Estimates of alpha/beta ratios for individual late urinary toxicity endpoints: analysis of a cohort trial
Rancati, T. Gioscio, E. Cicchetti, A. Rosenstein, B. Seibold, P. Avuzzi, B. Azria, D. De Ruysscher, D. Dunning, A. M.
Rancati, T.
Gioscio, E.
Cicchetti, A.
Rosenstein, B.
Seibold, P.
Avuzzi, B.
Azria, D.
De Ruysscher, D.
Dunning, A. M.
Citations
Altmetric:
Abstract
Purpose or Objective
Using data from an international prospective cohort study of prostate cancer (PCa) patients receiving radical radiotherapy
(RT), this analysis aims to estimate α/β ratios for individual urinary toxicity (tox) endpoints: grade 2+ (G2+) urinary
frequency, G2+ urinary incontinence and G1+ haematuria. Owing to a previously suggested consequential component of
late bladder damage, we also considered the impact of including the total treatment time in NTCP models.
Materials and Methods
Non-metastitic PCa patients (pts) were enrolled in 8 countries (04-2014/03-2016). RT was prescribed according to
local regimens, but centres used standardised data collection (including baseline symptoms). Tox was scored using
CTCAE. Pts in the study had full 3D dosimetric information; we used solid bladder DVHs. Data were available for 1009 pts.
We fitted the probability of late urinary tox within 24 months with the Logit-EUD sigmoid model, explicitly including the
α/β ratios and also allowing a term for the impact of total treatment time. The general expression for the NTCP model is
in fig 2a. Four parameters describe the model (EUD50, k, n, α/β). A fifth parameter γ was needed for RT time correction.
We used the Maximum Likelihood method (Optimization Toolbox, Matlab) to obtain the best estimates of the model
parameters.
We compared models including the new estimates of α/β with models with α/β=3Gy (conventional value for late tox).
Results
The cohort included 678 conventionally fractionated pts and 331 hypofractionated pts (Fig 1a). Fig 1b shows the
incidence of the tox endpoints within the different subcohorts and Fig 1c the distribution of toxicity events as a
function of dose and dose/fraction. We found a consequential effect between acute and late tox for all endpoints. Conclusion
We found a greater unexpected impact of hypofractionation on RT induced urinary tox. This could be explained by a
bladder α/β<0.3Gy or, radiobiologically more plausible, by introducing a time factor likely to represent a previously
hypothesised consequential component of late effect.
Description
Date
2022
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Rancati T, Gioscio E, Cicchetti A, Rosenstein B, Seibold P, Avuzzi B, et al. Estimates of alpha/beta ratios for individual late urinary toxicity endpoints: analysis of a cohort trial. Radiotherapy and Oncology. 2022 May;170:S485-S8. PubMed PMID: WOS:000806764200130.