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==Overview==
==Overview==
'''Retinoblastoma''' is a [[cancer]] of the [[retina]]. Development of this tumor is initiated by [[mutation]]s<ref>{{cite journal |author=Knudson A |title=Mutation and cancer: statistical study of retinoblastoma |journal=Proc Natl Acad Sci U S A |volume=68 |issue=4 |pages=820-3 |year=1971 |pmid=5279gadgqetqer523}}</ref> that inactivate both copies of the ''[[RB1]]'' gene, which codes for the [[retinoblastoma protein]].<ref>{{cite journal |author=Friend S, Bernards R, Rogelj S, Weinberg R, Rapaport J, Albert D, Dryja T |title=A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma |journal=Nature |volume=323 |issue=6089 |pages=643-6 |year= |pmid=2877398}}</ref>
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 [[Patient|patients]] die of [[Cranium|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. 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.
==Natural History, Complications, and Prognosis==


==Natural History==
=== Natural History ===
Retinoblastoma is a rapidly growing tumor. If left untreated, the tumor fills the eye and completely destroys the globe in six months. Metastatic spread begins after six months and metastasized tumor is very rare at presentation. The tumor may spread through the subarachnoid space to the contralateral optic nerve or through the cerebrospinal fluid to the central nervous system or hematogenously to the lung, bone, or brain or by lymphatics if the tumor spreads anteriorly into the conjunctivae and eyelids, or extends into extraocular tissue. The most common routes of metastatic spread are direct infiltration via the optic nerve to the central nervous system, or spread via the choroid to the orbit.
*Retinoblastoma usually presents with [[leukocoria]].<ref>{{cite book | last = Pizzo | first = Philip | title = Principles and practice of pediatric oncology | publisher = Wolters Kluwer/Lippincott Williams & Wilkins Health | location = Philadelphia, PA | year = 2011 | isbn = 160547682X }}</ref>
If untreated, death usually occurs in few years.
*If left untreated, retinoblastoma can be fatal. The [[tumor]] will continue growing and can invade the entire globe of the [[eye]] with subsequent [[metastasis]].
*The [[tumor]] remains within the globe of the [[eye]] and curable within 3 to 6 months of its first presentation (when it presents with [[leukocoria]]). Delay in the [[diagnosis]] will decrease the [[survival rate]].<ref name="pmid10574806">{{cite journal |vauthors=Goddard AG, Kingston JE, Hungerford JL |title=Delay in diagnosis of retinoblastoma: risk factors and treatment outcome |journal=Br J Ophthalmol |volume=83 |issue=12 |pages=1320–3 |date=December 1999 |pmid=10574806 |doi= |url=}}</ref>
*Death may occur within one year of [[metastasis]].
*[[Metastasis]] may occur via the following four possible pathways:<ref>Singh, Arun D., Carol L. Shields, and Jerry A. Shields. "Prognostic factors in retinoblastoma." Journal of pediatric ophthalmology and strabismus 37.3 (2000): 134.</ref><ref name="pmid8635145">{{cite journal |vauthors=Khelfaoui F, Validire P, Auperin A, Quintana E, Michon J, Pacquement H, Desjardins L, Asselain B, Schlienger P, Vielh P |title=Histopathologic risk factors in retinoblastoma: a retrospective study of 172 patients treated in a single institution |journal=Cancer |volume=77 |issue=6 |pages=1206–13 |date=March 1996 |pmid=8635145 |doi= |url=}}</ref><ref name="pmid18757474">{{cite journal |vauthors=Kim JW, Kathpalia V, Dunkel IJ, Wong RK, Riedel E, Abramson DH |title=Orbital recurrence of retinoblastoma following enucleation |journal=Br J Ophthalmol |volume=93 |issue=4 |pages=463–7 |date=April 2009 |pmid=18757474 |doi=10.1136/bjo.2008.138453 |url=}}</ref><ref name="pmid16632438">{{cite journal |vauthors=Leal-Leal CA, Rivera-Luna R, Flores-Rojo M, Juárez-Echenique JC, Ordaz JC, Amador-Zarco J |title=Survival in extra-orbital metastatic retinoblastoma:treatment results |journal=Clin Transl Oncol |volume=8 |issue=1 |pages=39–44 |date=January 2006 |pmid=16632438 |doi= |url=}}</ref>
**Direct [[invasion]] of the [[central nervous system]] via the [[optic nerve]]
**Through the [[subarachnoid space]] to the [[contralateral]] [[optic nerve]]
**Through the [[cerebrospinal fluid]] to the [[central nervous system]]
**To the [[lungs]], [[bone]], and [[brain]] via the hematogenous route
**The [[tumor]] may also spread via the [[lymphatic|lymphatics]] if the [[tumor]] invades [[Anatomical terms of location|anteriorly]] into the [[Conjunctiva|conjunctivae]], [[Eyelid|eyelids]], or [[Ocular|extraocular]] [[tissue]].  
*Spontaneous regression of the [[tumor]] is a rare occurrence but may occur in a small number of cases.<ref name="pmid898013">{{cite journal| author=Khodadoust AA, Roozitalab HM, Smith RE, Green WR| title=Spontaneous regression of retinoblastoma. | journal=Surv Ophthalmol | year= 1977 | volume= 21 | issue= 6 | pages= 467-78 | pmid=898013 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=898013  }} </ref>
===Complications===
* [[Metastasis]]
*Massive [[choroidal]] [[invasion]]
*[[Tumor]] [[invasion]] into the [[anterior chamber]]
*Large [[tumor]] size with [[vitreous]] seeding
*[[Neovascularization]] of the [[iris]]
*[[Glaucoma]]


The growth form of the cancer can be '''exophytic''', '''endophytic''', '''mixed''' or '''diffuse'''.<ref name="pmid16059563">{{cite journal |author=de Souza Filho JP, Martins MC, Torres VL, Dias AB, Lowen MS, Pires LA, Erwenne CM |title=[Histopathologic findings in retinoblastoma] |language=Portuguese |journal=[[Arquivos Brasileiros De Oftalmologia]] |volume=68 |issue=3 |pages=327–31 |year=2005 |pmid=16059563 |doi=/S0004-27492005000300010 |url=http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27492005000300010&lng=en&nrm=iso&tlng=en |accessdate=2012-05-07}}</ref>
* Recurrence of [[tumor]]
* Trilateral retinoblastoma<ref name="DunkelJubran2010">{{cite journal|last1=Dunkel|first1=Ira J.|last2=Jubran|first2=Rima F.|last3=Gururangan|first3=Sri|last4=Chantada|first4=Guillermo L.|last5=Finlay|first5=Jonathan L.|last6=Goldman|first6=Stewart|last7=Khakoo|first7=Yasmin|last8=O'Brien|first8=Joan M.|last9=Orjuela|first9=Manuela|last10=Rodriguez-Galindo|first10=Carlos|last11=Souweidane|first11=Mark M.|last12=Abramson|first12=David H.|title=Trilateral retinoblastoma: Potentially curable with intensive chemotherapy|journal=Pediatric Blood & Cancer|volume=54|issue=3|year=2010|pages=384–387|issn=15455009|doi=10.1002/pbc.22336}}</ref><ref name="KimDunkel2015">{{cite journal|last1=Kim|first1=Jonathan W.|last2=Dunkel|first2=Ira|title=Trilateral Retinoblastoma|year=2015|pages=209–213|doi=10.1007/978-3-662-43451-2_20}}</ref>


In the exophytic growth which occurs in the subretinal space is often associated with subretinal fluid accumulation and retinal detachment. The growth may infiltrate through the [[Bruch membrane]](the innermost layer of the choroid) in to the [[choroid]] and then invade the [[ciliary nerves]] and blood vessels. The increase in caliber and tortuosity of retinal vessels which are noted in exophytic growth is because they lie over the mass. It usually results in [[proptosis]] and [[retinal detachment]].
*Elevated [[intracranial pressure|intracranial pressure (ICP)]]


In the endophytic growth, the tumor breaks through the internal limiting membrane of retina and it is typically associated with vitreous seeding. There are no surface vessels in endophytic growth. It usually causes visual disturbance and [[white eye reflex]].
* Subsequent [[neoplasms]]<ref name="pmid19066271">{{cite journal |vauthors=Marees T, Moll AC, Imhof SM, de Boer MR, Ringens PJ, van Leeuwen FE |title=Risk of second malignancies in survivors of retinoblastoma: more than 40 years of follow-up |journal=J. Natl. Cancer Inst. |volume=100 |issue=24 |pages=1771–9 |date=December 2008 |pmid=19066271 |doi=10.1093/jnci/djn394 |url=}}</ref>
 
The mixed growth pattern is the most common growth pattern and cobine the clinical features of both exophytic and endophytic growth patterns.
 
In diffuse growth, there is relatively flat infiltration of the retina instead of a discrete mass. Diagnosis is very difficult and delayed. They produce a picture that may be mistaken for [[Vitritis]], [[Retinitis]] or [[Endophthalmitis]]
 
Spontaneous regression of the tumor is very rare and may occur due to unknown mechanism.(occlusion of the central retinal artery, severe inflammatory reaction and massive necrosis leading to [[pthisis bulbi]])
 
==Prognosis==
The prognosis of retinoblastoma depends on the following:
:*Whether or not the tumor can be removed by surgery.
:*The stage of the cancer: the size of the tumor, whether the cancer has spread
:*The child’s general health
 
==='''Reese-Ellsworth classification(REC) for Retinoblastoma''':===
 
The Reese-Ellsworh classification was developed in the 1960s by Dr.Algernon Reese and Dr.Robert Ellsworth, two prominent New York doctors specialising in retinoblastoma. The system was designed to predict outcome from treatment with [[External beam radiotherapy(EBRT)]], used internationally as the primary eye salvage treatment until intoduction of chemotherapy in the 1980s.
 
The REC is rarely used today as chemotherapy has superseded radiotherapy as the favoured treatment for eye salvage.
 
'''Group 1''': Very favourable for maintenance of sight
 
'''A''': Solitary tumor, smaller than 4 disc diameters(DD) at or behind the equator
 
'''B''': Multiple tumors, none larger than 4 DD, all at or behind the equator
 
'''Group 2''': Favourable for maintenance of sight
 
'''A''': Solitary tumor, 4 to 10 DD at or behind the equator
 
'''B''': Multiple tumors, 4 to 10 DD behind the equator
 
'''Group 3''': possible for maintenance of sight
 
'''A''': Any lesion anterior to the equator
 
'''B''': Solitary tumor, larger than 10 DD behind the equator
 
'''Group 4''': unfavourable for maintenance of sight
 
'''A''': Multiple tumors, some larger than 10 DD
 
'''B''': Any lesion extending anteriorly to the [[ora serrata]]
 
'''Group 5''': very unfavourable for maintenance of sight
 
'''A''': Massive tumors involving more than one half of the [[retina]]
 
'''B''': [[Vitreous]] seeding
 
===Essen classification:===
[[image:Essen classification.jpg|center|650px]]
<br clear="left"/>
 
===International retinoblastoma classification:===
<div>
{| cellspacing="3" cellpadding="2"
|-
| '''Stage 0: '''Patients treated conservatively (subject to presurgical ophthalmologic classifications)
|-
| '''Stage I: '''Eye enucleated, completely resected histologically
|-
|-
| '''Stage II: '''Eye enucleated, microscopic residual tumor
|-
|-
| '''Stage III: '''Regional extensiona
|-
| a) Overt orbital disease
|-
| b) Preauricular or cervical lymph node extension
|-
|-
| '''Stage IV: '''Metastatic disease
|-
| a) Hematogenous metastasis:
|-
| 1. single lesion
|-
| 2. multiple lesions
|-
| b) CNS extension:
|-
| 1. Prechiasmatic lesion
|-
| 2. CNS mass
|-
| 3. Leptomeningeal disease
|}
</div>
 
===The International Intraocular Retinoblastoma Classification(IIRC)or The ABC classification:===
 
{| cellspacing="3" cellpadding="2"
|-
| '''Group A: '''small tumors away from foveola and disc
|-
| • Tumors <3 mm in greatest dimension confined to the retina and
|-
| • Located at least 3 mm from the foveola and 1.5 mm from the optic disc
|-
| '''Group B: '''all remaining tumors confined to the retina
|-
| • All other tumors confined to the retina and not in group A
|-
| • Subretinal fluid (without subretinal seeding) < 3 mm from the base of the tumor
|-
| '''Group C: '''local subretinal fluid or vitreous seeding
|-
| • Subretinal fluid alone >3 mm and < 6 mm from the tumor
|-
| • Vitreous or subretinal seeding < 3 mm from the tumor
|-
| '''Group D: '''diffuse subretinal fluid or seeding
|-
| • Subretinal fluid > 6 mm from the tumor
|-
| • Vitreous or subretinal seeding > 3 mm from the tumor
|-
| '''Group E: '''presence of any one or more of these poor prognosis features
|-
| • More than 2/3 of the globe filled with tumor
|-
| • Tumor in the anterior segment or anterior to the vitreous
|-
| • Tumor in or on the ciliary body
|-
| • Iris neovascularisation
|-
| • Neovascular glaucoma
|-
| • Opaque media from hemorrhage
|-
| • Tumor necrosis with aseptic orbital celullitis
|-
| • Phthisis bulbi
|}
 
===Survival:===
 
The survival for children diagnosed with retinoblastoma in the period 1975-94 was quite favourable, with more than 93% alive at five years after diagnosis and males and females had similar 5 year survival rates for the period 1975-94 and black children had slightly lower survival rates than white children.(89% versus 94%)<ref>http://seer.cancer.gov/publications/childhood/retinoblastoma.pdf</ref>  Trilateral retinoblastoma has a poor prognosis, especially when tumor spreads to the sub-arachnoid space.<ref name="pmid15269048">{{cite journal |author=Provenzale JM, Gururangan S, Klintworth G |title=Trilateral retinoblastoma: clinical and radiologic progression |journal=[[AJR. American Journal of Roentgenology]] |volume=183 |issue=2 |pages=505–11 |year=2004 |month=August |pmid=15269048 |doi= |url=http://www.ajronline.org/cgi/pmidlookup?view=long&pmid=15269048 |accessdate=2012-05-02}}</ref> After a pineal or sellar mass is detected, the mean length of survival is 9.7 months in patients who undergo treatment and 1.3 months in those who do not.<ref name="pmid1985763">{{cite journal |author=Holladay DA, Holladay A, Montebello JF, Redmond KP |title=Clinical presentation, treatment, and outcome of trilateral retinoblastoma |journal=[[Cancer]] |volume=67 |issue=3 |pages=710–5 |year=1991 |month=February |pmid=1985763 |doi= |url= |accessdate=2012-05-02}}</ref>
 
==Possible complications==
*Local spread of tumor.
*Development of other tumors.
*Cataract from radiotherapy.
*Failure of tooth eruption after radiotherapy.
*Bony deformities


===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>
*Regarding the variable accessibility of [[patients]] to the resources, the [[survival rate]] may range from < 30% in low and middle income societies to > 90% in developed countries.<ref name="pmid22414599">{{cite journal |vauthors=Dimaras H, Kimani K, Dimba EA, Gronsdahl P, White A, Chan HS, Gallie BL |title=Retinoblastoma |journal=Lancet |volume=379 |issue=9824 |pages=1436–46 |date=April 2012 |pmid=22414599 |doi=10.1016/S0140-6736(11)61137-9 |url=}}</ref>
*The overall 5-year [[survival rate]] increased over the years and was reported 97.3% from 2000 to 2012.<ref name="FernandesPollock2018">{{cite journal|last1=Fernandes|first1=Arthur Gustavo|last2=Pollock|first2=Benjamin D.|last3=Rabito|first3=Felicia A.|title=Retinoblastoma in the United States: A 40-Year Incidence and Survival Analysis|journal=Journal of Pediatric Ophthalmology & Strabismus|volume=55|issue=3|year=2018|pages=182–188|issn=0191-3913|doi=10.3928/01913913-20171116-03}}</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>
*The [[survival rate]] is higher for unilateral involvement than the [[bilateral]] form of the [[tumor]].
*It has been observed that [[survival rate]] varies depending upon the following factors:
**Laterality of the [[tumor]]
**Age at the time of [[diagnosis]]
**Decade of [[diagnosis]]
*The overall [[prognosis]] of trilateral retinoblastoma is poor and [[Patient|patients]] usually die within the first year of the [[diagnosis]].<ref name="pmid8040018">{{cite journal |vauthors=Blach LE, McCormick B, Abramson DH, Ellsworth RM |title=Trilateral retinoblastoma--incidence and outcome: a decade of experience |journal=Int. J. Radiat. Oncol. Biol. Phys. |volume=29 |issue=4 |pages=729–33 |date=July 1994 |pmid=8040018 |doi= |url=}}</ref>
*Intraocular Classification of Retinoblastoma (ICRB) has been observed to have the ability to predict the outcome of [[chemotherapy]]:<ref name="pmid16996605">{{cite journal |vauthors=Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT, Shields JA |title=The International Classification of Retinoblastoma predicts chemoreduction success |journal=Ophthalmology |volume=113 |issue=12 |pages=2276–80 |date=December 2006 |pmid=16996605 |doi=10.1016/j.ophtha.2006.06.018 |url=}}</ref>
**Category A - C is associated with ≥ 90% chance to salvage the [[eye]].
**Category D is associated with a 47% chance to salvage the [[eye]].
**Category E is excluded due to eye [[enucleation]].
*[[Prognosis]] is usually poor with non-[[ocular]] [[tumor]] and it usually occurs in individuals who have received [[radiation therapy]] for their primary retinoblastoma [[tumors]].<ref name="pmid15196536">{{cite journal |vauthors=Aerts I, Pacquement H, Doz F, Mosseri V, Desjardins L, Sastre X, Michon J, Rodriguez J, Schlienger P, Zucker JM, Quintana E |title=Outcome of second malignancies after retinoblastoma: a retrospective analysis of 25 patients treated at the Institut Curie |journal=Eur. J. Cancer |volume=40 |issue=10 |pages=1522–9 |date=July 2004 |pmid=15196536 |doi=10.1016/j.ejca.2004.03.023 |url=}}</ref>
==References==
==References==
<references/>
{{reflist|2}}
 
==See also==
*[[Eye cancer]]
*[[Eye examination]]
 
{{Nervous tissue tumors}}


[[Category:Ophthalmology]]
[[Category:Medicine]]
[[Category:Types of cancer]]
[[Category:hereditary cancers]]
[[Category:Oncology]]
[[Category:Oncology]]
[[Category:Oncology stub]]
[[Category:Up-To-Date]]
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Latest revision as of 23:59, 29 July 2020

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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] Sahar Memar Montazerin, M.D.[3]

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. 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.

Natural History, Complications, and Prognosis

Natural History

Complications

Prognosis

  • Those with heritable form of the disease have 50% risk of transmitting the mutation to their offspring.[11]
  • Regarding the variable accessibility of patients to the resources, the survival rate may range from < 30% in low and middle income societies to > 90% in developed countries.[12]
  • The overall 5-year survival rate increased over the years and was reported 97.3% from 2000 to 2012.[13]
  • Prognosis is generally good, and the survival rate of patients with retinoblastoma with treatment is approximately 95%, in the United States.[14]
  • The survival rate is higher for unilateral involvement than the bilateral form of the tumor.
  • It has been observed that survival rate varies depending upon the following factors:
  • The overall prognosis of trilateral retinoblastoma is poor and patients usually die within the first year of the diagnosis.[15]
  • Intraocular Classification of Retinoblastoma (ICRB) has been observed to have the ability to predict the outcome of chemotherapy:[16]
    • Category A - C is associated with ≥ 90% chance to salvage the eye.
    • Category D is associated with a 47% chance to salvage the eye.
    • Category E is excluded due to eye enucleation.
  • Prognosis is usually poor with non-ocular tumor and it usually occurs in individuals who have received radiation therapy for their primary retinoblastoma tumors.[17]

References

  1. ↑ Pizzo, Philip (2011). Principles and practice of pediatric oncology. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins Health. ISBN 160547682X.
  2. ↑ Goddard AG, Kingston JE, Hungerford JL (December 1999). "Delay in diagnosis of retinoblastoma: risk factors and treatment outcome". Br J Ophthalmol. 83 (12): 1320–3. PMID 10574806.
  3. ↑ Singh, Arun D., Carol L. Shields, and Jerry A. Shields. "Prognostic factors in retinoblastoma." Journal of pediatric ophthalmology and strabismus 37.3 (2000): 134.
  4. ↑ Khelfaoui F, Validire P, Auperin A, Quintana E, Michon J, Pacquement H, Desjardins L, Asselain B, Schlienger P, Vielh P (March 1996). "Histopathologic risk factors in retinoblastoma: a retrospective study of 172 patients treated in a single institution". Cancer. 77 (6): 1206–13. PMID 8635145.
  5. ↑ Kim JW, Kathpalia V, Dunkel IJ, Wong RK, Riedel E, Abramson DH (April 2009). "Orbital recurrence of retinoblastoma following enucleation". Br J Ophthalmol. 93 (4): 463–7. doi:10.1136/bjo.2008.138453. PMID 18757474.
  6. ↑ Leal-Leal CA, Rivera-Luna R, Flores-Rojo M, Juárez-Echenique JC, Ordaz JC, Amador-Zarco J (January 2006). "Survival in extra-orbital metastatic retinoblastoma:treatment results". Clin Transl Oncol. 8 (1): 39–44. PMID 16632438.
  7. ↑ Khodadoust AA, Roozitalab HM, Smith RE, Green WR (1977). "Spontaneous regression of retinoblastoma". Surv Ophthalmol. 21 (6): 467–78. PMID 898013.
  8. ↑ Dunkel, Ira J.; Jubran, Rima F.; Gururangan, Sri; Chantada, Guillermo L.; Finlay, Jonathan L.; Goldman, Stewart; Khakoo, Yasmin; O'Brien, Joan M.; Orjuela, Manuela; Rodriguez-Galindo, Carlos; Souweidane, Mark M.; Abramson, David H. (2010). "Trilateral retinoblastoma: Potentially curable with intensive chemotherapy". Pediatric Blood & Cancer. 54 (3): 384–387. doi:10.1002/pbc.22336. ISSN 1545-5009.
  9. ↑ Kim, Jonathan W.; Dunkel, Ira (2015). "Trilateral Retinoblastoma": 209–213. doi:10.1007/978-3-662-43451-2_20.
  10. ↑ Marees T, Moll AC, Imhof SM, de Boer MR, Ringens PJ, van Leeuwen FE (December 2008). "Risk of second malignancies in survivors of retinoblastoma: more than 40 years of follow-up". J. Natl. Cancer Inst. 100 (24): 1771–9. doi:10.1093/jnci/djn394. PMID 19066271.
  11. ↑ 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.
  12. ↑ Dimaras H, Kimani K, Dimba EA, Gronsdahl P, White A, Chan HS, Gallie BL (April 2012). "Retinoblastoma". Lancet. 379 (9824): 1436–46. doi:10.1016/S0140-6736(11)61137-9. PMID 22414599.
  13. ↑ Fernandes, Arthur Gustavo; Pollock, Benjamin D.; Rabito, Felicia A. (2018). "Retinoblastoma in the United States: A 40-Year Incidence and Survival Analysis". Journal of Pediatric Ophthalmology & Strabismus. 55 (3): 182–188. doi:10.3928/01913913-20171116-03. ISSN 0191-3913.
  14. ↑ 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.
  15. ↑ Blach LE, McCormick B, Abramson DH, Ellsworth RM (July 1994). "Trilateral retinoblastoma--incidence and outcome: a decade of experience". Int. J. Radiat. Oncol. Biol. Phys. 29 (4): 729–33. PMID 8040018.
  16. ↑ Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT, Shields JA (December 2006). "The International Classification of Retinoblastoma predicts chemoreduction success". Ophthalmology. 113 (12): 2276–80. doi:10.1016/j.ophtha.2006.06.018. PMID 16996605.
  17. ↑ Aerts I, Pacquement H, Doz F, Mosseri V, Desjardins L, Sastre X, Michon J, Rodriguez J, Schlienger P, Zucker JM, Quintana E (July 2004). "Outcome of second malignancies after retinoblastoma: a retrospective analysis of 25 patients treated at the Institut Curie". Eur. J. Cancer. 40 (10): 1522–9. doi:10.1016/j.ejca.2004.03.023. PMID 15196536.
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