RADIATION-THERAPY AND FERROMAGNETIC HYPERTHERMIA IN THE TREATMENT OF MURINE TRANSGENIC RETINOBLASTOMA

Background: Combined modality therapy for childhood retinoblastoma hol ds the potential oi decreasing treatment-related morbidity while maint aining excellent tumor control rates. Objective: To evaluate the effic acy of external beam radiation therapy (EBRT), ferromagnetic hyperther mia (FMH), and the combination of bath modalities in the. control of o cular tumors in a transgenic murine model of retinoblastoma. Methods: One hundred sixty-six 4-week-old animals transgenically positive for s imian virus 40 large T antigen were treated with a total dose of 10, 1 5, 20, 30, 40, 45, or 50 Gy of EBRT in 5-Gy fractions twice daily, wit h 48 degrees C or 54 degrees C FMH for 20 minutes, or with combined EB RT 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 ex amined for the presence of tumor. Results: The tumor control dose for 50% of eyes (TCD50) treated with EBRT occurred at 27.6 Gy. Ferromagnet ic hyperthermia at 48 degrees C cured 30% (6/20) of eyes, while 54 deg rees C FMH resulted in a 100% (20/20) cure rate. Combined treatment wi th 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 t o secondary treatment complications. Conclusions: This represents the first documentation of tumor control via EBRT, ocular FMH, and a combi nation of these treatment modalities in this murine transgenic retinob lastoma model. The extent of treatment synergy in this: model suggests that combined treatment application may allow a reduction in total oc ular and periocular radial ion dose while maintaining excellent local tumor control.