Protocol for hypofractionated adaptive radiotherapy to the bladder within a multicentre phase II randomised trial: radiotherapy planning and delivery guidance

Abstract

Introduction: Patients with muscle invasive bladder cancer (MIBC) who are unfit and unsuitable for standard radical treatment with cystectomy or daily radiotherapy present a large unmet clinical need. Untreated, they suffer high cancer specific mortality and risk significant disease-related local symptoms. Hypofractionated radiotherapy (delivering higher doses in fewer fractions/visits) is a potential treatment solution but could be compromised by the mobile nature of the bladder, resulting in target misses in a significant proportion of fractions. Adaptive 'plan of the day' image-guided radiotherapy delivery may improve the precision and accuracy of treatment. We aim to demonstrate within a randomised multicentre phase II trial feasibility of plan of the day hypofractionated bladder radiotherapy delivery with acceptable rates of toxicity.

Methods and analysis: Patients with T2-T4aN0M0 MIBC receiving 36 Gy in 6-weekly fractions are randomised (1:1) between treatment delivered using a single-standard plan or adaptive radiotherapy using a library of three plans (small, medium and large). A cone beam CT taken prior to each treatment is used to visualise the anatomy and select the most appropriate plan depending on the bladder shape and size. A comprehensive radiotherapy quality assurance programme has been instituted to ensure standardisation of radiotherapy planning and delivery. The primary endpoint is to exclude >30% acute grade >3 non-genitourinary toxicity at 3 months for adaptive radiotherapy in patients who received >1 fraction (p0=0.7, p1=0.9, α=0.05, β=0.2). Secondary endpoints include local disease control, symptom control, late toxicity, overall survival, patient-reported outcomes and proportion of fractions benefiting from adaptive planning. Target recruitment is 62 patients.

Ethics and dissemination: The trial is approved by the London-Surrey Borders Research Ethics Committee (13/LO/1350). The results will be disseminated via peer-reviewed scientific journals, conference presentations and submission to regulatory authorities.

Trial registration number: NCT01810757.

Keywords: bladder disorders; oncology; radiation oncology; radiotherapy; urological tumours.

Conflict of interest statement

Competing interests: SH reports non-financial support from Elekta (Elekta AB, Stockholm, Sweden), non-financial support from Merck Sharp & Dohme, personal fees and non-financial support from Roche outside the submitted work; EP, AW, KW-O, VH, HM, EM, and RL have no conflicts to disclose; EH reports grants from Cancer Research UK during the conduct of the study; grants from Accuray, grants from Varian Medical Systems, outside the submitted work; RH reports non-financial support from Janssen, grants and personal fees from MSD, personal fees from Bristol Myers Squibb, grants from CRUK, other from Nektar, personal fees and non-financial support from Roche, outside the submitted work.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1

Trial schema. RTOG, Radiation TherapyOncology Group.