PURPOSE: To report initial mortality findings from the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of pre-enucleation radiation of large choroidal melanoma. METHODS: Patients were evaluated for eligibility at one of 43 participating centers in the United States and Canada. Eligible consenting patients were assigned randomly at the time of enrollment to standard enucleation or to external radiation of the orbit and globe prior to enucleation. Eligibility was confirmed at the COMS Coordinating Center, Echography Center, and Photograph Reading Center. Adherence to the radiotherapy protocol was monitored at the Radiological Physics Center. The diagnosis of choroidal melanoma was confirmed following enucleation by a three-member Pathology Review Committee. Patient accrual began in November 1986 and was completed in December 1994; 1,003 patients enrolled. Patients have been followed at annual clinical examinations. Cause of death was coded by a Mortality Coding Committee whose members were not involved in the care of COMS patients; the clinical trial was monitored by an independent Data and Safety Monitoring Committee. RESULTS: A total of 1,003 patients were enrolled; 506 were assigned to enucleation alone and 497 to pre-enucleation radiation. Treatment groups were well balanced on baseline characteristics. Only nine patients were found to be ineligible after enrollment, seven in the interval between randomization and enucleation and two after enucleation based on histopathology. All but nine patients were treated as assigned; in only six of 491 eyes treated with pre-enucleation radiation was there a major deviation from the radiotherapy protocol. With 5- year outcome known for 801 patients enrolled (80%), the estimated 5-year survival rates and 95% confidence intervals (CIs) were 57% (95% CI, 52% to 62%) for enucleation alone and 62% (95% CI, 57% to 66%) for pre-enucleation radiation. Among the baseline covariates evaluated, only age and longest basal diameter of the melanoma affected the prognosis for survival to a statistically significant degree. The risk of death among patients treated with pre-enucleation radiation relative to those treated with enucleation alone after adjustment for baseline characteristics of patients, eyes, and tumors was 1.03 (95% CI, 0.85 to 1.25). Of 435 deaths classified by the Mortality Coding Committee, 269 patients had histologically confirmed melanoma metastases at the time of death. Estimated 5-year survival rates for this secondary outcome were 72% (95% CI, 68% to 76%) for enucleation alone and 74/o (95% CI, 69% to 78%) for pre-enucleation radiation. CONCLUSIONS: No survival difference attributable to pre-enucleation radiation of large choroidal melanoma, using the COMS fractionation schedule, has been demonstrated to date in this randomized trial. The trial had statistical power of 90% to detect a relative difference in mortality rates between the two treatment arms of 20% or larger. A smaller difference is possible, but a clinically meaningful difference in mortality rates, whether from all causes or from metastatic melanoma, is unlikely.
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