1. 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).
- Author
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Song, Yee Pei, Mistry, Hitesh, Irlam, Joely, Valentine, Helen, Yang, Lingjian, Lane, Brian, West, Catharine, Choudhury, Ananya, Hoskin, Peter J., and Hoskin, Peter
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BLADDER cancer , *NICOTINAMIDE , *RADIOTHERAPY , *OVERALL survival , *HYPOXEMIA , *CLINICAL prediction rules , *CANCER invasiveness , *OXYGEN therapy , *RESEARCH , *CONFIDENCE intervals , *TIME , *RESEARCH methodology , *REGRESSION analysis , *PROGNOSIS , *MEDICAL cooperation , *EVALUATION research , *VITAMIN B complex , *TREATMENT effectiveness , *COMPARATIVE studies , *RANDOMIZED controlled trials , *CARBON dioxide , *RADIATION-sensitizing agents , *RESEARCH funding , *NECROSIS , *LONGITUDINAL method ,BLADDER tumors - Abstract
Purpose: Many muscle-invasive bladder cancers are hypoxic, which limits the efficacy of radiation therapy. Hypoxia modification using carbogen and nicotinamide has been tested in a phase 3 trial, Bladder Carbogen Nicotinamide. We present mature follow-up data with biomarker predictions of outcomes.Methods and Materials: Bladder Carbogen Nicotinamide is a prospective, phase 3, multicenter, randomized, 2-arm, nonblinded clinical trial. Participants were randomized to receive radical radiation therapy (RT; control arm) alone or with the addition of carbogen (98% O2; 2% CO2) and nicotinamide (CON). Patients with muscle-invasive or high-grade non-muscle invasive bladder cancer were included. Tumor tissue was collected at entry and was analyzed for tumor necrosis, hypoxia (24-gene signature), and basal and luminal tumor molecular subtypes. Overall survival (OS) and disease-free survival and relationships with biomarker status outcomes are analyzed using multivariable Cox regression and log-rank analysis.Results: We analyzed 333 patients with a median follow-up of 10.3 years. The 10-year OS rates were 30% (95% confidence interval [CI], 0.23-0.39) in RT + CON patients and 24% (95% CI, 0.18-0.33) in the RT-alone patients (hazard ratio [HR], 0.80; 95% CI, 0.61-1.04; P = .08). The greatest benefit from CON was seen in patients with tumor necrosis (n = 79; 5-year OS, 53% vs. 33% in patients without tumor necrosis; HR, 0.59; 95% CI, 0.36-0.99; P = .04). Cases with a high hypoxia gene score (n = 75) had a 5-year OS rate of 51%, compared to 34% for a low score (HR, 0.64; 95% CI, 0.38-1.08; P = .09); those with the basal molecular subtype (n = 70) had a 5-year OS rate of 58%, compared to 38% for those with the luminal subtype (HR, 0.58; 95% CI, 0.32-1.06; P = .08).Conclusions: Although the improvement in long-term OS in the whole population is not statistically significant, patients selected by necrosis and high hypoxia gene score benefitted from hypoxia modification. [ABSTRACT FROM AUTHOR]- Published
- 2021
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