Fitting NTCP models to bladder doses and acute urinary symptoms during post-prostatectomy radiotherapy

Abstract

Background: To estimate the radiobiological parameters of three popular normal tissue complication probability (NTCP) models, which describe the dose-response relations of bladder regarding different acute urinary symptoms during post-prostatectomy radiotherapy (RT). To evaluate the goodness-of-fit and the correlation of those models with those symptoms.

Methods: Ninety-three consecutive patients treated from 2010 to 2015 with post-prostatectomy image-guided intensity modulated radiotherapy (IMRT) were included in this study. Patient-reported urinary symptoms were collected pre-RT and weekly during treatment using the validated Prostate Cancer Symptom Indices (PCSI). The assessed symptoms were flow, dysuria, urgency, incontinence, frequency and nocturia using a Likert scale of 1 to 4 or 5. For this analysis, an increase by ≥2 levels in a symptom at any time during treatment compared to baseline was considered clinically significant. The dose volume histograms of the bladder were calculated. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS) and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC) and Odds Ratio methods.

Results: For the symptoms of urinary urgency, leakage, frequency and nocturia, the derived LKB model parameters were: 1) D₅₀ = 64.2Gy, m = 0.50, n = 1.0; 2) D₅₀ = 95.0Gy, m = 0.45, n = 0.50; 3) D₅₀ = 83.1Gy, m = 0.56, n = 1.00; and 4) D₅₀ = 85.4Gy, m = 0.60, n = 1.00, respectively. The AUC values for those symptoms were 0.66, 0.58, 0.64 and 0.64, respectively. The differences in AIC between the different models were less than 2 and ranged within 0.1 and 1.3.

Conclusions: Different dose metrics were correlated with the symptoms of urgency, incontinence, frequency and nocturia. The symptoms of urinary flow and dysuria were poorly associated with dose. The values of the parameters of three NTCP models were determined for bladder regarding four acute urinary symptoms. All the models could fit the clinical data equally well. The NTCP predictions of urgency showed the best correlation with the patient reported outcomes.

Keywords: Acute urinary symptoms; LKB; Logit; NTCP; Post-prostatectomy radiotherapy; Radiobiological parameters; Relative seriality.

Fig. 1

The dose-volume histograms (DVHs) of bladder for the acute symptom of urinary urgency. The DVHs of the patients with the symptom are represented by solid lines, whereas those without the symptoms by dashed lines. The thick lines represent the average DVHs, whereas the thin lines indicate the 68% confidence interval (one standard deviation)

Fig. 2

The dose-response curves of bladder, for the acute symptoms of urinary urgency, urinary incontinence, frequency and nocturia for the three models. The unit on the dose axis is either the biologically effective uniform dose ($\overline{\overline{D}}$ or BEUD), in the cases of the Relative Seriality (RS) model or the generalized equivalent uniform dose (gEUD) in the cases of the Lyman-Kutcher-Burman (LKB) and Logit models. The clinical response rates for different dose intervals (indicated by the horizontal error bars) are also plotted