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Esslingen, Germany

Untch M.,HELIOS Klinikum | Loibl S.,German Breast Group | Bischoff J.,Universitats Frauenklinik | Eidtmann H.,Universitats Frauenklinik | And 15 more authors.
The Lancet Oncology

Background: We compared the efficacy and safety of the addition of lapatinib versus trastuzumab to anthracycline-taxane-based neoadjuvant chemotherapy. Methods: In the GeparQuinto randomised phase 3 trial, patients with untreated HER2-positive operable or locally advanced breast cancer were enrolled between Nov 7, 2007, and July 9, 2010. Patients were eligible if their tumours were classified as cT3/4a-d, or hormone receptor (HR)-negative, HR-positive with clinically node-positive and cT2 disease (cT2 cN+), or HR-positive and pathologically node-positive in the sentinel lymph node for those with cT1 disease (cT1 pN SLN+). Patients were randomly assigned in a 1:1 ratio to receive neoadjuvant treatment with four cycles of EC (epirubicin [90 mg/m 2 intravenously] plus cyclophosphamide [600 mg/m 2 intravenously], every 3 weeks), and four cycles of docetaxel (100 mg/m 2 intravenously every 3 weeks) with either trastuzumab (6 mg/kg intravenously, with a starting loading dose of 8 mg/kg, for eight cycles, every 3 weeks) or lapatinib (1000-1250 mg per day orally) throughout all cycles before surgery. Randomisation was done by dynamic allocation with the minimisation method of Pocock and patients were stratified by participating site, HR status, and extent of disease (cT1-3 cN0-2 vs T4 or N3). The primary endpoint was pathological complete response (defined as ypT0 and ypN0) and was analysed in all patients who received at least one cycle of EC. Participants and investigators were not masked to treatment assignment. Pathologists in centres assessing surgery outcomes were masked to group assignment. This trial is registered with ClinicalTrials.gov, number NCT00567554. Findings: Of 620 eligible patients, 309 were randomly assigned to chemotherapy with trastuzumab (ECH-TH group) and 311 to chemotherapy with lapatinib (ECL-TL group). Two patients in the ECH-TH group and three patients in the ECL-TL group did not start treatment because of withdrawal of consent or immediate surgery. 93 (30·3%) of 307 patients in the ECH-TH group and 70 (22·7%) of 308 patients in the ECL-TL group had a pathological complete response (odds ratio [OR] 0·68 [95%CI 0·47-0·97]; p=0·04). Chemotherapy with trastuzumab was associated with more oedema (119 [39·1%] vs 88 [28·7%]) and dyspnoea (90 [29·6%] vs 66 [21·4%]), and ECL-TL with more diarrhoea (231 [75·0%] vs 144 [47·4%]) and skin rash (169 [54·9%] vs 97 [31·9%]). 43 (14·0%) patients discontinued in the ECH-TH group and 102 (33·1%) in the ECL-TL group. 70 serious adverse events were reported in the ECH-TH group and 87 in the ECL-TL group. Interpretation: This direct comparison of trastuzumab and lapatinib showed that pathological complete response rate with chemotherapy and lapatinib was significantly lower than that with chemotherapy and trastuzumab. Unless long-term outcome data show different results, lapatinib should not be used outside of clinical trials as single anti-HER2-treatment in combination with neoadjuvant chemotherapy. Funding: GlaxoSmithKline, Roche, and Sanofi-Aventis. © 2012 Elsevier Ltd. Source

The removal of axillary lymph nodes has been an important component of primary breast cancer surgery for more than a century. The clinical objective of lymph node surgery has, however, changed with the understanding of the biological behaviour of the disease and the modification of treatment strategies. Axillary lymph node dissection (ALD) was primarily regarded as a therapeutic procedure to remove all reachable tumour cells. ALD then changed to become a diagnostic tool when breast cancer was identified as a systemic disease and the lymph node status became the most important prognostic factor to determine systemic treatment decisions. For node-positive patients ALD remained the treatment of choice in order to ensure regional control. During the last decade the diagnostic role of ALD to identify node-positive patients was replaced by sentinel lymph node biopsy (SLNB), a targeted procedure that is associated with less morbidity compared to ALD. Recently the benefit of ALD has been questioned even for SLN-positive patients. However, ALD is still an important diagnostic tool for the cohort of node-positive patients. Women with pN2/3 disease derive benefit from a more intensive local and systemic treatment. Furthermore the data from a meta-analysis and a randomized trial indicate that patients with positive SLNs require regional treatment. Omission of SLNB requires new tools to define patients who derive a benefit from an intensified local and systemic treatment. Since local treatment is effective in node-positive patients, this treatment (radiotherapy vs surgery) must be clearly defined. © Springer-Verlag 2011. Source

Blohmer J.U.,Brustzentrum City am Sankt Gertrauden Krankenhaus | Rezai M.,Luisenkrankenhaus Dusseldorf | Kummel S.,Kliniken Essen Mitte | Kuhn T.,Klinikum Esslingen | And 6 more authors.
Journal of Medical Economics

Objective: The 21-gene assay (Oncotype DX Breast Cancer Test (Genomic Health Inc., Redwood City, CA)) is a well validated test that predicts the likelihood of adjuvant chemotherapy benefit and the 10-year risk of distant recurrence in patients with ER+, HER2- early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Germany. Methods: A Markov model was developed to make long-term projections of distant recurrence, survival, quality-adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative, or up to 3 node-positive early-stage breast cancer. Scenarios using conventional diagnostic procedures or the 21-gene assay to inform treatment recommendations for adjuvant chemotherapy were modeled based on a prospective, multi-center trial in 366 patients. Transition probabilities and risk adjustment were based on published landmark trials. Costs (2011 Euros (€)) were estimated from a sick fund perspective based on resource use in patients receiving chemotherapy. Future costs and clinical benefits were discounted at 3% annually. Results: The 21-gene assay was projected to increase mean life expectancy by 0.06 years and quality-adjusted life expectancy by 0.06 quality-adjusted life years (QALYs) compared with current clinical practice over a 30-year time horizon. Clinical benefits were driven by optimized allocation of adjuvant chemotherapy. Costs from a healthcare payer perspective were lower with the 21-gene assay by ∼€561 vs standard of care. Probabilistic sensitivity analysis indicated that there was an 87% probability that the 21-gene assay would be dominant (cost and life saving) to standard of care. Limitations: Country-specific data on the risk of distant recurrence and quality-of-life were not available. Conclusions: Guiding decision-making on adjuvant chemotherapy using the 21-gene assay was projected to improve survival, quality-adjusted life expectancy, and be cost saving vs the current standard of care women with ER+, HER2- early-stage breast cancer. © 2013 Informa UK Ltd. Source

Bodon G.,Klinikum Esslingen | Glasz T.,Semmelweis University | Olerud C.,Uppsala University Hospital
European Spine Journal

Purpose The purpose of this study was to examine the anatomic changes in a case of occipitalization of the atlas. Methods Occipitalization of the atlas was found accidentally in a 64-year-old male cadaver. Anatomic dissection was carried out to examine the posterior aspect of the upper cervical region and craniocervical junction. The occipitalized atlas was then harvested and macerated to study the bony anomaly. Results In this case of occipitalization, fusion was observed at both lateral masses and at the left posterior hemiarch of the atlas. We found the following soft tissue changes: the rectus capitis posterior minor muscle was lacking on the left side and was atrophic on the right, the obliquus capitis superior muscle was present on both sides showing moderate atrophy and fatty changes. The posterior atlanto-axial membrane was thinner and asymmetric, had a free edge on the right side. Lateral to this edge the dura was lying free. We believe that these changes of the posterior atlanto-axial membrane together with the increased distance between the fused posterior arch of the atlas and the lamina of the axis could cause the observed dura bulge at this level. The vertebral artery was entering the skull through a canal on the left side. Conclusions In our case, occipitalization considerably changed the anatomy of the upper cervical spine and craniocervical junction. Special care must be taken when using the posterior approach to avoid neurovascular injury in cases with occipitalization. © Springer-Verlag Berlin Heidelberg 2013. Source

Hartmann K.,Medizinisches Kinder und Jugendzentrum fur Endokrinologie und Diabetologie | Ittner J.,Endokrinologische Praxis | Muller-Rossberg E.,Klinikum Esslingen | Schonau E.,University of Cologne | And 5 more authors.
Hormone Research in Paediatrics

Background/Aims: Treatment of children with growth disorders with recombinant human growth hormone is necessary for improved outcomes, including final height. Methods: Adherence data from the Observational Study Saizen®-online, recorded with the easypod™ device collected between October 2009 and May 2011, were analyzed in pediatric patients receiving recombinant human growth hormone treatment for a variety of growth disorders. Results: Data from 75 children (46 boys, 29 girls) with different growth disorders were analyzed over a period of 343 ± 201 (SD) days. Boys and girls showed similar mean ± SD adherence rates of 90.5 ± 3.1% and 92.2 ± 10.7%, respectively. Pubertal children (n = 41) had a significantly lower adherence rate (89.1 ± 13.7%) than prepubertal children (n = 29) (96.5 ± 3.9%; p < 0.005). There were nonsignificant differences in adherence rates according to diagnosis: growth hormone deficiency (n = 48) 91.4 ± 11.0%, small for gestational age (n = 18) 91.1 ± 15.3%, Turner syndrome (n = 6) 86.0 ± 14.5%, and chronic renal failure (n = 3) 99.3 ± 1.0%, although the latter two groups were small. Conclusion: Our data indicate that only a small number of pediatric patients using the easypod device had poor adherence to treatment. Further reliable adherence data are required to identify factors affecting long-term adherence in this population. Copyright © 2013 S. Karger AG, Basel. Source

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