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Percutaneous Tumor Ablation: Reduced Tumor Growth with Combined Radio-frequency Ablation and Liposomal Doxorubicin in a Rat Breast Tumor Model¹

¹ From the Minimally Invasive Tumor Therapy Laboratory (G.D., M.A., G.D.G., K.E.S., J.B.K., S.N.G.), Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215; and DATA Group, Department of Radiology, Massachussets General Hospital, Harvard Medical School, Boston, Mass (E.F.H.). Supported by grants from the National Cancer Institute, National Institutes of Health, Bethesda, Md (RO1-CA87992-01A1) and Bracco, Milan, Italy. Received March 27, 2002; revision requested June 4; final revision received September 24; accepted October 14. Address correspondence to S.N.G. (e-mail: sgoldber@caregroup.harvard.edu).

PURPOSE: To determine whether combined intravenous liposomal doxorubicin and radio-frequency (RF) ablation decreases tumor growth and increases endpoint survival over those with RF or liposomal doxorubicin alone in an animal tumor model.

MATERIALS AND METHODS: Subcutaneous R3230 mammary adenocarcinoma (1.1–1.4 cm) was implanted in female Fischer rats. Initially, 35 tumors were randomized into four experimental groups: (a) conventional monopolar RF (70°C for 5 minutes) alone, (b) liposomal doxorubicin (1 mg) alone, (c) RF ablation followed by liposomal doxorubicin, and (d) no treatment. Ten additional tumors were randomized into two groups that received a 90°C RF dose either with or without liposomal doxorubicin. Tumor growth rates and the defined survival endpoint, the time at which the tumor reached 3.0 cm in diameter, were recorded. The effect of treatments on endpoint survival and tumor doubling time were analyzed by means of the Kaplan-Meier method and analysis of variance statistics.

RESULTS: Differences in endpoint survival and tumor doubling time in the six groups were highly significant (P < .001). Endpoint survivals were 9.1 days ± 2.5 for the control group, 16 days ± 3.7 for tumors treated with 70°C RF alone, 16.5 days ± 3.2 for tumors treated with liposomal doxorubicin alone, and 26.6 ± 5.3 days with combined treatment. For 90°C RF ablation, endpoint survivals were 16.6 days ± 1.2 and 31.5 days ± 3.0 without and with liposomal doxorubicin (P < .01). Mean endpoint survival and tumor doubling times for the three RF levels (0, 70°C, and 90°C) were all significantly different (P = .01). Additionally, animals that received combined liposomal doxorubicin and 90°C RF ablation survived longer than did animals that received combined liposomal doxorubicin and 70°C RF ablation (P < .01).

CONCLUSION: Combined RF ablation and liposomal doxorubicin retards tumor growth and may increase animal survival compared with that with either therapy alone or no therapy.

© RSNA, 2003

Index terms: Adenocarcinoma, 00.32 • Animals • Breast neoplasms, experimental studies, 00.1269 • Chemotherapy • Experimental study, 00.1269 • Radiofrequency (RF) ablation

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