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Percutaneous Tumor Ablation: Increased Necrosis with Combined Radio-Frequency Ablation and Intratumoral Doxorubicin Injection in a Rat Breast Tumor Model¹

¹ From the Departments of Radiology (S.N.G., J.C.H., J.B.K.), Surgical Oncology (P.F.S.), Medical Oncology (K.E.S.), and Pathology (T.J.), Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215; and Department of Radiology, Massachusetts General Hospital, Boston, (G.S.G.). Received October 5, 2000; revision requested November 16; final revision received February 9, 2001; accepted March 1. 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 intratumoral doxorubicin injection and radio-frequency (RF) ablation increases tumor destruction compared with RF ablation alone in an animal tumor model.

MATERIALS AND METHODS: R3230 mammary adenocarcinoma 1.2–1.5-cm- diameter nodules (n = 110) were implanted subcutaneously in 84 female Fischer rats. For initial experiments (n = 46), tumors were treated with (a) conventional, monopolar RF (250 mA ± 25 [SD] at 70°C ± 1 for 5 minutes) ablation alone; (b) direct intratumoral doxorubicin injection (volume, 250 µL; total dose, 0.5 mg) alone; (c) combined therapy (doxorubicin injection immediately followed by RF ablation); (d) RF ablation and injection of 250 µL of distilled water; or (e) no treatment. In subsequent experiments, amount of doxorubicin (0.02–2.50 mg; n = 40 additional tumors) and timing of doxorubicin administration (2 days before to 2 days after RF ablation; n = 24 more tumors) were varied. Pathologic examination, including staining for mitochondrial enzyme activity and perfusion, was performed, and the resultant tumor destruction from each treatment was evaluated.

RESULTS: Coagulation diameter was 6.7 mm ± 0.6 for tumors treated with RF ablation alone and 6.9 mm ± 0.7 for those treated with RF ablation and water (P = .52), while intratumoral doxorubicin injection alone produced only 2.0–3.0 mm of coagulation (P < .001). Increased coagulation was observed only with combined doxorubicin injection and RF therapy (P < .001). Coagulation was dependent on concentration and timing of doxorubicin administration, with greatest coagulation (11.5 mm ± 1.1) observed for doxorubicin administered within 30 minutes of RF ablation.

CONCLUSION: Adjuvant intratumoral doxorubicin injection increases coagulation in solid tumors compared with RF ablation alone. Increased tumor destruction is also seen when doxorubicin is administered after RF ablation, which suggests that RF ablation may sensitize tumors to chemotherapy. Such combination therapies may, therefore, offer improved methods for ablating solid tumors.

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

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