Retinoblastoma medical therapy: Difference between revisions

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{{Retinoblastoma}}
{{Retinoblastoma}}
{{CMG}}; {{AE}} {{Simrat}} {{Sahar}}
{{CMG}}; {{AE}} {{Sahar}} {{Simrat}}
==Overview==
==Overview==
==Medical therapy for intraocular tumors==
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.
The priority of retinoblastoma treatment is:<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
*Preserve vision
*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 pediatric oncologist. Children with the involvement of both eyes at diagnosis usually require multimodality therapy ([[chemotherapy]] and local 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
Treatment modalities which are currently available for retinoblastoma include:
===Enucleation of the eye===
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.
===External beam radiotherapy===
*This type of therapy is not recommended as first-line treatment of primary intra-ocular retinoblastoma due to the high risk of secondary malignancies following radiation in patients carrying RB1 gene mutation.<ref name="pmid23674091">{{cite journal |vauthors=MacCarthy A, Bayne AM, Brownbill PA, Bunch KJ, Diggens NL, Draper GJ, Hawkins MM, Jenkinson HC, Kingston JE, Stiller CA, Vincent TJ, Murphy MF |title=Second and subsequent tumors among 1927 retinoblastoma patients diagnosed in Britain 1951-2004 |journal=Br. J. Cancer |volume=108 |issue=12 |pages=2455–63 |date=June 2013 |pmid=23674091 |pmc=3694232 |doi=10.1038/bjc.2013.228 |url=}}</ref>
*This therapy may be helpful in salvage of the remaining eye which is resistant to another kind of therapies.
===Brachytherapy===
[[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===
==Medical Therapy==
[[Thermotherapy]] involves the application of heat directly to the tumor, usually in the form of infrared radiation. It is also used for small tumors.
*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>
**Save the life of the [[child]]
**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]]


===Laser photocoagulation===
===Systemic Chemotherapy===
*[[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 common [[Indication (medicine)|indications]] for [[systemic]] [[chemotherapy]] include:
**Unilateral intraocular retinoblastoma with high risk features
**Bilateral intraocular retinoblastoma
**[[Prophylaxis]] against [[metastasis]] following [[enucleation]] in the presence of [[histopathologic]] high-risk features
**Extraocular retinoblastoma with local and/or regional spread
**[[Metastatic]] retinoblastoma with or without [[CNS]] involvement
**Trilateral retinoblastoma
'''Chemotherapy Regimen'''<br>
*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>
**[[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]]:


[[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]].
*'''Groups I–II eyes:''' 95%
===Cryotherapy===
[[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.


===Systemic chemotherapy===
*'''Groups IV and V eyes:''' 50%
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:
*Large tumors
*Tumors  that cannot be treated with local therapies alone
*Bilateral tumors
*Invasion into the [[choroid]], [[optic nerve]], [[sclera]], [[orbit]], or [[anterior chamber]]


===Intra-arterial chemotherapy===
*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>
Chemotherapeutic drugs are administered locally via a thin catheter threaded through the groin, aorta, and the neck directly into the optic vessels.
*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>
===Management options of Retinoblastoma===
*[[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
 
===[[Brachytherapy]]===
*[[Indication (medicine)|Indications]]:
**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
 
===[[Thermotherapy|Thermo]]-[[chemotherapy]]===
*[[Indication (medicine)|Indications]]:
**[[Tumors]] not larger than 12 mm in [[diameter]] with no evidence of seeding, and located [[Anatomical terms of location|posterior]] to the equator
**[[Consolidation (medicine)|Consolidation]] treatment
===[[Laser photocoagulation|Laser Photocoagulation]]===
*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]]
**For the treatment of  small peripheral or [[Anatomical terms of location|posterior]] [[Tumor|tumors]] as the sole [[modality]]
**For the eradication of small [[tumor]] recurrences following [[chemotherapy]] and/or [[radiotherapy]]
*This method is suitable for treating [[tumors]] with the following characteristics:
**3.0 mm or less in [[diameter]]
**2.0 mm or less in thickness
**Without seeding into the adjacent [[vitreous]]
===[[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"
Line 47: Line 101:
! 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>
! 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>
|-
|-
|Unilateral retinoblastoma
!Unilateral retinoblastoma
|
|
* [[Enucleation]] followed by [[chemotherapy]]
*[[Enucleation]] followed by [[chemotherapy]]
*Conservative ocular salvage approaches:
*Conservative [[ocular]] salvage approaches:
**Chemoreduction with either systemic or [[ophthalmic artery]] infusion [[chemotherapy]] with or without [[intravitreal]] [[chemotherapy]]
**Chemoreduction with either [[systemic]] or [[ophthalmic artery]] [[infusion]] [[chemotherapy]] with or without [[intravitreal]] [[chemotherapy]]
**Local treatments ([[cryotherapy]], [[thermotherapy]], and plaque [[radiation therapy]])
**Local treatments ([[cryotherapy]], [[thermotherapy]], and plaque [[radiation therapy]])
|-
|-
|Bilateral retinoblastoma
!Bilateral retinoblastoma
|
|
* [[Enucleation]] for large intraocular [[tumors]], followed by risk-adapted [[chemotherapy]] when the eye and [[vision]] cannot be saved
*[[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:
* 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]]
**Chemoreduction with either [[systemic]] or [[ophthalmic artery]] [[infusion]] [[chemotherapy]] with or without [[intravitreal]] [[chemotherapy]]
**Local treatments ([[cryotherapy]], [[thermotherapy]], and plaque [[radiation therapy]])
**Local treatments ([[cryotherapy]], [[thermotherapy]], and plaque [[radiation therapy]])
**[[External beam radiotherapy|EBRT]]
**[[External beam radiotherapy|EBRT]]
|-
|-
|Cavitary retinoblastoma
!Cavitary retinoblastoma
|
|
* Systemic and/or intra-arterial [[chemotherapy]]
*[[Systemic]] and/or [[Intra-arterial Chemotherapy for Retinoblastoma|intra-arterial]] [[chemotherapy]]
|-
|-
|Progressive or recurrent intraocular retinoblastoma
!Progressive or recurrent intraocular retinoblastoma
|
|
* [[Enucleation]]
*[[Enucleation]]
* [[Radiation therapy]] ([[External beam radiation therapy|EBRT]] or plaque [[radiation therapy]])
*[[Radiation therapy]] ([[External beam radiation therapy|EBRT]] or plaque [[radiation therapy]])
* Local treatments ([[cryotherapy]] or [[thermotherapy]])
* Local treatments ([[cryotherapy]] or [[thermotherapy]])
* Salvage [[chemotherapy]] (systemic or [[Intra-arterial Chemotherapy for Retinoblastoma|intra-arterial]])
*[[Salvage therapy|Salvage]] [[chemotherapy]] ([[systemic]] or [[Intra-arterial Chemotherapy for Retinoblastoma|intra-arterial]])
* [[Intravitreal]] [[chemotherapy]]
*[[Intravitreal]] [[chemotherapy]]
|+
|+
! 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>
! 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>
|-
|-
|[[Orbit (anatomy)|Orbital]] and locoregional retinoblastoma
![[Orbit (anatomy)|Orbital]] and locoregional retinoblastoma
|
|
* [[Chemotherapy]]
* [[Chemotherapy]]
* [[Radiation therapy]]
* [[Radiation therapy]]
|-
|-
|[[CNS disease]]
![[CNS disease]]
|
|
* Systemic [[chemotherapy]] and [[CNS]]-directed [[therapy]]
*[[Systemic]] [[chemotherapy]] and [[CNS]]-directed [[therapy]]
* Systemic [[chemotherapy]] followed by myeloablative [[chemotherapy]] and [[stem cell]] rescue
*[[Systemic]] [[chemotherapy]] followed by myeloablative [[chemotherapy]] and [[stem cell]] rescue
|-
|-
|Trilateral retinoblastoma
!Trilateral retinoblastoma
|
|
* Systemic [[chemotherapy]] followed by [[surgery]] and myeloablative [[chemotherapy]] with [[stem cell]] rescue
*[[Systemic]] [[chemotherapy]] followed by [[surgery]] and myeloablative [[chemotherapy]] with [[stem cell]] rescue
* Systemic [[chemotherapy]] followed by [[surgery]] and [[radiation therapy]]
*[[Systemic]] [[chemotherapy]] followed by [[surgery]] and [[radiation therapy]]
|-
|-
|[[Extracranial]] [[metastatic]] retinoblastoma
![[Extracranial]] [[metastatic]] retinoblastoma
|
|
* Systemic [[chemotherapy]] followed by myeloablative [[chemotherapy]] with [[stem cell]] rescue and [[radiation therapy]]
*[[Systemic]] [[chemotherapy]] followed by myeloablative [[chemotherapy]] with [[stem cell]] rescue and [[radiation therapy]]
|-
|-
|Progressive or recurrent extraocular retinoblastoma
!Progressive or recurrent extraocular retinoblastoma
|
|
* Systemic [[chemotherapy]] and [[radiation therapy]] for [[orbital disease]]
*[[Systemic]] [[chemotherapy]] and [[radiation therapy]] for [[orbital disease]]
* Systemic [[chemotherapy]] followed by myeloablative [[chemotherapy]] with [[stem cell]] rescue, and [[radiation therapy]] for extra-[[Orbital Disease|orbital]] [[disease]]
*[[Systemic]] [[chemotherapy]] followed by myeloablative [[chemotherapy]] with [[stem cell]] rescue, and [[radiation therapy]] for extra-[[Orbital Disease|orbital]] [[disease]]
|}
|}
==References==
==References==
{{reflist|2}}
{{reflist|2}}
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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: 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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