Efficacy of Ablative High-Dose-per-Fraction Radiation for Implanted Human Renal Cell Cancer in a Nude Mouse Model

Objectives

Stereotactic body radiation therapy (SBRT) is a new therapeutic paradigm that uses a very large dose per fraction treatments (ablative hypofractionation). We investigated the use of ablative hypofractionation in treating human renal cell carcinoma using a nude mouse model.

Methods

Nude mice were injected subcutaneously with A498 human renal carcinoma cells. Tumour-bearing animals were radiated with three fractions (one per week) for a total dose of 48Gy (n=12), while untreated animals served as controls (n=7). The mice were weighed, and tumour volumes were measured at baseline and weekly until 7 weeks post-treatment.

Results

Control animals demonstrated progressive tumour growth and were sacrificed because of either tumour size or ulceration. Tumours in the treatment group grew to three times their initial size over the 3 weeks of treatment but subsequently decreased progressively to less than 30% of their initial volume. All treated tumours exhibited marked cytologic changes. Tumours from mice sacrificed before post-treatment week 4 had a mitotic count of 1–4/10hpf. Tumours from mice sacrificed more than 4 weeks post-treatment (n=4) demonstrated no mitoses.

Conclusions

Treatment with high-dose-per-fraction radiation to 48Gy resulted in a sustained decrease in tumour volume and marked cytologic changes. These results are preliminary—but promising—and encourage further research into this application of ablative hypofractionated radiation for kidney cancer.

Treatment of human RCC in an in vivo murine model with high-dose-per-fraction radiation to 48Gy in three fractions resulted in a sustained decrease in tumour volume and dramatic histologic changes in most mice. These results encourage further research into high-dose radiation for kidney cancer.