Trial Information

For more than 100 years, removal of the eye (enucleation) has been the standard treatment
for choroidal melanoma. Before the COMS was initiated in 1986, interest in radiation therapy
had increased because of the potential for saving the eye and perhaps some vision. However,
the merits of radiation with respect to prolonging patient survival were unknown. The best
data from nonrandomized studies suggested that there was no difference in length of
remaining life between patients treated with radiation and those whose eyes were enucleated.
Thus, it was appropriate and necessary to conduct a randomized, controlled clinical trial in
which a large number of patients would be followed for many years in order to compare
enucleation and radiation with respect to relative success in prolonging survival of
choroidal melanoma patients.

The Collaborative Ocular Melanoma Study (COMS) is a set of long-term, multicenter,
randomized controlled trials. In the trial for patients with tumors of medium size,
enucleation and irradiation with an iodine-125 episcleral plaque are compared on the basis
of length of remaining life. All randomized patients will be followed for 5 to 15 years or
until death. For patients randomly assigned to enucleation, the eye was removed following a
standard procedure. For patients assigned to plaque irradiation, the margins of the tumor
were located and the dimensions of the tumor were measured by the ophthalmic surgeon. A
gold plaque with a plastic seed carrier that contained the proper dosage and configuration
of radioactive iodine seeds was sutured to the outside (sclera) of the eye over the base of
the tumor. This procedure made possible the delivery of a high dose of radiation to a very
localized area (85 Gy [TG-43] to the tumor apex). The plaque typically was removed from the
eye after three to seven days. Enrollment was completed in this trial in July 1998 with
1,317 patients enrolled. Clinical follow-up of patients will end in July 2003.

In the COMS trial of preoperative radiation, patients with large tumors were randomized to
enucleation alone or to enucleation preceded by 20 Gy of external beam radiation. The two
randomly assigned groups of patients were followed for at least five years or until death
and have been compared on the basis of length of remaining life and other outcomes.
Enrollment in this trial was completed in December 1994, with 1,003 patients enrolled.
Clinical follow-up of all patients in this trial ended in July 2000.

Accrual to a nonrandomized pilot study to assess the feasibility of a randomized trial for
small tumors was halted in 1989. Additional followup of those 204 patients was carried out
from 1994 to 1996.

The COMS is conducted in 43 clinical centers located in major population areas of the United
States and Canada. Six resource centers participate and have major roles in quality
assurance for the study. Information gathered and analyzed includes time to death from all
causes, time to death from cancer (whether metastatic choroidal melanoma or not), diagnosis
of other tumors, complications of radiation, and changes in visual acuity. A parallel study
of quality of life for patients enrolled in the trial of radioactive plaque was initiated in
January 1995. From November 1986 through July 1998, 8,712 patients with choroidal melanoma
of all sizes were screened for eligibility for a COMS clinical trial.