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Introduction: Current inventories on quality of life used in oncology record mainly chemotherapeutical effects (EORTC QLQ C30) or the status of rehabilitative function (SF 36). There is a lack of [...]

Introduction: The network oncology (NO) comprises of several hospitals, community health centres, GP surgeries and outpatient departments specialising in oncology and aims to collect data on tumour diagnosis, therapy and [...]

The evaluation of the influence of standardized aqueous mistletoe extracts on health related quality of life (HRQOL) of tumor patients was object of several clinical investigations in the last years. [...]

Abstract Background Dementia is a major and increasing health problem worldwide. This study aims to investigate dementia treatment strategies among physicians specialised in complementary and alternative medicine (CAM) by analysing prescribing patterns and comparing them to current treatment guidelines in Germany. Methods Twenty-two primary care physicians in Germany participated in this prospective, multicentre observational study. Prescriptions and diagnoses were reported for each consecutive patient. Data were included if patients had at least one diagnosis of dementia according to the 10th revision of the International Classification of Diseases during the study period. Multiple logistic regression was used to determine factors associated with a prescription of any anti-dementia drug including Ginkgo biloba. Results During the 5-year study period (2004-2008), 577 patients with dementia were included (median age: 81 years (IQR: 74-87); 69% female). Dementia was classified as unspecified dementia (57.2%), vascular dementia (25.1%), dementia in Alzheimer's disease (10.4%), and dementia in Parkinson's disease (7.3%). The prevalence of anti-dementia drugs was 25.6%. The phytopharmaceutical Ginkgo biloba was the most frequently prescribed anti-dementia drug overall (67.6% of all) followed by cholinesterase inhibitors (17.6%). The adjusted odds ratio (AOR) for receiving any anti-dementia drug was greater than 1 for neurologists (AOR = 2.34; CI: 1.59-3.47), the diagnosis of Alzheimer's disease (AOR = 3.28; CI: 1.96-5.50), neuroleptic therapy (AOR = 1.87; CI: 1.22-2.88), co-morbidities hypertension (AOR = 2.03; CI: 1.41-2.90), and heart failure (AOR = 4.85; CI: 3.42-6.88). The chance for a prescription of any anti-dementia drug decreased with the diagnosis of vascular dementia (AOR = 0.64; CI: 0.43-0.95) and diabetes mellitus (AOR = 0.55; CI: 0.36-0.86). The prescription of Ginkgo biloba was associated with sex (female: AOR = 0.41; CI: 0.19-0.89), patient age (AOR = 1.06; CI: 1.02-1.10), treatment by a neurologist (AOR = 0.09; CI: 0.03-0.23), and the diagnosis of Alzheimer's disease (AOR = 0.07; CI: 0.04-0.16). Conclusions This study provides a comprehensive analysis of everyday practice for treatment of dementia in primary care in physicians with a focus on CAM. The prescribing frequency for anti-dementia drugs is equivalent to those found in other German studies, while the administration of Ginkgo biloba is significantly higher.

Abstract Background Current inventories on quality of life used in oncology mainly focus on functional aspects of patients in the context of disease adaption and treatments (side) effects (EORTC QLQ C30) or generically the status of common functions (Medical Outcome Study SF 36). Beyond circumscribed dimensions of quality of life (i.e., physical, emotional, social, cognitive etc.), there is a lack of inventories which also address other relevant dimensions such as the 'sense of coherence' (SOC) in cancer patients. SOC is important because of its potential prognostic relevance in cancer patients, but the current SOC scale has mainly been validated for psychiatric and psychosomatic patients. Our two-step validation study addresses the internal coherence (ICS) scale, which is based on expert rating, using specific items for oncological patients, with respect to its reliability, validity and sensitivity to chemotherapy. Methods The items were tested on 114 participants (57 cancer patients and a matched control group), alongside questions on autonomic regulation (aR), the Hospital Anxiety and Depression Scale (HADS), self-regulation (SRQ) and Karnofsky the Performance-Index (KPI). A retest of 65 participants was carried out after a median time span of four weeks. In the second part of the study, the ICS was used to assess internal coherence during chemotherapy in 25 patients with colorectal carcinoma (CRC) and 17 breast cancer patients. ICS was recorded before, during and 4 – 8 weeks after treatment. Results The 10-item scale of 'internal coherence' (ICS) shows good to very good reliability: Cronbach-α r = 0.91, retest-reliability r = 0.80. The ICS correlates with r = 0.43 – 0.72 to the convergence criteria (all p < 0.001). We are able to show decreased ICS-values after the third cycle for CRC and breast cancer patients, with a subsequent increase of ICS scores after the end of chemotherapy. Conclusion The ICS has good to very good reliability, validity and sensitivity to chemotherapy.

Background: Recent advancements in cancer treatment have shown the potential of immune checkpoint blockade (ICB) plus Viscum album L. therapy in improving survival rates for patients with advanced or metastatic non-small-cell lung cancer (NSCLC). The objective of this study was to investigate factors associated with improved survival in NSCLC patients treated with a combination of ICB and abnobaViscum ® . Methods : Patients with advanced or metastatic NSCLC from the accredited Network Oncology registry were included in this real-world data study adhering to ESMO-GROW criteria with ethics approval. Survival outcomes were compared between patients receiving ICB therapy alone versus those receiving combinational ICB plus abnobaViscum ® therapy using Kaplan-Meier and multivariable Cox proportional hazard analysis. Results : Among 300 patients (median age 68 years; male/female ratio 1.19), 222 received ICB alone (CTRL group) and 78 received combinational therapy (COMB group). Overall survival was significantly prolonged in the COMB group by 7 months compared to CTRL (13.8 months vs. 6.8 months, p = 0.005) with a survival rate of 16.5% in the COMB group vs. 8.0% in the CTRL group. In programmed death-ligand 1 positive (≥1%) patients treated with first-line ICB, the addition of abnobaViscum ® reduced the adjusted hazard of death by 75% (aHR: 0.25; 95%CI: 0.11-0.60, p = 0.02). Conclusions : The addition of abnobaViscum ® to ICB is significantly associated with improved survival in patients with advanced or metastatic NSCLC patients, irrespective of age, stage, Eastern cooperative oncology group status, surgery, or radiation. Potential mechanisms include immune modulation, reduced primary ICB resistance, and tumor microenvironment modifications. The findings warrant further validation in randomized controlled trials or registry-based randomized controlled trials. Trial registration: The study was registered (DRKS00013335).

Immunotherapy with PD-1/PD-L1 inhibitors has significantly improved the survival rates of patients with metastatic non-small-cell lung cancer (NSCLC). Results of a real-world data study investigating add-on VA ( Viscum album L.) to chemotherapy have shown an association with the improved overall survival of patients with NSCLC. We sought to investigate whether the addition of VA to PD-1/PD-L1 inhibitors in patients with advanced or metastasised NSCLC would have an additional survival benefit. In the present real-world data study, we enrolled patients from the accredited national registry, Network Oncology, with advanced or metastasised NSCLC. The reporting of data was performed in accordance with the ESMO-GROW criteria for the optimal reporting of oncological real-world evidence (RWE) studies. Overall survival was compared between patients receiving PD-1/PD-L1 inhibitor therapy (control, CTRL group) versus the combination of anti-PD-1/PD-L1 therapy and VA (combination, COMB group). An adjusted multivariate Cox proportional hazard analysis was performed to investigate variables associated with survival. From 31 July 2015 to 9 May 2023, 415 patients with a median age of 68 years and a male/female ratio of 1.2 were treated with anti-PD-1/PD-L1 therapy with or without add-on VA. Survival analyses included 222 (53.5%) patients within the CRTL group and 193 (46.5%) in the COMB group. Patients in the COMB group revealed a median survival of 13.8 months and patients in the CRTL group a median survival of 6.8 months (adjusted hazard ratio, aHR: 0.60, 95% CI: 0.43-0.85, p = 0.004) after adjustment for age, gender, tumour stage, BMI, ECOG status, oncological treatment, and PD-L1 tumour proportion score. A reduction in the adjusted hazard of death by 56% was seen with the addition of VA (aHR 0.44, 95% CI: 0.26-0.74, p = 0.002) in patients with PD-L1-positive tumours (tumour proportion score > 1%) treated with first-line anti-PD-1/PD-L1 therapy. Our findings suggest that add-on VA correlates with improved survival in patients with advanced or metastasised NSCLC who were treated with PD-1/PD-L1 inhibitors irrespective of age, gender, tumour stage, or oncological treatment. The underlying mechanisms may include the synergistic modulation of the immune response. A limitation of this study is the observational non-randomised study design, which only allows limited conclusions to be drawn and prospective randomised trials are warranted.

Background: Baseline quality of life (bQL) has been shown to be a predictor of the clinical outcome of oncological patients. The primary objective of the present study was to examine the role of bQL as a treatment predictor in oncological patients., Methods: In this prospective study, all-stage cancer patients registered in the Network Oncology registry were enrolled, and their bQL at diagnosis was evaluated., Results: Five hundred and thirty-eight oncological patients were eligible (median age 64 years). We show that survival-predicting bQL variables such as pain, low physical functioning or financial burden at tumor diagnosis were linked to lower systemic treatment ( p = 0.03), reduced surgery ( p = 0.007) or reduced oncological treatment compliance (0.01), respectively. Lastly, female gender and older cancer patients exhibited a tempered bQL., Conclusion: Our study is one of the first to reveal that bQL at tumor diagnosis is significantly associated with the prediction of oncological treatment with distinctive age- and gender-related patterns. Our results emphasize the need to address the physical, psychosocial, and financial burden of cancer patients prior to their oncological treatment with respect to age and gender. The associations found here pave the way for early integration of patient-reported outcomes into oncological supportive concepts.

Background: Chronic cancer-related fatigue is difficult to manage in breast cancer survivors. The tango trial showed that a six-week tango Argentino program was effective in reducing fatigue and improving quality of life, and here we investigated the sustainability of this tango program for breast cancer survivors., Methods: Stage I-III breast cancer survivors with increased fatigue symptoms were analyzed. The fifty participants in the tango trial were compared with a control cohort ( n = 108) who did not participate in the tango program. Using the European Organization for Research and Treatment of Cancer Questionnaire C30 (EORTC-QLQ-C30) and the German version of the cancer fatigue scale (CFS-D) self-reported quality of life parameters were assessed and longitudinal changes, correlations, and association factors were calculated., Results: Significant improvements in fatigue ( p = 0.006), physical functioning ( p = 0.01), and diarrhea ( p = 0.04) persisted in the 50 Tango participants at 6 months, but not in the control cohort. Twelve months after joining the tango program, increased fatigue was associated with reduced sporting activities ( p = 0.0005), but this was not the case for tango dancing., Conclusions: The present results suggest that tango may be appropriate as a component of early supportive and follow-up care programs, to promote health-related quality of life and physical activity and also eventually to improve long-term clinical outcomes of breast cancer survivors., Trial Registration: Trial registration numbers DRKS00013335 on 27 November 2017 and DRKS00021601 on 21 August 2020 retrospectively registered.

Background: Due to advances in the fight against breast cancer, aesthetic aspects and the prevention of breast deformities are playing an important role in surgical procedures. Currently the main form of breast cancer surgery is breast-conserving surgery (BCS), and even if mastectomy (MAS) is required, oncoplastic surgery and reconstruction options can improve outcomes, including health-related quality of life (QoL) of cancer patients. The purpose of this study was to assess whether surgery options induce different outcomes in self-reported QoL in guide-line treated breast cancer patients of the Network Oncology (NO)., Methods: This prospective Real-World-Data (RWD) study was conducted using data from the NO-clinical registry. QoL was assessed by evaluation of the European Organization of Research and Treatment Health-Related Quality of Life Core Questionnaire scale (EORTC QLQ-C30). Association factors between type of surgery options, without or with immediate breast reconstructions the EORTC QLQ-C30-scales at baseline after surgery, 6, 12, and 24 months later were analyzed with adjusted multivariate regression analysis, considering age, cancer stage, and treatment regimens, using software R., Results: A total of 623 primary breast cancer patients (all tumor stages, median age 58 (ICR: 50-68) diagnosed and guide-line treated between 2013 and 2021), 524 BCS and 99 MAS, 24 of whom received immediate breast reconstruction (MBR), were eligible for analyses. Compared with BCS patients, MBR patients self-reported considerably lower global health, physical and social functioning, and higher burden of pain and financial difficulties at baseline. In later follow-up surveys, functional scales increased and symptoms decreased in all patients, and the differences between MAS and BCS equalized. Longitudinal analyses after 24 months were obtained from 258 patients and revealed that compared to 224 BCS, the 34 MAS patients reported increased social functioning (p = 0.04)., Conclusions: At 24 months after MAS, breast cancer patients' QoL improved compared with BCS, although impairments in QoL were reported immediately after MAS. A growing expertise in surgical procedures as well as supportive care is critical to optimizing patients' well-being. These findings may be considered when counseling breast cancer patients pre- and post-surgery., Trial Registration Number: DRKS00013335 on 27/11/2017 retrospectively registered., (© 2023. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Background: Persistent impairments of quality of life-in particular, cancer-associated fatigue-are a major limitation for breast cancer survivors. As physical activity and mindfulness interventions have been shown to be effective in reducing fatigue symptoms, we investigated the efficacy of a six-week Argentine tango program., Methods: A randomized controlled trial was conducted with 60 breast cancer survivors diagnosed with stage I-III tumors 12-48 months prior to study enrollment and who had increased symptoms of fatigue. The participants were randomly assigned with a 1:1 allocation to either the tango or the waiting group. The treatment consisted of six weeks of supervised weekly one-hour tango group-sessions. Self-reported fatigue and further quality of life parameters were assessed at baseline and six weeks post-baseline. Longitudinal changes, correlations, Cohen's D ( d ) effect sizes, and association factors were also calculated., Results: Superiority of the tango intervention over the waiting list control was found in terms of improvement in fatigue ( d = -0.64; 95%CI, -1.2 to -0.08; p = 0.03), especially cognitive fatigue. In addition, a superiority of the tango intervention over the waiting list was found in the improvement of diarrhea ( d = -0.69; 95%CI, -1.25 to -0.13; p = 0.02). A pooled pre-post analysis of the 50 participants completing the six-week tango program revealed a close to 10% improvement of fatigue ( p = 0.0003), insomnia ( p = 0.008) and further quality of life outcomes. Adjusted multivariate linear regression analyses revealed the greatest improvements for participants who were more active in sports. In particular, survivors who received endocrine therapies, were obese, or had no prior dance experience seemed to especially benefit from the tango program., Conclusions: This randomized controlled trial demonstrated that a six-week Argentine tango program improves fatigue in breast cancer survivors. Further trials are warranted to determine whether such improvements lead to better long-term clinical outcomes., Trial Registration: trial registration number DRKS00021601. Retrospectively registered on 21 August 2020.

Background: Lung cancer (LC) is associated with high mortality and poor quality of life (QoL). The disease as well as oncological treatments such as radiation and chemotherapy with adverse effects can impair the QoL of patients. Add-on treatment with extracts of Viscum album L. (white-berry European mistletoe, VA) has been shown to be feasible and safe and to improve the QoL of cancer patients. The aim of this study was to analyze the changes in QoL of LC patients being treated with radiation according to oncological guidelines and add-on VA treatment in a real-world setting., Methods: A real-world data study was conducted using registry data. Self-reported QoL was assessed by the evaluation of the European Organization of Research and Treatment Health-Related Quality of Life Core Questionnaire scale (EORTC QLQ-C30). Adjusted multivariate linear regression analyses were performed to analyze factors associated with changes in QoL at 12 months., Results: A total of 112 primary LC patients (all stages, 92% non-small-cell lung cancer, median age 70 (ICR: 63-75)), answered the questionnaires at first diagnosis and 12 months later. Assessment of 12 months changes in QoL revealed significant improvement of 27 points for pain (p = 0.006) and 17 points for nausea/vomiting (p = 0.005) in patients who received combined radiation and VA. In addition, significant improvements of 15 to 21 points for role (p = 0.03), physical (p = 0.02), cognitive (p = 0.04), and social functioning (p = 0.04) were observed in guideline treated patients receiving no radiation but add-on VA., Conclusions: Add-on VA therapy reveals supportive effects for the QoL of LC patients. Particularly in combination with radiation a significant reduction in pain and nausea/ vomiting has been observed. Trial registration The study received ethics approval and was retrospectively registered (DRKS00013335 on 27/11/2017)., (© 2023. The Author(s).)

Numerous clinical studies have been conducted to improve the outcomes of patients suffering from pancreatic cancer. Different approaches using targeted therapeutic strategies and precision medicine methods have been investigated, and synergies and further therapeutic advances may be achieved through combinations with integrative methods. For pancreatic tumors, a particular challenge is the presence of a microenvironment and a dense stroma, which is both a physical barrier to drug penetration and a complex entity being controlled by the immune system. Therefore, the state of immunological tolerance in the tumor microenvironment must be overcome, which is a considerable challenge. Integrative approaches, such as hyperthermia, percutaneous irreversible electroporation, intra-tumoral injections, phytotherapeutics, or vitamins, in combination with standard-oncological therapies, may potentially contribute to the control of pancreatic cancer. The combined application of standard-oncological and integrative methods is currently being studied in ongoing clinical trials. An actual overview is given here.

Background: Newer personalized medicines including targeted therapies such as PARP inhibitors and CDK 4/6 inhibitors have been shown to improve the survival of breast and gynaecological cancer patients. However, efficacy outcomes may be ham5pered by treatment discontinuation due to targeted therapy-related adverse drug reactions or resistance. Studies have suggested that add-on mistletoe ( Viscum album L., VA) improves the quality of life and ameliorates the cytotoxic side effects of standard oncological therapy in cancer patients. The primary objective of this real-world data study was to determine the safety profile of targeted therapy in combination with add-on Helixor ® VA therapy compared to targeted therapy alone in breast and gynecological cancer patients., Methods: The present study is a real-world data observational cohort study utilizing demographic and treatment data from the accredited national Network Oncology (NO) registry. The study has received ethics approval. The safety profile of targeted therapies with or without Helixor ® VA therapy and safety-associated variables were evaluated by univariate and adjusted multivariable regression analyses., Results: All stages of breast and gynecological cancer patients ( n = 242) were on average 54.5 ± 14.2 years old. One hundred and sixty patients (66.1%) were in the control (CTRL, targeted therapy) and 82 patients (33.9%) were in the combinational (COMB, targeted plus Helixor ® VA therapy) group. The addition of Helixor ® VA did not hamper the safety profile (χ 2 = 0.107, p -value = 0.99) of targeted therapy. Furthermore, no adverse events and a trend towards an improved targeted therapy adherence were observed in the COMB group., Conclusions: The present study is the first of its kind showing the applicability of Helixor ® VA in combination with targeted therapies. The results indicate that add-on Helixor ® VA does not negatively alter the safety profile of targeted therapies in breast and gynaecological cancer patients.

Real-world evidence (RWE) is increasingly involved in the early benefit assessment of medicinal drugs. It is expected that RWE will help to speed up approval processes comparable to RWE developments in vaccine research during the COVID-19 pandemic. Definitions of RWE are diverse, marking the highly fluid status in this field. So far, RWE comprises information produced from data routinely collected on patient's health status and/or delivery of health care from various sources other than traditional clinical trials. These sources can include electronic health records, claims, patient-generated data including in home-use settings, data from mobile devices, as well as patient, product, and disease registries. The aim of the present update was to review current RWE developments and guidelines, mainly in the U.S. and Europe over the last decade. RWE has already been included in various approval procedures of regulatory authorities, reflecting its actual acceptance and growing importance in evaluating and accelerating new therapies. However, since RWE research is still in a transition process, and since a number of gaps in this field have been explored, more guidance and a consented definition are necessary to increase the implementation of real-world data.

Background: The fulminant course of COVID-19, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents with a high mortality rate and still lacks a causative treatment. C-reactive protein (CRP) has been shown to increase dramatically during the disease progression and correlates with deleterious outcomes. Selective CRP apheresis can reduce circulating CRP levels fast and effective. Methods: Seven hospitalized patients with documented severe COVID-19 progression, elevated CRP plasma levels (>100 mg/L) and signs of respiratory failure were treated with CRP apheresis. Two to twelve CRP apheresis sessions were performed generally in 24 h time intervals and depending on CRP plasma levels. Results: All patients had comorbidities. CRP apheresis reduced CRP plasma levels by up to 84% within a few hours, without exhibiting side effects in any patient. Despite signs of severe lung infiltration in all patients, only one patient died. The other patients showed improvements within the chest X-ray after CRP apheresis and were able to recover regardless of intubation and/or ECMO (4 patients). All remaining six patients were discharged from the hospital in good clinical condition. Conclusions: This case series presents a mortality rate of only 14%, which is dramatically lower than expected from the presented CRP levels as well as comorbidities and ventilation requirements. Our clinical observations regarding the here presented seven patients support the hypothesis that CRP is a candidate to be therapeutically targeted in the early stage of severe COVID-19.

Purpose: Since 2008, guidelines recommend that patients with HER2-positive early breast cancer (BC) should receive adjuvant chemotherapy in combination with trastuzumab in Germany. However, recent studies highlight that a substantial share of patients do not receive trastuzumab. We investigate which patient characteristics are associated with a tumor board recommendation for trastuzumab in Breast Cancer Centers (BCC) certified by the German Cancer Society (DKG) and the German Society for Senology, and if the recommendation differs between BCCs., Materials and Methods: Multi-level modeling was performed using quality assurance data based on 3052 HER2-positive, operated patients with a first diagnosis of early BC treated between 2006 and 2019 in 17 BCCs in Germany to investigate whether trastuzumab recommendation varies with patient sex, age, and disease characteristics, as well as over time and across BCCs., Results: Tumor board recommendations for trastuzumab differ substantially between BCCs (intraclass correlation coefficient [ICC] null model: 0.11). Our final model (ICC 0.17, Akaike Information Criterion [AIC], 1328.0, R 2 0.69) shows that physicians in BCCs more often recommend trastuzumab to patients who are younger than 60 years and those with a recommendation for any additional therapy (chemotherapy, radiation or endocrine therapy) (all p < 0.05). Furthermore, there is a significant time-dependent increase of trastuzumab recommendations (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 1.31-1.46, p < 0.05)., Conclusion: In certified BCCs in Germany, guideline concordant trastuzumab recommendation is increasing since 2006 (positive cohort effect). Recommendation of trastuzumab for HER2-positive BC patients in BCCs is significantly associated with patients' age and the recommendations for other additional therapy strategies, apart from surgery. The quality assurance data analyzed do not include potentially relevant confounders, such as socioeconomic status or comorbidities., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: A majority of oncological patients apply add-on white-berry European mistletoe (Viscum album L., VA) extracts to reduce disease- and treatment-related symptoms and to improve health-related quality of life (HRQL). VA extracts exert various antitumor, pro-apoptotic, anti-proliferative, and immunomodulatory effects. Two current meta-analyses attribute life-prolonging and HRQL-improving properties to additive VA therapy. The aim of the present update was to review the current knowledge on VA extracts in clinical oncology. Hereby, we concentrated on studies with the highest clinical relevance in the field of lung, gastric, colorectal and pancreatic, gynaecological, as well as breast cancer applying the anthroposophical mistletoe preparations., Summary: The present update provides a brief overview regarding the use of VA preparations in clinical oncology reviewing current guidelines, systematic reviews, randomized controlled and real-world data studies. We have searched the pubmed.gov database of the National Library of Medicine with the search terms "mistletoe" and "cancer." We found good evidence of add-on VA therapy to improve the HRQL of patients with breast cancer (American Society of Clinical Oncology - endorsed Society for Integrative Oncology guideline) and of HRQL-improving and survival-prolonging properties of VA therapy in pancreatic cancer. In the field of gastrointestinal, gynaecological, and lung cancer, new or updating integrative and/or oncological guidelines should consider clear recommendations on integrative therapies including VA therapy. Nevertheless, further clinical and real-world data trials need to be performed in this field., Key Messages: Evidence for add-on VA treatment for the improved management of cancer and cancer-related side effects is accumulating. Patients with breast cancer: good evidence for add-on VA therapy to improve the HRQL of oncological patients. Patients with pancreatic cancer: good evidence for add-on VA to improve HRQL and prolong survival. Patients with gastrointestinal, gynaecological, and lung cancer: update of guidelines is recommended with regards to integrative oncological therapies including add-on VA., (© 2022 S. Karger AG, Basel.)

Background: The majority of breast cancer patients suffer from persistent impairments after completion of their primary oncological therapy. Cancer-related fatigue (CRF) in particular is a multidimensional syndrome having a profound negative impact on the quality of life. To counter CRF symptoms, physical activities are suggested as first-line interventions, mind-body therapies have been shown to be effective, and music therapy can also reduce anxiety and stress in breast cancer patients. Tango therapy that combines various elements can have an impact on physical, psychological, and cognitive abilities and could therefore have a beneficial effect on breast cancer patients. The purpose of this study is to investigate whether a 6-week tango module is suited as a therapeutic approach for people after primary breast cancer therapy to favorably influence their quality of life, especially CRF levels., Methods: Sixty patients with a diagnosis for stage I-III breast cancer 12-48 months before enrollment and with CRF (age > 18) will be recruited and randomized 1:1 to a tango or a waiting-list group. Movement concepts using elements of Argentine tango (self-awareness, musical and spatial perception, self-perception, playfulness, shared experience) will be examined with the participants during six consecutive weekly 1-h tango sessions. The primary outcome will be the improvement of CRF (German version of the Cancer Fatigue Scale), and the secondary outcomes will be the improvement in sleep quality (Pittsburgh Sleep Quality Index) and quality of life (EORTC-QLQ-C30). Patient-reported outcomes will be measured at baseline and 6 weeks later; follow-up will be performed 6, 12, and 24 months after baseline. An evaluation will be performed by means of descriptive data analyses., Discussion: Argentine tango, as a music-based movement therapy, can influence different skills and may improve several outcomes. The therapeutic use of Argentine tango in the care of breast cancer patients has not yet been reported. It is anticipated that participants receiving the tango module will have improved CRF, sleep, and quality of life scores compared to a waitlist control., Trial Registration: German Clinical Trials Registry (DRKS) DRKS00021601 . Retrospectively registered on 21 August 2020., (© 2021. The Author(s).)

With the coronavirus disease 2019 (COVID-19) cases peaking and health systems reaching their limits in winter 2020/21, schools remained closed in many countries. To better understand teachers' risk perception, we conducted a survey in Germany. Participants were recruited through various associations and invited to take part in a cross-sectional COVID-19-specific online survey. Descriptive statistical analysis was performed. Factors associated with teachers' fears of contracting the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) were evaluated with an adjusted multivariable regression analysis. The median age of the 6753 participating teachers was 43 years, and 77% were female. Most teachers worked in high schools (29%) and elementary schools (26%). The majority of participants (73%) feared contracting SARS-CoV-2 at school, while 77% intended to receive their COVID-19 vaccination. Ninety-eight percent considered students to pose the greatest risk. Female and younger teachers were significantly more anxious to get infected and teachers who opposed the re-opening of schools had significantly higher odds of being more anxious ( p < 0.001). To the authors' knowledge, this is the first study to describe teachers' risk perception of COVID-19 and their attitudes towards vaccinations in a nationwide survey. The anxiety correlates with the COVID-19 protection measures demanded and appears to be a driving factor rather than rational logic.

Background: Integrated social care may help to mitigate social risk factors in order to achieve more equitable health outcomes. In cancer centers certified according to the criteria set out by the German Cancer Society, every patient must be given low-threshold access to qualified social workers at the center for in-house social service counseling (SSC). Previous analyses have demonstrated large variation in the utilization of these services across individual centers. Therefore, this research aims at investigating whether SSC utilization varies regarding breast cancer patient characteristics and center characteristics presenting a unique approach of using routine data., Methods: Multilevel modeling was performed using quality assurance data based on 6339 patients treated in 13 certified breast cancer centers in Germany in order to investigate whether SSC utilization varies with patient sex, age, and disease characteristics as well as over time and across centers., Results: In the sample, 80.3% of the patients used SSC. SSC use varies substantially between centers for the unadjusted model (ICC = 0.24). Use was statistically significantly (P < .001) more likely in women, patients with invasive (in comparison to tumor in situ/ductal carcinoma in situ) diseases (P < .001), patients with both breasts affected (P = .03), patients who received a surgery (P < .001), patients who were diagnosed in 2015 or 2017 compared to 2016 (P < .001) and patients older than 84 years as compared to patients between 55 and 64 years old (P = .002)., Conclusion: The analysis approach allows a unique insight into the reality of cancer care. Sociodemographic and disease-related patient characteristics were identified to explain SSC use to some extent.

Background: Treatments with non-pharmacological interventions (NPIs), comprising art and exercise therapies, nursing interventions, and educational components, are considered to improve quality of life of cancer patients. The aim of this study was to assess the longitudinal changes in self-reported quality of life of breast cancer patients receiving an integrative medicine program consisting of hospital-based NPIs and standard oncological treatments., Methods: This real-world data study was conducted using data from the Network Oncology clinical registry of the Gemeinschaftskrankenhaus Havelhöhe. Primary breast cancer patients of all tumor stages, who answered the European Organization of Research and Treatment Health-Related Quality of Life Core Questionnaire scale (EORTC QLQ-C30) at first diagnosis and 12 months later, were included. Association factors between received NPIs and longitudinal EORTC QLQ-C30-changes were analyzed with additive non-parametric regression tests, considering treatment regimens and demographic variables, using the software R., Results: A total of 231 primary breast cancer patients were enrolled and separate regression analyses were carried out. Significant associations between the received NPIs elaborate consultations and life review, nursing compresses, music and eurythmy therapy and improvements of 8-13 points for global health, all five functional EORTC-scales, and symptoms fatigue, dyspnea, insomnia, and financial difficulties were observed., Conclusion: Our findings support the beneficial impact of NPIs for breast cancer patients. Further research could be directed towards synergistic effects of multimodal applied NPIs., Trial Registration: Trial registration number DRKS00013335 on 27/11/2017 retrospectively registered.

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.

Purpose: In the breast cancer center at the Gemeinschaftskrankenhaus Havelhöhe (GKH), integrative strategies are implemented in the routine care of breast cancer patients. The aim of this breast cancer real-world study was to systematically evaluate changes in patients' internal coherence and resilience, associated with the use of non-pharmacological interventions (NPIs)., Methods: This study included 231 primary breast cancer patients treated with standard oncological therapy and NPIs, which comprise art and movement therapies, nursing interventions, and educational components, and had answered the internal coherence scale (ICS) questionnaire at first diagnosis and 12 months later. Data were collected from the Network Oncology clinical registry of the GKH, and effects of NPIs on ICS changes were analyzed with adjusted linear multivariable regression analyses, using the software R., Results: Two hundred twenty breast cancer patients of all tumor stages were eligible for a total of 27 separate adjusted multivariable linear regression analyses. The NPIs elaborate consultations and life review (ECLR); nursing compresses, music therapy, and rhythmic massages were significantly associated with increases of about 2-point changes in inner resilience and coherence (p < 0.05). Furthermore, a significant association with an elevation of the thermo coherence was observed for the application of nursing compresses., Conclusions: The evaluation of real-world data carried out here shows that the application of the multimodal treatment concept can lead to an enhancement of the internal coherence and resilience in breast cancer patients. To improve the care of cancer patients, this multimodal program should be further expanded into routine clinical practices., Trial Registration: Trial registration number DRKS00013335 on 27/11/2017 retrospectively registered.

Background: For stage IV lung cancer patients receiving add-on Viscum album L. (VA) treatment an improved overall survival was detected. Information regarding cost-effectiveness (CE) for comparisons between chemotherapy (CTx) and CTx plus additive VA in stage IV lung cancer treatment is limited. The present study assessed the costs and cost-effectiveness of CTx plus VA (V) compared to CTx alone (C) for stage IV non-small cell lung cancer (NSCLC) patients treatment in a hospital in Germany., Methods: In the observational real-world data study, data from the Network Oncology clinical registry were utilized. Enrolled stage IV lung cancer patients received the respective therapy (C or V) in a certified German Cancer Center. Cost and cost-effectiveness analyses from the hospital's perspective were investigated on the basis of overall survival (OS) and routine financial controlling data. In addition, the incremental cost-effectiveness ratio (ICER) was calculated. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis., Results: 118 patients (C: n = 86, V: n = 32) were included in the analysis, mean age 63.8 years, the proportion of male patients was 55.1%. Adjusted hospital's total mean costs for patients from the C and V group were €16,289, 95%CI: 13,834€-18,744€ (over an adjusted mean OS time of 13.4 months) and €17,992, 95%CI: 13,658-22,326 (over an adjusted mean OS time of 19.1 months), respectively. The costs per additional OS year gained (ICER) with the V-therapy compared to C therapy were €3,586., Conclusion: The findings of the present study suggest that the combined use of chemotherapy and VA was clinically effective and comparably cost-effective to chemotherapy alone in our analysed patient sample from the hospital's perspective. Further randomized and prospective cost-effectiveness studies are necessary to complement our findings., Competing Interests: CG reports grants from Iscador AG, outside the submitted work. BM received fees for lectures or advisory boards from AstraZeneca GmbH, Boehringer Ingelheim AG & Co. KG, Helixor Heilmittel GmbH, Kyowa-Kirin GmbH, Leo GmbH, Lilly Deutschland GmbH, Roche Deutschland Holding GmbH, Teva GmbH outside the submitted work. BM received grants for travelling from AstraZeneca GmbH, BMS GmbH & Co. KG, Boehringer Ingelheim AG & Co. KG, Celgene GmbH, Helixor Heilmittel GmbH, Iscador AG, Jannsen, Kyowa-Kirin GmbH, Leo, Lilly, Novartis, MSD Sharp & Dohme GmbH, Pfizer Deutschland GmbH, Roche Deutschland Holding GmbH, Teva GmbH, outside the submitted work. FS reports grants from ABNOBA GmbH, AstraZeneca GmbH, Helixor Heilmittel GmbH and Iscador AG outside the submitted work. Grants from AstraZeneca GmbH and Helixor Heilmittel GmbH include travel costs and honoraria for speaking. HM is a member of the board of directors of Weleda AG and a member of the Network Arbeitsgemeinschaft der Wissenschaftlichen Fachgesellschaften (AWMF e.V.) guideline committee for integrative oncology (Guideline for Complementary Medicine in the Treatment of Oncological Patients). HM has an endowed professorship at the Charité Universitätsmedizin Berlin, which is financed by the Software AG Foundation, outside the submitted work. The Network Oncology was funded by unrestricted research grants from Iscador AG Arlesheim, Switzerland; ABNOBA GmbH Pforzheim, Germany; and Helixor GmbH Rosenfeld, Germany. The funders had no role in study design, data collection, analysis, decision to publish, or preparation of the manuscript. By contract, researchers were independent from the funder. There are no other relevant declarations relating to employment and consultancy to declare. There are no patents, products in development or marketed products to declare. There are no other relationships/conditions/circumstances that present a potential conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials. No payment was received for any other aspects of the submitted work. The other authors have declared that no competing interests exist.

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., Competing Interests: FS reports grants from ABNOBA GmbH, AstraZeneca GmbH, Helixor Heilmittel GmbH, and Iscador AG, outside the submitted work. Dr. Grah reports grants from Iscador AG, outside the submitted work. Grants from AstraZeneca GmbH and Helixor Heilmittel GmbH include travel costs and honoraria for speaking. BM reports grants from AstraZeneca GmbH, Boehringer Ingelheim AG & Co. KG, Helixor Heilmittel GmbH, Kyowa-Kirin GmbH, Leo GmbH, Lilly Deutschland GmbH, Roche Deutschland Holding GmbH, Teva GmbH, BMS GmbH & Co. KG, Celgene GmbH, Iscador AG, Janssen-Cilag GmbH, Novartis Pharma GmbH, MSD Sharp & Dohme GmbH, and Pfizer Deutschland GmbH, outside the submitted work. There are no other relationships/conditions/circumstances that present a potential conflict of interest. There are no patents, products in development, or marketed products to declare. No payment was received for any other aspects of the submitted work. The other authors declared that no conflicts of interest exist., (Copyright © 2020 Anja Thronicke et al.)

Background: For patients receiving add-on Viscum album L. (VA) treatments for late-stage pancreatic cancer, an improved overall survival (OS) was observed. Only limited information regarding cost-effectiveness (CE) for comparisons between standard of care and standard of care plus add-on VA in stage IV pancreatic cancer treatment is available. The present study assessed the costs and cost-effectiveness of standard of care plus VA (V) compared to standard of care alone (C) for a hospital in Germany., Methods: An observational study was conducted using data from the Network Oncology clinical registry. Patients included had stage IV pancreatic cancer at diagnosis and received C or V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis., Results: 88 patients ( C or n  = 34; V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. n  = 34; C or V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. C or V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. C or V treatment in a certified German Cancer Center. Cost and cost-effectiveness analyses (CEA) including the analysis of the incremental cost-effectiveness ratios (ICER) were performed from the hospital's perspective based on routine data from the financial controlling department and observed data on OS. The primary result of the analysis was tested for robustness in a bootstrap-based sensitivity analysis. C or., Conclusion: Based on this CEA analysis, from the hospital's point of view, the costs per mean month of OS and per mean hospital stay were lower for patients under combinational standard of care plus VA compared to patients receiving standard of care alone for the treatment of stage IV pancreatic cancer. Further prospective cost-effectiveness studies are mandatory to reevaluate our findings., Competing Interests: FS reports grants from Helixor Heilmittel GmbH, grants from Abnoba GmbH, grants from Iscador AG, and grants from AstraZeneca outside the submitted work. Grants from Helixor Heilmittel GmbH and AstraZeneca included travel costs and honoraria for speaking. There are no other relationships/conditions/circumstances that present a potential conflict of interest. There are no patents, products in development, or marketed products to declare. No payment was received for any other aspects of the submitted work. The other authors have declared that no conflicts of interest exist., (Copyright © 2020 Anja Thronicke et al.)

Background: Up to 88% of oncological patients apply complementary therapies and up to 77% apply complementary mistletoe therapy in the context of integrative oncological approaches. An evidence-based consultation of oncological health professionals regarding complementary therapies used in Germany is missing. Therefore, a new S3-Guideline for Complementary Medicine in the Treatment of Oncological Patients is under development and is anticipated to be finalized in November 2020. It will be based on evidence-based publications and systematic reviews on complementary therapies in oncology. A recently published two-part systematic review on mistletoe treatment in oncology has been reevaluated., Methods: The latest published systematic two-part review on mistletoe has been systematically proofread and checked in compliance with the Cochrane Handbook for Systematic Reviews of Intervention and the AMSTAR 2 (A MeaSurement Tool to Assess Systematic Reviews) tool., Results: The here discussed two-part review is incomplete, lacks sound accuracy including insufficient assessment of the risk of bias, and contains imprecise statements. In addition, it does not sufficiently comply with the Cochrane Handbook for Systematic Reviews of Intervention and the AMSTAR 2 tool., Conclusion: In view of the approaching release of a new guideline in the field of complementary therapies in oncology, the present statement draws attention to a lack of profound methodology of conductance of a recently released systematic review on mistletoe. In consequence, a comprehensive overview of published mistletoe studies, i.e., a meta-analysis with a sound methodology of conductance, is necessary., Competing Interests: HM is a member of the board of directors of Weleda AG and a member of the Network Arbeitsgemeinschaft der Wissenschaftlichen Fachgesellschaften (AWMF e.V.) guideline committee for integrative oncology (Guideline for Complementary Medicine in the Treatment of Oncological Patients). HM has an endowed professorship at the Charité Universitätsmedizin Berlin, which is financed by the Software AG Foundation, outside the submitted work. FS reports grants from Helixor Heilmittel GmbH, grants from Abnoba GmbH, grants from Iscador AG, outside the submitted work; grants from Helixor Heilmittel GbmH include travel costs and honoraria for speaking. RoHu reports honoraria for speaking from Helixor Heilmittel GmbH, outside the submitted work. TB is the chair of the commission C (human medicine area and anthroposophic therapy approach) at the competent German national authority, the German Federal Institute for Drugs and Medical Devices (BfArM, Bundesinstitut für Arzneimittel und Medizinprodukte) and president of the International Federation of Anthroposophic Medical Associations (IVAA). The other authors have declared that no competing interests exist. No payment was received for any other aspects of the submitted work. There are no patents, products in development, or marketed products to declare. There are no other relationships/conditions/circumstances that present potential conflicts of interest., (Copyright © 2020 Harald Matthes et al.)

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.

Introduction: Cancer-related fatigue (CRF) occurs frequently in breast cancer patients. The aim of this real-world study was to analyze the longitudinal changes of CRF in breast cancer patients receiving an integrative medicine program, which includes the application of non-pharmacological interventions (NPIs) and Viscum album L. (VA) extracts., Methods: All data were collected from the clinical register of the Network Oncology of a German certified breast cancer center of the Gemeinschaftskrankenhaus Havelhöhe (GKH). Primary breast cancer patients, treated upon initial diagnosis with integrated NPIs, comprising art and exercise therapy, nursing interventions, and educational components, during their hospital stay, and who had answered the German Cancer-Fatigue Scale (CFS-D) questionnaire at first diagnosis and 12 months later, were included. The associations between NPIs and CFS-D changes were analyzed with adjusted multivariable regression analyses, considering received treatment regimens and demographic variables, using the software R., Results: 231 female breast cancer patients of all tumor stages were evaluated. While chemotherapy exhibited significant severe deterioration, add-on VA applications seem to partially mitigate this impairment on CRF. 36 separate multivariable regression analyses for all NPIs showed that in particular significant associations between CFS-D improvements and the interventions nursing compresses (6 point change; P  = .0002; R ² = 28%) or elaborate consultations and life review (ECLR) (4 point change; P  = .0002; R ² = 25%) were observed., Conclusions: Breast cancer patients benefit from a hospital-based integrative medicine program. To alleviate fatigue symptoms during oncological therapy, an expansion of this concept should be developed in the future.

Background: Recent data suggest a beneficial effect of add-on treatment with Viscum album L (VA) on the survival in cancer patients. The objective of this study was to compare the impact of standard oncological therapy plus add-on VA treatment (S+VA) versus standard oncological therapy alone (S) on the overall survival (OS) of patients with nonmetastasized non-small cell lung carcinoma (NSCLC)., Methods: The multicenter real-world data study was conducted using data from the Network Oncology Clinical Registry. The primary end point was OS. OS and impact on hazard in both treatment groups were compared., Results: A total of 275 patients with stages I to IIIA NSCLC were enrolled (mean age = 67.6 years, 57.2% male patients). No significant difference of OS was observed between both groups. Even though not significant, for a subgroup of unresected patients with stage I NSCLC, adenocarcinoma or squamous cell carcinoma, a medium effect size OS improvement was observed for S+VA compared to S., Conclusions: Our findings support the importance of surgery as the most effective intervention in nonmetastasized NSCLC patients. Add-on VA therapy shows here no additional effect in resected patients. However, a small subgroup analysis suggests a possible role of add-on VA for nonresected subgroups. Our results complement existing knowledge on the clinical impact of add-on VA therapy in NSCLC patients and may serve as hypothesis-generating data for further examinations in this cohort. Further research could be directed towards the role of combined therapy for nonresected early-stage NSCLC.

In early tumor development, cancer cells develop a plethora of strategies to escape surveillance from the adaptive and innate immune system. Cancer immunotherapies, in particular immune checkpoint inhibitors, are becoming a highly promising cancer therapeutic approach that has remarkable increased progress in combating various cancer types. Unfortunately, their mechanisms of action induce some complications, such as inflammatory reactions and immune-related adverse events. In the management of side effects during anticancer therapy, complementary and integrative therapy approaches are becoming of growing interest. Particularly, mistletoe, Viscum album L. (VA), has a long traditional history of about 100 years as an add-on therapy of cancer treatment in German-speaking countries. Besides antitumoral and quality of life-promoting activities, VA applications reduce side effects of modern conventional anticancer therapies and exert immunomodulatory characteristics. As these properties may provide a good basis for a combination with modern oncological therapies, the biological activities of VA applications and mechanisms involved have to be understood. In this review, the impact of VA compounds on different cellular pathways and immunological reactions in the fight against cancerous cells is discussed.

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.

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., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

Background : Despite improvement of tumor response rates, targeted therapy may induce toxicities in cancer patients. Recent studies indicate amelioration of adverse events (AEs) by add-on mistletoe ( Viscum album L., VA) in standard oncological treatment. The primary objective of this multicenter observational study was to determine the safety profile of targeted and add-on VA therapy compared to targeted therapy alone. Methods : Demographic and medical data were retrieved from the Network Oncology registry. Allocation to either control (targeted therapy) or combinational group (targeted/add-on VA) was performed. Safety-associated variables were evaluated by adjusted multivariable analyses. Results : The median age of the study population ( n = 310) at first diagnosis was 59 years; 67.4% were female. In total, 126 patients (40.6%) were in the control and 184 patients (59.4%) in the combination group. Significant differences were observed between both groups with respect to overall AE frequency (χ² = 4.1, p = 0.04) and to discontinuation of standard oncological treatment (χ² = 4.8, p = 0.03) with lower rates in the combinational group (20.1%, 35% respectively) compared to control (30.2%, 60.5%, respectively). Addition of VA to targeted therapy significantly reduced the probability of oncological treatment discontinuation by 70% (Odds ratio (OR) 0.30, p = 0.02). Conclusions : Our results indicate a highly significant reduction of AE-induced treatment discontinuation in all-stage cancer patients when treated with VA in addition to targeted therapy.

Background: Stage IV non-small cell lung cancer (NSCLC) is associated with a five-year survival rate of around 1%. Treatment with Viscum album L. (VA) extracts has been shown to reduce chemotherapy (CTx)-related adverse events, decrease CTx dose reductions and improve quality of life in a number of cancers. Recent data suggest a beneficial effect of add-on treatment with Viscum album L. (VA, European mistletoe) on survival in cancer patients. The objective of this study was to evaluate the effect of VA in addition to chemotherapy on survival in stage IV NSCLC patients., Methods: The observational study was conducted using data from the Network Oncology clinical registry which is an accredited conjoint clinical registry of German oncological hospitals, practitioners and out-patient centers.Patients were included if they had stage IV NSCLC at diagnosis, lived at least for four weeks post-diagnosis and received chemotherapeutic treatment. Patients with EGFR mutations as well as patients receiving tyrosine kinase inhibitors or immune checkpoint inhibitors were not included. Overall survival and impact on hazard in patients with chemotherapy (CTx) to patients receiving CTx plus VA were compared. To identify factors associated with survival and to address potential sources of bias a multivariate analyses using Cox proportional hazard model was performed., Results: The median age of the population was 64.1 years with 55.7% male patients. The highest proportion of patients had adenocarcinoma (72.2%) and most of the patients were current or past smokers (70.9%). Of 158 stage IV NSCLC patients, 108 received CTx only and 50 additional VA. Median survival was 17.0 months in the CTx plus VA group (95%CI: 11.0-40.0) and was 8.0 months (95%CI: 7.0-11.0) in the CTx only group (χ2 = 7.2, p = .007). Overall survival was significantly prolonged in the VA group (HR 0.44, 95%CI: 0.26-0.74, p = .002). One-year and three-year overall survival rates were greater with CTx plus VA compared to CTX alone (1y: 60.2% vs. 35.5%; 3y: 25.7% vs. 14.2%)., Conclusion: Our findings suggest that concomitant VA is positively associated with survival in stage IV NSCLC patients treated with standard CTx. These findings complement pre-existing knowldedge of add-on VA's clinical impact, however, results should be interpreted with caution in light of the study's observational character., Competing Interests: Dr. Schad reports grants from Helixor Heilmittel GmbH, grants from Abnoba GmbH, grants from Iscador AG, outside the submitted work. Dr. Grah reports grants from Iscador AG, outside the submitted work. Grants from Helixor Heilmittel GmbH include travel costs and honoraria for speaking. There are no other relationships/conditions/circumstances that present a potential conflict of interest. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. No payment was received for any other aspects of the submitted work. The other authors have declared that no competing interests exist.