Extended Duration of Dilator Use Beyond 1 Year May Reduce Vaginal Stenosis After Intravaginal High-Dose-Rate Brachytherapy

Abstract

Vaginal stenosis (VS) is a late toxicity associated with vaginal or pelvic radiotherapy (RT). Vaginal dilators are recommended after RT to prevent VS though the time course of this toxicity is not fully understood and the optimal duration of dilator use is unknown. We examined rates of VS among women treated with intravaginal brachytherapy (IVBT) for endometrial carcinoma (EC) and evaluated the effect of dilator use duration on VS. We reviewed the records of 243 stage IA-II EC patients who received adjuvant IVBT in a departmental database. The typical high-dose-rate IVBT dose was 18-21 Gy in 3 fractions delivered weekly. Patients were instructed to begin dilator use 2 weeks after the final IVBT fraction, 2-3 times/week, 10 minutes/session, for at least 1 year duration. The primary outcome was development of grade ≥ 1 VS as assessed by physical examination at any follow-up in the radiation oncology clinic (typically 3-6 months after final IVBT fraction and then yearly thereafter) and was graded using CTCAE v4.0. The Kaplan-Meier method was used to estimate VS over time. The log-rank test and multivariable Cox proportional hazards modeling were used to evaluate the effect of dilator use (noncompliance vs. standard compliance [up to 1 year] vs. extended compliance [over 1 year]) on VS. The median follow-up time was 14.8 months (range: 1.9-38.1). The median age was 65 years (range: 43-94) and the majority (70.2%) were not sexually active. At 12 and 24 months, freedom from VS was 71.1% and 53.3%, respectively. Regarding dilator compliance, 98 (40.3%) were noncompliant, 97 (39.9%) had standard compliance, and 48 (19.8%) had extended compliance. Freedom from VS at 12 months was 63.5% for noncompliant patients, 70.2% in those with standard compliance, and 81.2% in those with extended compliance (log-rank, P = 0.04). At 24 months, freedom from VS was 39.8%, 50.2% and 72.1%, respectively. The median time to VS was 17.5 months for noncompliant patients, 27 months for standard compliance, and was not yet reached for extended compliance. On multivariable analysis, after adjusting for other significant variables (gravidity, sexual activity, cylinder size, and vaginal percent length treated), there was a trend towards a difference in grade ≥ 1 VS based on dilator compliance (P = 0.069), with a statistically significant decrease in grade ≥ 1 VS for patients with extended compliance vs. noncompliance (hazard ratio 0.43, 95% confidence interval 0.20 – 0.89, P = 0.024). Among the 74 patients with recorded VS, 62 had grade 1, 11 had grade 2, and 1 had grade 3. Of all grade ≥ 2 VS, 7/12 (58.3%) cases were noted in noncompliant patients. Grade ≥ 2 VS was not observed among those with extended compliance. The risk of VS persists beyond 1 year after IVBT. Extended vaginal dilator compliance beyond 1 year may mitigate this risk. Further studies are needed to determine the optimal frequency and duration of vaginal dilator use, as well as factors affecting compliance.