Side effects of proton beam therapy of choroidal melanoma in dependence of the dose to the optic disc and the irradiated length of the optic nerve

Abstract

Purpose

To analyze the impact of the dose to the optic disc and the irradiated length of the optic nerve on radiation-induced optic neuropathy, radiation-induced retinopathy, iris neovascularization, secondary glaucoma, enucleation, and local tumor control after proton beam therapy (PBT) of choroidal melanoma.

Method

Retrospective analysis of 1129 patients, who received primary PBT for the treatment of choroidal melanoma with a dose of 60 cobalt gray equivalents (CGE) between 1998 and 2013 at the Helmholtz-Zentrum Berlin, Germany. Kaplan-Meier curves and logrank test have been used for time-to-event analyses. Adjustment for potential confounders was done using multiple Cox regression models with forward and backward selection.

Results

We found a significant correlation between the irradiated length of the optic nerve and the dose to the optic disc (correlation coefficient, 0.93). Multivariate Cox regression revealed the dose to the optic disc as an independent predictive risk factor for the development of radiation-induced optic neuropathy (p < 0.001, HR 1.023, 95 CI 1.016–1.029), iris neovascularization (p < 0.001, HR 1.013, 95% CI 1.008–1.019), secondary glaucoma (p < 0.001, HR 1.017, 95% CI: 1.011-1.023) and enucleation (p < 0.001, HR 1.037, 95% CI 1.020-1.053). The irradiated length of the optic nerve was not a statistically independent predictive risk factor in multivariate analysis.

Conclusion

Our data implicate the predominance of the dose to the optic disc over the irradiated length of the optic nerve regarding radiation-induced optic neuropathy, iris neovascularization, secondary glaucoma, and enucleation.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. 1.

    Damato B (2012) Progress in the management of patients with uveal melanoma. The 2012 Ashton Lecture. Eye (Lond) 26:1157–1172. https://doi.org/10.1038/eye.2012.126

    CAS  Article  Google Scholar 

  2. 2.

    Riechardt AI, Cordini D, Willerding G, Georgieva I, Weber A, Seibel I, Lakotka N, Bechrakis NE, Foerster MH, Moser L, Joussen AM (2014) Proton beam therapy of parapapillary choroidal melanoma. Am J Ophthalmol 157:1258–1265

    Article  Google Scholar 

  3. 3.

    Mishra KK, Daftari IK, Weinberg V, Cole T, Quivey JM, Castro JR, Phillips TL, Char DH (2013) Risk factors for neovascular glaucoma after proton beam therapy of uveal melanoma: a detailed analysis of tumor and dose-volume parameters. Int J Radiat Oncol Biol Phys 87:330–336

    Article  Google Scholar 

  4. 4.

    Seibel I, Cordini D, Hager A, Tillner J, Riechardt AI, Heufelder J, Davids AM, Rehak M, Joussen AM (2016) Predictive risk factors for radiation retinopathy and optic neuropathy after proton beam therapy for uveal melanoma. Graefes Arch Clin Exp Ophthalmol 254:1787–1792

    CAS  Article  Google Scholar 

  5. 5.

    Akbaba S, Foerster R, Nicolay NH, Arians N, Bostel T, Debus J, Hauswald H (2018) Linear accelerator-based stereotactic fractionated photon radiotherapy as an eye-conserving treatment for uveal melanoma. Radiat Oncol 13:140

    Article  Google Scholar 

  6. 6.

    Somani S, Sahgal A, Krema H, Heydarian M, McGowan H, Payne D, Xu W, Michaels H, Laperriere N, Simpson ER (2009) Stereotactic radiotherapy in the treatment of juxtapapillary choroidal melanoma: 2-year follow-up. Can J Ophthalmol 44:61–65. https://doi.org/10.3129/i08-177

    Article  PubMed  Google Scholar 

  7. 7.

    Siedlecki J, Reiterer V, Leicht S, Foerster P, Kortüm K, Schaller U, Priglinger S, Fuerweger C, Muacevic A, Eibl-Lindner K (2017) Incidence of secondary glaucoma after treatment of uveal melanoma with robotic radiosurgery versus brachytherapy. Acta Ophthalmol 95:e734–e739. https://doi.org/10.1111/aos.13418

    Article  PubMed  Google Scholar 

  8. 8.

    Yazici G, Kiratli H, Ozyigit G, Sari SY, Cengiz M, Tarlan B, Mocan BO, Zorlu F (2017) Stereotactic radiosurgery and fractionated stereotactic radiation therapy for the treatment of uveal melanoma. Int J Radiat Oncol Biol Phys 98:152–158. https://doi.org/10.1016/j.ijrobp.2017.02.017

    Article  PubMed  Google Scholar 

  9. 9.

    Eibl-Lindner K, Fürweger C, Nentwich M, Foerster P, Wowra B, Schaller U, Muacevic A (2016) Robotic radiosurgery for the treatment of medium and large uveal melanoma. Melanoma Res 26:51–57. https://doi.org/10.1097/CMR.0000000000000199

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Krema H, Heydarian M, Beiki-Ardakani A, Weisbrod D, Xu W, Simpson ER, Sahgal A (2013) A comparison between 125Iodine brachytherapy and stereotactic radiotherapy in the management of juxtapapillary choroidal melanoma. Br J Ophthalmol 97:327–332

    Article  Google Scholar 

  11. 11.

    Maheshwari A, Finger PT (2018) A 12-year study of slotted palladium-103 plaque radiation therapy for choroidal melanoma: near, touching, or surrounding the optic nerve. Am J Ophthalmol 188:60–69. https://doi.org/10.1016/j.ajo.2018.01.025

    Article  PubMed  Google Scholar 

  12. 12.

    Filì M, Trocme E, Bergman L, See TRO, André H, Bartuma K, Girnita L, All-Eriksson C, Seregard S, Stålhammar G (2020) Ruthenium-106 versus iodine-125 plaque brachytherapy of 571 choroidal melanomas with a thickness of ≥5.5 mm. Br J Ophthalmol 104:26–32

    Article  Google Scholar 

  13. 13.

    Goitein M, Miller T (1983) Planning proton therapy of the eye. Med Phys 10:275–283

    CAS  Article  Google Scholar 

  14. 14.

    Denker A, Cordini D, Heufelder J, Homeyer H, Kluge H, Simiantonakis I, Stark R, Weber A (2007) Ion accelerator applications in medicine and cultural heritage. Nucl Instrum Methods Phys Res A 580:457–461

    CAS  Article  Google Scholar 

  15. 15.

    Amin MB, Edge S, Greene F, Byrd DR, Brookland RK American Joint Committee on Cancer (eds) et al (2017) AJCC Cancer Staging Manual, EightEdition, Springer, New York

  16. 16.

    Riechardt AI, Pilger D, Cordini D, Seibel I, Gundlach E, Hager A, Joussen AM (2017) Neovascular glaucoma after proton beam therapy of choroidal melanoma: incidence and risk factors. Graefes Arch Clin Exp Ophthalmol 255:2263–2269. https://doi.org/10.1007/s00417-017-3737-3

    Article  PubMed  Google Scholar 

  17. 17.

    Le BHA, Kim JW, Deng H, Rayess N, Jennelle RL, Zhou SY, Astrahan MA, Berry JL (2018) Outcomes of choroidal melanomas treated with eye physics plaques: a 25-year review. Brachytherapy 17:981–989

    Article  Google Scholar 

  18. 18.

    Nürnberg D, Seibel I, Riechardt AI, Brockmann C, Zeitz O, Heufelder J, Joussen AM (2018) Multimodal imaging of the choroidal melanoma, with differential diagnosis, therapy (radiation planning) and follow-up [Article in German]. Klin Monatsbl Augenheilkd 235:1001–1002

    Article  Google Scholar 

  19. 19.

    Chowdhury MM, Dagash H, Pierro A (2007) A systematic review of the impact of volume of surgery and specialization on patient outcome. Br J Surg 94:145–161

    CAS  Article  Google Scholar 

  20. 20.

    Hrbacek J, Mishra KK, Kacperek A, Dendale R, Nauraye C, Auger M, Herault J, Daftari IK, Trofimov AV, Shih HA, Chen YL, Denker A, Heufelder J, Horwacik T, Swakoń J, Hoehr C, Duzenli C, Pica A, Goudjil F, Mazal A, Thariat J, Weber DC (2016) Practice patterns analysis of ocular proton therapy centers: the International OPTIC Survey. Int J Radiat Oncol Biol Phys 95:336–343. https://doi.org/10.1016/j.ijrobp.2016.01.040

    Article  PubMed  Google Scholar 

  21. 21.

    Mayo C, Martel MK, Marks LB, Flickinger J, Nam J, Kirkpatrick J (2010) Radiation dose-volume effects of optic nerves and chiasm. Int J Radiat Oncol Biol Phys 76:28–35

    Article  Google Scholar 

  22. 22.

    Zeisberg A, Seibel I, Cordini D, Lakotka N, Willerding G, Moser L, Heufelder J, Joussen AM (2014) Long-term (4 years) results of choroidal hemangioma treated with proton beam irradiation. Graefes Arch Clin Exp Ophthalmol 252:1165–1170. https://doi.org/10.1007/s00417-014-2635-1

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Egger E, Schalenbourg A, Zografos L, Bercher L, Boehringer T, Chamot L, Goitein G (2001) Maximizing local tumor control and survival after proton beam radiotherapy of uveal melanoma. Int J Radiat Oncol Biol Phys 51:138–147

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Aline I. Riechardt.

Ethics declarations

Conflict of interest

A.I. Riechardt: reimbursements of travel expense: EURETINA 2015/Novartis. A. Stroux, I. Seibel, J. Heufelder, O. Zeitz, D. Böhmer, A. M. Joussen, and J. Gollrad state that there are no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required. This article does not contain any studies with animals performed by any of the authors.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Riechardt, A.I., Stroux, A., Seibel, I. et al. Side effects of proton beam therapy of choroidal melanoma in dependence of the dose to the optic disc and the irradiated length of the optic nerve. Graefes Arch Clin Exp Ophthalmol 258, 2523–2533 (2020). https://doi.org/10.1007/s00417-020-04780-y

Download citation

Keywords

  • Choroidal melanoma
  • Proton beam therapy
  • Irradiated nerve length
  • Dose to the optic disc
  • Secondary glaucoma