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Management of High-Risk Retinoblastoma

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Part of the Essentials in Ophthalmology book series (ESSENTIALS)

Abstract

Invasion to the choroid, the sclera, and the optic nerve all constitute risk factors for extraocular relapse detected in enucleated eyes with retinoblastoma. Specifically, different degrees of invasion to these structures are associated with different risk and adjuvant therapy is tailored according to their presence. The relapse risk of children with isolated choroidal invasion is lower than 6 %, even in the higher risk subgroups with massive invasion and up to two thirds of those who relapse may be retrieved with intensive therapy. Hence, some groups use adjuvant therapy to further reduce the rate of extraocular relapse, while others do not give any treatment after enucleation. Most groups use adjuvant chemotherapy for children with postlaminar optic nerve invasion, but those with minor degrees of invasion may not need it. Since the relapse rate of these patients is low, the decision to use adjuvant therapy should be balanced in each setting with the possibility of fatal toxicities associated to chemotherapy.

Most groups use adjuvant therapy for those with scleral invasion and those with tumor at the resection margin of the optic nerve and more intensive regimens or orbital radiotherapy are recommended. Relapse in the central nervous system is the most common site for extraocular relapse in children receiving adjuvant therapy and it may become a sanctuary site when lower doses or drugs with low penetration to the cerebrospinal fluid are used. Molecular studies to determine the kinetics of minimal disease dissemination may provide more information.

Keywords

Retinoblastoma Optic nerve Choroid Scleral Pathology Chemotherapy Metastasis 

Notes

Compliance with Ethical Requirements

Guillermo L. Chantada and Maria T.G. de Davila declare that they have no conflict of interest.

No human or animal studies were carried out by the authors for this article.

References

  1. Abramson DH. Retinoblastoma: saving life with vision. Annu Rev Med. 2014;65:171–84. doi:10.1146/annurev-med-061312-123455.CrossRefPubMedGoogle Scholar
  2. Aerts I, Sastre-Garau X, Savignoni A, Lumbroso-Le Rouic L, Thebaud-Leculee E, Frappaz D, et al. Results of a multicenter prospective study on the postoperative treatment of unilateral retinoblastoma after primary enucleation. J Clin Oncol. 2013;31(11):1458–63. doi: 10.1200/JCO.2012.42.3962.CrossRefPubMedGoogle Scholar
  3. Antoneli CB, Steinhorst F, de Cassia Braga Ribeiro K, Novaes PE, Chojniak MM, Arias V, et al. Extraocular retinoblastoma: a 13-year experience. Cancer. 2003;98(6):1292–8. doi: 10.1002/cncr.11647.CrossRefPubMedGoogle Scholar
  4. Antoneli CB, Ribeiro KB, Rodriguez-Galindo C, Soares FA, Arias VA, Novaes PE, 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(10):700–4. doi: 10.1097/MPH.0b013e31814fb7ea.CrossRefPubMedGoogle Scholar
  5. Beiske K, Burchill SA, Cheung IY, Hiyama E, Seeger RC, Cohn SL, et al. Consensus criteria for sensitive detection of minimal neuroblastoma cells in bone marrow, blood and stem cell preparations by immunocytology and QRT-PCR: recommendations by the International Neuroblastoma Risk Group Task Force. Br J Cancer. 2009;100(10):1627–37. doi: 10.1038/sj.bjc.6605029.CrossRefPubMedCentralPubMedGoogle Scholar
  6. Bellaton E, Bertozzi AI, Behar C, Chastagner P, Brisse H, Sainte-Rose C, et al. Neoadjuvant chemotherapy for extensive unilateral retinoblastoma. Br J Ophthalmol. 2003;87(3):327–9.CrossRefPubMedCentralPubMedGoogle Scholar
  7. Biojone E, Queiroz Rde P, Valera ET, Odashima NS, Takayanagui OM, Viana MB, et al. Minimal residual disease in cerebrospinal fluid at diagnosis: a more intensive treatment protocol was able to eliminate the adverse prognosis in children with acute lymphoblastic leukemia. Leuk Lymphoma. 2012;53(1):89–95. doi: 10.3109/10428194.2011.606939.CrossRefPubMedGoogle Scholar
  8. Bosaleh A, Sampor C, Solernou V, Fandino A, Dominguez J, de Davila MT, et al. Outcome of children with retinoblastoma and isolated choroidal invasion. Arch Ophthalmol. 2012;130(6):724–9. doi: 10.1001/archophthalmol.2012.567.CrossRefPubMedGoogle Scholar
  9. Chantada G, Fandino A, Davila MT, Manzitti J, Raslawski E, Casak S, et al. Results of a prospective study for the treatment of retinoblastoma. Cancer. 2004a;100(4):834–42. doi: 10.1002/cncr.11952.CrossRefPubMedGoogle Scholar
  10. Chantada GL, Dunkel IJ, de Davila MT, Abramson DH. Retinoblastoma patients with high risk ocular pathological features: who needs adjuvant therapy? Br J Ophthalmol. 2004b;88(8):1069–73. doi: 10.1136/bjo.2003.037044.CrossRefPubMedCentralPubMedGoogle Scholar
  11. Chantada GL, Casco F, Fandino AC, Galli S, Manzitti J, Scopinaro M, et al. Outcome of patients with retinoblastoma and postlaminar optic nerve invasion. Ophthalmology. 2007a;114(11):2083–9. doi: 10.1016/j.ophtha.2007.01.012.CrossRefPubMedGoogle Scholar
  12. Chantada GL, Dunkel IJ, Antoneli CB, de Davila MT, Arias V, Beaverson K, et al. Risk factors for extraocular relapse following enucleation after failure of chemoreduction in retinoblastoma. Pediatr Blood Cancer. 2007b;49(3):256–60. doi: 10.1002/pbc.21067.CrossRefPubMedGoogle Scholar
  13. Chantada GL, Gonzalez A, Fandino A, de Davila MT, Demirdjian G, Scopinaro M, et al. Some clinical findings at presentation can predict high-risk pathology features in unilateral retinoblastoma. J Pediatr Hematol Oncol. 2009a;31(5):325–9. doi: 10.1097/MPH.0b013e3181923cc5.CrossRefPubMedGoogle Scholar
  14. Chantada GL, Guitter MR, Fandino AC, Raslawski EC, de Davila MT, Vaiani E, et al. Treatment results in patients with retinoblastoma and invasion to the cut end of the optic nerve. Pediatr Blood Cancer. 2009b;52(2):218–22. doi: 10.1002/pbc.21735.CrossRefPubMedGoogle Scholar
  15. Chantada GL, Fandino AC, Guitter MR, Raslawski EC, Dominguez JL, Manzitti J, et al. Results of a prospective study for the treatment of unilateral retinoblastoma. Pediatr Blood Cancer. 2010;55(1):60–6. doi: 10.1002/pbc.22503.PubMedGoogle Scholar
  16. Chantada G, Luna-Fineman S, Sitorus RS, Kruger M, Israels T, Leal-Leal C, et al. SIOP-PODC recommendations for graduated-intensity treatment of retinoblastoma in developing countries. Pediatr Blood Cancer. 2013a;60(5):719–27. doi: 10.1002/pbc.24468.CrossRefPubMedGoogle Scholar
  17. 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. 2013b;131(9):1127–34. doi: 10.1001/jamaophthalmol.2013.260.CrossRefPubMedGoogle Scholar
  18. 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(5):821–6. doi: 10.1002/pbc.24857.CrossRefPubMedGoogle Scholar
  19. Cuenca A, Giron F, Castro D, Fandino A, Guitter M, de Davila MT, et al. Microscopic scleral invasion in retinoblastoma: clinicopathological features and outcome. Arch Ophthalmol. 2009;127(8):1006–10. doi: 10.1001/archophthalmol.2009.174.CrossRefPubMedGoogle Scholar
  20. de Graaf P, Goricke S, Rodjan F, Galluzzi P, Maeder P, Castelijns JA, et al. Guidelines for imaging retinoblastoma: imaging principles and MRI standardization. Pediatr Radiol. 2012;42(1):2–14. doi: 10.1007/s00247-011-2201-5.CrossRefPubMedCentralPubMedGoogle Scholar
  21. Dimaras H, Rushlow D, Halliday W, Doyle JJ, Babyn P, Abella EM, et al. Using RB1 mutations to assess minimal residual disease in metastatic retinoblastoma. Transl Res. 2010;156(2):91–7. doi: 10.1016/j.trsl.2010.05.009.CrossRefPubMedGoogle Scholar
  22. Dimaras H, Kimani K, Dimba EA, Gronsdahl P, White A, Chan HS, et al. Retinoblastoma. Lancet. 2012;379(9824):1436–46. doi: 10.1016/S0140-6736(11)61137-9.CrossRefPubMedGoogle Scholar
  23. Eagle Jr RC. High-risk features and tumor differentiation in retinoblastoma: a retrospective histopathologic study. Arch Pathol Lab Med. 2009;133(8):1203–9. doi: 10.1043/1543-2165-133.8.1203.PubMedGoogle Scholar
  24. Edry Botzer L, Maman S, Sagi-Assif O, Meshel T, Nevo I, Bauerle T, et al. Lung-residing metastatic and dormant neuroblastoma cells. Am J Pathol. 2011;179(1):524–36. doi: 10.1016/j.ajpath.2011.03.020.CrossRefPubMedCentralPubMedGoogle Scholar
  25. Friedman DN, Sklar CA, Oeffinger KC, Kernan NA, Khakoo Y, Marr BP, 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(4):694–9. doi: 10.1002/pbc.24280.CrossRefPubMedGoogle Scholar
  26. Kaliki S, Shields CL, Shah SU, Eagle Jr RC, Shields JA, Leahey A. Postenucleation adjuvant chemotherapy with vincristine, etoposide, and carboplatin for the treatment of high-risk retinoblastoma. Arch Ophthalmol. 2011;129(11):1422–7. doi: 10.1001/archophthalmol.2011.289.CrossRefPubMedGoogle Scholar
  27. 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. doi: 10.1016/j.ophtha.2012.10.044.CrossRefPubMedGoogle Scholar
  28. Kashyap S, Meel R, Pushker N, Sen S, Bakhshi S, Sreenivas V, et al. Clinical predictors of high risk histopathology in retinoblastoma. Pediatr Blood Cancer. 2012a;58(3):356–61. doi: 10.1002/pbc.23239.CrossRefPubMedGoogle Scholar
  29. Kashyap S, Sethi S, Meel R, Pushker N, Sen S, Bajaj MS, et al. A histopathologic analysis of eyes primarily enucleated for advanced intraocular retinoblastoma from a developing country. Arch Pathol Lab Med. 2012b;136(2):190–3. doi: 10.5858/arpa.2010-0759-OA.CrossRefPubMedGoogle Scholar
  30. Killer HE, Flammer J, Miller NR. Glaucoma and cerebrospinal fluid pressure. Ophthalmology. 2008;115(12):2316–7. doi: 10.1016/j.ophtha.2008.06.037. author reply 7.CrossRefPubMedGoogle Scholar
  31. Laurent VE, Sampor C, Solernou V, Rossi J, Gabri M, Eandi-Eberle S, 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(13):2892–9. doi: 10.1016/j.ejca.2013.04.021.CrossRefPubMedGoogle Scholar
  32. 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(11):1487–9. doi: 10.1001/archophthalmol.2011.304.CrossRefPubMedGoogle Scholar
  33. Linn Murphree A. Intraocular retinoblastoma: the case for a new group classification. Ophthalmol Clin North Am. 2005;18(1):41–53, viii. doi:10.1016/j.ohc.2004.11.003.Google Scholar
  34. Magramm I, Abramson DH, Ellsworth RM. Optic nerve involvement in retinoblastoma. Ophthalmology. 1989;96(2):217–22.CrossRefPubMedGoogle Scholar
  35. Potter SL, Berg S, Ingle AM, Krailo M, Adamson PC, Blaney SM. Phase 2 clinical trial of intrathecal topotecan in children with refractory leptomeningeal leukemia: a Children’s Oncology Group trial (P9962). Pediatr Blood Cancer. 2012;58(3):362–5. doi: 10.1002/pbc.23317.CrossRefPubMedCentralPubMedGoogle Scholar
  36. 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(1):52–8. doi: 10.1136/bjophthalmol-2012-301977.CrossRefPubMedGoogle Scholar
  37. Rubin CM, Robison LL, Cameron JD, Woods WG, Nesbit Jr ME, Krivit W, et al. Intraocular retinoblastoma group V: an analysis of prognostic factors. J Clin Oncol. 1985;3(5):680–5.PubMedGoogle Scholar
  38. 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. doi: 10.1043/1543-2165-133.8.1199.PubMedGoogle Scholar
  39. 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(9):544–8.CrossRefPubMedCentralPubMedGoogle Scholar
  40. Shields CL, Shields JA, Baez K, Cater JR, De Potter P. Optic nerve invasion of retinoblastoma. Metastatic potential and clinical risk factors. Cancer. 1994;73(3):692–8.CrossRefPubMedGoogle Scholar
  41. 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. doi: 10.1016/j.ophtha.2006.06.018.CrossRefPubMedGoogle Scholar
  42. Stannard C, Lipper S, Sealy R, Sevel D. Retinoblastoma: correlation of invasion of the optic nerve and choroid with prognosis and metastases. Br J Ophthalmol. 1979;63(8):560–70.CrossRefPubMedCentralPubMedGoogle Scholar
  43. Stannard C, Sealy R, Hering E, Hough J, Knowles R, Lecuona K, et al. Postenucleation orbits in retinoblastoma: treatment with 125I brachytherapy. Int J Radiat Oncol Biol Phys. 2002;54(5):1446–54.CrossRefPubMedGoogle Scholar
  44. 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. doi: 10.1097/MPH.0000000000000141.CrossRefPubMedCentralPubMedGoogle Scholar
  45. Torbidoni AV, Laurent VE, Sampor C, Ottaviani D, Vazquez V, Gabri MR, Rossi J, de Dávila MT, Alonso C, Alonso DF, Chantada GL. Association of Cone-Rod Homeobox Transcription Factor Messenger RNA With Pediatric Metastatic Retinoblastoma. JAMA Ophthalmol. 2015 2015. doi:  10.1001/jamaophthalmol.2015.0900 [Epub ahead of print].
  46. Wilson MW, Qaddoumi I, Billups C, Haik BG, Rodriguez-Galindo C. clinicopathological correlation of 67 eyes primarily enucleated for advanced intraocular retinoblastoma. Br J Ophthalmol. 2011;95(4):553–8. doi: 10.1136/bjo.2009.177444.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Hematology/OncologyHospital JP GarrahanBuenos AiresArgentina
  2. 2.Department of OncologyHospital Sant Joan de DéuBarcelonaSpain
  3. 3.Department of PathologyHospital JP GarrahanBuenos AiresArgentina

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