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Management of Retinoblastoma in Children: Current Status

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Abstract

In recent years, there have been dramatic changes in the management of intraocular retinoblastoma. Intraocular retinoblastoma is a highly curable malignancy and current treatments are aimed to preserve vision while reducing the late effects such as treatment-induced secondary malignancies. The advent of intra-arterial chemotherapy changed the treatment paradigm from systemic treatment with chemotherapy to local treatment, and new questions emerged. While intra-arterial chemotherapy achieved encouraging results, only experience from major referral centers is reported, so its indications, advantages and risks are still to be elucidated. Many factors should be considered when choosing the appropriate conservative therapy. When the disease has extended outside the eye, the chances of cure are significantly lower and treatment should be tailored by the presence of pathology risk factors such as invasion of the choroid, the optic nerve, and the sclera. Adjuvant therapy is decided upon this information. Children with overt extraocular disease are treated with higher dose neoadjuvant therapy followed by delayed enucleation and adjuvant therapy.

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References

  1. Moll AC, Kuik DJ, Bouter LM, et al. Incidence and survival of retinoblastoma in The Netherlands: a register based study 1862–1995. Br J Ophthalmol. 1997;81:559–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Dean M, Bendfeldt G, Lou H, et al. Increased incidence and disparity of diagnosis of retinoblastoma patients in Guatemala. Cancer Lett. 2014;351:59–63.

    Article  CAS  PubMed  Google Scholar 

  3. Lanier AP, Holck P, Ehrsam Day G, Key C. Childhood cancer among Alaska Natives. Pediatrics. 2003;112:e396.

    Article  PubMed  Google Scholar 

  4. Amozorrutia-Alegria V, Bravo-Ortiz JC, Vazquez-Viveros J, et al. Epidemiological characteristics of retinoblastoma in children attending the Mexican Social Security Institute in Mexico City, 1990–94. Paediatr Perinat Epidemiol. 2002;16:370–4.

    Article  PubMed  Google Scholar 

  5. Moreno F, Sinaki B, Fandino A, Dussel V, Orellana L, Chantada G. A population-based study of retinoblastoma incidence and survival in Argentine children. Pediatr Blood Cancer. 2014;61:1610–5.

    Article  PubMed  Google Scholar 

  6. Orjuela MA, Titievsky L, Liu X, et al. Fruit and vegetable intake during pregnancy and risk for development of sporadic retinoblastoma. Cancer Epidemiol Biomarkers Prev. 2005;14:1433–40.

    Article  PubMed  Google Scholar 

  7. Palazzi MA, Yunes JA, Cardinalli IA, et al. Detection of oncogenic human papillomavirus in sporadic retinoblastoma. Acta Ophthalmol Scand. 2003;81:396–8.

    Article  CAS  PubMed  Google Scholar 

  8. Antoneli CB, Ribeiro KB, Sredni ST, et al. Low prevalence of HPV in Brazilian children with retinoblastoma. J Med Virol. 2011;83:115–8.

    Article  PubMed  Google Scholar 

  9. Marees T, Dommering CJ, Imhof SM, et al. Incidence of retinoblastoma in Dutch children conceived by IVF: an expanded study. Hum Reprod. 2009;24:3220–4.

    Article  CAS  PubMed  Google Scholar 

  10. Foix-L’Helias L, Aerts I, Marchand L, et al. Are children born after infertility treatment at increased risk of retinoblastoma? Hum Reprod. 2012;27:2186–92.

    Article  PubMed  Google Scholar 

  11. Xu K, Rosenwaks Z, Beaverson K, Cholst I, Veeck L, Abramson DH. Preimplantation genetic diagnosis for retinoblastoma: the first reported liveborn. Am J Ophthalmol. 2004;137:18–23.

    Article  PubMed  Google Scholar 

  12. Kleinerman RA, Yu CL, Little MP, et al. Variation of second cancer risk by family history of retinoblastoma among long-term survivors. J Clin Oncol. 2012;30:950–7.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Marees T, van Leeuwen FE, de Boer MR, Imhof SM, Ringens PJ, Moll AC. Cancer mortality in long-term survivors of retinoblastoma. Eur J Cancer. 2009;45:3245–53.

    Article  CAS  PubMed  Google Scholar 

  14. Moll AC, Imhof SM, Schouten-Van Meeteren AY, Kuik DJ, Hofman P, Boers M. Second primary tumors in hereditary retinoblastoma: a register-based study, 1945–1997: is there an age effect on radiation-related risk? Ophthalmology. 2001;108:1109–14.

    Article  CAS  PubMed  Google Scholar 

  15. Abramson DH, Frank CM, Susman M, Whalen MP, Dunkel IJ, Boyd NW 3rd. Presenting signs of retinoblastoma. J Pediatr. 1998;132:505–8.

    Article  CAS  PubMed  Google Scholar 

  16. Kaimbo WK, Mvitu MM, Missotten L. Presenting signs of retinoblastoma in Congolese patients. Bull Soc Belge Ophtalmol. 2002;282:37–41.

    Google Scholar 

  17. Parulekar MV. Retinoblastoma—current treatment and future direction. Early Hum Dev. 2010;86:619–25.

    Article  PubMed  Google Scholar 

  18. Linn Murphree A. Intraocular retinoblastoma: the case for a new group classification. Ophthalmol. Clin. North Am. 2005;18:41–53, viii.

  19. Kivela T. Trilateral retinoblastoma: a meta-analysis of hereditary retinoblastoma associated with primary ectopic intracranial retinoblastoma. J Clin Oncol. 1999;17:1829–37.

    CAS  PubMed  Google Scholar 

  20. Turaka K, Shields CL, Meadows AT, Leahey A. Second malignant neoplasms following chemoreduction with carboplatin, etoposide, and vincristine in 245 patients with intraocular retinoblastoma. Pediatr Blood Cancer. 2012;59:121–5.

    Article  PubMed  Google Scholar 

  21. Draper GJ, Sanders BM, Kingston JE. Second primary neoplasms in patients with retinoblastoma. Br J Cancer. 1986;53:661–71.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Sitorus RS, Moll AC, Suhardjono S, et al. The effect of therapy refusal against medical advice in retinoblastoma patients in a setting where treatment delays are common. Ophthalmic Genet. 2009;30:31–6.

    Article  PubMed  Google Scholar 

  23. Canturk S, Qaddoumi I, Khetan V, et al. Survival of retinoblastoma in less-developed countries impact of socioeconomic and health-related indicators. Br J Ophthalmol. 2010;94:1432–6.

    Article  CAS  PubMed  Google Scholar 

  24. Gupta R, Vemuganti GK, Reddy VA, Honavar SG. Histopathologic risk factors in retinoblastoma in India. Arch Pathol Lab Med. 2009;133:1210–4.

    PubMed  Google Scholar 

  25. Chantada GL, Dunkel IJ, de Davila MT, Abramson DH. Retinoblastoma patients with high risk ocular pathological features: who needs adjuvant therapy? Br J Ophthalmol. 2004;88:1069–73.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. de Graaf P, Goricke S, Rodjan F, et al. Guidelines for imaging retinoblastoma: imaging principles and MRI standardization. Pediatr Radiol. 2012;42:2–14.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Kashyap S, Meel R, Pushker N, et al. Clinical predictors of high risk histopathology in retinoblastoma. Pediatr Blood Cancer. 2012;58:356–61.

    Article  PubMed  Google Scholar 

  28. Chantada GL, Gonzalez A, Fandino A, et al. Some clinical findings at presentation can predict high-risk pathology features in unilateral retinoblastoma. J Pediatr Hematol Oncol. 2009;31:325–9.

    Article  CAS  PubMed  Google Scholar 

  29. 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.

    Article  PubMed  Google Scholar 

  30. Wilson MW, Qaddoumi I, Billups C, Haik BG, Rodriguez-Galindo C. A clinicopathological correlation of 67 eyes primarily enucleated for advanced intraocular retinoblastoma. Br J Ophthalmol. 2011;95:553–8.

    Article  PubMed  Google Scholar 

  31. Laurent VE, Sampor C, Solernou V, et al. Detection of minimally disseminated disease in the cerebrospinal fluid of children with high-risk retinoblastoma by reverse transcriptase-polymerase chain reaction for GD2 synthase mRNA. Eur J Cancer. 2013;49:2892–9.

    Article  CAS  PubMed  Google Scholar 

  32. McCormick B, Ellsworth R, Abramson D, LoSasso T, Grabowski E. Results of external beam radiation for children with retinoblastoma: a comparison of two techniques. J Pediatr Ophthalmol Strabismus. 1989;26:239–43.

    CAS  PubMed  Google Scholar 

  33. Levin MH, Gombos DS, O’Brien JM. Intra-arterial chemotherapy for advanced retinoblastoma: is the time right for a prospective clinical trial? Arch Ophthalmol. 2011;129:1487–9.

    Article  PubMed  Google Scholar 

  34. Suzuki S, Yamane T, Mohri M, Kaneko A. Selective ophthalmic arterial injection therapy for intraocular retinoblastoma: the long-term prognosis. Ophthalmology. 2011;118:2081–7.

    Article  PubMed  Google Scholar 

  35. Gobin YP, Dunkel IJ, Marr BP, Brodie SE, Abramson DH. Intra-arterial chemotherapy for the management of retinoblastoma: four-year experience. Arch Ophthalmol. 2011;129:732–7.

    Article  PubMed  Google Scholar 

  36. Lee V, Hungerford JL, Bunce C, Ahmed F, Kingston JE, Plowman PN. Globe conserving treatment of the only eye in bilateral retinoblastoma. Br J Ophthalmol. 2003;87:1374–80.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Grigorovski N, Lucena E, Mattosinho C, et al. Use of intra-arterial chemotherapy for retinoblastoma: results of a survey. Int J Ophthalmol. 2014;7:726–30.

    PubMed Central  PubMed  Google Scholar 

  38. Shields CL, Fulco EM, Arias JD, et al. Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy. Eye (Lond). 2013;27:253–64.

    Article  CAS  Google Scholar 

  39. Abramson DH. Retinoblastoma: saving life with vision. Annu Rev Med. 2014;65:171–84.

    Article  CAS  PubMed  Google Scholar 

  40. Shields CL, Shields JA. Retinoblastoma management: advances in enucleation, intravenous chemoreduction, and intra-arterial chemotherapy. Curr Opin Ophthalmol. 2010;21:203–12.

    Article  PubMed  Google Scholar 

  41. Willard VW, Qaddoumi I, Chen S, et al. Developmental and adaptive functioning in children with retinoblastoma: a longitudinal investigation. J Clin Oncol. 2014;32:2788–93.

    Article  PubMed  Google Scholar 

  42. van Dijk J, Imhof SM, Moll AC, et al. Quality of life of adult retinoblastoma survivors in The Netherlands. Health Qual Life Outcomes. 2007;5:30.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Eagle RC Jr, Shields CL, Bianciotto C, Jabbour P, Shields JA. Histopathologic observations after intra-arterial chemotherapy for retinoblastoma. Arch Ophthalmol. 2011;129:1416–21.

    Article  PubMed  Google Scholar 

  44. Bosaleh A, Sampor C, Solernou V, et al. Outcome of children with retinoblastoma and isolated choroidal invasion. Arch Ophthalmol. 2012;130:724–9.

    Article  PubMed  Google Scholar 

  45. Olteanu C, Dimaras H. Enucleation refusal for retinoblastoma: a global study. Ophthalmic Genet. 2014;31:1–7.

    Article  Google Scholar 

  46. Chantada GL, Qaddoumi I, Canturk S, et al. Strategies to manage retinoblastoma in developing countries. Pediatr Blood Cancer. 2011;56:341–8.

    Article  PubMed  Google Scholar 

  47. Zhao J, Dimaras H, Massey C, et al. Pre-enucleation chemotherapy for eyes severely affected by retinoblastoma masks risk of tumor extension and increases death from metastasis. J Clin Oncol. 2011;29:845–51.

    Article  PubMed  Google Scholar 

  48. Kingston JE, Hungerford JL, Madreperla SA, Plowman PN. Results of combined chemotherapy and radiotherapy for advanced intraocular retinoblastoma. Arch Ophthalmol. 1996;114:1339–43.

    Article  CAS  PubMed  Google Scholar 

  49. Shields CL, Mashayekhi A, Au AK, et al. The International Classification of Retinoblastoma predicts chemoreduction success. Ophthalmology. 2006;113:2276–80.

    Article  PubMed  Google Scholar 

  50. Naseripour M, Nazari H, Bakhtiari P, Modarres-zadeh M, Vosough P, Ausari M. Retinoblastoma in Iran: outcomes in terms of patients’ survival and globe survival. Br J Ophthalmol. 2009;93:28–32.

    Article  CAS  PubMed  Google Scholar 

  51. Shields CL, Bianciotto CG, Jabbour P, et al. Intra-arterial chemotherapy for retinoblastoma: report No. 2, treatment complications. Arch Ophthalmol. 2011;129:1407–15.

    Article  CAS  PubMed  Google Scholar 

  52. Dunkel IJ, Shi W, Salvaggio K, et al. Risk factors for severe neutropenia following intra-arterial chemotherapy for intra-ocular retinoblastoma. PLoS One. 2014;9:e108692.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  53. Chantada GL, Fandino AC, Schvartzman E, Raslawski E, Schaiquevich P, Manzitti J. Impact of chemoreduction for conservative therapy for retinoblastoma in Argentina. Pediatr Blood Cancer. 2014;61:821–6.

    Article  PubMed  Google Scholar 

  54. Gombos DS, Hungerford J, Abramson DH, et al. Secondary acute myelogenous leukemia in patients with retinoblastoma: is chemotherapy a factor? Ophthalmology. 2007;114:1378–83.

    Article  PubMed  Google Scholar 

  55. Qaddoumi I, Bass JK, Wu J, et al. Carboplatin-associated ototoxicity in children with retinoblastoma. J Clin Oncol. 2012;30:1034–41.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Jehanne M, Lumbroso-Le Rouic L, Savignoni A, et al. Analysis of ototoxicity in young children receiving carboplatin in the context of conservative management of unilateral or bilateral retinoblastoma. Pediatr Blood Cancer. 2009;52:637–43.

    Article  PubMed  Google Scholar 

  57. Shields CL, Shields JA, Meadows AT. Chemoreduction for retinoblastoma may prevent trilateral retinoblastoma. J Clin Oncol. 2000;18:236–7.

    CAS  PubMed  Google Scholar 

  58. Qaddoumi I, Billups CA, Tagen M, et al. Topotecan and vincristine combination is effective against advanced bilateral intraocular retinoblastoma and has manageable toxicity. Cancer. 2012;118:5663–70.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Lumbroso L, Doz F, Urbieta M, et al. Chemothermotherapy in the management of retinoblastoma. Ophthalmology. 2002;109:1130–6.

    Article  PubMed  Google Scholar 

  60. Greenwald MJ, Strauss LC. Combining cyclosporin with chemotherapy controls intraocular retinoblastoma without requiring radiation. Clin Cancer Res. 1997;3:491–2.

    CAS  PubMed  Google Scholar 

  61. Berry JL, Jubran R, Kim JW, et al. Long-term outcomes of Group D eyes in bilateral retinoblastoma patients treated with chemoreduction and low-dose IMRT salvage. Pediatr Blood Cancer. 2013;60:688–93.

    Article  PubMed  Google Scholar 

  62. Abramson DH, Dunkel IJ, Brodie SE, Kim JW, Gobin YP. A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results. Ophthalmology. 2008;115:1398–404, 404 e1.

  63. Suzuki S, Kaneko A. Management of intraocular retinoblastoma and ocular prognosis. Int J Clin Oncol. 2004;9:1–6.

    Article  PubMed  Google Scholar 

  64. Schaiquevich P, Buitrago E, Taich P, et al. Pharmacokinetic analysis of melphalan after superselective ophthalmic artery infusion in preclinical models and retinoblastoma patients. Invest Ophthalmol Vis Sci. 2012;53:4205–12.

    Article  CAS  PubMed  Google Scholar 

  65. Munier FL, Beck-Popovic M, Balmer A, Gaillard MC, Bovey E, Binaghi S. Occurrence of sectoral choroidal occlusive vasculopathy and retinal arteriolar embolization after superselective ophthalmic artery chemotherapy for advanced intraocular retinoblastoma. Retina. 2011;31:566–73.

    Article  CAS  PubMed  Google Scholar 

  66. Gobin YP, Rosenstein LM, Marr BP, Brodie SE, Abramson DH. Radiation exposure during intra-arterial chemotherapy for retinoblastoma. Arch Ophthalmol. 2012;130:403–4 (author reply 4–5).

    Article  PubMed  Google Scholar 

  67. Francis JH, Gobin YP, Nagiel A, et al. Thrombophilia in patients with retinoblastoma receiving ophthalmic artery chemosurgery. Arch Ophthalmol. 2012;130:1605–8.

    Article  PubMed  Google Scholar 

  68. Shields CL, Manjandavida FP, Lally SE, et al. Intra-arterial chemotherapy for retinoblastoma in 70 eyes: outcomes based on the international classification of retinoblastoma. Ophthalmology. 2014;121:1453–60.

    Article  PubMed  Google Scholar 

  69. Venturi C, Bracco S, Cerase A, et al. Superselective ophthalmic artery infusion of melphalan for intraocular retinoblastoma: preliminary results from 140 treatments. Acta Ophthalmol. 2013;91:335–42.

    Article  CAS  PubMed  Google Scholar 

  70. Francis JH, Gobin YP, Brodie SE, Marr BP, Dunkel IJ, Abramson DH. Experience of intra-arterial chemosurgery with single agent carboplatin for retinoblastoma. Br J Ophthalmol. 2012;96:1270–1.

    Article  PubMed  Google Scholar 

  71. Marr BP, Brodie SE, Dunkel IJ, Gobin YP, Abramson DH. Three-drug intra-arterial chemotherapy using simultaneous carboplatin, topotecan and melphalan for intraocular retinoblastoma: preliminary results. Br J Ophthalmol. 2012;96:1300–3.

    Article  PubMed  Google Scholar 

  72. Palioura S, Gobin YP, Brodie SE, Marr BP, Dunkel IJ, Abramson DH. Ophthalmic artery chemosurgery for the management of retinoblastoma in eyes with extensive (>50 %) retinal detachment. Pediatr Blood Cancer. 2012;59:859–64.

    Article  PubMed  Google Scholar 

  73. Abramson DH, Marr BP, Brodie SE, Dunkel I, Palioura S, Gobin YP. Ophthalmic artery chemosurgery for less advanced intraocular retinoblastoma: five year review. PLoS One. 2012;7:e34120.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  74. Biswas J, Das D, Krishnakumar S, Shanmugam MP. Histopathologic analysis of 232 eyes with retinoblastoma conducted in an Indian tertiary-care ophthalmic center. J Pediatr Ophthalmol Strabismus. 2003;40:265–7.

    PubMed  Google Scholar 

  75. Chan MP, Hungerford JL, Kingston JE, Plowman PN. Salvage external beam radiotherapy after failed primary chemotherapy for bilateral retinoblastoma: rate of eye and vision preservation. Br J Ophthalmol. 2009;93:891–4.

    Article  CAS  PubMed  Google Scholar 

  76. Chantada GL, Dunkel IJ, Antoneli CB, et al. Risk factors for extraocular relapse following enucleation after failure of chemoreduction in retinoblastoma. Pediatr Blood Cancer. 2007;49:256–60.

    Article  PubMed  Google Scholar 

  77. Schaiquevich P, Ceciliano A, Millan N, et al. Intra-arterial chemotherapy is more effective than sequential periocular and intravenous chemotherapy as salvage treatment for relapsed retinoblastoma. Pediatr Blood Cancer. 2013;60:766–70.

    Article  CAS  PubMed  Google Scholar 

  78. Shields CL, Manjandavida FP, Arepalli S, Kaliki S, Lally SE, Shields JA. Intravitreal melphalan for persistent or recurrent retinoblastoma vitreous seeds: preliminary results. JAMA Ophthalmol. 2014;132:319–25.

    Article  PubMed  Google Scholar 

  79. Munier FL, Gaillard MC, Balmer A, Beck-Popovic M. Intravitreal chemotherapy for vitreous seeding in retinoblastoma: recent advances and perspectives. Saudi J Ophthalmol. 2013;27:147–50.

    Article  PubMed Central  PubMed  Google Scholar 

  80. Seregard S, Kock E, af Trampe E. Intravitreal chemotherapy for recurrent retinoblastoma in an only eye. Br J Ophthalmol. 1995;79:194–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  81. Kaneko A, Suzuki S. Eye-preservation treatment of retinoblastoma with vitreous seeding. Jpn J Clin Oncol. 2003;33:601–7.

    Article  PubMed  Google Scholar 

  82. Ghassemi F, Shields CL, Ghadimi H, Khodabandeh A, Roohipoor R. Combined intravitreal melphalan and topotecan for refractory or recurrent vitreous seeding from retinoblastoma. JAMA Ophthalmol. 2014;132:936–41.

    Article  PubMed  CAS  Google Scholar 

  83. Francis JH, Schaiquevich P, Buitrago E, et al. Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma: a preclinical and clinical study. Ophthalmology. 2014;121:1810–7.

    Article  PubMed  Google Scholar 

  84. Sastre X, Chantada GL, Doz F, et al. Proceedings of the consensus meetings from the International Retinoblastoma Staging Working Group on the pathology guidelines for the examination of enucleated eyes and evaluation of prognostic risk factors in retinoblastoma. Arch Pathol Lab Med. 2009;133:1199–202.

    PubMed  Google Scholar 

  85. Leal-Leal CA, Rivera-Luna R, Flores-Rojo M, Juarez-Echenique JC, Ordaz JC, Amador-Zarco J. Survival in extra-orbital metastatic retinoblastoma: treatment results. Clin Transl Oncol. 2006;8:39–44.

    Article  PubMed  Google Scholar 

  86. Baroni LV, Sampor C, Fandino A, et al. Anterior segment invasion in retinoblastoma: is it a risk factor for extraocular relapse? J Pediatr Hematol Oncol. 2014;36:509–12.

    Article  Google Scholar 

  87. Khelfaoui F, Validire P, Auperin A, et al. Histopathologic risk factors in retinoblastoma: a retrospective study of 172 patients treated in a single institution. Cancer. 1996;77:1206–13.

    Article  CAS  PubMed  Google Scholar 

  88. Aerts I, Sastre-Garau X, Savignoni A, et al. Results of a multicenter prospective study on the postoperative treatment of unilateral retinoblastoma after primary enucleation. J Clin Oncol. 2013;31:1458–63.

    Article  CAS  PubMed  Google Scholar 

  89. Chantada GL, Guitter MR, Fandino AC, et al. Treatment results in patients with retinoblastoma and invasion to the cut end of the optic nerve. Pediatr Blood Cancer. 2009;52:218–22.

    Article  PubMed  Google Scholar 

  90. Chantada GL, Sampor C, Bosaleh A, Solernou V, Fandino A, de Davila MT. Comparison of staging systems for extraocular retinoblastoma: analysis of 533 patients. JAMA Ophthalmol. 2013;131:1127–34.

    Article  PubMed  Google Scholar 

  91. Shields CL, Shields JA, Baez KA, Cater J, De Potter PV. Choroidal invasion of retinoblastoma: metastatic potential and clinical risk factors. Br J Ophthalmol. 1993;77:544–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  92. Kaliki S, Shields CL, Shah SU, Eagle RC Jr, Shields JA, Leahey A. Postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin for the treatment of high-risk retinoblastoma. Arch Ophthalmol. 2011;129:1422–7.

    Article  CAS  PubMed  Google Scholar 

  93. Chantada GL, Fandino AC, Guitter MR, et al. Results of a prospective study for the treatment of unilateral retinoblastoma. Pediatr Blood Cancer. 2010;55:60–6.

    PubMed  Google Scholar 

  94. Friedman DN, Sklar CA, Oeffinger KC, et al. Long-term medical outcomes in survivors of extra-ocular retinoblastoma: the Memorial Sloan-Kettering Cancer Center (MSKCC) experience. Pediatr Blood Cancer. 2013;60:694–9.

    Article  PubMed  Google Scholar 

  95. Magramm I, Abramson DH, Ellsworth RM. Optic nerve involvement in retinoblastoma. Ophthalmology. 1989;96:217–22.

    Article  CAS  PubMed  Google Scholar 

  96. Sullivan EM, Wilson MW, Billups CA, et al. Pathologic risk-based adjuvant chemotherapy for unilateral retinoblastoma following enucleation. J Pediatr Hematol Oncol. 2014;36:e335–40.

    Article  CAS  PubMed  Google Scholar 

  97. Chantada GL, Casco F, Fandino AC, et al. Outcome of patients with retinoblastoma and postlaminar optic nerve invasion. Ophthalmology. 2007;114:2083–9.

    Article  PubMed  Google Scholar 

  98. Cuenca A, Giron F, Castro D, et al. Microscopic scleral invasion in retinoblastoma: clinicopathological features and outcome. Arch Ophthalmol. 2009;127:1006–10.

    Article  PubMed  Google Scholar 

  99. Antoneli CB, Ribeiro KB, Rodriguez-Galindo C, et al. The addition of ifosfamide/etoposide to cisplatin/teniposide improves the survival of children with retinoblastoma and orbital involvement. J Pediatr Hematol Oncol. 2007;29:700–4.

    Article  CAS  PubMed  Google Scholar 

  100. Ali MJ, Honavar SG, Reddy VA. Orbital retinoblastoma: present status and future challenges—a review. Saudi J Ophthalmol. 2011;25:159–67.

    Article  PubMed Central  PubMed  Google Scholar 

  101. Brisse HJ, de Graaf P, Galluzzi P, et al. Assessment of early-stage optic nerve invasion in retinoblastoma using high-resolution 1.5 Tesla MRI with surface coils: a multicentre, prospective accuracy study with histopathological correlation. Eur Radiol. 2014. doi:10.1007/s00330-014-3514-1.

    Google Scholar 

  102. Doz F, Khelfaoui F, Mosseri V, et al. The role of chemotherapy in orbital involvement of retinoblastoma. The experience of a single institution with 33 patients. Cancer. 1994;74:722–32.

    Article  CAS  PubMed  Google Scholar 

  103. Ali MJ, Reddy VA, Honavar SG, Naik M. Orbital retinoblastoma: where do we go from here? J Cancer Res Ther. 2011;7:11–4.

    Article  PubMed  Google Scholar 

  104. Radhakrishnan V, Sharma S, Vishnubhatla S, Bakhshi S. MRI findings at baseline and after neoadjuvant chemotherapy in orbital retinoblastoma (IRSS stage III). Br J Ophthalmol. 2013;97:52–8.

    Article  PubMed  Google Scholar 

  105. Dunkel IJ, Khakoo Y, Kernan NA, et al. Intensive multimodality therapy for patients with stage 4a metastatic retinoblastoma. Pediatr Blood Cancer. 2010;55:55–9.

    PubMed  Google Scholar 

  106. Palma J, Sasso DF, Dufort G, et al. Successful treatment of metastatic retinoblastoma with high-dose chemotherapy and autologous stem cell rescue in South America. Bone Marrow Transplant. 2012;47:522–7.

    Article  CAS  PubMed  Google Scholar 

  107. Dunkel IJ, Chan HS, Jubran R, et al. High-dose chemotherapy with autologous hematopoietic stem cell rescue for stage 4B retinoblastoma. Pediatr Blood Cancer. 2010;55:149–52.

    PubMed  Google Scholar 

  108. Dimaras H, Heon E, Budning A, et al. Retinoblastoma CSF metastasis cured by multimodality chemotherapy without radiation. Ophthalmic Genet. 2009;30:121–6.

    Article  CAS  PubMed  Google Scholar 

  109. Bellaton E, Bertozzi AI, Behar C, et al. Neoadjuvant chemotherapy for extensive unilateral retinoblastoma. Br J Ophthalmol. 2003;87:327–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  110. Shields CL, Honavar S, Shields JA, Demirci H, Meadows AT. Vitrectomy in eyes with unsuspected retinoblastoma. Ophthalmology. 2000;107:2250–5.

    Article  CAS  PubMed  Google Scholar 

  111. Chantada G, Leal-Leal C, Brisse H, et al. Is it pre-enucleation chemotherapy or delayed enucleation of severely involved eyes with intraocular retinoblastoma that risks extraocular dissemination and death? J Clin Oncol. 2011;29:3333–4 (author reply 5–6).

    Article  PubMed  Google Scholar 

  112. Schaiquevich P, Carcaboso AM, Buitrago E, et al. Ocular pharmacology of topotecan and its activity in retinoblastoma. Retina. 2014;34:1719–27.

    Article  CAS  PubMed  Google Scholar 

  113. Hayden BC, Jockovich ME, Murray TG, et al. Pharmacokinetics of systemic versus focal Carboplatin chemotherapy in the rabbit eye: possible implication in the treatment of retinoblastoma. Invest Ophthalmol Vis Sci. 2004;45:3644–9.

    Article  PubMed  Google Scholar 

  114. Requejo F, Sierre S, Marelli J, et al. Ophtalmic artery microcatheterization for research purposes in pigs. A technical note. J Invest Surg. 2014;27:291–3.

    Article  PubMed  Google Scholar 

  115. 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;53:2439–45.

    Article  PubMed Central  PubMed  Google Scholar 

  116. Tse BC, Steinle JJ, Johnson D, Haik BG, Wilson MW. Superselective intraophthalmic artery chemotherapy in a nonhuman primate model: histopathologic findings. JAMA Ophthalmol. 2013;131:903–11.

    Article  PubMed Central  PubMed  Google Scholar 

  117. Dyer MA, Rodriguez-Galindo C, Wilson MW. Use of preclinical models to improve treatment of retinoblastoma. PLoS Med. 2005;2:e332.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  118. Pontes de Carvalho RA, Krausse ML, Murphree AL, Schmitt EE, Campochiaro PA, Maumenee IH. Delivery from episcleral exoplants. Invest Ophthalmol Vis Sci. 2006;47:4532–9.

    Article  PubMed  Google Scholar 

  119. Martin NE, Kim JW, Abramson DH. Fibrin sealant for retinoblastoma: where are we? J Ocul Pharmacol Ther. 2008;24:433–8.

    Article  CAS  PubMed  Google Scholar 

  120. Mallipatna AC, Dimaras H, Chan HS, Heon E, Gallie BL. Periocular topotecan for intraocular retinoblastoma. Arch Ophthalmol. 2011;129:738–45.

    Article  PubMed  Google Scholar 

  121. Houston SK, Pina Y, Murray TG, et al. Novel retinoblastoma treatment avoids chemotherapy: the effect of optimally timed combination therapy with angiogenic and glycolytic inhibitors on LH(BETA)T(AG) retinoblastoma tumors. Clin Ophthalmol. 2011;5:129–37.

    CAS  PubMed Central  PubMed  Google Scholar 

  122. Boutrid H, Jockovich ME, Murray TG, et al. Targeting hypoxia, a novel treatment for advanced retinoblastoma. Invest Ophthalmol Vis Sci. 2008;49:2799–805.

    Article  PubMed  Google Scholar 

  123. Brennan RC, Federico S, Bradley C, et al. Targeting the p53 pathway in retinoblastoma with subconjunctival Nutlin-3a. Cancer Res. 2011;71:4205–13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  124. Laurie NA, Shih CS, Dyer MA. Targeting MDM2 and MDMX in retinoblastoma. Curr Cancer Drug Targets. 2007;7:689–95.

    Article  CAS  PubMed  Google Scholar 

  125. Zhang F, Tagen M, Throm S, et al. Whole-body physiologically based pharmacokinetic model for nutlin-3a in mice after intravenous and oral administration. Drug Metab Dispos Biol Fate Chem. 2011;39:15–21.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  126. Zhang J, Benavente CA, McEvoy J, et al. A novel retinoblastoma therapy from genomic and epigenetic analyses. Nature. 2012;481:329–34.

    CAS  PubMed Central  PubMed  Google Scholar 

  127. Pritchard EM, Stewart E, Zhu F, et al. Pharmacokinetics and efficacy of the spleen tyrosine kinase inhibitor R406 after ocular delivery for retinoblastoma. Pharm Res. 2014;31:3060–72.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  128. Rushlow DE, Mol BM, Kennett JY, et al. Characterisation of retinoblastomas without RB1 mutations: genomic, gene expression, and clinical studies. Lancet Oncol. 2013;14:327–34.

    Article  CAS  PubMed  Google Scholar 

  129. Kapatai G, Brundler MA, Jenkinson H, et al. Gene expression profiling identifies different sub-types of retinoblastoma. Br J Cancer. 2013;109:512–25.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  130. Dimaras H, Rushlow D, Halliday W, et al. Using RB1 mutations to assess minimal residual disease in metastatic retinoblastoma. Transl Res. 2010;156:91–7.

    Article  CAS  PubMed  Google Scholar 

  131. de Graaf P, Pouwels PJ, Rodjan F, et al. Single-shot turbo spin-echo diffusion-weighted imaging for retinoblastoma: initial experience. AJNR Am J Neuroradiol. 2012;33:110–8.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors wish to acknowledge Dr. David Abramson for his constant and unconditional intellectual support to their group. The support of the Fund for Ophthalmic Knowledge (NY, USA), the Fundacion Natali Dafne Flexer (Buenos Aires, Argentina), the CONICET (Buenos Aires, Argentina) and the Hospital JP Garrahan (Buenos Aires, Argentina) is acknowledged. G. L. Chantada and P. S. Schaiquevich have no conflicts of interest to declare. No sources of funding were used in the preparation of this manuscript.

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  1. Hematology-Oncology Service, Hospital JP Garrahan, Combate de los Pozos 1881, C1245AAL, Buenos Aires, Argentina

    Guillermo Chantada

  2. Clinical Pharmacokinetics Unit, Hospital JP Garrahan/CONICET, Combate de los Pozos 1881, C1245AAL, Buenos Aires, Argentina

    Paula Schaiquevich

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  1. Guillermo Chantada
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  2. Paula Schaiquevich
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Correspondence to Guillermo Chantada.

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Chantada, G., Schaiquevich, P. Management of Retinoblastoma in Children: Current Status. Pediatr Drugs 17, 185–198 (2015). https://doi.org/10.1007/s40272-015-0121-9

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