Uveal melanoma natural history, complications and prognosis: Difference between revisions

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==Overview==
==Overview==
If left untreated, 50% of patients with uveal melanoma may progress to develop [[metastasis]]. Common [[complications]] of uveal melanoma include [[glaucoma]], [[vision loss]], and [[metastasis]]. [[Prognosis]] is generally good for [[Patient|patients]] with [[iris]] [[melanoma]], and the 10 year-survival for iris melanoma is approximately 95 percent and for ciliochoroidal [[tumors]] is 77 percent respectively.
==Natural History, Complications, and Prognosis==


==Natural History==
=== Natural history ===


* The clinical course is unpredictable and [[metastatic]] [[disease]] can develop very late after a long [[disease]]-free interval. <ref name="pmid10661768">{{cite journal| author=Wöll E, Bedikian A, Legha SS| title=Uveal melanoma: natural history and treatment options for metastatic disease. | journal=Melanoma Res | year= 1999 | volume= 9 | issue= 6 | pages= 575-81 | pmid=10661768 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10661768  }} </ref><ref name="pmid23826405">{{cite journal| author=Jovanovic P, Mihajlovic M, Djordjevic-Jocic J, Vlajkovic S, Cekic S, Stefanovic V| title=Ocular melanoma: an overview of the current status. | journal=Int J Clin Exp Pathol | year= 2013 | volume= 6 | issue= 7 | pages= 1230-44 | pmid=23826405 | doi= | pmc=PMC3693189 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23826405  }} </ref>
*[[Uvea (anatomy)|Uveal]] melanoma [[Metastasis|metastasizes]] haematogenously, predominantly to the [[liver]].
* Less than 4% of [[Patient|patients]] with uveal melanoma have detectable [[metastatic]] [[disease]], at the time of [[diagnosis]].
* However in further course about half of [[Patient|patients]] will develop [[Metastasis|metastases]].
* When [[metastatic]] disease appears it unavoidably leads to death because of lack of effective systemic treatment.
===Complications===
[[Complications]] of eye [[melanoma]] include the following:<ref>Singh, Arun D., and Bertil Damato. Clinical ophthalmic oncology : uveal tumors. Heidelberg: Springer, 2014. Print.</ref>


==Complications==
*[[Glaucoma]]
Complications of eye melanoma may include:
*[[Cataract]]
===Glaucoma===
*[[Anterior chamber]] [[hemorrhage]]
Eye melanoma that is growing may cause glaucoma. Signs and symptoms of glaucoma may include the following:
*[[Corneal]] decompensation with [[edema]] and band [[keratopathy]]
*Eye pain
*[[Metastasis]]
*Redness
**Eye melanoma can spread outside of the [[Eye-eating amoebas|eye]] and to distant areas of the [[body]], including the [[liver]], [[lungs]] and [[bones]].
*Blurry vision
*[[Vision loss]]
===Vision loss===
Eye melanomas that are large often cause vision loss in the affected eye and may cause complications, such as retinal detachment, that also cause vision loss.
If small eye melanomas occur in critical parts of the eye they may cause some vision loss. There may be  difficulty seeing in the center of the vision or on the side. Advanced eye melanomas can cause complete vision loss.


===Metastasis===
:* Eye melanomas that are large often cause [[vision loss]] in the affected [[Acanthamoeba|eye]] and may cause [[complications]], such as [[retinal detachment]], that also cause [[vision loss]].
Eye melanoma can spread outside of the eye and to distant areas of the body, including the liver, lungs and bones.
:* If small [[eye]] melanomas occur in critical parts of the eye they may cause some [[vision loss]].
:* There may be  difficulty seeing in the center of the [[vision]] or on the side.
:* Advanced eye melanomas can cause complete [[vision loss]].
===Complications of therapy of uveal melanoma===
*[[Complications]] of [[radiotherapy]] include the following:<ref name="SummanenImmonen1996">{{cite journal|last1=Summanen|first1=P|last2=Immonen|first2=I|last3=Kivela|first3=T|last4=Tommila|first4=P|last5=Heikkonen|first5=J|last6=Tarkkanen|first6=A|title=Radiation related complications after ruthenium plaque radiotherapy of uveal melanoma.|journal=British Journal of Ophthalmology|volume=80|issue=8|year=1996|pages=732–739|issn=0007-1161|doi=10.1136/bjo.80.8.732}}</ref>
**[[Radiation]] [[retinopathy]]
**[[Radiation]] [[maculopathy]]
**[[Radiation]] opticopathy
**[[Maculopathy]]
**[[Cataract]]
**[[Neovascular glaucoma]]
**[[Vitreous]] [[haemorrhage]]
**[[Retinal detachment]] and dryness
**[[Radiation therapy|Radiation]] [[retinopathy]], opticopathy and neovascular [[glaucoma]] are responsible for the majority of secondary [[Vision loss|visual loss]] and secondary enucleations after therapy.


==Prognosis==
===Prognosis===
Poor prognostic factors for systemic disease include the follwing:
*Older age: >60 years of age<ref name="pmid2208011">{{cite journal| author=Augsburger JJ, Gamel JW| title=Clinical prognostic factors in patients with posterior uveal malignant melanoma. | journal=Cancer | year= 1990 | volume= 66 | issue= 7 | pages= 1596-600 | pmid=2208011 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2208011  }} </ref>
*Larger tumor size<ref name="pmid12470140">{{cite journal| author=Gragoudas E, Li W, Goitein M, Lane AM, Munzenrider JE, Egan KM| title=Evidence-based estimates of outcome in patients irradiated for intraocular melanoma. | journal=Arch Ophthalmol | year= 2002 | volume= 120 | issue= 12 | pages= 1665-71 | pmid=12470140 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12470140  }} </ref><ref name="pmid16344433">{{cite journal| author=Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD et al.| title=Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. | journal=Arch Ophthalmol | year= 2005 | volume= 123 | issue= 12 | pages= 1639-43 | pmid=16344433 | doi=10.1001/archopht.123.12.1639 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16344433  }} </ref><ref name="pmid23664467">{{cite journal| author=Shields CL, Kaliki S, Furuta M, Fulco E, Alarcon C, Shields JA| title=American Joint Committee on Cancer classification of posterior uveal melanoma (tumor size category) predicts prognosis in 7731 patients. | journal=Ophthalmology | year= 2013 | volume= 120 | issue= 10 | pages= 2066-71 | pmid=23664467 | doi=10.1016/j.ophtha.2013.03.012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23664467  }} </ref><ref name="pmid23816968">{{cite journal| author=Kujala E, Damato B, Coupland SE, Desjardins L, Bechrakis NE, Grange JD et al.| title=Staging of ciliary body and choroidal melanomas based on anatomic extent. | journal=J Clin Oncol | year= 2013 | volume= 31 | issue= 22 | pages= 2825-31 | pmid=23816968 | doi=10.1200/JCO.2012.45.2771 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23816968  }} </ref><ref name="pmid25555246">{{cite journal| author=AJCC Ophthalmic Oncology Task Force| title=International Validation of the American Joint Committee on Cancer's 7th Edition Classification of Uveal Melanoma. | journal=JAMA Ophthalmol | year= 2015 | volume= 133 | issue= 4 | pages= 376-83 | pmid=25555246 | doi=10.1001/jamaophthalmol.2014.5395 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25555246  }} </ref>
*Ciliary body involvement<ref name="pmid10922199">{{cite journal| author=Li W, Gragoudas ES, Egan KM| title=Metastatic melanoma death rates by anatomic site after proton beam irradiation for uveal melanoma. | journal=Arch Ophthalmol | year= 2000 | volume= 118 | issue= 8 | pages= 1066-70 | pmid=10922199 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10922199  }} </ref>
*Presence of orange pigment overlying the tumor<ref name="pmid12470140">{{cite journal| author=Gragoudas E, Li W, Goitein M, Lane AM, Munzenrider JE, Egan KM| title=Evidence-based estimates of outcome in patients irradiated for intraocular melanoma. | journal=Arch Ophthalmol | year= 2002 | volume= 120 | issue= 12 | pages= 1665-71 | pmid=12470140 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12470140  }} </ref>
*Extrascleral extension<ref name="pmid3014416">{{cite journal| author=Gragoudas ES, Seddon JM, Egan KM, Polivogianis L, Hsieh CC, Goitein M et al.| title=Prognostic factors for metastasis following proton beam irradiation of uveal melanomas. | journal=Ophthalmology | year= 1986 | volume= 93 | issue= 5 | pages= 675-80 | pmid=3014416 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3014416  }} </ref><ref name="pmid15519510">{{cite journal| author=Schmittel A, Bechrakis NE, Martus P, Mutlu D, Scheibenbogen C, Bornfeld N et al.| title=Independent prognostic factors for distant metastases and survival in patients with primary uveal melanoma. | journal=Eur J Cancer | year= 2004 | volume= 40 | issue= 16 | pages= 2389-95 | pmid=15519510 | doi=10.1016/j.ejca.2004.06.028 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15519510  }} </ref><ref name="pmid8248556">{{cite journal| author=Kleineidam M, Guthoff R, Bentzen SM| title=Rates of local control, metastasis, and overall survival in patients with posterior uveal melanomas treated with ruthenium-106 plaques. | journal=Radiother Oncol | year= 1993 | volume= 28 | issue= 2 | pages= 148-56 | pmid=8248556 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8248556  }} </ref><ref name="pmid7436829">{{cite journal| author=Affeldt JC, Minckler DS, Azen SP, Yeh L| title=Prognosis in uveal melanoma with extrascleral extension. | journal=Arch Ophthalmol | year= 1980 | volume= 98 | issue= 11 | pages= 1975-9 | pmid=7436829 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7436829  }} </ref>
*Histological and cytological factors associated with higher risk of metastasis includes the following:
**Presence and extent of cells with epitheliod morphology
**Presence of looping extracellular matrix patterns
**Increased infiltration of immune cells<ref>Robbins, Stanley L., Vinay Kumar, and Ramzi S. Cotran. Robbins and Cotran pathologic basis of disease. Philadelphia, PA: Saunders/Elsevier, 2010. Print.</ref>
**Staining with several immunohistochemical markers<ref name="pmid17425462">{{cite journal| author=Pardo M, Dwek RA, Zitzmann N| title=Proteomics in uveal melanoma research: opportunities and challenges in biomarker discovery. | journal=Expert Rev Proteomics | year= 2007 | volume= 4 | issue= 2 | pages= 273-86 | pmid=17425462 | doi=10.1586/14789450.4.2.273 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17425462  }} </ref>
*Cell type
:Cell type is the most commonly used predictor of outcome following enucleation, with spindle-A cell melanomas carrying the best prognosis and epithelioid cell melanomas carrying the least favorable prognosis. Nevertheless, most tumors have an admixture of cell types, and there is no clear consensus regarding the proportion of epithelioid cells that constitutes designation of a tumor as mixed or epithelioid.
*Overall survival depends on tumour size, extraocular spread, and metastases. Even small (<10 mm diameter, <3 mm thickness) tumors still carry a 10-15% 5-year mortality.
*The 10 year-survival for iris melanoma is approximately 95 percent and for ciliochoroidal tumors is 77 percent respectively.
*Several additional microscopic features can affect the prognosis of intraocular melanoma, including:<ref name="NIH">  Uveal melanoma. National Cancer Institute(2015) http://www.cancer.gov/types/eye/hp/intraocular-melanoma-treatment-pdq#link/_304_toc Accessed on October 23, 2015</ref>
**Mitotic activity.
**Lymphocytic infiltration.
**Fibrovascular loops
**Extraocular extension, recurrence, and metastasis are associated with an extremely poor prognosis, and long-term survival cannot be expected. Systemic metastases may be wide spread, with the liver > lung > bone > kidney > brain being a common sites for tumor deposits. 
**The 5-year mortality rate associated with metastasis from ciliary body or choroidal melanoma is approximately 30%, compared with a rate of 2% to 3% for iris melanomas.
 
*The most important genetic alteration associated with poor prognosis in uveal melanoma is inactivation of BAP1, which most often occurs through mutation of one allele and subsequent loss of an entire copy of Chromosome 3 (Monosomy 3) to unmask the mutant copy.<ref name="pmid21051595">{{cite journal| author=Harbour JW, Onken MD, Roberson ED, Duan S, Cao L, Worley LA et al.| title=Frequent mutation of BAP1 in metastasizing uveal melanomas. | journal=Science | year= 2010 | volume= 330 | issue= 6009 | pages= 1410-3 | pmid=21051595 | doi=10.1126/science.1194472 | pmc=PMC3087380 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21051595  }} </ref> Because of this function in inactivation of BAP1, monosomy 3 correlates strongly with metastatic spread.<ref name="pmid8622452">{{cite journal| author=Prescher G, Bornfeld N, Hirche H, Horsthemke B, Jöckel KH, Becher R| title=Prognostic implications of monosomy 3 in uveal melanoma. | journal=Lancet | year= 1996 | volume= 347 | issue= 9010 | pages= 1222-5 | pmid=8622452 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8622452  }} </ref>
*Where BAP1 mutation status is not available, gains on chromosomes 6 and 8 can be used to refine the predictive value of the Monosomy 3 screen, with gain of 6p indicating a better prognosis and gain of 8q indicating a worse prognosis in disomy 3 tumors.<ref name="pmid19182252">{{cite journal| author=Damato B, Dopierala J, Klaasen A, van Dijk M, Sibbring J, Coupland SE| title=Multiplex ligation-dependent probe amplification of uveal melanoma: correlation with metastatic death. | journal=Invest Ophthalmol Vis Sci | year= 2009 | volume= 50 | issue= 7 | pages= 3048-55 | pmid=19182252 | doi=10.1167/iovs.08-3165 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19182252  }} </ref>
*In rare instances, monosomy 3 tumors may duplicate the BAP1-mutant copy of the chromosome to return to a disomic state referred to as isodisomy.[18] Thus, isodisomy 3 is prognostically equivalent to monosomy 3, and both can be detected by tests for chromosome 3 loss of heterozygosity.<ref name="pmid17504992">{{cite journal| author=Onken MD, Worley LA, Person E, Char DH, Bowcock AM, Harbour JW| title=Loss of heterozygosity of chromosome 3 detected with single nucleotide polymorphisms is superior to monosomy 3 for predicting metastasis in uveal melanoma. | journal=Clin Cancer Res | year= 2007 | volume= 13 | issue= 10 | pages= 2923-7 | pmid=17504992 | doi=10.1158/1078-0432.CCR-06-2383 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17504992  }} </ref>
*Monosomy 3, along with other chromosomal gains, losses, amplifications, and LOH, can be detected in fresh or paraffin embedded samples by virtual karyotyping.


*The 5-year [[mortality rate]] associated with [[metastasis]] from [[ciliary body]] or choroidal melanoma is approximately 30%, compared with a rate of 2% to 3% for [[iris]] [[Melanoma|melanomas]].<ref name="ShieldsMellen2013">{{cite journal|last1=Shields|first1=CarolL|last2=Mellen|first2=PhoebeL|last3=Morton|first3=SpenserJ|title=American joint committee on cancer staging of uveal melanoma|journal=Oman Journal of Ophthalmology|volume=6|issue=2|year=2013|pages=116|issn=0974-620X|doi=10.4103/0974-620X.116652}}</ref><ref name="pmid23664467">{{cite journal| author=Shields CL, Kaliki S, Furuta M, Fulco E, Alarcon C, Shields JA| title=American Joint Committee on Cancer classification of posterior uveal melanoma (tumor size category) predicts prognosis in 7731 patients. | journal=Ophthalmology | year= 2013 | volume= 120 | issue= 10 | pages= 2066-71 | pmid=23664467 | doi=10.1016/j.ophtha.2013.03.012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23664467  }} </ref>
*Overall [[Survival rate|survival]] depends on [[tumor]] size, extraocular spread, and [[metastases]]. Even small (<10 mm diameter, <3 mm thickness) [[tumors]] still carry a 10-15% 5-year [[Mortality rate|mortality]].
*The 10 year-[[Survival rate|survival]] for [[iris]] [[melanoma]] is approximately 95 percent and for ciliochoroidal tumors is 77 percent respectively.
*The [[tumor]] node [[metastasis]] (TNM) staging system of the American Joint Committee on Cancer takes into account the key factors involved which are known to be of [[Prognosis|prognostic]] significance.
*The [[prognosis]] is usually poor when local control is not achieved with the initial treatment.<ref name="pmid12605964">{{cite journal| author=Egger E, Zografos L, Schalenbourg A, Beati D, Böhringer T, Chamot L et al.| title=Eye retention after proton beam radiotherapy for uveal melanoma. | journal=Int J Radiat Oncol Biol Phys | year= 2003 | volume= 55 | issue= 4 | pages= 867-80 | pmid=12605964 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12605964  }} </ref><ref name="pmid9514491">{{cite journal| author=Egan KM, Ryan LM, Gragoudas ES| title=Survival implications of enucleation after definitive radiotherapy for choroidal melanoma: an example of regression on time-dependent covariates. | journal=Arch Ophthalmol | year= 1998 | volume= 116 | issue= 3 | pages= 366-70 | pmid=9514491 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9514491  }} </ref>
*Detection of circulating [[tumor]] cells at the time of [[diagnosis]] is an independent [[risk factor]] for relapse and shortened survival in patients at high-risk based upon clinical parameters.<ref name="pmid17317826">{{cite journal| author=Schuster R, Bechrakis NE, Stroux A, Busse A, Schmittel A, Scheibenbogen C et al.| title=Circulating tumor cells as prognostic factor for distant metastases and survival in patients with primary uveal melanoma. | journal=Clin Cancer Res | year= 2007 | volume= 13 | issue= 4 | pages= 1171-8 | pmid=17317826 | doi=10.1158/1078-0432.CCR-06-2329 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17317826  }} </ref><ref name="pmid16314735">{{cite journal| author=Boldin I, Langmann G, Richtig E, Schwantzer G, Ardjomand N, Wegscheider B et al.| title=Five-year results of prognostic value of tyrosinase in peripheral blood of uveal melanoma patients. | journal=Melanoma Res | year= 2005 | volume= 15 | issue= 6 | pages= 503-7 | pmid=16314735 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16314735  }} </ref>
*The [[prognosis]] for any patient with recurring or relapsing disease is poor, regardless of [[cell type]] or stage.


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2]

Overview

If left untreated, 50% of patients with uveal melanoma may progress to develop metastasis. Common complications of uveal melanoma include glaucoma, vision loss, and metastasis. Prognosis is generally good for patients with iris melanoma, and the 10 year-survival for iris melanoma is approximately 95 percent and for ciliochoroidal tumors is 77 percent respectively.

Natural History, Complications, and Prognosis

Natural history

Complications

Complications of eye melanoma include the following:[3]

Complications of therapy of uveal melanoma

Prognosis

  • The 5-year mortality rate associated with metastasis from ciliary body or choroidal melanoma is approximately 30%, compared with a rate of 2% to 3% for iris melanomas.[5][6]
  • Overall survival depends on tumor size, extraocular spread, and metastases. Even small (<10 mm diameter, <3 mm thickness) tumors still carry a 10-15% 5-year mortality.
  • The 10 year-survival for iris melanoma is approximately 95 percent and for ciliochoroidal tumors is 77 percent respectively.
  • The tumor node metastasis (TNM) staging system of the American Joint Committee on Cancer takes into account the key factors involved which are known to be of prognostic significance.
  • The prognosis is usually poor when local control is not achieved with the initial treatment.[7][8]
  • Detection of circulating tumor cells at the time of diagnosis is an independent risk factor for relapse and shortened survival in patients at high-risk based upon clinical parameters.[9][10]
  • The prognosis for any patient with recurring or relapsing disease is poor, regardless of cell type or stage.

References

  1. ↑ Wöll E, Bedikian A, Legha SS (1999). "Uveal melanoma: natural history and treatment options for metastatic disease". Melanoma Res. 9 (6): 575–81. PMID 10661768.
  2. ↑ Jovanovic P, Mihajlovic M, Djordjevic-Jocic J, Vlajkovic S, Cekic S, Stefanovic V (2013). "Ocular melanoma: an overview of the current status". Int J Clin Exp Pathol. 6 (7): 1230–44. PMC 3693189. PMID 23826405.
  3. ↑ Singh, Arun D., and Bertil Damato. Clinical ophthalmic oncology : uveal tumors. Heidelberg: Springer, 2014. Print.
  4. ↑ Summanen, P; Immonen, I; Kivela, T; Tommila, P; Heikkonen, J; Tarkkanen, A (1996). "Radiation related complications after ruthenium plaque radiotherapy of uveal melanoma". British Journal of Ophthalmology. 80 (8): 732–739. doi:10.1136/bjo.80.8.732. ISSN 0007-1161.
  5. ↑ Shields, CarolL; Mellen, PhoebeL; Morton, SpenserJ (2013). "American joint committee on cancer staging of uveal melanoma". Oman Journal of Ophthalmology. 6 (2): 116. doi:10.4103/0974-620X.116652. ISSN 0974-620X.
  6. ↑ Shields CL, Kaliki S, Furuta M, Fulco E, Alarcon C, Shields JA (2013). "American Joint Committee on Cancer classification of posterior uveal melanoma (tumor size category) predicts prognosis in 7731 patients". Ophthalmology. 120 (10): 2066–71. doi:10.1016/j.ophtha.2013.03.012. PMID 23664467.
  7. ↑ Egger E, Zografos L, Schalenbourg A, Beati D, Böhringer T, Chamot L; et al. (2003). "Eye retention after proton beam radiotherapy for uveal melanoma". Int J Radiat Oncol Biol Phys. 55 (4): 867–80. PMID 12605964.
  8. ↑ Egan KM, Ryan LM, Gragoudas ES (1998). "Survival implications of enucleation after definitive radiotherapy for choroidal melanoma: an example of regression on time-dependent covariates". Arch Ophthalmol. 116 (3): 366–70. PMID 9514491.
  9. ↑ Schuster R, Bechrakis NE, Stroux A, Busse A, Schmittel A, Scheibenbogen C; et al. (2007). "Circulating tumor cells as prognostic factor for distant metastases and survival in patients with primary uveal melanoma". Clin Cancer Res. 13 (4): 1171–8. doi:10.1158/1078-0432.CCR-06-2329. PMID 17317826.
  10. ↑ Boldin I, Langmann G, Richtig E, Schwantzer G, Ardjomand N, Wegscheider B; et al. (2005). "Five-year results of prognostic value of tyrosinase in peripheral blood of uveal melanoma patients". Melanoma Res. 15 (6): 503–7. PMID 16314735.

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