Hypofractionated radiotherapy can be used to treat patients with muscle invasive bladder cancer unable to have radical therapy. Toxicity is a key concern but adaptive "plan-of the day" (POD) image guided radiotherapy delivery (IGRT) could improve outcomes by minimising volume of normal tissue irradiated. The XXXX trial assessed multi-centre implementation, safety and efficacy of this strategy.
XXXX is a phase II randomised trial conducted at 14 UK hospitals. Patients with T2-T4aN0M0 muscle invasive bladder cancer unsuitable for radical therapy received 36Gray in 6 weekly fractions, randomised (1:1) to standard planning (SP) or adaptive planning (AP) using a minimisation algorithm. For AP a pre-treatment cone beam CT was used to select the POD from three plans (small, medium, large). Follow-up included standard cystoscopic, radiological, and clinical assessments. The primary endpoint was non-genitourinary CTCAE ≥grade 3 (>G3) toxicity within 3-months of radiotherapy. A non-comparative single stage design aimed to exclude >30% toxicity rate in each planning group in patients who received >1 fraction of radiotherapy. Local control at 3-months (both groups combined) was a key secondary endpoint.
Between April 15 2014 and August 10 2016, 65 patients were enrolled (SP32; AP33). Median follow up was 38·8 months (IQR 36·8-51·3). Median age was 85 years (IQR 81-89); 68% (44/65) were male, 98% had grade 3 TCC. In 63 evaluable participants, CTCAE >G3 non-GU toxicity rates were 6% (2/33, 95% CI: 0·7-20·2%) for AP and 13% (4/30, 95% CI: 3·8-30·7%) for SP. Disease was present in 9/48 participants assessed at 3 months, giving a local control rate of 81·3% (95% CI: 67·4-91·1%).
Plan of the day adaptive radiotherapy was successfully implemented across multiple centres. Weekly ultra-hypofractionated 36 Gray/6 fraction radiotherapy is safe and provides good local control rates in this older patient population.
International journal of radiation oncology, biology, physics. 2020 Dec 11 [Epub ahead of print]
Robert Huddart, Shaista Hafeez, Rebecca Lewis, Helen McNair, Isabelle Syndikus, Ann Henry, John Staffurth, Monisha Dewan, Catalina Vassallo-Bonner, Syed Ali Moinuddin, Alison Birtle, Gail Horan, Yvonne Rimmer, Ramachandran Venkitaraman, Vincent Khoo, Anita Mitra, Simon Hughes, Stephanie Gibbs, Gaurav Kapur, Angela Baker, Vibeke Nordmark Hansen, Emma Patel, Emma Hall, HYBRID Investigators
The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK. Electronic address: ., The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK., The Institute of Cancer Research, London, UK., Royal Marsden NHS Foundation Trust, London, UK., Radiotherapy Department, Oxford University Hospitals NHS Foundation Trust., Leeds Teaching Hospitals NHS Trust., Velindre University NHS Trust., The Institute of Cancer Research, London, UK. Electronic address: ., Patient representative., Academic unit of Oncology, Department of Oncology and Metabolism, Medical School, University of Sheffield., Lancashire Teaching Hospitals NHS Foundation Trust., Queen Elizabeth Hospital Kings Lynn NHS Trust., Cambridge University Hospitals NHS Foundation Trust., East Suffolk and North Essex NHS Foundation Trust., University College London Hospitals NHS Foundation Trust., Guy's and St Thomas' NHS Foundation Trust., Barking, Havering and Redbridge University Hospitals NHS Trust., Norfolk and Norwich University Hospitals NHS Foundation Trust., Odense University Hospital, Denmark., Radiotherapy Trials QA Group (RTTQA), Mount Vernon Cancer Centre.