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Brenner H.,German Cancer Research Center | Bouvier A.M.,Registre bourguignon des cancers digestifs | Foschi R.,Istituto Nazionale Tumori | Hackl M.,Austrian National Cancer Registry | And 4 more authors.
International Journal of Cancer | Year: 2012

Colorectal cancer (CRC) is the second most common cause of death due to cancer causing death in Europe, accounting for more than 200,000 deaths per year. Prognosis strongly depends on stage at diagnosis, and the disease can be cured in most cases if diagnosed at an early stage. We aimed to assess trends and recent developments in 5-year relative survival in European countries, with a special focus on age, stage at diagnosis and anatomical cancer subsite. Data from 25 population-based cancer registries from 16 European countries collected in the context of the EUROCARE-4 project were analyzed. Using period analysis, age-adjusted and age-specific 5-year relative survival was calculated by country, European region, stage and cancer subsite for time periods from 1988-1990 to 2000-2002. Survival substantially increased over time in all European regions. In general, increases were more pronounced in younger than in older patients, for earlier than for more advanced cancer stages and for rectum than for colon cancer. Substantial variation of CRC survival between European countries and between age groups persisted and even tentatively increased over time. There is a huge potential for reducing the burden of CRC in Europe by more widespread and equal delivery of existing options of effective early detection and curative treatment to the European population. Copyright © 2011 UICC.


Hackl M.,Austrian National Cancer Registry | Waldhoer T.,Medical University of Vienna
European Journal of Public Health | Year: 2013

Background: The international comparability of data from population-based cancer registries depends strongly on the completeness of case ascertainment. Furthermore, Austrian observed incidence rates suggest that the completeness of case ascertainment differs between Austrian federal states. Completeness of case ascertainment is to be investigated on national and regional level. Methods: We used the flow method to evaluate the completeness of the Austrian National Cancer Registry. This method is based on the logical flow of data in the registration system, and on the time distribution of various probabilities inherent in this flow. Results: Overall completeness of the Austrian cancer incidence data 2005 was 94.2% after a registration period of 5 years. The flow method found striking differences in completeness between the federal states, which are contrary to the time series analyses. Conclusion: Overall completeness of the Austrian National Cancer Registry is in concordance with estimates from international registries. The biggest part of the decrease of incidence rates in the past 2 published years seems to be a result of incompleteness. The importance of the registration date of a cancer case and the survival time on completeness estimation using the flow method has become apparent. Further investigation into the comparability of registration date between the federal states and into the quality of survival time estimates is recommended. © 2012 The Author 2012. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.


Berghoff A.S.,Medical University of Vienna | Ilhan-Mutlu A.,Medical University of Vienna | Wohrer A.,Medical University of Vienna | Hackl M.,Austrian National Cancer Registry | And 8 more authors.
Strahlentherapie und Onkologie | Year: 2014

Background. Survival upon diagnosis of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) is highly variable and established prognostic scores do not include tissue-based parameters. Methods. Patients who underwent neurosurgical resection as first-line therapy for newly diagnosed NSCLC BM were included. Microvascular density (MVD), Ki67 tumor cell proliferation index and hypoxia-inducible factor 1 alpha (HIF-1 alpha) index were determined by immunohistochemistry. Results. NSCLC BM specimens from 230 patients (151 male, 79 female; median age 56 years; 199 nonsquamous histology) and 53/230 (23.0%) matched primary tumor samples were available. Adjuvant whole-brain radiation therapy (WBRT) was given to 153/230 (66.5%) patients after neurosurgical resection. MVD and HIF-1 alpha indices were significantly higher in BM than in matched primary tumors. In patients treated with adjuvant WBRT, low BM HIF-1 alpha expression was associated with favorable overall survival (OS), while among patients not treated with adjuvant WBRT, BM HIF-1 alpha expression did not correlate with OS. Low diagnosis-specific graded prognostic assessment score (DS-GPA), low Ki67 index, high MVD, low HIF-1 alpha index and administration of adjuvant WBRT were independently associated with favorable OS. Incorporation of tissue-based parameters into the commonly used DS-GPA allowed refined discrimination of prognostic subgroups. Conclusion. Ki67 index, MVD and HIF-1 alpha index have promising prognostic value in BM and should be validated in further studies. © 2014 Springer-Verlag.


Spanberger T.,Medical University of Vienna | Berghoff A.S.,Medical University of Vienna | Dinhof C.,Medical University of Vienna | Ilhan-Mutlu A.,Medical University of Vienna | And 12 more authors.
Clinical and Experimental Metastasis | Year: 2013

To analyze the prognostic value of the extent of peritumoral brain edema in patients operated for single brain metastases (BM), we retrospectively evaluated pre-operative magnetic resonance images in a discovery cohort of 129 patients and a validation cohort of 118 patients, who underwent neurosurgical resection of a single BM in two different hospitals. We recorded clinical parameters and immunohistochemically assessed the Ki67 index, the microvascularization patterns and the expression of hypoxia-induced factor 1 alpha (HIF1a) in the BM tissue specimens retrieved at neurosurgery. Statistical analysis including uni- and multivariate survival analyses were performed. Baseline characteristics were well balanced between the discovery and validation cohorts. In univariate analysis, we found a significant association of favorable overall survival time with young patient age, high Karnofsky performance score, low graded prognostic assessment (GPA) class, absence of extracranial metastases, adjuvant treatment with whole brain radiotherapy and, surprisingly, large brain edema. In multivariate analysis, only GPA and extent of brain edema remained independent prognostic parameters. The prognostic impact of the extent of brain edema was consistent in the two patient cohorts. Furthermore, we found a significant correlation of small brain edema with brain-invasive tumor growth pattern as assessed intraoperatively by the neurosurgeon, low neo-angiogenic activity and low expression of HIF1a. Extent of brain edema independently correlates with prognosis in patients operated for single BM. In conclusion, patients with small peritumoral edema have shorter survival times and their tumors are characterized by a more brain-invasive growth, lower HIF1a expression and less angiogenic activity. © 2012 Springer Science+Business Media Dordrecht.


Berghoff A.S.,Medical University of Vienna | Ilhan-Mutlu A.,Medical University of Vienna | Dinhof C.,Medical University of Vienna | Magerle M.,Medical University of Vienna | And 12 more authors.
Neuropathology and Applied Neurobiology | Year: 2015

Aim: We aimed to characterize angiogenesis and proliferation and their correlation with clinical characteristics in a large brain metastasis (BM) series. Methods: Ki67 proliferation index, microvascular density (MVD) and hypoxia-inducible factor 1 alpha (HIF-1 alpha) index were determined by immunohistochemistry in BM and primary tumour specimens. Results: Six hundred thirty-nine BM specimens of 639 patients with lung cancer (344/639; 53.8%), breast cancer (105/639; 16.4%), melanoma (67/639; 10.5%), renal cell carcinoma (RCC; 52/639; 8.1%) or colorectal cancer (CRC; 71/639; 11.1%) were available. Specimens of the corresponding primary tumour were available in 113/639 (17.7%) cases. Median Ki67 index was highest in CRC BM and lowest in RCC BM (P<0.001). MVD and HIF-1 alpha index were both highest in RCC BM and lowest in melanoma BM (P<0.001). Significantly higher Ki67 indices, MVD and HIF-1 alpha indices in the BM than in matched primary tumours were observed for breast cancer, non-small cell lung cancer (NSCLC) and CRC. Correlation of tissue-based parameters with overall survival in individual tumour types showed a favourable and independent prognostic impact of low Ki67 index [hazard ratio (HR) 1.015; P<0.001] in NSCLC BM and of low Ki67 index (HR 1.027; P=0.008) and high angiogenic activity (HR 1.877; P=0.002) in RCC. Conclusion: Our data argue for differential pathobiological and clinical relevance of Ki67 index, HIF1-alpha index and MVD between primary tumour types in BM patients. An independent prognostic impact of tissue-based characteristics was observed in patients with BM from NSCLC and RCC, supporting the incorporation of these tissue-based parameters into diagnosis-specific prognostic scores. © 2014 British Neuropathological Society.

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