Time-dependent dose-response relation for absence of vaginal elasticity after gynecological radiation therapy

Abstract

Background and purpose: To investigate the dose-response relation between the dose to the vagina and the patient-reported symptom 'absence of vaginal elasticity' and how time to follow-up influences this relation.

Material and methods: The study included 78 long-term gynecological cancer survivors treated between 1991 and 2003 with external beam radiation therapy. Of those, 24 experienced absence of vaginal elasticity. A normal tissue complication model is introduced that takes into account the influence of time to follow-up on the dose-response relation and the patient's age. The best estimates of the dose-response parameters were calculated using Probit, Probit-Relative Seriality (RS) and Probit-time models. Log likelihood (LL) values and the Akaike Information Criterion (AIC) were used to evaluate the model fit.

Results: The dose-response parameters for 'absence of vaginal elasticity' according to the Probit and Probit-time models with the 68% Confidence Intervals (CI) were: LL=-39.8, D₅₀=49.7 (47.2-52.4) Gy, γ₅₀=1.40 (1.12-1.70) and LL=-37.4, D₅₀=46.9 (43.5-50.9) Gy, γ₅₀=1.81 (1.17-2.51) respectively.

Conclusions: The proposed model, which describes the influence of time to follow-up on the dose-response relation, fits our data best. Our data indicate that the steepness of the dose-response curve of the dose to the vagina and the symptom 'absence of vaginal elasticity' increases with time to follow-up, while D₅₀ decreases.

Keywords: Dose–response relation; Gynecological radiation therapy; NTCP; Time–response relation; Vaginal elasticity.