Advertisement

The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma II: initial mortality findings COMS report no. 10

  • Collaborative Ocular Melanoma Study Group
    ∗*

      Abstract

      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% (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.
      To read this article in full you will need to make a payment

      Subscribe:

      Subscribe to American Journal of Ophthalmology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Scotto J.
        • Fraumeni F.J.
        • Lee J.A.H.
        Melanomas of the eye and other noncutaneous sites.
        J Natl Cancer Inst. 1976; 56: 489-491
        • Zimmerman L.E.
        • McLean I.W.
        • Foster W.D.
        Does enucleation of the eye containing a malignant melanoma prevent or accelerate the dissemination of tumour cells?.
        Br J Ophthalmol. 1978; 62: 420-425
        • Zimmerman L.E.
        • McLean I.W.
        An evaluation of enucleation in the management of uveal melanomas.
        Am J Ophthalmol. 1979; 87: 741-760
        • Zimmerman L.E.
        • McLean I.W.
        • Foster W.D.
        Statistical analysis of follow-up data concerning uveal melanomas, and the influence of enucleation.
        Ophthalmology. 1980; 87: 557-564
        • Zimmerman L.E.
        Metastatic disease from uveal melanoma. A review of current concepts with comments concerning future research and prevention.
        Trans Ophthalmol Soc UK. 1980; 100: 34-54
        • McLean I.W.
        • Foster W.D.
        • Zimmerman L.E.
        • Martin D.G.
        Inferred natural history of uveal melanoma.
        Invest Ophthalmol Vis Sci. 1980; 19: 760-770
        • Seigel D.
        • Myers M.
        • Ferris F.
        • Steinhorn S.C.
        Survival rates after enucleation of eyes with malignant melanoma.
        Am J Ophthalmol. 1979; 87: 760-765
        • Jakobiec F.A.
        A moratorium on enucleation for choroidal melanoma?.
        Am J Ophthalmol. 1979; 87: 842-846
        • Maumenee A.E.
        An evaluation of enucleation in the management of uveal melanomas.
        Am J Ophthalmol. 1979; 87: 846-847
        • Manschot W.A.
        • van Peperzeel H.A.
        Choroidal melanoma: enucleation or observation? A new approach.
        Arch Ophthalmol. 1980; 98: 71-77
        • Lommatzsch P.
        • Dietrich B.
        The effect of orbital irradiation on the survival rate in patients with choroidal melanoma.
        Ophthalmologica. 1976; 173: 49-52
        • Char D.H.
        • Phillips T.L.
        The potential for adjuvant radiotherapy in choroidal melanoma.
        Arch Ophthalmol. 1982; 100: 247-248
        • Char D.H.
        • Phillips T.L.
        Pre-enucleation irradiation of uveal melanoma.
        Br J Ophthalmol. 1985; 69: 177-179
        • Benediktsdóttir K.
        • Edenholm M.
        • Lindholm Å.
        • Mårtensson B.
        • Ståhl L.
        • Zetterlund B.
        Preoperative irradiation of malignant melanoma.
        Acta Radiol Oncol. 1984; 23: 315-320
        • Bornfeld N.
        • Alberti W.
        • Foerster M.H.
        • Gerke E.
        • Wessing A.
        • Meyer-Schwickerath G.
        External beam therapy of choroidal melanomata.
        Trans Ophthalmol Soc U K. 1983; 103: 68-71
        • Fournier G.A.
        • Saulenas A.M.
        • Seddon J.M.
        • et al.
        The effects of pre-enucleation irradiation on the development of metastases from intraocular Greene melanoma in hamsters.
        Am J Ophthalmol. 1985; 100: 669-677
        • Rousseau A.
        • Boudreault G.
        • Deschênes J.
        • Pelletier G.
        • Tardif Y.
        Malignant melanoma.
        in: Henkind P. ACTA XXIV International Congress of Ophthalmology. Lippincott, Philadelphia1983: 983-987
        • Sanborn G.E.
        • Ngyuen P.
        • Gamel J.
        • Niederkorn J.Y.
        Reduction of enucleation-induced metastasis in intraocular melanoma by periorbital irradiation.
        Arch Ophthalmol. 1987; 105: 1260-1264
        • Augsburger J.J.
        • Eagle R.C.
        • Chiu M.
        • Shields J.A.
        The effect of pre-enucleation radiotherapy on mitotic activity of choroidal and ciliary body melanomas.
        Ophthalmology. 1987; 94: 1627-1630
        • Burch F.E.
        • Camp W.F.
        Results of irradiation of malignant melanomas of the uveal tract.
        Trans Am Acad Ophthalmol Ototlaryngol. 1943; 47: 335-353
        • Sobanski J.
        • Zeydler-Grzedzielewska L.
        • Szusterowska-Martinowa E.
        Decreased mortality of patients with intranuclear malignant melanoma after enucleation of the eyeball followed by orbit X-ray irradiation.
        Polish Med J. 1972; 11: 1512-1516
        • Fraunfelder F.T.
        • Boozman F.W.
        • Wilson R.S.
        • Thomas A.H.
        No-touch technique for intraocular malignant melanomas.
        Arch Ophthalmol. 1977; 95: 1616-1620
        • McCubbin J.A.
        • Spratt J.S.
        The value of no-touch isolation technique for resection of cancer.
        Arch Surg. 1980; 115: 224-228
        • Char D.H.
        Current treatments and trials in uveal melanoma.
        Oncology. 1989; 3: 113-121
        • McLean I.W.
        • Berd D.
        • Mastrangelo M.J.
        • et al.
        A randomized study of methanol-extraction residue of bacille Calmette-Guérin as postsurgical adjuvant therapy of uveal melanoma.
        Am J Ophthalmol. 1990; 110: 522-526
        • Cummings B.J.
        A critical review of adjuvant preoperative irradiation for adenocarcinoma of the rectum.
        Br J Surg. 1986; 73: 332-338
        • Hoye R.C.
        • Smith R.R.
        The effectiveness of small amounts of pre-operative irradiation in preventing the growth of tumor cells disseminated at surgery.
        Cancer. 1961; 14: 284-295
        • Miller L.S.
        Bladder cancer.
        Cancer. 1977; 39: 973-980
        • Gérard A.
        • Buyse M.
        • Nordlinger B.
        • et al.
        Preoperative radiotherapy as adjuvant treatment in rectal cancer.
        Ann Surg. 1988; 208: 606-614
        • Rider W.D.
        • Palmer J.A.
        • Mahoney L.J.
        • Robertson C.T.
        Preoperative irradiation in operable cancer of the rectum.
        Can J Surg. 1977; 20: 335-338
        • Roswit B.
        • Higgins G.A.
        • Humphrey E.W.
        • Robinette C.D.
        Preoperative irradiation of operable adenocarcinoma of the rectum and rectosigmoid colon.
        Ther Radiol. 1973; 108: 389-395
        • Stearns M.W.
        • Deddish M.R.
        • Quan S.H.Q.
        • Leaming R.H.
        Preoperative roentgen therapy for cancer of the rectum and rectosigmoid.
        Surg Gynecol Obstet. 1974; 138: 584-586
        • Stevens K.R.
        • Allen C.V.
        • Fletcher W.S.
        Preoperative radiotherapy for adenocarcinoma of the rectosigmoid.
        Cancer. 1976; 37: 2866-2874
        • Lawrence W.
        • Terz J.J.
        • Rogers C.
        • King R.E.
        • Wolf J.S.
        • King E.R.
        Preoperative irradiation for head and neck cancer.
        Cancer. 1974; 33: 318-323
        • Snow J.B.
        • Gelber R.D.
        • Kramer S.
        • Davis L.W.
        • Marcial V.A.
        • Lowry L.D.
        Evaluation of randomized preoperative and postoperative radiation therapy for supraglottic carcinoma.
        Ann Otol. 1978; 87: 686-691
        • Augsburger J.J.
        • Lauritzen K.
        • Gamel J.W.
        • Lowry J.C.
        • Brady L.W.
        Matched group study of preenucleation radiotherapy versus enucleation alone for primary malignant melanoma of the choroid and ciliary body.
        Am J Clin Oncol. 1990; 13: 372-387
        • Char D.H.
        • Phillips T.L.
        • Andejeski Y.
        • Crawford J.B.
        • Kroll S.
        Failure of preenucleation radiation to decrease uveal melanoma mortality.
        Am J Ophthalmol. 1988; 106: 21-26
        • Luyten G.P.M.
        • Mooy C.M.
        • Eijkenboom W.M.H.
        • et al.
        No demonstrated effect of pre-enucleation irradiation on survival of patients with uveal melanoma.
        Am J Ophthalmol. 1995; 119: 786-791
        • Bornfeld N.
        • Huser U.
        • Sauerwein W.
        • Wessing A.
        • Sack H.
        Präoperative Bestrahlung vor Enukleation bei malignem Melanom der Uvea. Literaturübersicht und erste eigene Erfahrungen.
        Klin Monatsbl Augenheilkd. 1989; 194: 252-260
        • Kreissig I.
        • Rohrbach M.
        • Lincoff H.
        Irradiation of choroidal melanomas before enucleation?.
        Retina. 1989; 9: 101-104
        • Collaborative Ocular Melanoma Study Group
        Design and methods of a clinical trial for a rare condition: the Collaborative Ocular Melanoma Study. COMS report no. 3.
        Controlled Clin Trials. 1993; 14: 362-391
        • Collaborative Ocular Melanoma Study Group
        The Collaborative Ocular Melanoma Study (COMS) trial of pre-enucleation radiation of large choroidal melanoma, I: characteristics of patients enrolled and not enrolled. COMS report no. 9.
        Am J Ophthalmol. 1998; 125: 767-778
        • Collaborative Ocular Melanoma Study Group
        Accuracy of diagnosis of choroidal melanomas in the Collaborative Ocular Melanoma Study. COMS report no. 1.
        Arch Ophthalmol. 1990; 108: 1268-1273
        • Straatsma B.R.
        • Fine S.L.
        • Earle J.D.
        • Hawkins B.S.
        • Diener-West M.
        • McLaughlin J.A.
        • Collaborative Ocular Melanoma Study Research Group
        Enucleation versus plaque irradiation for choroidal melanoma.
        Ophthalmology. 1988; 95: 1000-1004
        • Collaborative Ocular Melanoma Study Group
        Collaborative Ocular Melanoma Study Group. Complications of enucleation surgery.
        in: Franklin R.M. Proceedings of the New Orleans Academy of Ophthalmology Symposium on Retina and Vitreous. Kugler, New York1993: 181-190
        • Collaborative Ocular Melanoma Study Group
        COMS manual of procedures. Accession no. PB95-179693. National Technical Information Service, Springfield, Virginia1995
        • Collaborative Ocular Melanoma Study Group
        COMS forms book. Accession no. PB91-217315. National Technical Information Service, Springfield, Virginia1991
        • Bailey I.L.
        • Lovie J.E.
        New design principles for visual acuity letter charts.
        Am J Optom Physiol Opt. 1976; 53: 740-745
        • Ferris F.L.
        • Kassoff A.
        • Bresnick G.H.
        • Bailey I.
        New visual acuity charts for clinical research.
        Am J Ophthalmol. 1982; 94: 91-96
        • Diener-West M.
        • Hawkins B.S.
        • Markowitz J.A.
        • Schachat A.P.
        A review of mortality from choroidal melanoma, II.
        Arch Ophthalmol. 1992; 110: 245-250
        • Collaborative Ocular Melanoma Study Group
        Histopathologic characteristics of uveal melanomas in eyes enucleated from the Collaborative Ocular Melanoma Study. COMS report no. 6.
        Am J Ophthalmol. 1998; 125: 745-766
        • Melia B.M.
        • Diener-West M.
        Modeling interrater agreement for pathologic features of choroidal melanoma.
        in: Lange N. Ryan L. Billard L. Brillinger D. Conquest L. Greenhouse J. Case studies in biometry. Wiley & Sons, New York1994: 323-338
        • McLean I.W.
        • Foster W.D.
        • Zimmerman L.E.
        • Gamel J.W.
        Modification of Callender’s classification of uveal melanoma at the Armed Forces Institute of Pathology.
        Am J Ophthalmol. 1983; 96: 502-509
        • Snedecor G.W.
        • Cochran W.G.
        Statistical methods. 7th ed. Iowa State University Press, Ames, Iowa1980: 144-145
        • Armitage P.
        • Berry G.
        Statistical methods in medical research. 2nd ed. Blackwell Scientific, Boston, Massachusetts1987: 372-374
        • Kaplan E.L.
        • Meier P.
        Nonparametric estimation from incomplete observations.
        J Am Stat Assoc. 1958; 53: 457-481
        • Mantel N.
        Evaluation of survival data and two new rank order statistics arising in its consideration.
        Cancer Chemother Rep. 1966; 50: 163-170
        • Peto R.
        • Peto J.
        Asymptotically efficient rank invariant procedures.
        J R Stat Soc A. 1972; 135: 185-206
        • Simon R.
        Confidence intervals for reporting results of clinical trials.
        Ann Intern Med. 1986; 105: 429-435
        • Cox D.R.
        Regression models and life-tables.
        J R Stat Soc B. 1972; 134: 187-220
      1. Collaborative Ocular Melanoma Study Group. The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma, III: local complications with and without pre-enucleation radiation. COMS report no. 11. Am J Ophthalmol. Forthcoming.

      2. Grossniklaus HE, Albert DM, Green WR, Conway BP, Hovland KR, for the Collaborative Ocular Melanoma Study Group. Clear cell differentiation in choroidal melanoma. COMS report no. 8. Arch Ophthalmol 1997;115:894–898.

        • Glicksman A.S.
        • Reinstein L.E.
        • Laurie F.
        Quality assurance of radiotherapy in clinical trials.
        Cancer Treat Rep. 1985; 69: 1199-1205
        • Reinstein L.E.
        • Peachey S.
        • Laurie F.
        • Glicksman A.S.
        Impact of a dosimetry review program on radiotherapy in group trials.
        Int J Radiation Oncol Biol Physics. 1985; 11: 1179-1184
        • Seegenschmiedt M.H.
        • Sauerbrei W.
        • Sauer R.
        • et al.
        Quality control review for radiotherapy of small breast cancer.
        Strahlenther Onkol. 1993; 169: 339-350
        • Albert D.M.
        • Niffenegger A.S.
        • Willson J.K.V.
        Treatment of metastatic uveal melanoma.
        Surv Ophthalmol. 1992; 36: 429-438
        • Curb J.D.
        • Babcock C.
        • Pressel S.
        • Tung B.
        • Remington R.D.
        • Hawkins C.M.
        Nosological coding of cause of death.
        Am J Epidemiol. 1983; 118: 122-128
        • Remington R.D.
        Who should code cause of death in a clinical trial?.
        Controlled Clin Trials. 1984; 5: 241-244
        • Bangdiwala S.I.
        • Cohn R.
        • Hazard C.
        • Davis C.E.
        • Prineas R.J.
        Comparisons of cause of death verification methods and costs in the Lipid Research Clinics Program Mortality Follow-up Study.
        Controlled Clin Trials. 1989; 10: 167-187
        • Percy C.
        • Muir C.
        The international comparability of cancer mortality data.
        Am J Epidemiol. 1989; 129: 934-946
        • Hayman J.A.
        • Fairclough D.L.
        • Harris J.R.
        • Weeks J.C.
        Patient preferences concerning the trade-off between the risks and benefits of routine radiation therapy after conservative surgery for early-stage breast cancer.
        J Clin Oncol. 1997; 15: 1252-1260