Dosimetric Predictors of Radiation-Induced Vaginal Stenosis After Pelvic Radiation Therapy for Rectal and Anal Cancer

Abstract

Purpose: Although vaginal stenosis (VS) is a recognized toxicity in women who receive pelvic radiation therapy (RT), the relationship between RT dose and the volume and extent of toxicity has not been analyzed. We modeled this relationship to identify predictors of VS.

Methods and materials: We evaluated 54 women, aged 29 to 78 years, who underwent pelvic RT for rectal or anal cancer during 2008 to 2011 and were enrolled in a prospective study evaluating vaginal dilator use. Maximum dilator size was measured before RT (baseline) and 1 month and 12 months after RT. Dilator use was initiated at 1 month. The difference (D) in dilator size before and after RT was recorded. Those with D ≤-1 were classified as having VS (n=35); those with D ≥0 were classified as having no VS (n=19 at 1 month). Dose-volume parameters were extracted, and the generalized equivalent uniform dose (gEUD) was used to build a predictive model.

Results: The mean vaginal doses were 50.0 Gy and 36.8 Gy for anal and rectal cancer patients, respectively. One month after RT, a gEUD model using a wide range of a values suggests that sparing of vaginal volume to a low dose may be important. When gEUD (a = -1) was <35 Gy and the mean vaginal dose was <43 Gy, severe VS was reduced (P=.02). A 1-year analysis suggests increasingly negative D values with increasing mean dose. However, patients with compliance <40% were more likely to have toxicity.

Conclusions: Vaginal stenosis is influenced by multiple RT dose-volume characteristics. Mean dose and gEUD constraints together may reduce the risk of severe VS. Patients receiving higher mean vaginal doses should have greater compliance with dilator therapy to minimize risk of toxicity. Further validation with independent datasets is needed.

Fig. 1

Representative radiation plans for (A) a rectal cancer patient treated with 3-dimensional conformal radiation therapy and (B) an anal cancer patient treated with IMRT.

Fig. 2

Vaginal dilator size differences (D) plotted against mean vaginal dose 1 month after RT (A) and 12 months after RT (B). Red circles indicate the mean dilator difference (± standard deviation) for samples falling into 10-Gy intervals. Blue line indicates the fitted line to original dilator difference against mean dose data. The regression correlation is weak but statistically significant (P = .003, R² = 0.16 at 1 month and P = .048, R² = 0.1 at 12 months). A color version of this figure is available at www.redjournal.org.

Fig. 3

Univariate Spearman correlation analysis with different a values in the generalized equivalent uniform dose (gEUD) equation. In this model, geometric mean dose was used for gEUD with a = 0.

Fig. 4

Distribution of mean dose against generalized equivalent uniform dose (gEUD) (a = −1) by dilator difference, D. The patients were split into 3 groups—severe stenosis (D <−1), mild stenosis (D = −1), and no stenosis (D ≥0)—where D = (postradiation dilator size at 1 month) – (preradiation dilator size). The thick solid lines are at gEUD = 35 Gy and mean dose = 43 Gy.

Fig. 5

(A) Dilator difference versus compliance with dilator use 12 months after radiation therapy. (B) Vaginal stenosis as a function of compliance and mean vaginal dose 12 months after radiation therapy.