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    Necrosis predicts benefit from hypoxia-modifying therapy in patients with high risk bladder cancer enrolled in a phase III randomised trial.

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    Authors
    Eustace, Amanda
    Irlam, Joely J
    Taylor, Janet
    Denley, H
    Agrawal, S
    Choudhury, Ananya
    Ryder, W David J
    Ord, J
    Harris, A
    Rojas, A
    Hoskin, P
    West, Catharine M L
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    Affiliation
    Translational Radiobiology Group, Institute of Cancer Sciences, The University of Manchester, Manchester Academic Health Centre, Christie Hospital, Manchester.
    Issue Date
    2013-06-14
    
    Metadata
    Show full item record
    Abstract
    BACKGROUND AND PURPOSE: Addition of carbogen and nicotinamide (hypoxia-modifying agents) to radiotherapy improves the survival of patients with high risk bladder cancer. The study investigated whether histopathological tumour features and putative hypoxia markers predicted benefit from hypoxia modification. MATERIALS AND METHODS: Samples were available from 231 patients with high grade and invasive bladder carcinoma from the BCON phase III trial of radiotherapy (RT) alone or with carbogen and nicotinamide (RT+CON). Histopathological tumour features examined were: necrosis, growth pattern, growing margin, and tumour/stroma ratio. Hypoxia markers carbonic anhydrase-IX and glucose transporter-1 were examined using tissue microarrays. RESULTS: Necrosis was the only independent prognostic indicator (P=0.04). Necrosis also predicted benefit from hypoxia modification. Five-year overall survival was 48% (RT) versus 39% (RT+CON) (P=0.32) in patients without necrosis and 34% (RT) versus 56% (RT+CON) (P=0.004) in patients with necrosis. There was a significant treatment by necrosis strata interaction (P=0.001 adjusted). Necrosis was an independent predictor of benefit from RT+CON versus RT (hazard ratio [HR]: 0.43, 95% CI 0.25-0.73, P=0.002). This trend was not observed when there was no necrosis (HR: 1.64, 95% CI 0.95-2.85, P=0.08). CONCLUSIONS: Necrosis predicts benefit from hypoxia modification in patients with high risk bladder cancer and should be used to select patients; it is simple to identify and easy to incorporate into routine histopathological examination.
    Citation
    Necrosis predicts benefit from hypoxia-modifying therapy in patients with high risk bladder cancer enrolled in a phase III randomised trial. 2013: Radiother Oncol
    Journal
    Radiotherapy and Oncology
    URI
    http://hdl.handle.net/10541/297453
    DOI
    10.1016/j.radonc.2013.05.017
    PubMed ID
    23773411
    Type
    Article
    Language
    en
    ISSN
    1879-0887
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.radonc.2013.05.017
    Scopus Count
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