title: Hyperfractionated external beam radiation therapy in the treatment of murine transgenic retinoblastoma.
abstract: OBJECTIVE
  To determine the in vivo efficacy of hyperfractionated external beam radiation therapy (EBRT) in comparison with standard daily EBRT in a murine model of heritable retinoblastoma.
  
  
  METHODS
  Two hundred twenty eyes from 6-week-old simian virus-40 large T-antigen--positive mice were treated with a total dose of EBRT ranging from 10-76 Gy (1000 to 7600 rad). One hundred ten eyes underwent EBRT administered in 2.0-Gy (200-rad) fractions once per day. Forty-two eyes received hyperfractionated EBRT administered in 1.2-Gy (120-rad) fractions twice per day, while 48 eyes received EBRT twice daily in fractions of 5.0 Gy (500 rad). Twenty eyes served as untreated controls. All eyes were obtained for histopathologic examination and graded positive if any tumor was present.
  
  
  RESULTS
  A dose-dependent inhibition of ocular tumor was observed for EBRT in these transgenic retinoblastoma mice. The tumor control dose for 50% of eyes (TCD(50)) treated with 2.0 Gy fractions of EBRT was 45 Gy (4500 rad) when treatments were administered once daily. A significant increase in tumor control was observed when treatments were administered twice per day at fractions of 1.2 Gy, resulting in a TCD(50) of 33 Gy (3300 rad) (P =.003). A further increase in tumor control was observed when twice-daily EBRT was administered in 5.0 Gy fractions resulting in a TCD(50) of 28 Gy (2800 rad).
  
  
  CONCLUSIONS
  Hyperfractionated EBRT safely and effectively controls intraocular retinoblastoma in this transgenic animal model. Use of hyperfractionation allows for a reduction in total radiation delivered dose, while shortening the total treatment time.
  
  
  CONCLUSIONS
  This treatment approach may be applicable in the management of pediatric retinoblastoma by maintaining excellent tumor control, while reducing treatment-associated complications.
authors.affiliation: Bascom Palmer Eye Institute, PO Box 016880, Miami, FL 33101, USA.
authors.forename: Brandy C
authors.initials: BC
authors.lastname: Hayden
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Murray
authors.forename: Nicole
authors.initials: N
authors.lastname: Cicciarelli
authors.forename: Ingrid U
authors.initials: IU
authors.lastname: Scott
authors.forename: Anastassia
authors.initials: A
authors.lastname: Alexandridou
authors.forename: Eleut
authors.initials: E
authors.lastname: Hernandez
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wu
authors.forename: Arnold M
authors.initials: AM
authors.lastname: Markoe
authors.forename: William
authors.initials: W
authors.lastname: Feuer
authors.forename: Lilia
authors.initials: L
authors.lastname: Fulton
authors.forename: Joan M
authors.initials: JM
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D008822:Mice, Transgenic; D019572:Retinal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D012175:Retinoblastoma / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D000952:Antigens, Polyomavirus Transforming