Reduced Tumor Growth with Combined Radiofrequency Ablation and Radiation Therapy in a Rat Breast Tumor Model

Abstract

To determine whether use of combined radiofrequency (RF) ablation and external-beam radiation therapy increases end-point survival beyond that with either RF ablation or radiation therapy alone in an animal tumor model. With a protocol approved by the institutional animal care and use committee, R3230 mammary adenocarcinoma (12.5 mm +/- 0.6 [standard deviation]) was implanted subcutaneously into 107 female Fischer 344 rats. Initially, 42 tumors were randomized into four treatment groups: (a) RF ablation (70 degrees C for 5 minutes) alone, (b) RF ablation followed by radiation therapy with a total dose of 20 Gy, (c) 20-Gy radiation alone, and (d) no treatment. Another 19 tumors were randomized to receive (e) RF ablation (70 degrees C for 5 minutes) followed by 5-Gy radiation, (f) 5-Gy radiation alone, or (g) no treatment. Animals were followed up until survival end point (either until tumor growth to 30 mm in diameter, or for 120 days if no tumor was seen in mammary fat pad or chest wall). Results were analyzed with the Kaplan-Meier method. Histopathologic analysis was performed in 15 additional tumors at survival end point and 18 other representative tumors at other specified end points. Combined RF ablation and 20-Gy radiation resulted in complete local control in nine (82%) of 11 tumors, compared with one (9%) of 11 tumors treated with RF ablation alone and one (17%) of six treated with RF ablation and 5-Gy radiation (P < .001). No local control was achieved in rats with radiation therapy alone or in controls. Median end-point survival was 12 days for controls, 20 days with RF ablation or 5-Gy radiation alone, 30 days with RF ablation plus 5-Gy radiation, 40 days with 20-Gy radiation alone, and 120 days with RF ablation plus 20-Gy radiation. Mean end-point survival was 13 days +/- 5 (standard deviation) for the control group, 34 days +/- 31 with RF ablation alone, and 43 days +/- 16 with 20-Gy radiation alone. Mean survival was significantly greater with 20-Gy radiation and RF ablation combined: 94 days +/- 34 (P < .001 compared with all other groups). Mean survival for rats that received 5-Gy radiation with RF ablation versus without was 46 days +/- 37 versus 24 days +/- 11, respectively. Combined RF ablation and external-beam radiation therapy increased animal survival compared with that with either of the treatments alone or with no treatment.