Clinical Outcomes of a Randomized Trial of Adaptive Plan-of-the-Day Treatment in Patients Receiving Ultra-hypofractionated Weekly Radiation Therapy for Bladder Cancer

Published on Dec 11, 2020in International Journal of Radiation Oncology Biology Physics5.859
· DOI :10.1016/J.IJROBP.2020.11.068
Robert Huddart83
Estimated H-index: 83
(ICR: Institute of Cancer Research),
Shaista Hafeez13
Estimated H-index: 13
(ICR: Institute of Cancer Research)
+ 21 AuthorsHybrid Investigators1
Estimated H-index: 1
Purpose Hypofractionated radiation therapy 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 radiation therapy delivery could improve outcomes by minimizing the volume of normal tissue irradiated. The HYBRID trial assessed the multicenter implementation, safety, and efficacy of this strategy. Methods HYBRID is a Phase II randomized trial that was conducted at 14 UK hospitals. Patients with T2-T4aN0M0 muscle-invasive bladder cancer unsuitable for radical therapy received 36 Gy in 6 weekly fractions, randomized (1:1) to standard planning (SP) or adaptive planning (AP) using a minimization algorithm. For AP, a pretreatment cone beam computed tomography (CT) was used to select the POD from 3 plans (small, medium, and large). Follow-up included standard cystoscopic, radiologic, and clinical assessments. The primary endpoint was nongenitourinary Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 (≥G3) toxicity within 3 months of radiation therapy. A noncomparative single stage design aimed to exclude ≥30% toxicity rate in each planning group in patients who received ≥1 fraction of radiation therapy. Local control at 3-months (both groups combined) was a key secondary endpoint. Results Between April 15, 2014, and August 10, 2016, 65 patients were enrolled (SP, n = 32; AP, n = 33). The median follow-up time was 38.8 months (interquartile range [IQR], 36.8-51.3). The median age was 85 years (IQR, 81-89); 68% of participants (44 of 65) were male; and 98% of participants had grade 3 urothelial cancer. In 63 evaluable participants, CTCAE ≥G3 nongenitourinary toxicity rates were 6% (2 of 33; 95% confidence interval [CI], 0.7%-20.2%) for the AP group and 13% (4 of 30; 95% CI, 3.8%-30.7%) for the SP group. 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%). Conclusions POD adaptive radiation therapy was successfully implemented across multiple centers. Weekly ultrahypofractionated 36 Gy/6 fraction radiation therapy is safe and provides good local control rates in this older patient population.
#1Joseph B. JohnH-Index: 1
Last. Susan Harden (Cambridge University Hospitals NHS Foundation Trust)H-Index: 21
view all 8 authors...
Abstract Background UK Bladder cancer survival remains low. Nonmetastatic muscle-invasive bladder cancer (MIBC) is potentially curable. It is unclear how many patients receive nonradical treatment owing to advanced age, comorbidities, or alternative factors. Objective To describe treatments and assess survival by disease stage and sex for all newly diagnosed nonmetastatic MIBC in England in 2016, and to observe associations between comorbidities and treatments. Design, setting, and participants ...
4 CitationsSource
#1Shaista Hafeez (ICR: Institute of Cancer Research)H-Index: 13
#2Emma Patel (Mount Vernon Hospital)H-Index: 1
Last. Robert Huddart (ICR: Institute of Cancer Research)H-Index: 83
view all 10 authors...
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 ta...
10 CitationsSource
#1Emma Patel (UCLH: University College London Hospitals NHS Foundation Trust)H-Index: 5
#1Emma Patel (UCLH: University College London Hospitals NHS Foundation Trust)H-Index: 1
Last. Robert Huddart (The Royal Marsden NHS Foundation Trust)H-Index: 83
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Abstract Background and Purpose Hypofractionated bladder RT with or without image guided adaptive planning (HYBRID) is a multicentre clinical trial investigating “Plan of the Day” (PoD) adaptive radiotherapy for bladder cancer. To ensure correct PoD selection a pre-accrual guidance and assessment module was developed as part of an image guided radiotherapy quality assurance (IGRT QA) credentialing programme. This study aimed to evaluate its feasibility and effectiveness across multiple recruitin...
7 CitationsSource
#1M. VarugheseH-Index: 1
#2S. TreeceH-Index: 1
Last. K. Drinkwater (Royal College of Radiologists)H-Index: 12
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Abstract Aims With the failure to improve outcomes of patients with bladder cancer over the last 30 years, this study was developed to benchmark contemporary UK radiotherapy practice for the management of muscle invasive bladder cancer (MIBC) against published national guidance. Materials and methods All UK radiotherapy centres were invited to complete a questionnaire for each patient with MIBC starting bladder radiotherapy over a 16-week period from December 2016. Results Sixty-nine per cent (4...
9 CitationsSource
#1Dan-Olle Westergren (Uppsala University)H-Index: 2
#2Truls Gårdmark (Danderyds sjukhus)H-Index: 1
Last. Per-Uno Malmström (Uppsala University)H-Index: 62
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AbstractPurpose:While radical cystectomy remains the standard treatment for muscle-invasive bladder cancer, the natural history of patients unable or unwilling to receive curative intent therapy (CIT) is not well understood. The study objective was to identify these patients in a population-based cohort and investigate the clinical profile and describe time to mortality.Material and Methods:BladderBaSE, a database collected 1997-2014 was analyzed. 9 811 patients with stage T2-T4 were identified....
16 CitationsSource
#1Shaista Hafeez (ICR: Institute of Cancer Research)H-Index: 13
#2Fiona McDonald (The Royal Marsden NHS Foundation Trust)H-Index: 20
Last. Robert Huddart (ICR: Institute of Cancer Research)H-Index: 83
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Purpose and Objectives We report on the clinical outcomes of a phase 2 study assessing image guided hypofractionated weekly radiation therapy in bladder cancer patients unsuitable for radical treatment. Methods and Materials Fifty-five patients with T2-T4aNx-2M0-1 bladder cancer not suitable for cystectomy or daily radiation therapy treatment were recruited. A "plan of the day" radiation therapy approach was used, treating the whole (empty) bladder to 36 Gy in 6 weekly fractions. Acute toxicity ...
27 CitationsSource
#1Helen McNairH-Index: 30
#2Shaista HafeezH-Index: 13
Last. Robert HuddartH-Index: 83
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Objective:The implementation of plan of the day selection for patients receiving radiotherapy (RT) for bladder cancer requires efficient and confident decision-making. This article describes the development of a training programme and maintenance of competency.Methods:Cone beam CT (CBCT) images acquired on patients receiving RT for bladder cancer were assessed to establish baseline competency and training needs. A training programme was implemented, and observers were asked to select planning ta...
21 CitationsSource
#1Anne Vestergaard (Aarhus University Hospital)H-Index: 12
#2Ludvig Paul Muren (Aarhus University Hospital)H-Index: 31
Last. Morten Høyer (Aarhus University Hospital)H-Index: 43
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AbstractBackground. Patients with urinary bladder cancer often display large changes in the shape and size of their bladder target during a course of radiotherapy (RT), making adaptive RT (ART) appealing for this tumour site. We are conducting a clinical phase II trial of daily plan selection-based ART for bladder cancer and here report dose-volume data from the first 20 patients treated in the trial.Material and methods. All patients received 60 Gy in 30 fractions to the bladder; in 13 of the p...
48 CitationsSource
#1Robert Huddart (The Royal Marsden NHS Foundation Trust)H-Index: 83
#2Fiona McDonald (The Royal Marsden NHS Foundation Trust)H-Index: 20
Last. Emma HallH-Index: 57
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4 CitationsSource
#1Fiona McDonald (The Royal Marsden NHS Foundation Trust)H-Index: 20
#2Susan Lalondrelle (The Royal Marsden NHS Foundation Trust)H-Index: 12
Last. Robert Huddart (The Royal Marsden NHS Foundation Trust)H-Index: 83
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Abstract Aims Adaptive bladder radiotherapy, with plan of the day selection and plan library development based on individual filling patterns, has been previously modelled in patients receiving weekly hypofractionated treatment and improved geometric accuracy has been shown. The aim of this study was to assess the clinical implementation of the technique. Materials and methods Conformal plans (with small, intermediate and large planning target volumes) were developed for 25 patients. After pre-t...
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Cited By4
#1Valérie Fonteyne (Ghent University Hospital)H-Index: 27
#2P. SargosH-Index: 1
External beam radiotherapy (EBRT), as part of a trimodality approach, is an attractive bladder-preserving alternative to radical cystectomy. Several EBRT regimens with different treatment volumes have been described with similar tumour control and, so far, clear recommendations on the optimal radiotherapy regimen and treatment volume are lacking. The current review summarises EBRT literature on dose prescription, fractionation as well as treatment volume in order to guide clinicians in their dai...
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#1Paul SargosH-Index: 18
#2Brian C. Baumann (WashU: Washington University in St. Louis)H-Index: 16
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#1V. Kong (Princess Margaret Cancer Centre)H-Index: 1
#1Adham Hijab (ICR: Institute of Cancer Research)H-Index: 1
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Technological advancement has facilitated patient-specific radiotherapy in bladder cancer. This has been made possible by developments in image-guided radiotherapy (IGRT). Particularly transformative has been the integration of volumetric imaging into the workflow. The ability to visualise the bladder target using cone beam computed tomography and magnetic resonance imaging initially assisted with determining the magnitude of inter- and intra-fraction target change. It has led to greater confide...
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#1Abhishek A. Solanki (Loyola University Medical Center)H-Index: 11
#2B.P. Venkatesulu (Loyola University Medical Center)H-Index: 1
Last. J.A. Efstathiou (Harvard University)H-Index: 1
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Abstract Advances in the field of cancer biology and molecular techniques have led to a better understanding of the molecular underpinnings driving cancer development and outcomes. Simultaneously, advances in imaging have allowed for improved sensitivity in initial staging, radiotherapy planning and follow-up of numerous cancers. These two phenomena have led to the development of biomarkers that can guide therapy in multiple malignancies. In bladder cancer, there is extensive ongoing research in...
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#1F. Slevin (University of Leeds)
#1F. Slevin (University of Leeds)H-Index: 3
Last. Ann Henry (University of Leeds)H-Index: 32
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Abstract Muscle-invasive bladder cancer is most frequently diagnosed in older patients and the presence of multimorbidity and frailty is common. This means that many patients are unsuitable for definitive treatment with radical cystectomy/(chemo)radiotherapy and are at risk of poor survival outcomes and considerable disease-related morbidity. Screening tools for functional status may be useful to determine the most appropriate treatment for an older person and to identify patients most likely to...