Radiation therapy and ferromagnetic hyperthermia in the treatment of murine transgenic retinoblastoma

Background: Combined modality therapy for childhood retinoblastoma holds the potential of decreasing treatment related morbidity while maintaining excellent tumor control rates. Objective: To evaluate the efficacy of external beam radiation therapy (EBRT), ferromagnetic hyperthermia (FMH), and the combination of both modalities in the control of ocular tumors in a transgenic murine model of retinoblastoma. Methods: One hundred sixty-six mouse eyes from 4-week-old animals transgenically positive for simian virus 40 large T antigen were treated with a total dose of 10, 15, 20, 30, 40, 45, or 50 Gy of EBRT in 5-Gy fractions twice daily, with 48°C or 54°C FMH for 20 minutes, or with combined EBRT at 10 or 30 Gy and 48°C or 54°C FMH for 20 minutes. Serial histologic sections, obtained 8 weeks after treatment, were examined for the presence of tumor. Results: The tumor control dose for 50% of eyes (TCD₅₀) treated with EBRT occurred at 27.6 Gy. Ferromagnetic hyperthermia at 48°C cured 30% (6/20) of eyes, while 54°C FMH resulted in a 100% (20/20) cure rate. Combined treatment with 48°C FMH and EBRT exhibited a TCD₅₀ at 3.3 Gy. The thermal enhancement ratio was 8.4. Ferromagnetic hyperthermia at 54°C exhibited tumor cure in all animals, but 25% of eyes were lost owing to secondary treatment complications. Conclusions: This represents the first documentation of tumor control via EBRT, ocular FMH, and a combination of these treatment modalities in this murine transgenic retinoblastoma model. The extent of treatment synergy in this model suggests that combined treatment application may allow a reduction in total ocular and periocular radiation dose while maintaining excellent local tumor control.