 |
|
Metastatic Melanoma Death Rates by Anatomic Site After Proton Beam Irradiation for Uveal Melanoma
Wenjun Li, MS;
Evangelos S. Gragoudas, MD;
Kathleen M. Egan, ScD
Arch Ophthalmol. 2000;118:1066-1070.
ABSTRACT
| |
Background Ciliary body location is an established prognostic factor for metastasis-related death from uveal melanoma. We evaluated alternative approaches for classifying this covariate when constructing predictive models of patient survival.
Methods and Design The analyses were based on a consecutive series of 1848 primary choroidal and/or ciliary body melanoma patients treated with proton beam irradiation (70 cobalt gray equivalent in 5 fractions) at the Harvard Cyclotron Laboratory, Boston, Mass, between July 1975 and December 1995. For each patient, the anatomic site of the tumor was classified according to an estimate of the proportion of the tumor base lying anterior to the ora serrata. Using proportional hazards regression, we estimated relative risk ratios and death rates from melanoma metastasis according to the extent of ciliary body involvement. All estimates were adjusted for other established prognostic factors.
Results Patients were followed up through April 30, 1998; none were lost to follow-up. Of 1848 patients analyzed, 378 died of melanoma metastasis. The median follow-up period among survivors was 9.5 years. Ciliary body origin (>50% of tumor base anterior to the ora serrata) was positively associated with tumor pigmentation (P<.001), tumor height (P<.001), and extrascleral extension of the tumor (P<.001). Compared with tumors involving only the choroid, melanoma-associated death rates increased with the proportion of the tumor base lying within the ciliary body (P = .006); the multivariate-adjusted relative risk ratio for greater than 75% involvement was 2.30 (95% confidence interval [CI], 1.26-4.23). The covariate-adjusted 5-year death rates for ciliary body origin and choroidal origin were 15.9% (95% CI, 11.3%-21.2%) and 9.8% (95% CI, 8.3%-11.7%), respectively.
Conclusion Patients with melanomas of presumed ciliary body origin seem to be subject to a higher risk of death resulting from melanoma metastasis.
INTRODUCTION
ANTERIOR TUMOR location is an adverse prognostic factor for patient survival after treatment for intraocular melanoma.1-30 In past studies, tumor location has been classified according to the location of the most anterior margin,1-14 presence or absence of ciliary body involvement,15-20,31-32 anatomic location,25-28 or a combination of these.13-14,25-26 The location of the most anterior margin has generally been classified as iris, ciliary body, or anterior or posterior to the equator.
Recent cytogenetic and tumor vascular studies provided a biological explanation for the prognostic importance of tumor location. It has been shown that tumors involving the ciliary body have a predilection for 2 chromosomal abnormalities (monosomy 3 and multiple copies of 8q)18, 33-39 that are associated with a poor prognosis.35-37 Tumors with ciliary body involvement also express vascular patterns17, 28, 40 that are correlated with decreased patient survival.17, 27-28,31, 40-43
If a single site of origin is assumed for ciliochoroidal tumors, the presumed anatomic site of origin determined by the proportion of the tumor base lying anterior to the ora serrata might better reflect a differential path of disease progression and clinical course of these tumors. In this article, we describe the importance of considering the extent of ciliary body involvement in prognostic models of metastasis-free survival in an analysis based on a large series of patients treated by proton beam irradiation.
SUBJECTS AND METHODS
The subjects consisted of a consecutive series of 1848 patients treated with proton beam irradiation for uveal melanoma between 1975 and 1995. Patients were United States or Canadian citizens with unilateral tumors, having no evidence of metastasis at pretreatment examination. Iris-only melanomas were excluded from analysis. Most patients were treated with the standard therapeutic dose of 70 cobalt gray equivalents (CGE) (96.5%) (range, 54-100 CGE [3.5%]) at the Harvard Cyclotron Laboratory, Boston, Mass. All patients were treated by the same physician (E.S.G.) and were followed up annually through April 30, 1998. The study protocol was approved by the Massachusetts Eye and Ear Infirmary Human Studies Committee, and written informed consent was obtained from all patients.
In our analyses, tumor location was defined according to the extent of ciliary body involvement (Figure 1).44-45 Tumors were classified into 6 groups according to the location of the tumor with respect to the equator. Ciliary body–involved tumors were classified according to the proportion of the anteroposterior axis of the tumor base lying anterior to the ora serrata: (I) posterior to the equator, (II) anterior to the equator but posterior to the ora serrata, or (III) involving the ciliary body and anterior to the ora serrata by 1% to 25%, (IV) 26% to 50%, (V) 51% to 75%, or (VI) greater than 75% of the anteroposterior tumor diameter.
|
|
|
|
Figure 1. Dimension of standard eye with 24.6-mm anteroposterior axial length
|
|
|
Margins and anteroposterior diameter were obtained from surgical reports. For tumors extending posterior to the equator, distances between the anterior margin and limbus, posterior margin to limbus, and anteroposterior axial diameter of the tumor (APD) were recorded at the time of surgical placement of tantalum rings used for tumor localization during proton treatments. For ciliary body tumors treated without prior surgical localization, these distances were estimated by transillumination of the eye during pretreatment simulation. In both cases, the proportion of the tumor base lying within the ciliary body was estimated as the ratio between the anteroposterior axial length of the tumor lying anterior to ora serrata (LAO) and the APD: [proportion of the tumor base lying within the ciliary body] = [LAO/APD] x 100%. For tumors with the anterior margin posterior to the limbus, the LAO was approximated by subtracting the distance between the anterior margin and limbus from the length of ciliary body zone (LCB). For tumors with an anterior margin extending anterior to the limbus, the LAO was estimated as [APD-distance between the posterior margin to limbus + LCB]. To control for variation in eye size, the LCB used for calculation was estimated for each patient using the following equation:
Ciliary body–only and iridociliary tumors were classified as having 100% of the tumor base lying within the ciliary body. For analysis purposes, a tumor was considered to have a ciliary body origin if more than 50% of its anteroposterior axis fell anterior to the ora serrata.
The end point in this study was death from melanoma metastasis after irradiation (documented by autopsy, biopsy, death certificates, or reported by physicians or next of kin). The prognostic value of anteroposterior tumor location was evaluated with multivariate Cox proportional hazards models46 and adjusted for established prognostic factors, ie, sex, age at treatment, time from first visit to treatment, iris color, symptoms at first visit, tumor basal area, presence or absence of extrascleral extension, and tumor pigmentation. Interaction terms were evaluated using the procedures outlined by Hosmer and Lemeshow.47 The proportional hazard assumption was examined via the Grambsch and Therneau48 procedure. The covariate-adjusted 5-, 10-, 15-, and 20-year death rates were computed using the modified risk score method,47 and associated 95% confidence intervals (CIs) were constructed using bootstrap methods.49 The baseline survivorship function was estimated for 60-year-old women with dark- or moderate-colored irises, no symptoms at first visit, and a time from first visit to treatment of 3 months, whose tumors had heavy tumor pigmentation, no extrascleral extension, and a tumor basal area of 125 mm2.
RESULTS
There were no losses to follow-up. Of 1848 patients analyzed, 378 died of melanoma metastasis. The median follow-up among survivors was 9.5 years. The unadjusted 5-, 10-, and 15-year metastatic death rates in the cohort were 14.9%, 23.9%, and 27.2%, respectively.
Table 1 gives a comparison of patient and tumor characteristics according to presumed ciliary body origin (>50% of tumor base). Ciliary body origin was associated with greater tumor pigmentation (P<.01), female sex (P<.04), larger tumor height (P<.001), and extrascleral extension (P<.001).
|
|
|
|
Table 1. Patient and Tumor Characteristics by Presumed Anatomic Site of Tumor*
|
|
|
Multivariate relative risk (RR) ratios for anterior location are given in Table 2. Compared with choroid-only tumors, the rate of metastatic death increased with the proportion of the tumor base lying within the ciliary body (P = .006, based on 4 categories of >0% of tumor base lying anterior to the ora serrata); the RR ratios for 51% to 75% and greater than 75% were 1.62 (95% CI, 1.06-2.47) and 2.30 (95% CI, 1.26-4.23), respectively. The RR for tumors with 100% ciliary body involvement (ciliary body–only or iridociliary tumors; n = 31) was 3.61 (95% CI, 1.74-7.47). Patients with choroidal tumors having only peripheral involvement of the ciliary body (<50%) had no greater risk for metastatic death (P>.75) than patients with lesions confined to the posterior pole. The covariate-adjusted 5-, 10-, 15-, and 20-year death rates and associated 95% CIs for tumors with presumed ciliary body origin (n = 145) and choroidal origin (n = 1703) are listed in Table 3, and the covariate-adjusted cumulative failure function is shown in Figure 2. The relation of ciliary origin (>50% of the tumor base within the ciliary body) to melanoma-free survival was similar across categories of other prognostic factors (data not shown).
|
|
|
|
Table 2. Adjusted Relative Risk Ratios for Metastatic Death by Presumed Anatomic Site of Tumor*
|
|
|
|
|
|
Table 3. Adjusted Metastatic Death 22p Rates and Their 95% Confidence Intervals (CIs)* by Presumed Anatomic Site of Tumor
|
|
|
|
|
|
|
Figure 2. Covariate-adjusted metastatic death rates by anatomic site.
|
|
|
A comparison of 3 methods for classifying tumor location is given in Table 4. Most (77%) of 513 tumors with a margin anterior to the ora serrata likely arose from the choroid (eg, <50% of the tumor base resided in the ciliary body). The effect of such misclassification is bias to the null: the multivariate-adjusted RR ratios for any ciliary body involvement was only modestly and nonsignificantly elevated (RR, 1.16; 95% CI, 0.83-1.62).
|
|
|
|
Table 4. Presumed Anatomic Site by Anterior Margin and Area of Involvement of Tumor*
|
|
|
COMMENT
In this article, we demonstrate that ciliochoroidal melanomas presumed to have arisen from the ciliary body exhibit more aggressive behavior (with respect to patient survival) than those arising from the choroid. Less quantitative approaches for classifying the anterior extent of the tumor will not adequately reflect this phenomenon, which in turn may lead to misclassification of prognosis. Based on these results, of 513 tumors involving the ciliary body to any extent, 368 (72%) with up to 50% of the tumor base anterior to the ora serrata carried no excess risk of metastatic death (RR, 0.93; 95% CI, 0.70-1.3) compared with tumors posterior to the equator (Table 2). The overall RR for any ciliary body involvement, without regard to extent, was only modestly and nonsignificantly elevated (RR, 1.16; 95% CI, 0.83-1.62). Increasing magnitude of excessive risk with the increasing proportion of the tumor base anterior to the ora serrata is consistent with progressively less misclassification of tumor origin and supports the inherently more aggressive clinical course of tumors originating in the ciliary body. Misclassification may have contributed to the null results in some previous studies31-32,50 that found no excess risk for ciliary body location. McLean et al6 noted the importance of the extent of ciliary body involvement. These authors reported that only tumors with angle or iris involvement had a significantly worse prognosis, which is consistent with our data showing a worsened prognosis confined to the most anterior tumors. Higher death rates specific to ciliary body origin are consistent with recent reports indicating that genetic defects in ciliary body tumors may be distinct from and carry a poorer prognosis than those giving rise to melanomas in the choroid.33-34,37-38,51-52 In addition, microvascular networks linked to poor patient survival17, 28 tend to develop preferentially in the ciliary body relative to the choroid.17, 28, 40
We excluded from analysis iris melanomas, which rarely if ever metastasize.53-55 However, it is possible that some of the most anterior tumors may have originated in the iris. The fact that the RR ratios for ciliary body–only melanoma (RR, 4.4; 95% CI, 1.6-12.2; n = 10) was substantially higher than the RR for iridociliary tumors (RR, 2.9; 95% CI, 1.1-8.1; n = 21) suggests that RR ratios for presumed ciliary body origin (>50% of the tumor base) were attenuated by the inclusion of some tumors with low malignant potential. Sensitivity analysis, performed by varying reported cutoff points (25%, 50%, and 75%) from 1% to 5%, suggested that the reported estimates and trend of RR ratios for the 4 location categories were robust and not sensitive to slight changes in the cutoff points used.
In summary, our results confirm recent findings indicating an excess risk for metastatic death in patients with ciliary body tumors linked to specific chromosomal alterations and/or vascular patterns. Since tumor location and chromosome changes are intimately linked,37 tumor location as classified here may provide a useful surrogate when cytogenetic parameters are not available.
AUTHOR INFORMATION
Accepted for publication February 12, 2000.
This study was supported by the Melanoma Research Fund and by the Retina Research Foundation, Houston, Tex.
Presented in part at the Association for Research in Vision and Ophthalmology 1999 Annual Meeting, Fort Lauderdale, Fla, May 9-14, 1999.
Dr Gragoudas is a Research to Prevent Blindness Inc, New York, NY, senior scientific investigator.
Corresponding author: Kathleen Egan, ScD, Retina Service, Massachusetts Eye and Ear Infirmary, Boston, MA 02114 (e-mail: kathleen.egan{at}channing.harvard.edu).
From the Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston (Drs Gragoudas and Egan and Mr Li); the Department of Biostatistics and Epidemiology, University of Massachusetts, Amherst (Mr Li); and the Department of Epidemiology, Harvard School of Public Health, Boston (Dr Egan).
REFERENCES
1. McLean MJ, Foster WD, Zimmerman LE. Prognostic factors in small malignant melanomas of choroid and ciliary body. Arch Ophthalmol. 1977;95:48-58.
FREE FULL TEXT
2. Kidd MN, Lyness RW, Patterson CC, Johnston PB, Archer DB. Prognostic factors in malignant melanoma of the choroid:a retrospective survey of cases occurring in Northern Ireland between 1965 and 1980. Trans Ophthalmol Soc U K. 1986;105:114-121.
ISI
| PUBMED
3. Gragoudas ES, Seddon JM, Egan KM, et al. Prognostic factors for metastasis following proton beam irradiation of uveal melanomas. Ophthalmology. 1986;93:675-680.
ISI
| PUBMED
4. Gragoudas E, Seddon J, Egan K, et al. Metastasis from uveal melanoma after proton beam irradiation. Ophthalmology. 1988;95:992-999.
ISI
| PUBMED
5. Gragoudas E, Egan K, Seddon J, Walsh S, Munzenrider J. Intraocular recurrence of uveal melanoma after proton beam irradiation. Ophthalmology. 1992;99:760-766.
ISI
| PUBMED
6. McLean IW, Ainbinder DJ, Gamel JW, McCurdy JB. Choroidal-ciliary body melanoma: a multivariate survival analysis of tumor location. Ophthalmology. 1995;102:1060-1064.
ISI
| PUBMED
7. Collaborative Ocular Melanoma Study Group. Mortality in patients with small choroidal melanoma: COMS Report No. 4. Arch Ophthalmol. 1997;115:886-893.
FREE FULL TEXT
8. Harbour J, Char D, Kroll S, Quivey J, Castro J. Metastatic risk for distinct patterns of postirradiation local recurrence of posterior uveal melanoma. Ophthalmology. 1997;104:1785-1792.
ISI
| PUBMED
9. Augsburger JJ, Correa ZM, Freire J, Brady LW. Long-term survival in choroidal and ciliary body melanoma after enucleation versus plaque radiation therapy. Ophthalmology. 1998;105:1670-1678.
FULL TEXT
|
ISI
| PUBMED
10. Kroll S, Char DH, Quivey J, Castro J. A comparison of cause-specific melanoma mortality and all-cause mortality in survival analyses after radiation treatment for uveal melanoma. Ophthalmology. 1998;105:2035-2045.
FULL TEXT
|
ISI
| PUBMED
11. Egan K, Giovannucci E, Lane A, Gragoudas E. A prospective study of diet as a prognostic factor in choroidal melanoma [abstract]. Invest Ophthalmol Vis Sci. 1998;39(ARVO suppl):S464.
12. Egan KM, Quinn JL, Gragoudas ES. Childbearing history associated with improved survival in choroidal melanoma. Arch Ophthalmol. 1999;117:939-942.
FREE FULL TEXT
13. Char DH, Kroll SM, Castro J. Long-term follow-up after uveal melanoma charged particle therapy. Trans Am Ophthalmol Soc. 1997;95:171-187.
PUBMED
14. Char DH, Kroll SM, Castro J. Ten-year follow-up of helium ion therapy for uveal melanoma. Am J Ophthalmol. 1998;125:81-89.
FULL TEXT
|
ISI
| PUBMED
15. Glynn R, Seddon J, Gragoudas E, Egan K, Hart L. Evaluation of tumor regression and other prognostic factors for early and late metastasis after proton irradiation of uveal melanoma. Ophthalmology. 1989;96:1566-1573.
ISI
| PUBMED
16. Decker M, Castro JR, Linstadt DE, et al. Ciliary body melanoma treated with helium particle irradiation. Int J Radiat Oncol Biol Phys. 1990;19:243-247.
ISI
| PUBMED
17. Rummelt V, Folberg R, Woolson RF, Hwang T, Pe'er J. Relation between the microcirculation architecture and the aggressive behavior of ciliary body melanomas. Ophthalmology. 1995;102:844-851.
ISI
| PUBMED
18. Prescher G, Bornfeld N, Hirche H, Horsthemke B, Jockel KH, Becher R. Prognostic implications of monosomy 3 in uveal melanoma. Lancet. 1996;347:1222-1225.
FULL TEXT
|
ISI
| PUBMED
19. Castro JR, Char DH, Petti PL, et al. 15 years experience with helium ion radiotherapy for uveal melanoma. Int J Radiat Oncol Biol Phys. 1997;39:989-996.
FULL TEXT
|
ISI
| PUBMED
20. Daftari IK, Char DH, Verhey LJ, et al. Anterior segment sparing to reduce charged particle radiotherapy complications in uveal melanoma. Int J Radiat Oncol Biol Phys. 1997;39:997-1010.
FULL TEXT
|
ISI
| PUBMED
21. Barr CC, McLean IW, Zimmerman LE. Uveal melanoma in children and adolescents. Arch Ophthalmol. 1981;99:2133-2136.
FREE FULL TEXT
22. Seddon JM, Albert DM, Lavin PT, Robinson N. A prognostic factor study of disease-free interval and survival following enucleation for uveal melanoma. Arch Ophthalmol. 1983;101:1894-1899.
FREE FULL TEXT
23. Seddon JM, Gragoudas ES, Egan KM, et al. Relative survival rates after alternative therapies for uveal melanoma. Ophthalmology. 1990;97:769-777.
ISI
| PUBMED
24. Augsburger JJ, Gamel JW. Clinical prognostic factors in patients with posterior uveal malignant melanoma. Cancer. 1990;66:1596-1600.
FULL TEXT
|
ISI
| PUBMED
25. Augsburger JJ, Gamel JW, Sardi VF, Greenberg RA, Shields JA, Brady LW. Enucleation vs cobalt plaque radiotherapy for malignant melanomas of the choroid and ciliary body. Arch Ophthalmol. 1986;104:655-661.
FREE FULL TEXT
26. Summanen P, Immonen I, Heikkonen J, Tommila P, Laatikainen L, Tarkkanen A. Survival of patients and metastatic and local recurrent tumor growth in malignant melanoma of the uvea after ruthenium plaque radiotherapy. Ophthalmic Surg. 1993;24:82-90.
ISI
| PUBMED
27. Seregard S, Spangberg B, Juul C, Oskarsson M. Prognostic accuracy of the mean of the largest nucleoli, vascular patterns, and PC-10 in posterior uveal melanoma. Ophthalmology. 1998;105:485-491.
FULL TEXT
|
ISI
| PUBMED
28. Folberg R, Rummelt V, Parys-Van Ginderdeuren R, et al. The prognostic value of tumor blood vessel morphology in primary uveal melanoma. Ophthalmology. 1993;100:1389-1398.
ISI
| PUBMED
29. Seregard S, Kock E. Prognostic indicators following enucleation for posterior uveal melanoma: a multivariate analysis of long-term survival with minimized loss to follow-up. Acta Ophthalmol Scand. 1995;73:340-344.
ISI
| PUBMED
30. Foss AJ, Cree IA, Dolin PJ, Hungerford JL. Modelling uveal melanoma. Br J Ophthalmol. 1999;83:588-594.
FREE FULL TEXT
31. Foss AJ, Alexander RA, Jefferies LW, Hungerford JL, Harris AL, Lightman S. Microvessel count predicts survival in uveal melanoma. Cancer Res. 1996;56:2900-2903.
FREE FULL TEXT
32. Damato BE, Paul J, Foulds WS. Risk factors for metastatic uveal melanoma after trans-scleral local resection. Br J Ophthalmol. 1996;80:109-116.
FREE FULL TEXT
33. Sisley K, Rennie IG, Cottam DW, Potter AM, Potter CW, Rees RC. Cytogenetic findings in six posterior uveal melanomas: involvement of chromosomes 3, 6, and 8. Genes Chromosomes Cancer. 1990;2:205-209.
ISI
| PUBMED
34. Sisley K, Cottam DW, Rennie IG, et al. Non-random abnormalities of chromosomes 3, 6, and 8 associated with posterior uveal melanoma. Genes Chromosomes Cancer. 1992;5:197-200.
ISI
| PUBMED
35. Prescher G, Bornfeld N, Horsthemke B, Becher R. Chromosomal aberrations defining uveal melanoma of poor prognosis [letter]. Lancet. 1992;339:691-692.
FULL TEXT
|
ISI
| PUBMED
36. Horsman DE, White VA. Cytogenetic analysis of uveal melanoma: consistent occurrence of monosomy 3 and trisomy 8q. Cancer. 1993;71:811-819.
FULL TEXT
|
ISI
| PUBMED
37. Sisley K, Rennie IG, Parsons MA, et al. Abnormalities of chromosomes 3 and 8 in posterior uveal melanoma correlate with prognosis. Genes Chromosomes Cancer. 1997;19:22-28.
FULL TEXT
|
ISI
| PUBMED
38. Prescher G, Bornfeld N, Friedrichs W, Seeber S, Becher R. Cytogenetics of twelve cases of uveal melanoma and patterns of nonrandom anomalies and isochromosome formation. Cancer Genet Cytogenet. 1995;80:40-46.
FULL TEXT
|
ISI
| PUBMED
39. Singh AD, Boghosian-Sell L, Wary KK, et al. Cytogenetic findings in primary uveal melanoma. Cancer Genet Cytogenet. 1994;72:109-115.
FULL TEXT
|
ISI
| PUBMED
40. Rummelt V, Folberg R, Rummelt C, et al. Microcirculation architecture of melanocytic nevi and malignant melanomas of the ciliary body and choroid: a comparative histopathologic and ultrastructural study. Ophthalmology. 1994;101:718-727.
ISI
| PUBMED
41. Folberg R, Mehaffey M, Gardner LM, Meyer M, Rummelt V, Pe'er J. The microcirculation of choroidal and ciliary body melanomas. Eye. 1997;11:227-238.
ISI
| PUBMED
42. Folberg R, Pe'er J, Gruman LM, et al. The morphologic characteristics of tumor blood vessels as a marker of tumor progression in primary human uveal melanoma: a matched case-control study. Hum Pathol. 1992;23:1298-1305.
FULL TEXT
|
ISI
| PUBMED
43. Pe'er J, Rummelt V, Mawn L, Hwang T, Woolson RF, Folberg R. Mean of the ten largest nucleoli, microcirculation architecture, and prognosis of ciliochoroidal melanomas. Ophthalmology. 1994;101:1227-1235.
ISI
| PUBMED
44. Olsen K, Curtin V. Enucleation and plaque treatment. In: Albert D, Jakobiec F, eds. Principles and Practice of Ophthalmology: Clinical Practice. Philadelphia, Pa: WB Saunders Co; 1994:3217-3233.
45. Bron A, Tripathi R, Tripathi B. Wolff's Anatomy of the Eye and Orbit. 8th ed. London, England: Chapman & Hall Medical; 1997.
46. Cox D. Regression models and life-tables. J Roy Stat Soc Ser. 1972;34:187-220.
47. Hosmer D, Lemeshow S. Applied Survival Analysis: Regression Modeling of Time to Event. New York, NY: John Wiley & Sons Inc; 1999.
48. Grambsch P, Therneau T. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika. 1994;81:515-526.
FREE FULL TEXT
49. StataCorp. Bstrap: Bootstrap Sampling and Estimation: Stata Reference Manual: Release 6.0. College Station, Tex: Stata Press; 1999:157-167.
50. Linstadt D, Castro J, Char D, et al. Long-term results of helium ion irradiation of uveal melanoma. Int J Radiat Oncol Biol Phys. 1990;19:613-618.
ISI
| PUBMED
51. Sisley K, Nichols C, Parsons MA, Farr R, Rees RC, Rennie IG. Clinical applications of chromosome analysis, from fine needle aspiration biopsies, of posterior uveal melanomas. Eye. 1998;12:203-207.
ISI
| PUBMED
52. Speicher MR, Prescher G, du Manoir S, et al. Chromosomal gains and losses in uveal melanomas detected by comparative genomic hybridization. Cancer Res. 1994;54:3817-3823.
FREE FULL TEXT
53. Davidorf FH. The melanoma controversy: a comparison of choroidal, cutaneous, and iris melanomas. Surv Ophthalmol. 1981;25:373-377.
FULL TEXT
|
ISI
| PUBMED
54. Geisse LJ, Roberston DM. Iris melanoma. Am J Ophthalmol. 1985;99:638-648.
ISI
| PUBMED
55. Jensen OA. Malignant melanoma of the iris: a 25-year analysis of Danish cases. Eur J Ophthalmol. 1993;3:181-188.
PUBMED
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
RELATED ARTICLE
Archives of Ophthalmology Reader's Choice: Continuing Medical Education
Arch Ophthalmol. 2000;118(8):1145.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Proton Beam Irradiation of Uveal Melanomas: The First 30 Years The Weisenfeld Lecture
Gragoudas
IOVS 2006;47:4666-4673.
FULL TEXT
Post-brachytherapy initial tumour regression rate correlates with metastatic spread in posterior uveal melanoma
Kaiserman et al.
Br J Ophthalmol 2004;88:892-895.
ABSTRACT
| FULL TEXT
Tumor Basal Area and Metastatic Death After Proton Beam Irradiation for Choroidal Melanoma
Li et al.
Arch Ophthalmol 2003;121:68-72.
ABSTRACT
| FULL TEXT
|
