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Treatment of retinoblastoma: Current status and future perspectives

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Treatment of retinoblastoma must be individualized. Most patients with unilateral, non-metastatic retinoblastoma can be cured with enucleation alone. In patients with histologic risk factors, adjuvant chemotherapy is recommended, with the addition of orbital radiation for patients with trans-scleral involvement or tumor present at the level of the cut end of the optic nerve. Patients with metastases require intensive chemotherapy and consolidation with autologous hematopoietic stem cell rescue. Patients with bilateral or multifocal disease represent a major challenge. Cure of the disease is the first priority, but the therapeutic approach also has to consider eye and vision preservation. The approach is conservative, and only eyes with very advanced disease are enucleated upfront. Patients are treated with chemotherapy and intensive focal treatments, with the aim of delaying or avoiding radiation therapy and enucleation. For patients with early intraocular stage (Reese-Ellsworth groups I-III and International Groups A-B), the two-drug combination of vincristine and carboplatin is recommended. Patients with more advanced intraocular disease (Reese-Ellsworth groups IV-V and International Groups C-D) require more intensive chemotherapy. Standard of care for these patients incorporates etoposide into the regimen. Effective agents with good intraocular penetration, such as topotecan, are being investigated. Because most failures are secondary to progression of the vitreous seeds, subconjunctival carboplatin is added in cases with poor response of the vitreous tumors. Patients must be monitored very closely, with examinations under anesthesia every 4 to 6 weeks, and focal treatments are applied during the procedure. These include cryotherapy for small anterior tumors, thermotherapy and laser photocoagulation for small posterior tumors, and brachytherapy for larger tumors. New treatment approaches under development include the refinement of periocular chemotherapy administration using slow-release devices, the use of suicide gene therapy with local delivery of the herpes simplex thyrosine kinase gene (followed by systemic administration of ganciclovir), and the development of smallmolecule inhibitors of the MDMX-p53 interaction.

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References and Recommended Reading

  1. Young JL, Smith MA, Roffers SD, et al.: Retinoblastoma. In Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program 1975–1995. NIH Pub. No. 99-4649. Edited by Ries LA. Bethesda, MD: National Cancer Institute, SEER Program; 1999:73–78.

    Google Scholar 

  2. Richter S, Vandezande K, Chen N, et al.: Sensitive and efficient detection of RB1 gene mutations enhances care for families with retinoblastoma. Am J Hum Genet 2003, 72:253–269.

    Article  PubMed  CAS  Google Scholar 

  3. Laurie NA, Donovan SL, Shih CS, et al.: Inactivation of the p53 pathway in retinoblastoma. Nature 2006, 444:61–66.

    Article  PubMed  CAS  Google Scholar 

  4. Draper GJ, Sanders BM, Brownhill PA, Hawkins MM: Patterns of risk of hereditary retinoblastoma and applications to genetic counseling. Br J Cancer 1992, 66:211–219.

    PubMed  CAS  Google Scholar 

  5. Abramson DH, Frank CM, Susman M, et al.: Presenting signs of retinoblastoma. J Pediatr 1998, 132:505–508.

    Article  PubMed  CAS  Google Scholar 

  6. Murphree AL: Intraocular retinoblastoma: the case for a new group classification. Ophthalmol Clin N Am 2005, 18:41–53.

    Article  Google Scholar 

  7. Shields CL, Mashayekhi A, Au AK, et al.: The international classification of retinoblastoma predicts chemoreduction success. Ophthalmology 2006, 113:2276–2280.

    Article  PubMed  Google Scholar 

  8. Chantada G, Doz F, Antonelli CBG, et al.: A proposal for an international retinoblastoma staging system. Pediatr Blood Cancer 2006, 47:801–805.

    Article  PubMed  Google Scholar 

  9. 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, 77:1206–1213.

    Article  PubMed  CAS  Google Scholar 

  10. Chantada G, Fandiño A, Dávila MTG, et al.: Results of a prospective study for the treatment of retinoblastoma. Cancer 2004, 100:834–842.

    Article  PubMed  CAS  Google Scholar 

  11. Shields CL, Shields JA: Recent developments in the management of retinoblastoma. J Pediatr Ophthalmol Strabismus 1999, 36:8–18.

    PubMed  CAS  Google Scholar 

  12. Uusitalo MS, Van Quill KR, Scott IU, et al.: Evaluation of chemoprophylaxis in patients with unilateral retinoblastoma with high-risk features on histopathologic examination. Arch Ophthalmol 2001, 119:41–48.

    PubMed  CAS  Google Scholar 

  13. Honavar SG, Singh AD, Shields CL, et al.: Postenucleation adjuvant therapy in high-risk retinoblastoma. Arch Ophthalmol 2002, 120:923–931.

    PubMed  Google Scholar 

  14. Mohney BG, Robertson DM, Schomberg PJ, Hodge DO: Second nonocular tumors in survivors of heritable retinoblastoma and prior radiation therapy. Am J Ophthalmol 1998, 126:269–277.

    Article  PubMed  CAS  Google Scholar 

  15. Kaste SC, Chen G, Fontanesi J, et al.: Orbital development in long-term survivors of retinoblastoma. J Clin Oncol 1997, 15:1183–1189.

    PubMed  CAS  Google Scholar 

  16. Shields CL, Honavar SG, Meadows AT, et al.: Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need for treatment with external beam radiotherapy or enucleation. Am J Ophthalmol 2002, 133:657–664.

    Article  PubMed  Google Scholar 

  17. Nenadov Beck M, Balmer A, Dessing C, et al.: First-line chemotherapy with local treatment can prevent external-beam irradiation and enucleation in low-stage intraocular retinoblastoma. J Clin Oncol 2000, 18:2881–2887.

    Google Scholar 

  18. Wilson MW, Haik BG, Liu T, et al.: Effect on ocular survival of adding early intensive focal treatments to a two-drug chemotherapy regimen in patients with retinoblastoma. Am J Ophthalmol 2005, 140:397–406.

    PubMed  CAS  Google Scholar 

  19. Chantada GL, Fandiño A, Raslawski EC, et al.: Experience with chemoreduction and focal therapy for intraocular retinoblastoma in a developing country. Pediatr Blood Cancer 2005, 44:455–460.

    Article  PubMed  Google Scholar 

  20. Rodriguez-Galindo C, Wilson MW, Haik BG, et al.: Treatment of intraocular retinoblastoma with vincristine and carboplatin. J Clin Oncol 2003, 21:2019–2025.

    Article  PubMed  CAS  Google Scholar 

  21. Gallie BL, Budning A, DeBoer G, et al.: Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy. Arch Ophthalmol 1996, 114:1321–1328.

    PubMed  CAS  Google Scholar 

  22. Friedman DL, Himelstein B, Shields CL, et al.: Chemoreduction and local ophthalmic therapy for intraocular retinoblastoma. J Clin Oncol 2000, 18:12–17.

    PubMed  CAS  Google Scholar 

  23. Mendelsohn ME, Abramson DH, Madden T, et al.: Intraocular concentrations of chemotherapeutic agents after systemic or local administration. Arch Ophthalmol 1998, 116:1209–1212.

    PubMed  CAS  Google Scholar 

  24. Murray TG, Cicciarelli N, O’Brien JM, et al.: Subconjunctival carboplatin therapy and cryotherapy in the treatment of transgenic murine retinoblastoma. Arch Ophthalmol 1997, 115:1286–1290.

    PubMed  CAS  Google Scholar 

  25. Hayden BH, Murray TG, Scott IU, et al.: Subconjunctival carboplatin in retinoblastoma. Impact of tumor burden and dose schedule. Arch Ophthalmol 2000, 118:1549–1554.

    PubMed  CAS  Google Scholar 

  26. Abramson D, Frank CM, Dunkel IJ: A phase I/II study of subconjunctival carboplatin for intraocular retinoblastoma. Ophthalmology 1999, 106:1947–1950.

    Article  PubMed  CAS  Google Scholar 

  27. Schmack I, Hubbard B, Kang SJ, et al.: Ischemic necrosis and atrophy of the optic nerve after periocular carboplatin injection for intraocular retinoblastoma. Am J Ophthalmol 2006, 142:310–315.

    Article  PubMed  CAS  Google Scholar 

  28. Scott IU, Murray TG, Feuer WJ, et al.: External beam radiotherapy in retinoblastoma. Tumor control and comparison of 2 techniques. Arch Ophthalmol 1999, 117:766–770.

    PubMed  CAS  Google Scholar 

  29. Hungerford JL, Toma NMG, Plowman PN, Kingston JE: External beam radiotherapy for retinoblastoma: I. Whole eye technique. Br J Ophthalmol 1995, 79:109–111.

    Article  PubMed  CAS  Google Scholar 

  30. Toma NMG, Hungerford JL, Plowman PN, et al.: External beam radiotherapy for retinoblastoma: II. Lens sparing technique. Br J Ophthalmol 1995, 79:112–117.

    Article  PubMed  CAS  Google Scholar 

  31. Gombos DS, Kelly A, Coen PG, et al.: Retinoblastoma treated with primary chemotherapy alone: the significance of tumor size, location, and age. Br J Ophthalmol 2002, 86:80–83.

    Article  PubMed  Google Scholar 

  32. Schefler AC, Cicciarelli N, Feuer W, et al.: Macular retinoblastoma: evaluation of tumor control, local complications, and visual outcomes for eyes treated with chemotherapy and repetitive foveal laser ablation. Ophthalmology 2007, 114:162–169.

    Article  PubMed  Google Scholar 

  33. Shields CL, Honavar SG, Shields JA, et al.: Factors predictive of recurrence of retinal tumors, vitreous seeds, and subretinal seeds following chemoreduction for retinoblastoma. Arch Ophthalmol 2002, 120:460–464.

    PubMed  Google Scholar 

  34. Kingston JE, Hungerford JL, Madreperla SA, Plowman PN: Results of combined chemotherapy and radiotherapy for advanced intraocular retinoblastoma. Arch Ophthalmol 1996, 114:1339–1343.

    PubMed  CAS  Google Scholar 

  35. Jubran RF, Erdreich-Epstein A, Butturini A, et al.: Approaches to treatment for extraocular retinoblastoma. Children’s Hospital Los Angeles experience. J Pediatr Hematol Oncol 2004, 26:31–34.

    Article  PubMed  Google Scholar 

  36. Menon BS, Reddy SC, Maziah W, et al.: Extraocular retinoblastoma. Med Pediatr Oncol 2000, 35:75–76.

    Article  PubMed  CAS  Google Scholar 

  37. Doz F, Khelfaoui F, Mosseri V, et al.: The role of chemotherapy in orbital involvement of retinoblastoma. Cancer 1994, 74:722–732.

    Article  PubMed  CAS  Google Scholar 

  38. Chantada GL, Rossi J, Casco F, et al.: An aggressive bone marrow evaluation including immunocytology with GD2 for advanced retinoblastoma. J Pediatr Hematol Oncol 2006, 28:369–373.

    Article  PubMed  Google Scholar 

  39. Doz F, Neuenschwander S, Plantaz D, et al.: Etoposide and carboplatin in extraocular retinoblastoma: a study by the Société Française d’Oncologie Pédiatrique. J Clin Oncol 1995, 13:902–909.

    PubMed  CAS  Google Scholar 

  40. Antonelli CBG, Steinhorst F, Ribeiro KCB, et al.: Extraocular retinoblastoma: a 13-year experience. Cancer 2003, 98:1292–1298.

    Article  Google Scholar 

  41. Chantada G, Fandiño A, Casak S, et al.: Treatment of overt extraocular retinoblastoma. Med Pediatr Oncol 2003, 40:158–161.

    Article  PubMed  Google Scholar 

  42. Gündüz K, Muftuoglu O, Gunalp I, et al.: Metastatic retinoblastoma: clinical features, treatment, and prognosis. Ophthalmology 2006, 113:1558–1566.

    Article  PubMed  Google Scholar 

  43. Matsubara H, Makimoto A, Higa T, et al.: Multidisciplinary treatment strategy that includes high-dose chemotherapy for metastatic retinoblastoma without CNS involvement. Bone Marrow Transplant 2005, 35:763–766.

    Article  PubMed  CAS  Google Scholar 

  44. Blaney SM, Heideman R, Berg S, et al.: Phase I clinical trial of intrathecal topotecan in patients with neoplastic meningitis. J Clin Oncol 2003, 21:143–147.

    Article  PubMed  CAS  Google Scholar 

  45. Fisher PG, Kadan-Lottick NS, Koroner DN: Intrathecal thiotepa: reappraisal of an established therapy. J Pediatr Hematol Oncol 2002, 24:274–278.

    Article  PubMed  Google Scholar 

  46. Dunkel IJ, Aledo A, Kernan NA, et al.: Successful treatment of metastatic retinoblastoma. Cancer 2000, 89:2117–2121.

    Article  PubMed  CAS  Google Scholar 

  47. Namouni F, Doz F, Tanguy ML, et al.: High-dose chemotherapy with carboplatin, etoposide and cyclophosphamide followed by a haematopoietic stem cell rescue in patients with high-risk retinoblastoma: a SFOP and SFGM study. Eur J Cancer 1997, 33:2368–2375.

    Article  PubMed  CAS  Google Scholar 

  48. Kremens B, Wieland R, Reinhard H, et al.: High-dose chemotherapy with autologous stem cell rescue in children with retinoblastoma. Bone Marrow Transplant 2003, 31:281–284.

    Article  PubMed  CAS  Google Scholar 

  49. Rodriguez-Galindo C, Wilson MW, Haik BG, et al.: Treatment of metastatic retinoblastoma. Ophthalmology 2003, 110:1237–1240.

    Article  PubMed  Google Scholar 

  50. Laurie NA, Gray JK, Zhang J, et al.: Topotecan combination chemotherapy in two new rodent models of retinoblastoma. Clin Cancer Res 2005, 11:7569–7578.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  52. Rodriguez-Galindo C, Radomski KM, Stewart CF, et al.: Clinical use of topoisomerase I inhibitors in anticancer treatment. Med Pediatr Oncol 2000, 35:385–402.

    Article  PubMed  CAS  Google Scholar 

  53. Baker SD, Heideman RL, Crom WR, et al.: Cerebrospinal fluid pharmacokinetics and penetration of continuous infusion topotecan in children with central nervous system tumors. Cancer Chemother Pharmacol 1996, 37:195–202.

    Article  PubMed  CAS  Google Scholar 

  54. Athale UH, Stewart C, Kuttesch JF, et al.: Phase I study of combination topotecan and carboplatin in pediatric solid tumors. J Clin Oncol 2001, 20:88–95.

    Article  Google Scholar 

  55. Carcaboso AM, Bramuglia G, Chantada GL, et al.: Topotecan enters the vitreous after periocular or intravenous delivery in rabbits: an alternative for retinoblastoma chemotherapy. Invest Ophthalmol Vis Sci 2007, In press.

  56. Gorodetsky R, Peylan-Ramu N, Reshef A, et al.: Interactions of carboplatin with fibrin(ogen), implications for local slow release chemotherapy. J Control Rel 2005, 102:235–245.

    Article  CAS  Google Scholar 

  57. Chevez-Barrios P, Chintagumpala M, Mieler W, et al.: Response of retinoblastoma with vitreous tumor seeding to adenovirus-mediated delivery of thymidine kinase followed by gancyclovir. J Clin Oncol 2005, 23:7927–7935.

    Article  PubMed  CAS  Google Scholar 

  58. 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.

    Article  PubMed  Google Scholar 

  59. Shields CL, Mashayekhi A, Sun H, et al.: Iodine 125 plaque radiotherapy as salvage treatment for retinoblastoma recurrence after chemoreduction in 84 tumors. Ophthalmology 2006, 113:2087–2092.

    Article  PubMed  Google Scholar 

  60. Schouten-van Meeteren AYN, Moll AC, Imhof SM, Veerman AJP: Chemotherapy for retinoblastoma: an expanding area of clinical research. Med Pediatr Oncol 2002, 38:428–438.

    Article  PubMed  CAS  Google Scholar 

  61. Levy C, Doz F, Quintana E, et al.: Role of chemotherapy alone or in combination with hyperthermia in the primary treatment of intraocular retinoblastoma: preliminary results. Br J Ophthalmol 1998, 82:1154–1158.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, St. Jude Children’s Research Hospital, 332 N. Lauderdale, Memphis, TN, 38105, USA

    Carlos Rodriguez-Galindo MD

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  1. Carlos Rodriguez-Galindo MD
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  2. Guillermo L. Chantada MD
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  3. Barrett G. Haik MD
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  4. Matthew W. Wilson MD
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Correspondence to Carlos Rodriguez-Galindo MD.

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Rodriguez-Galindo, C., Chantada, G.L., Haik, B.G. et al. Treatment of retinoblastoma: Current status and future perspectives. Curr Treat Options Neurol 9, 294–307 (2007). https://doi.org/10.1007/s11940-007-0015-4

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