tested the superiority of both multimodal therapies versus AT for all questionnaires at T1 and T2. Results: MT and CT were superior to AT to improve self-regulation and patients' satisfaction at T1. Additionally, CT showed superiority for self-regulation at T2 (all P < .05). Compared with AT, internal coherence was significantly higher for patients in the MT arms at T2, respectively (all P < .01). Pearson's correlations between self-regulation, internal coherence, and CRF improved from baseline to T2 (Mean r = -0.60). Qualitative feedback confirmed patients' benefits in several health-related categories. Conclusions: Self-regulation and internal coherence are manipulable variables with relevant CRF associations. They can be positively affected by multimodal therapies. Alongside patients' satisfaction and qualitative feedback they help refine treatment.

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

Introduction:Viscum album L extracts (VA) are frequently used in integrative oncology. Aim of this study was to evaluate the impact of add-on VA applications on various patient-reported outcome measures. Methods: A longitudinal real-world study was conducted, using data from the Network Oncology clinical registry. Primary, nonmetastasized breast cancer patients treated with oncological standard therapy partly combined with VA applications were included. Internal Coherence Cancer-related Fatigue, and EORTC QLQ-C30 questionnaires were assessed at baseline and 6, 12, and 24 months later. Results: A total of 319 patients received standard oncological therapy and 40% of them additionally VA applications. After 6 and 12 months for patients treated with chemotherapy (Ctx) only a significant decline of the thermo-coherence, and worsening of fatigue was observed. For patients receiving VA applications but no Ctx, significant beneficial effects on thermo-coherence, fatigue, and seven EORTC QLQ-C30 scales were observed 24 months later. Adjusted multivariable long-term subgroup (n = 106) regression analysis revealed that Ctx, immuno-, and endocrine therapies had a worsening of 17, 17, and 6 point changes, respectively, for EORTC QLQ-C30 fatigue (P = .0004), while VA applications showed an improvement of 12 point change. A similar impact of improvement (add-on VA) and worsening (standard oncological treatment regimens) on EORTC QLQ-C30 insomnia (P = .009) and physical functioning (P = .005) were observed. Conclusions: In the present real-world study, add-on VA applications had a supportive effect on cancer-related fatigue, insomnia, physical functioning, and thermo-coherence. Thus, VA applications might be suited to alleviate symptom burden during anticancer therapy in breast cancer patients.

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

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

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

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

Influence of a Multimodal and Multimodal-Aerobic Therapy Concept on Health-Related Quality of Life in Breast Cancer Survivors.

CONTEXT: Cancer-related fatigue (CRF) is one of the most burdensome symptoms in breast cancer survivors (BCSs), accompanied by reduced health-related quality of life (HRQOL). OBJECTIVES: This study investigated the influence of a multimodal therapy (MT; psychoeducation, eurythmy therapy, painting therapy, and sleep education/restriction), or a combination therapy (CT; MT plus aerobic training [AT]) on HRQOL in BCS with chronic CRF in comparison with AT alone. METHODS: One hundred and twenty-six BCSs with CRF were included in a pragmatic comprehensive cohort study and allocated either per randomization or by preference to MT, CT, or AT. The EORTC QLQ-C30 core questionnaire was used to measure HRQOL. All analyses on HRQOL parameters were done in an explorative intention. RESULTS: Patients were assigned to MT (n = 44), CT (n = 54), or AT (n = 28). CT was significantly superior to AT after 10 weeks of intervention (T1) in improving physical function. MT was found to have significant superiority over AT at T1 and T2 for physical functioning, emotional functioning, insomnia, and financial problems as well as role functioning, cognitive, social functioning, and fatigue 6 months later (T2). CONCLUSION: A multimodal approach appears to be a suitable concept for BCS with chronic CRF. A confirmatory study with larger samples should demonstrate the superiority of MT and adapted CT in HRQOL compared with the current treatment AT found in these explorative analyses.

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

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

Integrative cancer care in a certified Cancer Centre of a German Anthroposophic hospital.

OBJECTIVE: The concept of integrative oncology (IO) comprising guideline-oriented standard and add-on complementary medicine has gained growing importance. The Anthroposophic-integrative Cancer Centre (CC) at the hospital Gemeinschaftskrankenhaus (GKH) in Berlin has been implementing IO concepts during recent years. Furthermore, it is a certified CC and has been annually audited by national cancer authorities since 2012. The objective of the present study was to evaluate IO concepts of the certified CC GKH. METHODS: Clinical, demographic, integrative treatment and follow-up data were analyzed between 2011 and 2016. In addition, CC GKH quality measures were compared with those of nationwide benchmarking CCs. RESULTS: Between 2011 and 2016, 2.382 primary cancer patients, median age 66 years, were treated at the CC GKH. 70.1% of the patients showed either Union for International Cancer Control (UICC) stage 0, I, II or III and 25.6% were in UICC stage IV. IO therapies included surgery (64.4% of patients), radiation (41.2%), and application of cytostatic drugs (53.9%), add-on mistletoe therapy (30.5%), and non-pharmacological interventions (87.3%). Regarding psycho-oncological support and quota of patient's enrollment in studies the CC GKH performs above nationwide benchmarks. Research outcomes including safety issues, clinical impact as well as patient's health-related quality of life are continuously evaluated and integrated into hospital's decision-management. CONCLUSION: This analysis reveals that IO concepts are applied to a high proportion of male and female primary cancer patients of all age groups, indicating a successful implementation at the certified CC GKH. Ongoing clinical evaluations have been initiated and cost-effectiveness comparisons are under analyses.

Psychosocial, Cognitive, and Physical Impact of Elaborate Consultations and Life Review in Female Patients with Non-Metastasized Breast Cancer.

BACKGROUND: Elaborate consultations and life review (ECLR) has been regularly applied in patients of various cancer entities and stages within Anthroposophic-integrative oncology concepts. However, a lack of systematic research in this field has been detected. To close this gap of knowledge, we evaluated the impact of ECLR in patients with non-metastasized breast cancer before, during, and after primary oncological treatment. METHODS: Patient-reported outcome measures were evaluated by analyzing European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30) in patients with non-metastasized breast cancer who had received either oncological standard therapy alone or in combination with ECLR. RESULTS: 95 female patients were eligible for questionnaire analysis (median age 58 years). Adjusted multivariable linear regression analysis revealed that ECLR was associated with significant improvements in medium-term global health/quality of life and emotional, social, and cognitive functioning. Furthermore, ECLR was associated with significant reductions of short-term appetite loss burden, pain, and short- and medium-term financial difficulties. Subgroup analyses revealed significant improvements in pivotal quality-of-life aspects including fatigue (p = 0.002) in chemotherapy-treated patients after ECLR. CONCLUSIONS: 12 months of surveillance of breast cancer patients reveals medium-term recovery of the global health status/quality of life and cognitive and psychosocial well-being associated with ECLR. In addition, our data indicate a possible association between ECLR and reduced short-term fatigue burden, which has to be re-confirmed prospectively in a larger study cohort. As long-term cancer survivors develop psychological symptoms similar to patients with chronic diseases, prospective studies should evaluate the impact of ECLR on the psychosocial well-being in these patients.

Implementation of an Integrative Oncological Concept in the Daily Care of a German Certified Breast Cancer Center.

BACKGROUND: In recent decades the concept of integrative medicine has attracted growing interest in patients and professionals. At the Gemeinschaftskrankenhaus Havelhöhe (GKH), a hospital specialized in anthroposophical medicine, a breast cancer center (BCC) has been successfully certified for more than 5 years. The objective of the present study was to analyze how integrative strategies were implemented in the daily care of primary breast cancer patients. METHODS: Clinical, demographic, and follow-up data as well as information on non-pharmacological interventions were analyzed. In addition, BCC quality measures were compared with data of the National Breast Cancer Benchmarking Report 2016. RESULTS: Between 2011 and 2016, 741 primary breast cancer patients (median age 57.4 years) were treated at the GKH BCC. 91.5% of the patients showed Union for International Cancer Control (UICC) stage 0, I, II, or III and 8.2% were in UICC stage IV. 97% of the patients underwent surgery, 53% radiation, 38% had hormone therapy, and 25% received cytostatic drugs. 96% of the patients received non-pharmacological interventions and 32% received Viscum album L. THERAPY: Follow-up was performed in up to 93% of the patients 2 years after first diagnosis. Compared to nationwide benchmarking BCCs, the GKH BCC met the requirements in central items. CONCLUSIONS: The results of the present study show that integrative therapies offered by the concept of anthroposophical medicine can be implemented in the daily care and treatment of a certified BCC. However, as national guidelines on integrative concepts in oncology are missing, further studies are needed for a systematic evaluation of integrative treatment and care concepts in this field.

Safety of Combined Treatment With Monoclonal Antibodies and Viscum album L Preparations.

Combination strategies involving chemotherapy and monoclonal antibodies (mAb) are commonly used in attempts to produce better clinical outcomes. This practice has led to new and ongoing toxicities that may lead to reductions in dose or noncompliance, limiting the effectiveness of treatment. Viscum album L (VA) preparations are widely used in Europe as additive therapy and have been associated with reduced chemotherapy-related adverse reactions and increased health-related quality of life. Concomitant VA therapy might also reduce toxicity related to mAb. This retrospective study investigated the safety of combined treatment with VA and mAb in cancer patients. A total of 43 patients had combined therapy (474 exposures); 12 had VA without mAb (129 exposures), and 8 had mAb without VA (68 exposures). Most patients (89.3%) received concomitant chemotherapy or supportive therapies. A total of 34 patients (60.7%) experienced 142 adverse events (AEs). Leucopenia (14.1% of all events), acneiform rash (8.5%), and stomatitis (6.3%) occurred most frequently. Longitudinal logistic regression analysis suggested a nearly 5 times higher odds of experiencing an AE following treatment with mAb compared with mAb plus VA (95% CI = 1.53-16.14). Our results, together with theoretical consideration of potential botanical-drug interactions, suggest that combined treatment with VA and mAb is safe.

Treatment of Chronic Lower Back Pain: Study Protocol of a Comparative Effectiveness Study on Yoga, Eurythmy Therapy, and Physiotherapeutic Exercises.

BACKGROUND: We aim to compare the effectiveness of 3 active interventions, i.e., yoga, eurythmy therapy, and physiotherapeutic exercise, on chronic lower back pain. METHODS: In this randomized controlled trial over 16 weeks (8 weeks of intervention, 8 weeks of follow-up), data of individuals with chronic lower back pain will be analyzed. Interventions are implemented as group sessions (75 min) once per week. Participants receive a manual for home-based practice and are assessed before and at the end of the 8-week intervention period, and at the end of an 8-week follow-up period. Standardized questionnaires are: the Roland-Morris Disability Score, visual analog scales measuring intensity of pain, the Brief Multidimensional Life Satisfaction Scale, the Perceived Stress Scale, the Inner Correspondence with the Practices questionnaire, the Freiburg Mindfulness Questionnaire, the General Self-Efficacy Scale, a self-regulation questionnaire, the Internal Coherence Scale, a pain diary (registering the need of analgesic medication), and a questionnaire on the patients' expectation that the interventions will be effective in reducing pain and how strong this reduction might be (2 single items), etc. DISCUSSION: This large multicenter study will provide evidence on the effectiveness of 3 contrasting movement-orientated treatments that share some similarities but differ in essential details: yoga, eurythmy therapy, and physiotherapeutic exercises. It will provide important data on non-pharmacological options to treat lower back pain in a large group of affected individuals.

Impact of a combined multimodal-aerobic and multimodal intervention compared to standard aerobic treatment in breast cancer survivors with chronic cancer-related fatigue - results of a three-armed pragmatic trial in a comprehensive cohort design.

BACKGROUND: Cancer-related fatigue (CRF) and insomnia are major complaints in breast cancer survivors (BC). Aerobic training (AT), the standard therapy for CRF in BC, shows only minor to moderate treatment effects. Other evidence-based treatments include cognitive behavioral therapy, e.g., sleep education/restriction (SE) and mindfulness-based therapies. We investigated the effectiveness of a 10-week multimodal program (MT) consisting of SE, psycho-education, eurythmy- and painting-therapy, administered separately or in combination with AT (CT) and compared both arms to AT alone. METHODS: In a pragmatic comprehensive cohort study BC with chronic CRF were allocated randomly or by patient preference to (a) MT, (b) CT (MT + AT) or (c) AT alone. Primary endpoint was a composite score of the Pittsburgh Sleep Quality Index and the Cancer Fatigue Scale after 10 weeks of intervention (T1); a second endpoint was a follow-up assessment 6 months later (T2). The primary hypothesis stated superiority of CT and non-inferiority of MT vs. AT at T1. A closed testing procedure preserved the global α-level. The intention-to-treat analysis included propensity scores for the mode of allocation and for the preferred treatment, respectively. RESULTS: Altogether 126 BC were recruited: 65 were randomized and 61 allocated by preference; 105 started the intervention. Socio-demographic parameters were generally balanced at baseline. Non-inferiority of MT to AT at T1 was confirmed (p < 0.05), yet the confirmative analysis stopped as it was not possible to confirm superiority of CT vs. AT (p = 0.119). In consecutive exploratory analyses MT and CT were superior to AT at T1 and T2 (MT) or T2 alone (CT), respectively. CONCLUSIONS: The multimodal CRF-therapy was found to be confirmatively non-inferior to standard therapy and even yielded exploratively sustained superiority. A randomized controlled trial including a larger sample size and a longer follow-up to evaluate multimodal CRF-therapy is highly warranted. TRIAL REGISTER: DRKS-ID: DRKS00003736 . Recruitment period June 2011 to March 2013. Date of registering 19 June 2012.

The questionnaire on autonomic regulation: a useful concept for integrative medicine?

The concept of autonomic regulation (aR) reflects the relevance of the function of different autonomic systems for health. aR can be captured by questionnaires. We differentiate between a trait or constitutional aR questionnaire version including 12 (short-version) or 18 items, respectively, with three subscales (orthostatic-circulatory, rest/activity and digestive regulation), and an 18-item state aR questionnaire on the preceding week with four subscales (rest/activity, orthostatic-circulatory, thermo- and digestive regulation). The validated questionnaires show satisfying to good reliability and robust validity with clear construct validity. In this article, we summarized the actually available literature on aR and the use of aR questionnaires in clinical and observational studies. We described the relationship of high aR with health and in case of low aR or loss of regulation with disease and functional disorder in the three (four) different subscales and functional systems, such as rest/activity, orthostatic-circulatory or digestive regulation (thermoregulation) with the consecutive therapeutic need. Finally, we gave perspectives of its further application in clinical research.

Health services research of integrative oncology in palliative care of patients with advanced pancreatic cancer.

BACKGROUND: Pancreatic cancer has a dire prognosis and is associated with a high mortality. Palliative patients have special needs and often seek help in integrative oncological concepts (IO) that combine conventional and complementary therapies. Nevertheless there are few recommendations regarding IO in current cancer guidelines. The aims of this study were to report on implementation of IO in everyday palliative care and to analyze patient survival in advanced pancreatic cancer. METHODS: This multicenter observational study investigates the implementation of IO and length of survival of patients suffering from advanced pancreatic cancer (stage IV). We analyzed patient's survival by employing multivariable proportional hazard models using different parametric distribution functions and compared patients receiving chemotherapy only, a combination of chemotherapy and Viscum album (VA) treatment, and VA treatment only. RESULTS: Records of 240 patients were analyzed. Complementary therapy showed high acceptance (93 %). Most frequent therapy was VA treatment (74 %) that was often administered concomitantly to chemotherapy (64 %). Both therapies had positive effects on patient survival as they had significant negative effects on the hazard in our log-normal model. A second analysis showed that patients with combined chemotherapy and VA therapy performed significantly better than patients receiving only chemotherapy (12.1 to 7.3 month). Patients receiving only VA therapy showed longer survival than those receiving neither chemotherapy nor VA therapy (5.4 to 2.5 months). Our data demonstrates that IO can be implemented in the everyday care of patients without disregarding conventional treatment. Patients combining VA with chemotherapy showed longest survival. CONCLUSIONS: Our data demonstrate the importance and potential of health services research showing that IO treatment can be successfully implemented in the every-day care of patients suffering from advanced pancreatic cancer. Patients combining VA with chemotherapy showed longest survival. To address patients' needs adequately, future cancer guidelines might increasingly include comments on complementary treatment options in addition to conventional therapies. Further studies should investigate the effect of complementary treatments on survival and quality of life in more detail.

Use and safety of intratumoral application of European mistletoe (Viscum album L) preparations in Oncology.

BACKGROUND: Intratumoral (IT) injection of European mistletoe (Viscum album L) preparations might induce local tumor response through combined cytotoxic and immunomodulatory actions of the preparations. Although promising in vitro and in vivo data, along with clinical case studies suggest the need for validation of this hypothesis in prospective trials, the safety of IT mistletoe injections has yet to be thoroughly assessed. METHODS: The present study summarizes the practice and safety of off-label IT mistletoe therapy within the Network Oncology, a conjoint clinical registry of German hospitals and outpatients specialized in anthroposophic and integrative medicine. Demographic, diagnosis and treatment data of cancer patients who received IT mistletoe applications between 2007 and 2013 were assessed. Suspected adverse drug reactions (ADRs) were analyzed in terms of type, frequency, severity, seriousness and potential risk factors. RESULTS: A total of 123 cancer patients received 862 IT mistletoe injections (preparations from Abnoba, Helixor and Iscucin). The most commonly applied preparations were Abnoba viscum Fraxini (71 patients) and Helixor Mali (54 patients). Of the total patients, 26 patients (21.1%) experienced 74 ADRs. All ADRs were in response to either Abnoba viscum Fraxini (25.4% of exposed patients) or Helixor Mali (18.5% of exposed patients). ADRs were mostly body temperature or immune related and of mild (83.8%) or moderate (14.9%) intensity. Only one possible ADR was described as severe (hypertension) and no serious ADRs occurred. The frequency of ADRs to IT mistletoe injections was 3 times and 5 times higher than has previously been found for subcutaneous and intravenous applications of mistletoe, respectively. CONCLUSION: IT injection of mistletoe preparations resulted in a relatively high frequency of ADRs. Nearly all ADRs were mild to moderate however, and no serious ADRs occurred. Furthermore, it is possible that immune-related ADRs such as pyrexia and local inflammatory reactions might be critical for tumor response. In light of these results, IT mistletoe therapy seems to be safe and prospective trials are recommended.