Skip to main content
SpringerLink
Log in

Changing Trends in Retinoblastoma Management and What Is in Store for the Future

  • Chapter
  • First Online:
Intraocular Tumors

  • 525 Accesses

Abstract

Retinoblastoma (Rb) is the most common intraocular cancer of childhood with an incidence of 1 in 15,000 live births or about 12 per million children ages 0–4 years [1, 2]. Retinoblastoma accounts for 2% of all childhood cancers and approximately 8% percent of cancer in the first 4 years of life [3]. Worldwide there are 9000 new cases annually with the greatest number of cases seen in Asia and Africa where the birth rate is higher [4]. However the rate per live birth remains the same and no significant gender or racial predilection for the development of Rb has been described [5]. Maternal nutrition [6], HPV infection [7, 8], and advanced paternal age [9] have been suggested as predisposing etiologies but have not been definitively confirmed. Worldwide, the survival of children with retinoblastoma has improved [10] however disparities in the treatment and survival of children with this ocular cancer remain [11–16]. The treatment of Retinoblastoma continues to evolve with a focus on more localized therapies to spare systemic toxicity. Nonetheless, there remains a critical need for personalized therapies for retinoblastoma. Retinoblastoma was one of the first cancers with a known genetic underpinning due to a mutation in the RB1 retinoblastoma tumor suppressor gene (RB1) [17, 18], and has provided enormous insights into cancer biology; however, because this tumor cannot be safely biopsied, we still know very little about the genetic, genomic and epigenetic changes in this tumor that may affect treatment and prognosis for eye salvage [19]. This chapter will discuss the diagnosis, staging, and current treatment paradigms for retinoblastoma as well as discuss the future of this disease.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Broaddus E, Topham A, Singh AD. Incidence of retinoblastoma in the USA: 1975-2004. Br J Ophthalmol. 2009;93(1):21–3.

    Article  CAS  PubMed  Google Scholar 

  2. Seregard S, Lundell G, Svedberg H, Kivela T. Incidence of retinoblastoma from 1958 to 1998 in Northern Europe: advantages of birth cohort analysis. Ophthalmology. 2004;111(6):1228–32.

    Article  PubMed  Google Scholar 

  3. 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  PubMed  PubMed Central  Google Scholar 

  4. Kivela T. The epidemiological challenge of the most frequent eye cancer: retinoblastoma, an issue of birth and death. Br J Ophthalmol. 2009;93(9):1129–31.

    Article  PubMed  Google Scholar 

  5. Dimaras H, Kimani K, Dimba EA, Gronsdahl P, White A, Chan HS, et al. Retinoblastoma. Lancet. 2012;379(9824):1436–46.

    Article  PubMed  Google Scholar 

  6. Lombardi C, Ganguly A, Bunin GR, Azary S, Alfonso V, Ritz B, et al. Maternal diet during pregnancy and unilateral retinoblastoma. Cancer Causes Control. 2015;26(3):387–97.

    Article  PubMed  Google Scholar 

  7. Anand B, Ramesh C, Appaji L, Kumari BS, Shenoy AM, Nanjundappa, et al. Prevalence of high-risk human papillomavirus genotypes in retinoblastoma. Br J Ophthalmol. 2011;95(7):1014–8.

    Article  PubMed  Google Scholar 

  8. Shetty OA, Naresh KN, Banavali SD, Shet T, Joshi R, Qureshi S, et al. Evidence for the presence of high risk human papillomavirus in retinoblastoma tissue from nonfamilial retinoblastoma in developing countries. Pediatr Blood Cancer. 2012;58(2):185–90.

    Article  PubMed  Google Scholar 

  9. Mills MB, Hudgins L, Balise RR, Abramson DH, Kleinerman RA. Mutation risk associated with paternal and maternal age in a cohort of retinoblastoma survivors. Hum Genet. 2012;131(7):1115–22.

    Article  PubMed  Google Scholar 

  10. Tamboli D, Topham A, Singh N, Singh AD. Retinoblastoma: a SEER dataset evaluation for treatment patterns, survival, and second malignant neoplasms. Am J Ophthalmol. 2015;160(5):953–8.

    Article  PubMed  Google Scholar 

  11. Gichigo EN, Kariuki-Wanyoike MM, Kimani K, Nentwich MM. Retinoblastoma in Kenya: survival and prognostic factors. Ophthalmologe. 2015;112(3):255–60.

    Article  CAS  PubMed  Google Scholar 

  12. Waddell KM, Kagame K, Ndamira A, Twinamasiko A, Picton SV, Simmons IG, et al. Clinical features and survival among children with retinoblastoma in Uganda. Br J Ophthalmol. 2015;99(3):387–90.

    Article  PubMed  Google Scholar 

  13. Waddell KM, Kagame K, Ndamira A, Twinamasiko A, Picton SV, Simmons IG, et al. Improving survival of retinoblastoma in Uganda. Br J Ophthalmol. 2015;99(7):937–42.

    Article  PubMed  Google Scholar 

  14. 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  PubMed  Google Scholar 

  15. Li SY, Chen SC, Tsai CF, Sheu SM, Yeh JJ, Tsai CB. Incidence and survival of retinoblastoma in Taiwan: a nationwide population-based study 1998-2011. Br J Ophthalmol. 2016;100(6):839–42.

    Article  PubMed  Google Scholar 

  16. Temming P, Arendt M, Viehmann A, Eisele L, Le Guin CH, Schundeln MM, et al. How eye-preserving therapy affects long-term overall survival in heritable retinoblastoma survivors. J Clin Oncol. 2016;34(26):3183–8.

    Article  PubMed  Google Scholar 

  17. Benedict WF, Murphree AL, Banerjee A, Spina CA, Sparkes MC, Sparkes RS. Patient with 13 chromosome deletion: evidence that the retinoblastoma gene is a recessive cancer gene. Science. 1983;219(4587):973–5.

    Article  CAS  PubMed  Google Scholar 

  18. Dryja TP, Friend S, Weinberg RA. Genetic sequences that predispose to retinoblastoma and osteosarcoma. Symp Fundam Cancer Res. 1986;39:115–9.

    CAS  PubMed  Google Scholar 

  19. Berry JL, Xu L, Murphree AL, Krishnan S, Stachelek K, Zolfaghari E, et al. Potential of aqueous humor as a surrogate tumor biopsy for retinoblastoma. JAMA Ophthalmol. 2017;135(11):1221–30.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Abramson DH, Beaverson K, Sangani P, Vora RA, Lee TC, Hochberg HM, et al. Screening for retinoblastoma: presenting signs as prognosticators of patient and ocular survival. Pediatrics. 2003;112(6 Pt 1):1248–55.

    Article  PubMed  Google Scholar 

  21. Foster BS, Mukai S. Intraocular retinoblastoma presenting as ocular and orbital inflammation. Int Ophthalmol Clin. 1996;36(1):153–60.

    Article  CAS  PubMed  Google Scholar 

  22. Maki JL, Marr BP, Abramson DH. Diagnosis of retinoblastoma: how good are referring physicians? Ophthalmic Genet. 2009;30(4):199–205.

    Article  CAS  PubMed  Google Scholar 

  23. Nawaiseh I, Al-Hussaini M, Alhamwi A, Meyar M, Sultan I, Alrawashdeh K, et al. The impact of growth patterns of retinoblastoma (endophytic, exophytic, and mixed patterns). Turk Patoloji Derg. 2015;31(1):45–50.

    PubMed  Google Scholar 

  24. Novotny A, Krasny J. Diagnosis of retinoblastoma using ultrasound. Cas Lek Cesk. 1990;129(12):364–5.

    CAS  PubMed  Google Scholar 

  25. Kaufman LM, Mafee MF, Song CD. Retinoblastoma and simulating lesions. Role of CT, MR imaging and use of Gd-DTPA contrast enhancement. Radiol Clin N Am. 1998;36(6):1101–17.

    Article  CAS  PubMed  Google Scholar 

  26. Danziger A, Price HI. CT findings in retinoblastoma. AJR Am J Roentgenol. 1979;133(4):695–7.

    Article  CAS  PubMed  Google Scholar 

  27. Razek AA, Elkhamary S. MRI of retinoblastoma. Br J Radiol. 2011;84(1005):775–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ainbinder DJ, Haik BG, Frei DF, Gupta KL, Mafee MF. Gadolinium enhancement: improved MRI detection of retinoblastoma extension into the optic nerve. Neuroradiology. 1996;38(8):778–81.

    Article  CAS  PubMed  Google Scholar 

  29. 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  PubMed  Google Scholar 

  30. Kim JW, Madi I, Lee R, Zolfaghari E, Jubran R, Lee TC, et al. Clinical significance of optic nerve enhancement on magnetic resonance imaging in enucleated retinoblastoma patients. Ophthalmol Retina. 2017;1(5):369–74.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kim JW, Ngai LK, Sadda S, Murakami Y, Lee DK, Murphree AL. Retcam fluorescein angiography findings in eyes with advanced retinoblastoma. Br J Ophthalmol. 2014;98(12):1666–71.

    Article  PubMed  Google Scholar 

  32. Shields CL, Mashayekhi A, Luo CK, Materin MA, Shields JA. Optical coherence tomography in children: analysis of 44 eyes with intraocular tumors and simulating conditions. J Pediatr Ophthalmol Strabismus. 2004;41(6):338–44.

    Article  PubMed  Google Scholar 

  33. Shields CL, Materin MA, Shields JA. Review of optical coherence tomography for intraocular tumors. Curr Opin Ophthalmol. 2005;16(3):141–54.

    Article  PubMed  Google Scholar 

  34. Sony P, Garg SP. Optical coherence tomography in children with retinoblastoma. J Pediatr Ophthalmol Strabismus. 2005;42(3):134.

    Article  PubMed  Google Scholar 

  35. Yousef YA, Shroff M, Halliday W, Gallie BL, Heon E. Detection of optic nerve disease in retinoblastoma by use of spectral domain optical coherence tomography. J AAPOS. 2012;16(5):481–3.

    Article  PubMed  Google Scholar 

  36. Rootman DB, Gonzalez E, Mallipatna A, Vandenhoven C, Hampton L, Dimaras H, et al. Hand-held high-resolution spectral domain optical coherence tomography in retinoblastoma: clinical and morphologic considerations. Br J Ophthalmol. 2013;97(1):59–65.

    Article  PubMed  Google Scholar 

  37. Cao C, Markovitz M, Ferenczy S, Shields CL. Hand-held spectral-domain optical coherence tomography of small macular retinoblastoma in infants before and after chemotherapy. J Pediatr Ophthalmol Strabismus. 2014;51(4):230–4.

    Article  PubMed  Google Scholar 

  38. Pierro L, De Francesco S, Hadjistilianou D, Casalino G, Fusco F, Sergenti J, et al. Spectral-domain optical coherence tomography appearance of a posterior pole retinoma. J Pediatr Ophthalmol Strabismus. 2014;51(5):320.

    Article  PubMed  Google Scholar 

  39. Hasanreisoglu M, Dolz-Marco R, Ferenczy SR, Shields JA, Shields CL. Spectral domain optical coherence tomography reveals hidden fovea beneath extensive vitreous seeding from retinoblastoma. Retina. 2015;35(7):1486–7.

    Article  PubMed  Google Scholar 

  40. Berry JL, Cobrinik D, Kim JW. Detection and intraretinal localization of an ‘invisible’ retinoblastoma using optical coherence tomography. Ocul Oncol Pathol. 2016;2(3):148–52.

    Article  PubMed  Google Scholar 

  41. Park K, Sioufi K, Shields CL. Clinically invisible retinoblastoma recurrence in an infant. Retin Cases Brief Rep. 2017;13(2):108–10.

    Article  Google Scholar 

  42. Malhotra PP, Bhushan B, Mitra A, Sen A. Spectral-domain optical coherence tomography and fundus autofluorescence features in a case of typical retinocytoma. Eur J Ophthalmol. 2015;25(6):e123–6.

    Article  PubMed  Google Scholar 

  43. Seider MI, Grewal DS, Mruthyunjaya P. Portable optical coherence tomography detection or confirmation of ophthalmoscopically invisible or indeterminate active retinoblastoma. Ophthalmic Surg Lasers Imaging Retina. 2016;47(10):965–8.

    Article  PubMed  Google Scholar 

  44. Berry JL, Anulao K, Kim JW. Optical coherence tomography imaging of a large spherical seed in retinoblastoma. Ophthalmology. 2017;124(8):1208.

    Article  PubMed  Google Scholar 

  45. Saktanasate J, Vongkulsiri S, Khoo CT. Invisible retinoblastoma. JAMA Ophthalmol. 2015;133(7):e151123.

    Article  PubMed  Google Scholar 

  46. Xu XL, Singh HP, Wang L, Qi DL, Poulos BK, Abramson DH, et al. Rb suppresses human cone-precursor-derived retinoblastoma tumours. Nature. 2014;514(7522):385–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Xu XL, Fang Y, Lee TC, Forrest D, Gregory-Evans C, Almeida D, et al. Retinoblastoma has properties of a cone precursor tumor and depends upon cone-specific MDM2 signaling. Cell. 2009;137(6):1018–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  49. 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  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  51. 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  PubMed  Google Scholar 

  52. Berry JL, Jubran R, Kim JW, Wong K, Bababeygy SR, Almarzouki H, et al. Long-term outcomes of Group D eyes in bilateral retinoblastoma patients treated with chemoreduction and low-dose IMRT salvage. Pediatr Blood Cancer. 2013;60(4):688–93.

    Article  PubMed  Google Scholar 

  53. Abramson DH, Frank CM. Second nonocular tumors in survivors of bilateral retinoblastoma: a possible age effect on radiation-related risk. Ophthalmology. 1998;105(4):573–9.

    Article  CAS  PubMed  Google Scholar 

  54. Abramson DH, Ronner HJ, Ellsworth RM. Second tumors in nonirradiated bilateral retinoblastoma. Am J Ophthalmol. 1979;87(5):624–7.

    Article  CAS  PubMed  Google Scholar 

  55. Abramson DH, Ellsworth RM, Kitchin FD, Tung G. Second nonocular tumors in retinoblastoma survivors. Are they radiation-induced? Ophthalmology. 1984;91(11):1351–5.

    Article  CAS  PubMed  Google Scholar 

  56. Eng C, Li FP, Abramson DH, Ellsworth RM, Wong FL, Goldman MB, et al. Mortality from second tumors among long-term survivors of retinoblastoma. J Natl Cancer Inst. 1993;85(14):1121–8.

    Article  CAS  PubMed  Google Scholar 

  57. Moll AC, Imhof SM, Bouter LM, Kuik DJ, Den Otter W, Bezemer PD, et al. Second primary tumors in patients with hereditary retinoblastoma: a register-based follow-up study, 1945-1994. Int J Cancer. 1996;67(4):515–9.

    Article  CAS  PubMed  Google Scholar 

  58. Li FP, Abramson DH, Tarone RE, Kleinerman RA, Fraumeni JF Jr, Boice JD Jr. Hereditary retinoblastoma, lipoma, and second primary cancers. J Natl Cancer Inst. 1997;89(1):83–4.

    Article  CAS  PubMed  Google Scholar 

  59. Moll AC, Imhof SM, Bouter LM, Tan KE. Second primary tumors in patients with retinoblastoma. A review of the literature. Ophthalmic Genet. 1997;18(1):27–34.

    Article  CAS  PubMed  Google Scholar 

  60. Rubin CZ, Rosenfield NS, Abramson SJ, Abramson DH, Dunkel IJ. The location and appearance of second malignancies in patients with bilateral retinoblastoma. Sarcoma. 1997;1(2):89–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Dunkel IJ, Gerald WL, Rosenfield NS, Strong EW, Abramson DH, Ghavimi F. Outcome of patients with a history of bilateral retinoblastoma treated for a second malignancy: the memorial sloan-kettering experience. Med Pediatr Oncol. 1998;30(1):59–62.

    Article  CAS  PubMed  Google Scholar 

  62. Hasegawa T, Matsuno Y, Niki T, Hirohashi S, Shimoda T, Takayama J, et al. Second primary rhabdomyosarcomas in patients with bilateral retinoblastoma: a clinicopathologic and immunohistochemical study. Am J Surg Pathol. 1998;22(11):1351–60.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  64. Schlienger P, Campana F, Vilcoq JR, Asselain B, Dendale R, Desjardins L, et al. Nonocular second primary tumors after retinoblastoma: retrospective study of 111 patients treated by electron beam radiotherapy with or without TEM. Am J Clin Oncol. 2004;27(4):411–9.

    Article  PubMed  Google Scholar 

  65. 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 I. 2008;100(24):1771–9.

    Article  Google Scholar 

  66. Sheen V, Tucker MA, Abramson DH, Seddon JM, Kleinerman RA. Cancer screening practices of adult survivors of retinoblastoma at risk of second cancers. Cancer. 2008;113(2):434–41.

    Article  PubMed  Google Scholar 

  67. Balaguer J, Harto M, Serra I, Oltra S, HernAndez M, Castel V. Mortality from second tumors among long-term survivors of retinoblastoma: an 87 case series report. Pediatr Blood Cancer. 2009;53(5):811.

    Google Scholar 

  68. Woo KI, Harbour JW. Review of 676 second primary tumors in patients with retinoblastoma: association between age at onset and tumor type. Arch Ophthalmol. 2010;128(7):865–70.

    Article  PubMed  Google Scholar 

  69. Kleinerman RA, Yu CL, Little MP, Li Y, Abramson D, Seddon J, et al. Variation of second cancer risk by family history of retinoblastoma among long-term survivors. J Clin Oncol. 2012;30(9):950–7.

    Article  PubMed  PubMed Central  Google Scholar 

  70. MacCarthy A, Bayne AM, Brownbill PA, Bunch KJ, Diggens NL, Draper GJ, et al. Second and subsequent tumours among 1927 retinoblastoma patients diagnosed in Britain 1951-2004. Br J Cancer. 2013;108(12):2455–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Rodjan F, Graaf P, Brisse HJ, Verbeke JI, Sanchez E, Galluzzi P, et al. Second cranio-facial malignancies in hereditary retinoblastoma survivors previously treated with radiation therapy: clinic and radiologic characteristics and survival outcomes. Eur J Cancer. 2013;49(8):1939–47.

    Article  PubMed  Google Scholar 

  72. Fujiwara T, Fujiwara M, Numoto K, Ogura K, Yoshida A, Yonemoto T, et al. Second primary osteosarcomas in patients with retinoblastoma. Jpn J Clin Oncol. 2015;45(12):1139–45.

    PubMed  Google Scholar 

  73. Abramson DH, Melson MR, Dunkel IJ, Frank CM. Third (fourth and fifth) nonocular tumors in survivors of retinoblastoma. Ophthalmology. 2001;108(10):1868–76.

    Article  CAS  PubMed  Google Scholar 

  74. Melson MR, Dunkel IJ, Frank CM, Abramson DH. Third (fourth and fifth) nonocular tumors in survivors of retinoblastoma. Invest Ophthalmol Vis Sci. 2000;41(4):S469.

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  76. Gallie BL, Budning A, DeBoer G, Thiessen JJ, Koren G, Verjee Z, et al. Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy. Arch Ophthalmol. 1996;114(11):1321–8.

    Article  CAS  PubMed  Google Scholar 

  77. Murphree AL, Villablanca JG, Deegan WF, 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  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  79. Abramson DH, Dunkel IJ, Brodie SE, Kim JW, Gobin YP. A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with melphalan for intraocular retinoblastoma initial results. Ophthalmology. 2008;115(8):1398–404.

    Article  PubMed  Google Scholar 

  80. Shields CL, De Potter P, Himelstein BP, Shields JA, Meadows AT, Maris JM. Chemoreduction in the initial management of intraocular retinoblastoma. Arch Ophthalmol. 1996;114(11):1330–8.

    Article  CAS  PubMed  Google Scholar 

  81. Berry JL, Jubran R, Lee TC, Murphree AL, Lee D, Kim JW. Low-dose chemoreduction for infants diagnosed with retinoblastoma before 6 months of age. Ocul Oncol Pathol. 2015;1:103–10.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Zhu DBJL, Ediriwickrema L, Wong K, Lee TC, Murphree AL, Kim JW, Jubran R. Long-term outcomes of group b eyes in patients with retinoblastoma treated with short-course chemoreduction: experience from Children’s Hospital Los Angeles/University of Southern California. Ocul Oncol Pathol. 2016;2:105–11.

    Article  Google Scholar 

  83. Mora E, Smith EM, Donohoe C, Hertz DL. Vincristine-induced peripheral neuropathy in pediatric cancer patients. Am J Cancer Res. 2016;6(11):2416–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Jehanne M, Lumbroso-Le Rouic L, Savignoni A, Aerts I, Mercier G, Bours D, et al. Analysis of ototoxicity in young children receiving carboplatin in the context of conservative management of unilateral or bilateral retinoblastoma. Pediatr Blood Cancer. 2009;52(5):637–43.

    Article  PubMed  Google Scholar 

  85. Weintraub M, Revel-Vilk S, Charit M, Aker M, Pe’er J. Secondary acute myeloid leukemia after etoposide therapy for retinoblastoma. J Pediatr Hematol Oncol. 2007;29(9):646–8.

    Article  CAS  PubMed  Google Scholar 

  86. Gombos DS, Hungerford J, Abramson DH, Kingston J, Chantada G, Dunkel IJ, et al. Secondary acute myelogenous leukemia in patients with retinoblastoma: is chemotherapy a factor? Ophthalmology. 2007;114(7):1378–83.

    Article  PubMed  Google Scholar 

  87. Nishimura S, Sato T, Ueda H, Ueda K. Acute myeloblastic leukemia as a second malignancy in a patient with hereditary retinoblastoma. J Clin Oncol. 2001;19(21):4182–3.

    Article  CAS  PubMed  Google Scholar 

  88. Rizzuti AE, Dunkel IJ, Abramson DH. The adverse events of chemotherapy for retinoblastoma: what are they? Do we know? Arch Ophthalmol. 2008;126(6):862–5.

    Article  CAS  PubMed  Google Scholar 

  89. Suzuki S, Aihara Y, Fujiwara M, Sano S, Kaneko A. Intravitreal injection of melphalan for intraocular retinoblastoma. Jpn J Ophthalmol. 2015;59(3):164–72.

    Article  CAS  PubMed  Google Scholar 

  90. Klufas MA, Gobin YP, Marr B, Brodie SE, Dunkel IJ, Abramson DH. Intra-arterial chemotherapy as a treatment for intraocular retinoblastoma: alternatives to direct ophthalmic artery catheterization. AJNR Am J Neuroradiol. 2012;33(8):1608–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Abramson DH, Marr BP, Brodie SE, Dunkel I, Palioura S, Gobin YP. Ophthalmic artery chemosurgery for less advanced intraocular retinoblastoma: five year review. PLoS One. 2012;7(4):e34120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Abramson DH, Dunkel IJ, Brodie SE, Marr B, Gobin YP. Superselective ophthalmic artery chemotherapy as primary treatment for retinoblastoma (chemosurgery). Ophthalmology. 2010;117(8):1623–9.

    Article  PubMed  Google Scholar 

  93. Abramson DH, Dunkel IJ, Brodie SE, Marr B, Gobin YP. Bilateral superselective ophthalmic artery chemotherapy for bilateral retinoblastoma: tandem therapy. Arch Ophthalmol. 2010;128(3):370–2.

    Article  PubMed  Google Scholar 

  94. Brodie SE, Pierre Gobin Y, Dunkel IJ, Kim JW, Abramson DH. Persistence of retinal function after selective ophthalmic artery chemotherapy infusion for retinoblastoma. Doc Ophthalmol. 2009;119(1):13–22.

    Article  PubMed  Google Scholar 

  95. Abramson DH, Daniels AB, Marr BP, Francis JH, Brodie SE, Dunkel IJ, et al. Intra-arterial chemotherapy (ophthalmic artery chemosurgery) for group D retinoblastoma. PLoS One. 2016;11(1):e0146582.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Chung CY, Medina CA, Aziz HA, Singh AD. Retinoblastoma: evidence for stage-based chemotherapy. Int Ophthalmol Clin. 2015;55(1):63–75.

    Article  PubMed  Google Scholar 

  97. MacCarthy A, Birch JM, Draper GJ, Hungerford JL, Kingston JE, Kroll ME, et al. Retinoblastoma: treatment and survival in Great Britain 1963 to 2002. Br J Ophthalmol. 2009;93(1):38–9.

    Article  CAS  PubMed  Google Scholar 

  98. Naseripour M, Nazari H, Bakhtiari P, Modarres-zadeh M, Vosough P, Ausari M. Retinoblastoma in Iran: outcomes in terms of patients’ survival and globe survival. Br J Ophthalmol. 2009;93(1):28–32.

    Article  CAS  PubMed  Google Scholar 

  99. Dimaras H, Dimba EA, Gallie BL. Challenging the global retinoblastoma survival disparity through a collaborative research effort. Br J Ophthalmol. 2010;94(11):1415–6.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  101. Al-Nawaiseh I, Jammal HM, Khader YS, Jaradat I, Barham R. Retinoblastoma in Jordan, 2003-2013: ocular survival and associated factors. Ophthalmic Epidemiol. 2014;21(6):406–11.

    Article  PubMed  Google Scholar 

  102. Moreno F, Sinaki B, Fandino A, Dussel V, Orellana L, Chantada G. A population-based study of retinoblastoma incidence and survival in Argentine children. Pediatr Blood Cancer. 2014;61(9):1610–5.

    Article  PubMed  Google Scholar 

  103. Shields CL, Manjandavida FP, Lally SE, Pieretti G, Arepalli SA, Caywood EH, et al. Intra-arterial chemotherapy for retinoblastoma in 70 eyes: outcomes based on the international classification of retinoblastoma. Ophthalmology. 2014;121(7):1453–60.

    Article  PubMed  Google Scholar 

  104. Munier FL, Mosimann P, Puccinelli F, Gaillard MC, Stathopoulos C, Houghton S, et al. First-line intra-arterial versus intravenous chemotherapy in unilateral sporadic group D retinoblastoma: evidence of better visual outcomes, ocular survival and shorter time to success with intra-arterial delivery from retrospective review of 20 years of treatment. Br J Ophthalmol. 2017;101(8):1086–93.

    Article  PubMed  Google Scholar 

  105. Abruzzo T, Patino M, Leach J, Rahme R, Geller J. Cerebral vasoconstriction triggered by sympathomimetic drugs during intra-atrerial chemotherapy. Pediatr Neurol. 2013;48(2):139–42.

    Article  PubMed  Google Scholar 

  106. 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  PubMed  Google Scholar 

  107. Marr B, Gobin PY, Dunkel IJ, Brodie SE, Abramson DH. Spontaneously resolving periocular erythema and ciliary madarosis following intra-arterial chemotherapy for retinoblastoma. Middle East Afr J Ophthalmol. 2010;17(3):207–9.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Dalvin LA, Ancona-Lezama D, Lucio-Alvarez JA, Masoomian B, Jabbour P, Shields CL. Primary intra-arterial chemotherapy for retinoblastoma in the intravitreal chemotherapy era: five years of experience. Ocul Oncol Pathol. 2019;5:139–46.

    Article  PubMed  Google Scholar 

  109. Mathew AA, Sachdev N, Staffieri SE, McKenzie JD, Elder JE. Superselective intra-arterial chemotherapy for advanced retinoblastoma complicated by metastatic disease. J AAPOS. 2015;19(1):72–4.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  111. 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  PubMed  Google Scholar 

  112. 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  PubMed  Google Scholar 

  113. Yannuzzi NA, Francis JH, Abramson DH. Incidence of orbital recurrence after enucleation or ophthalmic artery chemosurgery for advanced intraocular retinoblastoma--reply. JAMA Ophthalmol. 2016;134(1):114–5.

    Article  PubMed  Google Scholar 

  114. Yannuzzi NA, Francis JH, Marr BP, Belinsky I, Dunkel IJ, Gobin YP, et al. Enucleation vs ophthalmic artery chemosurgery for advanced intraocular retinoblastoma: a retrospective analysis. JAMA Ophthalmol. 2015;133(9):1062–6.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Berry JL, Kogachi K, Aziz HA, McGovern K, Zolfaghari E, Murphree AL, et al. Risk of metastasis and orbital recurrence in advanced retinoblastoma eyes treated with systemic chemoreduction versus primary enucleation. Pediatr Blood Cancer. 2017;64(4):26270.

    Article  Google Scholar 

  116. 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  PubMed  Google Scholar 

  117. Munier FL, Gaillard MC, Balmer A, Beck-Popovic M. Intravitreal chemotherapy for vitreous seeding in retinoblastoma: recent advances and perspectives. Saudi J Ophthalmol. 2013;27(3):147–50.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Ildefonso CJ, Kong L, Leen A, Chai SJ, Petrochelli V, Chintagumpala M, et al. Absence of systemic immune response to adenovectors after intraocular administration to children with retinoblastoma. Mol Ther. 2010;18(10):1885–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Chevez-Barrios P, Chintagumpala M, Mieler W, Paysse E, Boniuk M, Kozinetz C, et al. Response of retinoblastoma with vitreous tumor seeding to adenovirus-mediated delivery of thymidine kinase followed by ganciclovir. J Clin Oncol. 2005;23(31):7927–35.

    Article  CAS  PubMed  Google Scholar 

  120. Ericson LA, Rosengren BH. Tests of intravitreous chemotherapy in retinoblastoma. Acta Ophthalmol. 1962;40:121–2.

    CAS  Google Scholar 

  121. Seregard S, Kock E, af Trampe E. Intravitreal chemotherapy for recurrent retinoblastoma in an only eye. Br J Ophthalmol. 1995;79(2):194–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Kivela T, Eskelin S, Paloheimo M. Intravitreal methotrexate for retinoblastoma. Ophthalmology. 2011;118(8):1689.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  124. Shields CL, Fulco EM, Arias JD, Alarcon C, Pellegrini M, Rishi P, et al. Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy. Eye (Lond). 2013;27(2):253–64.

    Article  CAS  Google Scholar 

  125. Smith SJ, Smith BD. Evaluating the risk of extraocular tumour spread following intravitreal injection therapy for retinoblastoma: a systematic review. Br J Ophthalmol. 2013;97(10):1231–6.

    Article  PubMed  Google Scholar 

  126. Sun YB, Hui P, Punyara K, Bi MC, Li SH, Teng SY, et al. Intravitreal injection of melphalan in the treatment of retinoblastoma with vitreous cavity seeding. Chin Med J. 2013;126(8):1587.

    PubMed  Google Scholar 

  127. Francis JH, Schaiquevich P, Buitrago E, Del Sole MJ, Zapata G, Croxatto JO, et al. Local and systemic toxicity of intravitreal melphalan for vitreous seeding in retinoblastoma: a preclinical and clinical study. Ophthalmology. 2014;121(9):1810–7.

    Article  PubMed  Google Scholar 

  128. Ghassemi F, Shields CL, Ghadimi H, Khodabandeh A, Roohipoor R. Combined intravitreal melphalan and topotecan for refractory or recurrent vitreous seeding from retinoblastoma. JAMA Ophthalmol. 2014;132(8):936–41.

    Article  PubMed  CAS  Google Scholar 

  129. Lawson BM, Saktanasate J, Say EA, Shields CL. Intravitreal chemotherapy provides control for massive vitreous seeding from retinoblastoma. J Pediatr Ophthalmol Strabismus. 2014;51:e92–4.

    Article  PubMed  Google Scholar 

  130. Smith SJ, Smith BD, Mohney BG. Ocular side effects following intravitreal injection therapy for retinoblastoma: a systematic review. Br J Ophthalmol. 2014;98(3):292–7.

    Article  PubMed  Google Scholar 

  131. Manjandavida FP, Shields CL. The role of intravitreal chemotherapy for retinoblastoma. Indian J Ophthalmol. 2015;63(2):141–5.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Tuncer S, Balci O, Tanyildiz B, Kebudi R, Shields CL. Intravitreal lower-dose (20 microg) melphalan for persistent or recurrent retinoblastoma vitreous seeds. Ophthalmic Surg Lasers Imaging Retina. 2015;46(9):942–8.

    Article  PubMed  Google Scholar 

  133. Francis JH, Marr BP, Brodie SE, Gobin P, Dunkel IJ, Abramson DH. Intravitreal melphalan as salvage therapy for refractory retinal and subretinal retinoblastoma. Retin Cases Brief Rep. 2016;10(4):357–60.

    Article  PubMed  PubMed Central  Google Scholar 

  134. Aziz HA, Kim JW, Munier FL, Berry JL. Acute hemorrhagic retinopathy following intravitreal melphalan injection for retinoblastoma: a report of two cases and technical modifications to enhance the prevention of retinal toxicity. Ocul Oncol Pathol. 2017;3(1):34–40.

    Article  PubMed  Google Scholar 

  135. Berry JL, Shah S, Bechtold M, Zolfaghari E, Jubran R, Kim JW. Long-term outcomes of Group D retinoblastoma eyes during the intravitreal melphalan era. Pediatr Blood Cancer. 2017;64:26696.

    Article  CAS  Google Scholar 

  136. Kiratli H, Koc I, Varan A, Akyuz C. Intravitreal chemotherapy in the management of vitreous disease in retinoblastoma. Eur J Ophthalmol. 2017;27(4):423–7.

    Article  PubMed  Google Scholar 

  137. Berry JL, Bechtold M, Shah S, Zolfaghari E, Reid M, Jubran R, et al. Not all seeds are created equal: seed classification is predictive of outcomes in retinoblastoma. Ophthalmology. 2017;124(12):1817–25.

    Article  PubMed  Google Scholar 

  138. Francis JH, Marr BP, Brodie SE, Abramson DH. Anterior ocular toxicity of intravitreous melphalan for retinoblastoma. JAMA Ophthalmol. 2015;133(12):1459–63.

    Article  PubMed  PubMed Central  Google Scholar 

  139. Francis JH, Brodie SE, Marr B, Zabor EC, Mondesire-Crump I, Abramson DH. Efficacy and toxicity of intravitreous chemotherapy for retinoblastoma: four-year experience. Ophthalmology. 2017;124(4):488–95.

    Article  PubMed  Google Scholar 

  140. Munier FL. Intracameral chemotherapy (melphalan) for aqueous seeding in retinoblastoma: bicameral injection technique and related toxicity in a pilot case study. Ocul Oncol Pathol. 2017;3:149–55.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  142. Francis JH, Abramson DH, Gaillard MC, Marr BP, Beck-Popovic M, Munier FL. The classification of vitreous seeds in retinoblastoma and response to intravitreal melphalan. Ophthalmology. 2015;122(6):1173–9.

    Article  PubMed  Google Scholar 

  143. 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  PubMed  Google Scholar 

  144. Kim JW. Retinoblastoma: evidence for postenucleation adjuvant chemotherapy. Int Ophthalmol Clin. 2015;55(1):77–96.

    Article  PubMed  Google Scholar 

  145. Magramm I, Abramson DH, Ellsworth RM. Optic nerve involvement in retinoblastoma. Ophthalmology. 1989;96(2):217–22.

    Article  CAS  PubMed  Google Scholar 

  146. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Yasui N, Kawamoto H, Fujiwara M, Aihara Y, Ogawa C, Hosono A, et al. High-dose chemotherapy for high-risk retinoblastoma: clinical course and outcome of 14 cases in the National Cancer Center, Japan. Bone Marrow Transplant. 2015;50(2):221–4.

    Article  CAS  PubMed  Google Scholar 

  148. 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  PubMed  Google Scholar 

  149. Kremens B, Wieland R, Reinhard H, Neubert D, Beck JD, Klingebiel T, et al. High-dose chemotherapy with autologous stem cell rescue in children with retinoblastoma. Bone Marrow Transplant. 2003;31(4):281–4.

    Article  CAS  PubMed  Google Scholar 

  150. 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.

    PubMed  Google Scholar 

  151. Dunkel IJ, Jubran RF, Gururangan S, Chantada GL, Finlay JL, Goldman S, et al. Trilateral retinoblastoma: potentially curable with intensive chemotherapy. Pediatr Blood Cancer. 2010;54(3):384–7.

    Article  PubMed  Google Scholar 

  152. Dunkel IJ, Khakoo Y, Kernan NA, Gershon T, Gilheeney S, Lyden DC, et al. Intensive multimodality therapy for patients with stage 4a metastatic retinoblastoma. Pediatr Blood Cancer. 2010;55(1):55–9.

    PubMed  Google Scholar 

  153. Matsubara H, Makimoto A, Higa T, Kawamoto H, Sakiyama S, Hosono A, et al. A multidisciplinary treatment strategy that includes high-dose chemotherapy for metastatic retinoblastoma without CNS involvement. Bone Marrow Transplant. 2005;35(8):763–6.

    Article  CAS  PubMed  Google Scholar 

  154. Lee SH, Yoo KH, Sung KW, Kim JY, Cho EJ, Koo HH, et al. Tandem high-dose chemotherapy and autologous stem cell rescue in children with bilateral advanced retinoblastoma. Bone Marrow Transplant. 2008;42(6):385–91.

    Article  CAS  PubMed  Google Scholar 

  155. Girnius S, Seldin DC, Skinner M, Finn KT, Quillen K, Doros G, et al. Hepatic response after high-dose melphalan and stem cell transplantation in patients with AL amyloidosis associated liver disease. Haematologica. 2009;94(7):1029–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. 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  PubMed  Google Scholar 

  157. Tien HF, Chuang SM, Chen MS, Lee FY, Hou PK. Cytogenetic evidence of multifocal origin of a unilateral retinoblastoma. A help in genetic counseling. Cancer Genet Cytogenet. 1989;42(2):203–8.

    Article  CAS  PubMed  Google Scholar 

  158. Lee SY, Jeon DG, Lee JS, Hwang CS, Huh K, Lee TW, et al. Deletion of Rb1 gene in late osteosarcoma from survivor of unilateral retinoblastoma--a case report. J Korean Med Sci. 1996;11(1):94–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Kim JW, Lee CG, Han SM, Kim KS, Kim JO, Lee JM, et al. Loss of heterozygosity of the retinoblastoma and p53 genes in primary cervical carcinomas with human papillomavirus infection. Gynecol Oncol. 1997;67(2):215–21.

    Article  CAS  PubMed  Google Scholar 

  160. Fung YK, Murphree AL, T'Ang A, Qian J, Hinrichs SH, Benedict WF. Structural evidence for the authenticity of the human retinoblastoma gene. Science. 1987;236(4809):1657–61.

    Article  CAS  PubMed  Google Scholar 

  161. Benedict WF, Fung YK, Murphree AL. The gene responsible for the development of retinoblastoma and osteosarcoma. Cancer. 1988;62(8 Suppl):1691–4.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  163. American Academy of P, Section on O, American Association for Pediatric O, Strabismus, American Academy of O, American Association of Certified O. Red reflex examination in neonates, infants, and children. Pediatrics. 2008;122(6):1401–4.

    Article  Google Scholar 

  164. Abramson DH, Schefler AC. Update on retinoblastoma. Retina. 2004;24(6):828–48.

    Article  PubMed  Google Scholar 

  165. Ayari-Jeridi H, Moran K, Chebbi A, Bouguila H, Abbes I, Charradi K, et al. Mutation spectrum of RB1 gene in unilateral retinoblastoma cases from Tunisia and correlations with clinical features. PLoS One. 2015;10(1):e0116615.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  166. Berry JL, Lewis L, Zolfaghari E, Green S, Le BHA, Lee TC, et al. Suprasellar arachnoid cyst presenting with bobble-head doll movements: a report of 3 cases. Neurol India. 2018;51(3):407–9.

    Google Scholar 

  167. Tang G, Paik S, Baehner FL, Liu Q, Jeong JH, Kim SR, et al. Prognostic impact of the 21-gene recurrence score (RS) on disease-free and overall survival of node-positive, ER-positive breast cancer patients (pts) treated with adjuvant chemotherapy: results from NSABP B-28. J Clin Oncol. 2012;30(27_suppl):1.

    Article  Google Scholar 

  168. Torres-Torres B, Soberino J, Rios S, Gonzalez Rivas CS, Ruiz Vozmediano J, Castillo L, et al. The prognostic value of detection methylation level panel of gene in DNA circulating after and before treatment in patients with breast cancer. J Clin Oncol. 2012;30(30_suppl):67.

    Article  Google Scholar 

  169. Tian S, Wang C, Chang HH, Sun J. Identification of prognostic genes and gene sets for early-stage non-small cell lung cancer using bi-level selection methods. Sci Rep. 2017;7:46164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Peretti U, Ferrara R, Pilotto S, Kinspergher S, Caccese M, Santo A, et al. ALK gene copy number gains in non-small-cell lung cancer: prognostic impact and clinico-pathological correlations. Respir Res. 2016;17(1):105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Lopes GL, Vattimo EF, Castro Junior G. Identifying activating mutations in the EGFR gene: prognostic and therapeutic implications in non-small cell lung cancer. J Bras Pneumol. 2015;41(4):365–75.

    Article  PubMed  PubMed Central  Google Scholar 

  172. Tao KY, Li XX, Xu WZ, Wang Y, Zhu SM, Xie HX, et al. Prognostic role of apoptosis-related gene functional variants in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy. Onco Targets Ther. 2015;8:147–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Hauke RJ Jr, Sissung TM, Figg WD. Discussing the predictive, prognostic, and therapeutic value of germline DNA-repair gene mutations in metastatic prostate cancer patients. Cancer Biol Ther. 2017;18(8):545–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Berg KD. The prognostic and predictive value of TMPRSS2-ERG gene fusion and ERG protein expression in prostate cancer biopsies. Dan Med J. 2016;63:12.

    Google Scholar 

  175. Kulda V, Topolcan O, Kucera R, Kripnerova M, Srbecka K, Hora M, et al. Prognostic significance of TMPRSS2-ERG fusion gene in prostate cancer. Anticancer Res. 2016;36(9):4787–93.

    Article  CAS  PubMed  Google Scholar 

  176. Mendoza PR, Specht CS, Hubbard GB, Wells JR, Lynn MJ, Zhang Q, et al. Histopathologic grading of anaplasia in retinoblastoma. Am J Ophthalmol. 2015;159(4):764–76.

    Article  PubMed  Google Scholar 

  177. Mendoza PR, Geisert EE, Ziesel AC, Specht CS, Hubbard GB, Wells JR, et al. Gene expression profiling of retinoblastoma and retinocytoma. Invest Ophthalmol Vis Sci. 2015;56:3444.

    Google Scholar 

  178. Kooi IE, Mol BM, Massink MP, Ameziane N, Meijers-Heijboer H, Dommering CJ, et al. Somatic genomic alterations in retinoblastoma beyond RB1 are rare and limited to copy number changes. Sci Rep. 2016;6:25264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Kooi IE, Mol BM, Massink MP, de Jong MC, de Graaf P, van der Valk P, et al. A meta-analysis of retinoblastoma copy numbers refines the list of possible driver genes involved in tumor progression. PLoS One. 2016;11(4):e0153323.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  180. Francis JH, Abramson DH, Ji X, Shields CL, Teixeira LF, Schefler AC, et al. Risk of extraocular extension in eyes with retinoblastoma receiving intravitreous chemotherapy. JAMA Ophthalmol. 2017;135(12):1426–9.

    Article  PubMed  PubMed Central  Google Scholar 

  181. Berry JL, Xu L, Kooi I, Murphree AL, Prabakar RK, Reid M, et al. Genomic cfDNA analysis of aqueous humor in retinoblastoma predicts eye salvage: the surrogate tumor biopsy for retinoblastoma. Mol Cancer Res. 2018;16(11):1701–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. 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  PubMed  Google Scholar 

Download references

Acknowledgments

Dr. Berry has grant support from the National Cancer Institute of the National Institute of Health Award Number K08CA232344, The Robert E. and May R. Wright Foundation, The Knights Templar Eye Foundation, the American Cancer Society #IRG-16-181-57, Hyundai Hope on Wheels and the Childhood Eye Cancer Trust.

Disclosure Statement The authors have no financial disclosures or conflicts of interests to disclose regarding the materials presented herein.

Author information

Authors and Affiliations

  1. The Vision Center, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Jesse L. Berry

  2. Department of Ophthalmology, USC Roski Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA

    Jesse L. Berry

Authors
  1. Jesse L. Berry
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jesse L. Berry .

Editor information

Editors and Affiliations

  1. Sankara Nethralaya, Chennai, Tamil Nadu, India

    Vikas Khetan

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Berry, J.L. (2020). Changing Trends in Retinoblastoma Management and What Is in Store for the Future. In: Khetan, V. (eds) Intraocular Tumors. Springer, Singapore. https://doi.org/10.1007/978-981-15-0395-5_3

Download citation

  • DOI: https://doi.org/10.1007/978-981-15-0395-5_3

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-15-0394-8

  • Online ISBN: 978-981-15-0395-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation