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Landshut, Germany

von Minckwitz G.,German Breast Group | von Minckwitz G.,University Hospital | Rezai M.,Breast Center | Fasching P.A.,University Hospital | And 15 more authors.
Annals of Oncology

Background: The GeparQuattro study showed that adding capecitabine or prolonging the duration of anthracyclinetaxane-based neoadjuvant chemotherapy from 24 to 36 weeks did not increase pathological complete response (pCR) rates. Trastuzumab-treated patients with HER2-positive disease showed a higher pCR rate than patients with HER2-negative disease treated with chemotherapy alone. We here present disease-free (DFS) and overall survival (OS) analyses. Patients and methods: Patients (n = 1495) with cT ≥ 3 tumors, or negative hormone-receptor status, or positive hormone-receptor and clinically node-positive disease received four times epirubicin/cyclophosphamide and were thereafter randomly assigned to four times docetaxel (Taxotere), or four times docetaxel/capecitabine over 24 weeks, or four times docetaxel followed by capecitabine over 36 weeks. Patients with HER2-positive tumors received 1 year of trastuzumab, starting with the first chemotherapy cycle. Follow-up was available for a median of 5.4 years. Results: Outcome was not improved for patients receiving capecitabine (HR 0.92; P = 0.463 for DFS and HR 93; P = 0.618 for OS) as well as for patients receiving 36 weeks of chemotherapy (HR 0.97; P = 0.818 for DFS and HR 0.97; P = 0.825 for OS). Trastuzumab-treated patients with HER2-positive disease showed similar DFS (P = 0.305) but a significantly better adjusted OS (P = 0.040) when compared with patients with HER2-negative disease treated with chemotherapy alone. Recorded long-term cardiac toxicity was low. Conclusions: Long-term results, similar to the results of pCR, do not support the use of capecitabine in the neoadjuvant setting in addition to an anthracycline-taxane-based chemotherapy. However, the results support previous data showing a benefit of trastuzumab as predicted by higher pCR rates. Clinical trial number: NCT 00288002, www.clinicaltrials.gov. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. Source

Heckmann J.G.,Klinikum Landshut | Dutsch M.,Sana Klinik Rummelsberg
European Journal of Neurology

To present two patients with Miller Fisher syndrome (MFS) recurrence after 35 and 44years and review of the literature on recurring MFS. All identified cases with recurrent MFS were evaluated. Age, gender, clinical features of first and recurrent MFS, course of disease, laboratory findings, therapy and outcome were transformed into tables. Twenty-eight patients (16 men, 12 women; mean age at the first episode 34years (range 13-57years); mean age at the latest episode 47years (range 21-66years) with a total of 70 MFS episodes were identified. Twenty-one patients had a single recurrence, five patients had two recurrences, one patient had four recurrences and one patient had seven recurrences. The mean interval between attacks was 9.45years (3months to 44years). In 76% of the initial episodes and in 81% of the recurrent episodes, an infectious disease preceded MFS. Additional facial and bulbar symptoms and autonomic disturbances were frequent findings. Cerebrospinal fluid (CSF) and electrodiagnostic findings were unspecific. If tested, autoantibodies against GQ1b had been positive in all episodes. In about half of the patients, immunotherapy was applied. The outcome was favourable in most patients. Recurrence of MFS is a rare quite uniform condition with a mostly favourable prognosis. © 2011 The Author(s) European Journal of Neurology © 2011 EFNS. Source

Di Gioia D.,Ludwig Maximilians University of Munich | Heinemann V.,Ludwig Maximilians University of Munich | Nagel D.,Ludwig Maximilians University of Munich | Untch M.,HELIOS Klinikum | And 4 more authors.
Tumor Biology

The aim of this retrospective analysis is to determine the correlation between tumour marker kinetics (TMK) like carcinoembryonic antigen (CEA) and/or cancer antigen (CA) 15-3 and imaging concerning effectiveness of chemotherapy in metastatic breast cancer (MBC) patients. TMK (CEA, AxSYM, Abbott; CA15-3, Elecsys, Roche) were evaluated in MBC patients (n=77) at the beginning of chemotherapy (pre-treatment value=A), after 20-30 days (first intermediate value=B), after 40-60 days (second intermediate value=C) and at the time the effectiveness of chemotherapy was evaluated with imaging (D). Response to treatment was assessed by standard WHO criteria criteria. For the assessment of biochemical progression and response, four criteria based on TMK were established. The first criterion of progression required that there was an increase ?25% after 40-60 days (C) and the slope per day from B to C exceeds the slope from A to B. The second criterion of progression required that, at the time of staging, the value be ?25% of the pre-treatment value (A), and also, increasing values from C until staging (D) were required. The first criterion of response required that the second intermediate value (C) be decreased by ?25% compared to A (pre-treatment value) and C be lower than B (first intermediate value). The second criterion of response required that D be ?25% of B and D be lower than C. Fifty-four (70%) patients showed a correlation between TMK and imaging results during chemotherapy. In 10 (13%) patients, no correlation was obtained, and in 13 (17%) patients, no biochemical statement was possible because of divergent TMK. In summary, after 1 month, no statement about treatment response was possible by using TMK. The effectiveness or ineffectiveness of treatment could be determined correctly in 40% of patients after 2 months and in 70% of patients after approximately 3 months. The data presented support the hypothesis that TMK are clinically relevant tools to monitor treatment response. Further improvements on their sensitivity can be probably achieved by a prospective study design and by combining with other biomarkers like CA-125 and HER2 shed antigen. © International Society of Oncology and BioMarkers (ISOBM) 2011. Source

Murawski N.,Medical School Hamburg | Held G.,Medical School Hamburg | Ziepert M.,University of Leipzig | Kempf B.,Klinikum Landshut | And 9 more authors.

To define the role of radiotherapy and intrathecal prophylaxis in extralymphatic craniofacial involvement (ECFI) of aggressive B-cell lymphoma, we analyzed 11 consecutive German High-Grade Non-Hodgkin Lymphoma Study Group trials. ECFI occurred in 290/4155 (7.0%) patients (orbita, 31; paranasal sinuses, 93; main nasal cavity, 38; tongue, 27; remaining oral cavity, 99; salivary glands, 54). In a multivariable analysis adjusted for International Prognostic Index rituximab improved event-free and overall survival both in patients with and without ECFI. Three-year event-free (79% vs 79%; P = .842) and overall survival (86% vs 88%; P = .351) rates were similar in 145 patients receiving and 57 not receiving radiotherapy. Without rituximab, the 2-year cumulative rate of central nervous system (CNS) disease was increased in 205 ECFI patients compared with 2586 non-ECFI patients (4.2% vs 2.8%; P = .038), whereas this was not observed with rituximab (1.6% in 83 ECFI vs 3.4% in 1252 non-E CFI patients; P = .682). In 88 ECFI patients who received intrathecal prophylaxis with methotrexate, the 2-year rate of CNS disease was 4.2% compared with 2.3% in 191 patientswho did not ( P = .981). In conclusion, rituximab eliminates the increased risk for CNS disease in patients with E CFI. This retrospective analysis does not support intrathecal prophylaxis or radiotherapy to ECFI patients in complete remission/unconfirmed complete remission. These findings should be confirmed in a prospective study. © 2014 by The American Society of Hematology. Source

Brand C.,Universitatsklinikum Ulm | Alber B.,Klinik fur Neurologie und Neurologische Rehabilitation | Fladung A.-K.,Universitatsklinikum Ulm | Knauer K.,Universitatsklinikum Ulm | And 8 more authors.
British Journal of Neurosurgery

Objective. The exact cause of cognitive deficits following intracranial haemorrhage is unclear. This prospective study examines the abilities after spontaneous subarachnoid haemorrhage (SAH), intracerebral haemorrhage (ICH) and chronic subdural haematoma (SDH) to elucidate the cognitive outcome. Patients and methods. Ninety-nine patients with SAH (N = 60), ICH (N = 25), and SDH (N = 14) were followed up for an average of 6 and 12 months post-haemorrhage. Cognitive tests were used to examine attention, memory, concentration, and executive function. Following were used for analysis: 1. the percentage of patients falling below the 25th percentile per test, 2. the general development from the first to second test point and 3. the incidence of significant changes between the test points. Significance was established as p ≤ 0.05. Results. All three types of haemorrhage resulted in deficits as concerns abstract language (53%-75%). The processing speed was below the normal levels in more than 70% of the patients tested. The cognitive performance of SAH patients was similar to that of patients with SDH and ICH patients after 6 months. The number of patients with outcomes falling below the 25th percentile (to some extent more than 75% in patients post-SAH) is high in all patient groups and mostly decreases over the course. Nevertheless, patients with SAH reveal improvements in many more areas than with ICH and SDH (p ≤ 0.006). Conclusions. The cognitive impairments following SAH, ICH and SDH deficits appear to develop in a similar way regardless of the type of haemorrhage. Cognitive improvement is most pronounced in patients with SAH. © 2014 The Neurosurgical Foundation. Source

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