Hybrid Photodynamic Therapy as a Component of Combined Treatment of Uveal Melanoma (Preliminary Results)

Objective. To develop a technique of hybrid photodynamic therapy (PDT) and present its preliminary results in combined organ-preserving treatment of uveal melanoma (UM).

Materials and methods. 4 patients with UM (T2aN0M0 — 2 patients, T3aN0M0 — 2 patients) were treated by hybrid PDT followed by Ru-106 + Rh-106 brachytherapy (BT). The initial UM prominence ranged from 7 to 8.6 mm (7.92 ± 0.67 mm), and the tumor base diameter ranged from 10.3 to 14 mm (12.10 ± 1.89 mm). PDT was performed using a chlorine photosensitizer at a rate of 1.0 mg/kg weight using a new hybrid technology, which consists of transpupillary and transscleral exposure to the tumor in one treatment session. Ru-106 + Rh-106 BT was performed according to the standard technique for up to 1 month after PDT.

Results. The combined approach contributed to rapid rates of tumor regression at the early terms of dynamic follow-up and achievement of complete regression at the period of 12 months in 2 cases with initially “large” UM sizes. Decrease in the signs of intratumoral vascularization of UM was noted from the first month of follow-up and this tendency was maintained throughout the whole period.

Conclusions. The presented preliminary results of hybrid PDT in combined treatment of UM expand the possibilities of organ-preserving treatment of largesized tumors due to direct cytotoxic and antiangiogenic effects on tumor substrate, as well as potentiation of radiation therapy.

1. Brovkina AF. Local removal of choroidal melanoma: pro and contra. OFTALMOLOGIYA AZ. 2018;1(26):48–53 (In Russ.).

2. Kaliki S, Shields CL. Uveal melanoma: relatively rare but deadly cancer. Eye. 2017;31(2):241–257. doi: 10.1038/eye.2016.275.

3. Saakyan SV, Amiryan AG, Valsky VV, Mironova IS, Tsygankov AYu. Reasons for enucleation after brachytherapy for uveal melanomas. Russian ophthalmological journal. 2016;9(4):46–51 (In Russ.). doi: 10.21516/2072-0076-2016-9-4-46-51.

4. Shields CL, Kaliki S, Furuta M, Fulco E, Alarcon C, Shields JA. American Joint Committee on Cancer Classification of Uveal Melanoma (Anatomic Stage) Predicts Prognosis in 7731 Patients. Ophthalmology. 2015;122(6):1180–1186. doi: 10.1016/j.ophtha.2015.01.026.

5. Afshar AR, Damato, BE. Uveal Melanoma: Evidence for Efficacy of Therapy. International Ophthalmology Clinics. 2015;55(1):23–43. doi: 10.1097/iio.0000000000000053.

6. Brovkina AF, Stoyukhina AS, Chesalin IP. Choroidal melanoma brachyterapy and secondary enucleation. Ophthalmology journal. 2014;7(7-2):69–77 (In Russ.). doi: 10.17816/OV2014269-77.

7. Blasi ML, Tagliaferri L, Scupola A, Villano A, Caputo CG, Pagliara MM. Brachytherapy alone or with neoadjuvant photodynamic therapy for amelanotic choroidal melanoma. Retina. 2016;36(11):2205–2212. doi: 10.1097/iae.0000000000001048.

8. Bely YuA, Tereshchenko AV, Volodin PL, Kaplan MA. Photodynamic therapy with the photosensitizer Photoditazine in ophthalmology. Kaluga: MNTK “Microsurgery of the eye”; 2008 (In Russ.).

9. Boiko EV, Panova IE, Petrosyan YuM, Samkovich EV. Photodynamic therapy in the treatment of choroidal melanoma. Review. Medicine. 2022;10(2):73–92 (In Russ.). doi: 10.29234/2308-9113-2022-10-2-73-92.

10. Kessel D. Photodynamic therapy: critical PDT theory. Photochemistry and photobiology. 2023;99(2):199–203. doi: 10.1111/php.13616.

11. Naumenko LV. Fiveyear results of combined treatment of patients with large uveal melanoma. Magazine “Healthcare”. 2021;8(893):68–76 (In Russ.).

12. Li XY, Tan LC, Dong LW, Zhang WQ, Shen XX. Susceptibility and Resistance Mechanisms during Photodynamic Therapy of Melanoma. Frontiers in Oncology. 2020;75:718–721. doi: 10.3389/fonc.2020.00597.

13. Mazloumi M, Dalvin LA, Abtahi SH, Yavari N, Yaghy A, Mashayekhi A, Shields JA, Shields CL. Photodynamic therapy in ocular oncology. Journal of Ophthalmic & Vision Research. 2020;15(4):547. doi: 10.18502/jovr.v15i4.7793.

14. Ganusevich ON, Nesterovich TN, Achinovich SL, Fedorkevich IV. Experience of neoadjuvant photodynamic therapy for melanoma. Research’n Practical Medicine Journal. 2019;6(special issue):94 (In Russ.).

15. Likhvantseva VG, Akopyan VS, Sultanova EO. Method of organpreserving treatment of intraocular tumors Patent RU 2452444, 10.06.2012.

16. Boyko EV, Shishkin MM, Sukhoterina AN, Kulikov AN. Possibilities of diode laser transscleral retinopexy (compared to cryopexy) in vitreoretinal surgery. Ophthalmic surgery and therapy. 2001;1(1):47–52. (In Russ.).

17. Berezin YuD, Eremenko SA, Malinin BG, Boiko EV, Kochergin VA, Shishkin MM. Experimental study of endoscleral and transscleral actions of IR radiation of diode, neodymium, and holmium lasers on the retina of the eye. Journal of Optical Technology. 1999;66(12):1040.

18. Keung EZ, Gershenwald JE. The eighth edition American Joint Committee on Cancer (AJCC) melanoma staging system: implications for melanoma treatment and care. Expert Rev Anticancer Ther. 2018;18(8):775–784. doi: 10.1080/14737140.2018.1489246.

19. Panova IE, Samkovich EV. Method of organpreserving treatment of choroidal melanoma based on the use of hybrid photodynamic therapy. Patent RU 2785609/09.12.2022.

20. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M., Rubinstein L. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). European journal of cancer, 2009;45(2):228–247. doi: 10.1016/j.ejca.2008.10.026.

21. Bely YuA, Tereshchenko AV, Volodin PL, Teschin VV. Method for determining indicationsfor photodynamic therapy of choroidal melanomas. Patent RU 2343831, 20.01.2009.

22. Bely YuA, Tereshchenko AV, Teschin VV. Method for determining the effectiveness of photodynamic therapy for choroidal melanomas. Patent RU 2374992, 10.12.2009.

23. Campbell WG, Pejnovic TM. Treatment of amelanotic choroidal melanoma with photodynamic therapy. Retina. 2012;32(7):1356–1362. doi: 10.1097/iae.10.1097/iae.0b013e31822c28ec.

24. Fabian ID, Stacey AW, Harby LA, Arora AK, Sagoo MS, Cohen VML. Primary photodynamic therapy with verteporfin for pigmented posterior pole cT1a choroidal melanoma: a 3year retrospective analysis. Br. J. Ophthalmol. 2018;102(12):1705– 1710. doi: 10.1136/bjophthalmol-2017-311747.

25. Fabian ID, Stacey AW., Papastefanou V, Harby LA, Arora AK, Sagoo MS, Cohen VM. Primary photodynamic therapy with verteporfin for small pigmented posterior pole choroidal melanoma. Eye (Lond). 2017;31(4):519–528. doi: 10.1038/eye.2017.22.