title: Manifestation pattern of early-late vaginal morbidity after definitive radiation (chemo)therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer: an analysis from the EMBRACE study.
abstract: OBJECTIVE
  Brachytherapy in the treatment of locally advanced cervical cancer has changed substantially because of the introduction of combined intracavitary/interstitial applicators and an adaptive target concept, which is the focus of the prospective, multi-institutional EMBRACE study (www.embracestudy.dk) on image-guided adaptive brachytherapy (IGABT). So far, little has been reported about the development of early to late vaginal morbidity in the frame of IGABT. Therefore, the aim of the present EMBRACE analysis was to evaluate the manifestation pattern of vaginal morbidity during the first 2 years of follow-up.
  
  
  METHODS
  In total, 588 patients with a median follow-up time of 15 months and information on vaginal morbidity were included. Morbidity was prospectively assessed at baseline, every 3 months during the first year, and every 6 months in the second year according to the Common Terminology Criteria for Adverse Events, version 3, regarding vaginal stenosis, dryness, mucositis, bleeding, fistula, and other symptoms. Crude incidence rates, actuarial probabilities, and prevalence rates were analyzed.
  
  
  RESULTS
  At 2 years, the actuarial probability of severe vaginal morbidity (grade ≥3) was 3.6%. However, mild and moderate vaginal symptoms were still pronounced (grade ≥1, 89%; grade ≥2, 29%), of which the majority developed within 6 months. Stenosis was most frequently observed, followed by vaginal dryness. Vaginal bleeding and mucositis were mainly mild and infrequently reported.
  
  
  CONCLUSIONS
  Severe vaginal morbidity within the first 2 years after definitive radiation (chemo)therapy including IGABT with intracavitary/interstitial techniques for locally advanced cervical cancer is limited and is significantly less than has been reported from earlier studies. Thus, the new adaptive target concept seems to be a safe treatment with regard to the vagina being an organ at risk. However, mild to moderate vaginal morbidity is still pronounced with currently applied IGABT, and it needs further attention.
authors.affiliation: Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna/General Hospital of Vienna, Austria; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Austria. Electronic address: kathrin.kirchheiner@meduniwien.ac.at.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kirchheiner
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, The Netherlands.
authors.forename: Remi A
authors.initials: RA
authors.lastname: Nout
authors.affiliation: Department of Oncology, Aarhus University Hospital, Denmark.
authors.forename: Kari
authors.initials: K
authors.lastname: Tanderup
authors.affiliation: Department of Oncology, Aarhus University Hospital, Denmark.
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Lindegaard
authors.affiliation: Department of Radiotherapy, Academic Medical Centre, University of Amsterdam, The Netherlands.
authors.forename: Henrike
authors.initials: H
authors.lastname: Westerveld
authors.affiliation: Department of Radiotherapy, Gustave-Roussy, Villejuif, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Haie-Meder
authors.affiliation: Department of Radiotherapy, Institute of Oncology Ljubljana, Slovenia; Department of Radiotherapy, National Center for Cancer Care and Research, Doha, Qatar.
authors.forename: Primož
authors.initials: P
authors.lastname: Petrič
authors.affiliation: Department of Radiation Oncology, Tata Memorial Hospital, Mumbai, India.
authors.forename: Umesh
authors.initials: U
authors.lastname: Mahantshetty
authors.affiliation: Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna/General Hospital of Vienna, Austria; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dörr
authors.affiliation: Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna/General Hospital of Vienna, Austria; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Pötter
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000009:adverse effects* / Q000379:methods; D018196:Carcinoma, Adenosquamous / Q000473:pathology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000379:methods; D003251:Constriction, Pathologic / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D058958:Organs at Risk / Q000528:radiation effects*; D011446:Prospective Studies; D011832:Radiation Injuries / Q000473:pathology*; D011879:Radiotherapy Dosage; D011881:Radiotherapy, Computer-Assisted / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000628:therapy*; D014621:Vagina / Q000528:radiation effects*; D014623:Vaginal Diseases / Q000209:etiology / Q000473:pathology; D055815:Young Adult