Aspects of dose, dose rate and radioisotopes in brachytherapy of uveal melanoma

Uveal melanomas constitute melanomas arising from the choroid, the ciliary body or the iris, and in adults stands for the most common primary malignant intraocular tumor. It has a high risk of metastatic spread followed by inevitable death, and unfortunately the prognosis has not improved over the last decades. In the beginning the only considerable treatment was enucleation, i.e. removal of the entire eye. However, brachytherapy has since the 70’s become the primary treatment for medium sized tumors, and the survival rate has been shown to be equal compared to primary enucleation.

The aim of our studies included in this thesis was to investigate the efficacy of today’s brachytherapy treatment regime and if any differences in ocular or patient survival could be found considering different brachytherapy aspects. When investigating only ruthenium-106 brachytherapy, no association was found between high or low dose rate and the risk of secondary enucleation, i.e. enucleation due to extensive unwanted side effects, insufficient treatment effect on the tumor or tumor relapse. In further analysis with both ruthenium-106 and iodine-125 brachytherapy included in the study and the risk of tumor related mortality considered, there was no statistical difference in outcome related to either dose or dose rate applied and we found no negative consequences for patients that received lower dose and dose rates than intended. As there is a gender difference in survival outcome for some cancers, we investigated this issue regarding uveal melanoma, but no differences could be found indicating this should be a factor to consider when planning treatment. Ruthenium-106 brachytherapy is generally used throughout Europe. In Sweden, iodine-125 for larger medium sized tumors became available 20 years after ruthenium-106 brachytherapy had begun. We therefore had a great opportunity to analyze the larger tumors treated with ruthenium-106 in the earlier years and compare them to same size tumors treated with iodine-125. There was no difference in survival between matched groups, but ruthenium-106-treated patients had a significantly higher risk of needing retreatment, thus making iodine-125 the preferred nuclide for thicker tumors.

In conclusion gender is not a factor that needs considering when planning treatment for uveal melanoma. Treatment with brachytherapy is both safe and effective within the current recommended doses and dose rates. Our findings suggest that lower doses and dose rates still would be adequate, and this should be investigated further. The current protocol for radioisotope selection based on tumor thickness also seems adequate for the best possible ocular and survival outcome.

List of scientific papers

I. Fili, M., Lundell, G., Lundell, M., & Seregard, S. (2014). High dose rate and low dose rate ruthenium brachytherapy for uveal melanoma. No association with ocular outcome. Br J Ophthalmol. 98(10), 1349-1354.
https://doi.org/10.1136/bjophthalmol-2014-305055

II. Fili, M., Trocme, E., Bergman, L., See, T. R. O., Andre, H., Bartuma, K., ... Stalhammar, G. (2020). Ruthenium-106 versus iodine-125 plaque brachytherapy of 571 choroidal melanomas with a thickness of >/=5.5 mm. Br J Ophthalmol. 104(1), 26-32.
https://doi.org/10.1136/bjophthalmol-2018-313419

III. Stalhammar, G., See, T. R., Fili, M., & Seregard, S. (2019). No Gender Differences in Long-Term Survival after Brachytherapy of 1,541 Patients with Uveal Melanoma. Ocul Oncol Pathol. 5(6), 432-439.
https://doi.org/10.1159/000497186

IV. Fili, M., Trocme, E., Herrspiegel, C., Seregard, S., & Stalhammar, G. (2020). Effect of plaque brachytherapy dose and dose rate on risk for disease-related mortality in 1238 patients with choroidal melanoma. Br J Ophthalmol.
https://doi.org/10.1136/bjophthalmol-2019-315722