Esophageal brachytherapy: a phantom menace?

Concerns have been raised within the past few years regarding the safety and efficacy of esophageal brachytherapy as a boost to concurrent chemoradiation (1). In this issue of the journal, Okawa and colleagues describe the results of a multi-institutional randomized trial of external beam radiation, with or without an intraluminal brachytherapy boost for squamous cancer of the esophagus. This article is an important publication given the relatively few published prospective studies of esophageal brachytherapy. Does this article clarify the risk/benefit of esophageal brachytherapy? Yes and no. This study by Okawa et al. had an unusual design. Patients with squamous cell cancer of the thoracic esophagus were first treated with external beam radiation alone to a dose of 60 Gy in 6–7 weeks. Those patients with a complete or partial response were then randomized to further external beam radiation (10 Gy/5 fractions/1 week) or an intraluminal boost of 10 Gy in 2 fractions 1 week apart. Brachytherapy was either high-dose rate (HDR) or low-dose rate (LDR), utilizing the same total dose, dose/fractionation scheme, and dose prescription point of 5 mm below esophageal submucosa. Patients with progressive or stable disease were only randomized on the study “if intraluminal brachytherapy was indicated.” (Isn’t that the real problem here—we just don’t know when it is indicated!) Approximately one-third of patients were deemed ineligible for randomization after 60 Gy. Chemotherapy was unusual by North American standards, consisting of “maintenance” etoposide following radiation therapy (2). The 5-year actuarial survival rate was not significantly different according to treatment group; 38% and 27% for the patients who did and did not receive the boost by brachytherapy, respectively (p 5 0.385). However, for the subset of patients with tumors 5 cm or less in length, the 5-year actuarial survival was significantly better in those receiving the boost by brachytherapy as opposed to further external beam (64% vs. 31.5%, p 5 0.025). Although not statistically significant, a trend toward improved survival with the brachytherapy boost was suggested in the patients with T1 and T2 tumors. Several questions come to mind while reading the article by Okawa et al. Why randomize patients after 60 Gy external beam rather than prior to external beam radiation? How did investigators decide which patients to exclude from randomization? Why choose the same dose/fractionation scheme for HDR and LDR? How many of the patients received HDR versus LDR brachytherapy? Were the patient sample sizes appropriate for the chosen endpoints of the study? Despite the unusual methodology and statistical design of this study, several interesting points are made. One of the most important points made by Okawa et al. concerns the low incidence of acute or chronic complications observed following brachytherapy. The low incidence of toxicity in this study, as well as several other published reports, suggests that brachytherapy is safe under certain conditions such as: total brachytherapy dose no more than 10 Gy specified at a depth 5 mm below the esophageal mucosa, brachytherapy catheter diameter of 10 mm, no concurrent chemotherapy and brachytherapy (3, 4). Another interesting observation made by Okawa et al. was the significant improvement in cause-specific survival rate following brachytherapy boost in those patients with tumors 5 cm or less in size. The 5-year cause-specific survival rate was 64% for brachytherapy boost, and 31.5% for external beam only (p 5 0.025). There was a tendency to improved cause-specific survival rate for patients with T1-2 disease as opposed to T3-4 tumors. As Okawa et al. point out, small superficial tumors are more effectively encompassed in a relatively uniform brachytherapy dose. However, if uniformity was the major prerequisite for successful treatment, external beam radiation should be superior to brachytherapy. It could be the “nonuniformity” of brachytherapy with hot spots falling within the target that makes brachytherapy more effective than external beam radiation in the treatment of superficial tumors. Concerns regarding the toxicity of esophageal brachytherapy were fueled by the 12% incidence of treatmentrelated esophageal fistulas reported by the Radiation Therapy Oncology Group (RTOG) Phase II study of concurrent chemoradiation followed by brachytherapy boost (1). This unexpectedly high incidence of serious complications, without a corresponding high rate of local tumor control or 1-year survival, stopped further investigation of esophageal