HERMES: Randomized Trial of 2-Fraction or 5-Fraction Magnetic Resonance Imaging–Guided Adaptive Prostate Radiation Therapy
Sian Cooper, Rosalyne Westley, Katie Biscombe, Alex Dunlop, Adam Mitchell, Uwe Oelfke, Simeon Nill, Georgina Manning, Stephanie Burnett, Julia Murray, Anna Wilkins, Nina Tunariu, Derek Price, Aidan Adkins, Angela Pathmanathan, Greta Bucinskaite, S. Hafeez, Chris Parker, Ragu Ratnakumaran, Helena M. Verkooijen, S. Alexander, Trina Herbert, Emma Hall, Alison Tree
Abstract
PURPOSE: To demonstrate the safety and feasibility of 2-fraction stereotactic body radiation therapy (SBRT) for prostate cancer. METHODS AND MATERIALS: This single-center, noncomparative, phase 2/R-IDEAL 2b trial randomized 46 patients with intermediate/lower high-risk prostate cancer with visible gross tumor volume on multiparametric magnetic resonance imaging to receive 36.25 Gy in 5 fractions over 10 days or 24 Gy in 2 fractions with a gross tumor volume boost up to 27 Gy over 8 days. All treatment was delivered on a magnetic resonance linac with daily adaptive replanning. The primary endpoint was acute grade ≥2 (G2+) genitourinary (GU) toxicity (Common Terminology Criteria for Adverse Events version 5.0). Secondary endpoints include gastrointestinal (GI) toxicity and patient-reported outcomes. RESULTS: G2+ GU acute toxicity was observed in 6 of 22 patients (27.3%; 95% CI, 0.11-0.50) in the 2-fraction group and 7 of 24 patients (29.2%; 95% CI, 0.13-0.50) in the 5-fraction group. There were no grade 3 GU toxicities. G2+ urinary frequency rose from 4.5% (1 of 22) at week 2 to 13.6% (3 of 22) at week 4 in 2-fraction SBRT. G2+ urinary frequency peaked earlier in 5-fraction SBRT at 16.7% (4 of 24) in week 2, falling to 12.5% (3 of 24) at week 4. At 12 weeks, median Expanded Prostate Cancer Index Composite-26 urinary incontinence score was 85.5 (IQR, 75-100) for 2-fraction SBRT and 100 (IQR, 93.8-100) for 5-fraction SBRT. Urinary irritative-obstructive scores were higher at 12 weeks in the 2-fraction group (93.8; IQR, 87.5-100) than in the 5-fraction group (87.5; IQR, 81.3-93.8). Peak International Prostate Symptoms Score was lower in the 2-fraction group (8; IQR, 4-11) than in the 5-fraction group (13.5; IQR, 10-17). G2+ GI acute toxicity occurred in 3 of 24 (6.8%) after 5-fraction SBRT, but none after 2-fraction SBRT. CONCLUSIONS: Acceptable acute GU toxicity was seen after 2-fraction SBRT. Acute GI toxicity was low. Randomized trials are warranted to explore late toxicity and biochemical control.