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Hypofractionated radiotherapy for prostate cancer – Authors' reply
Correspondence
Hypofractionated radiotherapy for prostate cancer Authors’ reply Radiation oncologists are wise to be cautious and demand highquality evidence before altering their standards of care. Once given, radiotherapy cannot be taken away, and it is the late side-effects occurring at least 6 months, but often years, after treatment that determine safety outcomes. We were particularly concerned about safety in the CHHiP trial and demanded 2 year outcome data1 before fully expanding the multicentre study. We collected multifaceted side-effect data using well established physician-reported and patient-reported outcome measures to comprehensively capture treatment-related toxicity. These safety data at both 2 years1,2 and 5 years3 post treatment have been reassuring, and 10 year outcomes will be reported in due course. Of note, gastrointestinal side-effects from radiotherapy have more than halved since the previous UK Medical Research Council RT01 study.2–4 This reduction is probably due to both a refinement of the radiotherapy technique with a three-stage simultaneous integrated boost and rigorous application of normal tissue dose constraints. We agree with Sabin B Motwani and Rahul D Tedulkar that we have established the safety of hypofractionation in the CHHiP trial, but that extrapolation to methods using more generous overall target volume margins could be unwise.5 Further analysis of long-term patientreported outcomes is in progress, but presently we have no evidence of increased bowel, bladder, or sexual dysfunction issues at 5 years for the hypofractionated schedules. Full sets of radiation dose distributions have been collected for most patients. Sophisticated assessment of the
association between dose volume and dose surface toxicity is in progress to include the anal canal, rectum, bowel, bladder, and urethral bulb to generate dose constraints specifically for the hypofractionation schedules. These results might permit further treatment refinement, but we do not believe that a delay in the introduction of quality-controlled modest hypofractionation for prostate cancer is necessary.5 We declare no competing interests.
David Dearnaley, Emma Hall [email protected] The Institute of Cancer Research, London SM2 5NG, UK (DD, EH) and Royal Marsden NHS Foundation Trust, London, UK (DD) 1
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www.thelancet.com/oncology Vol 17 December 2016
Dearnaley D, Syndikus I, Sumo G, et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial. Lancet Oncol 2012; 13: 43–54. Wilkins A, Mossop H, Syndikus I, et al. Hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate-risk localised prostate cancer: 2-year patient-reported outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol 2015; 16: 1605–16. Dearnaley D, Syndikus I, Mossop H, et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol 2016; 17: 1047–60. Dearnaley DP, Jovic G, Syndikus I, et al. Escalated-dose versus control-dose conformal radiotherapy for prostate cancer: long-term results from the MRC RT01 randomised controlled trial. Lancet Oncol 2014; 15: 464–73. Dearnaley D, P., Syndikus I, Gulliford S, Hall E. Hypofractionation for prostate cancer: time to change. Clin Oncol (R Coll Radiol) 2016; published online Oct 22. DOI:10.1016/j. clon.2016.09.020.
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Hypofractionated radiotherapy for prostate cancer Authors’ reply Radiation oncologists are wise to be cautious and demand highquality evidence before altering their standards of care. Once given, radiotherapy cannot be taken away, and it is the late side-effects occurring at least 6 months, but often years, after treatment that determine safety outcomes. We were particularly concerned about safety in the CHHiP trial and demanded 2 year outcome data1 before fully expanding the multicentre study. We collected multifaceted side-effect data using well established physician-reported and patient-reported outcome measures to comprehensively capture treatment-related toxicity. These safety data at both 2 years1,2 and 5 years3 post treatment have been reassuring, and 10 year outcomes will be reported in due course. Of note, gastrointestinal side-effects from radiotherapy have more than halved since the previous UK Medical Research Council RT01 study.2–4 This reduction is probably due to both a refinement of the radiotherapy technique with a three-stage simultaneous integrated boost and rigorous application of normal tissue dose constraints. We agree with Sabin B Motwani and Rahul D Tedulkar that we have established the safety of hypofractionation in the CHHiP trial, but that extrapolation to methods using more generous overall target volume margins could be unwise.5 Further analysis of long-term patientreported outcomes is in progress, but presently we have no evidence of increased bowel, bladder, or sexual dysfunction issues at 5 years for the hypofractionated schedules. Full sets of radiation dose distributions have been collected for most patients. Sophisticated assessment of the
association between dose volume and dose surface toxicity is in progress to include the anal canal, rectum, bowel, bladder, and urethral bulb to generate dose constraints specifically for the hypofractionation schedules. These results might permit further treatment refinement, but we do not believe that a delay in the introduction of quality-controlled modest hypofractionation for prostate cancer is necessary.5 We declare no competing interests.
David Dearnaley, Emma Hall [email protected] The Institute of Cancer Research, London SM2 5NG, UK (DD, EH) and Royal Marsden NHS Foundation Trust, London, UK (DD) 1
2
3
4
5
www.thelancet.com/oncology Vol 17 December 2016
Dearnaley D, Syndikus I, Sumo G, et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial. Lancet Oncol 2012; 13: 43–54. Wilkins A, Mossop H, Syndikus I, et al. Hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate-risk localised prostate cancer: 2-year patient-reported outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol 2015; 16: 1605–16. Dearnaley D, Syndikus I, Mossop H, et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol 2016; 17: 1047–60. Dearnaley DP, Jovic G, Syndikus I, et al. Escalated-dose versus control-dose conformal radiotherapy for prostate cancer: long-term results from the MRC RT01 randomised controlled trial. Lancet Oncol 2014; 15: 464–73. Dearnaley D, P., Syndikus I, Gulliford S, Hall E. Hypofractionation for prostate cancer: time to change. Clin Oncol (R Coll Radiol) 2016; published online Oct 22. DOI:10.1016/j. clon.2016.09.020.
e518