Comparison of Two Different Adjuvant High Dose Rate Vaginal Brachytherapy Fractionation Regimens in Early-Stage Endometrial Cancer

Abstract

Adjuvant vaginal brachytherapy (VBT) as monotherapy is commonly used as treatment for early-stage uterine cancer following hysterectomy. No ABS guidelines existed at the onset of our institution's high dose rate (HDR) brachytherapy program, so a regimen of 30 Gy in six fractions was adopted in this setting. Due to the COVID pandemic in 2020, we implemented the use of 22 Gy in four fractions as our primary regimen to reduce overall treatment duration and healthcare exposure risks. In this analysis, we seek to compare outcomes and toxicities between the two treatment regimens. This is a single institution retrospective review of patients with Stage I-II endometrial cancer who received adjuvant VBT as monotherapy between 1998 and 2022. HDR VBT was delivered via a vaginal cylinder prescribed to a depth of 5 mm, to a dose of 22 or 30 Gy in four or six fractions, respectively. We evaluated maximum acute and chronic toxicities, defined as ≤6 months and ≥ 6 months following treatment completion, respectively. Toxicities were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) criteria. We evaluated clinical outcomes including local recurrence (LR), distant metastasis (DM), cause-specific survival (CSS) and overall survival (OS). P-values <0.05 were considered significant. A total of 270 patients were included in our analysis, with a median follow up of 4.98 years (7.7 and 1.3 years for six-fraction and 4-fraction regimen, respectively, p<0.001). The median age at the time of treatment was 66 (range 31-89). 195 patients (72.2%) were treated with six fractions and 75 (27.8%) were treated with four fractions. There was significantly less chronic vaginal dryness (p = 0.017) and vaginal stenosis (p<0.001) with the four-fraction compared to the 6-fraction regimen. There was no difference in acute toxicity (p = 0.468). There were no grade ≥3 toxicities in either group. The 2-year LR, DM, CSS, and OS rates for four/six fractions were 2.4%/3.7%, 6.8%/3.7%, 95.8%/97.9%, and 95.8%/95.8%, respectively. There were no significant differences in outcomes between the two groups. Our experience supports that VBT in four fractions is well tolerated with minimal acute and chronic toxicities. When comparing to our institution's historical data for a six-fraction regimen, the use of a four-fraction regimen resulted in less chronic vaginal dryness and stenosis, supporting its continued use. The clinical outcomes have been similar thus far. Further analysis with a longer follow-up duration and a match-pair analysis is warranted.