Skip to main content
SpringerLink
Log in

Uveal Melanoma: Proton Beam Radiation Therapy

  • Chapter
  • First Online:
Clinical Ophthalmic Oncology

Abstract

Radiotherapy (RT) is the standard of care for the vast majority of malignant melanomas of the uveal tract. Brachytherapy and external beam radiation with heavy charged particles, such as protons, are used to treat most choroidal and ciliary body tumors, and high rates of local control are achieved with both modalities. However, highly localized and uniform dose distributions can be delivered with proton beam radiotherapy, which makes it particularly advantageous for treating large tumors and tumors located close to the optic nerve or macula. Eye conservation and, in many cases, maintenance of useful vision are possible, but vision-threatening complications such as maculopathy and papillopathy can occur. Despite high rates of local control and maintenance of ocular function, primary treatment modality has no effect on survival, with similar rates of metastasis- and melanoma-related mortality observed in patients who undergo enucleation or receive radiotherapy. Currently there are no effective treatments for metastatic uveal melanoma, which develops in the liver in most cases. Further research to discover new therapies and preventive strategies is necessary to improve survival.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Nag S, Quivey JM, Earle JD, et al. The American Brachytherapy Society recommendations for brachytherapy of uveal melanomas. Int J Radiat Oncol Biol Phys. 2003;56(2):544–55.

    Article  PubMed  Google Scholar 

  2. Gragoudas E, Goitein M, Koehler A, et al. Proton irradiation of choroidal melanomas: preliminary results. Arch Ophthalmol. 1978;96:1583–91.

    Article  Google Scholar 

  3. Char DH, Kroll S, Castro J. Ten-year follow-up of helium ion therapy for uveal melanoma. Am J Ophthalmol. 1998;125(1):81–9.

    Article  CAS  PubMed  Google Scholar 

  4. Seddon JM, Gragoudas ES, Egan KM, et al. Relative survival rates after alternative therapies for uveal melanoma. Ophthalmology. 1990;97(6):769–77.

    Article  CAS  PubMed  Google Scholar 

  5. Puusaari I, Heikkonen J, Summanen P, et al. Iodine brachytherapy as an alternative to enucleation for large uveal melanomas. Ophthalmology. 2003;110(11):2223–34.

    Article  PubMed  Google Scholar 

  6. 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):969–82.

    Article  CAS  PubMed  Google Scholar 

  7. Gragoudas E, Goitein M, Seddon J, et al. Preliminary results of proton beam irradiation of macular and paramacular melanomas. Br J Ophthalmol. 1984;68(7):479–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Gragoudas ES, Goitein M, Verhey L, et al. Proton beam irradiation of uveal melanomas. Results of 5 1/2-year study. Arch Ophthalmol. 1982;100(6):928–34.

    Article  CAS  PubMed  Google Scholar 

  9. Mueller AJ, Talies S, Schaller UC, et al. Stereotactic radiosurgery of large uveal melanomas with the gamma-knife. Ophthalmology. 2000;107(7):1381–7; discussion 7–8.

    Article  CAS  PubMed  Google Scholar 

  10. Haas A, Pinter O, Papaefthymiou G, et al. Incidence of radiation retinopathy after high-dosage single-fraction gamma knife radiosurgery for choroidal melanoma. Ophthalmology. 2002;109(5):909–13.

    Article  PubMed  Google Scholar 

  11. Krema H, Heydarian M, Beiki-Ardakani A, et al. A comparison between 125Iodine brachytherapy and stereotactic radiotherapy in the management of juxtapapillary choroidal melanoma. Br J Ophthalmol. 2013;97(3):327–32.

    Article  PubMed  Google Scholar 

  12. Sikuade M, Salvi S, Rundle P, et al. Outcomes of treatment with stereotactic radiosurgery or proton beam therapy for choroidal melanoma. Eye (Lond). 2015;29(9):1194–8.

    Article  CAS  Google Scholar 

  13. Suit HD, Gotein M, Tepper J, et al. Exploratory study of proton radiation therapy using large field techniques and fractionated dose schedules. Cancer. 1975;35:1646–57.

    Article  CAS  PubMed  Google Scholar 

  14. Suit H. The gray lecture 2001: coming technical advances in radiation oncology. Int J Radiat Oncol Biol Phys. 2002;53(4):798–809.

    Article  PubMed  Google Scholar 

  15. Koehler A, Schneider R, Sisterson J. Range modulators for protons and heavy ions. Nucl Instr Meth. 1975;131:437–40.

    Article  CAS  Google Scholar 

  16. Wilson R. Radiological use of fast protons. Radiology. 1946;47:487–91.

    Article  CAS  PubMed  Google Scholar 

  17. Gragoudas ES, Lane AM. Charged-particle irradiation of uveal melanoma. In: Ryan SJ, editor. Retina. 4th ed. Philadelphia: Mosby; 2006. p. 761–8.

    Chapter  Google Scholar 

  18. Goitein M, Miller T. Planning proton therapy of the eye. Med Phys. 1983;10(3):275–83.

    Article  CAS  PubMed  Google Scholar 

  19. Gragoudas ES, Goitein M, Koehler A, et al. Proton irradiation of malignant melanoma of the ciliary body. Br J Ophthalmol. 1979;63(2):135–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gragoudas E, Goitein M, Verhey L, et al. Proton beam irradiation. An alternative to enucleation for intraocular melanomas. Ophthalmology. 1980;87(6):571–81.

    Article  CAS  PubMed  Google Scholar 

  21. Gragoudas E, Seddon J, Egan K, et al. Long-term result of proton beam irradiated uveal melanomas. Ophthalmology. 1987;94(4):349–53.

    Article  CAS  PubMed  Google Scholar 

  22. Gragoudas ES, Lane AM, Regan S, et al. A randomized controlled trial of varying radiation doses in the treatment of choroidal melanoma. Arch Ophthalmol. 2000;118(6):773–8.

    Article  CAS  PubMed  Google Scholar 

  23. Patel A, Lane AM, Morrison M, et al. Visual outcomes after proton beam irradiation for choroidal melanomas involving the fovea. Ophthalmology. 2016;123(2):369–77.

    Article  PubMed  Google Scholar 

  24. Egger E, Schalenbourg A, Zografos L, et al. Maximizing local tumor control and survival after proton beam radiotherapy of uveal melanoma. Int J Radiat Oncol Biol Phys. 2001;51(1):138–47.

    Article  CAS  PubMed  Google Scholar 

  25. Damato B, Kacperek A, Chopra M, et al. Proton beam radiotherapy of choroidal melanoma: the Liverpool-Clatterbridge experience. Int J Radiat Oncol Biol Phys. 2005;62(5):1405–11.

    Article  PubMed  Google Scholar 

  26. Dendale R, Lumbroso-Le Rouic L, Noel G, et al. Proton beam radiotherapy for uveal melanoma: results of Curie Institut–Orsay Proton Therapy Center (ICPO). Int J Radiat Oncol Biol Phys. 2006;65(3):780–7.

    Article  PubMed  Google Scholar 

  27. Gragoudas E, Li W, Goitein M, et al. Evidence-based estimates of outcome in patients irradiated for intraocular melanoma. Arch Ophthalmol 2002;120(12):1665–1671.

    Article  PubMed  Google Scholar 

  28. Gragoudas E, Egan K, Seddon J, et al. Intraocular recurrence of uveal melanoma after proton beam irradiation. Ophthalmology. 1992;99(5):760–6.

    Article  CAS  PubMed  Google Scholar 

  29. Marucci L, Lane AM, Li W, et al. Conservation treatment of the eye: conformal proton reirradiation for recurrent uveal melanoma. Int J Radiat Oncol Biol Phys. 2006;64(4):1018–22.

    Article  PubMed  Google Scholar 

  30. Harbour J, Murray T, Byrne S, et al. Intraoperative echographic localization of iodine 125 episcleral radioactive plaques for posterior uveal melanoma. Retina. 1996;16(2):129–34.

    Article  CAS  PubMed  Google Scholar 

  31. Lane A, Kim I, Gragoudas E. Proton irradiation for peripapillary and parapapillary melanomas. Arch Ophthalmol. 2011;128(9):1127–30.

    Article  Google Scholar 

  32. Sagoo MS, Shields CL, Mashayekhi A, et al. Plaque radiotherapy for juxtapapillary choroidal melanoma overhanging the optic disc in 141 consecutive patients. Arch Ophthalmol. 2008;126(11):1515–22.

    Article  PubMed  Google Scholar 

  33. Finger PT. Finger’s “slotted” eye plaque for radiation therapy: treatment of juxtapapillary and circumpapillary intraocular tumours. Br J Ophthalmol. 2007;91(7):891–4.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Sagoo MS, Shields CL, Mashayekhi A, et al. Plaque radiotherapy for choroidal melanoma encircling the optic disc (circumpapillary choroidal melanoma). Arch Ophthalmol. 2007;125(9):1202–9.

    Article  PubMed  Google Scholar 

  35. Egan K, Ryan L, Gragoudas E. Survival implications of enucleation after definitive radiotherapy for choroidal melanoma: an example of regression on time-dependent covariates. Arch Ophthalmol. 1998;116(3):366–70.

    Article  CAS  PubMed  Google Scholar 

  36. Egger E, Zografos L, Schalenbourg A, et al. Eye retention after proton beam radiotherapy for uveal melanoma. Int J Radiat Oncol Biol Phys. 2003;55(4):867–80.

    Article  PubMed  Google Scholar 

  37. Fuss M, Loredo L, Blacharski P, et al. Proton radiation therapy for medium and large choroidal melanoma: preservation of the eye and its functionality. Int J Radiat Oncol Biol Phys. 2001;49(4):1053–9.

    Article  CAS  PubMed  Google Scholar 

  38. Papakostas TD, Lane AM, Morrison M, et al. Long-term outcomes after proton beam irradiation in patients with large choroidal melanomas. JAMA Ophthalmol. 2017;135(11):1191–6.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Bensoussan E, Thariat J, Maschi C, et al. Outcomes after proton beam therapy for large choroidal melanomas in 492 patients. Am J Ophthalmol. 2016;165:78–87.

    Article  PubMed  Google Scholar 

  40. Saornil M, Egan K, Gragoudas E, et al. Histopathology of proton beam-irradiated vs enucleated uveal melanomas. Arch Ophthalmol. 1992;110(8):1112–8.

    Article  CAS  PubMed  Google Scholar 

  41. Regan S, Egan KM, Hart L, et al. Color Doppler imaging of untreated and irradiated choroidal melanomas. Eur J Ophthalmol. 2001;11(2):150–5.

    Article  CAS  PubMed  Google Scholar 

  42. Seddon JM, Gragoudas ES, Polivogianis L, et al. Visual outcome after proton beam irradiation of uveal melanoma. Ophthalmology. 1986;93(5):666–74.

    Article  CAS  PubMed  Google Scholar 

  43. Gragoudas ES, Li W, Lane AM, et al. Risk factors for radiation maculopathy and papillopathy after intraocular irradiation. Ophthalmology. 1999;106(8):1571–8.

    Article  CAS  PubMed  Google Scholar 

  44. Gragoudas ES, Lane AM. Uveal melanoma: proton beam irradiation. Ophthalmol Clin N Am. 2005;18(1):111–8.

    Article  Google Scholar 

  45. Weber B, Paton K, Ma R, et al. Outcomes of proton beam radiotherapy for large non-peripapillary choroidal and ciliary body melanoma at TRIUMF and the BC Cancer Agency. Ocul Oncol Pathol. 2015;2(1):29–35.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Foss AJ, Whelehan I, Hungerford JL, et al. Predictive factors for the development of rubeosis following proton beam radiotherapy for uveal melanoma. Br J Ophthalmol. 1997;81(9):748–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Gragoudas ES, Egan KM, Walsh SM, et al. Lens changes after proton beam irradiation for uveal melanoma. Am J Ophthalmol. 1995;119(2):157–64.

    Article  CAS  PubMed  Google Scholar 

  48. Gragoudas ES, Egan KM, Arrigg PG, et al. Cataract extraction after proton beam irradiation for malignant melanoma of the eye. Arch Ophthalmol. 1992;110(4):475–9.

    Article  CAS  PubMed  Google Scholar 

  49. Seibel I, Cordini D, Hager A, et al. Cataract development in patients treated with proton beam therapy for uveal melanoma. Graefes Arch Clin Exp Ophthalmol. 2016;254(8):1625–30.

    Article  PubMed  Google Scholar 

  50. Oxenreiter M, Lane A, Kim I, et al. A comparison of treatment outcomes in patients receiving standard dose vs. reduced dose proton radiation for uveal melanoma. Invest Ophthalmol Vis Sci. 2018;59:ARVO E-Abstract 3626.

    Google Scholar 

  51. Gragoudas ES, Lane AM, Kim IK. Charged-particle irradiation of uveal melanoma. In: Schachat AP, editor. Ryan’s Retina. 6th ed. Edinburgh: Elsevier; 2018. p. 2582–90.

    Google Scholar 

  52. Kim I, Lane A, Egan K, et al. Natural history of radiation papillopathy after proton beam irradiation of parapapillary melanoma. Ophthalmology. 2010;117(8):1617–22.

    Article  PubMed  Google Scholar 

  53. Courdi A, Caujolle JP, Grange JD, et al. Results of proton therapy of uveal melanomas treated in Nice. Int J Radiat Oncol Biol Phys. 1999;45(1):5–11.

    Article  CAS  PubMed  Google Scholar 

  54. Kodjikian L, Roy P, Rouberol F, et al. Survival after proton beam irradiation of uveal melanomas. Am J Ophthalmol. 2004;137(6):1002–10.

    Article  CAS  PubMed  Google Scholar 

  55. Kim IK, Lane AM, Gragoudas ES. Survival in patients with presymptomatic diagnosis of metastatic uveal melanoma. Arch Ophthalmol. 2010;128(7):871–5.

    Article  PubMed  Google Scholar 

  56. Gragoudas E, Egan K, Seddon J, et al. Survival of patients with metastases from uveal melanoma. Ophthalmology. 1991;98(3):383–90.

    Article  CAS  PubMed  Google Scholar 

  57. Bedikian AY, Legha SS, Mavligit G, et al. Treatment of uveal melanoma metastatic to the liver: a review of the M. D. Anderson Cancer Center experience and prognostic factors. Cancer. 1995;76(9):1665–70.

    Article  CAS  PubMed  Google Scholar 

  58. Eskelin S, Pyrhonen S, Hahka-Kemppinen M, et al. A prognostic model and staging for metastatic uveal melanoma. Cancer. 2003;97(2):465–75.

    Article  PubMed  Google Scholar 

  59. Flaherty LE, Unger JM, Liu PY, et al. Metastatic melanoma from intraocular primary tumors: the Southwest Oncology Group experience in phase II advanced melanoma clinical trials. Am J Clin Oncol. 1998;21(6):568–72.

    Article  CAS  PubMed  Google Scholar 

  60. Alexander HR Jr, Libutti SK, Pingpank JF, et al. Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver. Clin Cancer Res. 2003;9(17):6343–9.

    CAS  PubMed  Google Scholar 

  61. Agarwala S, Panikkar R, Kirkwood J. Phase I/II randomized trial of intrahepatic arterial infusion chemotherapy with cisplatin and chemoembolization with cisplatin and polyvinyl sponge in patients with ocular melanoma metastatic to the liver. Melanoma Res. 2004;14(3):217–22.

    Article  CAS  PubMed  Google Scholar 

  62. Aoyama T, Mastrangelo MJ, Berd D, et al. Protracted survival after resection of metastatic uveal melanoma. Cancer. 2000;89(7):1561–8.

    Article  CAS  PubMed  Google Scholar 

  63. Hsueh EC, Essner R, Foshag LJ, et al. Prolonged survival after complete resection of metastases from intraocular melanoma. Cancer. 2004;100(1):122–9.

    Article  PubMed  Google Scholar 

  64. Lane AM, Kim IK, Gragoudas ES. Survival rates in patients after treatment for metastasis from uveal melanoma. JAMA Ophthalmol. 2018;136(9):981–6.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Leyvraz S, Piperno-Neumann S, Suciu S, et al. Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial. Ann Oncol. 2014;25(3):742–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. 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):2397–405.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Komatsubara KM, Manson DK, Carvajal RD. Selumetinib for the treatment of metastatic uveal melanoma: past and future perspectives. Future Oncol. 2016;12(11):1331–44.

    Article  CAS  PubMed  Google Scholar 

  68. Kottschade LA, McWilliams RR, Markovic SN, et al. The use of pembrolizumab for the treatment of metastatic uveal melanoma. Melanoma Res. 2016;26(3):300–3.

    Article  CAS  PubMed  Google Scholar 

  69. Algazi AP, Tsai KK, Shoushtari AN, et al. Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-L1 antibodies. Cancer. 2016;122(21):3344–53.

    Article  CAS  PubMed  Google Scholar 

  70. Luke JJ, Callahan MK, Postow MA, et al. Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience. Cancer. 2013;119(20):3687–95.

    Article  CAS  PubMed  Google Scholar 

  71. Zheng J, Irani Z, Lawrence D, et al. Combined effects of yttrium-90 transarterial radioembolization around immunotherapy for hepatic metastases from uveal melanoma: a preliminary retrospective case series. JVIR. 2018;29(10):1369–75.

    Article  PubMed  Google Scholar 

  72. Kirchberger MC, Moreira A, Erdmann M, et al. Real world experience in low-dose ipilimumab in combination with PD-1 blockade in advanced melanoma patients. Oncotarget. 2018;9(48):28903–9.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Heppt MV, Heinzerling L, Kahler KC, et al. Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte antigen-4 inhibition. Eur J Cancer. 2017;82:56–65.

    Article  CAS  PubMed  Google Scholar 

  74. Valsecchi ME, Terai M, Eschelman DJ, et al. Double-blinded, randomized phase II study using embolization with or without granulocyte-macrophage colony-stimulating factor in uveal melanoma with hepatic metastases. JVIR. 2015;26(4):523–32. e2.

    Article  PubMed  Google Scholar 

  75. Itchins M, Ascierto PA, Menzies AM, et al. A multireferral centre retrospective cohort analysis on the experience in treatment of metastatic uveal melanoma and utilization of sequential liver-directed treatment and immunotherapy. Melanoma Res. 2017;27(3):243–50.

    Article  PubMed  Google Scholar 

  76. Yang J, Manson DK, Marr BP, et al. Treatment of uveal melanoma: where are we now? Ther Adv Med Oncol. 2018;10:1758834018757175.

    PubMed  PubMed Central  Google Scholar 

  77. Shields C, Demirci H, Marr B, et al. Intravitreal triamcinolone acetonide for acute radiation papillopathy. Retina. 2006;26(5):537–44.

    Article  PubMed  Google Scholar 

  78. Finger PT, Chin K. Anti-vascular endothelial growth factor bevacizumab (Avastin) for radiation retinopathy. Arch Ophthalmol. 2007;125(6):751–6.

    Article  CAS  PubMed  Google Scholar 

  79. Finger PT. Anti-VEGF bevacizumab (Avastin) for radiation optic neuropathy. Am J Ophthalmol. 2007;143(2):335–8.

    Article  CAS  PubMed  Google Scholar 

  80. Kim IK, Lane AM, Jain P, et al. Ranibizumab for the prevention of radiation complications in patients treated with proton beam irradiation for choroidal melanoma. Trans Am Ophthalmol Soc. 2016;114:T2.

    PubMed  PubMed Central  Google Scholar 

  81. Lane AM, KM E, Harmon D, et al. Adjuvant interferon therapy for patients with uveal melanoma at high risk of metastasis. Ophthalmology. 2009;116(11):2206–12.

    Article  PubMed  Google Scholar 

Download references

Disclosure

The authors have no financial interest in the subject or materials discussed in this article.

Author information

Authors and Affiliations

  1. Ocular Melanoma Center, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary/Harvard Medical School, Boston, MA, USA

    Anne Marie Lane, Ivana K. Kim & Evangelos S. Gragoudas

Authors
  1. Anne Marie Lane
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ivana K. Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Evangelos S. Gragoudas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Evangelos S. Gragoudas .

Editor information

Editors and Affiliations

  1. University of Oxford, Oxford, UK

    Bertil E. Damato

  2. Cole Eye Institute Cleveland Clinic, Cleveland, OH, USA

    Arun D. Singh

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lane, A.M., Kim, I.K., Gragoudas, E.S. (2019). Uveal Melanoma: Proton Beam Radiation Therapy. In: Damato, B., Singh, A. (eds) Clinical Ophthalmic Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-17879-6_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-17879-6_13

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-17878-9

  • Online ISBN: 978-3-030-17879-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation