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{{Retinoblastoma}}
{{Retinoblastoma}}
 
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==Overview==
==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==
==Medical Therapy==
*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]]


Until recently the only treatment was to remove the affected eyeball before the cancer spread. Chemotherapy is the treatment of choice for most unilateral cases. However with locally advanced disease external beam radiation may be needed and if both eyes are involved [[enucleation]] may be the only option. Affected children in developing countries present with advanced features and usually die of metastatic spread. In its initial stages, retinoblastoma is very similar to [[Coats disease]], a non-cancerous retina disease. Coats' Disease should be ruled out before enucleation is done. A mis-diagnosis of Retinoblastoma accounts for the greatest number of Coats' disease eyes being enucleated.
===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]]:


Many children with bilateral retinoblastoma can be treated with a preservation attempt. Tumor [[chemotherapy|chemoreduction]] with [[carboplatin]] and other drugs may reduce the tumor volume making them amenable to local therapies <ref>{{cite journal |author=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. |pmid=17301956 }}</ref>
*'''Groups I–II eyes:''' 95%


Local therapies include-
*'''Groups IV and V eyes:''' 50%


[[Laser therapy]] (Uses infrared laser light to precisely destroy the blood vessels surrounding a tumor.)
*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>
* [[Cryotherapy]] (use of a cold gas which is injected into the affected part of the retina to shrink the tumor.)
*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>
* [[Thermotherapy]] (A relatively new technique used mainly in new testing. It uses the principle that if heat is applied to the affected area, a tumor will sustain more damage than healthy cells because healthy cells can cool themselves better using healthy surrounding blood vessels. If this technique is not immediately successful it may increase the efficacy of other treatments such as chemotherapy and focused radiation plaques.)
*[[Contraindications]] of [[External beam radiotherapy|EBRT]]:
* [[Radiotherapy]] (Generally used as a last resort, radiotherapy was previously the treatment of choice before the above mentioned treatments were developed.  Radiotherapy destroys cancerous growths  using [[gamma ray|gamma radiation]] but it carries with it many drawbacks, including:-
**Children less than 1 year of age (due to the risk of secondary [[malignancies]])
** Possibility of secondary cancerous growths which present themselves months or years later.
**[[Eye|Eyes]] with dismal [[visual]] potential
** Destruction of healthy cells in the area surrounding the treated tumor.
** Bone deformation due to the destruction of the growth plates mainly in the area of the [[temple (anatomy)|temple]].)


It is important that children with retinoblastoma are treated in specialist centers.
===[[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


[[Brachytherapy]] with [[beta ray|beta]]-emitting eye applicators have also been a successful major treatment. BEBIG (GmbH-Berlin-Germany) produces various kinds of [[ruthenium]] ophthalmic applicators for treating retinoblastoma.
===[[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"
|+
! 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
|
*[[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]])
|-
!Bilateral retinoblastoma
|
*[[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]]
|-
!Cavitary retinoblastoma
|
*[[Systemic]] and/or [[Intra-arterial Chemotherapy for Retinoblastoma|intra-arterial]] [[chemotherapy]]
|-
!Progressive or recurrent intraocular retinoblastoma
|
*[[Enucleation]]
*[[Radiation therapy]] ([[External beam radiation therapy|EBRT]] or plaque [[radiation therapy]])
* Local treatments ([[cryotherapy]] or [[thermotherapy]])
*[[Salvage therapy|Salvage]] [[chemotherapy]] ([[systemic]] or [[Intra-arterial Chemotherapy for Retinoblastoma|intra-arterial]])
*[[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>
|-
![[Orbit (anatomy)|Orbital]] and locoregional retinoblastoma
|
* [[Chemotherapy]]
* [[Radiation therapy]]
|-
![[CNS disease]]
|
*[[Systemic]] [[chemotherapy]] and [[CNS]]-directed [[therapy]]
*[[Systemic]] [[chemotherapy]] followed by myeloablative [[chemotherapy]] and [[stem cell]] rescue
|-
!Trilateral retinoblastoma
|
*[[Systemic]] [[chemotherapy]] followed by [[surgery]] and myeloablative [[chemotherapy]] with [[stem cell]] rescue
*[[Systemic]] [[chemotherapy]] followed by [[surgery]] and [[radiation therapy]]
|-
![[Extracranial]] [[metastatic]] retinoblastoma
|
*[[Systemic]] [[chemotherapy]] followed by myeloablative [[chemotherapy]] with [[stem cell]] rescue and [[radiation therapy]]
|-
!Progressive or recurrent extraocular retinoblastoma
|
*[[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]]
|}


==References==
==References==
<references/>
{{reflist|2}}
 
==See also==
*[[Eye cancer]]
*[[Eye examination]]
 
 
{{Nervous tissue tumors}}
 
[[Category:Ophthalmology]]
[[Category:Types of cancer]]
[[Category:hereditary cancers]]
[[Category:Oncology stub]]


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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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