Hypofractionation, known as delivering higher doses of radiation in fewer fractions, appears to be feasible and non-inferior compared with conventional fractionated radiotherapy.
Hypofractionation, known as delivering higher doses of radiation in fewer fractions, appears to be feasible and non-inferior compared with conventional fractionated radiotherapy, according to 5-year follow-up results of the randomized HYPRO trial, which were reported at the 2015 ASTRO Annual Meeting.
The rates of relapse-free survival (RFS), the primary endpoint of the trial, were comparable in both arms: 80% for hypofractionated radiotherapy versus 77% for conventional fractionated radiotherapy. Acute toxicities were similar, with slightly higher gastrointestinal (GI) toxicities reported in the hypofractionated arm.
“Hypofractionated radiotherapy achieved a higher relapse-free survival rate compared with conventional fractionated radiotherapy, but the difference between the two arms was not statistically significantly different. The acute and late toxicity are comparable between the two schedules. At this point, we can say that hypofractionated radiotherapy is safe and of interest to be introduced in the clinic,” said lead author Luca Incrocci, MD, Department of Radiation Oncology, Erasmus MC Cancer Institute in Rotterdam, the Netherlands, who reported the results during the meeting.
The study enrolled 820 patients with intermediate- or high-risk prostate cancer (stage T1b to T4) at seven centers in the Netherlands between March 2007 and December 2010. Patients were randomized 1:1 to receive hypofractionated radiotherapy (19 fractions of 3.4 Gy in 6.5 weeks, 3 fractions per week) or conventional fractionated radiotherapy (39 fractions of 2 Gy in 8 weeks, 5 fractions per week). Both groups had a similar distribution of demographic and disease characteristics. Median age was 71 years (range, 44-85 years).
HYPRO was a non-inferiority trial designed to detect an absolute reduction of 10% in relapse rate at 5 years in the hypofractionated arm.
Patients were stratified into three risk groups according to seminal vesicle involvement. Low-risk patients were excluded, and concomitant hormone therapy was allowed.
At a median follow-up of 5 years, 804 patients were evaluable for RFS. Almost two-thirds of patients were treated with hormonal therapy. A multivariate analysis found that a Gleason score of 7 or lower and use of hormonal therapy for 12 months or longer were each statistically significantly associated with higher RFS.
Overall survival at 5 years was 86% in both arms, though follow-up was too short to detect a survival benefit, Incrocci said.
“With new radiation schedules, we need to worry about toxicity,” he continued.
Acute GI toxicity (grade 2 or higher) at 120 days was slightly higher in the hypofractionated arm: 31.2% versus 42%, respectively, for an absolute difference of 10.8%. Acute genitourinary (GU) toxicity was 57.8% for the conventional arm versus 60.5% for hypofractionation, an absolute difference of 2.7%. These differences were not statistically significant, Incrocci said.
Unpublished data show no significant difference in late toxicity (GU, GI, and sexual function) between the two arms. Further analysis on the data will be forthcoming, Incrocci added.