Concurrent versus sequential application of ferromagnetic hyperthermia and 125I brachytherapy of melanoma in an animal model

Abstract

Objective: To determine the efficacy of concurrent versus sequential ferromagnetic hyperthermia (FMH), combined with Iodine-125 (125I) brachytherapy, in the treatment of uveal melanoma in a rabbit model.

Materials and methods: A Greene melanoma cell line was implanted in rabbit eyes to establish a tumor model comparable to a uveal melanoma. Seventy-one tumor-containing rabbit eyes were treated with 125I brachytherapy at 20, 25, 35, 45, or 55 Gray (Gy)(38 eyes), and with either concurrent (15 eyes) or sequential (18 eyes) FMH, delivered at 48.2 degrees C for 1 hour. An additional 13 eyes were treated with FMH alone at 48.2 degrees C, either in a single heat application (5 eyes), or in a repetitive mode (8 eyes). The radiation and heat were delivered via an episcleral plaque. All tumors were followed with indirect ophthalmoscopy and echography.

Results: Tumors treated with 125I brachytherapy alone exhibited complete tumor regression in 50% of eyes at 42 Gy with none of the tumors responding to less than 35 Gy. FMH alone at 48.2 degrees C applied in one cycle limited tumor growth in 20% of eyes, while all eyes treated with repetitive heating exhibited complete tumor control. With concurrent application of FMH and 125I, the 50% tumor control rate occurred at 9.5 Gy, thus resulting in a thermal enhancement ratio (TER) of 4.4. With sequential treatment, the 50% tumor control rate was at 30 Gy, with a resultant TER of 1.4. No complications related to 125I brachytherapy were noted in any eyes, while transient retinal whitening was seen with the FMH.

Conclusion: This study documents the enhanced synergistic interaction of concurrent FMH and 125I brachytherapy, compared to sequential treatment, in this rabbit melanoma model.