Trends found in a small retrospective study comparing primary chemotherapy and primary external-beam radiation therapy in the treatment of retinoblastoma could set the stage for a more comprehensive, international study. The initial study of 25 cases of bilateral retinoblastoma meeting strict inclusion criteria found that chemotherapy was associated with a slightly higher frequency of enucleation whereas radiation was associated with a slightly higher frequency of death.
Fort Lauderdale, FL-In a small, retrospective comparison study of external-beam radiation therapy (EBRT) versus chemotherapy in the treatment of bilateral retinoblastoma, investigators found that EBRT may yield a slightly higher ocular preservation rate than primary chemotherapy but that chemotherapy has a more favorable survival prognosis.
These results, however, have minimal statistical or clinical value because of the study's small enrollment, said James J. Augsburger, MD, at the annual meeting of the Association for Research in Vision and Ophthalmology.
"At best, we can say that this is an intriguing finding, but by no means do we suggest that it's definitive or that we should make any changes in our practice based on that kind of information," said Dr. Augsburger, chairman and professor, Department of Ophthalmology, and director of ocular oncology, University of Cincinnati College of Medicine. He is planning a larger, international study that should yield enough cases for a valid statistical analysis.
Another factor relegating EBRT to second-line therapy was the development of an effective, multidrug chemotherapy regimen for retinoblastoma, including the intraocular form of the disease, that made almost all tumors shrink substantially.
"Up until that time, there was no effective chemotherapeutic regimen available for intraocular retinoblastoma," he said. "Some regimens available were effective in certain tumors, but in most cases, they would fail."
These pharmacological developments produced a dramatic shift in retinoblastoma treatment in favor of chemotherapy. A comparative trial of chemotherapy versus radiation had not been conducted, however; neither are any side-by-side comparison data available on the effectiveness or the risks of one treatment versus the other, he said.
Finally, after more than 10 years of experience involving these chemotherapy regimens, enough evidence has been accumulated to conduct such a study. Dr. Augsburger and colleagues recently performed a preliminary retrospective chart review of this nature, determining and comparing the rates of ocular preservation and survival in children with bilateral retinoblastoma treated initially by either chemotherapy or EBRT. They conducted a review of all patients with retinoblastoma evaluated by Dr. Augsburger between 1980 and 2006, a period that was chosen to include the era when EBRT was the primary therapy as well as the years since chemotherapy became the preferred approach.
Although 300 patients with retinoblastoma were evaluated during the study, 253 cases were excluded due to one or more exclusion criteria. Exclusion criteria were unilateral ocular involvement, prior treatment of any type, and/or any concurrent treatment (i.e., within 1 month following the start of the primary chemotherapy or EBRT), and cases evaluated exclusively for a second opinion.
"It was surprising to me that there were so few kids who qualified for inclusion in this study," Dr. Augsburger said. Many children were excluded, he added, because they had been referred from other centers after receiving treatment there.
Of the 47 children included in the review, the initial treatment consisted of bilateral chemotherapy in 10, bilateral EBRT in 15, primary enucleation of the worse eye followed by EBRT to the better eye in six, primary enucleation of the worse eye followed by chemotherapy in one, enucleation of the worse eye and cryotherapy and/or laser therapy to the better eye in five, cryotherapy and/or laser therapy to both eyes in three, and other methods or combinations of methods in seven. These other methods included plaque radiotherapy.
In total, the review yielded 25 satisfactory cases: 15 children (30 eyes) whose initial treatment was bilateral EBRT and 10 children (20 eyes) whose initial treatment was bilateral chemotherapy.
Data showed that children treated by EBRT had a slightly higher rate of eventual death. The statistic, however, was based on the deaths of only two of the 15 children (13.3%) who had initial bilateral EBRT. One death was due to metastasis and the other to pineoblastoma. No deaths due to retinoblastoma or another malignancy occurred among the 10 children who had initial bilateral chemotherapy.