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==Overview==
==Overview==
The priorities in the treatment of retinoblastoma are to preserve life, preserve globe and preserve vision, in that specific order. Minimizing side effects and complications of treatment are also of paramount importance in these very young patients. Treatment modalities that may be successful in globe salvage include systemic chemotherapy with focal consolidation, intra-arterial chemotherapy, and for small tumors, focally destructive therapy (cryopexy, laser photocoagulation, hyperthermia and plaque irradiation).<ref>http://eyewiki.org/Retinoblastoma#General_treatment</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==
1. '''External Beam Radiation (EBRT)'''
*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>
:* Prior to the 1990s, external beam radiation (EBRT) played a central role in the treatment of retinoblastoma. Due to disappointingly high recurrence rates, chemotherapy was limited largely to the treatment of metastatic cases. However, with long term follow-up clinicians began realizing how significant an impact external beam radiation had on the prevalence of secondary tumors, especially in patients with germline mutations.The growing reluctance to use external beam radiation coincided with the rise of more effective chemotherapeutic regimens.
**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]]


2. '''Systemic Chemotherapy'''
===Systemic Chemotherapy===
:* Systemic chemotherapy is administered with focal consolidative therapy. This treatment approach has been coined "chemoreduction" because the goal is to shrink the tumor. Shrinking the tumor increases the success of focal therapies, which are less successful with thicker tumors. Focal therapy is directly destructive to tumor cells and also breaks down the blood ocular barrier and increases penetration of chemotherapeutic agents into the eye. Today, systemic chemotherapy, applied in conjunction with local therapy, is one of the main globe salvaging options in retinoblastoma management.
*[[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]]:


3. '''Advanced Bilateral Retinoblastoma Medical Therapy'''
*'''Groups I–II eyes:''' 95%
:* In patients with advanced bilateral retinoblastoma, traditionally the more severely affected eye has been enucleated, while the less severely affected eye has undergone chemoreduction with or without external beam irradiation. In cases where only one eye harbors tumor, enucleation is usually considered when the tumor is large and there is poor vision potential. As chemoreduction has proven its efficacy, clinicians are expanding its clinical indications to allow more eyes to be saved.


4. '''Intra-arterial Chemotherapy for Retinoblastoma'''
*'''Groups IV and V eyes:''' 50%


The Children’s Oncology Group (COG) currently has multiple trials evaluating chemotherapy regimens in conjunction with focal consolidation.
*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>
:* Since group A eyes are often easily managed with focal therapies alone, no COG trial exists for this group.
*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>
:* For group B tumors, a two agent protocol involving [[Vincristine]] and low-dose [[Carboplatin]] along with local therapy was being evaluated but has now reached a stopping point.
*[[Contraindications]] of [[External beam radiotherapy|EBRT]]:
:* Group C and D tumors were being treated with three agent chemotherapy involving [[Vincristine]], high-dose [[Carboplatin]], and [[Etoposide]] along with local therapy as well as subtenon injection of [[Carboplatin]]. These trials have also reached stopping points.
**Children less than 1 year of age (due to the risk of secondary [[malignancies]])
:* Enucleation is recommended for group E eyes.
**[[Eye|Eyes]] with dismal [[visual]] potential
:* Children with tumor massively involving the optic nerve, orbit, brain or present at distant sites are currently being enrolled in a COG group F trial.


==Adverse effects==
===[[Brachytherapy]]===
The risk of second malignancy is increased more than threefold by external beam radiation (EBRT), especially if the patient is less than 1 year of age.
*[[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


==Medical Treatment of Extraocular Retinoblastoma==
===[[Thermotherapy|Thermo]]-[[chemotherapy]]===
Historically, extraocular retinoblastoma was nearly universally fatal.  If the retinoblastoma remained confined to the orbit, there was only  a 10% survival rate, and cases of survival with metastatic retinoblastoma was anecdotal.[16] However, as chemotherapeutic regimens have improved, the prognosis has also improved.
*[[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
For extraocular retinoblastoma limited to the orbit, clinicians are finding success with neoadjuvant chemotherapy to shrink the tumor.  This is followed by surgical debulking and post-operative chemotherapy and radiation if necessary.[17][18] For systemic metastases, especially cases with CNS involvement, aggressive treatment with high dose chemotherapy (HDC) and autologous stem cell rescue (ASCR) is recommended.  HDC involves the administration of high doses of chemotherapeutic agents with the aim to overcome tumor resistance and completely eradicate neoplastic cells.  Unfortunately, these lethal doses are also myeloablative and concurrent ASCR must be performed to allow future reconstitution of the bone marrow. Though toxic, case series of survival after this treatment regimen are being reported.[19][20]
**[[Consolidation (medicine)|Consolidation]] treatment
 
===[[Laser photocoagulation|Laser Photocoagulation]]===
Currently there is a Children’s Oncology Group (COG) trial evaluating high dose systemic chemotherapy using four cycles of induction chemotherapy with vincristine, cisplatin, cyclophosphamide and etoposide followed by one cycle of high-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for malignant brain and spinal tumors. Though promising, treatment efforts remain focused on early detection and treatment to prevent extraocular disease in the first place.
*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]]
==Trilateral Retinoblastoma treatment==
**For the treatment of small peripheral or [[Anatomical terms of location|posterior]] [[Tumor|tumors]] as the sole [[modality]]
The treatment regimen for patients with primitive neuroectodermal tumors (PNET) is similar to patients with CNS metastases<ref>http://eyewiki.org/Retinoblastoma#Trilateral_Retinoblastoma</ref>. The prognosis is also dismal. As such, early detection and treatment of primitive neuroectodermal tumors (PNET) is recommended.  Recently it was noted that there was a decrease in the incidence of primitive neuroectodermal tumors as clinicians came to rely more on chemotherapy over EBRT. This is hypothesized to be secondary to either a prophylactic effect due to systemic chemotherapy or because fewer patients are receiving radiation. Regardless, systemic chemotherapy should be strongly considered for germline cases of retinoblastoma over local (i.e. intra-arterial ) delivery.
**For the eradication of small [[tumor]] recurrences following [[chemotherapy]] and/or [[radiotherapy]]
{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align=center
*This method is suitable for treating [[tumors]] with the following characteristics:
|valign=top|
**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"
! 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-color: #0080FF; font-weight: bold;" | Patient Group
! style="background-color: #0080FF; font-weight: bold;" | Treatment line
! style="background-color: #0080FF; font-weight: bold;" | Treatment
|-
|-
| style="background-color: #819FF7; font-weight: bold;" | With vitreous seeding
!Unilateral retinoblastoma
| colspan="2" |
|
*[[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" | 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="3" | Without gross anterior chamber involvement or neovascular glaucoma or orbital inflammation
!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
|-
| style="background-color: #819FF7; font-weight: bold;" | Without vitreous seeding
| colspan="2" |  
|-
| rowspan="3" | 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
![[Orbit (anatomy)|Orbital]] and locoregional retinoblastoma
| Enucleation
|
* [[Chemotherapy]]
* [[Radiation therapy]]
|-
|-
| rowspan="3" | Tumor 2 disc diameters or less in size
![[CNS disease]]
| First
|
| Focal laser ablation alone
*[[Systemic]] [[chemotherapy]] and [[CNS]]-directed [[therapy]]
*[[Systemic]] [[chemotherapy]] followed by myeloablative [[chemotherapy]] and [[stem cell]] rescue
|-
|-
| Second
!Trilateral retinoblastoma
| Systemic or intra-arterial chemotherapy
|
*[[Systemic]] [[chemotherapy]] followed by [[surgery]] and myeloablative [[chemotherapy]] with [[stem cell]] rescue
*[[Systemic]] [[chemotherapy]] followed by [[surgery]] and [[radiation therapy]]
|-
|-
| Plus
![[Extracranial]] [[metastatic]] retinoblastoma
| Concurrent laser ablation or cryotherapy
|
|-
*[[Systemic]] [[chemotherapy]] followed by myeloablative [[chemotherapy]] with [[stem cell]] rescue and [[radiation therapy]]
| Third
| External beam radiation therapy
|-
| Fourth
| Periocular carboplatin therapy
|-
| Fifth
| Enucleation
|-
| style="background-color: #819FF7; font-weight: bold;" | Metastatic disease
| colspan="2" |
|-
| rowspan="3" |
| First
| Multimodal 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==
{{reflist|2}}
{{reflist|2}}


==See also==
[[Category:Medicine]]
*[[Eye cancer]]
[[Category:Oncology]]
*[[Eye examination]]
[[Category:Up-To-Date]]
 
[[Category:Surgery]]
 
{{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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