%0 Journal Article %T Dose-Escalated Hypofractionated Intensity-Modulated Radiotherapy in High-Risk Carcinoma of the Prostate: Outcome and Late Toxicity %A David Thomson %A Sophie Merrick %A Ric Swindell %A Joanna Coote %A Kay Kelly %A Julie Stratford %A James Wylie %A Richard Cowan %A Tony Elliott %A John Logue %A Ananya Choudhury %A Jacqueline Livsey %J Prostate Cancer %D 2012 %I Hindawi Publishing Corporation %R 10.1155/2012/450246 %X Background. The benefit of dose-escalated hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) in prostate cancer is not established. We report 5-year outcome and long-term toxicity data within a phase II clinical trial. Materials and Methods. 60 men with predominantly high-risk prostate cancer were treated. All patients received neoadjuvant hormone therapy, completing up to 6 months in total. Thirty patients were treated with 57£¿Gy in 19 fractions and 30 patients with 60£¿Gy in 20 fractions. Acute and 2-year toxicities were reported and patients followed longitudinally to assess 5 year outcomes and long-term toxicity. Toxicity was measured using RTOG criteria and LENT/SOMA questionnaire. Results. Median followup was 84 months. Five-year overall survival (OS) was 83% and biochemical progression-free survival (bPFS) was 50% for 57£¿Gy. Five-year OS was 75% and bPFS 58% for 60£¿Gy. At 7 years, toxicity by RTOG criteria was acceptable with no grade 3 or above toxicity. Compared with baseline, there was no significant change in urinary symptoms at 2 or 7 years. Bowel symptoms were stable between 2 and 7 years. All patients continued to have significant sexual dysfunction. Conclusion. In high-risk prostate cancer, dose-escalated hypofractionated radiotherapy using IMRT results in encouraging outcomes and acceptable late toxicity. 1. Introduction Dose-escalated radiotherapy improves local and biochemical disease control in localised prostate cancer [1¨C4]. However, this is at the expense of increased late normal tissue toxicity and overall treatment time [3¨C6].There is increasing evidence that the ¦Á/¦Â ratio for prostate cancer may be low [7¨C9], and in one analysis of nearly 6000 patients the calculated ¦Á/¦Â ratio was 1.4 [10]. This suggests that a hypofractionated regimen should be biologically advantageous. A shortened overall treatment time also provides benefits in terms of patient acceptability and health economics [11]. Our group has previously published data on patients treated with 50£¿Gy in 16 daily fractions (equivalent total dose of 66£¿Gy, assuming an ¦Á/¦Â ratio for prostate cancer of 1.5) [12]. However, the biochemical outcome for patients with intermediate or high risk disease was inferior to dose-escalated series using 2£¿Gy per fraction [13]. This finding was replicated in a later study using low-dose hypofractionated radiotherapy [14]. Although there is evidence for improved bPFS with increasing doses of radiotherapy, no overall survival benefit has yet been demonstrated. Indeed, the MRC RT01 study showed equivalent overall %U http://www.hindawi.com/journals/pc/2012/450246/