title: Prospective randomized trial of HDR brachytherapy as a sole modality in palliation of advanced esophageal carcinoma--an International Atomic Energy Agency study.
abstract: BACKGROUND
  Previous studies from South Africa have established that fractionated high-dose-rate (HDR) brachytherapy gives the best results in terms of palliation and survival in advanced esophageal cancer. A multicenter, prospective randomized study was therefore conducted under the auspices of the International Atomic Energy Agency to evaluate two HDR regimens.
  
  
  METHODS
  Surgically inoperable patients with histologically proven squamous cell cancer of the esophagus, tumor >5 cm in length on barium swallow and/or endoscopy, Karnofsky performance score >50, age 17-70 years, primary disease in the thoracic esophagus, no prior malignancy within the past 5 years, and any N or M status were included in the study. Exclusion criteria included cervical esophagus location, tumor extending <1 cm from the gastroesophageal junction, tracheoesophageal fistula, Karnofsky performance score <50, altered mental status, and extension to great vessels on CT. Patients were randomized to receive 18 Gy in 3 fractions on alternate days (6 Gy per fraction, Group A) or 16 Gy in 2 fractions on alternate days (8 Gy per fraction, Group B). The HDR dose was prescribed at 1 cm from the center of the source axis after dose optimization. A margin of 2 cm was included proximally and distally. The respective hospital and university committees gave approval for the study, and all patients provided informed consent.
  
  
  RESULTS
  A total of 232 patients were entered into the study (112 in Group A and 120 in Group B). There was no difference between the groups for any of the prognostic variables. All patients were followed until death. The dysphagia-free survival for the whole group was 7.1 months (Group A, 7.8 months; Group B, 6.3 months; p >0.05). The overall survival was 7.9 months for the whole group (Group A, 9.1 months; Group B, 6.9 months; p >0.05). On univariate analysis, the presenting weight (p = 0.0083), gender (p = 0.0038), race (p = 0.0105), the presenting dysphagia score (p = 0.0083), the treatment center (p = 0.0029), and tumor grade (p = 0.0029) had an impact on the dysphagia-free survival, and gender (p = 0.0011) and performance score (p = 0.0060) had an impact on dysphagia-free survival on multivariate analysis. Only age had an impact on overall survival on both univariate (p = 0.0430) and multivariate (p = 0.0331) analysis. The incidence of strictures (Group A, n = 12; Group B, n = 13; p >0.05) and fistulas (Group A, n = 11; Group B, n = 12; p >0.05) was similar in both groups.
  
  
  CONCLUSIONS
  Fractionated HDR brachytherapy alone is an effective method of palliating advanced esophageal cancers, surpassing the results of any other modality of treatment presently available. Dose fractions of 6 Gy x 3 and 8 Gy x 2 give similar results for dysphagia-free survival, overall survival, strictures, and fistulas and are equally effective in palliation of advanced esophageal cancer.
authors: University of the Witwatersrand, Box 4280, Cresta 2118, Johannesburg, South Africa. rksur@global.co.za
authors: Ranjan K
authors: RK
authors: Sur
authors: C Victor
authors: CV
authors: Levin
authors: Bernard
authors: B
authors: Donde
authors: Vinay
authors: V
authors: Sharma
authors: Leszek
authors: L
authors: Miszczyk
authors: Subir
authors: S
authors: Nag
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001918:Brachytherapy / Q000379:methods*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D011379:Prognosis; D011446:Prospective Studies; D011879:Radiotherapy Dosage