External beam radiation "salvage" therapy in transgenic murine retinoblastoma.
OBJECTIVE
To determine the efficacy of low-dose "salvage" external beam radiation therapy (EBRT) following failed subconjunctival carboplatin chemotherapy in a murine model of heritable retinoblastoma.


METHODS
Eighty-four eyes from 8-week-old, simian virus 40, T-antigen-positive mice were treated with 6 serial subconjunctival carboplatin injections (100 microg/25 microL). At 12 weeks of age, 64 eyes received EBRT for a total dose of 480 (4.8 Gy), 1200 (12.0 Gy), 1560 (15.6 Gy), or 3000 (30.0 Gy) rad. Twenty eyes received no additional therapy following subconjunctival carboplatin injections. Ten eyes received a total dose EBRT of only 3000 rad. Eight eyes received subconjuctival injections of only an isotonic sodium chloride solution. Ten eyes served as untreated controls.


METHODS
Eyes were enucleated at 20 weeks to assess the presence of tumor on histopathological examination.


RESULTS
Salvage therapy using low-dose EBRT was able to reestablish tumor control in a dose-dependent manner. Increasing the EBRT dose to 3000 rad resulted in 100% tumor control. The dose-dependent curves were significantly different between the treatment groups-EBRT alone vs salvage EBRT after receiving subconjunctival carboplatin injections (P<.001).


CONCLUSIONS
Low-dose hyperfractionated salvage EBRT following failed primary subconjunctival carboplatin chemotherapy is efficacious in the treatment of retinoblastoma in this animal model. Clinical Relevance Salvage EBRT using a reduced total radiation dose could be associated with a radiation-related treatment enhancement in pediatric retinoblastoma.
Sobrin
Lucia
L
Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miami, FL 33101, USA.
Hayden
Brandy C
BC
Murray
Timothy G
TG
Cicciarelli
Nicole
N
Scott
Ingrid U
IU
Hernandez
Eleut
E
Wu
Xiaodong
X
Markoe
Arnold M
AM
Feuer
William
W
Fulton
Lilia
L
O'Brien
Joan M
JM
D000818:Animals; D000952:Antigens, Polyomavirus Transforming; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016190:Carboplatin / Q000627:therapeutic use; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D008822:Mice, Transgenic; D011879:Radiotherapy Dosage; D019572:Retinal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D012175:Retinoblastoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D016879:Salvage Therapy; D013539:Simian virus 40; D017211:Treatment Failure
D000952:Antigens, Polyomavirus Transforming; D000970:Antineoplastic Agents; D016190:Carboplatin