THE COLLABORATIVE OCULAR MELANOMA STUDY (COMS) RANDOMIZED TRIAL OF PREENUCLEATION RADIATION OF LARGE CHORNIDAL MELANOMA - II - INITIAL MORTALITY FINDINGS COMS REPORT NO. 10

PURPOSE: To report initial mortality findings from the Collaborative O cular Melanoma Study (COMS) randomized clinical trial of pre-nucleatio n radiation of large choroidal melanoma. METHODS: Patients were evalua ted for eligibility at one of 43 participating centers in the United S tates and Canada. Eligible consenting patients were assigned randomly at the time of enrollment to standard enucleation or to external radia tion of the orbit and globe prior to enucleation. Eligibility was conf irmed at the COMS Coordinating Center, Echography Center, and Photogra ph Reading Center. Adherence to the radiotherapy protocol was monitore d at the Radiological Physics Center. The diagnosis of choroidal melan oma was confirmed following enucleation by a three-member Pathology Re view Committee, Patient accrual began in November 1986 and was complet ed in December 1994; 1,003 patients enrolled. Patients have been follo wed at annual clinical examinations. Cause of death was coded by a Mor tality Coding Committee whose members were not involved in the care of COMS patients; the clinical trial was monitored by an independent Dat a and Safety Monitoring Committee. RESULTS: A total of 1,003 patients were enrolled; 506 were assigned to enucleation alone and 497 to pre-e nucleation 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 enucleatio n and two after enucleation based on histopathology. All but nine pati ents were treated as assigned; in only six of 491 eyes treated with pr e-enucleation radiation was there a major deviation from the radiother apy protocol. With 5-year outcome known for 801 patients enrolled (80% ), the estimated 5-year survival rates and 95% confidence intervals (C Is) were 57% (95% CI, 52% to 62%) for enucleation alone and 62% (95% C I, 57% to 66%) for pre enucleation radiation. Among the baseline covar iates evaluated, only age and longest basal diameter of the melanoma a ffected the prognosis for survival to a statistically significant degr ee. The risk of death among patients treated with pre-enucleation radi ation relative to those treated with enucleation alone after adjustmen t 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 Codi ng Committee, 269 patients had histologically confirmed melanoma metas tases at the time of death. Estimated 1-year survival rates for this s econdary outcome were 72% (95% CI, 68% to 76%) for enucleation alone a nd 74% (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 b een demonstrated to date in this randomized trial. The trial had stati stical power of 90% to detect a relative difference in mortality rates be tween the two treatment arms of 20% or larger. A smaller differenc e is possible, but a clinically meaningful difference in mortality rat es, whether from all causes or from metastatic melanoma, is unlikely. (C) 1998 by Elsevier Science Inc. All rights reserved.).