A randomized hypofractionation dose escalation trial for high risk prostate cancer patients: interim analysis of acute toxicity and quality of life in 124 patients

Darius Norkus,Mark De Ridder,Ernestas Janulionis,Eduardas Aleknavicius,Harijati Versmessen,Romas Griskevicius,Benedikt Engels,Guy Storme,Agata Karklelyte,Konstantinas Povilas Valuckas

doi:10.1186/1748-717x-8-206

Abstract

BackgroundThe α/β ratio for prostate cancer is postulated being in the range of 0.8 to 2.2 Gy, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. To do so, we carried out a randomized trial comparing hypofractionated and conventionally fractionated image-guided intensity modulated radiotherapy (IG-IMRT) in high-risk prostate cancer. Here, we report on acute toxicity and quality of life (QOL) for the first 124 randomized patients.MethodsThe trial compares 76 Gy in 38 fractions (5 fractions/week) (Arm 1) to 63 Gy in 20 fractions (4 fractions/week) (Arm 2) (IG-IMRT). Prophylactic pelvic lymph node irradiation with 46 Gy in 23 fractions sequentially (Arm 1) and 44 Gy in 20 fractions simultaneously (Arm 2) was applied. All patients had long term androgen deprivation therapy (ADT) started before RT. Both physician-rated acute toxicity and patient-reported QOL using EPIC questionnaire are described.ResultsThere were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity. Compared to conventional fractionation (Arm 1), GI and GU toxicity both developed significantly earlier but also disappeared earlier in the Arm 2, reaching significant differences from Arm 1 at week 8 and 9. In multivariate analyses, only parameter shown to be related to increased acute Grade ≥1 GU toxicity was the study Arm 2 (p = 0.049). There were no statistically significant differences of mean EPIC scores in any domain and sub-scales. The clinically relevant decrease (CRD) in EPIC urinary domain was significantly higher in Arm 2 at month 1 with a faster recovery at month 3 as compared to Arm 1.ConclusionsHypofractionation at 3.15 Gy per fraction to 63 Gy within 5 weeks was well tolerated. The GI and GU physician-rated acute toxicity both developed earlier but recovered faster using hypofractionation. There was a correlation between acute toxicity and bowel and urinary QOL outcomes. Longer follow-up is needed to determine the significance of these associations with late toxicity.

Highlights

The α/β ratio for prostate cancer is postulated being in the range of 0.8 to 2.2 Gy, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation
If the prostate cancer α/β value is consistently lower than the appropriate values considered for late normaltissue morbidity, significant increases in tumor control can be expected by changing from conventional fractionation to fewer larger fractions, without increasing the risk of acute and late toxicity
In this interim report we describe both, physicianrelated acute toxicities and patient-reported quality of life (QOL) measurements by validated Expanded Prostate Cancer Index Composite (EPIC), from the prospective randomized trial comparing hypofractionated and conventionally fractionated image guided IMRT (IG-IMRT) combined with androgen deprivation therapy for the first 124 high risk prostate cancer patients that were randomized in this study

Summary

Introduction

The α/β ratio for prostate cancer is postulated being in the range of 0.8 to 2.2 Gy, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. We carried out a randomized trial comparing hypofractionated and conventionally fractionated image-guided intensity modulated radiotherapy (IG-IMRT) in high-risk prostate cancer. Fractionated dose escalation, There is increasing evidence that the α/β ratio for prostate cancer may be low and is in the range of 0.8 to 2.2 Gy [11]. If the prostate cancer α/β value is consistently lower than the appropriate values considered for late normaltissue morbidity, significant increases in tumor control can be expected by changing from conventional fractionation to fewer larger fractions, without increasing the risk of acute and late toxicity. The fear of severe acute and late genitourinary (GU) and gastrointestinal (GI) toxicity has been an argument against hypofractionated dose escalation to the prostate and pelvic lymph nodes. No significant increase has been seen in the acute toxicity or the late adverse events as compared to standart dose regiments [3,4,5,6]

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Discussion

Conclusion