Urethral and bladder dose–effect relations for late genitourinary toxicity following external beam radiotherapy for prostate cancer in the FLAME trial

•Dose to the bladder and urethra is related to GU toxicity.•Focal boost treatment plans should include a urethral dose constraint.•Urethral dose-effect relations for hypofractionated schemes should be analyzed. The FLAME trial (NCT01168479) showed that by adding a focal boost to conventional fractio...

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Published in:Radiotherapy and oncology 2022-02, Vol.167, p.127-132
Main Authors: Groen, Veerle H., van Schie, Marcel, Zuithoff, Nicolaas P.A., Monninkhof, Evelyn M., Kunze-Busch, Martina, de Boer, Johannes C.J., van der Voort van Zijp, Jochem, Pos, Floris J., Smeenk, Robert Jan, Haustermans, Karin, Isebaert, Sofie, Draulans, Cédric, Depuydt, Tom, Verkooijen, Helena M., van der Heide, Uulke A., Kerkmeijer, Linda G.W.
Format: Article
Language:English
Subjects:
Bladder dose
Brachytherapy
Dose-effect relations
External beam radiotherapy
Focal boosting
Genitourinary toxicity
Humans
Male
Prostate cancer
Prostatic Neoplasms - radiotherapy
Radiation Injuries - epidemiology
Radiation Injuries - etiology
Radiotherapy Dosage
Urethra - radiation effects
Urethral dose
Urinary Bladder - radiation effects
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Summary:•Dose to the bladder and urethra is related to GU toxicity.•Focal boost treatment plans should include a urethral dose constraint.•Urethral dose-effect relations for hypofractionated schemes should be analyzed. The FLAME trial (NCT01168479) showed that by adding a focal boost to conventional fractionated EBRT in the treatment of localized prostate cancer, the five-year biochemical disease-free survival increased, without significantly increasing toxicity. The aim of the present study was to investigate the association between radiation dose to the bladder and urethra and genitourinary (GU) toxicity grade ≥2 in the entire cohort. The dose–effect relations of the urethra and bladder dose, separately, and GU toxicity grade ≥2 (CTCAE 3.0) up to five years after treatment were assessed. A mixed model analysis for repeated measurements was used, adjusting for age, diabetes mellitus, T-stage, baseline GU toxicity grade ≥1 and institute. Additionally, the association between the dose and separate GU toxicity subdomains were investigated. Dose-effect relations were observed for the dose (Gy) to the bladder D2 cm3 and urethra D0.1 cm3, with adjusted odds ratios of 1.14 (95% CI 1.12–1.16, p 
ISSN:0167-8140
1879-0887
DOI:10.1016/j.radonc.2021.12.027