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Moradi B.,University of Heidelberg | Zahlten-Hinguranage A.,National Center for Tumour Diseases | Lehner B.,University of Heidelberg | Zeifang F.,University of Heidelberg
International Orthopaedics | Year: 2010

The primary objective of this study was to investigate the implications of pathological fractures on therapy outcome in patients with primary malignant bone tumours and to determine whether limb salvage can be safely performed. A retrospective analysis of 447 patients with primary malignant bone tumours, treated between 1985 and 2005, was performed. Multivariate Cox regression analysis was used to investigate the influence of pathological fractures and further independent variables on survival rate. In 52 of the 447 patients, the primary malignant bone tumour was complicated by a pathological fracture. These fractures were more common in malignant fibrous histiocytoma (MFH) of the bone and in the tumour stages IIa/b and III. Ablative surgery was performed in ten patients and limb salvage surgery in 42 patients. The mortality risk for patients with pathological fractures was significantly increased by a factor of 1.82 (p = 0.015), and overall duration of survival was significantly lower in the fracture group, with a median of 6.2 years (p < 0.00001). In univariate and multivariate analysis, fracture, higher tumour stages and resection margins remained a significant predictor of worse survival. Overall survival, rate of local recurrence and distant metastases were not affected by the type of surgical treatment selected; there was no difference between the patients who underwent limb salvage and those who underwent an amputation. Pathological fracture in patients with primary malignant bone tumours is a predictor of worse survival and significantly increases mortality risk. Reconstructive surgery did not influence the survival rate, showing that limb salvage therapy is safe when adequate resection margins are achieved. © 2009 Springer-Verlag.

Moradi B.,University of Heidelberg | Zahlten-Hinguranage A.,National Center for Tumour Diseases | Barie A.,University of Heidelberg | Caldeira F.,University of Erfurt | And 3 more authors.
European Journal of Pain | Year: 2010

Background: Musculoskeletal pain represents a continuous process ranging from single-site to multiple-site pain, with an increase in pain sites accompanied by an increasing risk of chronification and the development of further comorbidities. Within this context, the impact of pain spread on therapy outcome is still unknown. Aims: This prospective clinical study aimed to evaluate whether and to what extent patients with pain at multiple sites would also benefit from multidisciplinary therapy or whether therapy success is limited by pain spread. Methods: Patients' characteristics were assessed, including socio-demographic variables, occupational and workplace characteristics, pain intensity and dimensions of pain, psychological aspects and functional back capacity, as well as the generic health status. Data were prospectively collected at day 1 (baseline) and at 6-month follow-up from a sample of 389 patients undergoing multidisciplinary treatment. Patients were distributed into three groups based on the number of pain sites (single-site, dual-site and multiple-site) and the outcome parameters were compared. Results: All three groups improved significantly from baseline to the 6-month follow-up. Compared to patients with multiple-site pain, patients with single-site and dual-site pain displayed significantly better outcome on almost all measures. Only the subcategory mental health of the SF-36 did not show any statistically significant differences among the three groups. Conclusions: Our results display that patients with two or more pain sites also improve significantly in the outcome measures. Therefore, treatment should be offered independent of the extent of pain spread. However, therapy is significantly less successful in patients with pain at multiple sites. © 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Schouten P.C.,Netherlands Cancer Institute | Marme F.,Netherlands Cancer Institute | Marme F.,University of Heidelberg | Aulmann S.,University of Heidelberg | And 8 more authors.
Clinical Cancer Research | Year: 2015

Purpose: Breast cancers in carriers of inactivating mutations of the BRCA1 gene carry a specific DNA copy-number signature ("BRCA1-like"). This signature is shared with cancers that inactivate BRCA1 through other mechanisms. Because BRCA1 is important in repair of DNA double-strand breaks through error-free homologous recombination, patients with a BRCA1-like tumor may benefit from high-dose alkylating (HD) chemotherapy, which induces DNA double-strand breaks. Experimental Design: We investigated a single institution cohort of high-risk patients that received tandem HD chemotherapy schedule comprising ifosfamide, epirubicin, and carboplatin or conventional chemotherapy. We classified copy-number profiles to be BRCA1-like or non-BRCA1- like and analyzed clinical associations and performed survival analysis with a treatment by biomarker interaction design. Results: BRCA1-like status associated with high-grade and triple-negative breast cancers. BRCA1-like cases benefitted from the HD compared with a conventional regimen on disease-free survival (DFS): [hazard ratio (HR), 0.05; 95% confidence interval (CI), 0.01-0.38; P 1/4 0.003]; distant DFS (DDFS): (HR, 0.06; 95% CI, 0.01-0.43; P 1/4 0.01); and overall survival (OS; HR, 0.15; 95% CI, 0.03-0.83; P0.03) after correction for prognostic factors.No such benefit was observed in the non-BRCA1-like cases on DFS (HR, 0.74; 95% CI, 0.38-1.46; P 1/4 0.39), DDFS (HR, 0.79; 95% CI, 0.41-1.52; P 1/4 0.47), and OS (HR, 0.93; 95% CI, 0.52-1.64; P 1/4 0.79). The P values for interaction were 0.01 (DFS), 0.01 (DDFS), and 0.045 (OS). Conclusions: BRCA1-like tumors recurred significantly less often after HD than conventional chemotherapy. BRCA1-like copy-number profile classification may be a predictive marker for HD alkylating chemotherapy. © 2015 American Association for Cancer Research.

Goeppert B.,University of Heidelberg | Frauenschuh L.,University of Heidelberg | Zucknick M.,German Cancer Research Center | Roessler S.,University of Heidelberg | And 10 more authors.
British Journal of Cancer | Year: 2015

Background:Biliary tract cancers (BTC) are rare malignant tumours with a poor prognosis. Previously, we have presented a detailed characterisation of the inflammatory infiltrate in BTC. Here, we analysed the impact of the expression of major histocompatibility complex class I (MHC I) on patient survival and the quantity, as well as the quality of tumour-infiltrating immune cell types in BTC.Methods:MHC I expression was assessed semi-quantitatively in 334 BTC, including extrahepatic (n=129) and intrahepatic cholangiocarcinomas (n=146), as well as adenocarcinomas of the gallbladder (n=59). In addition, 71 high-grade biliary intraepithelial lesions (BilIN 3) were included. Results were correlated with data on antitumour inflammation and investigated with respect to their association with clinicopathological variables and patient survival.Results:BTC showed a wide spectrum of different MHC I expression patterns ranging from complete negativity in some tumours to strong homogenous expression in others. In BilIN 3, significantly higher MHC I expression levels were seen compared to invasive tumours (P=0.004). Patients with strong tumoural MHC I expression had a significantly higher overall survival probability (median survival benefit: 8 months; P=0.006). MHC I expression strongly correlated with the number of tumour-infiltrating T-lymphocytes (CD4 + and CD8 +) and macrophages.Conclusions:Differences of MHC I expression predict patient outcome and show correlations with specific components of the inflammatory infiltrate in BTC. These findings contribute to a better understanding of immune response and immune escape phenomena in cholangiocarcinogenesis. © 2015 Cancer Research UK. All rights reserved.

Hillengass J.,University of Heidelberg | Hillengass J.,German Cancer Research Center | Bauerle T.,German Cancer Research Center | Bartl R.,Ludwig Maximilians University of Munich | And 17 more authors.
British Journal of Haematology | Year: 2011

Bone marrow plasma cell infiltration is a crucial parameter of disease activity in monoclonal plasma cell disorders. Until now, the only way to quantify such infiltration was bone marrow biopsy or aspiration. Diffusion-weighted imaging (DWI) is a magnetic resonance imaging-technique that may mirror tissue cellularity by measuring random movements of water molecules. To investigate if DWI is capable of assessing bone marrow cellularity in monoclonal plasma cell disease, we investigated 56 patients with multiple myeloma or monoclonal gammopathy of undetermined significance, and 30 healthy controls using DWI of the pelvis and/or the lumbar spine. In 25 of 30 patients who underwent biopsy, bone marrow trephine and DWI could be compared. Of the patients with symptomatic disease 15 could be evaluated after systemic treatment. There was a positive correlation between the DWI-parameter apparent diffusion coefficient (ADC) and bone marrow cellularity as well as micro-vessel density (P<0·001 respectively). ADC was significantly different between patients and controls (P<0·01) and before and after systemic therapy (P<0·001). In conclusion, DWI enabled bone marrow infiltration to be monitored in a non-invasive, quantitative way, suggesting that after further investigations on larger patient groups this might become an useful tool in the clinical work-up to assess tumour burden. © 2011 Blackwell Publishing Ltd.

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