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

Abstract

Combined modality therapy for childhood retinoblastoma holds the potential of decreasing treatment-related morbidity while maintaining excellent tumor control rates. 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. 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 degrees C or 54 degrees C FMH for 20 minutes, or with combined EBRT at 10 or 30 Gy and 48 degrees C or 54 degrees C FMH for 20 minutes. Serial histologic sections, obtained 8 weeks after treatment, were examined for the presence of tumor. The tumor control dose for 50% of eyes (TCD50) treated with EBRT occurred at 27.6 Gy. Ferromagnetic hyperthermia at 48 degrees C cured 30% (6/20) of eyes, while 54 degrees C FMH resulted in a 100% (20/20) cure rate. Combined treatment with 48 degrees C FMH and EBRT exhibited a TCD50 at 3.3 Gy. The thermal enhancement ratio was 8.4. Ferromagnetic hyperthermia at 54 degrees C exhibited tumor cure in all animals, but 25% of eyes were lost owing to secondary treatment complications. 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.