title: Role of radiotherapy, in particular intraluminal brachytherapy, in the treatment of proximal bile duct carcinoma.
abstract: OBJECTIVE
  To perform an analysis of the results obtained with radiotherapy in patients with either resectable or unresectable cholangiocarcinoma of the proximal bile ducts. Emphasis will be paid to analyse the role of radiotherapy, particularly brachytherapy.
  
  
  METHODS
  Between 1985 and 1997, 109 patients received radiotherapy. In 71 patients (group I) tumor resection was combined with postoperative irradiation in 52 patients and pre- plus post-operative irradiation in 19 patients. Among this group, 41 patients had a boost of 10 Gy to the biliodigestive anastomosis using intraluminal brachytherapy. Median total dose was between 50-55 Gy. The other 38 patients (group II) had an unresectable tumor at laparotomy (16 patients) or were considered primary unresectable because locoregional tumor extension (22 patients). Brachytherapy boost through a nasobiliary approach was given to 19 patients (22-25 Gy). The median total dose varied between 60 to 68 Gy. Mean follow-up was 25 +/- 23 months.
  
  
  RESULTS
  In group I, the survival rates at 1, 3, and 5 year were 84%, 37%, and 24%, respectively. Median survival was 24 months. Sixteen patients did live longer than 4 years. Analysis of prognostic factors among resected patients showed the tumor differentiation grade, microscopically involved margins other than the upper (hepatic) and lower (choledocus) resection parameters analysed, only the total dose had influence on margins, and elevated alkaline phosphatase as factors which significantly influence survival. From the different radiotherapy prognosis, patients receiving a total dose above 55 Gy had a shorter survival. It is important to note that patients receiving brachytherapy boost did not have a better survival than patients treated with external beam irradiation alone. Preoperative radiotherapy did not have impact on survival but recurrences in the surgical scars were not observed as compared to 15% recurrences if preoperative radiotherapy was not given. In group II the median survival was 10.4 months. Survival rates at 1 and 2 year were 43% and 10%, respectively. The only significant prognostic factor found was if unresectability was defined primarily or during laparotomy. As it was the case in group I, brachytherapy boost did not have influence on prognosis as compared to external beam irradiation alone. Observed late complications consisted of duodenal stenosis, upper digestive tract bleeding and cholangitis. Probably these complications were not only attributable to radiotherapy, as tumor relapse was also present in the majority of the cases.
  
  
  CONCLUSIONS
  The role of radiotherapy either as adjuvant or as primary treatment remains to be demonstrated in prospective randomised studies. From our results, it seems that high radiation doses could be dangerous and could detriment prognosis. Brachytherapy boost was not superior to treatment with external beam irradiation alone.
authors.affiliation: Department of Radiation Oncology, University of Amsterdam, Academic Medical Centre, The Netherlands. D.Gonzalez@amc.uva.nl
authors.forename: D
authors.initials: D
authors.lastname: González González
authors.forename: D J
authors.initials: DJ
authors.lastname: Gouma
authors.forename: E A
authors.initials: EA
authors.lastname: Rauws
authors.forename: T M
authors.initials: TM
authors.lastname: van Gulik
authors.forename: A
authors.initials: A
authors.lastname: Bosma
authors.forename: C
authors.initials: C
authors.lastname: Koedooder
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D001918:Brachytherapy / Q000009:adverse effects; D002423:Cause of Death; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D015996:Survival Rate