Cryotherapy of retinoblastoma: 13-year experience

Introduction. Cryotherapy (CT) is one of the main methods of small retinoblastoma (Rb) treatment and remains the “gold standard” for the treatment of small tumors of pre-equatorial localization, however, the number of studies in the literature on this problem is small, and they are represented only by single studies.

Purpose of the study – to evaluate long-term results of CT of Rb.

Materials and methods. During the period from 2008 to 2021 CT was performed in 87 children (98 eyes, 169 tumors) with Rb. 49 (56 %) patients were boys, 38 (44 %) were girls. The average age at the time of treatment was 22 months (from 0 to 73 months). Bilateral RB was observed in 70 (80 %) patients, unilateral – in 17 (20 %). In 19 (22 %) cases, CT was performed on a single eye. A total of 169 tumors were treated by CT. Most of the treated tumors (138 foci, 82 %) had pre-equatorial localization (35 tumors – on the mid periphery and 103 tumors – on the far periphery of the fundus). 31 (18 %) tumors located postequatorially. The mean tumor thickness was 1.2 (from 0.4 to 2.9) mm, the mean basal diameter was 2.2 (from 0.9 to 4.9) mm.

In the vast majority of cases (n = 78, 87 %), CT was performed with an incision of the conjunctiva and separation of the tenon capsule in the projection of the tumor, then a double application with an exposure of 60 seconds was carried out according to the “classic” technology (“freeze–thaw”). In 13 % of cases (n = 9), CT was performed transconjunctivally without a conjunctival incision. In all cases, carbon dioxide (–78 ºC) was used as a refrigerant.

Results. Complete tumor regression after CT was achieved in 63 % of cases (106 tumors), of which in 91 % of cases (96 tumors) – after one CT session, in 8 % (9 tumors) – after 2 sessions, in one (1 %) case– after 4 CT sessions. In 10 % of cases (17 tumors) an incomplete regression was observed and subsequent transpupillary laser thermotherapy was performed. In 27 % of cases (43 tumors), continued tumor growth or recurrence of the tumor was detected, and therefore other methods of local treatment were used (brachytherapy, laser thermotherapy, intra-arterial and intravitreal chemotherapy). As a result of organ-preserving treatment, 90 (92 %) eyes were preserved, 8 (8 %) eyes were enucleated.

Complications after CT included vitreous hemorrhage in 3 (3 %) patients, preretinal hemorrhage in 7 (8 %) cases, subretinal hemorrhage in 2 %, local retinal detachment in 2 %, one (1 %) case of retinal tear, and vitreoretinal traction in 2 (2 %) patients. The mean follow-up time after CT was 44 months (from 4 to 121 months).

Conclusion. CT still takes an important place in Rb local treatment, especially in the treatment of small tumors of peripheral localization. However, long-term results have shown that one session of CT is often not enough to achieve complete tumor regression and it requires either repeated use of CT or application of other local methods, mostly transpupillary laser thermotherapy. However, the use of CT is especially relevant in the treatment of small tumors of pre-equatorial localization, which are resistant to thermotherapy, especially in cases of a tumor height more than 1 mm and basal diameter more than 2 mm, which are too large and inconvenient for thermotherapy of peripheral Rb.

1. Rao R., Honavar S.G. Retinoblastoma. Indian J Pediatr. 2017;84(12):937–44. doi: 10.1007/s12098-017-2395-0.

2. Broaddus E., Topham A., Singh A. D. Incidence of retinoblastoma in the USA: 1975-2004. Br J Ophthalmol. 2009;93(1):21–3. doi: 10.1136/bjo.2008.138750.

3. Ushakova T.L. Etiology, pathogenesis, clinical picture, diagnosis of retinoblastoma. Problems of organpreserving treatment. Detskaya onkologiya = Pediatric Oncology. 2003;1:40–5. (In Russ.)

4. Fabian I.D., Abdallah E., Abdullahi S.U., Abdulqader R.A., Boubacar S.A., Ademola-Popoola D.S., Adio A., Afshar A.R., Aggarwal P., Aghaji A.E., Ahmad A. Global retinoblastoma presentation and analysis by national income level. JAMA Oncol. 2020;6(5):685–95. doi: 10.1001/jamaoncol.2019.6716.

5. Ancona-Lezama D., Dalvin L.A., Shields C.L. Modern treatment of retinoblastoma: A 2020 review. Indian J Ophthalmol. 2020;68(11):2356–65. doi: 10.4103/ijo.IJO_721_20.

6. Polyakov V.G. Clinical Recommendations “Retinoblastoma”. Ministry of Health of the Russian Federation, 2017. (In Russ.).

7. Ushakova T.L., Trofimov I.A., Gorovtsova O.V., Yarovoy A.A., Saakyan S.V., Letyagin I.A., Matinyan N.V., Kukushkin A.V., Martynov L.A., Pogrebnyakov I.V., Ivanova O.A., Serov Y.A., Yarovaya V.A., Glekov I.V., Virshke E.R., Dolgushin B.I., Polyakov V.G. A New Era of Organ-Preserving Treatment in Pediatric Intraocular Retinoblastoma in Russia: A Multicentre Study. Onkopediatria = Oncopediatrics. 2018;5(1):51–69. (In Russ.) doi: 10.15690/onco.v5i1.1866.

8. Yarovoy A.A., Ushakova T.L., Polyakov V.G., Bulgakova E.S., Krivovyaz O.S., Gorovtsova O.V. Results of local treatment of retinoblastoma after polychemotherapy. Oftal’mokhirurgiya = Fyodorov Journal of Ophthalmic Surgery. 2014;(1):79–84. (In Russ.).

9. Abramson D.H., Ellsworth R.M., Rozakis G.W. Cryotherapy for retinoblastoma. Arch Ophthalmol. 1982;100(8):1253–6. doi: 10.1001/archopht.1982.01030040231003.

10. Shields J.A., Parsons H., Shields C.L., Giblin M.E. The role of cryotherapy in the management of retinoblastoma. Am J Ophthalmol. 1989;108(3):260–4. doi: 10.1016/0002-9394(89)90116-5.

11. Kotova E.S., Yarovoy A.A., Buzurtanov M.B. Ehffektivnost’ lokal’nogo lecheniya retinoblastomy na krainei periferii glaznogo dna. Sovremennye tekhnologii v oftal’mologii = Modern Technologies in Ophthalmology. 2020;(3):110–1. (In Russ.) doi: 10.25276/2312-4911-2020-3-110-111.

12. TNM8: The updated TNM classification for retinoblastoma. Community Eye Health. 2018;31(101):34. PMID: 29915471.

13. Gage A.A., Baust J. Mechanisms of tissue injury in cryosurgery. Cryobiology. 1998;37(3):171–86. doi: 10.1006/cryo.1998.2115.

14. Lincoff H., McLean J., Long R. The cryosurgical treatment of intraocular tumors. Am J Ophthalmol. 1967;63(3):389–99. doi: 10.1016/0002-9394(67)90234-6.

15. Rubin M.L. Cryopexy treatment for retinoblastoma. Am J Ophthalmol. 1968;66(5):870–1. doi: 10.1016/0002-9394(68)92802-x.

16. Tolentino F.I., Tablante R.T. Cryotherapy of retinoblastoma. Arch Ophthalmol. 1972;87(1):52–5. doi: 10.1001/archopht.1972.01000020054011.

17. Molteno A.C. Efficacy of cryotherapy in retinoblastoma. S Afr Med J. 1976;50(28):1089–92. PMID: 959914.

18. Hamel P., Heon E., Gallie B.L., Budning A.S. Focal therapy in the management of retinoblastoma: when to start and when to stop. J AAPOS. 2000;4(6):334–7. doi: 10.1067/mpa.2000.107902.

19. Shields C.L., Santos M.C.M., Diniz W., Gündüz K., Mercado G., Cater J.R., Shields J.A. Thermotherapy for Retinoblastoma. Arch. Ophthalmol. 1999;117(7):885–93. doi: 10.1001/archopht.117.7.885.

20. Yarovoy A.A., Doga A.V., Loginov R.A., Yarovaya V.A., Kotel’nikova A.V. Method for laser treatment of pathology of the extreme periphery of the fundus during reverse ophthalmoscopy. Patent for invention No. RU 2 715 194 C1, 2020. (In Russ.).

21. Yarovoy A.A., Volodin D.P., Yarovaya V.A., Ushakova T.L., Kotova E.S., Chochaeva A.M., Polyakov V.G. Transpupillary laser thermotherapy of retinoblastoma. Rossiyskiy zhurnal detskoy gematologii i onkologii = Russian Journal of Pediatric Hematology and Oncology. 2021;8(3):43–9. (In Russ.) doi: 10.21682/2311-1267-2021-8-3-43-49.

22. Anagnoste S.R., Scott I.U., Murray T.G., Kramer D., Toledano S. Rhegmatogenous retinal detachment in retinoblastoma patients undergoing chemoreduction and cryotherapy. Am J Ophthalmol. 2000;129(6):817–9. doi: 10.1016/s0002-9394(00)00407-4.

23. Baumal C.R., Shields C.L., Shields J.A., Tasman W.S. Surgical repair of rhegmatogenous retinal detachment after treatment for retinoblastoma. Ophthalmology. 1998;105(11):2134–9. doi: 10.1016/S0161-6420(98)91139-3.