A randomised assessment of image guided radiotherapy within a phase 3 trial of conventional or hypofractionated high dose intensity modulated radiotherapy for prostate cancer.

Image-guided radiotherapy (IGRT) improves treatment set-up accuracy and provides the opportunity to reduce target volume margins. We introduced IGRT methods using standard (IGRT-S) or reduced (IGRT-R) margins in a randomised phase 2 substudy within CHHiP trial. We present a pre-planned analysis of the impact of IGRT on dosimetry and acute/late pelvic side effects using gastrointestinal and genitourinary clinician and patient-reported outcomes (PRO) and evaluate efficacy.

CHHiP is a randomised phase 3, non-inferiority trial for men with localised prostate cancer. 3216 patients were randomly assigned to conventional (74 Gy in 2 Gy/fraction (f) daily) or moderate hypofractionation (60 or 57 Gy in 3 Gy/f daily) between October 2002 and June 2011. The IGRT substudy included a second randomisation assigning to no-IGRT, IGRT-S (standard CTV-PTV margins), or IGRT-R (reduced CTV-PTV margins). Primary substudy endpoint was late RTOG bowel and urinary toxicity at 2 years post-radiotherapy.

Between June 2010 to July 2011, 293 men were recruited from 16 centres. Median follow-up is 56.9(IQR 54.3-60.9) months. Rectal and bladder dose-volume and surface percentages were significantly lower in IGRT-R compared to IGRT-S group; (p < 0.0001). Cumulative proportion with RTOG grade ≥ 2 toxicity reported to 2 years for bowel was 8.3(95% CI 3.2-20.7)%, 8.3(4.7-14.6)% and 5.8(2.6-12.4)% and for urinary 8.4(3.2-20.8)%, 4.6(2.1-9.9)% and 3.9(1.5-9.9)% in no IGRT, IGRT-S and IGRT-R groups respectively. In an exploratory analysis, treatment efficacy appeared similar in all three groups.

Introduction of IGRT was feasible in a national randomised trial and IGRT-R produced dosimetric benefits. Overall side effect profiles were acceptable in all groups but lowest with IGRT and reduced margins.

97182923.

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2019 Nov 22 [Epub ahead of print]

Julia Murray, Clare Griffin, Sarah Gulliford, Isabel Syndikus, John Staffurth, Miguel Panades, Christopher Scrase, Chris Parker, Vincent Khoo, Jamie Dean, Helen Mayles, Philip Mayles, Simon Thomas, Olivia Naismith, Angela Baker, Helen Mossop, Clare Cruickshank, Emma Hall, David Dearnaley, CHHiP Investigators

The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK., The Institute of Cancer Research, London, UK., The Institute of Cancer Research, London, UK; Department of Radiotherapy, University College London Hospitals NHS Foundation Trust, UK., Clatterbridge Cancer Centre, Wirral, UK., Cardiff University/Velindre Cancer Centre, UK., Lincoln County Hospital, UK., Ipswich Hospital, UK., Addenbrooke's Hospital, Cambridge, UK., Royal Marsden NHS Foundation Trust, London, UK., Royal Berkshire Hospital, Reading, UK., The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK. Electronic address: .