Randomized prospective study comparing high dose rate intraluminal brachytherapy (HDRILBT) alone to HDRILBT and external beam radiotherapy (EBRT) in the palliation of advanced esophageal cancer

Abstract

Purpose/Objective: Previous studies have shown that HDRILBT is the best method of palliation for advanced esophageal cancer offering lasting palliation by improving dysphagia-free survival (DFS) in more than 60% of cases for prolonged periods of time. This, in turn, improves the overall survival (OS) in patients with advanced disease with a good quality of life. Encouraged by the results of HDRILBT alone in palliation of advanced cases, a study was designed to determine if the addition of EBRT would further improve the outcome in terms of DFS for advanced esophageal cancers. Materials/Methods: Patients with advanced inoperable esophageal cancer were entered into a randomized prospective study at the Johannesburg Hospital, University of the Witwatersrand, South Africa. All patients were initially investigated and found to be inoperable due to advanced lesions (extra esophageal spread or long lesions) by our surgical colleagues. Chemoradiotherapy was not considered as a suitable option in these patients as all these patients had lost more than 30–40% of their body weight in the past 6 months, and had presented to us with severe dehydration and wasting which precluded them from undergoing aggressive chemoradiotherapy regimes successfully. Selection criteria included lesion in the thoracic esophagus, inoperable advanced disease, histologically proven squamous cell carcinoma, no evidence of distant metastasis, no involvement of the tracheo-bronchial tree on bronchoscopy and/or barium swallow and an ECOG performance score of 0 or 1 or 2. HDRILBT of 16 Gy in 2 fractions over 3 days was prescribed at 1 cm from the center of the source axis and a margin of 2 cm was given proximal and distal to the tumor. Following treatment, patients were randomized to either receive no further treatment (Group A) or additional EBRT of 30 Gy in 10 fractions over 2 weeks (Group B). Following treatment all patients were followed up for a year. Statistical analysis of the data was done using the SAS statistical software package (SAS Institute, Cary, NC). Prognostic variables were analyzed using the chi square and log rank tests and survival curves were drawn using the Kaplan Meier method. Multivariate survival analysis was done using the Cox proportional hazards model. Results: Sixty patients were entered into the study. The mean length was 8.06 cm and the mean weight 46.15 kg. Of the 30 patients, who received initial HDRILBT and were then randomized to receive additional EBRT, two refused additional EBRT as they did not have any dysphagia. These two patients were therefore excluded from the survival analysis and their outcome is mentioned separately. At 6 months more than 50% had dysphagia-free survival in the two groups and this was comparable. There was no difference statistically (p> 0.05) in the dysphagia free survival between the two groups at the end of 12 months. The overall survival amongst the two groups was also similar (p>0.05). The median survival for Group A was 7. 23 months while for Group B it was 7. 5 months. The addition of additional EBRT did not improve the dysphagia free or overall survival in the preliminary analysis. Eleven patients developed strictures related to radiotherapy and all were dilated successfully (Group A-7, Group B- 4, p>0.05). Four patients had progressive luminal disease, which progressed, to fistula (Group A- 3, Group B- 1, p>0.05). There was no effect of age, sex, race, location of tumor, grade of tumour, pain, presenting dysphagia scores, mean length and protocol of treatment on dysphagia free or overall survival on univariate and multivariate analysis. Presenting weight and ECOG score had an impact on overall survival but not on DFS. Conclusions: From the preliminary analysis, it appears that additional EBRT to HDRILBT does not improve dysphagia free survival and outcomes in advanced inoperable esophageal cancer.