Necrosis predicts benefit from hypoxia-modifying therapy in patients with high risk bladder cancer enrolled in a phase III randomised trial.
Irlam, Joely J
Ryder, W David J
West, Catharine M L
AffiliationTranslational Radiobiology Group, Institute of Cancer Sciences, The University of Manchester, Manchester Academic Health Centre, Christie Hospital, Manchester.
MetadataShow full item record
AbstractBACKGROUND 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.
CitationNecrosis predicts benefit from hypoxia-modifying therapy in patients with high risk bladder cancer enrolled in a phase III randomised trial. 2013: Radiother Oncol
JournalRadiotherapy and Oncology
- Long-Term Outcomes of Radical Radiation Therapy with Hypoxia Modification with Biomarker Discovery for Stratification: 10-Year Update of the BCON (Bladder Carbogen Nicotinamide) Phase 3 Randomized Trial (ISRCTN45938399).
- Authors: Song YP, Mistry H, Irlam J, Valentine H, Yang L, Lane B, West C, Choudhury A, Hoskin PJ
- Issue date: 2021 Aug 1
- Expression of hypoxia-inducible factor-1α predicts benefit from hypoxia modification in invasive bladder cancer.
- Authors: Hunter BA, Eustace A, Irlam JJ, Valentine HR, Denley H, Oguejiofor KK, Swindell R, Hoskin PJ, Choudhury A, West CM
- Issue date: 2014 Jul 29
- A 26-gene hypoxia signature predicts benefit from hypoxia-modifying therapy in laryngeal cancer but not bladder cancer.
- Authors: Eustace A, Mani N, Span PN, Irlam JJ, Taylor J, Betts GN, Denley H, Miller CJ, Homer JJ, Rojas AM, Hoskin PJ, Buffa FM, Harris AL, Kaanders JH, West CM
- Issue date: 2013 Sep 1
- A Gene Signature for Selecting Benefit from Hypoxia Modification of Radiotherapy for High-Risk Bladder Cancer Patients.
- Authors: Yang L, Taylor J, Eustace A, Irlam JJ, Denley H, Hoskin PJ, Alsner J, Buffa FM, Harris AL, Choudhury A, West CML
- Issue date: 2017 Aug 15
- Carbogen and nicotinamide in locally advanced bladder cancer: early results of a phase-III randomized trial.
- Authors: Hoskin PJ, Rojas AM, Saunders MI, Bentzen SM, Motohashi KJ, BCON investigators.
- Issue date: 2009 Apr