Retinoblastoma medical therapy: Difference between revisions

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{{Retinoblastoma}}
{{Retinoblastoma}}
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{{CMG}}; {{AE}} {{Sahar}} {{Simrat}}
==Overview==
==Overview==
The optimal therapy for retinoblastoma depends on several factors such as [[tumor]] size, tumor location, presence or absence of vitreous or subretinal seeds, and patient age. The various treatment modalities for retinoblastoma include [[enucleation]], external beam [[radiation therapy]], radioactive plaques (I-125 [[brachytherapy]]), [[cryotherapy]], laser photoablation, thermotherapy, and [[chemotherapy]] (which includes systemic, intra-arterial, and [[intravitreal]]).<ref name="wiki">  Retinoblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Retinoblastoma Accessed on October 10 2015</ref>
The optimal [[therapy]] for retinoblastoma depends on the stage at [[diagnosis]]. [[Systemic]] [[chemotherapy]] via [[carboplatin]], [[etoposide]], and [[vincristine]] (CEV) is the most common regimen used to treat retinoblastoma.


==Medical therapy for intraocular tumors==
==Medical Therapy==
The priority of retinoblastoma treatment is to preserve the life of the child, then to preserve vision, and then to minimize complications or side effects of treatment. The exact course of treatment will depend on the individual case and will be decided by the [[ophthalmologist]] in discussion with the paediatric oncologist. Children with involvement of both eyes at diagnosis usually require multimodality therapy ([[chemotherapy]] and local therapies).<ref name="wiki">  Retinoblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Retinoblastoma Accessed on October 10 2015</ref>  
*The priority of retinoblastoma treatment is to:<ref name="NIH">Retinoblastoma Treatment. National Cancer Institute(2015) http://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq#section/_53 Accessed on October 13, 2015</ref>
The goals of therapy are the following:<ref name="NIH"> Retinoblastoma Treatment. National Cancer Institute(2015) http://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq#section/_53 Accessed on October 13 2015</ref>  
**Save the life of the [[child]]
*Eradicate the disease to save the patient's life
**Preserve [[vision]]
**Minimize [[Complication (medicine)|complications]] or [[Adverse effect (medicine)|side effects]] of treatment
*The exact course of treatment will depend upon the individual case and will be decided by the [[ophthalmologist]] in discussion with the [[pediatric]] [[oncologist]].
*[[Child|Children]] with the involvement of both [[Eye|eyes]] at [[diagnosis]] usually require multimodality [[therapy]] ([[chemotherapy]] and local [[Therapy|therapies]]).<br>
*The choice of [[therapy]] depends upon several factors, such as:<ref name="pmid9972509">{{cite journal| author=Shields CL, Shields JA| title=Recent developments in the management of retinoblastoma. | journal=J Pediatr Ophthalmol Strabismus | year= 1999 | volume= 36 | issue= 1 | pages= 8-18; quiz 35-6 | pmid=9972509 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9972509  }} </ref>
**[[Tumor]] size
**[[Tumor]] location
**Presence or absence of [[vitreous]] or subretinal seeds
**Age of the [[patient]]


*Preserve as much vision as possible
===Systemic Chemotherapy===
*Decrease risk of late sequelae from treatment, particularly subsequent neoplasms
*[[Systemic]] [[chemotherapy]] has become the forefront of treatment in the past decade, in search of [[Eyeball|globe]] preserving measures and to avoid the [[adverse effects]] of [[radiation therapy]].<ref name="VenkatramaniJubran2015">{{cite journal|last1=Venkatramani|first1=Rajkumar|last2=Jubran|first2=Rima Fuad|title=Retinoblastoma: Intravenous Chemotherapy|year=2015|pages=119–127|doi=10.1007/978-3-662-43451-2_11}}</ref><br>
The choice of therapy depends upon several factors such as:<ref name="pmid9972509">{{cite journal| author=Shields CL, Shields JA| title=Recent developments in the management of retinoblastoma. | journal=J Pediatr Ophthalmol Strabismus | year= 1999 | volume= 36 | issue= 1 | pages= 8-18; quiz 35-6 | pmid=9972509 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9972509  }} </ref>
*The common [[Indication (medicine)|indications]] for [[systemic]] [[chemotherapy]] include:
*Tumor size
**Unilateral intraocular retinoblastoma with high risk features
*[[Tumor]] location
**Bilateral intraocular retinoblastoma
*Presence or absence of [[vitreous]] or subretinal seeds
**[[Prophylaxis]] against [[metastasis]] following [[enucleation]] in the presence of [[histopathologic]] high-risk features
*Patient age
**Extraocular retinoblastoma with local and/or regional spread
The various treatment modalities for retinoblastoma include:
**[[Metastatic]] retinoblastoma with or without [[CNS]] involvement
===Enucleation of the eye===
**Trilateral retinoblastoma
Most patients with unilateral disease present with advanced intraocular disease and therefore usually undergo [[enucleation]], which results in a cure rate of 95%. In bilateral retinoblastoma, enucleation is usually reserved for eyes that have failed all known effective therapies or without useful vision.
'''Chemotherapy Regimen'''<br>
===External beam radiotherapy (EBR)===
*The most common [[chemotherapy]] regimen for retinoblastoma is the combination of the following:<ref name="Rodriguez-GalindoWilson2003">{{cite journal|last1=Rodriguez-Galindo|first1=Carlos|last2=Wilson|first2=Matthew W.|last3=Haik|first3=Barrett G.|last4=Merchant|first4=Thomas E.|last5=Billups|first5=Catherine A.|last6=Shah|first6=Nirali|last7=Cain|first7=Alvida|last8=Langston|first8=James|last9=Lipson|first9=Mindy|last10=Kun|first10=Larry E.|last11=Pratt|first11=Charles B.|title=Treatment of Intraocular Retinoblastoma With Vincristine and Carboplatin|journal=Journal of Clinical Oncology|volume=21|issue=10|year=2003|pages=2019–2025|issn=0732-183X|doi=10.1200/JCO.2003.09.103}}</ref><ref name="pmid8906022">{{cite journal |vauthors=Gallie BL, Budning A, DeBoer G, Thiessen JJ, Koren G, Verjee Z, Ling V, Chan HS |title=Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy |journal=Arch. Ophthalmol. |volume=114 |issue=11 |pages=1321–8 |date=November 1996 |pmid=8906022 |doi= |url=}}</ref><ref name="pmid17301956">{{cite journal |vauthors=Dunkel IJ, Lee TC, Shi W, Beaverson KL, Novetsky D, Lyden D, Finlay JL, McCormick B, Abramson DH |title=A phase II trial of carboplatin for intraocular retinoblastoma |journal=Pediatr Blood Cancer |volume=49 |issue=5 |pages=643–8 |date=October 2007 |pmid=17301956 |doi=10.1002/pbc.21163 |url=}}</ref>
The most common indication for EBR is for the eye in a young child with bilateral retinoblastoma who has active or recurrent disease after completion of [[chemotherapy]] and local therapies. However, patients with hereditary disease who received EBR therapy are reported to have a 35% increased risk of recurrence.
**[[Carboplatin]]
**[[Etoposide]]
**[[Vincristine]]
*This combination may be used with different [[dose]] of [[medication]] and frequency depending upon the [[Cancer staging|stage]] of the [[tumor]].
**Usually, the treatment regimen is comprised of either three sessions of high [[dose]] regimen or six sessions of low [[dose]] regimen.
**Low [[dose]] regimen:
***[[Carboplatin]] 18.6 mg/kg IV q24h for one day and repeated every (21 - 28) days
***[[Etoposide]] 5 mg/kg IV q24h for two days and repeated (21 - 28) days
***[[Vincristine]] 0.05 mg/kg IV q24h for one day and repeated every (21 - 28) days
**High [[dose]] regimen:
***[[Carboplatin]] 28 mg/kg IV q24h for one day and repeated every (21 - 28) days
***[[Etoposide]] 12 mg/kg IV q24h for two days and repeated every (21 - 28) days
***[[Vincristine]] 0.05 mg/kg IV q24h for one day and repeated every (21 - 28) days
**The above mentioned [[dosage]] is recommended for orbital retinoblastoma and is subject to change for other types of tumor presentation.
===Intra-arterial Chemotherapy===
*[[Chemotherapeutic agents|Chemotherapeutic drugs]] are administered locally via a thin [[catheter]] threaded through the [[groin]], [[aorta]], and the [[neck]] directly into the [[optic]] [[Blood vessel|vessels]].
==Other Interventions==
*Other treatment [[Modality|modalities]] which are currently available for retinoblastoma include:<ref name="KimMurphree2015">{{cite journal|last1=Kim|first1=Jonathan W.|last2=Murphree|first2=A. Linn|last3=Singh|first3=Arun D.|title=Retinoblastoma: Treatment Options|year=2015|pages=89–107|doi=10.1007/978-3-662-43451-2_9}}</ref>
===[[External beam radiotherapy|External Beam Radiotherapy (EBRT)]]===
*The feasibility of [[external beam radiotherapy]] depends on the [[Cancer staging|stage]] of retinoblastoma at the time of [[diagnosis]].<br>
*The globe preservation rate with this method varies according to the [[Cancer staging|stage]] of the [[tumor]] at the time of [[diagnosis]]:


===Brachytherapy===
*'''Groups I–II eyes:''' 95%
[[Brachytherapy]] involves the placement of a radioactive implant (plaque), usually on the sclera adjacent to the base of a tumor. It is used as the primary treatment or, more frequently, in patients with small tumors or in those who had failed initial therapy including previous EBR therapy.


===Thermotherapy===
*'''Groups IV and V eyes:''' 50%
[[Thermotherapy]] involves the application of heat directly to the tumor, usually in the form of infrared radiation. It is also used for small tumors.


===Laser photocoagulation===
*This method is [[Indication (medicine)|indicated]] as [[salvage therapy]] for seeding following unsuccessful [[chemotherapy]], however, the decision to use this method of treatment must be made on a case by case basis.<br>
*The [[dose]] to target [[Tumor|tumor cells]] of [[retina]] ranges from 3,600 to 4,500 cGy administered in 180 - 200 cGy daily fractions 5 times/week.<br>
*[[Contraindications]] of [[External beam radiotherapy|EBRT]]:
**Children less than 1 year of age (due to the risk of secondary [[malignancies]])
**[[Eye|Eyes]] with dismal [[visual]] potential


[[Laser photocoagulation]] is recommended only for small posterior tumors. An argon or diode laser or a xenon arc is used to coagulate all the blood supply to the [[tumor]].
===[[Brachytherapy]]===
===Cryotherapy===
*[[Indication (medicine)|Indications]]:
[[Cryotherapy]] induces damage to the vascular endothelium with secondary [[thrombosis]] and infarction of the tumor tissue by rapidly freezing it. Cryotherapy may be used as primary therapy for small peripheral tumors or small recurrent tumors previously treated with other methods.
**Primary treatment
**Residual [[tumor]] following [[Laser therapy|photocoagulation]]/[[thermotherapy]]/[[Thermotherapy|thermo]]-[[chemotherapy]]/[[cryotherapy]]
**[[Tumor]] recurrence
**[[Tumor]] size less than 15 mm in [[diameter]]
*[[Contraindication]]:
**Presence of [[diffuse]] [[vitreous]] seeding
===[[Thermotherapy]]===
*[[Indication (medicine)|Indications]]:
**[[Tumor|Tumors]] not larger than 3 mm in [[diameter]] with no evidence of seeding, and located [[Anatomical terms of location|posterior]] to the equator
**Primary treatment
**[[Consolidation (medicine)|Consolidation]] treatment
**[[Tumor]] recurrence


===Systemic chemotherapy===
===[[Thermotherapy|Thermo]]-[[chemotherapy]]===
Systemic [[chemotherapy]] has become forefront of treatment in the past decade, in search of globe preserving measures and to avoid the adverse effects of EBR therapy. The common indications for chemotherapy for intraocular retinoblastoma include:
*[[Indication (medicine)|Indications]]:
*Large tumors  
**[[Tumors]] not larger than 12 mm in [[diameter]] with no evidence of seeding, and located [[Anatomical terms of location|posterior]] to the equator
*Tumors that cannot be treated with local therapies alone
**[[Consolidation (medicine)|Consolidation]] treatment
*Bilateral tumors
===[[Laser photocoagulation|Laser Photocoagulation]]===
*Invasion into the [[choroid]], [[optic nerve]], [[sclera]], [[orbit]], or [[anterior chamber]]
*This method is [[Indication (medicine)|indicated]] for intraocular retinoblastoma and one of the following factors:
 
**[[Consolidation (medicine)|Consolidation]] of large [[Tumor|tumors]] after [[systemic]] [[chemotherapy]]
===Intra-arterial chemotherapy===
**For the treatment of small peripheral or [[Anatomical terms of location|posterior]] [[Tumor|tumors]] as the sole [[modality]]
Chemotherapeutic drugs are administered locally via a thin catheter threaded through the groin, aorta, and the neck directly into the optic vessels.
**For the eradication of small [[tumor]] recurrences following [[chemotherapy]] and/or [[radiotherapy]]
 
*This method is suitable for treating [[tumors]] with the following characteristics:
===Nano-particulate chemotherapy===
**3.0 mm or less in [[diameter]]
To reduce the adverse effects of systemic therapy, subconjuctival (local) injection of nanoparticle carriers containing chemotherapeutic agents ([[carboplatin]]) has been developed which has shown promising results in the treatment of retinoblastoma in animal models without adverse effects
**2.0 mm or less in thickness
{| style="border: 0px; font-size: 90%; margin: 3px; width: 800px" align=center
**Without seeding into the adjacent [[vitreous]]
|valign=top|
===[[Cryotherapy]]===
*[[Indication (medicine)|Indications]]:
**[[Tumors]] not larger than 3 mm in [[diameter]], with no evidence of seeding, and located [[Anatomical terms of location|anterior]] to the equator
**Primary treatment
**[[Consolidation (medicine)|Consolidation]] treatment
**[[Tumor]] recurrence
===Management Options of Retinoblastoma===
:*
{| class="wikitable"
|+
|+
{| class="wikitable"
! colspan="2" |Treatment options for Intraocular [[tumor]]<ref name="urlRetinoblastoma Treatment (PDQ®)—Health Professional Version - National Cancer Institute">{{cite web |url=https://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq#_13 |title=Retinoblastoma Treatment (PDQ®)—Health Professional Version - National Cancer Institute |format= |work= |accessdate=}}</ref>
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Patient Group}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Treatment Line}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Treatment}}
|-
|-
| colspan="3" style="font-weight: bold;" | With vitreous seeding
!Unilateral retinoblastoma
|
*[[Enucleation]] followed by [[chemotherapy]]
*Conservative [[ocular]] salvage approaches:
**Chemoreduction with either [[systemic]] or [[ophthalmic artery]] [[infusion]] [[chemotherapy]] with or without [[intravitreal]] [[chemotherapy]]
**Local treatments ([[cryotherapy]], [[thermotherapy]], and plaque [[radiation therapy]])
|-
|-
| rowspan="2" style="font-weight: bold;" | With gross anterior chamber involvement or neovascular glaucoma or orbital  inflammation
!Bilateral retinoblastoma
| First
|
| Enucleation
*[[Enucleation]] for large intraocular [[tumors]], followed by risk-adapted [[chemotherapy]] when the [[eye]] and [[vision]] cannot be saved
* Conservative [[ocular]] salvage approaches when the [[eye]] and [[vision]] can be saved:
**Chemoreduction with either [[systemic]] or [[ophthalmic artery]] [[infusion]] [[chemotherapy]] with or without [[intravitreal]] [[chemotherapy]]
**Local treatments ([[cryotherapy]], [[thermotherapy]], and plaque [[radiation therapy]])
**[[External beam radiotherapy|EBRT]]
|-
|-
| Adjunct
!Cavitary retinoblastoma
| Postoperative systemic chemotherapy
|
*[[Systemic]] and/or [[Intra-arterial Chemotherapy for Retinoblastoma|intra-arterial]] [[chemotherapy]]
|-
|-
| rowspan="5" style="font-weight: bold;" | Without gross anterior chamber involvement  or neovascular glaucoma or orbital inlammation
!Progressive or recurrent intraocular retinoblastoma
| First
|
| Systemic or intra-arterial chemotherapy
*[[Enucleation]]
|-
*[[Radiation therapy]] ([[External beam radiation therapy|EBRT]] or plaque [[radiation therapy]])
| Plus
* Local treatments ([[cryotherapy]] or [[thermotherapy]])
| Concurrent laser ablation or chemotherapy
*[[Salvage therapy|Salvage]] [[chemotherapy]] ([[systemic]] or [[Intra-arterial Chemotherapy for Retinoblastoma|intra-arterial]])
|-
*[[Intravitreal]] [[chemotherapy]]
| Second
|+
| External beam radiation therapy
! colspan="2" |Treatment options for Extraocular [[tumor]]<ref name="urlRetinoblastoma Treatment (PDQ®)—Health Professional Version - National Cancer Institute">{{cite web |url=https://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq#_13 |title=Retinoblastoma Treatment (PDQ®)—Health Professional Version - National Cancer Institute |format= |work= |accessdate=}}</ref>
|-
| Third
| Periocular carboplatin therapy
|-
| Fourth
| Enucleation
|-
| colspan="3" style="font-weight: bold;" | Without vitreous seeding
|-
| rowspan="5" style="font-weight: bold;" | Tumor >2 disc diameters in size
| First
| Systemic or intra-arterial chemotherapy
|-
| Plus
| Concurrent laser ablation or cryotherapy
|-
| Second
| External beam radiation therapy
|-
| Third
| Periocular carboplatin therapy
|-
| Fourth
| Enucleation
|-
|-
| rowspan="6" style="font-weight: bold;" | Tumor 2 disc diameters or less in size
![[Orbit (anatomy)|Orbital]] and locoregional retinoblastoma
| First
|
| Focal laser ablation alone
* [[Chemotherapy]]
* [[Radiation therapy]]
|-
|-
| Second
![[CNS disease]]
| Systemic or intra-arterial chemotherapy
|
*[[Systemic]] [[chemotherapy]] and [[CNS]]-directed [[therapy]]
*[[Systemic]] [[chemotherapy]] followed by myeloablative [[chemotherapy]] and [[stem cell]] rescue
|-
|-
| Plus
!Trilateral retinoblastoma
| Concurrent laser ablation or cryotherapy
|
*[[Systemic]] [[chemotherapy]] followed by [[surgery]] and myeloablative [[chemotherapy]] with [[stem cell]] rescue
*[[Systemic]] [[chemotherapy]] followed by [[surgery]] and [[radiation therapy]]
|-
|-
| Third
![[Extracranial]] [[metastatic]] retinoblastoma
| External beam radiation therapy
|
*[[Systemic]] [[chemotherapy]] followed by myeloablative [[chemotherapy]] with [[stem cell]] rescue and [[radiation therapy]]
|-
|-
| Fourth
!Progressive or recurrent extraocular retinoblastoma
| Periocular carboplatin therapy
|
|-
*[[Systemic]] [[chemotherapy]] and [[radiation therapy]] for [[orbital disease]]
| Fifth
*[[Systemic]] [[chemotherapy]] followed by myeloablative [[chemotherapy]] with [[stem cell]] rescue, and [[radiation therapy]] for extra-[[Orbital Disease|orbital]] [[disease]]
| Enucleation
|-
| style="font-weight: bold;" | Metastatic disease
| First
| Multimodal therapy
|-
| colspan="3" style="font-weight: bold;" | Recurrence
|-
| style="font-weight: bold;" | Post globe-salvaging therapy
| First
| Brachytherapy
|-
| rowspan="2" style="font-weight: bold;" | Post enucleation
| First
| External beam radiation therapy
|-
| Adjunct
| Systemic chemotherapy
|}
|}
|}


==References==
==References==
{{reflist|2}}
{{reflist|2}}
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{{WikiDoc Sources}}


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[[Category:Oncology]]
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[[Category:Up-To-Date]]
[[Category:Surgery]]

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: Sahar Memar Montazerin, M.D.[2] Simrat Sarai, M.D. [3]

Overview

The optimal therapy for retinoblastoma depends on the stage at diagnosis. Systemic chemotherapy via carboplatin, etoposide, and vincristine (CEV) is the most common regimen used to treat retinoblastoma.

Medical Therapy

Systemic Chemotherapy

Chemotherapy Regimen

  • The most common chemotherapy regimen for retinoblastoma is the combination of the following:[4][5][6]
  • This combination may be used with different dose of medication and frequency depending upon the stage of the tumor.
    • Usually, the treatment regimen is comprised of either three sessions of high dose regimen or six sessions of low dose regimen.
    • Low dose regimen:
      • Carboplatin 18.6 mg/kg IV q24h for one day and repeated every (21 - 28) days
      • Etoposide 5 mg/kg IV q24h for two days and repeated (21 - 28) days
      • Vincristine 0.05 mg/kg IV q24h for one day and repeated every (21 - 28) days
    • High dose regimen:
      • Carboplatin 28 mg/kg IV q24h for one day and repeated every (21 - 28) days
      • Etoposide 12 mg/kg IV q24h for two days and repeated every (21 - 28) days
      • Vincristine 0.05 mg/kg IV q24h for one day and repeated every (21 - 28) days
    • The above mentioned dosage is recommended for orbital retinoblastoma and is subject to change for other types of tumor presentation.

Intra-arterial Chemotherapy

Other Interventions

  • Other treatment modalities which are currently available for retinoblastoma include:[7]

External Beam Radiotherapy (EBRT)

  • Groups I–II eyes: 95%
  • Groups IV and V eyes: 50%

Brachytherapy

Thermotherapy

Thermo-chemotherapy

Laser Photocoagulation

Cryotherapy

Management Options of Retinoblastoma

Treatment options for Intraocular tumor[8]
Unilateral retinoblastoma
Bilateral retinoblastoma
Cavitary retinoblastoma
Progressive or recurrent intraocular retinoblastoma
Treatment options for Extraocular tumor[8]
Orbital and locoregional retinoblastoma
CNS disease
Trilateral retinoblastoma
Extracranial metastatic retinoblastoma
Progressive or recurrent extraocular retinoblastoma

References

  1. ↑ Retinoblastoma Treatment. National Cancer Institute(2015) http://www.cancer.gov/types/retinoblastoma/hp/retinoblastoma-treatment-pdq#section/_53 Accessed on October 13, 2015
  2. ↑ Shields CL, Shields JA (1999). "Recent developments in the management of retinoblastoma". J Pediatr Ophthalmol Strabismus. 36 (1): 8–18, quiz 35-6. PMID 9972509.
  3. ↑ Venkatramani, Rajkumar; Jubran, Rima Fuad (2015). "Retinoblastoma: Intravenous Chemotherapy": 119–127. doi:10.1007/978-3-662-43451-2_11.
  4. ↑ Rodriguez-Galindo, Carlos; Wilson, Matthew W.; Haik, Barrett G.; Merchant, Thomas E.; Billups, Catherine A.; Shah, Nirali; Cain, Alvida; Langston, James; Lipson, Mindy; Kun, Larry E.; Pratt, Charles B. (2003). "Treatment of Intraocular Retinoblastoma With Vincristine and Carboplatin". Journal of Clinical Oncology. 21 (10): 2019–2025. doi:10.1200/JCO.2003.09.103. ISSN 0732-183X.
  5. ↑ Gallie BL, Budning A, DeBoer G, Thiessen JJ, Koren G, Verjee Z, Ling V, Chan HS (November 1996). "Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy". Arch. Ophthalmol. 114 (11): 1321–8. PMID 8906022.
  6. ↑ Dunkel IJ, Lee TC, Shi W, Beaverson KL, Novetsky D, Lyden D, Finlay JL, McCormick B, Abramson DH (October 2007). "A phase II trial of carboplatin for intraocular retinoblastoma". Pediatr Blood Cancer. 49 (5): 643–8. doi:10.1002/pbc.21163. PMID 17301956.
  7. ↑ Kim, Jonathan W.; Murphree, A. Linn; Singh, Arun D. (2015). "Retinoblastoma: Treatment Options": 89–107. doi:10.1007/978-3-662-43451-2_9.
  8. ↑ 8.0 8.1 "Retinoblastoma Treatment (PDQ®)—Health Professional Version - National Cancer Institute".
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