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Percutaneous Tumor Ablation: Increased Necrosis with Combined Radio-frequency Ablation and Intravenous Liposomal Doxorubicin in a Rat Breast Tumor Model¹

¹ From the Depts of Radiology (S.N.G., M.A., W.L.M., J.C.H., J.B.K.), Medical Oncology (K.E.S.), and Pathology (T.J.), Beth Israel Deaconess Med Ctr, Harvard Med School, 330 Brookline Ave, Boston, MA 02215; Dept of Cancer Biology, Dana Farber Cancer Institute, Boston, Mass (G.D.G.); Dept of Pharmaceutical Sciences, Bouve Coll of Health Sciences, Northeastern Univ, Boston, Mass (A.N.L., V.P.T.); and Dept of Radiology, Massachusetts Gen Hosp, Boston, Mass (G.S.G., E.F.H.). Received Apr 30, 2001; revision requested Jun 14; revision received Jul 30; accepted Sept 7. Supported in part by grants from Radionics. Address correspondence to S.N.G. (e-mail: sgoldber@caregroup.harvard.edu).

PURPOSE: To determine whether a combination of intravenous liposomal doxorubicin and radio-frequency (RF) ablation increases tumor destruction compared with RF alone in an animal tumor model.

MATERIALS AND METHODS: R3230 mammary adenocarcinoma 1.4–1.8-cm- diameter nodules were implanted subcutaneously in 132 female Fischer rats. Initially, tumors were treated with (a) conventional, monopolar RF (mean, 250 mA ± 25 [SD] at 70°C ± 1 for 5 minutes) ablation alone, (b) RF ablation followed by intravenous administration of 1 mg of liposomal doxorubicin, (c) RF ablation followed by intravenous administration of 1 mg of empty liposomes, (d) RF ablation and direct intratumoral administration of liposomal doxorubicin, or (e) no treatment. Subsequently, the dose (0.06–2.00 mg) of liposomal doxorubicin, the timing of administration (3 days before to 3 days after RF ablation), and the time of pathologic examination (0–72 hours after treatment) were varied.

RESULTS: Mean coagulation diameter for treated tumors follows: 6.7 mm ± 0.6, RF ablation alone; 11.1 mm ± 1.5, RF ablation and intravenous administration of empty liposomes (P < .05, compared with RF ablation alone); and 8.4 mm ± 1.1, RF ablation with intratumoral administration of liposomal doxorubicin (P < .05, compared with RF ablation alone). Maximal increased mean coagulation diameter (13.1 mm ± 1.5) was observed with a combination of liposomal doxorubicin and RF ablation (P < .001, for all comparisons). The increased coagulation for combination therapy developed over 48 hours after therapy. Coagulation diameter did not vary with the doxorubicin concentration range and was not dependent on the timing of administration of liposomal doxorubicin from 3 days before to 24 hours after RF ablation.

CONCLUSION: Intravenous administration of liposomal doxorubicin can improve RF ablation, since it increases coagulation diameter in solid tumors compared with RF ablation alone or a combination of RF ablation with administration of empty liposomes.

© RSNA, 2002

Index terms: Animals • Breast neoplasms, therapy, 00.32 • Chemotherapy • Hyperthermia • Radiofrequency (RF) ablation

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