Retinoblastoma natural history, complications, and prognosis: Difference between revisions

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==Prognosis==
==Prognosis==
*Those with heritable form of the disease have 50% risk of transmitting the mutation to their offspring.<ref name="pmid15637391">{{cite journal |vauthors=Garber JE, Offit K |title=Hereditary cancer predisposition syndromes |journal=J. Clin. Oncol. |volume=23 |issue=2 |pages=276–92 |date=January 2005 |pmid=15637391 |doi=10.1200/JCO.2005.10.042 |url=}}</ref>
*Prognosis is generally good, and the survival rate of patients with retinoblastoma with treatment is approximately 95%, in the United States.<ref name="pmid19477707">{{cite journal| author=Lin P, O'Brien JM| title=Frontiers in the management of retinoblastoma. | journal=Am J Ophthalmol | year= 2009 | volume= 148 | issue= 2 | pages= 192-8 | pmid=19477707 | doi=10.1016/j.ajo.2009.04.004 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19477707  }} </ref> However, the prognosis for eye salvage is far less and  usually depends on the stage of retinoblastoma at diagnosis.
*Prognosis is generally good, and the survival rate of patients with retinoblastoma with treatment is approximately 95%, in the United States.<ref name="pmid19477707">{{cite journal| author=Lin P, O'Brien JM| title=Frontiers in the management of retinoblastoma. | journal=Am J Ophthalmol | year= 2009 | volume= 148 | issue= 2 | pages= 192-8 | pmid=19477707 | doi=10.1016/j.ajo.2009.04.004 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19477707  }} </ref> However, the prognosis for eye salvage is far less and  usually depends on the stage of retinoblastoma at diagnosis.
*The one year to eighteen month survival rates in patients with hematogenous [[metastases]] are approximately 50 percent.<ref name="pmid3746592">{{cite journal| author=Abramson DH, Ellsworth RM, Grumbach N, Sturgis-Buckhout L, Haik BG| title=Retinoblastoma: correlation between age at diagnosis and survival. | journal=J Pediatr Ophthalmol Strabismus | year= 1986 | volume= 23 | issue= 4 | pages= 174-7 | pmid=3746592 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3746592  }} </ref><ref name="pmid8622068">{{cite journal| author=Schvartzman E, Chantada G, Fandiño A, de Dávila MT, Raslawski E, Manzitti J| title=Results of a stage-based protocol for the treatment of retinoblastoma. | journal=J Clin Oncol | year= 1996 | volume= 14 | issue= 5 | pages= 1532-6 | pmid=8622068 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8622068  }} </ref><ref name="pmid8060814">{{cite journal| author=Pratt CB, Fontanesi J, Chenaille P, Kun LE, Jenkins JJ, Langston JW et al.| title=Chemotherapy for extraocular retinoblastoma. | journal=Pediatr Hematol Oncol | year= 1994 | volume= 11 | issue= 3 | pages= 301-9 | pmid=8060814 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8060814  }} </ref><ref name="pmid12518344">{{cite journal| author=Chantada G, Fandiño A, Casak S, Manzitti J, Raslawski E, Schvartzman E| title=Treatment of overt extraocular retinoblastoma. | journal=Med Pediatr Oncol | year= 2003 | volume= 40 | issue= 3 | pages= 158-61 | pmid=12518344 | doi=10.1002/mpo.10249 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12518344  }} </ref><ref name="pmid7707117">{{cite journal| author=Doz F, Neuenschwander S, Plantaz D, Courbon B, Gentet JC, Bouffet E et al.| title=Etoposide and carboplatin in extraocular retinoblastoma: a study by the Société Française d'Oncologie Pédiatrique. | journal=J Clin Oncol | year= 1995 | volume= 13 | issue= 4 | pages= 902-9 | pmid=7707117 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7707117  }} </ref>
*The one year to eighteen month survival rates in patients with hematogenous [[metastases]] are approximately 50 percent.<ref name="pmid3746592">{{cite journal| author=Abramson DH, Ellsworth RM, Grumbach N, Sturgis-Buckhout L, Haik BG| title=Retinoblastoma: correlation between age at diagnosis and survival. | journal=J Pediatr Ophthalmol Strabismus | year= 1986 | volume= 23 | issue= 4 | pages= 174-7 | pmid=3746592 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3746592  }} </ref><ref name="pmid8622068">{{cite journal| author=Schvartzman E, Chantada G, Fandiño A, de Dávila MT, Raslawski E, Manzitti J| title=Results of a stage-based protocol for the treatment of retinoblastoma. | journal=J Clin Oncol | year= 1996 | volume= 14 | issue= 5 | pages= 1532-6 | pmid=8622068 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8622068  }} </ref><ref name="pmid8060814">{{cite journal| author=Pratt CB, Fontanesi J, Chenaille P, Kun LE, Jenkins JJ, Langston JW et al.| title=Chemotherapy for extraocular retinoblastoma. | journal=Pediatr Hematol Oncol | year= 1994 | volume= 11 | issue= 3 | pages= 301-9 | pmid=8060814 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8060814  }} </ref><ref name="pmid12518344">{{cite journal| author=Chantada G, Fandiño A, Casak S, Manzitti J, Raslawski E, Schvartzman E| title=Treatment of overt extraocular retinoblastoma. | journal=Med Pediatr Oncol | year= 2003 | volume= 40 | issue= 3 | pages= 158-61 | pmid=12518344 | doi=10.1002/mpo.10249 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12518344  }} </ref><ref name="pmid7707117">{{cite journal| author=Doz F, Neuenschwander S, Plantaz D, Courbon B, Gentet JC, Bouffet E et al.| title=Etoposide and carboplatin in extraocular retinoblastoma: a study by the Société Française d'Oncologie Pédiatrique. | journal=J Clin Oncol | year= 1995 | volume= 13 | issue= 4 | pages= 902-9 | pmid=7707117 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7707117  }} </ref>

Revision as of 18:54, 19 April 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2]

Overview

If left untreated, retinoblastoma may progress to develop seeding in the eye, leading to retinal detachment, necrosis and invasion of the orbit, optic nerve invasion, and central nervous system invasion. The majority of untreated patients die of intracranial extension and disseminated disease within one year. Spontaneous regression of the tumor is a rare occurrence but may occur in a small number of cases.[1][2][3] Common complications of retinoblastoma include metastasis, tumor recurrence, trilateral retinoblastoma, and subsequent neoplasms. Prognosis is generally good, and the survival rate of patients with retinoblastoma with treatment is approximately 95% in the United States.[4]

Natural History

If left untreated, retinoblastoma may progress to develop seeding in the eye, leading to retinal detachment, necrosis and invasion of the orbit, optic nerve invasion, and central nervous system invasion. Generally, metastasis may begin within 4 months of diagnosis. Metastasis usually occurs through direct invasion of the central nervous system via the optic nerve. Retinoblastoma may spread through the subarachnoid space to the contralateral optic nerve or through the cerebrospinal fluid to the central nervous system and may spread hematogenously to the lungs, bone, and brain.[5] The majority of untreated patients die of intracranial extension and disseminated disease within one year. Spontaneous regression of the tumor is a rare occurrence but may occur in a small number of cases.[1][2][3]

Prognosis

  • Those with heritable form of the disease have 50% risk of transmitting the mutation to their offspring.[6]
  • Prognosis is generally good, and the survival rate of patients with retinoblastoma with treatment is approximately 95%, in the United States.[4] However, the prognosis for eye salvage is far less and usually depends on the stage of retinoblastoma at diagnosis.
  • The one year to eighteen month survival rates in patients with hematogenous metastases are approximately 50 percent.[7][8][9][10][11]
  • The five-year survival for patients with pineal trilateral retinoblastoma is 44 percent and five-year survival for nonpineal trilateral retinoblastoma is 57 percent.[12]
  • With improvements in the diagnosis and management of retinoblastoma over the past several decades, metastatic retinoblastoma is observed less frequently in the United States and other developed nations. As a result, other causes of retinoblastoma-related mortality in the first and subsequent decades of life, such as trilateral retinoblastoma and subsequent neoplasms (SNs), have become significant contributors to retinoblastoma-related mortality. Death from a subsequent neoplasms is the most common cause of death and contributes to more than 50% of deaths for patients with bilateral disease. In the United States, before the advent of chemoreduction as a means of treating heritable or bilateral disease, trilateral retinoblastoma contributed to more than 50% of retinoblastoma-related mortality in the first decade after diagnosis.[13]
  • The prognosis for vision in children with bilateral retinoblastoma depends upon the effectiveness of therapy and extent of tumor involvement. The prognosis is better if the tumors do not involve the fovea, are small, and there is a limited seeding and retinal detachment.[14] The prognosis for vision in the unaffected eye of children with unilateral retinoblastoma is excellent.
  • While cure rates for orbital recurrences of retinoblastoma remain high, there is greater than 50 percent mortality rate for extra-orbital metastatic disease.[15][16]
  • For patients with germline retinoblastoma, the most common cause of death is a secondary malignancy, due to RB1 deletion, and not the initial primary malignancy.[17]
  • Given the poor prognosis of trilateral retinoblastoma and the short interval between the diagnosis of retinoblastoma and the occurrence of trilateral disease, routine neuroimaging could potentially detect most cases within 2 years of first diagnosis.
  • Prognosis depends on stage and grade of retinoblastoma.[18] Children who have a lower grade of retinoblastoma or a well-differentiated tumor have a more favourable prognosis than children with a higher grade or poorly differentiated tumor.
MRI component Features
Grade 1
  • Well differentiated or low grade – slow growing, less likely to spread
Grade 2
  • Moderately well differentiated or moderate grade
Grade 3
  • Poorly differentiated or high grade – tend to grow quickly, more likely to spread
Grade 4
  • Undifferentiated or high grade – tend to grow very quickly, likely to spread

The features associated with poor prognosis in retinoblastoma include:[19]

Complications

Complications of retinoblastoma

  • Metastasis
  • Recurrence of tumor
  • Trilateral retinnoblastoma
    • Trilateral retinoblastoma is a well-recognized syndrome that occurs in 5% to 15% of patients with heritable retinoblastoma and is defined by the development of an intracranial midline neuroblastic tumor, which typically develops between the ages of 20 and 36 months.[13] Approximately 5% to 10% of children with heritable retinoblastoma develop pineal gland cysts detected by MRI; these cyst abnormalities must be distinguished from the pineoblastoma that typically defines trilateral retinoblastoma.
  • Subsequent neoplasms
    • Patients with retinoblastoma have a high risk of developing subsequent neoplasms. Osteogenic or soft tissue sarcomas are the common subsequent neoplasms that develop in children.[33][27][34][35][36][37] Factors that influence the risk of having subsequent neoplasms include:
      • Heritable retinoblastoma- There is increased risk of developing secondary primary tumors, including osteogenic sarcoma, soft tissue sarcomas (particularly leiomyosarcoma) and malignant melanoma in patients with the genetic abnormality associated with heritable forms of retinoblastoma.[38][33][27][39][34][35]
      • Past treatment of retinoblastoma with radiation therapy.[13]
      • Age at time of radiation therapy- The risk of subsequent neoplasms appears to be dependent on the patient's age at the time that external-beam radiation therapy is administered, especially in children younger than 12 months, and the histopathologic types of subsequent neoplasms may be influenced by age.[13]
      • Previous subsequent neoplasms- Those who survive subsequent neoplasms are at a sevenfold increased risk for developing another subsequent neoplasm.[34] An additional threefold increase in risk is seen for patients treated with radiation therapy.[40]

Complications of retinoblastoma therapy

  • Potential complications of enucleation include scleral perforation with seeding of tumor cells into the orbit.

References

  1. ↑ 1.0 1.1 Sanborn GE, Augsburger JJ, Shields JA (1982). "Spontaneous regression of bilateral retinoblastoma". Br J Ophthalmol. 66 (11): 685–90. PMC 1039901. PMID 7126513.
  2. ↑ 2.0 2.1 Kao LY, Yang ML (2005). "Spontaneous regression of retinoblastoma in a Taiwan series". J Pediatr Ophthalmol Strabismus. 42 (4): 228–32. PMID 16121553.
  3. ↑ 3.0 3.1 Khodadoust AA, Roozitalab HM, Smith RE, Green WR (1977). "Spontaneous regression of retinoblastoma". Surv Ophthalmol. 21 (6): 467–78. PMID 898013.
  4. ↑ 4.0 4.1 Lin P, O'Brien JM (2009). "Frontiers in the management of retinoblastoma". Am J Ophthalmol. 148 (2): 192–8. doi:10.1016/j.ajo.2009.04.004. PMID 19477707.
  5. ↑ Singh, Arun D., Carol L. Shields, and Jerry A. Shields. "Prognostic factors in retinoblastoma." Journal of pediatric ophthalmology and strabismus 37.3 (2000): 134.
  6. ↑ Garber JE, Offit K (January 2005). "Hereditary cancer predisposition syndromes". J. Clin. Oncol. 23 (2): 276–92. doi:10.1200/JCO.2005.10.042. PMID 15637391.
  7. ↑ Abramson DH, Ellsworth RM, Grumbach N, Sturgis-Buckhout L, Haik BG (1986). "Retinoblastoma: correlation between age at diagnosis and survival". J Pediatr Ophthalmol Strabismus. 23 (4): 174–7. PMID 3746592.
  8. ↑ Schvartzman E, Chantada G, Fandiño A, de Dávila MT, Raslawski E, Manzitti J (1996). "Results of a stage-based protocol for the treatment of retinoblastoma". J Clin Oncol. 14 (5): 1532–6. PMID 8622068.
  9. ↑ Pratt CB, Fontanesi J, Chenaille P, Kun LE, Jenkins JJ, Langston JW; et al. (1994). "Chemotherapy for extraocular retinoblastoma". Pediatr Hematol Oncol. 11 (3): 301–9. PMID 8060814.
  10. ↑ Chantada G, Fandiño A, Casak S, Manzitti J, Raslawski E, Schvartzman E (2003). "Treatment of overt extraocular retinoblastoma". Med Pediatr Oncol. 40 (3): 158–61. doi:10.1002/mpo.10249. PMID 12518344.
  11. ↑ Doz F, Neuenschwander S, Plantaz D, Courbon B, Gentet JC, Bouffet E; et al. (1995). "Etoposide and carboplatin in extraocular retinoblastoma: a study by the Société Française d'Oncologie Pédiatrique". J Clin Oncol. 13 (4): 902–9. PMID 7707117.
  12. ↑ de Jong MC, Kors WA, de Graaf P, Castelijns JA, Kivelä T, Moll AC (2014). "Trilateral retinoblastoma: a systematic review and meta-analysis". Lancet Oncol. 15 (10): 1157–67. doi:10.1016/S1470-2045(14)70336-5. PMID 25126964.
  13. ↑ 13.0 13.1 13.2 13.3 Retinoblastoma related mortality. National Cancer Institute(2015) http://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq#link/_488_toc Accessed on October 10, 2015
  14. ↑ Berry JL, Jubran R, Wong K, Lee TC, Murphree AL, Kim JW (2014). "Factors predictive of long-term visual outcomes of Group D eyes treated with chemoreduction and low-dose IMRT salvage: the Children's Hospital Los Angeles experience". Br J Ophthalmol. 98 (8): 1061–5. doi:10.1136/bjophthalmol-2013-304411. PMID 24671926.
  15. ↑ Kim JW, Kathpalia V, Dunkel IJ, Wong RK, Riedel E, Abramson DH (2009). "Orbital recurrence of retinoblastoma following enucleation". Br J Ophthalmol. 93 (4): 463–7. doi:10.1136/bjo.2008.138453. PMID 18757474.
  16. ↑ Leal-Leal CA, Rivera-Luna R, Flores-Rojo M, Juárez-Echenique JC, Ordaz JC, Amador-Zarco J (2006). "Survival in extra-orbital metastatic retinoblastoma:treatment results". Clin Transl Oncol. 8 (1): 39–44. PMID 16632438.
  17. ↑ Abramson DH (1999). "Second nonocular cancers in retinoblastoma: a unified hypothesis. The Franceschetti Lecture". Ophthalmic Genet. 20 (3): 193–204. PMID 10610188.
  18. ↑ Grades of Retinoblastoma. Canadian Cancer Society(2015) http://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq#cit/section_1.45 Accessed on October 13 2015
  19. ↑ Singh AD, Shields CL, Shields JA (2000). "Prognostic factors in retinoblastoma". J Pediatr Ophthalmol Strabismus. 37 (3): 134–41, quiz 168-9. PMID 10845413.
  20. ↑ 20.0 20.1 Mendoza PR, Specht CS, Hubbard GB, Wells JR, Lynn MJ, Zhang Q; et al. (2015). "Histopathologic grading of anaplasia in retinoblastoma". Am J Ophthalmol. 159 (4): 764–76. doi:10.1016/j.ajo.2014.12.014. PMC 4361305. PMID 25528954.
  21. ↑ 21.0 21.1 Messmer EP, Heinrich T, Höpping W, de Sutter E, Havers W, Sauerwein W (1991). "Risk factors for metastases in patients with retinoblastoma". Ophthalmology. 98 (2): 136–41. PMID 2008269.
  22. ↑ Goddard AG, Kingston JE, Hungerford JL (1999). "Delay in diagnosis of retinoblastoma: risk factors and treatment outcome". Br J Ophthalmol. 83 (12): 1320–3. PMC 1722906. PMID 10574806.
  23. ↑ Erwenne CM, Franco EL (1989). "Age and lateness of referral as determinants of extra-ocular retinoblastoma". Ophthalmic Paediatr Genet. 10 (3): 179–84. PMID 2587030.
  24. ↑ Kaliki S, Srinivasan V, Gupta A, Mishra DK, Naik MN (2015). "Clinical features predictive of high-risk retinoblastoma in 403 Asian Indian patients: a case-control study". Ophthalmology. 122 (6): 1165–72. doi:10.1016/j.ophtha.2015.01.018. PMID 25841975.
  25. ↑ Stevenson KE, Hungerford J, Garner A (1989). "Local extraocular extension of retinoblastoma following intraocular surgery". Br J Ophthalmol. 73 (9): 739–42. PMC 1041868. PMID 2804029.
  26. ↑ Shields CL, Honavar S, Shields JA, Demirci H, Meadows AT (2000). "Vitrectomy in eyes with unsuspected retinoblastoma". Ophthalmology. 107 (12): 2250–5. PMID 11097606.
  27. ↑ 27.0 27.1 27.2 Wong FL, Boice JD, Abramson DH, Tarone RE, Kleinerman RA, Stovall M; et al. (1997). "Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk". JAMA. 278 (15): 1262–7. PMID 9333268.
  28. ↑ Abramson DH, Frank CM (1998). "Second nonocular tumors in survivors of bilateral retinoblastoma: a possible age effect on radiation-related risk". Ophthalmology. 105 (4): 573–9, discussion 579-80. doi:10.1016/S0161-6420(98)94006-4. PMID 9544627.
  29. ↑ Moll AC, Imhof SM, Bouter LM, Tan KE (1997). "Second primary tumors in patients with retinoblastoma. A review of the literature". Ophthalmic Genet. 18 (1): 27–34. PMID 9134547.
  30. ↑ Finger PT, Harbour JW, Karcioglu ZA (2002). "Risk factors for metastasis in retinoblastoma". Surv Ophthalmol. 47 (1): 1–16. PMID 11801265.
  31. ↑ Shields CL, Shields JA, Baez K, Cater JR, De Potter P (1994). "Optic nerve invasion of retinoblastoma. Metastatic potential and clinical risk factors". Cancer. 73 (3): 692–8. PMID 8299091.
  32. ↑ Shields CL, Shields JA, Baez KA, Cater J, De Potter PV (1993). "Choroidal invasion of retinoblastoma: metastatic potential and clinical risk factors". Br J Ophthalmol. 77 (9): 544–8. PMC 513947. PMID 8218048.
  33. ↑ 33.0 33.1 Eng C, Li FP, Abramson DH, Ellsworth RM, Wong FL, Goldman MB; et al. (1993). "Mortality from second tumors among long-term survivors of retinoblastoma". J Natl Cancer Inst. 85 (14): 1121–8. PMID 8320741.
  34. ↑ 34.0 34.1 34.2 Abramson DH, Melson MR, Dunkel IJ, Frank CM (2001). "Third (fourth and fifth) nonocular tumors in survivors of retinoblastoma". Ophthalmology. 108 (10): 1868–76. PMID 11581064.
  35. ↑ 35.0 35.1 Kleinerman RA, Tucker MA, Abramson DH, Seddon JM, Tarone RE, Fraumeni JF (2007). "Risk of soft tissue sarcomas by individual subtype in survivors of hereditary retinoblastoma". J Natl Cancer Inst. 99 (1): 24–31. doi:10.1093/jnci/djk002. PMID 17202110.
  36. ↑ Kleinerman RA, Tucker MA, Tarone RE, Abramson DH, Seddon JM, Stovall M; et al. (2005). "Risk of new cancers after radiotherapy in long-term survivors of retinoblastoma: an extended follow-up". J Clin Oncol. 23 (10): 2272–9. doi:10.1200/JCO.2005.05.054. PMID 15800318.
  37. ↑ MacCarthy A, Bayne AM, Brownbill PA, Bunch KJ, Diggens NL, Draper GJ; et al. (2013). "Second and subsequent tumours among 1927 retinoblastoma patients diagnosed in Britain 1951-2004". Br J Cancer. 108 (12): 2455–63. doi:10.1038/bjc.2013.228. PMC 3694232. PMID 23674091.
  38. ↑ Kleinerman RA, Schonfeld SJ, Tucker MA (2012). "Sarcomas in hereditary retinoblastoma". Clin Sarcoma Res. 2 (1): 15. doi:10.1186/2045-3329-2-15. PMC 3499233. PMID 23036192.
  39. ↑ DerKinderen DJ, Koten JW, Nagelkerke NJ, Tan KE, Beemer FA, Den Otter W (1988). "Non-ocular cancer in patients with hereditary retinoblastoma and their relatives". Int J Cancer. 41 (4): 499–504. PMID 3356485.
  40. ↑ Marees T, van Leeuwen FE, Schaapveld M, Imhof SM, de Boer MR, Kors WA; et al. (2010). "Risk of third malignancies and death after a second malignancy in retinoblastoma survivors". Eur J Cancer. 46 (11): 2052–8. doi:10.1016/j.ejca.2010.03.029. PMID 20400293.
  41. ↑ Rivera GK, Pui CH, Santana VM, Pratt CB, Crist WM (1994). "Epipodophyllotoxins in the treatment of childhood cancer". Cancer Chemother Pharmacol. 34 Suppl: S89–95. PMID 8070034.
  42. ↑ Abramson DH, Melson MR, Servodidio C (2004). "Visual fields in retinoblastoma survivors". Arch Ophthalmol. 122 (9): 1324–30. doi:10.1001/archopht.122.9.1324. PMID 15364711.
  43. ↑ Qaddoumi I, Bass JK, Wu J, Billups CA, Wozniak AW, Merchant TE; et al. (2012). "Carboplatin-associated ototoxicity in children with retinoblastoma". J Clin Oncol. 30 (10): 1034–41. doi:10.1200/JCO.2011.36.9744. PMC 3341147. PMID 22370329.
  44. ↑ Leahey A (2012). "A cautionary tale: dosing chemotherapy in infants with retinoblastoma". J Clin Oncol. 30 (10): 1023–4. doi:10.1200/JCO.2011.39.4254. PMID 22370322.
  45. ↑ Mulvihill A, Budning A, Jay V, Vandenhoven C, Heon E, Gallie BL; et al. (2003). "Ocular motility changes after subtenon carboplatin chemotherapy for retinoblastoma". Arch Ophthalmol. 121 (8): 1120–4. doi:10.1001/archopht.121.8.1120. PMID 12912689.
  46. ↑ Schmack I, Hubbard GB, Kang SJ, Aaberg TM, Grossniklaus HE (2006). "Ischemic necrosis and atrophy of the optic nerve after periocular carboplatin injection for intraocular retinoblastoma". Am J Ophthalmol. 142 (2): 310–5. doi:10.1016/j.ajo.2006.02.044. PMID 16876514.

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