Sir Peter MacCallum Department of Oncology - Research Publications
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ItemA retrospective review of the long-term outcomes of online adaptive radiation therapy and conventional radiation therapy for muscle invasive bladder cancer(ELSEVIER IRELAND LTD, 2021-09)BACKGROUND AND PURPOSE: To report long-term outcomes of online image-guided (IG) adaptive radiation therapy (aRT) versus conventional IG radiation therapy (cRT) for bladder preservation in muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: A retrospective review of patients with histologically proven MIBC who were prescribed radical intent radiation therapy (RT) following trans-urethral resection of bladder tumour (TURBT) was conducted. There were three groups based on their RT treatment modality: conventional RT (cRT), margin 5 mm adaptive RT (aRT5mm) and margin 7 mm adaptive RT (aRT7mm). RESULTS: 171 patients were included in this study, with median age of 79.4 years (41-90). Approximately half of all patients received concurrent chemotherapy. N = 57 underwent cRT, n = 39 underwent aRT5mm, and n = 75 underwent aRT7mm. Response evaluable patients in all three groups (n = 133) had high rates of complete response (CR, 83%) on first post-RT cystoscopy with no significant differences between the groups. At a median follow-up of 54 months, the 5-year freedom from muscle-invasive failure survival (FFMIFS) in the cRT, aRT5mm, and aRT7mm groups were 75%, 59%, and 98%, respectively. The estimated cancer specific survival (CSS) at 5 years were 60%, 30%, and 59%, respectively. The estimated overall survival (OS) at 5 years were 43%, 26%, and 38%, respectively. The incidence of late grade 3 or 4 toxicity was n = 5 in aRT5mm, n = 2 in cRT group, and n = 1 in aRT7mm. CONCLUSION: IG aRT with 7 mm expansion for MIBC provides higher rates of FFMIFS, similar 5-year CSS and OS, as well as toxicity outcomes when compared to cRT. aRT with 5 mm expansion with this RT protocol is not recommended for treatment.
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ItemPersonalising treatment plan quality review with knowledge-based planning in the TROG 15.03 trial for stereotactic ablative body radiotherapy in primary kidney cancer(BMC, 2021-08-03)INTRODUCTION: Quality assurance (QA) of treatment plans in clinical trials improves protocol compliance and patient outcomes. Retrospective use of knowledge-based-planning (KBP) in clinical trials has demonstrated improved treatment plan quality and consistency. We report the results of prospective use of KBP for real-time QA of treatment plan quality in the TROG 15.03 FASTRACK II trial, which evaluates efficacy of stereotactic ablative body radiotherapy (SABR) for kidney cancer. METHODS: A KBP model was generated based on single institution data. For each patient in the KBP phase (open to the last 31 patients in the trial), the treating centre submitted treatment plans 7 days prior to treatment. A treatment plan was created by using the KBP model, which was compared with the submitted plan for each organ-at-risk (OAR) dose constraint. A report comparing each plan for each OAR constraint was provided to the submitting centre within 24 h of receiving the plan. The centre could then modify the plan based on the KBP report, or continue with the existing plan. RESULTS: Real-time feedback using KBP was provided in 24/31 cases. Consistent plan quality was in general achieved between KBP and the submitted plan. KBP review resulted in replan and improvement of OAR dosimetry in two patients. All centres indicated that the feedback was a useful QA check of their treatment plan. CONCLUSION: KBP for real-time treatment plan review was feasible for 24/31 cases, and demonstrated ability to improve treatment plan quality in two cases. Challenges include integration of KBP feedback into clinical timelines, interpretation of KBP results with respect to clinical trade-offs, and determination of appropriate plan quality improvement criteria.
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ItemProtocol for tumour-focused dose-escalated adaptive radiotherapy for the radical treatment of bladder cancer in a multicentre phase II randomised controlled trial (RAIDER): radiotherapy planning and delivery guidance(BMJ PUBLISHING GROUP, 2020)INTRODUCTION: Daily radiotherapy delivered with radiosensitisation offers patients with muscle invasive bladder cancer (MIBC) comparable outcomes to cystectomy with functional organ preservation. Most recurrences following radiotherapy occur within the bladder. Increasing the delivered radiotherapy dose to the tumour may further improve local control. Developments in image-guided radiotherapy have allowed bladder tumour-focused 'plan of the day' radiotherapy delivery. We aim to test within a randomised multicentre phase II trial whether this technique will enable dose escalation with acceptable rates of toxicity. METHODS AND ANALYSIS: Patients with T2-T4aN0M0 unifocal MIBC will be randomised (1:1:2) between standard/control whole bladder single plan radiotherapy, standard dose adaptive tumour-focused radiotherapy or dose-escalated adaptive tumour-focused radiotherapy (DART). Adaptive tumour-focused radiotherapy will use a library of three plans (small, medium and large) for treatment. A cone beam CT taken prior to each treatment will be used to visualise the anatomy and inform selection of the most appropriate plan for treatment.Two radiotherapy fractionation schedules (32f and 20f) are permitted. A minimum of 120 participants will be randomised in each fractionation cohort (to ensure 57 evaluable DART patients per cohort).A comprehensive radiotherapy quality assurance programme including pretrial and on-trial components is instituted to ensure standardisation of radiotherapy planning and delivery.The trial has a two-stage non-comparative design. The primary end point of stage I is the proportion of patients meeting predefined normal tissue constraints in the DART group. The primary end point of stage II is late Common Terminology Criteria for Adverse Events grade 3 or worse toxicity aiming to exclude a rate of >20% (80% power and 5% alpha, one sided) in each DART fractionation cohort. Secondary end points include locoregional MIBC control, progression-free survival overall survival and patient-reported outcomes. ETHICS AND DISSEMINATION: This clinical trial is approved by the London-Surrey Borders Research Ethics Committee (15/LO/0539). The results when available will be disseminated via peer-reviewed scientific journals, conference presentations and submission to regulatory authorities. TRIAL REGISTRATION NUMBER: NCT02447549; Pre-results.