Modelling the impact of fractionation on late urinary toxicity after postprostatectomy radiation therapy.

Abstract

PURPOSE:

To fit urinary toxicity data of patients treated with postprostatectomy radiation therapy with the linear quadratic (LQ) model with/without introducing a time factor.

METHODS AND MATERIALS:

Between 1993 and 2010, 1176 patients were treated with conventional fractionation (1.8 Gy per fraction, median 70.2 Gy, n=929) or hypofractionation (2.35-2.90 Gy per fraction, n=247). Data referred to 2004-2010 (when all schemes were in use, n=563; conventional fractionation: 316; hypofractionation: 247) were fitted as a logit function of biological equivalent dose (BED), according to the LQ model with/without including a time factor γ (fixing α/β = 5 Gy). The 3-year risks of severe urethral stenosis, incontinence, and hematuria were considered as endpoints. Best-fit parameters were derived, and the resulting BEDs were taken in multivariable backward logistic models, including relevant clinical variables, considering the whole population.

RESULTS:

The 3-year incidences of severe stenosis, incontinence, and hematuria were, respectively, 6.6%, 4.8%, and 3.3% in the group treated in 2004-2010. The best-fitted α/β values were 0.81 Gy and 0.74 Gy for incontinence and hematuria, respectively, with the classic LQ formula. When fixing α/β = 5 Gy, best-fit values for γ were, respectively, 0.66 Gy/d and 0.85 Gy/d. Sensitivity analyses showed reasonable values for γ (0.6-1.0 Gy/d), with comparable goodness of fit for α/β values between 3.5 and 6.5 Gy. Likelihood ratio tests showed that the fits with/without including γ were equivalent. The resulting multivariable backward logistic models in the whole population included BED, pT4, and use of antihypertensives (area under the curve [AUC] = 0.72) for incontinence and BED, pT4, and year of surgery (AUC = 0.80) for hematuria. Stenosis data could not be fitted: a 4-variable model including only clinical factors (acute urinary toxicity, pT4, year of surgery, and use of antihypertensives) was suggested (AUC = 0.73).

CONCLUSIONS:

The unexpected impact of moderate hypofractionation on severe incontinence and hematuria after postprostatectomy radiation therapy may be explained by a bladder α/β value <1 Gy or, radiobiologically more plausible, by introducing a time factor likely to represent a previously hypothesized consequential component of late effect.

• Authors: Claudio Fiorino, Cesare Cozzarini, Tiziana Rancati, Alberto Briganti, Giovanni Mauro Cattaneo, Paola Mangili, Nadia Gisella Di Muzio, Riccardo Calandrino
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 90 Issue 5 Pg. 1250-7 (Dec 01 2014) ISSN: 1879-355X [Electronic] United States
• PMID: 25442349 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Topics

• Aged
• Area Under Curve
• Dose Fractionation, Radiation
• Dose-Response Relationship, Radiation
• Hematuria (epidemiology)
• Humans
• Incidence
• Linear Models
• Male
• Middle Aged
• Postoperative Period
• Prostatectomy
• Prostatic Neoplasms (radiotherapy, surgery)
• Radiation Injuries (complications, epidemiology)
• Relative Biological Effectiveness
• Sensitivity and Specificity
• Time Factors
• Urethral Stricture (epidemiology)
• Urinary Incontinence (epidemiology)