Clinical Outcomes of a Randomized Trial of Adaptive Plan-of-the-Day Treatment in Patients Receiving Ultra-hypofractionated Weekly Radiation Therapy for Bladder Cancer.
Date
2021-06-01Author
Huddart, R
Hafeez, S
Lewis, R
McNair, H
Syndikus, I
Henry, A
Staffurth, J
Dewan, M
Vassallo-Bonner, C
Moinuddin, SA
Birtle, A
Horan, G
Rimmer, Y
Venkitaraman, R
Khoo, V
Mitra, A
Hughes, S
Gibbs, S
Kapur, G
Baker, A
Hansen, VN
Patel, E
Hall, E
HYBRID Investigators,
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
HYBRID Investigators
Research team
Clinical Trials & Statistics Unit
ICR-CTSU Urology and Head and Neck Trials Team
Clinical Academic Radiotherapy (Huddart)
Language
eng
Date accepted
2020-11-25
License start date
2020-12-11
Citation
International journal of radiation oncology, biology, physics, 2020
Publisher
ELSEVIER SCIENCE INC