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Copenhagen, Denmark

Hoff C.M.,Aarhus University Hospital | Hansen H.S.,Finsen Center | Overgaard M.,Aarhus University Hospital | Grau C.,Aarhus University Hospital | And 3 more authors.
Radiotherapy and Oncology | Year: 2011

Background and purpose: Patients with head and neck squamous cell carcinoma (HNSCC) and a low level of haemoglobin (Hb) often have a poor response to radiation which may be related to hypoxia induced radioresistance. The aim of the study was to evaluate the prognostic significance of low Hb level and its modification by transfusion in HNSCC patients treated with radiotherapy. The study was performed as a subrandomization in the DAHANCA 5 trial. Material and methods: Patients were randomized to treatment with the hypoxic radiosensitizer nimorazole or placebo, and in addition, patients with "low" pre-irradiation Hb values (females < 13 g/dL; males < 14.5 g/dL) were subrandomized to plus or minus transfusion. Transfusion was given with packed red blood cells with the aim to achieve a Hb level in the "high" value range. Results: A total of 414 patients were included, 243 patients had high Hb levels and 171 patients had low Hb levels. Of the low Hb patients, 82 were randomized to receive transfusion and 89 not to receive transfusion. The treatment arms were well balanced. In the majority of patients, transfusion resulted in increased Hb levels although this tended to decline throughout treatment. Patients with high Hb levels had a significantly better probability of locoregional control, disease-specific survival and overall survival compared to 'low Hb no transfusion' patients. In the low Hb group, transfusion did not improve the outcome in locoregional control, disease-specific survival or overall survival. In multivariate analyses, T and N classifications were significant for all outcome measures, whereas there was no significant influence of transfusion or Hb level on endpoints. Conclusion: The univariate prognostic significance of high Hb level was demonstrated in patients with HNSCC treated with radiotherapy; however, transfusion prior to and during treatment did not improve the outcome in patients with low Hb values. © 2010 Elsevier Ireland Ltd. All rights reserved. Source

Langer S.W.,Finsen Center | Thougaard A.V.,Lundbeck | Sehested M.,Diagnostic Center | Jensen P.B.,Buhl Oncology
Cancer Chemotherapy and Pharmacology | Year: 2012

Purpose: Dexrazoxane is an established treatment option in extravasation of the classic anthracyclines such as doxorubicin, epirubicin, and daunorubicin. However, it is not known whether the protection against the devastating tissue injuries extends into extravasation with new types of anthracyclines, the anthracenediones, or the liposomal pegylated anthracycline formulations. We therefore tested the antidotal efficacy of dexrazoxane against extravasation of amrubicin, mitoxantrone, and liposomal pegylated doxorubicin in mice. Methods: A total of 80 female B6D2F1 mice were tested in an established mouse extravasation model. The mice had experimental extravasations of amrubicin, mitoxtanrone, and Caelyx and were immediately hereafter treated with systemic dexrazoxane or saline. Results and conclusion: Systemic treatment with dexrazoxane resulted in significant protection against extravasation injuries from all three drugs. Moreover, the vesicant potential of the three test drugs was weaker than seen in previous experiments with the classic anthracyclines. © 2011 Springer-Verlag. Source

This paper consists of reflections in relation to how follow-up is organized in the growing population of cancer survivors. It also includes focus on late effects in cancer patients. The paper also highlights research contributions in the area of depression in cancer patients and discusses these findings in relation to the daily clinical practice. Parts of this paper were a lecture given as a humble response to the Arthur M. Sutherland Award 2014. © 2015 John Wiley & Sons, Ltd. Source

Vilmar A.C.,Finsen Center | Santoni-Rugiu E.,Copenhagen University | Sorensen J.B.,Finsen Center
Annals of Oncology | Year: 2010

Background: Customized chemotherapy is likely to improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a promising biomarker; however, current evidence is inadequate. Impact of ERCC1 status was evaluated among patients participating in a large randomized chemotherapy trial. Patients and methods: Four hundred and forty-three patients with advanced NSCLC were enrolled in a phase III trial and were randomly allocated to triplet chemotherapy or standard doublet regimen. Immunohistochemical evaluation for ERCC1 status was mainly carried out on bioptic material. Results: Two hundred and sixty-four (59.5%) patients had representative tissue samples for ERCC1 evaluation. Median overall survival (OS) in the ERCC1-negative and ERCC1-positive population was 11.8 and 9.8 months, respectively (P = 0.028). The median OS among patients with adenocarcinomas (n = 122) was 15.2 and 8.3 months, respectively (P = 0.007). Interaction analysis between ERCC1-negative status and adenocarcinomas yielded a hazard ratio of 0.64 for death (P = 0.002). Conclusions: Clinically applicable evaluation of ERCC1 status predicted cisplatin sensitivity in the largest randomized patient population with advanced NSCLC reported to date. The predictive value can be ascribed to the adenocarcinomas emphasizing the relevance of ERCC1 expression in this subgroup. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source

Gjetting T.,Finsen Center | Arildsen N.S.,Finsen Center | Christensen C.L.,Finsen Center | Poulsen T.T.,Finsen Center | And 3 more authors.
International Journal of Nanomedicine | Year: 2010

Background: DOTAP/cholesterol-based lipoplexes are successfully used for delivery of plasmid DNA in vivo especially to the lungs, although low systemic stability and circulation have been reported. To achieve the aim of discovering the best method for systemic delivery of DNA to disseminated tumors we evaluated the potential of formulating DOTAP/cholesterol lipoplexes with a polyethylene glycol (PEG)-modified lipid, giving the benefit of the shielding and stabilizing properties of PEG in the bloodstream. Method: A direct comparison of properties in vitro and in vivo of 4 different DOTAP/cholesterol-based lipoplexes containing 0%, 2%, 4%, and 10% PEG was performed using reporter gene activity and radioactive tracer lipid markers to monitor biodistribution. Results: We found that 10% PEGylation of lipoplexes caused reduced retention in lung and heart tissues of nude mice compared to nonPEGylated lipoplexes, however no significant delivery to xenograft flank tumors was observed. Although PEGylated and nonPEGylated lipoplexes were delivered to cells the ability to mediate successful transfection is hampered upon PEGylation, presumably due to a changed uptake mechanism and intracellular processing. Conclusion: The eminent in vivo transfection potency of DOTAP/cholesterol-based lipoplexes is well established for expression in lung tumors, but it is unsuitable for expression in non first pass organs such as xenograft flank tumors in mice even after addition of a PEG-lipid in the formulation. © 2010 Gjetting et al, publisher and licensee Dove Medical Press Ltd. Source

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