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==Medical Therapy==
==Medical Therapy==
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>  
*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
**Save the life of the child
*Preserve vision
**Preserve vision
*Minimize complications or side effects of treatment.
**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 exact course of treatment will depend on the individual case and will be decided by the [[ophthalmologist]] in discussion with the pediatric oncologist.  
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>
*Children with the involvement of both eyes at diagnosis usually require multimodality therapy ([[chemotherapy]] and local therapies).<br>
*[[Tumor]] size
*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]] location
**[[Tumor]] size
*Presence or absence of [[vitreous]] or subretinal seeds
**[[Tumor]] location
*Age of the patient
**Presence or absence of [[vitreous]] or subretinal seeds
**Age of the patient
===Systemic Chemotherapy===
===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>
*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|indications]] for systemic [[chemotherapy]] include:
*The common [[Indication|indications]] for systemic [[chemotherapy]] include:
*Unilateral intraocular retinoblastoma with high risk feature
**Unilateral intraocular retinoblastoma with high risk feature
*Bilateral intraocular retinoblastoma
**Bilateral intraocular retinoblastoma
*[[Prophylaxis]] against [[metastasis]] following [[enucleation]] in the presence of [[histopathologic]] high-risk features
**[[Prophylaxis]] against [[metastasis]] following [[enucleation]] in the presence of [[histopathologic]] high-risk features
*Extraocular retinoblastoma with local and/or regional spread
**Extraocular retinoblastoma with local and/or regional spread
*[[Metastatic]] retinoblastoma with or without [[CNS]] involvement
**[[Metastatic]] retinoblastoma with or without [[CNS]] involvement
*Trilateral retinoblastoma
**Trilateral retinoblastoma
'''Chemotherapy Regimen'''<br>
'''Chemotherapy Regimen'''<br>
The most common [[chemotherapy]] regimen for retinoblastoma is the combination of the followings:<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 [[chemotherapy]] regimen for retinoblastoma is the combination of the followings:<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]]
**[[Carboplatin]]
*[[Etoposide]]
**[[Etoposide]]
*[[Vincristine]]
**[[Vincristine]]
This combination may be used with different dose of medication and frequency depending on the stage of the [[tumor]].
*This combination may be used with different dose of medication and frequency depending on the stage of the [[tumor]].
*Usually, treatment regimen comprised of either three sessions of high dose regimen or six sessions of low [[dose]] regimen.
**Usually, treatment regimen comprised of either three sessions of high dose regimen or six sessions of low [[dose]] regimen.
*Low [[dose]] regimen:
**Low [[dose]] regimen:
**[[Carboplatin]] 18.6 mg/kg IV q24h for one day and be repeated every (21-28) days
***[[Carboplatin]] 18.6 mg/kg IV q24h for one day and be repeated every (21-28) days
**[[Etoposide]] 5 mg/kg IV q24h for two days be repeated (21-28) days
***[[Etoposide]] 5 mg/kg IV q24h for two days be repeated (21-28) days
**[[Vincristine]] 0.05 mg/kg IV q24h for one day and be repeated every (21-28) days  
***[[Vincristine]] 0.05 mg/kg IV q24h for one day and be repeated every (21-28) days  
*High [[dose]] regimen:
**High [[dose]] regimen:
**[[Carboplatin]] 28 mg/kg IV q24h for one day and be repeated every (21-28) days
***[[Carboplatin]] 28 mg/kg IV q24h for one day and be repeated every (21-28) days
**[[Etoposide]] 12 mg/kg IV q24h for two days and be repeated every (21-28) days
***[[Etoposide]] 12 mg/kg IV q24h for two days and be repeated every (21-28) days
**[[Vincristine]] 0.05 mg/kg IV q24h for one day and be repeated every (21-28) days
***[[Vincristine]] 0.05 mg/kg IV q24h for one day and be repeated every (21-28) days
*The above afromentioned dosage is recommended for orbital retinoblastoma and is subject to change for other type of tumor spread.
**The above afromentioned dosage is recommended for orbital retinoblastoma and is subject to change for other type of tumor spread.
===Intra-arterial Chemotherapy===
===Intra-arterial Chemotherapy===
Chemotherapeutic drugs are administered locally via a thin catheter threaded through the groin, aorta, and the neck directly into the optic vessels.
*Chemotherapeutic drugs are administered locally via a thin catheter threaded through the groin, aorta, and the neck directly into the optic vessels.
==Other interventions==
==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>
*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]]===
The feasibility of [[external beam radiotherapy]] depends on the stage of retinoblastoma at the time of [[diagnosis]].<br>
*The feasibility of [[external beam radiotherapy]] depends on the stage of retinoblastoma at the time of [[diagnosis]].<br>
The globe preservation rate with this method varies according to the stage of the [[tumor]] at the time of [[diagnosis]]:
*The globe preservation rate with this method varies according to the stage of the [[tumor]] at the time of [[diagnosis]]:


Groups I–II eyes:95%
*Groups I–II eyes:95%


Groups IV and V eyes:50%
*Groups IV and V eyes:50%


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>
*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 cells of [[retina]] ranges from 3,600 to 4,500 cGy administered in 180–200 cGy daily fractions 5 times/week.<br>
*The dose to target 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]]:
*[[Contraindications]] of [[External beam radiotherapy|EBRT]]:
*Children less than 1 year of age due to the risk secondary [[malignancies]]
**Children less than 1 year of age due to the risk secondary [[malignancies]]
*For eyes with dismal visual potential
**For eyes with dismal visual potential
*In primary therapy of retinoblastoma
**In primary therapy of retinoblastoma


===[[Brachytherapy]]===
===[[Brachytherapy]]===
[[Indication (medicine)|Indications]]:
*[[Indication (medicine)|Indications]]:
*Primary treatment
**Primary treatment
*Residual tumor following [[Laser therapy|photocoagulation]]/[[thermotherapy]]/thermo-chemotherapy/[[cryotherapy]]
**Residual tumor following [[Laser therapy|photocoagulation]]/[[thermotherapy]]/thermo-chemotherapy/[[cryotherapy]]
*[[Tumor]] recurrence
**[[Tumor]] recurrence
*[[Tumor]] less than 15 mm in diameter
**[[Tumor]] less than 15 mm in diameter
[[Contraindication]]:
*[[Contraindication]]:
*Presence of diffuse [[vitreous]] seeding  
**Presence of diffuse [[vitreous]] seeding  
===[[Thermotherapy]]===
===[[Thermotherapy]]===
*[[Tumor|Tumors]] not more than 3 mm in diameter, with no and traction, [[retinal]] vascular occlusion evidence of seeding, and located posterior to the equator
*[[Indication (medicine)|Indications]]:
*Primary treatment
**[[Tumor|Tumors]] not more than 3 mm in diameter, with no and traction, [[retinal]] vascular occlusion evidence of seeding, and located posterior to the equator
*[[Consolidation (medicine)|Consolidation]] treatment
**Primary treatment
*[[Tumor]] recurrence
**[[Consolidation (medicine)|Consolidation]] treatment
**[[Tumor]] recurrence
===Thermochemotherapy===
===Thermochemotherapy===
[[Indication (medicine)|Indications]]:
*[[Indication (medicine)|Indications]]:
*[[Tumors]] not more than 12 mm in diameter with no evidence of seeding, and located posterior to the equator
**[[Tumors]] not more than 12 mm in diameter with no evidence of seeding, and located posterior to the equator
*[[Consolidation (medicine)|Consolidation]] treatment
**[[Consolidation (medicine)|Consolidation]] treatment
===[[Laser photocoagulation]]===
===[[Laser photocoagulation]]===
This method is [[Indication (medicine)|indicated]] for intraocular retinoblastoma and one of the following factors:
*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]]
**[[Consolidation (medicine)|Consolidation]] of large [[Tumor|tumors]] after systemic [[chemotherapy]]
*For the treatment of  small peripheral or posterior tumors as the sole [[modality]]
**For the treatment of  small peripheral or posterior tumors as the sole [[modality]]
*For the eradication of small [[tumor]] recurrences following [[chemotherapy]] and/or [[radiotherapy]]
**For the eradication of small [[tumor]] recurrences following [[chemotherapy]] and/or [[radiotherapy]]
This method is suitable for treating [[tumors]] with the following characteristics:
*This method is suitable for treating [[tumors]] with the following characteristics:
* 3.0 mm or less in diameter
**3.0 mm or less in diameter
* 2.0 mm or less in thickness
**2.0 mm or less in thickness
*Without seeding into the adjacent [[vitreous]]
**Without seeding into the adjacent [[vitreous]]
===[[Cryotherapy]]===
===[[Cryotherapy]]===
[[Indication (medicine)|Indications]]:
*[[Indication (medicine)|Indications]]:
*[[Tumors]] not more than 3 mm in diameter with no evidence of seeding, and located anterior to the equator
**[[Tumors]] not more than 3 mm in diameter with no evidence of seeding, and located anterior to the equator
*Primary treatment
**Primary treatment
*[[Consolidation (medicine)|Consolidation]] treatment
**[[Consolidation (medicine)|Consolidation]] treatment
*[[Tumor]] recurrence
**[[Tumor]] recurrence
===Management Options of Retinoblastoma===
===Management Options of Retinoblastoma===
:*  
:*  

Revision as of 14:02, 28 June 2019

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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

  • The priority of retinoblastoma treatment is:[1]
    • 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).
  • The choice of therapy depends upon several factors such as:[2]
    • Tumor size
    • Tumor location
    • Presence or absence of vitreous or subretinal seeds
    • Age of the patient

Systemic Chemotherapy

Chemotherapy Regimen

  • The most common chemotherapy regimen for retinoblastoma is the combination of the followings:[4][5][6]
  • This combination may be used with different dose of medication and frequency depending on the stage of the tumor.
    • Usually, treatment regimen 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 be repeated every (21-28) days
      • Etoposide 5 mg/kg IV q24h for two days be repeated (21-28) days
      • Vincristine 0.05 mg/kg IV q24h for one day and be repeated every (21-28) days
    • High dose regimen:
      • Carboplatin 28 mg/kg IV q24h for one day and be repeated every (21-28) days
      • Etoposide 12 mg/kg IV q24h for two days and be repeated every (21-28) days
      • Vincristine 0.05 mg/kg IV q24h for one day and be repeated every (21-28) days
    • The above afromentioned dosage is recommended for orbital retinoblastoma and is subject to change for other type of tumor spread.

Intra-arterial Chemotherapy

  • Chemotherapeutic drugs are administered locally via a thin catheter threaded through the groin, aorta, and the neck directly into the optic vessels.

Other interventions

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

External beam radiotherapy

  • Groups I–II eyes:95%
  • Groups IV and V eyes:50%
  • This method is 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.
  • The dose to target tumor cells of retina ranges from 3,600 to 4,500 cGy administered in 180–200 cGy daily fractions 5 times/week.
  • Contraindications of EBRT:
    • Children less than 1 year of age due to the risk secondary malignancies
    • For eyes with dismal visual potential
    • In primary therapy of retinoblastoma

Brachytherapy

Thermotherapy

  • Indications:
    • Tumors not more than 3 mm in diameter, with no and traction, retinal vascular occlusion evidence of seeding, and located posterior to the equator
    • Primary treatment
    • Consolidation treatment
    • Tumor recurrence

Thermochemotherapy

Laser photocoagulation

  • This method is indicated for intraocular retinoblastoma and one of the following factors:
  • 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

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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