Acute and Late Genitourinary Toxicity Among Patients Receiving Vaginal High Dose Rate Interstitial Brachytherapy

Abstract

High dose rate (HDR) interstitial brachytherapy (ISBT) is an effective modality to deliver highly conformal doses of radiation for treatment of malignancies centered within the vagina. The aim of this study was to evaluate urethral dose and its correlation to the incidence of genitourinary complications among patients undergoing vaginal ISBT. 39 patients treated with ISBT between January 2017 and April 2018 were retrospectively reviewed after REB approval. Clinical characteristics were collected from their electronic medical records and CTCAE was used to grade toxicity. ISBT dosimetric information was collected through review of individual treatment plans as generated in a treatment planning system. Urethral contours were retrospectively added to the structure sets using a 1 cm diameter brush and dose to 0.1cc (D0.1cc), D0.2cc and D0.5cc of urethra were obtained. Then, the total (ISBT +/- EBRT) equivalent dose in 2Gy fractions (EQD2) received by HRCTV (Gy10) and OARs (Gy3) were calculated. Numerical counts (%) and medians (Inter-Quartile-Range) were used to characterize the data. Fisher’s exact and the Mann-Whitney-Wilcox tests were used as appropriate to determine statistical significance. The median age and follow-up was 66 years (57-73) and 9.3 months (6.4-15.3). 21 (54%) patients had endometrial, 13 (33%) had vaginal, 4 (10%) had vulvar primaries and one (3%) had metastasis from the rectum. 30 (77%) patients received external beam radiation prior to ISBT. 17 (44%) underwent a single brachytherapy insertion and 22 (56%) received two. A median of 4 (3-6) ISBT fractions were delivered to each patient and a median of 15 needles (13-17) were used. Median total EQD2 were 55.4 (46.4-72.5), 52.3 (46.0-67.1), 50.9 (45.6-62.5) Gy for Urethral D0.1cc, D0.2cc and D0.5cc respectively. Median bladder D2cc was 65.5 (46.2-75.1). 16 of 39 (41%) patients experienced any acute and 8 of 30 (27%) any late GU toxicity (9 patients did not have follow-up >6 months). 4 (10%) had grade 2 and 0 (0%) had grade 3+ acute GU toxicity. 1 (3%) patient had grade 2 and 1 (3%) had grade 3 late GU toxicity. Median urethral D0.1cc, D0.2cc and D0.5cc were 73 Gy (51.7-93.8) and 50.5 Gy (45.2-63.7; p=0.009), 69.2 Gy (48.9-87.4) and 49.6 Gy (42.7-58.4; p=0.011) and 62.9 Gy (47.9-79.6) and 48.6 Gy (39.2-55.7; p=0.015), respectively in patients with or without any CTCAE GU toxicity. Additionally, 7 (44%) patients with and 1 (4%) without genitourinary toxicity had bladder intrusion (p=0.004). There was no significant difference in urethral dosimetry between patients experiencing and not experiencing late toxicity. Urethral dose appears to predict acute genitourinary toxicity in ISBT of vaginal tumors. Further study with an expanded cohort and longer follow-up is warranted.