Intraarterial Chemotherapy for Retinoblastoma – Initial Experiences of a German Reference Centre

Abstract

Background Adequate management of retinoblastoma requires a multidisciplinary and individual approach to treatment. Intraarterial chemotherapy (IAC) is one of the most commonly used treatment modalities, and enables supraselective application of chemotherapy via the ophthalmic artery and is now established in almost all treatment centres. However, published treatment success rates are heterogeneous. There are some unanswered issues regarding sight-threatening ocular complications and the long-term occurrence of secondary malignancies and metastatic disease. The objective of the present study is to analyse the results of a German national reference centre.

Methods Retrospective analysis of all children with an indication for at least one IAC from April 2010 to April 2020. IAC was used either as primary or recurrence therapy. Obligatory follow-up was at least 6 months.

Results 137 eyes of 127 children with an indication for IAC could be included. 12 eyes with a follow-up of less than 6 months and 37 eyes in which IAC was technically not feasible were excluded. In summary, 88 eyes of 79 children were finally analysed. Mean follow-up was 38 months, ranging from 7 to 117 months. In total, 195 procedures were completed. In 30 eyes (34.1%) IAC was conducted as primary and in 58 (65.9%) as secondary therapy. There was an initial IAC treatment response in 75 eyes (85.2%) with a recurrence-free rate of 61.3%. Eye salvage rate was 68.1% with 28 enucleated eyes in total. Ocular complications were observed in 36 eyes (40.9%), with 19 eyes (21.6%) showing severe sight-threatening and 11 eyes (12.5%) presenting minor non-sight-threatening toxic reactions. During follow-up, 1 child developed a secondary malignancy, 1 child developed metastasis and 1 child died as a consequence of trilateral retinoblastoma.

Conclusion In summary, IAC is a potent modality for retinoblastoma treatment and has been very successful, even in advanced disease and heavily pretreated eyes. However, ocular complications should be taken in consideration, especially when the only seeing eye is treated. Long term incidences of secondary malignancies and metastatic diseases should be further investigated in prospective studies.

Key words

retinoblastoma - ocular tumours - intraarterial chemotherapy

• References/Literatur

• 1 Bornfeld N, Lohmann D, Bechrakis NE. et al. [Retinoblastoma]. Ophthalmologe 2020; 117: 389-402
• 2 Biewald E, Schluter S, Kiefer T. et al. [Tumors and Pseudotumors of the Retina and the Ciliary Epithelium]. Klin Monbl Augenheilkd 2020; 237: 1359-1378
• 3 Kleinerman RA, Tucker MA, Tarone RE. et al. Risk of new cancers after radiotherapy in long-term survivors of retinoblastoma: An extended follow-up. J Clin Oncol 2005; 23: 2272-2279
• 4 Temming P, Arendt M, Viehmann A. et al. Incidence of second cancers after radiotherapy and systemic chemotherapy in heritable retinoblastoma survivors: A report from the German reference center. Pediatr Blood Cancer 2017; 64: 71-80
• 5 Yamane T, Kaneko A, Mohri M. The technique of ophthalmic arterial infusion therapy for patients with intraocular retinoblastoma. Int J Clin Oncol 2004; 9: 69-73
• 6 Abramson DH, Dunkel IJ, Brodie SE. et al. A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results. Ophthalmology 2008; 115: 1398-1404 1404.e1
• 7 Yousef YA, Soliman SE, Astudillo PPP. et al. Intra-arterial Chemotherapy for Retinoblastoma: A Systematic Review. JAMA Ophthalmol 2016; 134: 584-591
• 8 Pekacka A. The Role of Intraarterial Chemotherapy in the Management of Retinoblastoma. J Ophthalmol 2020; 2020: 3638410
• 9 Shields CL, Mashayekhi A, Au AK. et al. The International Classification of Retinoblastoma predicts chemoreduction success. Ophthalmology 2006; 113: 2276-2280
• 10 Biewald EM, Bornfeld N, Metz KA. et al. Histopathology of retinoblastoma eyes enucleated after intra-arterial chemotherapy. Br J Ophthalmol 2020; 104: 1171-1175
• 11 Munier FL, Mosimann P, Puccinelli F. et al. First-line intra-arterial versus intravenous chemotherapy in unilateral sporadic group D retinoblastoma: evidence of better visual outcomes, ocular survival and shorter time to success with intra-arterial delivery from retrospective review of 20 years of treatment. Br J Ophthalmol 2017; 101: 1086-1093
• 12 Hua J, Gang S, Yizhou J. et al. Intra-arterial chemotherapy as second-line treatment for advanced retinoblastoma: A 2-year single-center study in China. J Cancer Res Ther 2018; 14: 106-110
• 13 Suzuki S, Yamane T, Mohri M. et al. Selective ophthalmic arterial injection therapy for intraocular retinoblastoma: the long-term prognosis. Ophthalmology 2011; 118: 2081-2087
• 14 Francis JH, Brodie SE, Marr B. et al. Efficacy and Toxicity of Intravitreous Chemotherapy for Retinoblastoma: Four-Year Experience. Ophthalmology 2017; 124: 488-495
• 15 Stenzel E, Goricke S, Temming P. et al. Feasibility of intra-arterial chemotherapy for retinoblastoma: experiences in a large single center cohort study. Neuroradiology 2019; 61: 351-357
• 16 Bertelli E, Leonini S, Galimberti D. et al. Hemodynamic and Anatomic Variations Require an Adaptable Approach during Intra-Arterial Chemotherapy for Intraocular Retinoblastoma: Alternative Routes, Strategies, and Follow-Up. AJNR Am J Neuroradiol 2016; 37: 1289-1295
• 17 Munier FL, Beck-Popovic M, Balmer A. et al. Occurrence of sectoral choroidal occlusive vasculopathy and retinal arteriolar embolization after superselective ophthalmic artery chemotherapy for advanced intraocular retinoblastoma. Retina 2011; 31: 566-573
• 18 Shields CL, Bianciotto CG, Jabbour P. et al. Intra-arterial chemotherapy for retinoblastoma: report No. 2, treatment complications. Arch Ophthalmol 2011; 129: 1407-1415
• 19 Bianciotto C, Shields CL, Iturralde JC. et al. Fluorescein angiographic findings after intra-arterial chemotherapy for retinoblastoma. Ophthalmology 2012; 119: 843-849
• 20 Steinle JJ, Zhang Q, Thompson KE. et al. Intra-ophthalmic artery chemotherapy triggers vascular toxicity through endothelial cell inflammation and leukostasis. Invest Ophthalmol Vis Sci 2012; 53: 2439-2445
• 21 Reddy MA, Naeem Z, Duncan C. et al. Reduction of severe visual loss and complications following intra-arterial chemotherapy (IAC) for refractory retinoblastoma. Br J Ophthalmol 2017; 101: 1704-1708
• 22 Stacey AW, De Francesco S, Borri M. et al. The addition of topotecan to melphalan in the treatment of retinoblastoma with intra-arterial chemotherapy. Ophthalmol Retina 2020;
• 23 Taich P, Ceciliano A, Buitrago E. et al. Clinical pharmacokinetics of intra-arterial melphalan and topotecan combination in patients with retinoblastoma. Ophthalmology 2014; 121: 889-897
• 24 Guasti A, Leonini S, Bertelli E. et al. Intra-arterial chemotherapy for retinoblastoma: the dosimetric impact. Neuroradiology 2019; 61: 1083-1091
• 25 Opitz M, Bos D, Deuschl C. et al. Estimation of radiation exposure of children undergoing superselective intra-arterial chemotherapy for retinoblastoma treatment: assessment of local diagnostic reference levels as a function of age, sex, and interventional success. Neuroradiology 2021; 63: 391-398
• 26 Habib LA, Francis JH, Fabius AW. et al. Second primary malignancies in retinoblastoma patients treated with intra-arterial chemotherapy: the first 10 years. Br J Ophthalmol 2018; 102: 272-275
• 27 Moll AC, Imhof SM, Schouten-Van Meeteren AY. et al. Second primary tumors in hereditary retinoblastoma: a register-based study, 1945–1997: is there an age effect on radiation-related risk?. Ophthalmology 2001; 108: 1109-1114
• 28 Kaliki S, Shields CL, Rojanaporn D. et al. High-risk retinoblastoma based on international classification of retinoblastoma: analysis of 519 enucleated eyes. Ophthalmology 2013; 120: 997-1003