International Journal of Radiation Oncology*Biology*Physics
Clinical investigationEyeRadiation complications and tumor control after 125I plaque brachytherapy for ocular melanoma
Introduction
Choroidal melanoma is a rare but deadly ocular malignancy. Untreated ocular melanoma has a high rate of systemic metastasis. As no cure exists for systemic spread, death typically ensues within months. The focus of treatment is to halt progression of the tumor and limit it to the eye. The standard therapy for more than 100 years was surgical enucleation, which drastically improved tumor control and overall survival. Modern techniques of radiation therapy for ocular melanoma have resulted in survival rates at least as good as with enucleation (1). Episcleral plaque brachytherapy by use of isotopes such as 60Co, 106Ru, and 125I have achieved local control rates in the range of 88% to 98% at 5 years (2, 3, 4, 5). Trials with charged particles such as helium ions and proton beams have been even more promising; reported local control rates were as high as 99% at 5-years (5, 6).
Plaque brachytherapy with 125I is currently the most common treatment modality for ocular melanoma in the United States. Despite the favorable dose distribution of 125I, this therapy carries a high rate of delayed radiation damage to the retina, optic nerve, and other ipsilateral eye structures. Patients often experience variable amounts of decline or loss of visual acuity from cataract formation and other ocular morbidities over the subsequent 1 to 3 years. However, radiation therapy has potential advantages over enucleation, such as delay or reduction of vision loss and a more favorable cosmetic effect.
An ongoing controversy existed for years as to whether radiation therapy was as effective as enucleation at halting local progression and decreasing mortality. This question was definitively answered by the Collaborative Ocular Melanoma Study (COMS). This series of multicenter, randomized controlled trials enrolled and treated more than 1,300 patients with medium-sized choroidal melanoma and reported no significant 5-year survival advantage of enucleation versus 125I irradiation (7). However, although the COMS group answered the question of survival versus treatment modality, it did not address certain strategies of radiotherapy dosing techniques that might maximize the local control and survival while minimizing the treatment-related morbidities such as visual decline and other ocular toxicities (1). Ocular melanoma patients now have the option of retaining their eye, but the benefits of organ conservation may be reduced by lost visual function and symptomatic radiation toxicities. Few published studies have investigated how treatment factors such as dose rate influence the final outcome of visual acuity (8, 9). The ideal total dose and dose rate for achieving local and systemic control without incurring a high risk of decreased visual acuity remains undefined. Few studies have adequately examined the incidence of other clinically significant toxicities, such as ocular discomfort. This information is important because other radiotherapy modalities, (e.g., 106Ru or proton beam) might have a better toxicity profile than 125I. The COMS did not answer the question of how to manage choroidal melanomas located adjacent to the optic disc or small choroidal melanomas, because these conditions were considered exclusion criteria for the study (5, 10).
We wanted to better understand how survival and ocular function after the 125I plaque treatment of patients with ocular melanoma at our institution compared with studies previously published in literature. Here, we review our experience with all ocular melanoma patients treated by this modality at our institution over a 15-year span and include factors that affect the occurrence of ocular complications, visual acuity outcome, and rates of local control and metastasis.
Section snippets
Patients and methods
We analyzed the records of all patients who had choroidal melanoma treated with 125I plaque radiotherapy at the Mayo Clinic between April 1985 and August 2000. Patients who had been treated with a plaque design different than the design used in the COMS Study were excluded, although 6 patients treated with COMS-style plaques modified with a notch to accommodate the optic nerve or ciliary body were included. Patients were not excluded on the basis of tumor size, location, or local extension into
Results
Between September 1986 and August 2000, 156 patients (156 eyes) with choroidal melanoma received radiation by means of a COMS-design 125I episcleral plaque. Of these patients, 80 were female and 76 were male. All patients described their race as Caucasian, except 1 patient who was of Arabic origin. The median age was 63 years (range, 24 to 87 years). Fifty-three patients (34%) had systemic hypertension, 26 patients (17%) had diabetes mellitus (Type I or II), 26 patients (17%) had
Discussion
The primary outcomes of interest in this study were tumor control and patient survival. Kaplan-Meier estimates showed a 5-year local control of 92%, which corresponds to an initial local treatment failure of 7% at 5 years. Of the 156 patients in this study, 138 (88%) experienced permanent tumor regression after therapy and 6 (4%) experienced stable tumor control without evidence of regression. Twelve patients (8%) experienced progression of the tumor, of which only 9 subsequently proceeded to
Conclusion
The ideal parameters for the treatment of ocular melanoma with 125I have yet to be defined. Local control of this malignancy is excellent, especially when successful secondary procedures for initial failures are taken into account. Because distant failure accounts for the vast majority of cause-specific mortality, the primary goal of therapy must be to prevent systemic metastases. The secondary goal of 125I therapy is to maintain ocular function while limiting radiation toxicities. Higher
Acknowledgment
The authors thank the statisticians at the Mayo Clinic Center for Patient-Oriented Research for their invaluable statistical assistance.
References (22)
Uveal melanomasConservation treatment
Hematol Oncol Clin North Am
(2001)Recurrence of posterior uveal melanoma after 60Co episcleral plaque therapy
Ophthalmology
(1989)- et al.
St Bartholomew’s Hospital, Comparison of episcleral plaque and proton beam radiation therapy for the treatment of choroidal melanoma
Ophthalmology
(1999) - et al.
Late radiation failures after iodine 125 brachytherapy for uveal melanoma compared with charged-particle (proton or helium ion) therapy
Ophthalmology
(2002) Changing concepts in the management of choroidal melanoma
Am J Ophthalmol
(2003)- et al.
Maximizing local tumor control and survival after proton beam radiotherapy of uveal melanoma
Int J Radiat Oncol Biol Phys
(2001) - et al.
High intensity 125-iodine (125I) plaque treatment of uveal melanoma
Int J Radiat Oncol Biol Phys
(1993) - et al.
Posttreatment visual acuity in patients treated with episcleral plaque therapy for choroidal melanomasDose and dose rate effects
Int J Radiat Oncol Biol Phys
(2002) - et al.
The COMS randomized trial of iodine 125 brachytherapy for choroidal melanomaIV
Local treatment failure and enucleation in the first 5 years after brachytherapy. COMS Report No. 19. Ophthalmology
(2002) - et al.
Radiation complications and tumor control after plaque radiotherapy of choroidal melanoma with macular involvement
Am J Ophthalmol
(1999)