Skip to main content
SpringerLink
Log in

Retinoblastoma

  • Living reference work entry
  • First Online:
Pediatric Surgical Oncology

Abstract

Retinoblastoma is the most common primary intraocular malignancy of childhood and represents 3–4% of all pediatric cancers. Without treatment, retinoblastoma is uniformly fatal. Early diagnosis and intervention can provide cure rates of greater than 97% in areas with advanced medical resources. Advanced disease is more common in developing countries as a result of delayed diagnosis, limited access to healthcare, and socioeconomic issues that correlate to a poorer prognosis. The management of retinoblastoma is individualized to each patient, and both the intraocular and extraocular stages must be considered. Multimodal treatment strategies with surgery, chemotherapy, and focal treatment modalities remain the mainstays of therapy. Enucleation remains a highly successful and cost-effective cure for advanced intraocular retinoblastoma with poor visual potential that is available in most centers worldwide. While emerging treatments continue to improve ocular salvage and preserve vision, the guiding principle among all specialists remains “save the life, save the eye, save the sight.”

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Similar content being viewed by others

References

  1. Parkin DM, Stiller CA, Draper GJ, Bieber CA. The international incidence of childhood cancer. Int J Cancer. 1988;42(4):511–20.

    Article  CAS  Google Scholar 

  2. Butros LJ, Abramson DH, Dunkel IJ. Delayed diagnosis of retinoblastoma: analysis of degree, cause, and potential consequences. Pediatrics. 2002;109(3):E45.

    Article  Google Scholar 

  3. Wong JR, Tucker MA, Kleinerman RA, Devesa SS. Retinoblastoma incidence patterns in the US surveillance, epidemiology, and end results program. JAMA Ophthalmol. 2014;132(4):478–83.

    Article  Google Scholar 

  4. Shields J, Shields C. Intraocular Tumours. A Textbook and Atlas. Philedelphia: Saunders; 1992.

    Google Scholar 

  5. Andreoli MT, Chau FY, Shapiro MJ, Leiderman YI. Epidemiological trends in 1452 cases of retinoblastoma from the surveillance, epidemiology, and end results (SEER) registry. Can J Ophthalmol. 2017;52(6):592–8.

    Article  Google Scholar 

  6. de Aguirre Neto JC, Antoneli CB, Ribeiro KB, Castilho MS, Novaes PE, Chojniak MM, et al. Retinoblastoma in children older than 5 years of age. Pediatr Blood Cancer. 2007;48(3):292–5.

    Article  Google Scholar 

  7. Fernandes AG, Pollock BD, Rabito FA. Retinoblastoma in the United States: a 40-year incidence and survival analysis. J Pediatr Ophthalmol Strabismus. 2018;55(3):182–8.

    Article  Google Scholar 

  8. Siegel DA, Li J, Henley SJ, Wilson RJ, Lunsford NB, Tai E, et al. Geographic variation in pediatric cancer incidence – United States, 2003-2014. MMWR Morb Mortal Wkly Rep. 2018;67(25):707–13.

    Article  Google Scholar 

  9. Stiller CA, Parkin DM. Geographic and ethnic variations in the incidence of childhood cancer. Br Med Bull. 1996;52(4):682–703.

    Article  CAS  Google Scholar 

  10. de Camargo B, de Oliveira SM, Rebelo MS, de Souza RR, Ferman S, Noronha CP, et al. Cancer incidence among children and adolescents in Brazil: first report of 14 population-based cancer registries. Int J Cancer. 2010;126(3):715–20.

    Article  Google Scholar 

  11. Fajardo-Gutierrez A, Juarez-Ocana S, Gonzalez-Miranda G, Palma-Padilla V, Carreon-Cruz R, Ortega-Alvarez MC, et al. Incidence of cancer in children residing in ten jurisdictions of the Mexican Republic: importance of the cancer registry (a population-based study). BMC Cancer. 2007;7:68.

    Article  Google Scholar 

  12. Steliarova-Foucher E, Colombet M, Ries LAG, Moreno F, Dolya A, Bray F, et al. International incidence of childhood cancer, 2001-10: a population-based registry study. Lancet Oncol. 2017;18(6):719–31.

    Article  Google Scholar 

  13. Heck JE, Lombardi CA, Meyers TJ, Cockburn M, Wilhelm M, Ritz B. Perinatal characteristics and retinoblastoma. Cancer Causes Control. 2012;23(9):1567–75.

    Article  Google Scholar 

  14. Sivakumaran TA, Ghose S, Kumar H, A S, Kucheria K. Parental age in Indian patients with sporadic hereditary retinoblastoma. Ophthalmic Epidemiol. 2000;7(4):285–91.

    Article  CAS  Google Scholar 

  15. Yip BH, Pawitan Y, Czene K. Parental age and risk of childhood cancers: a population-based cohort study from Sweden. Int J Epidemiol. 2006;35(6):1495–503.

    Article  Google Scholar 

  16. Bunin GR, Felice MA, Davidson W, Friedman DL, Shields CL, Maidment A, et al. Medical radiation exposure and risk of retinoblastoma resulting from new germline RB1 mutation. Int J Cancer. 2011;128(10):2393–404.

    Article  CAS  Google Scholar 

  17. Abdolahi A, van Wijngaarden E, McClean MD, Herrick RF, Allen JG, Ganguly A, et al. A case-control study of paternal occupational exposures and the risk of childhood sporadic bilateral retinoblastoma. Occup Environ Med. 2013;70(6):372–9.

    Article  Google Scholar 

  18. Bunin GR, Meadows AT, Emanuel BS, Buckley JD, Woods WG, Hammond GD. Pre- and postconception factors associated with sporadic heritable and nonheritable retinoblastoma. Cancer Res. 1989;49(20):5730–5.

    CAS  Google Scholar 

  19. Azary S, Ganguly A, Bunin GR, Lombardi C, Park AS, Ritz B, et al. Sporadic retinoblastoma and parental smoking and alcohol consumption before and after conception: a report from the children’s oncology group. PLoS One. 2016;11(3):e0151728.

    Article  Google Scholar 

  20. Heck JE, Omidakhsh N, Azary S, Ritz B, von Ehrenstein OS, Bunin GR, et al. A case-control study of sporadic retinoblastoma in relation to maternal health conditions and reproductive factors: a report from the children’s oncology group. BMC Cancer. 2015;15:735.

    Article  Google Scholar 

  21. Moll AC, Imhof SM, Cruysberg JR, Schouten-van Meeteren AY, Boers M, van Leeuwen FE. Incidence of retinoblastoma in children born after in-vitro fertilisation. Lancet. 2003;361(9354):309–10.

    Article  Google Scholar 

  22. Marees T, Dommering CJ, Imhof SM, Kors WA, Ringens PJ, van Leeuwen FE, et al. Incidence of retinoblastoma in Dutch children conceived by IVF: an expanded study. Hum Reprod. 2009;24(12):3220–4.

    Article  CAS  Google Scholar 

  23. Richter S, Vandezande K, Chen N, Zhang K, Sutherland J, Anderson J, et al. Sensitive and efficient detection of RB1 gene mutations enhances care for families with retinoblastoma. Am J Hum Genet. 2003;72(2):253–69.

    Article  CAS  Google Scholar 

  24. Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, et al. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature. 1986;323(6089):643–6.

    Article  CAS  Google Scholar 

  25. de Jong MC, Kors WA, de Graaf P, Castelijns JA, Moll AC, Kivela T. The incidence of trilateral retinoblastoma: a systematic review and meta-analysis. Am J Ophthalmol. 2015;160(6):1116–26 e5.

    Article  Google Scholar 

  26. Kivela T. Trilateral retinoblastoma: a meta-analysis of hereditary retinoblastoma associated with primary ectopic intracranial retinoblastoma. J Clin Oncol. 1999;17(6):1829–37.

    Article  CAS  Google Scholar 

  27. Knudson AG Jr. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971;68(4):820–3.

    Article  Google Scholar 

  28. Knudson AG Jr. Retinoblastoma: a prototypic hereditary neoplasm. Semin Oncol. 1978;5(1):57–60.

    Google Scholar 

  29. Kivela T. 200 years of success initiated by James Wardrop’s 1809 monograph on retinoblastoma. Acta Ophthalmol. 2009;87(8):810–2.

    Article  Google Scholar 

  30. Verhoeff F, Jackson E, eds. Minutes of the proceedings. 62nd Annual Meeting Trans Am Ophthalmol Soc; 1926.

    Google Scholar 

  31. Brantley MA Jr, Harbour JW. The molecular biology of retinoblastoma. Ocul Immunol Inflamm. 2001;9(1):1–8.

    Article  CAS  Google Scholar 

  32. Ali MJ, Parsam VL, Honavar SG, Kannabiran C, Vemuganti GK, Reddy VA. RB1 gene mutations in retinoblastoma and its clinical correlation. Saudi J Ophthalmol. 2010;24(4):119–23.

    Article  Google Scholar 

  33. He MY, An Y, Gao YJ, Qian XW, Li G, Qian J. Screening of RB1 gene mutations in Chinese patients with retinoblastoma and preliminary exploration of genotype-phenotype correlations. Mol Vis. 2014;20:545–52.

    Google Scholar 

  34. Chen Z, Moran K, Richards-Yutz J, Toorens E, Gerhart D, Ganguly T, et al. Enhanced sensitivity for detection of low-level germline mosaic RB1 mutations in sporadic retinoblastoma cases using deep semiconductor sequencing. Hum Mutat. 2014;35(3):384–91.

    Article  CAS  Google Scholar 

  35. Rushlow D, Piovesan B, Zhang K, Prigoda-Lee NL, Marchong MN, Clark RD, et al. Detection of mosaic RB1 mutations in families with retinoblastoma. Hum Mutat. 2009;30(5):842–51.

    Article  CAS  Google Scholar 

  36. Dyer MA, Bremner R. The search for the retinoblastoma cell of origin. Nat Rev Cancer. 2005;5(2):91–101.

    Article  CAS  Google Scholar 

  37. Liu H, Zhang Y, Zhang YY, Li YP, Hua ZQ, Zhang CJ, et al. Human embryonic stem cell-derived organoid retinoblastoma reveals a cancerous origin. Proc Natl Acad Sci U S A. 2020;117(52):33628–38.

    Article  CAS  Google Scholar 

  38. Zhang J, Schweers B, Dyer MA. The first knockout mouse model of retinoblastoma. Cell Cycle. 2004;3(7):952–9.

    Article  CAS  Google Scholar 

  39. Ajioka I, Martins RA, Bayazitov IT, Donovan S, Johnson DA, Frase S, et al. Differentiated horizontal interneurons clonally expand to form metastatic retinoblastoma in mice. Cell. 2007;131(2):378–90.

    Article  CAS  Google Scholar 

  40. Manning AL, Longworth MS, Dyson NJ. Loss of pRB causes centromere dysfunction and chromosomal instability. Genes Dev. 2010;24(13):1364–76.

    Article  CAS  Google Scholar 

  41. Zhang J, Benavente CA, McEvoy J, Flores-Otero J, Ding L, Chen X, et al. A novel retinoblastoma therapy from genomic and epigenetic analyses. Nature. 2012;481(7381):329–34.

    Article  CAS  Google Scholar 

  42. Corson TW, Gallie BL. One hit, two hits, three hits, more? Genomic changes in the development of retinoblastoma. Genes Chromosomes Cancer. 2007;46(7):617–34.

    Article  CAS  Google Scholar 

  43. Theriault BL, Dimaras H, Gallie BL, Corson TW. The genomic landscape of retinoblastoma: a review. Clin Exp Ophthalmol. 2014;42(1):33–52.

    Article  Google Scholar 

  44. Rushlow DE, Mol BM, Kennett JY, Yee S, Pajovic S, Theriault BL, et al. Characterisation of retinoblastomas without RB1 mutations: genomic, gene expression, and clinical studies. Lancet Oncol. 2013;14(4):327–34.

    Article  CAS  Google Scholar 

  45. Inti A, Rincón-Arano H, Benítez-Bribiesca L, Recillas-Targa F. Epigenetic regulation of the human retinoblastoma tumor suppressor gene promoter by CTCF. Cancer Res. 2007;67(6):2577–85.

    Article  Google Scholar 

  46. Tosi GM, Trimarchi C, Macaluso M, La Sala D, Ciccodicola A, Lazzi S, et al. Genetic and epigenetic alterations of RB2/p130 tumor suppressor gene in human sporadic retinoblastoma: implications for pathogenesis and therapeutic approach. Oncogene. 2005;24(38):5827–36.

    Article  CAS  Google Scholar 

  47. Sakai T, Toguchida J, Ohtani N, Yandell DW, Rapaport JM, Dryja TP. Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene. Am J Hum Genet. 1991;48(5):880–8.

    CAS  Google Scholar 

  48. Price EA, Price K, Kolkiewicz K, Hack S, Reddy MA, Hungerford JL, et al. Spectrum of RB1 mutations identified in 403 retinoblastoma patients. J Med Genet. 2014;51(3):208–14.

    Article  CAS  Google Scholar 

  49. Kanber D, Berulava T, Ammerpohl O, Mitter D, Richter J, Siebert R, et al. The human retinoblastoma gene is imprinted. PLoS Genet. 2009;5(12):e1000790.

    Article  Google Scholar 

  50. Lan X, Xu W, Tang X, Ye H, Song X, Lin L, et al. Spectrum of RB1 germline mutations and clinical features in unrelated Chinese patients with retinoblastoma. Front Genet. 2020;11:142.

    Article  CAS  Google Scholar 

  51. Munier FL. Classification and management of seeds in retinoblastoma. Ellsworth lecture Ghent august 24th 2013. Ophthalmic Genet. 2014;35(4):193–207.

    Article  Google Scholar 

  52. Amram AL, Rico G, Kim JW, Chintagumpala M, Herzog CE, Gombos DS, et al. Vitreous seeds in retinoblastoma: Clinicopathologic classification and correlation. Ophthalmology. 2017;124(10):1540–7.

    Article  Google Scholar 

  53. de Jong MC, de Graaf P, Noij DP, Goricke S, Maeder P, Galluzzi P, et al. Diagnostic performance of magnetic resonance imaging and computed tomography for advanced retinoblastoma: a systematic review and meta-analysis. Ophthalmology. 2014;121(5):1109–18.

    Article  Google Scholar 

  54. Brisse HJ, Guesmi M, Aerts I, Sastre-Garau X, Savignoni A, Lumbroso-Le Rouic L, et al. Relevance of CT and MRI in retinoblastoma for the diagnosis of postlaminar invasion with normal-size optic nerve: a retrospective study of 150 patients with histological comparison. Pediatr Radiol. 2007;37(7):649–56.

    Article  Google Scholar 

  55. Marees T, Moll AC, Imhof SM, de Boer MR, Ringens PJ, van Leeuwen FE. Risk of second malignancies in survivors of retinoblastoma: more than 40 years of follow-up. J Natl Cancer Inst. 2008;100(24):1771–9.

    Article  Google Scholar 

  56. Wong FL, Boice JD Jr, Abramson DH, Tarone RE, Kleinerman RA, Stovall M, et al. Cancer incidence after retinoblastoma. Radiation Dose Sarcoma Risk JAMA. 1997;278(15):1262–7.

    CAS  Google Scholar 

  57. Albrecht P, Ansperger-Rescher B, Schüler A, Zeschnigk M, Gallie B, Lohmann D. Spectrum of gross deletions and insertions in the RB1 gene in patients with retinoblastoma and association with phenotypic expression. Hum Mutat. 2005;26(5):437–45.

    Article  CAS  Google Scholar 

  58. Chantada GL, Dunkel IJ, Qaddoumi I, Antoneli CB, Totah A, Canturk S, et al. Familial retinoblastoma in developing countries. Pediatr Blood Cancer. 2009;53(3):338–42.

    Article  Google Scholar 

  59. Skalet AH, Gombos DS, Gallie BL, Kim JW, Shields CL, Marr BP, et al. Screening children at risk for retinoblastoma: consensus report from the American Association of Ophthalmic Oncologists and Pathologists. Ophthalmology. 2018;125(3):453–8.

    Article  Google Scholar 

  60. Reese AB, Ellsworth RM. The evaluation and current concept of retinoblastoma therapy. Trans Am Acad Ophthalmol Otolaryngol. 1963;67:164–72.

    CAS  Google Scholar 

  61. Linn MA. Intraocular retinoblastoma: the case for a new group classification. Ophthalmol Clin N Am. 2005;18(1):41–53.

    Article  Google Scholar 

  62. Scelfo C, Francis JH, Khetan V, Jenkins T, Marr B, Abramson DH, et al. An international survey of classification and treatment choices for group D retinoblastoma. Int J Ophthalmol. 2017;10(6):961–7.

    Google Scholar 

  63. Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT, et al. The international classification of retinoblastoma predicts chemoreduction success. Ophthalmology. 2006;113(12):2276–80.

    Article  Google Scholar 

  64. Shields CL, Shields JA. Basic understanding of current classification and management of retinoblastoma. Curr Opin Ophthalmol. 2006;17(3):228–34.

    Article  Google Scholar 

  65. Grabowski EF, Abramson DH. Intraocular and extraocular retinoblastoma. Hematol Oncol Clin North Am. 1987;1(4):721–35.

    Article  CAS  Google Scholar 

  66. Pratt CB, Fontanesi J, Lu X, Parham DM, Elfervig J, Meyer D. Proposal for a new staging scheme for intraocular and extraocular retinoblastoma based on an analysis of 103 globes. Oncologist. 1997;2(1):1–5.

    Article  CAS  Google Scholar 

  67. Chantada G, Doz F, Antoneli CB, Grundy R, Clare Stannard FF, Dunkel IJ, et al. A proposal for an international retinoblastoma staging system. Pediatr Blood Cancer. 2006;47(6):801–5.

    Article  Google Scholar 

  68. Mallipatna A, Gallie B, Chévez-Barrios P, Lumbroso-Le Rouic L, Chantada G, Doz F, et al. Retinoblastoma. AJCC Cancer Staging Manual. 2017;8:819–31.

    Google Scholar 

  69. Tomar AS, Finger PT, Gallie B, Mallipatna A, Kivela TT, Zhang C, et al. A multicenter, international collaborative study for American joint committee on cancer staging of retinoblastoma: part II: treatment success and globe salvage. Ophthalmology. 2020;127(12):1733–46.

    Article  Google Scholar 

  70. Yousef YA, Mohammad M, Mehyar M, Sultan I, Al-Hussaini M, Alhourani J, et al. The predictive value of the eighth edition of the clinical TNM staging system for the likelihood of eye salvage for intraocular retinoblastoma by systemic chemotherapy and focal therapy. J Pediatr Hematol Oncol. 2021;

    Google Scholar 

  71. Naseripour M. “Retinoblastoma survival disparity”: the expanding horizon in developing countries. Saudi J Ophthalmol. 2012;26(2):157–61.

    Article  Google Scholar 

  72. Sant M, Capocaccia R, Badioni V, Group UW. Survival for retinoblastoma in Europe. Eur J Cancer. 2001;37(6):730–5.

    Article  CAS  Google Scholar 

  73. Global Retinoblastoma Study G, Fabian ID, Abdallah E, Abdullahi SU, Abdulqader RA, Adamou Boubacar S, et al. Global retinoblastoma presentation and analysis by National Income Level. JAMA Oncologia. 2020;6(5):685–95.

    Article  Google Scholar 

  74. Shields CL, Honavar SG, Meadows AT, Shields JA, Demirci H, Singh A, et al. Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need for treatment with external beam radiotherapy or enucleation. Am J Ophthalmol. 2002;133(5):657–64.

    Article  Google Scholar 

  75. Murphree AL, Villablanca JG, Deegan WF 3rd, Sato JK, Malogolowkin M, Fisher A, et al. Chemotherapy plus local treatment in the management of intraocular retinoblastoma. Arch Ophthalmol. 1996;114(11):1348–56.

    Article  CAS  Google Scholar 

  76. Kaliki S, Shields CL, Rojanaporn D, Al-Dahmash S, McLaughlin JP, Shields JA, et al. High-risk retinoblastoma based on international classification of retinoblastoma: analysis of 519 enucleated eyes. Ophthalmology. 2013;120(5):997–1003.

    Article  Google Scholar 

  77. Friedman DL, Krailo M, Villaluna D, Gombos D, Langholz B, Jubran R, et al. Systemic neoadjuvant chemotherapy for group B intraocular retinoblastoma (ARET0331): A report from the Children’s oncology group. Pediatr Blood Cancer. 2017;64(7)

    Google Scholar 

  78. Jubran RF, Villablanca JG, Krailo M, Piao J, Huang L, Murphree AL, et al. A single-arm study of systemic and sub-Tenon chemotherapy for groups C and D intraocular retinoblastoma: a children’s oncology group study (ARET 0231). Pediatr Blood Cancer. 2020;67(9):e28502.

    Article  CAS  Google Scholar 

  79. Chévez-Barrios P, Eagle RC Jr, Krailo M, Piao J, Albert DM, Gao Y, et al. Study of unilateral retinoblastoma with and without histopathologic high-risk features and the role of adjuvant chemotherapy: a children’s oncology group study. J Clin Oncol. 2019;37(31):2883.

    Article  Google Scholar 

  80. Dunkel IJ, Krailo MD, Chantada GL, Banerjee A, Abouelnaga S, Buchsbaum J, et al. Intensive multi-modality therapy for extra-ocular retinoblastoma (RB): a children’s oncology group (COG) trial (ARET0321). Am Soc Clin Oncol. 2017.

    Google Scholar 

  81. Beck MN, Balmer A, Dessing C, Pica A, Munier F. First-line chemotherapy with local treatment can prevent external-beam irradiation and enucleation in low-stage intraocular retinoblastoma. J Clin Oncol. 2000;18(15):2881–7.

    Article  CAS  Google Scholar 

  82. Shields CL, Lally SE, Leahey AM, Jabbour PM, Caywood EH, Schwendeman R, et al. Targeted retinoblastoma management: when to use intravenous, intra-arterial, periocular, and intravitreal chemotherapy. Curr Opin Ophthalmol. 2014;25(5):374–85.

    Article  Google Scholar 

  83. Rodriguez-Galindo C, Chantada GL, Haik BG, Wilson MW. Treatment of retinoblastoma: current status and future perspectives. Curr Treat Options Neurol. 2007;9(4):294–307.

    Article  Google Scholar 

  84. Sullivan EM, Wilson MW, Billups CA, Wu J, Merchant TE, Brennan RC, et al. Pathologic risk-based adjuvant chemotherapy for unilateral retinoblastoma following enucleation. J Pediatr Hematol Oncol. 2014;36(6):e335–40.

    Article  CAS  Google Scholar 

  85. Wilson MW, Rodriguez-Galindo C, Haik BG, Moshfeghi DM, Merchant TE, Pratt CB. Multiagent chemotherapy as neoadjuvant treatment for multifocal intraocular retinoblastoma. Ophthalmology. 2001;108(11):2106–14. discussion 14–5

    Article  CAS  Google Scholar 

  86. Rodriguez-Galindo C, Wilson MW, Haik BG, Merchant TE, Billups CA, Shah N, et al. Treatment of intraocular retinoblastoma with vincristine and carboplatin. J Clin Oncol. 2003;21(10):2019–25.

    Article  CAS  Google Scholar 

  87. Schiavetti A, Hadjistilianou T, Clerico A, Bonci E, Ragni G, Castello MA. Conservative therapy in intraocular retinoblastoma: response/recurrence rate. J Pediatr Hematol Oncol. 2005;27(1):3–6.

    Article  Google Scholar 

  88. Brennan RC, Qaddoumi I, Billups CA, Kaluzny T, Furman WL, Wilson MW. Patients with retinoblastoma and chromosome 13q deletions have increased chemotherapy-related toxicities. Pediatr Blood Cancer. 2016;63(11):1954–8.

    Article  CAS  Google Scholar 

  89. Short BG. Safety evaluation of ocular drug delivery formulations: techniques and practical considerations. Toxicol Pathol. 2008;36(1):49–62.

    Article  CAS  Google Scholar 

  90. Abramson DH, Marr BP, Dunkel IJ, Brodie S, Zabor EC, Driscoll SJ, et al. Intra-arterial chemotherapy for retinoblastoma in eyes with vitreous and/or subretinal seeding: 2-year results. Br J Ophthalmol. 2012;96(4):499–502.

    Article  Google Scholar 

  91. Francis JH, Levin AM, Zabor EC, Gobin YP, Abramson DH. Ten-year experience with ophthalmic artery chemosurgery: ocular and recurrence-free survival. PLoS One. 2018;13(5):e0197081.

    Article  Google Scholar 

  92. Ravindran K, Dalvin LA, Pulido JS, Brinjikji W. Intra-arterial chemotherapy for retinoblastoma: an updated systematic review and meta-analysis. J Neurointerv Surg. 2019;11(12):1266–72.

    Article  Google Scholar 

  93. Yousef YA, Soliman SE, Astudillo PPP, Durairaj P, Dimaras H, Chan HSL, et al. Intra-arterial chemotherapy for retinoblastoma: a systematic review. JAMA Ophthalmol. 2016;134(5):584–91.

    Article  Google Scholar 

  94. Shields CL, Gorge R, Say EA, Leahey AM, Jabbour P, Shields JA. Intra-arterial chemotherapy versus intravenous chemotherapy for unilateral retinoblastoma who wins? J Am Assoc Pediatric Ophthalmol Strabismus {JAAPOS}. 2017;21(4):e12.

    Article  Google Scholar 

  95. Shields CL, Bianciotto CG, Jabbour P, Griffin GC, Ramasubramanian A, Rosenwasser R, et al. Intra-arterial chemotherapy for retinoblastoma: report no. 2, treatment complications. Arch Ophthalmol. 2011;129(11):1407–15.

    Article  CAS  Google Scholar 

  96. 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(6):732–7.

    Article  Google Scholar 

  97. Hayden BC, Jockovich ME, Murray TG, Voigt M, Milne P, Kralinger M, 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(10):3644–9.

    Article  Google Scholar 

  98. Mendelsohn ME, Abramson DH, Madden T, Tong W, Tran HT, Dunkel IJ. Intraocular concentrations of chemotherapeutic agents after systemic or local administration. Arch Ophthalmol. 1998;116(9):1209–12.

    Article  CAS  Google Scholar 

  99. Schmack I, Hubbard GB, Kang SJ, Aaberg TM Jr, Grossniklaus HE. Ischemic necrosis and atrophy of the optic nerve after periocular carboplatin injection for intraocular retinoblastoma. Am J Ophthalmol. 2006;142(2):310–5.

    Article  CAS  Google Scholar 

  100. Mulvihill A, Budning A, Jay V, Vandenhoven C, Heon E, Gallie BL, et al. Ocular motility changes after subtenon carboplatin chemotherapy for retinoblastoma. Arch Ophthalmol. 2003;121(8):1120–4.

    Article  CAS  Google Scholar 

  101. Carcaboso AM, Chiappetta DA, Opezzo JA, Hocht C, Fandino AC, Croxatto JO, et al. Episcleral implants for topotecan delivery to the posterior segment of the eye. Invest Ophthalmol Vis Sci. 2010;51(4):2126–34.

    Article  Google Scholar 

  102. Munier FL, Gaillard MC, Balmer A, Soliman S, Podilsky G, Moulin AP, et al. Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: from prohibition to conditional indications. Br J Ophthalmol. 2012;96(8):1078–83.

    Article  Google Scholar 

  103. Kaneko A, Suzuki S. Eye-preservation treatment of retinoblastoma with vitreous seeding. Jpn J Clin Oncol. 2003;33(12):601–7.

    Article  Google Scholar 

  104. Munier FL, Soliman S, Moulin AP, Gaillard MC, Balmer A, Beck-Popovic M. Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track. Br J Ophthalmol. 2012;96(8):1084–7.

    Article  Google Scholar 

  105. Rao R, Honavar SG, Sharma V, Reddy VAP. Intravitreal topotecan in the management of refractory and recurrent vitreous seeds in retinoblastoma. Br J Ophthalmol. 2018;102(4):490–5.

    Article  Google Scholar 

  106. Rishi P, Sharma T, Agarwal V, Dhami A, Maitray A, Sharma M, et al. Complications of Intravitreal Chemotherapy in Eyes with Retinoblastoma: See Editorial on pg. 359. Ophthalmol Retina. 2017;1(5):448–50.

    Article  Google Scholar 

  107. 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(3):319–25.

    Article  Google Scholar 

  108. Yousef YA, Noureldin AM, Sultan I, Deebajah R, Al-Hussaini M, Shawagfeh M, et al. Intravitreal Melphalan chemotherapy for vitreous seeds in retinoblastoma. J Ophthalmol. 2020;2020:8628525.

    Article  Google Scholar 

  109. Ghassemi F, Shields CL. Intravitreal melphalan for refractory or recurrent vitreous seeding from retinoblastoma. Arch Ophthalmol. 2012;130(10):1268–71.

    Article  Google Scholar 

  110. Ji X, Hua P, Li J, Li J, Zhao J, Zhao P. Intravitreal Melphalan for vitreous seeds: initial experience in China. J Ophthalmol. 2016;2016:4387286.

    Article  Google Scholar 

  111. Shields CL, Santos MC, Diniz W, Gunduz K, Mercado G, Cater JR, et al. Thermotherapy for retinoblastoma. Arch Ophthalmol. 1999;117(7):885–93.

    Article  CAS  Google Scholar 

  112. Hasanreisoglu M, Saktanasate J, Schwendeman R, Shields JA, Shields CL. Indocyanine green-enhanced Transpupillary thermotherapy for retinoblastoma: analysis of 42 tumors. J Pediatr Ophthalmol Strabismus. 2015;52(6):348–54.

    Article  Google Scholar 

  113. Shields JA, Shields CL, De Potter P. Photocoagulation of retinoblastoma. Int Ophthalmol Clin. 1993;33(3):95–9.

    Article  CAS  Google Scholar 

  114. Anagnoste SR, Scott IU, Murray TG, Kramer D, Toledano S. Rhegmatogenous retinal detachment in retinoblastoma patients undergoing chemoreduction and cryotherapy. Am J Ophthalmol. 2000;129(6):817–9.

    Article  CAS  Google Scholar 

  115. Soliman SE, Bansal A, De Nicola ML, Bhambhwani V, Laperriere N, Gallie BL, et al. Applications of iodine-125 plaque radiotherapy for residual or recurrent retinoblastoma. Can J Ophthalmol. 2021;

    Google Scholar 

  116. Merchant TE, Gould CJ, Wilson MW, Hilton NE, Rodriguez-Galindo C, Haik BG. Episcleral plaque brachytherapy for retinoblastoma. Pediatr Blood Cancer. 2004;43(2):134–9.

    Article  Google Scholar 

  117. Shields CL, Shields JA, Cater J, Othmane I, Singh AD, Micaily B. Plaque radiotherapy for retinoblastoma: long-term tumor control and treatment complications in 208 tumors. Ophthalmology. 2001;108(11):2116–21.

    Article  CAS  Google Scholar 

  118. Kaste SC, Chen G, Fontanesi J, Crom DB, Pratt CB. Orbital development in long-term survivors of retinoblastoma. J Clin Oncol. 1997;15(3):1183–9.

    Article  CAS  Google Scholar 

  119. Kim JW, Kathpalia V, Dunkel IJ, Wong RK, Riedel E, Abramson DH. Orbital recurrence of retinoblastoma following enucleation. Br J Ophthalmol. 2009;93(4):463–7.

    Article  CAS  Google Scholar 

  120. Honavar SG, Singh AD, Shields CL, Meadows AT, Demirci H, Cater J, et al. Postenucleation adjuvant therapy in high-risk retinoblastoma. Arch Ophthalmol. 2002;120(7):923–31.

    Article  Google Scholar 

  121. Sastre X, Chantada GL, Doz F, Wilson MW, de Davila MT, Rodriguez-Galindo C, 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(8):1199–202.

    Article  Google Scholar 

  122. Eagle RC Jr. High-risk features and tumor differentiation in retinoblastoma: a retrospective histopathologic study. Arch Pathol Lab Med. 2009;133(8):1203–9.

    Article  Google Scholar 

  123. Marback EF, Arias VE, Paranhos A Jr, Soares FA, Murphree AL, Erwenne CM. Tumour angiogenesis as a prognostic factor for disease dissemination in retinoblastoma. Br J Ophthalmol. 2003;87(10):1224–8.

    Article  Google Scholar 

  124. Hungerford J, Kingston J, Plowman N. Orbital recurrence of retinoblastoma. Ophthalmic Paediatr Genet. 1987;8(1):63–8.

    Article  CAS  Google Scholar 

  125. Honavar SG, Singh AD. Management of advanced retinoblastoma. Ophthalmol Clin N Am. 2005;18(1):65–73.

    Article  Google Scholar 

  126. Merchant TE, Gould CJ, Hilton NE, Kun LE, Rodriguez-Galindo C, Pratt CB, et al. Ocular preservation after 36 Gy external beam radiation therapy for retinoblastoma. J Pediatr Hematol Oncol. 2002;24(4):246–9.

    Article  Google Scholar 

  127. Biewald E, Kiefer T, Geismar D, Schlüter S, Manthey A, Westekemper H, et al. Feasibility of proton beam therapy as a rescue therapy in heavily pre-treated retinoblastoma eyes. Cancers. 2021;13(8):1862.

    Article  Google Scholar 

  128. Sahgal A, Millar B-A, Michaels H, Jaywant S, Chan H, Heon E, et al. Focal stereotactic external beam radiotherapy as a vision-sparing method for the treatment of peripapillary and perimacular retinoblastoma: preliminary results. Clin Oncol. 2006;18(8):628–34.

    Article  CAS  Google Scholar 

  129. Ellsworth RM. Orbital retinoblastoma. Trans Am Ophthalmol Soc. 1974;72:79–88.

    CAS  Google Scholar 

  130. Honavar SG, Manjandavida FP, Reddy VAP. Orbital retinoblastoma: an update. Indian J Ophthalmol. 2017;65(6):435–42.

    Article  Google Scholar 

  131. Chawla B, Hasan F, Azad R, Seth R, Upadhyay AD, Pathy S, et al. Clinical presentation and survival of retinoblastoma in Indian children. Br J Ophthalmol. 2016;100(2):172–8.

    Article  Google Scholar 

  132. Kao LY, Su WW, Lin YW. Retinoblastoma in Taiwan: survival and clinical characteristics 1978-2000. Jpn J Ophthalmol. 2002;46(5):577–80.

    Article  Google Scholar 

  133. Badhu B, Sah SP, Thakur SK, Dulal S, Kumar S, Sood A, et al. Clinical presentation of retinoblastoma in Eastern Nepal. Clin Exp Ophthalmol. 2005;33(4):386–9.

    Article  Google Scholar 

  134. Singh AD, Shields CL, Shields JA. Prognostic factors in retinoblastoma. J Pediatr Ophthalmol Strabismus. 2000;37(3):134–41. quiz 68-9

    Article  CAS  Google Scholar 

  135. Hungerford J. Factors influencing metastasis in retinoblastoma. Br J Ophthalmol. 1993;77(9):541.

    Article  CAS  Google Scholar 

  136. Chawla B, Hasan F, Seth R, Pathy S, Pattebahadur R, Sharma S, et al. Multimodal therapy for stage III retinoblastoma (international retinoblastoma staging system): a prospective comparative study. Ophthalmology. 2016;123(9):1933–9.

    Article  Google Scholar 

  137. Dunkel IJ, Chan HS, Jubran R, Chantada GL, Goldman S, Chintagumpala M, et al. High-dose chemotherapy with autologous hematopoietic stem cell rescue for stage 4B retinoblastoma. Pediatr Blood Cancer. 2010;55(1):149–52.

    Google Scholar 

  138. Shields CL, Meadows AT, Shields JA, Carvalho C, Smith AF. Chemoreduction for retinoblastoma may prevent intracranial neuroblastic malignancy (trilateral retinoblastoma). Arch Ophthalmol. 2001;119(9):1269–72.

    Article  CAS  Google Scholar 

  139. Yamanaka R, Hayano A, Takashima Y. Trilateral retinoblastoma: a systematic review of 211 cases. Neurosurg Rev. 2019;42(1):39–48.

    Article  Google Scholar 

  140. Blach LE, McCormick B, Abramson DH, Ellsworth RM. Trilateral retinoblastoma--incidence and outcome: a decade of experience. Int J Radiat Oncol Biol Phys 1994;29(4):729–733.

    Google Scholar 

  141. Turcotte LM, Neglia JP, Reulen RC, Ronckers CM, Van Leeuwen FE, Morton LM, et al. Risk, risk factors, and surveillance of subsequent malignant neoplasms in survivors of childhood cancer: a review. J Clin Oncol. 2018;36(21):2145.

    Article  CAS  Google Scholar 

  142. Fidler MM, Reulen RC, Winter DL, Allodji RS, Bagnasco F, Bárdi E, et al. Risk of subsequent bone cancers among 69 460 five-year survivors of childhood and adolescent cancer in Europe. JNCI: J Nat Cancer Instit. 2018;110(2):183–94.

    Article  Google Scholar 

  143. Kleinerman RA, Tucker MA, Tarone RE, Abramson DH, Seddon JM, Stovall M, et al. Risk of new cancers after radiotherapy in long-term survivors of retinoblastoma: an extended follow-up. J Clin Oncol. 2005;23(10):2272–9.

    Article  Google Scholar 

  144. Mohney BG, Robertson DM, Schomberg PJ, Hodge DO. Second nonocular tumors in survivors of heritable retinoblastoma and prior radiation therapy. Am J Ophthalmol. 1998;126(2):269–77.

    Article  CAS  Google Scholar 

  145. Abramson DH. Second nonocular cancers in retinoblastoma: a unified hypothesis. Franceschetti Lecture Ophthalmic Genet. 1999;20(3):193–204.

    Article  CAS  Google Scholar 

  146. Fletcher O, Easton D, Anderson K, Gilham C, Jay M, Peto J. Lifetime risks of common cancers among retinoblastoma survivors. J Natl Cancer Inst. 2004;96(5):357–63.

    Article  Google Scholar 

  147. Pedersen-Bjergaard J, Andersen MT, Andersen MK. Genetic pathways in the pathogenesis of therapy-related myelodysplasia and acute myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2007:392–7.

    Google Scholar 

  148. Chauveinc L, Mosseri V, Quintana E, Desjardins L, Schlienger P, Doz F, et al. Osteosarcoma following retinoblastoma: age at onset and latency period. Ophthalmic Genet. 2001;22(2):77–88.

    Article  CAS  Google Scholar 

  149. Eng C, Li FP, Abramson DH, Ellsworth RM, Wong FL, Goldman MB, et al. Mortality from second tumors among long-term survivors of retinoblastoma. JNCI: J Nat Cancer Instit 1993;85(14):1121-1128.

    Google Scholar 

  150. Gregersen PA, Olsen MH, Urbak SF, Funding M, Dalton SO, Overgaard J, et al. Incidence and mortality of second primary cancers in danish patients with retinoblastoma, 1943–2013. JAMA Network Open. 2020;3(10):e2022126.

    Article  Google Scholar 

  151. Fontanesi J, Parham DM, Pratt C, Meyer D. Second malignant neoplasms in children with retinoblastoma: the St. Jude Children’s Research Hospital experience. Ophthalmic Genet. 1995;16(3):105–8.

    Article  CAS  Google Scholar 

  152. Group CsO. Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers. Version 3.0. http://www survivor-shipguidelines org/. 2008.

    Google Scholar 

  153. Xue K, Ren H, Meng F, Zhang R, Qian J. Ocular toxicity of intravitreal melphalan for retinoblastoma in Chinese patients. BMC Ophthalmol. 2019;19(1):1–8.

    Article  Google Scholar 

  154. Chodick G, Kleinerman RA, Stovall M, Abramson DH, Seddon JM, Smith SA, et al. Risk of cataract extraction among adult retinoblastoma survivors. Arch Ophthalmol. 2009;127(11):1500–4.

    Article  Google Scholar 

  155. Watts P, Westall C, Colpa L, MacKeen L, Abdolell M, Gallie B, et al. Visual results in children treated for macular retinoblastoma. Eye. 2002;16(1):75–80.

    Article  CAS  Google Scholar 

  156. Fabian ID, Stacey AW, Naeem Z, Onadim Z, Chowdhury T, Duncan C, et al. Strabismus in retinoblastoma survivors with long-term follow-up. J Am Assoc Pediatric Ophthalmol Strabismus. 2018;22(4):276.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. St. Jude Children’s Research Hospital, Memphis, TN, USA

    Jacquelyn F. Laplant

  2. University of Tennessee Health Science Center, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Ilyse I. Kornblau

  3. Department of Vitreoretinal Surgery and Ocular Oncology, University of Tennessee Health Science Center, Memphis, TN, USA

    Benjamin A. King

  4. Department of Ocular Oncology and Ophthalmic Plastic and Reconstructive Surgery, St. Jude Children’s Research Hospital, University of Tennessee Health Science Center, Memphis, TN, USA

    Matthew W. Wilson

Authors
  1. Jacquelyn F. Laplant
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ilyse I. Kornblau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Benjamin A. King
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Matthew W. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jacquelyn F. Laplant .

Editor information

Editors and Affiliations

  1. University of Oxford, Oxford, UK

    Kokila Lakhoo

  2. St. Jude Children's Research Hospital, Memphis, TN, USA

    Abdelhafeez H. Abdelhafeez

  3. Federal University of Sao Paulo, Sao Paulo, Brazil

    Simone Abib

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Laplant, J.F., Kornblau, I.I., King, B.A., Wilson, M.W. (2022). Retinoblastoma. In: Lakhoo, K., Abdelhafeez, A.H., Abib, S. (eds) Pediatric Surgical Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-71113-9_101-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-71113-9_101-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-71113-9

  • Online ISBN: 978-3-030-71113-9

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation