International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationsRandomized study of brachytherapy in the initial management of patients with malignant astrocytoma☆
Introduction
Despite the fact that two randomized studies have demonstrated a statistically significant improvement in survival with the use of postoperative radiation therapy in patients with malignant astrocytomas, patients continue to recur locally and die of their disease 1, 2. A retrospective review of radiation dose in three sequential Brain Tumor Study Group studies demonstrated a statistically significant improvement in survival in the 60 Gray (Gy) group over the 50 Gy group (3). Subsequently, a joint Radiation Therapy Oncology Group (RTOG) and Eastern Cooperative Oncology Group (ECOG) randomized study found no advantage for patients who had received 70 Gy as opposed to 60 Gy (4).
It has been well documented that most patients with malignant astrocytoma recur at the site of their original tumor mass 5, 6. Brachytherapy has both radiobiologic and dose distribution advantages over conventional external beam radiation therapy that were compelling, and led to an increased interest in the use of brachytherapy as a means of boosting the dose at the site of the original tumor in these patients 7, 8.
Accordingly, investigators began developing brachytherapy techniques for brain tumors, and reports started appearing in the literature in the early 1980s. These were Phase II studies, where brachytherapy was being utilized for recurrence in previously irradiated patients 9, 10, 11, 12, 13, 14, 15. Subsequent reports described the use of brachytherapy as a boost following external beam radiation in the initial management of patients with malignant gliomas 13, 14, 16, 17, 18, 19. Although these authors were reporting encouraging results, by necessity, patients with smaller more peripherally located tumors were undergoing brachytherapy, and it was not possible to discern whether their improved survival was due to brachytherapy or partially due to a selection of patients with better prognoses. Additionally, brachytherapy is an invasive procedure that can be associated with significant toxicity. It was for these reasons that our group decided to embark on a randomized study of brachytherapy as a boost to conventional external radiation therapy in the initial management of patients with malignant astrocytomas.
Section snippets
Methods and materials
The trial was designed to compare conventional external radiation therapy alone vs. conventional radiation therapy plus a brachytherapy boost in patients with malignant astrocytoma. The primary end point was the overall survival from the date of initial surgery. Patients satisfying the eligibility criteria below were randomized by a telephone call to the biostatistics department at the Princess Margaret Hospital. All patients were treated with external radiation therapy at one of the two
Results
Between 1986 and 1996, 142 patients were randomized on the study. On pathologic review, two patients were excluded on the basis of wrong histology (both were metastases, one from each arm of the study). This left a study population of 140 patients, 71 randomized to the implant arm and 69 to the nonimplant arm. Two patients had gliosarcomas, and all others had malignant astrocytomas.
Table 1 outlines the pretreatment characteristics, surgical procedures, the completion rates for external
Discussion
The report by Walker et al. suggested an advantage of 60 over 50 Gy in patients with malignant astrocytoma, but this was a retrospective review in which dose was not a randomized variable (3). In 1991, the Medical Research Council published the results of their randomized study comparing 60 Gy in 30 fractions to 45 Gy in 20 fractions in 474 patients (24). After adjusting for a slight imbalance in age distribution between the two arms, the Cox proportional hazards model estimated an improvement
Conclusions
This randomized study of a brachytherapy boost in addition to conventional external beam radiation therapy has not shown a statistically significant improvement in survival. Because of the relatively small number of patients randomized in this study, it is possible that a larger study might demonstrate a small benefit. There was a decrease in local recurrence and a trend for improved survival in the implant arm, and it is possible that brachytherapy concurrent with other therapies may be useful
Acknowledgements
The authors are grateful to their radiation oncology (in particular, Dr. Charlene Young) and neurosurgical colleagues for having referred their patients for inclusion in this study, and to Dr. Juan Bilbao for acting as the reference neuropathologist.
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This study in part was supported by a grant from the National Cancer Institute of Canada.