OpenLB
Open Library of Bioscience
Advanced Search
Clinical & experimental ophthalmology
07, 2023;51 (5): 484-494.

Current management of uveal melanoma: A review.

Haixia Bai, Jacobus J Bosch, Ludwig M Heindl
Author Information
  1. Haixia Bai: Eye Center, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
  2. Jacobus J Bosch: Centre for Human Drug Research, Leiden, Netherlands.
  3. Ludwig M Heindl: Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany. ORCID
PMID: 37076276 DOI: 10.1111/ceo.14214

Abstract

Uveal melanoma is the most frequent primary intraocular cancer in adulthood and is mostly localised to the choroid. It can be treated using radiation therapy, laser therapy, local resection and enucleation, with the best results achieved by combining these procedures. However, up to half of patients develop metastatic disease. There are no efficacious treatment methods for patients in advanced stage or with metastasis. In recent years, several novel treatment modalities aimed at improving tumour control and reducing adverse events have emerged. This review summarises current clinical treatment methods and new therapeutic perspectives for uveal melanoma.

Keywords

eye tumour immunotherapy metastasis radiotherapy uveal melanoma

References

  1. Damato EM, Damato BE. Detection and time to treatment of uveal melanoma in the United Kingdom: an evaluation of 2,384 patients. Ophthalmology. 2012;119(8):1582-1589.
  2. Shields CL, Kaliki S, Furuta M, Mashayekhi A, Shields JA. Clinical spectrum and prognosis of uveal melanoma based on age at presentation in 8,033 cases. Retina. 2012;32(7):1363-1372.
  3. Shields CL, Kaliki S, Shah SU, Luo W, Furuta M, Shields JA. Iris melanoma: features and prognosis in 317 children and adults. J AAPOS. 2012;16(1):10-16.
  4. Oittinen HA, O'Shaughnessy M, Cullinane AB, et al. Malignant melanoma of the ciliary body presenting as extraocular metastasis in the temporalis muscle. J Clin Pathol. 2007;60(7):834-835.
  5. Toro MD, Gozzo L, Tracia L, et al. New therapeutic perspectives in the treatment of uveal melanoma: a systematic review. Biomedicine. 2021;9(10):1311.
  6. Augsburger JJ, Correa ZM, Shaikh AH. Effectiveness of treatments for metastatic uveal melanoma. Am J Ophthalmol. 2009;148(1):119-127.
  7. Jager MJ, Shields CL, Cebulla CM, et al. Uveal melanoma. Nat Rev Dis Primers. 2020;6(1):24.
  8. Reichstein DA, Brock AL. Radiation therapy for uveal melanoma: a review of treatment methods available in 2021. Curr Opin Ophthalmol. 2021;32(3):183-190.
  9. Diener-West M, Earle JD, Fine SL, et al. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS report No. 18. Arch Ophthalmol. 2001;119(7):969-982.
  10. Karimi S, Arabi A, Siavashpour Z, Shahraki T, Ansari I. Efficacy and complications of ruthenium-106 brachytherapy for uveal melanoma: a systematic review and meta-analysis. J Contemp Brachytherapy. 2021;13(3):358-364.
  11. Maheshwari A, Finger PT. Regression patterns of choroidal melanoma: after palladium-103 ((103)Pd) plaque brachytherapy. Eur J Ophthalmol. 2018;28(6):722-730.
  12. Kaliki S, Shields CL, Rojanaporn D, et al. Scleral necrosis after plaque radiotherapy of uveal melanoma: a case-control study. Ophthalmology. 2013;120(5):1004-1011.
  13. Shields CL, Shields JA, Cater J, et al. Plaque radiotherapy for uveal melanoma: long-term visual outcome in 1106 consecutive patients. Arch Ophthalmol. 2000;118(9):1219-1228.
  14. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28. Arch Ophthalmol. 2006;124(12):1684-1693.
  15. Jampol LM, Moy CS, Murray TG, et al. The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: IV. Local treatment failure and enucleation in the first 5 years after brachytherapy. COMS report No. 19. Ophthalmology. 2020;127(4S):S148-S157.
  16. Melia BM, Abramson DH, Albert DM, et al. Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years COMS report no. 16. Ophthalmology. 2001;108(2):348-366.
  17. Hawkins BS. The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma: IV. Ten-year mortality findings and prognostic factors. COMS report number 24. Am J Ophthalmol. 2004;138(6):936-951.
  18. Desjardins L, Lumbroso-Le RL, Levy-Gabriel C, et al. Treatment of uveal melanoma by accelerated proton beam. Dev Ophthalmol. 2012;49:41-57.
  19. Lane AM, Kim IK, Gragoudas ES. Long-term risk of melanoma-related mortality for patients with uveal melanoma treated with proton beam therapy. JAMA Ophthalmol. 2015;133(7):792-796.
  20. Bellocq D, Roy P, Kodjikian L, et al. 20-year assessment of metastatic latency and subsequent time to death after proton therapy for uveal melanomas. Melanoma Res. 2020;30(3):272-278.
  21. Papakostas TD, Lane AM, Morrison M, Gragoudas ES, Kim IK. Long-term outcomes after proton beam irradiation in patients with large choroidal melanomas. JAMA Ophthalmol. 2017;135(11):1191-1196.
  22. Toyama S, Tsuji H, Mizoguchi N, et al. Long-term results of carbon ion radiation therapy for locally advanced or unfavorably located choroidal melanoma: usefulness of CT-based 2-port orthogonal therapy for reducing the incidence of neovascular glaucoma. Int J Radiat Oncol Biol Phys. 2013;86(2):270-276.
  23. Riechardt AI, Klein JP, Cordini D, et al. Salvage proton beam therapy for recurrent iris melanoma: outcome and side effects. Graefes Arch Clin Exp Ophthalmol. 2018;256(7):1325-1332.
  24. Akbaba S, Foerster R, Nicolay NH, et al. Linear accelerator-based stereotactic fractionated photon radiotherapy as an eye-conserving treatment for uveal melanoma. Radiat Oncol. 2018;13(1):140.
  25. Siedlecki J, Reiterer V, Leicht S, et al. Incidence of secondary glaucoma after treatment of uveal melanoma with robotic radiosurgery versus brachytherapy. Acta Ophthalmol. 2017;95(8):e734-e739.
  26. Biltekin F, Yazici G. Dosimetric comparison and secondary malignancy risk estimation for linac-based and robotic stereotactic radiotherapy in uveal melanoma. Med Dosim. 2021;46(4):364-369.
  27. Gragoudas ES, Lane AM, Munzenrider J, et al. Long-term risk of local failure after proton therapy for choroidal/ciliary body melanoma. Trans Am Ophthalmol Soc. 2002;100:43-49.
  28. Peddada KV, Sangani R, Menon H, Verma V. Complications and adverse events of plaque brachytherapy for ocular melanoma. J Contemp Brachytherapy. 2019;11(4):392-397.
  29. Romano MR, Catania F, Confalonieri F, et al. Vitreoretinal surgery in the prevention and treatment of toxic tumour syndrome in uveal melanoma: a systematic review. Int J Mol Sci. 2021;22(18):1-11.
  30. Qiang Z, Cairns JD. Laser photocoagulation treatment of choroidal melanoma. Aust N Z J Ophthalmol. 1993;21(2):87-92.
  31. Maheshwari A, Finger PT. Laser treatment for choroidal melanoma: current concepts. Surv Ophthalmol. 2022;68(2):211-224.
  32. Rundle P. Treatment of posterior uveal melanoma with multi-dose photodynamic therapy. Br J Ophthalmol. 2014;98(4):494-497.
  33. Blasi MA, Laguardia M, Tagliaferri L, et al. Brachytherapy alone or with neoadjuvant photodynamic therapy for amelanotic choroidal melanoma: functional outcomes and local tumor control. Retina. 2016;36(11):2205-2212.
  34. Shields CL, Shields JA, Perez N, Singh AD, Cater J. Primary transpupillary thermotherapy for small choroidal melanoma in 256 consecutive cases: outcomes and limitations. Ophthalmology. 2002;109(2):225-234.
  35. Desjardins L, Lumbroso-Le RL, Levy-Gabriel C, et al. Combined proton beam radiotherapy and transpupillary thermotherapy for large uveal melanomas: a randomized study of 151 patients. Ophthalmic Res. 2006;38(5):255-260.
  36. Mashayekhi A, Shields CL, Rishi P, et al. Primary transpupillary thermotherapy for choroidal melanoma in 391 cases: importance of risk factors in tumor control. Ophthalmology. 2015;122(3):600-609.
  37. Aaberg TJ, Bergstrom CS, Hickner ZJ, et al. Long-term results of primary transpupillary thermal therapy for the treatment of choroidal malignant melanoma. Br J Ophthalmol. 2008;92(6):741-746.
  38. Shields JA, Shields CL, Shah P, Sivalingam V. Partial lamellar sclerouvectomy for ciliary body and choroidal tumors. Ophthalmology. 1991;98(6):971-983.
  39. Damato B. The role of eyewall resection in uveal melanoma management. Int Ophthalmol Clin. 2006;46(1):81-93.
  40. Popovic M, Ahmed IIK, DiGiovanni J, Shields CL. Radiotherapeutic and surgical management of iris melanoma: a review. Surv Ophthalmol. 2017;62(3):302-311.
  41. Rahmi A, Mammar H, Thariat J, et al. Proton beam therapy for presumed and confirmed iris melanomas: a review of 36 cases. Graefes Arch Clin Exp Ophthalmol. 2014;252(9):1515-1521.
  42. Klauber S, Jensen PK, Prause JU, Kessing SV. Surgical treatment of iris and ciliary body melanoma: follow-up of a 25-year series of patients. Acta Ophthalmol. 2012;90(2):122-126.
  43. Marigo FA, Finger PT. Anterior segment tumors: current concepts and innovations. Surv Ophthalmol. 2003;48(6):569-593.
  44. Gunduz K, Bechrakis NE. Exoresection and endoresection for uveal melanoma. Middle East Afr J Ophthalmol. 2010;17(3):210-216.
  45. Shields JA, Shields CL. Surgical approach to lamellar sclerouvectomy for posterior uveal melanomas: the 1986 Schoenberg lecture. Ophthalmic Surg. 1988;19(11):774-780.
  46. Rusnak S, Hecova L, Kasl Z, et al. Uveal melanoma biopsy. A review. Cesk Slov Oftalmol. 2020;76(6):247-252.
  47. Kivela T, Puusaari I, Damato B. Transscleral resection versus iodine brachytherapy for choroidal malignant melanomas 6 millimeters or more in thickness: a matched case-control study. Ophthalmology. 2003;110(11):2235-2244.
  48. Bechrakis NE, Petousis V, Willerding G, et al. Ten-year results of transscleral resection of large uveal melanomas: local tumour control and metastatic rate. Br J Ophthalmol. 2010;94(4):460-466.
  49. Konstantinidis L, Groenewald C, Coupland SE, Damato B. Long-term outcome of primary endoresection of choroidal melanoma. Br J Ophthalmol. 2014;98(1):82-85.
  50. Rice JC, Liebenberg L, Scholtz RP, Torr G. Fatal air embolism during endoresection of choroidal melanoma. Retin Cases Brief Rep. 2014;8(2):127-129.
  51. Joussen AM, Wong D. Egress of large quantities of heavy liquids from exposed choroid: a route for possible tumor dissemination via vortex veins in endoresection of choroidal melanoma. Graefes Arch Clin Exp Ophthalmol. 2015;253(2):177-178.
  52. Damato B, Jones AG. Uveal melanoma: resection techniques. Ophthalmol Clin North Am. 2005;18(1):119-128.
  53. Damato B, Groenewald C, Mcgalliard J, et al. Endoresection of choroidal melanoma. Br J Ophthalmol. 1998;82(3):213-218.
  54. Damato B. Endoresection of uveal melanoma without radiotherapy. Acta Ophthalmol. 2017;95:259.
  55. Bechrakis NE, Foerster MH. Neoadjuvant proton beam radiotherapy combined with subsequent endoresection of choroidal melanomas. Int Ophthalmol Clin. 2006;46(1):95-107.
  56. Hamza HS, Elhusseiny AM. Choroidal melanoma resection. Middle East Afr J Ophthalmol. 2018;25(2):65-70.
  57. Shields JA, Shields CL, Suvarnamani C, Tantisira M, Shah P. Orbital exenteration with eyelid sparing: indications, technique, and results. Ophthalmic Surg. 1991;22(5):292-297.
  58. Blanco PL, Lim LA, Miyamoto C, Burnier MN. Uveal melanoma dormancy: an acceptable clinical endpoint? Melanoma Res. 2012;22(5):334-340.
  59. Pereira PR, Odashiro AN, Marshall JC, Correa Z, Belfort R, Burnier MN. The role of c-kit and imatinib mesylate in uveal melanoma. J Carcinog. 2005;4:19.
  60. Penel N, Delcambre C, Durando X, et al. O-Mel-Inib: a Cancero-pole Nord-Ouest multi-center phase II trial of high-dose imatinib mesylate in metastatic uveal melanoma. Invest New Drugs. 2008;26(6):561-565.
  61. Mahipal A, Tijani L, Chan K, Laudadio MA, Mastrangelo MJ, Sato T. A pilot study of sunitinib malate in patients with metastatic uveal melanoma. Melanoma Res. 2012;22(6):440-446.
  62. Valsecchi ME, Orloff M, Sato R, et al. Adjuvant sunitinib in high-risk patients with uveal melanoma: comparison with institutional controls. Ophthalmology. 2018;125(2):210-217.
  63. Khan S, Lutzky J, Shoushtari AN, et al. Adjuvant crizotinib in high-risk uveal melanoma following definitive therapy. Front Oncol. 2022;12:976837.
  64. Missotten GS, Notting IC, Schlingemann RO, et al. Vascular endothelial growth factor a in eyes with uveal melanoma. Arch Ophthalmol. 2006;124(10):1428-1434.
  65. Yang H, Jager MJ, Grossniklaus HE. Bevacizumab suppression of establishment of micrometastases in experimental ocular melanoma. Invest Ophthalmol Vis Sci. 2010;51(6):2835-2842.
  66. Lima BR, Schoenfield LR, Singh AD. The impact of intravitreal bevacizumab therapy on choroidal melanoma. Am J Ophthalmol. 2011;151(2):323-328.
  67. Francis JH, Kim J, Lin A, Folberg R, Iyer S, Abramson DH. Growth of uveal melanoma following intravitreal bevacizumab. Ocul Oncol Pathol. 2017;3(2):117-121.
  68. Mahdjoubi A, Najean M, Lemaitre S, et al. Intravitreal bevacizumab for neovascular glaucoma in uveal melanoma treated by proton beam therapy. Graefes Arch Clin Exp Ophthalmol. 2018;256(2):411-420.
  69. Lee J, Kwon HJ, Kim M, Lee CS, Lee SC. Treatment response to intravitreal bevacizumab in small pigmented choroidal lesions with subretinal fluid. BMC Ophthalmol. 2019;19(1):103.
  70. Ma J, Roelofs KA, Russell L, Weis E, Chen SH. Rapid growth of primary uveal melanoma following intravitreal bevacizumab injection: a case report and review of the literature. Digit J Ophthalmol. 2021;26(3):27-30.
  71. Tura A, Pawlik VE, Rudolf M, et al. Uptake of ranibizumab but not bevacizumab into uveal melanoma cells correlates with a sustained decline in VEGF-A levels and metastatic activities. Cancers (Basel). 2019;11(6):1-17.
  72. Hussain RN, Heimann H, Damato B. Neoadjuvant intravitreal ranibizumab treatment in high-risk ocular melanoma patients: a two-stage single-centre phase II single-arm study. Melanoma Res. 2020;30(1):102-106.
  73. Mouriaux F, Servois V, Parienti JJ, et al. Sorafenib in metastatic uveal melanoma: efficacy, toxicity and health-related quality of life in a multicentre phase II study. Br J Cancer. 2016;115(1):20-24.
  74. Khalili JS, Yu X, Wang J, et al. Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012;18(16):4345-4355.
  75. Carvajal RD, Sosman JA, Quevedo JF, et al. Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. Jama. 2014;311(23):2397-2405.
  76. Carvajal RD, Schwartz GK, Mann H, Smith I, Nathan PD. Study design and rationale for a randomised, placebo-controlled, double-blind study to assess the efficacy of selumetinib (AZD6244; ARRY-142886) in combination with dacarbazine in patients with metastatic uveal melanoma (SUMIT). BMC Cancer. 2015;15:467.
  77. Komatsubara KM, Carvajal RD. Immunotherapy for the treatment of uveal melanoma: current status and emerging therapies. Curr Oncol Rep. 2017;19(7):45.
  78. Damato BE, Dukes J, Goodall H, Carvajal RD. Tebentafusp: T cell redirection for the treatment of metastatic uveal melanoma. Cancers (Basel). 2019;11(7):971.
  79. Lane AM, Egan KM, Harmon D, Holbrook A, Munzenrider JE, Gragoudas ES. Adjuvant interferon therapy for patients with uveal melanoma at high risk of metastasis. Ophthalmology. 2009;116(11):2206-2212.
  80. Richtig E, Langmann G, Schlemmer G, et al. Safety and efficacy of interferon alfa-2b in the adjuvant treatment of uveal melanoma. Ophthalmologe. 2006;103(6):506-511.
  81. Danielli R, Ridolfi R, Chiarion-Sileni V, et al. Ipilimumab in pretreated patients with metastatic uveal melanoma: safety and clinical efficacy. Cancer Immunol Immunother. 2012;61(1):41-48.
  82. Zimmer L, Vaubel J, Mohr P, et al. Phase II DeCOG-study of ipilimumab in pretreated and treatment-naive patients with metastatic uveal melanoma. PLoS One. 2015;10(3):e118564.
  83. Pelster MS, Gruschkus SK, Bassett R, et al. Nivolumab and ipilimumab in metastatic uveal melanoma: results from a single-arm phase II study. J Clin Oncol. 2021;39(6):599-607.
  84. Middleton MR, Steven NM, Evans TJ, et al. Safety, pharmacokinetics and efficacy of IMCgp100, a first-in-class soluble TCR-antiCD3 bispecific t cell redirector with solid tumour activity: results from the FIH study in melanoma. ASCO Meeting Abstracts. 2016;34(15_suppl):3016.
  85. Middleton MR, McAlpine C, Woodcock VK, et al. Tebentafusp, a TCR/anti-CD3 bispecific fusion protein targeting gp100, potently activated antitumor immune responses in patients with metastatic melanoma. Clin Cancer Res. 2020;26(22):5869-5878.
  86. Sacco JJ, Carvajal R, Butler MO, et al. 64MO A phase (ph) II, multi-center study of the safety and efficacy of tebentafusp (tebe) (IMCgp100) in patients (pts) with metastatic uveal melanoma (mUM). Ann Oncol. 2020;31:S1442-S1443.
  87. Carvajal RD, Butler MO, Shoushtari AN, et al. Clinical and molecular response to tebentafusp in previously treated patients with metastatic uveal melanoma: a phase 2 trial. Nat Med. 2022;28:2364-2373.
  88. Nathan P, Hassel JC, Rutkowski P, et al. Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med. 2021;385(13):1196-1206.
  89. Bilmin K, Synoradzki KJ, Czarnecka AM, et al. New perspectives for eye-sparing treatment strategies in primary uveal melanoma. Cancers (Basel). 2021;14(1):1-21.
  90. Singh AD. Light-activated therapy of choroidal melanoma. A new modality could be an effective alternative to radiation. Retin Physician. 2019;16:41-45.

Grants

  1. FOR2240/German Research Foundation

MeSH Term

Humans
Uveal Neoplasms
Melanoma
Treatment Outcome
Uveal Melanoma
Journal Article Review
Article has an altmetric score of 14

Word Cloud

Created with Highcharts 10.0.0melanomatreatmentuvealtherapypatientsmethodsmetastasistumourreviewUvealfrequentprimaryintraocularcanceradulthoodmostlylocalisedchoroidcantreatedusingradiationlaserlocalresectionenucleationbestresultsachievedcombiningproceduresHoweverhalfdevelopmetastaticdiseaseefficaciousadvancedstagerecentyearsseveralnovelmodalitiesaimedimprovingcontrolreducingadverseeventsemergedsummarisescurrentclinicalnewtherapeuticperspectivesCurrentmanagementmelanoma:eyeimmunotherapyradiotherapy

Similar Articles

Cited By