Researchers have found that the survival rates for two alternative treatments for primary eye cancer — radiation therapy and removal of the eye — are about the same. Prior to this finding, there was a question in the medical community as to whether either treatment might result in lower mortality. Also, as a consequence of this research, the capability of doctors nationwide to provide more accurate diagnoses and state-of-the-art treatments for eye cancer has been greatly expanded. Mortality data are compared in the July 2001 issue of Archives of Ophthalmology.
“These findings are reassuring to patients with medium-sized eye tumors who have to choose between the option of radiation therapy vs. removal of the eye,” said Paul A. Sieving, M.D., Ph.D., director of the National Eye Institute (NEI). “Patients now know that their choice will not impact their survival. Equally important, more information is now available about how each treatment will affect a patient’s life, so patients and their doctors can make informed treatment decisions.”
The clinical trial — called the Collaborative Ocular Melanoma Study (COMS) — was supported by the NEI and the National Cancer Institute (NCI), components of the Federal government’s National Institutes of Health.
“The COMS findings are a striking example of the role that clinical trials play in improving patient care,” said Richard Klausner, M.D., director of the NCI. “Without this important trial, patients would not have known that they have a choice between radiation and surgery for treatment of their ocular melanoma, with the same opportunity for long-term survival.”
With the data showing similar survival rates for radiation therapy vs. removal of the eye, quality of life issues become important factors when deciding which of the two treatment options is better for the individual patient.
“Most patients who received the radiation therapy had some vision loss, and some eyes receiving radiation therapy were later removed because of tumor regrowth or other complications,” said Stuart Fine, M.D., chairman of the Department of Ophthalmology at the University of Pennsylvania in Philadelphia and chair of the COMS clinical trial. “However, many people diagnosed with primary eye cancer may consider these problems worth risking in comparison to immediate loss of the eye.
“COMS researchers have initiated a parallel study to assess the quality of life for patients enrolled in this clinical trial,” Dr. Fine said. “The findings of this study — when released in a few years — should provide more information on which to base a treatment decision.”
For more than a century, removal of the eye has been the standard treatment for primary eye cancer, also known as ocular melanoma. During the past 25 years, interest in radiation therapy has increased because of the potential for saving the eye — and with it, some vision.
In the COMS, patients with medium-sized tumors were studied in a randomized clinical trial to determine which of two treatments — radiation therapy or removal of the eye — is more likely to prolong survival.
The affected eyes of one group received a form of radiation therapy called I-125 brachytherapy (pronounced BRAK-e-ther-a-pe), in which a small plaque containing radioactive iodine pellets is placed over the tumor.
The other group had the eye removed. Approximately one-third of the patients have been followed for 10 years; over 80 percent were followed for five years. Researchers found that the survival rates were essentially the same in the two groups.
In the COMS clinical trial, researchers also found that the five-year survival rate of patients who were treated with either radiation therapy or eye removal was 82 percent, considerably better than the 70 percent five-year survival rate that had been projected when the study was designed in 1985. Moreover, there is no evidence that either treatment causes harm to the other eye. All patients in the study will continue to be followed for up to 15 years.
The type of eye cancer studied by COMS researchers is choroidal melanoma, a tumor of the eye that arises from pigmented cells of the choroid, a layer of tissue in the back of the eye. Although it is rare, choroidal melanoma is the most common primary eye cancer in adults. These tumors enlarge over time and may lead to vision loss. More importantly, these tumors can spread, or metastasize, to other parts of the body; once metastasis is clinically detected, death typically occurs within months.
Because there is no cure for metastatic melanoma, treatment is aimed at keeping the cancer confined to the eye. Researchers estimate that between 1600 and 2400 new cases of ocular melanoma are diagnosed annually in the United States and Canada, a rate of about six-to-eight new cases per million people each year. Choroidal melanoma is much more common in whites of northern European descent.
In June 1998, in a separate but related COMS clinical trial, researchers released results concerning whether a type of preoperative radiation therapy, called external beam radiation, prolonged life for patients whose ocular melanoma tumors were so large that removal of the eye was a medical necessity.
Researchers reported that patients had similar survival rates regardless of whether their eyes were treated with external beam radiation prior to removal of the eye, or had their eyes removed without prior radiation therapy.
The COMS trials were conducted at 43 institutions, including medical schools, hospitals, and doctors’ offices, throughout the United States and Canada. A list of current study centers and principal investigators is attached.
The National Eye Institute (NEI) and the National Cancer Institute (NCI) are both part of the National Institutes of Health (NIH). The NEI is the Federal government’s lead agency for vision research that leads to sight-saving treatments and plays a key role in reducing visual impairment and blindness. The NCI is the Federal government’s primary agency for cancer research. The NIH is an agency of the US Department of Health and Human Services.
Background
The Collaborative Ocular Melanoma Study (COMS) Randomized Trial of I-125 Brachytherapy for Medium Choroidal Melanoma
Choroidal melanoma is a tumor of the eye that forms from pigmented cells of the choroid, a layer of vascular tissue in the back of the eye. These tumors enlarge over time and can lead to loss of vision. Melanoma cells also can spread to other parts of the body and may cause death. Although it is a rare cancer, choroidal melanoma is the most common primary eye cancer in adults.
Choroidal melanoma may produce symptoms of blurry vision. However, there are often no symptoms in the disease’s early stages, and the cancer may grow before the problem becomes noticeable. Choroidal melanoma is usually detected during a dilated eye exam, when an eye care professional dilates the pupils and examines the back of the eye.
Since the late 19th century, removal of the eye has been the standard treatment for choroidal melanoma of all sizes; radiation has been used experimentally to treat choroidal melanoma since World War II. During the past 20 years, interest in different methods of radiation therapy has increased because of the potential for saving eyes with small to medium-sized tumors.
However, many in the medical community questioned whether patients treated with eye-conserving radiation therapy experienced higher death rates than those whose eyes were removed. Researchers concluded that the only way to determine this conclusively was to conduct a clinical trial in which a large number of choroidal melanoma patients would randomly receive the two different treatments and be followed for many years. The survival rates of the two treatments could then be compared.
The Collaborative Ocular Melanoma Study (COMS)
The Collaborative Ocular Melanoma Study (COMS) includes two separate, long-term, multicenter, randomized controlled trials that compare treatments with respect to survival rates of patients with choroidal melanoma.
The two COMS clinical trials are:
- 1. The Randomized Trial of Pre-Enucleation Radiation for Large Choroidal Melanoma. This trial determined whether a type of preoperative radiation therapy, called external beam radiation, prolongs life for patients whose tumors are so large as to require removal of the eye. Researchers found that for at least five years after diagnosis and treatment, patients with large choroidal melanoma had similar survival rates regardless of whether they were treated with radiation prior to removal of the eye or had their eye removed without prior radiation therapy. Previous to this clinical trial, there had been uncertainty in the medical community about the value of irradiating the eye prior to eye removal in patients with large choroidal melanoma. These results were reported in the June 1998 issue of the American Journal of Ophthalmology.
- 2. The Randomized Trial of I-125 Brachytherapy for Medium Choroidal Melanoma. This trial was designed to determine which of two standard treatments — removal of the eye or therapy with small radioactive iodine pellets placed over the tumor (brachytherapy) — is more likely to prolong survival of eligible patients with medium-sized tumors. It is the results of this trial that are reported in the July 2001 issue of the Archives of Ophthalmology.
The Randomized Trial of I-125 Brachytherapy for Medium Choroidal Melanoma
Patient enrollment in the COMS’ Randomized Trial of I-125 Brachytherapy for Medium Choroidal Melanoma began in February 1987 and was completed in July 1998. To be eligible for this trial, a patient had to have choroidal melanoma from 2.5 to 10.0 mm in apical height and no more than 16.0 mm in longest basal diameter. Eligible patients were at least 21 years old, had no other primary tumor, and had no other disease that threatened their lives within the next five years. Previous treatment related to the eye cancer rendered a patient ineligible. Eligible patients enrolled and received treatment at 43 clinical centers located in major population areas of the United States and Canada.
The study enrolled 1317 patients with medium-sized choroidal melanoma. About 98 percent were non-Hispanic whites. The group was evenly divided by gender, and the mean age was approximately 60 years. Patients were assigned to one of two treatment groups by randomization. One group — 660 patients — was assigned to have the affected eye removed. The other group — 657 patients — was assigned to radiation treatment.
The radiation treatment was delivered via an iodine-125 episcleral plaque. Prior to the treatment, the dimensions of the tumor were measured. A gold plaque with a plastic seed carrier containing the proper dosage and configuration of radioactive iodine seeds was sutured to the outside of the eye over the base of the tumor. This procedure delivered a high dose of radiation to the tumor. The plaque typically was removed from the eye after three-to-five days.
COMS Clinical Trial Current Principal Investigators & Study Centers
Arizona
Leonard Joffe, M.D.
Retina Associates Southwest
Tucson, AZ
California
Bradley R. Straatsma, M.D.
Jules Stein Eye Institute
University of California at Los Angeles
Los Angeles, CA
A. Linn Murphree, M.D.
Estelle Doheny Eye Foundation
University of Southern California
Los Angeles, CA
Man M. Singh Hayreh, M.D.
Southern California Permanente Group
Panorama City, CA
Robert N. Johnson, M.D.
Schatz, McDonald, Johnson, and Ai
San Francisco, CA
Colorado
Kenneth R. Hovland, M.D.
Adventist Hospital
Denver, CO
Florida
Timothy G. Murray, M.D.
Bascom Palmer Eye Institute
University of Miami School of Medicine
Miami, FL
W. Sanderson Grizzard, M.D.
Retina Associates of Florida, P.A.
South Tampa Medical Center
Tampa, FL
Georgia
Paul Sternberg, Jr., M.D.
Emory Eye Center
Emory University
Atlanta, GA
James H. Frank, M.D.
Piedmont Hospital
Eye Consultants of Atlanta, P.C.
Atlanta, GA
Illinois
Lee M. Jampol, M.D.
Northwestern University Medical School
Chicago, IL
Norman P. Blair, M.D.
University of Illinois
Chicago, IL
Indiana
John T. Minturn, M.D.
Midwest Eye Institute
Indianapolis, IN
Iowa
Thomas A. Weingeist, M.D., Ph.D.
University of Iowa Hospitals and Clinics
Iowa City, IA
Louisiana
Gerald Cohen, M.D.
Touro Infirmary
New Orleans, LA
Maryland
Andrew P. Schachat, M.D.
The Wilmer Ophthalmological Institute
The Johns Hopkins Medical Institutions
Baltimore, MD
Massachusetts
Clement L. Trempe, M.D.
Schepens Retina Associates
Boston, MA
Michigan
Andrew K. Vine, M.D.
W. K. Kellogg Eye Center
University of Michigan
Ann Arbor, MI
Antonio Capone, M.D.
Associated Retinal Consultants, P.C.
Royal Oak, MI
Minnesota
Dennis M. Robertson, M.D.
Mayo Foundation
Rochester, MN
Missouri
J. William Harbour, M.D.
Washington University School of Medicine
St. Louis, MO
New York
David H. Abramson, M.D.
Cornell University Medical Center
Paul T. Finger, M.D.
New York Eye and Ear Infirmary
New York, NY and North Shore University Hospital
Great Neck, NY
North Carolina
Jonathan J. Dutton, M.D., Ph.D.
Atlantic Eye and Face Center
Cary, NC
Ohio
Z. Nicholas Zakov, M.D.
Retina Associates of Cleveland/Case Western Reserve University
Beachwood, OH
Froncie A. Gutman, M.D.
Cleveland Clinic Foundation
Cleveland, OH
Frederick H. Davidorf, M.D.
Ohio State University College of Medicine
Columbus, OH
Oklahoma
Reagan H. Bradford, Jr. M.D.
Dean A. McGee Eye Institute
Oklahoma City, OK
Oregon
David J. Wilson, M.D.
Casey Eye Institute
Oregon Health Sciences University
Portland, OR
Pennsylvania
Karl R. Olsen, M.D.
Retina-Vitreous Consultants
Pittsburgh, PA
Texas
Dwain G. Fuller, M.D.
Texas Retina Associates
Dallas, TX
Richard S. Ruiz, M.D.
Hermann Eye Center
Houston, TX
Wichard A. Van Heuven, M.D.
University of Texas
Health Science Center
San Antonio, TX
J. Paul Dieckert, M.D.
Scott and White Memorial Hospital
Temple, TX
Virginia
Brian P. Conway, M.D.
University of Virginia
Health Sciences Center
Charlottesville, VA
Washington
Edward B. McLean, M.D.
Ophthalmic Consultants Northwest, Inc.
Seattle, WA
Craig G. Wells, M.D.
University of Washington
School of Medicine
Seattle, WA
Wisconsin
Suresh R. Chandra, M.D.
University of Wisconsin
Madison, WI
Judith E. Kim, M.D.
Medical College of Wisconsin
Milwaukee, WI
Canada
E. Rand Simpson, M.D.
Ontario Cancer Institute/Princess
Margaret Hospital
Toronto, Ontario, Canada
Christina Corriveau, M.D.
Notre Dame Hospital
Montreal, Quebec, Canada
Resource Centers
Chairman’s Office
Stuart L. Fine, M.D.
Scheie Eye Institute
University of Pennsylvania
51 North 39th Street
Philadelphia, PA 19104
Telephone: 215-662-9679
Coordinating Center
Barbara S. Hawkins, Ph.D.
Clinical Trials and Biometry Division
The Wilmer Ophthalmological Institute
The Johns Hopkins Medical Institutions
Baltimore, MD 21205-2010
Telephone: 410-955-8943
Echography Center
Sandra Byrne
Mars Hill College
Mars Hill, NC
Pathology Center
Daniel M. Albert, M.D.
University of Wisconsin
Madison, WI
Photograph Reading Center
H. Culver Boldt, M.D.
University of Iowa
Iowa City, IA
Radiological Physics Center
William F. Hanson, Ph.D.
M.D. Anderson Cancer Center
Houston, TX
NEI Representative
Natalie Kurinij, Ph.D.
National Eye Institute
National Institutes of Health
Rockville, MD
Contact: National Eye Institute, 301-496-5248, mjc@nei.nih.gov.
Journal
Archives of Ophthalmology