Radiation therapy and ferromagnetic hyperthermia in the treatment of murine transgenic retinoblastoma
T. G. Murray, J. M. O'Brien, R. A. Steeves, B. J. Smith, D. M. Albert, N. Cicciarelli, A. M. Markoe, D. T. Tompkins and J. J. Windle
Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Fla, USA.
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 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.
RESULTS: 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. 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.
