Investigating the Relationship between the Dose to the Recto-Vaginal Reference Point and Vaginal Stenosis among Cervical Cancer Patients Treated at a North American Academic Institution

Abstract

In the treatment of locally advanced cervical cancer (LACC) with image-guided brachytherapy, there are limited data concerning the optimal vaginal dose constraints to minimize risk of vaginal stenosis (VS). While the dose to the recto-vaginal reference point (RV-RP) has been reported to be associated with VS, the EMBRACE dose constraint of 65Gy is a higher value than we typically measure at our institution. We hypothesize that there may be an association between the dose to the RV-RP and VS at lower values than previously reported. Following IRB approval, data were collected for 87 LACC patients treated at a single institution between 12/2012 - 4/2022 with available CTCAEv4.0 VS scores and minimum follow-up of 4 months. Only patients treated with tandem/ring or tandem/ovoid applicators, with or without interstitial needles, were included. Perineal template and cylinder-based applications were excluded. Dose to the RV-RP was retrieved from the treatment planning system. Primary endpoint was grade 2 or higher (G ≥ 2) VS. The Kaplan-Meier method was used to estimate the cumulative incidence of VS. The log-rank test and multivariable Cox proportional-hazards regression were used to evaluate the association between dose to the RV-RP with VS G ≥ 2. The cohort median age was 48 (IQR 38-61). 59 patients (68%) were stage I or II (FIGO 2009) and 28 (32%) were stage III. Ethnicity was Hispanic or Latino in 20 patients (23%). Technique was predominantly tandem/ring (78%), high-dose-rate (79%), and intracavitary without interstitial needles (83%). The most common dose-fractionation was 28Gy in 4 fractions (following 45Gy to the pelvis). The median cumulative HR-CTV D90% dose was 83.1Gy (IQR 79.7 - 86.5). Median dose to the RV-RP was 51.1Gy (IQR 49.2 - 55.8). Only 9 patients (10%) had a dose to the RV-RP higher than 65Gy (max 71.1). Median follow-up was 22.6 months (range: 4.2 - 114). The 2-year incidence of VS G ≥ 2 was 24.4%. Dose to the RV-RP was associated with VS G ≥ 2. The 2-year incidence of VS G ≥ 2 for patients with RV-RP dose <51 vs ≥51Gy was 13.1% vs 34.6% (p = 0.038). On multivariable regression, dose to the RV-RP ≥51Gy (HR 2.94 CI 1.16 -7.48, p = 0.024), Hispanic or Latino ethnicity (HR 3.71 CI 1.38 - 9.99, p = 0.01), and stage III (HR 2.33 CI 1.06 - 5.12, p = 0.035) were significantly associated with increased risk of VS G ≥ 2. We observed a statistically significant association between the dose to the RV-RP and VS G ≥ 2, when stratified by our median dose to the RV-RP of 51Gy, which is lower than the dose constraint of 65Gy previously reported by EMBRACE. These findings may be partially explained by differences in patient demographics or brachytherapy technique. Further investigation of the relationship between the dose to the RV-RP and development of VS G ≥ 2 across broader populations is warranted.