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COMS - Ancillary Studies
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- Pilot study for small choroidal melanoma
- Parallel study of quality of life in medium-tumor patients
- Physician factors influencing patient recruitment
- Analysis of the pattern of oncogene activation in the dna of patients with uveal melanoma
- Nucleolar organization regions in choroidal melanoma
- Natural history of untreated choroidal melanoma
- Intraoperative ultrasound
- Detection of melanocyte stimulating hormones (msh) receptors in ocular melanoma tissue
- A comparison of tumor measurements determined by transillumination and direct measurement in fresh, fixed and processed globes
- DNA flow cytometry in uveal malignant melanomas
- Histologic assessment of the microcirculation of uveal melanoma
- How clinic coordinators spend their time
- Apoptosis in uveal melanoma
- Melanoma inhibitory activity (mia) as an indicator of early metastatic disease
- Mortality follow-up of eligible patients not enrolling in the coms large tumor trial
PILOT STUDY FOR SMALL CHOROIDAL MELANOMA
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A nonrandomized prospective pilot study of small choroidal melanoma
(i.e., those no more than 3.0 mm in apical height and no more than
16.0 mm in longest basal diameter) was initiated
concurrently with COMS randomized trials of treatment for medium and
large choroidal melanoma.
The objectives of this pilot study were:
- To determine the number of patients with small tumors presenting
at COMS Clinical Centers or referred to them;
- To determine how these small tumors were being managed by the
ophthalmologic community as represented by the COMS investigators;
- To observe the rate of growth of these small tumors over a short
period of time;
- To determine, in a limited way, the impact of these small tumors
on survival, visual acuity, and metastatic disease;
- To identify methods of management that were candidates for evaluation
in a randomized controlled trial.
This group of cases may be the most important in terms of long-range
management of choroidal melanoma as these tumors are diagnosed much
earlier than previously because of improved methods of examination.
The ability to intervene early, before enucleation must be considered,
to preserve both life and vision is most promising in this group of
patients.
Publications
- Collaborative Ocular Melanoma Study Group: Mortality in patients
with small choroidal melanoma. COMS Report No. 4. Arch Ophthalmol
115:886-893, 1997.
- Collaborative Ocular Melanoma Study Group: Factors predictive
of growth and treatment of small choroidal melanoma. COMS Report
No. 5. Arch Ophthalmol 115:1537-1544, 1997.
- Melia BM, Diener-West M, Folk JC, Bennett SR, Montague PR, Weingeist
TA for the COMS
Group: Mortality and tumor growth in patients with small choroidal
melanoma: A report from
the COMS Group. Invest Ophthalmol Vis Sci 36(4, suppl):1036,
1995.
PARALLEL STUDY OF QUALITY OF LIFE IN MEDIUM-TUMOR PATIENTS
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In the COMS medium-tumor trial, the two treatments being compared
- enucleation and plaque - are likely to have different psychological
and physiological effects on the patients receiving them. Regardless
of the presence or magnitude of survival differences between treatment
groups, quality of life after treatment will become an important consideration
in determining the best form of therapy. The primary goals of the
COMS Quality of Life Study (QOLS) are 1) to estimate the quality of
life and how it changes in choroidal melanoma patients from the time
of diagnosis and enrollment into the COMS and through a 5-year follow-up
period, and 2) to compare quality of life and how it changes in patients
treated with plaque versus enucleation. The study incorporates multiple,
prospective quality of life assessments, with a baseline evaluation
made before randomization and follow-up assessments made six months
after enrollment and at yearly intervals thereafter. Interviews are
conducted on the telephone by interviewers located at the COMS Coordinating
Center.
Publications
- COMS Quality of Life Study Group: Incorporating a quality of life
assessment into an ongoing multi-center clinical trial: The COMS experience.
COMS-QOLS Report No. 2. (Submitted)
- COMS
Quality of Life Study Group: Quality of life assessment in the Collaborative
Ocular Melanoma Study: Design and methods. COMS-QOLS Report No. 1.
Ophthalmic Epidemiol 6:5-18, 1999.
- Melia
BM, Moy CS, McCaffrey L: Quality of life in patients with choroidal
melanoma: A pilot study. Ophthalmic Epidemiol 6:19-28, 1999.
- COMS-Quality of Life Study Manual of Procedures
- Manos KS, Moy CS for the COMS-QOLS Group: Incorporating a quality
of life assessment into an ongoing multi-center clinical trial: problems
and recommendations. Controlled Clin Trials 18:104, 1997.
PHYSICIAN FACTORS INFLUENCING PATIENT RECRUITMENT
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A survey of COMS ophthalmologists, radiation oncologists, and clinic
coordinators was conducted regarding their attitudes towards clinical
trials
and the impact of participating in clinical research on physicians'
perspectives. The goal was to correlate physician attitudes with
rate of
patient accrual in COMS clinical trials.
Publications
- Taylor KM: Integrating conflicting professional roles: physician
participation in randomized clinical trials. Soc Sci Med 35(2):217-224,
1992.
- Taylor KM: Physician participation in a randomized clinical trial
for ocular melanoma. Ann Ophthalmol 24:337-344, 1992.
ANALYSIS OF THE PATTERN OF ONCOGENE ACTIVATION IN THE DNA OF PATIENTS
WITH UVEAL MELANOMA
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Dr. Daniel Albert, Director of the COMS Pathology Center in Boston,
analyzed the pattern of oncogene activation in the DNA of tumor samples
of eyes of COMS patients received at the Pathology Center. The purpose
of the Study is to identify mutations which predispose to formation
of choroidal melanoma by investigating the correlations between oncogene
activation and histological data and between oncogene activation and
tumor prognosis.
Publication
- Soparker CN, O'Brien JM, Albert DM: Investigation of the role
of ras proto-oncogene point mutation in human uveal melanomas.
Invest Ophthalmol Vis Sci 34(7):2203-2209, 1993.
NUCLEOLAR ORGANIZATION REGIONS IN CHOROIDAL MELANOMA
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Drs. Dennis Marcus and Daniel Albert conducted an
ancillary study at the COMS Pathology Center to identify the malignant
potential of uveal melanocytic lesions and elucidate
the effect of radiation on the malignant potential of melanoma cells.
Publication
- Marcus DM, Minkovitz JB, Wardwell SC, Albert DM for the Collaborative
Ocular Melanoma Study Group: The value of nucleolar organizer regions
in uveal melanoma. Am J Ophthalmol 110:527-534, 1990.
NATURAL HISTORY OF UNTREATED CHOROIDAL MELANOMA
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Dr. Bradley Straatsma, of COMS Clinical Center 16 at Jules Stein Eye
Institute in Los Angeles, proposed to assess the natural history of
patients evaluated for the COMS who were eligible for either the medium
tumor trial or the large tumor trial but who elected to remain untreated.
Patients continue to be followed in this ongoing project.
INTRAOPERATIVE ULTRASOUND
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Sandra Frazier Byrne, the Director of the COMS Echography Center,
lead an informal study to investigate ultrasound plaque localization
techniques. Fifteen COMS clinical centers participated in this ancillary
study. Of 133 reported plaque localizations from these centers, 81
echogram sets taken at the time of plaque surgery had been received
by the Echography Center. Correct plaque position was confirmed in
about 85% of cases; the majority of the remaining echography studies
were ungradable due to technical deviations. Publication of results
from this study is contingent upon the availability of local control
rates and at least 2 years of follow-up.
DETECTION OF MELANOCYTE STIMULATING HORMONES (MSH) RECEPTORS IN OCULAR MELANOMA TISSUE
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Receptors for melanocyte stimulating hormones (MSH) have been found
to be expressed in most cutaneous melanoma metastases, but it is not
known whether MSH receptors are expressed in ocular or cutaneous melanoma
cells, or in normal or neoplastic ocular melanocytes. Expression
of MSH receptors in normal or diseased ocular melanocytes would have
implications for the basic biology of the target cells as well as
for the development of antineoplastic chemotherapeutic agents for
treatment of melanoma. The study was modified to incorporate evaluation
of estrogen receptors in uveal melanoma. A publication is in preparation.
A COMPARISON OF TUMOR MEASUREMENTS DETERMINED BY TRANSILLUMINATION AND DIRECT MEASUREMENT IN FRESH, FIXED AND PROCESSED GLOBES
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Dr. Daniel Albert of the COMS Pathology Center conducted this study
comparing tumor size as determined by transillumination and direct
observation at various stages of processing of enucleated globes containing
melanomas. A grading of subretinal fluid and shape of tumor based
upon histopathology was also undertaken to investigate differences
in tumor dimension measurements based on these characteristics.
Publications
- Umlas J, Albert D, Diener-West M for the Collaborative Ocular
Melanoma Study Group: Correlation of transillumination size and microscopic
measurement of choroidal melanoma. Invest Ophthalmol Vis Sci
35(4):1925, 1994.
- Umlas J, Diener-West M, Robinson NL, Green WR, Grossniklaus HE,
Albert DM: Comparison of transillumination and histologic slide measurements
of choroidal melanoma. Arch Ophthalmol 115(4):474-477, 1997.
DNA FLOW CYTOMETRY IN UVEAL MALIGNANT MELANOMAS
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Dr. Christine Corriveau and Dr. Jean Deschenes of the University of
Montreal investigated the DNA content and mitotic activity of uveal
melanoma using flow cytometry. In preliminary research utilizing
tissue from 45 uveal melanoma, they found that the percentage of cells
in the S phase of the cell cycle was strongly associated with more
aggressive histopathologic cell types; in addition, a quantification
of aneuploidy was a very strong predictor of mortality. The ancillary
study was designed to replicate the earlier work in COMS enucleated
patients.
Publications
- Tabesh T, Duclos AJ, Corriveau C, et al.: Cell-cycle analysis
of
uveal melanoma.
Inv Ophthalmol Vis Sci 37(3):S208, 1996.
HISTOLOGIC ASSESSMENT OF THE MICROCIRCULATION OF UVEAL MELANOMA
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Dr. Robert Folberg and Dr. Thomas Weingeist of the University of Iowa
proposed to assess vascular microcirculatory patterns from histologic
sections of eyes removed for choroidal melanoma in the COMS. In previous
research by Dr. Folberg and his colleagues, certain tumor vascular
patterns were found to be associated with death from metastatic disease.
Ultimately, the development of noninvasive techniques to identify
these prognostic vascular patterns would enhance the management of
choroidal melanoma. This study is ongoing.
HOW CLINIC COORDINATORS SPEND THEIR TIME
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A survey of COMS clinic coordinators was conducted to assess the types
of activities performed and the relative amount of time spent on each.
This study yielded a profile of clinic responsibilities across the
COMS group. Comparisons among subgroups of coordinators (e.g., nurses,
ophthalmic technicians, other) may be of interest. Evaluation of
the proportion of time spent on each activity and whether time spent
on COMS activities is correlated with the number of patients reported
and/or enrolled was also planned.
Publication
- Goldsborough IL, Church RY, Newhouse MM, Hawkins BS: How clinic
coordinators spend their time in a multicenter clinical trial. Applied
Clin Trials 7(1):33-40, 1998.
APOPTOSIS IN UVEAL MELANOMA
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Using previously cut sections from 100 randomly selected COMS melanomas
and from 20 randomly selected metastases, Dr. Daniel Albert evaluated
whether there is a correlation between cell type and degree of apoptosis,
whether protection of intraocular melanomas from the immune system
results in relative resistance to apoptosis, and whether bc1-2 or
FasL expression is involved in regulation of apoptosis in uveal melanoma.
Publication
- Imesch PD, Lovitt BT, Albert DM for the COMS Group: Apoptosis
in intraocular and metastatic melanomas. Inv Ophthalmol Vis Sci
39(4):S414, 1998.
MELANOMA INHIBITORY ACTIVITY (MIA) AS AN INDICATOR OF EARLY METASTATIC DISEASE
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Dr. Frederick Davidorf, principal investigator of the COMS clinical
center in Columbus, Ohio, and Dr. Greg LaValle, surgical oncologist,
initiated an investigation of the relationship between melanoma inhibitory
activity and early metastatic disease. It was hypothesized that this
method might be useful at the time of melanoma diagnosis for identifying
patients at greatest risk of metastatic disease. This study is ongoing.
MORTALITY FOLLOW-UP OF ELIGIBLE PATIENTS NOT ENROLLING IN THE COMS LARGE TUMOR TRIAL
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Ms. Marta Marsh of the COMS Coordinating Center proposed to determine
whether overall and cause-specific mortality differ among patients
who agreed to random treatment assignment and those who elected to
choose their own treatment. The availability of data for this group
of eligible patients who did not enroll in the large tumor trial provides
a rare opportunity to assess the external validity of the large tumor
trial mortality results. This study is ongoing.
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