External Beam Radiation "Salvage" Therapy in Transgenic Murine Retinoblastoma

Abstract

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 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 groups-EBRT alone vs salvage EBRT after receiving subconjunctival carboplatin injections (PϽ.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 radiationrelated treatment enhancement in pediatric retinoblastoma.

The Use of Preclinical Models to Improve the Treatment of Retinoblastoma

“…Other preclinical studies with retinoblastoma mouse models have used focal therapies, such as EBRT and cryotherapy, and found them to disrupt the blood-ocular barrier, increasing drug delivery [64,118,156]. Ideally, the use of cryotherapy is more attractive than EBRT due to the risks to patients with germline mutations.…”