Prostate cancer

Cohort

Surgery

Urethra

Androgen deprivation therapy

Urethral stricture

Urology

Adjuvant

External beam radiotherapy

Dose fractionation

Radiation therapy

Toxicity

Brachytherapy

Internal medicine

Prostate

Oncology

Medicine

Nuclear medicine

Cancer

International Journal of Radiation Oncology*Biology*Physics

For prostate cancer, comparable or superior biochemical control was reported when using external beam radiotherapy (EXBRT) in combination with High Dose Rate Brachytherapy (HDRB), compared to dose escalation with EXBRT alone. The conformal doses produced by HDRB could allow further beneficial prostate dose escalation, but this increase is limited by normal tissue toxicity, in particular for the urethra which is surrounded by prostate tissue. Previous work showed correlation between urethra dose and incidence of urinary toxicity, but there are still not clear guidelines on dose constraints to this organ due to the variety of fractionation regimes used in HDRB. This work aimed at fitting a Lyman Kutcher Burman (LKB) model to urethra stricture data collected at one institution and validating it with an external cohort looking also at the effect of using neo-adjuvant androgen deprivation (AD). For model development, clinical and dosimetric data of 258 patients, treated at a single institution (cohort1) with a variety of prescription doses (18 Gy in 3, 19 Gy in 2 and 17 Gy in 2 fractions) and toxicity rate of 12.8%, were prospectively collected to fit the LKB model with maximum likelihood. Due to the different fractionations, doses were converted into equi-effective doses in 2 Gy per fraction (α/β=5 Gy), and urethra stricture was used as end-point. For validation an external cohort of 187 patients (cohort2) treated as part of the TROG03.04 RADAR trial with 19.5 Gy in 3 fractions, and toxicity rate of 8.7%, was used. Both groups were treated with an EXBRT dose of 46 Gy in 2 Gy per fraction. Goodness of fit was assessed using calibration plots. The effect of AD was also studied. The incidence of urethra stricture of the combined treatment (HDRB+EXBRT) in cohort 1 was modelled by means of a sigmoid function of EUD. The LKB parameters TD50 (Gy), m and n are shown in Table 1a, and n was fixed to 0.3 based on numerical optimization of the likelihood. As internal validation the calibration plot showed a good agreement between the observed toxicity and the probability predicted by the model (slope=0.924, R2=0.71). Bootstrapping confirmed the results (Table 1b). For the external validation the calibration plot confirmed that the observed toxicity obtained with cohort2 was well represented by the LKB model fitted with cohort1 (slope=0.85, R2=0.94). When cohort1 was stratified by AD and the model re-fitted with n and m fixed, TD50 decreased when AD was not present (Table 1d).Abstract 1117; Table 1TD50 (Gy)mna cohort 1116.70.230.3b cohort 1 bootstrapping116.5 (CI:114.8-118.3)0.23 (CI:0.22-0.23)0.3c cohort 1 With AD (241/258)118.20.230.3d cohort 1 without AD (17/258)104.90.230.3 Open table in a new tab A LKB model was fitted to the risk of urethra stricture and externally validated with an independent cohort, to provide guidance on urethra tolerances for patients treated with HDRB boost. For patients that did not receive AD model fitting provided a lower TD50 suggesting a protective effect of AD on urethra toxicity.

Development and External Validation of a Predictive Model of Urethra Toxicity for Patients Treated with HDR Brachytherapy Boost Including the Effect of Neo-Adjuvant Androgen Deprivation