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Objective: This study aimed to determine whether the long-term melanoma-specific mortality rate of patients with a primary choroidal or ciliary body melanoma treated by enucleation is appreciably lower than that of similar patients treated by plaque radiation therapy., Design: Retrospective, nonrandomized, comparative clinical trial., Participants: A previously reported group of 237 patients, 140 treated by enucleation and 97 treated by cobalt-60 (Co-60) plaque between May 1976 and June 1980, and a residual group of 122 patients, 51 treated by enucleation and 71 treated by Co-60 plaque, were identified by variable-by-variable range matching., Intervention: Primary treatment by enucleation or Co-60 plaque radiation therapy was performed., Main Outcome Measures: Melanoma-specific mortality and duration of post-treatment survival were measured., Results: The melanoma-specific mortality rate was substantially worse in the original enucleation subgroup over the entire 15-year follow-up interval; however, differences in baseline prognostic factors between the subgroups are likely to explain the difference in survival curves. After elimination of patients with nonoverlapping values of individual clinical variables to adjust for recognized intergroup differences at baseline, there was no significant or clinically important difference in the 15-year mortality curves of the residual subgroups. The relative rate ratio for the treatment effect in the residual patients was 0.97 (95% confidence interval, 0.51-1.86). There was no late downturn in the survival curve of the plaque-treated patients or late crossing of the curves., Conclusion: A large difference in survival between equivalent groups of patients with primary choroidal or ciliary body melanoma treated by enucleation versus plaque radiation therapy appears to be unlikely.

Background: Radioactive episcleral plaque brachytherapy is a treatment method for selected retinoblastomas. The authors have used this technique since 1976 as both a primary and a secondary treatment method after other methods failed to achieve tumor control., Methods: A review of the records of 400 consecutive children with retinoblastoma showed that solitary plaque radiotherapy was used as a method of management in 103 cases. The authors' overall experience was evaluated, and the results between primary and secondary plaque therapies were compared in these 103 cases., Results: Of the 103 tumors, the mean basal diameter was 7 mm, and the mean thickness was 4 mm. Overlying vitreous seeds were clinically apparent in 50 cases (48%). The mean proximity of the tumor margin to the optic disc margin was 6 mm and to the foveola was 6 mm. The mean follow-up period was 40 months. In 89 cases (86%), the tumor was controlled by one plaque application, whereas in 13 cases (13%), tumor recurrence after initial tumor shrinkage necessitated subsequent treatment. Final visual outcome was good in 63 cases (62%), poor in 30 (29%), enucleation in 9 (9%), and unknown in 1 case. The poor vision was due to foveal retinoblastoma (with or without amblyopia) in 25 cases (83%). Eight of the nine enucleated eyes were treated initially with external beam radiotherapy then later with plaque radiotherapy. In 31 cases (30%), plaque radiotherapy was used as a primary treatment to the tumor, while in 72 cases (70%), it was a secondary form of management after failure of other methods to control the tumor. Statistical analysis showed that tumors treated with plaque radiotherapy as a primary measure were more likely to be larger in in base (P = 0.01) and thickness (P = 0.01) than secondary treated tumors. The secondary treated retinoblastomas were more likely to have vitreous seeds (P = 0.02) than the primary treated tumors. The rate of tumor control and patient survival was similar between the two groups., Conclusion: Plaque radiotherapy is very effective in treating selected retinoblastomas with a high rate of tumor control and patient survival. It can be used successfully as a primary or a secondary treatment for tumors that have not been adequately controlled by other therapeutic methods.

The authors investigated the impact of local intraocular tumor relapse on survival in a matched-group comparison study of patients with primary choroidal or ciliary body melanoma managed with cobalt 60 plaque radiotherapy. Sixty-two patients with local relapse were matched with an equal number of relapse-free patients in terms of known clinical prognostic factors for both melanoma-specific mortality (largest linear tumor dimension, location of anterior tumor margin, age) and local tumor relapse (location of posterior tumor margin). The follow-up of every relapse-free patient equaled or exceeded the interval to relapse for each matched patient with local relapse. The estimated 5-year survival (Kaplan-Meier) in the relapse-free patients was 87% (standard error = 4%), while that in the local relapse group was 58% (standard error = 6%). This difference is statistically significant (P less than 0.0001, log rank test). These results support the hypothesis that local tumor relapse after cobalt 60 plaque radiotherapy is an important post-treatment clinical indicator of the tumor's greater malignant potential and the patient's increased risk of melanoma-specific mortality.

A review of 1019 patients with posterior uveal melanomas, who were treated with episcleral plaque radiotherapy between April 1976 and December 1987, showed that 59 (6%) of these patients have thus far required enucleation of the affected eye. The most common clinical reasons for enucleation were tumor regrowth (51%) and neovascular glaucoma (31%). These irradiated melanomas were of mixed cell type in 40 cases (68%), spindle in 10 cases (17%), totally necrotic in 7 cases (12%), and epithelioid in 2 cases (3%). Some degree of tumor necrosis was seen in all cases. Overall, the median number of mitoses per 40 high-power fields in these irradiated tumors was 0. Most (64%) of the tumors had no identifiable mitosis in 40 high-power fields. A three-way simultaneous comparison of the following groups was made: irradiated eyes enucleated for tumor regrowth, irradiated eyes enucleated for neovascular glaucoma, and a matched group of nonirradiated posterior uveal melanomas. This comparison showed that the largest tumor dimension was significantly greater in the irradiated eyes enucleated for tumor regrowth than in the other two groups. Mitotic activity was significantly higher in the irradiated tumor regrowth and nonirradiated groups than in the irradiated neovascular group. There was no significant difference among the three groups in an analysis of height. The results suggested that mitotic activity may exist after plaque radiotherapy, especially when there is clinical evidence of tumor regrowth.

A method has been devised for evaluating the rate and extent of regression of the first 100 consecutive patients with a posterior uveal melanoma that we had managed by Cobalt-60 plaque radiotherapy at Wills Eye Hospital. It was found that the "average" posterior uveal melanoma in the series did not regress rapidly to a flat, depigmented scar but shrank slowly and persisted as a residual mass approximately 50% of the thickness of the original tumor at 54 months following Cobalt-60 plaque radiotherapy. We also found that the rate and extent of regression of the tumors in patients who subsequently developed metastatic melanoma were not appreciably different than the rate and extent of regression of the tumors in patients who remained well systemically. These observations indicate that the rate and extent of regression of posterior uveal melanomas following Cobalt-60 plaque radiotherapy are poor indicators of the prognosis of the affected patients for subsequent development of clinical metastatic disease.

The authors analyzed the clinical and follow-up data on 277 selected patients with primary choroidal or ciliochoroidal melanoma who were treated with 60Co plaque radiotherapy between 1976 and 1982. Local recurrence of the irradiated melanoma developed in 39 (14%) patients during the follow-up interval. The 5-year tumor recurrence rate (Kaplan-Meier) was estimated to be 12%. Multivariate prognostic factor analysis (Cox proportional hazards modeling) identified the largest linear tumor dimension and proximity of the posterior margin of the tumor to the optic nerve head as predictors of recurrence. The 5-year survival rate of patients whose tumors recurred (58%) was significantly (log-rank test P = 0.0023) worse than that of patients whose tumor remained clinically controlled (82%).

To determine the prognostic value of the regression rate of choroidal melanomas after cobalt-60 plaque radiotherapy, the authors performed a multivariate analysis on 159 patients treated with a cobalt plaque during the interval from 1976 through 1980. Thirty-three of the 159 patients had died as of the survey date; 29 of metastatic melanoma and 4 of other causes. Multivariate Cox proportional hazards modeling identified a two-term regression incorporating maximal basal tumor diameter at treatment and tumor thickness at 12 months posttreatment as the best model (P less than 0.005 for both parameters) for predicting length of tumor-free survival. These results are consistent with the hypothesis that rapid regression of a choroidal melanoma after cobalt-60 plaque radiotherapy is an unfavorable prognostic sign for prolonged metastasis-free survival.

The authors report their preliminary results of episcleral plaque radiotherapy (cobalt 60, iridium 192, ruthenium 106, and iodine 125 plaques) in 50 selected patients with retinoblastoma. There were 97 plaque applications to 51 affected eyes in these 50 patients. The plaque was used as primary treatment in 15 eyes and as secondary treatment after failure of external beam radiotherapy, photocoagulation, and/or cryotherapy in 36 eyes. Vitreous seeding of tumor cells was evident ophthalmoscopically in 49 of the 51 eyes, negating the possibility of ultimate success by further photocoagulation or cryotherapy. In 18 patients, the contralateral eye had been enucleated and the remaining eye was being considered for enucleation because all other treatment modalities had failed. In 2 of these 18 patients (11%), the remaining eye was salvaged with plaque radiotherapy and some vision was preserved. In 33 eyes with less advanced tumors, 31 had some degree of vitreous seeding by tumor cells. The eye has been retained in all 33 of these patients and useful vision preserved in most. On the basis of these preliminary observations, the authors conclude that plaque radiotherapy can be used successfully as a primary treatment for selected cases of unilateral or bilateral retinoblastoma or as a supplemental treatment after other treatment methods have failed. The current indications for plaque radiotherapy and its advantages over other therapeutic modalities are discussed.

One hundred patients with choroidal melanomas who were treated by the authors with cobalt plaque radiotherapy were analyzed with regard to tumor regression, visual results, complications, and mortality rate. The follow-up period at the time of this writing ranged from one to five years. These preliminary observations indicate that cobalt plaque radiotherapy induces tumor regression in 96% of cases, preserves useful vision in many cases and has fewer complications during the one- to five-year follow-up period than previously believed.

A review of 1019 patients with posterior uveal melanomas who were treated with episcleral plaque radiotherapy showed that 59 (6%) required enucleation of the affected eye. Seventeen of the enucleations were done within 1 year, 30 within 2 years, and 55 within 5 years. The enucleated eyes had been treated with a cobalt-60 plaque in 39 cases, a ruthenium-106 plaque in 13 cases, an iodine-125 plaque in four cases, and an iridium-192 plaque in three cases. The primary reasons for enucleation included tumor regrowth in 30 cases (51%), neovascular glaucoma in 18 (31%), patient request in five (8%), scleral melting in four (7%), painful bullous keratopathy in one (2%), and hemolytic glaucoma in one (2%). The time interval from plaque treatment to eventual enucleation averaged 29 months. Tumor regrowth requiring enucleation was detected clinically an average of 28 months after treatment. In these cases the average radiation dose to the tumor apex was 7700 cGy and to the tumor base 36,000 cGy. Uncontrollable neovascular glaucoma occurred an average of 38 months after plaque radiotherapy and, most commonly, after cobalt-60 plaques were used. Eyes with plaque-induced scleral melting eventually required enucleation after an average of 10 months. In all cases of scleral melting, the tumor was ciliochoroidal.