GPP03 Presentation Time: 8:20 AM: Short Course Adjuvant Vaginal Cuff Brachytherapy (VCB) in Early Endometrial Cancer: Preliminary Results of the SAVE Randomized Clinical Trial

Abstract

<h3>Purpose</h3> Prospective randomized trials in early stage endometrial cancer demonstrate increased locoregional control with adjuvant radiotherapy for patients with select high risk features. Vaginal cuff brachytherapy (VCB) is widely utilized, yet there is substantial practice variation and limited randomized data examining optimal dose/fractionation. We aimed to study the safety and efficacy of short course VCB compared to commonly used regimens, and herein report on short-term adverse events, patient reported outcomes, and recurrences. <h3>Materials and Methods</h3> We conducted a prospective, multi-center, randomized trial examining short course adjuvant VCB (11 Gy x 2 fractions at the surface delivered in 2 weeks) compared with the commonly used regimens (7 Gy x 3 fractions at 0.5 cm depth, 6 Gy x 5 fractions at the surface, or 5-5.5 Gy x 4 fractions at 0.5 cm depth). Eligible patients underwent hysterectomy and had pathologically confirmed endometrioid adenocarcinoma, serous, clear cell, or carcinosarcoma histology. Patients with stage I and II cancers were included, with additional risk factors required for stage IA (IAG1 with LVSI). The primary outcome was Global Health Status measured by the EORTC QLQ-C30. Secondary outcomes included differences in patient-reported outcomes using the EORTC EN24 for vaginal, bladder, and bowel symptoms, cost effectiveness, toxicities as assessed by CTCAEv4, and patterns of recurrence. Data were collected at each brachytherapy fraction and at 1, 6 and 12 month follow-up with a compliance rate of 94% at 1 month. <h3>Results</h3> 108 patients were enrolled. Of these, 52 patients experienced short-term AEs related to study treatment, 21 in the experimental arm and 31 in the control arm (p=0.05). All study treatment-related AEs were grade 1-2, except for 1 grade 3 urinary symptom in the control arm. In the experimental arm, the most frequent short-term AEs were fatigue (n=6), diarrhea (n=4), vaginal discharge (n=3), and vaginal dryness (n=3). In the control arm, the most frequent short-term AEs were vaginal dryness (n=8), urinary incontinence (n=6), urinary tract infection (n=5), and pelvic pain (n=5). At median follow-up of 12 months, 5 patients experienced recurrence including 2 distant recurrences and 1 distant and pelvic recurrence in the experimental arm and 2 pelvic recurrences in the control arm. There have been no isolated vaginal recurrences in either arm. The QLQ-C30 Global Health Status for the experimental arm was within the predefined boundary and thus 2 fractions was non-inferior to standard of care (p=0.00002) at one month. <h3>Conclusions</h3> Short course VCB is safe and well-tolerated with acceptable acute toxicity and non-inferior patient reported outcomes. Although longer follow-up data is pending, short course VCB shows promise to improve patient convenience and access to care for rural or underserved populations while providing similar local control and toxicity profile.