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External Beam Radiation "Salvage" Therapy in Transgenic Murine Retinoblastoma
Lucia Sobrin, MD;
Brandy C. Hayden, BS;
Timothy G. Murray, MD;
Nicole Cicciarelli;
Ingrid U. Scott, MD, MPH;
Eleut Hernandez;
Xiaodong Wu, PhD;
Arnold M. Markoe, MD;
William Feuer, MS;
Lilia Fulton, BA;
Joan M. O'Brien, MD
Arch Ophthalmol. 2004;122:251-257.
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-antigenpositive mice were treated with 6 serial subconjunctival carboplatin injections (100 µg/25 µL). 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.
Main Outcome Measures 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 groupsEBRT alone vs salvage EBRT after receiving subconjunctival carboplatin injections (P<.001).
Conclusion 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.
From the Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miami, Fla (Drs Sobrin, Murray, Scott, Wu, and Markoe, Mss Hayden and Cicciarelli, and Messrs Hernandez and Feuer); and the Department of Ophthalmology, University of California, San Francisco (Ms Fulton and Dr O'Brien). The authors have no relevant financial interest in this article.
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