Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2013 Sep 4:8:206.
doi: 10.1186/1748-717X-8-206.

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  1 , Agata Karklelyte, Benedikt Engels, Harijati Versmessen, Romas Griskevicius, Mark De Ridder, Guy Storme, Eduardas Aleknavicius, Ernestas Janulionis, Konstantinas Povilas Valuckas
Affiliations
Clinical Trial

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 et al. Radiat Oncol. .

Abstract

Background: 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. 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.

Methods: The 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.

Results: There 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.

Conclusions: Hypofractionation 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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Weekly changes in the mean GU and GI toxicity.
Figure 2
Figure 2
Mean change from baseline ± SE of urinary domain and subscales.
Figure 3
Figure 3
Mean change from baseline ± SE of bowel domain and subscales.
See this image and copyright information in PMC

References

    1. Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR. et al.Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys. 2008;70:67–74. doi: 10.1016/j.ijrobp.2007.06.054. - DOI - PubMed
    1. Cahlon O, Zelefsky MJ, Shippy A, Chan H, Fuks Z, Yamada Y. et al.Ultra-high dose (86.4 Gy) IMRT for localized prostate cancer: toxicity and biochemical outcomes. Int J Radiat Oncol Biol Phys. 2008;71:330–337. doi: 10.1016/j.ijrobp.2007.10.004. - DOI - PubMed
    1. Norkus D, Miller A, Kurtinaitis J. et al.A randomized trial comparing hypofractionated and conventionally fractionated three-dimensional external-beam radiotherapy for localized prostate adenocarcinoma : a report on acute toxicity. Strahlenther Onkol. 2009;185:715–721. doi: 10.1007/s00066-009-1982-z. - DOI - PubMed
    1. Arcangeli G, Fowler J, Gomellini S. et al.Acute and late toxicity in a randomized trial of conventional versus hypofractionated three-dimensional conformal radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2011;79:1013–1021. doi: 10.1016/j.ijrobp.2009.12.045. - DOI - PubMed
    1. Kupelian PA, Reddy CA, Klein EA. et al.Short-course intensity-modulated radiotherapy (70 GY at 2.5 GY per fraction) for localized prostate cancer: preliminary results on late toxicity and quality of life. Int J Radiat Oncol Biol Phys. 2001;51:988–993. doi: 10.1016/S0360-3016(01)01730-8. - DOI - PubMed

Publication types

MeSH terms