title: Acute and late vaginal toxicity after adjuvant high-dose-rate vaginal brachytherapy in patients with intermediate risk endometrial cancer: is local therapy with hyaluronic acid of clinical benefit?
abstract: OBJECTIVE
  The aim of the present study was to evaluate the effectiveness of hyaluronic acid (HA) in the prevention of acute and late vaginal toxicities after high-dose-rate (HDR) vaginal brachytherapy (BT).
  
  
  METHODS
  Between January 2011 and January 2015, we retrospectively analyzed 126 patients with endometrial cancer who underwent extrafascial hysterectomy with or without lymphadenectomy and adjuvant HDR-vaginal BT +/- adjuvant chemotherapy. The total dose prescription was 21 Gy in 3 fractions (one fraction for week). Vaginal ovules containing 5 mg of HA were given for whole duration of vaginal BT and for the two following weeks. Acute and late toxicities were evaluated according to CTCAE vs 4.02.
  
  
  RESULTS
  According to the revised FIGO 2009 classification, most tumors were in stage IA (30.9%) and in stage IB (57.9%). Thirty-three patients (26.2%) received adjuvant chemotherapy before vaginal BT. Five-year disease-free survival (DFS) and five-year overall survival (OS) were 88% and 93%, respectively. The most common grade 1-2 acute toxicities were vaginal inflammation (18 patients, 14.3%) and dyspareunia (7 patients, 5.5%). Two patients (1.6%) had more than one toxicity. Late toxicity occurred in 20 patients (15.9%). Grade 1-2 late toxicities were fibrosis (14 patients, 11.1%) and telangiectasias (7 patients, 5.5%). Six patients (4.8%) had more than one late toxicity. No grade 3 or higher acute or late toxicities were observed.
  
  
  CONCLUSIONS
  These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery. A randomized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity.
authors.affiliation: Department of Translational Medicine, Division of Radiation Oncology.
authors.forename: Concetta
authors.initials: C
authors.lastname: Laliscia
authors.affiliation: Department of Translational Medicine, Division of Radiation Oncology.
authors.forename: Durim
authors.initials: D
authors.lastname: Delishaj
authors.affiliation: Department of Translational Medicine, Division of Radiation Oncology.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Fabrini
authors.affiliation: Department of Translational Medicine, Division of Radiation Oncology.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gonnelli
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Statistics.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Morganti
authors.affiliation: Department of Translational Medicine, U.O Fisica Sanitaria.
authors.forename: Franco
authors.initials: F
authors.lastname: Perrone
authors.affiliation: Department of Experimental and Clinical Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Tana
authors.affiliation: Department of Translational Medicine, Division of Radiation Oncology.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Paiar
authors.affiliation: Department of Experimental and Clinical Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy.
authors.forename: Angiolo
authors.initials: A
authors.lastname: Gadducci
keywords: HDR vaginal brachytherapy; endometrial cancer; hyaluronic acid