title: Impact of post operative intensity modulated radiotherapy on acute gastro-intestinal toxicity for patients with endometrial cancer: results of the phase II RTCMIENDOMETRE French multicentre trial.
abstract: OBJECTIVE
  Whole "conventional" pelvic irradiation (up to 45-50Gy) following hysterectomy is associated with a high rate of adverse gastro-intestinal (GI) adverse events, of which around 60% correspond to acute grade 2 toxicity. The phase II RTCMIENDOMETRE trial was designed to test the hypothesis that IMRT could reduce the incidence of grade 2 or more acute GI toxicity to less than 30% in patients irradiated post-operatively for an endometrial cancer.
  
  
  METHODS
  Patients with post-operative stage Ib G3, Ic or II endometrial carcinomas with no history of chronic inflammatory bowel disease were eligible. Guidelines for volume delineation and dose prescription were detailed in the protocol. The investigators were advised to use a web-based atlas developed for the RTOG 0418 study. The dose of the vaginal and nodal PTV was 45Gy in 25 fractions. To assess the ability of the participating centres to comply with the protocol guidelines, they were requested to complete a dummy run procedure before inclusion of their 1st patient. GI and genito-urinary (GU) toxicity were graded according to the CTCAE V 3.0 classification and were prospectively recorded every week during irradiation, as well as at time of brachytherapy insertions and during the follow-up visit at week 15 (W15). Special attention was given to note any changes to the grade of adverse events between W5 and W15.
  
  
  RESULTS
  From May 2008 to April 2010, 49 patients from 6 centres were recruited for the trial. One patient could not be treated, one patient died of vascular stroke at W3 without toxicity, and 1 patient refused to be followed-up after treatment. Thus, 46 cases were available for analysis at W15. The distribution by stage was as follows: Ib 16.3%, Ic 64.2%, II 20.4%. Thirty six patients (75%) received an additional vaginal vault boost of 6-10Gy delivered by HDR brachytherapy in 1 or 2 fractions. Among the 47 patients who completed IMRT, 27% (95% CI 14.5-39.7%) developed at least 1 GI grade 2 adverse event (diarrhoea in 92% of cases), which mainly occurred at W4 and W5. No event corresponding to grade 3 or above was recorded. At W15, the number of patients complaining about GI events was low: 5 patients complained about persistent grade 1 diarrhoea, and 4 patients complained about haemorrhoids. Nineteen percent (95% CI 8.9-32.6%) of patients experienced grade 2 cystitis or urinary frequency which had disappeared by W15.
  
  
  CONCLUSIONS
  In accordance with our hypothesis, post-operative IMRT resulted in a low rate (less than 30%) of acute GI grade 2 toxicity, in patients with endometrial carcinomas. At W15, no patient demonstrated a grade 2 adverse event, and the prevalence of remaining grade 1 events was less than 20%.
authors.affiliation: CHU of Tours, France; François Rabelais University, Tours, France. Electronic address: i.barillot@chu-tours.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Barillot
authors.affiliation: Inserm CIC 202, Tours, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Tavernier
authors.affiliation: Georges François Leclerc Centre, Dijon, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Peignaux
authors.affiliation: Eugene Marquis Centre, Rennes, France.
authors.forename: Danièle
authors.initials: D
authors.lastname: Williaume
authors.affiliation: Oscar Lambret Centre, Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Nickers
authors.affiliation: Ouest Oncology Institute, Nantes, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Leblanc-Onfroy
authors.affiliation: François Baclesse Centre, Caen, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Lerouge
mesh_terms: D000368:Aged; D001918:Brachytherapy / Q000379:methods; D016889:Endometrial Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology* / Q000517:prevention & control*; D041981:Gastrointestinal Tract / Q000528:radiation effects; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D011182:Postoperative Care / Q000009:adverse effects / Q000379:methods; D011832:Radiation Injuries / Q000209:etiology* / Q000517:prevention & control*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods
keywords: Clinical trial; Endometrial carcinoma; Post-operative IMRT