Prospective randomized trial of HDR brachytherapy as a sole modality in palliation of advanced esophageal carcinoma--an International Atomic Energy Agency study.

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 AND MATERIALS: 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.
CONCLUSION: 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.

RCT Entities:   Population Interventions Outcomes