Anja Thronicke

Prospective multicenter German study on pulmonary colonization with Scedosporium /Lomentospora species in cystic fibrosis: Epidemiology and new association factors

Background An increasing rate of respiratory colonization and infection in cystic fibrosis (CF) is caused by fungi of the Scedosporium apiospermum species complex or Lomentospora prolificans (Sac-Lp). These fungi rank second among the filamentous fungi colonizing the CF airways, after Aspergillus fumigatus. However, the epidemiology, clinical relevance and risk of pulmonary colonization with Sac-Lp are rarely understood in CF. The objective of the present prospective multicenter study was to study pathogen distribution and determine association factors of pulmonary Sac-Lp colonization in patients with CF. Material and methods Clinical, microbiological and laboratory data of 161 patients aged 6–59 years with CF in Germany were analyzed for Sac-Lp distribution and association factors. The free statistical software R was utilized to investigate adjusted logistic regression models for association factors. Results Of the 161 patients included in the study, 74 (56%) were male. The median age of the study cohort was 23 years (interquartile range 13–32 years). 58 patients of the total cohort (36%) were < 18 years old. Adjusted multivariate regression analysis revealed that Sac-Lp colonization was associated with younger age (OR 0.8684, 95%CI: 0.7955–0.9480, p<0.005) and less colonization with H. influenzae (OR 0.0118, 95%CI: 0.0009–0.1585, p<0.001). In addition, Sac-Lp-colonized patients had more often allergic bronchopulmonary aspergillosis (ABPA) (OR 14.6663, 95%CI: 2.1873–98.3403, p<0.01) and have been colonized more often with the mucoid phenotype of Pseudomonas aeruginosa (OR 9.8941, 95%CI: 1.0518–93.0705, p<0.05). Conclusion Newly found association of ABPA and Pseudomonas revealed new probable risk factors for Sac-Lp colonization. Allergy might play a role in inducing immunologic host reactions which lead to a less effective response to species of Sac-Lp.

Allergic bronchopulmonary aspergillosis is associated with pet ownership in Cystic Fibrosis

Late diagnosis of allergic bronchopulmonary aspergillosis (ABPA) is associated with significant lung function decline and morbidity in cystic fibrosis (CF). The association of ABPA and domestic pet ownership in patients with CF has not been elucidated yet. Our objective was to determine the association of ABPA with pet ownership in patients with CF.

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.

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 patients enrollment in studies the CC GKH performs above nationwide benchmarks. Research outcomes including safety issues, clinical impact as well as patients health-related quality of life are continuously evaluated and integrated into hospitals 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.

Immune-related and adverse drug reactions to low versus high initial doses of Viscum album L. in cancer patients

BACKGROUND Immune-related adverse drug reactions (ADRs) to immunotherapy agents have been associated with beneficial clinical outcomes in oncology. Viscum album L. (VA, European mistletoe) is frequently used as an immunomodulatory agent alongside conventional cancer treatment in Europe. VA has been associated with improved quality of life and a reduction in chemotherapy-related ADRs. Beneficial effects of VA are believed to be related to its immunomodulatory properties. Current guidelines recommend commencing with a low dose and increasing slowly overtime, however, off-label prescribing of high initial doses is common. PURPOSE We investigated ADR profiles related to subcutaneous VA therapy commencing with low, recommended doses versus higher than recommended doses. STUDY DESIGN Retrospective cohort study. METHODS Medical records of 1361 cancer patients treated between 2003 and 2013 were assessed. Patients were divided into two groups based on whether the dose of their first VA injection adhered to current guidelines. Patient characteristics and suspected VA-related ADRs were compared between dose groups. RESULTS Of 1361 cancer patients, 516 (38%) started with a recommended, low dose of VA(≤0.02 mg) and 845 (62%) started with a higher dose(>0.02 mg). Groups did not differ by age or gender, but significant differences were observed for type (p < 0.001) and stage of cancer (p = 0.05). Starting with a high dose of VA was significantly associated with a higher incidence of VA-related ADRs compared to starting with a low dose (20.7% versus 0.8%, p < 0.001). Adjusting for age, gender, tumour type and stage of disease, produced an odds ratio of 37.5 (95% CI = 15.7-122.8, p < .001). Almost all ADRs, irrespective of the initial VA dose, were of mild or moderate intensity. Most ADRs were immune-related, general disorders and administration site conditions, many of which are desired reactions, such as pyrexia and local reactions. Overall, no serious ADRs occurred. CONCLUSIONS Starting VA therapy with a higher than recommended dose was associated with a high frequency of ADRs, however, nearly all ADRs were expected, of mild to moderate intensity and most were desired reactions. Future research is necessary to investigate whether higher incidences of immune-related events are indicators of beneficial immunomodulation and better clinical outcomes.

Impact of Long-Term Tiotropium Bromide Therapy on Annual Lung Function Decline in Adult Patients with Cystic Fibrosis.

Background Chronic lung disease is the leading cause of death in patients with Cystic Fibrosis (CF) and is often treated with bronchodilators. It is not known whether long-term tiotropium bromide treatment may have a positive impact on lung function. Methods This retrospective cohort study estimated annual lung function decline utilizing longitudinal data for forced expiratory volume in 1 s (FEV1). Results A total of 160 adult patients with CF were analyzed. The subjects treated for 24 months with tiotropium bromide had a significantly slower decline of mean annual change of FEV1 (treated: -0.3±4.0%; control: -2.3±5.0%; p = 0.0130). In patients with FEV1 ≥70% predicted, long-term tiotropium bromide treatment was associated with greater improvements in annual lung function decline (FEV1 ≥70% predicted: treated: +0.5±4.7%; control: -4.0±6.3%; p = 0.0132; FEV1 50–69% predicted: treated: -0.5±4.4%; control: -0.8±3.8%; p = 0.7142; FEV1 ≤49% predicted: treated: -0.6±3.4%; control: -2.4±4.8%; p = 0.0898). Conclusion This study suggests that long-term tiotropium bromide treatment may be associated with reduced annual decline of FEV1 in patients with CF, particularly in adults with a mild degree of severity.

Overall survival of stage IV non-small cell lung cancer patients treated with Viscum album L. in addition to chemotherapy, a real-world observational multicenter analysis

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.

Clinical Safety of Combined Targeted and Viscum album L. Therapy in Oncological Patients

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.

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.

136 Long-term tiotropium bromide therapy was retrospectively analyzed in adults with cystic fibrosis

Objectives The chronic and life-limiting pulmonary disease caused by cystic fibrosis is often treated with bronchodilators. We investigated, for the first time, the effect of 24 months long-term tiotropium bromide therapy in people with cystic fibrosis on pulmonary lung function and risk of exacerbation. Methods In this retrospective cohort study, we compare 24 months of tiotropium bromide therapy with a non-tiotropium bromide treated control group. Data was obtained from local patient registry (MUKO.doc). Forty-nine patients with 18 mg once-daily inhaled tiotropium bromide therapy were selected. Forty-nine non-tiotropium bromide treated control patients were identified and matched by gender, age and forced expiratory volume in 1 second at the beginning of 24 month observation period (FEV1 0M ). The primary end point was the mean annual change of FEV1. The secondary end point included measures of exacerbation. Results The study included 98 patients, divided into tiotropium bromide treated (n = 49) and non-tiotropium bromide treated control patients (n = 49). Patients treated with tiotropium bromide showed an improvement of 0.6% of mean annual change of FEV1 (control: −1.0±5.0%; treated: +0.6±4.2%). Furthermore, tiotropium bromide therapy was associated with a slightly lower exacerbation risk. Mean annual change of number of exacerbations was improved in tiotropium bromide treated patients (control: +0.2±1.8; treated: −0.1±1.9). Tiotropium bromide was well tolerated in all patients. Conclusion In patients with cystic fibrosis, long-term therapy with tiotropium bromide was associated with a positive tendency in lung function and exacerbation risk.