Routine treatment of patients with chronic lymphocytic leukaemia by office-based haematologists in Germany-data from the Prospective Tumour Registry Lymphatic Neoplasms.

Various treatment options exist for patients with chronic lymphocytic leukaemia (CLL). Clinical registries provide insight into routine treatment and identify changes in treatment over time. The Tumour Registry Lymphatic Neoplasms prospectively collects data on the treatment of patients with lymphoid B-cell neoplasm as administered by office-based haematologists in Germany. Data on patient and tumour characteristics, co-morbidities, systemic treatments, and outcome parameters are recorded. Eight hundred and six patients with CLL were recruited between May 2009 and August 2013. At the start of first-line treatment, median age was 71 years, 64% were male, and 44% had a Binet stage C disease. The most frequently used first-line/second-line regimens were bendamustine + rituximab (BR, 56%/55%), fludarabine + cyclophosphamide + rituximab (FCR, 22%/11%), and bendamustine (B, 5%/9%). Chlorambucil was used in only 7% (first-line) and 6% (second-line) of patients. Patients treated with FCR were younger and healthier than patients treated with BR. Overall, 91% of first-line treatments were successful (40% complete response). Real-life patient populations differ considerably from patients treated in randomized controlled trials. BR and FCR dominate the first-line and second-line treatments of CLL by office-based haematologists in Germany. Future analysis will investigate progression-free and overall survival times.

Safety of higher dosages of Viscum album L. in animals and humans--systematic review of immune changes and safety parameters.

BACKGROUND: Viscum album L extracts (VAE, mistletoe) and isolated mistletoe lectins (ML) have immunostimulating properties and a strong dose-dependent cytotoxic activity. They are frequently used in complementary cancer treatment, mainly to improve quality of life, but partly also to influence tumour growth, especially by injecting VAE locally and in high dosage. The question is raised whether these higher dosages can induce any harm or immunosuppressive effects. METHODS: Systematic review of all experiments and clinical studies investigating higher dosages of VAE in animals and humans (Viscum album > 1 mg in humans corresponding to > 0.02 mg/kg in animals or ML > 1 ng/kg) and assessing immune parameters or infections or adverse drug reactions. RESULTS: 69 clinical studies and 48 animal experiments reported application of higher doses of VAE or ML and had assessed immune changes and/or harm. In these studies, Viscum album was applied in dosages up to 1500 mg in humans and 1400 mg/kg in animals, ML was applied up to 6.4 µg/kg in humans and in animals up to 14 µg/kg subcutaneously, 50 µg/kg nasally and 500 µg/kg orally. A variety of immune parameters showed fluctuating or rising outcomes, but no immunosuppressive effect. Side effects consisted mainly of dose-dependent flu-like symptoms (FLS), fever, local reactions at the injection site and various mild unspecific effects. Occasionally, allergic reactions were reported. After application of high doses of recombinant ML, reversible hepatotoxicity was observed in some cases. CONCLUSIONS: Application of higher dosages of VAE or ML is not accompanied by immunosuppression; altogether VAE seems to exhibit low risk but should be monitored by clinicians when applied in high dosages.

A brief instrument to measure health-related quality-of-life in patients with bone metastasis: validation of the German version of Bone Metastases Quality-of-Life-10 (BOMET-QoL-10).

AIMS: This prospective, epidemiologic study was designed to translate the original Spanish Bone Metastases Quality-of-Life-10 (BOMET-QoL-10) questionnaire and undertake a validation of the translated German version of BOMET-QoL-10 in Germany to assess health-related quality-of-life (HRQoL) in patients with bone metastases (BM). METHODS: The translation process included forward and backward translations, and a linguistic validation. Patients aged ≥18 years with histological confirmation of cancer, diagnosed with BM, life expectancy ≥6 months, and fluency in German were eligible for this study (enrolled consecutively in 33 outpatient centers in Germany). Patients were given the German version of BOMET-QoL-10, together with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 and EORTC QLQ-BM22 questionnaires at inclusion, 6 weeks, 3 months, and 6 months after inclusion. A debriefing questionnaire was administered at inclusion to determine patient acceptability and understanding. RESULTS: Data include 364 patients with BM (median age = 68 years; females = 71.7%). The BOMET-QoL-10 is brief and clear (median completion time = 5 minutes; >90% of patients completed the questionnaire without assistance). The BOMET-QoL-10 forms only one overall scale. All 10 items showed a substantial correlation with the first factor (factor loading, range = 0.58-0.86). BOMET-QoL-10 exhibits high internal consistency and reproducibility (Cronbach's alpha = 0.91; intra-class correlation coefficient = 0.76). BOMET-QoL-10 showed significant correlations (range = 0.69-0.79) both with EORTC QLQ-C30 and EORTC QLQ-BM22 within the functioning (physical, social, interference) and symptom (fatigue, pain) scales, displayed significant sensitivity to change in EORTC QLQ-BM22 scores, and proved the potential ability to detect change in HRQoL in patients with different disease status. LIMITATIONS: There was a high proportion of females in this study, which might represent a limitation. CONCLUSIONS: The German version of BOMET-QoL-10 is a valid, reliable, brief, and clear instrument able to measure HRQoL in patients with BM.

The breast cancer-associated gene Di12 has oncogenic activity.

The breast cancer-associated gene Di12 encodes a novel protein, which was found overexpressed in invasive ductal carcinomas of the breast. In experiments designed to assess the role of the Di12 gene in oncogenesis, the overexpression of 339 N-terminal amino acids of this gene in NIH3T3 cells resulted in cellular transformation and in vivo tumorigenesis. NIH3T3-Di12 tumor cell growth was partly reversible upon Di12 antisense treatment. In addition, transformation of the ER+ human breast cancer cell line MCF-7 resulted in hormone independent growth of these tumors in nude mice. Di12 expression in NIH3T3 and MCF-7 tumor cells was confirmed by RT-PCR and mabDi12 immunostaining. Immunohistochemistry using mabDi12 on an arrayed collection of 106 invasive breast tumors further underlined the expression of the gene in over 75% of advanced stage breast cancers. Our data indicate that Di12 expression is oncogenic in in vitro transformation and in vivo tumorigenic assays.

Treatment of Non-transplant patients with multiple myeloma: routine treatment by office-based haematologists in Germany--data from the prospective Tumour Registry Lymphatic Neoplasms (TLN).

BACKGROUND: Various treatment options exist for patients with multiple myeloma (MM). Clinical registries provide insight into routine treatment and identify changes in treatment over time. PATIENTS AND METHODS: The Tumour Registry Lymphatic Neoplasms (TLN) prospectively collects data on the treatment of patients with lymphoid B cell neoplasms as administered by office-based haematologists in Germany. Data on patient and tumour characteristics, comorbidities, systemic treatments and outcome parameters are recorded. RESULTS: 371 non-transplant patients with MM were recruited between 2009 and 2011. At the start of first-line (second-line) treatment, the median age was 73 (75) years; 67% (74%) of the patients had stage III MM (classification of Durie and Salmon) and 19% (28%) had renal insufficiency. In the first line, 40% of the patients received bortezomib+melphalan+prednisone (VMP), 25% received bortezomib±dexamethasone (V±D) and 8% were treated with melphalan+prednisone+thalidomide (MPT). While use of bortezomib-based regimens increased from 67% (2009) to 85% (2011), use of melphalan-based regimens decreased from 68% to 48%. The overall objective response rate of treatment was 82%. In the second line, 34% of the patients received V±D and 16% lenalidomide+dexamethasone (LD). CONCLUSION: Bortezomib-based regimens dominate the first- and second-line treatment of MM. Future analyses will investigate outcome data, e.g. effectiveness of bortezomib retherapy compared to other second-line treatments.

[Clinical research on anthroposophic medicine:update of a health technology assessment report and status quo]. / Klinische Forschung zur Anthroposophischen Medizin - update eines «Health Technology Assessment¼-Berichts und status quo.

BACKGROUND AND OBJECTIVE: In 2005 a Health Technology Assessment (HTA) report analyzed efficacy, effectiveness, safety, utilization and costs of Anthroposophic Medicine (AM). After a recent referendum of the 'Swiss Population pro Complementary Medicine' (May 2009) this HTA report was updated. DESIGN: Update of the HTA report by a systematic review. METHODS: Methods corresponded to the existing HTA report and the guidelines of the Swiss Federal Office of Public Health. For clinical studies four databases and a specialized journal were searched, and extensive expert consultations were used. Studies were selected according to predefined inclusion criteria, data were extracted, and methodological quality was assessed individually. RESULTS: 70 new clinical studies were found. Altogether, 265 clinical studies investigated efficacy and effectiveness of AM: 38 randomized controlled trials, 36 prospective and 49 retrospective non-randomized controlled trials as well as 90 prospective and 52 retrospective trials without control groups. They investigated a wide spectrum of AM treatments in a multitude of diseases; the whole AM system in 38 trials, non-pharmacological therapies in 10 trials, AM mistletoe products in cancer therapy in 133 trials, and other AM medication treatments in 84 trials. Most studies showed a positive result for AM. Methodological quality differed substantially; some studies showed major limitations, others were reasonably well conducted. Trials with better quality still showed a positive result. External validity was usually high. Side effects or other risks were rare and usually described to be mild or moderate. Studies regarding safety showed a good tolerability altogether. CONCLUSION: Trials of varying design and quality in a variety of diseases predominantly describe good clinical outcomes for AM, only marginal side effects, high satisfaction of patients with regard to results and safety and presumably slightly less costs. Further high-quality evaluations are desirable.