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Combination Radiofrequency Ablation with Intratumoral Liposomal Doxorubicin: Effect on Drug Accumulation and Coagulation in Multiple Tissues and Tumor Types in Animals¹

¹ From the Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215 (M.A., Z.L., C.H., W.L.M., S.N.G.); Department of Medical Oncology, Dana Farber Cancer Institute–Harvard Medical School, Boston, Mass (A.N.L., V.P.T.); and Department of Pharmaceutical Sciences, Bouve College of Health Sciences, Northeastern University, Boston, Mass (S.S.). From the 2003 RSNA Annual Meeting. Received November 18, 2003; revision requested January 21, 2004; final revision received August 2; accepted August 17. Supported by a grant from the National Cancer Institute, National Institutes of Health, Bethesda, Md (RO1-CA87992-01A1), and Bracco Research, Milan, Italy. Address correspondence to S.N.G. (e-mail: sgoldber@caregroup.harvard.edu).

View larger version (101K): [in a new window]   Figure 1a. Pathologic specimens show gross coagulation in tumor and normal kidney tissue treated with RF ablation only and with combination RF ablation-liposomal doxorubicin (Doxil) therapy. (a) Two canine transmissible venereal sarcomas: one treated with RF ablation alone (top) and the other treated with combination RF ablation-liposomal doxorubicin therapy (bottom). The combined therapy led to significant increases in overall coagulation 48 hours after treatment. Although the central white zone of RF ablation-induced coagulation (arrows) is similar in both tumors, increased peripheral necrosis (arrowheads) is observed in a red zone of the tumor treated with the combined therapy (bottom) compared with a much smaller peripheral zone in the tumor treated with RF ablation alone (top). (b) In normal kidney tissue treated with the combination therapy, a central zone of RF-induced coagulation (white arrows) is surrounded by a wide zone of peripheral necrosis (black arrows) similar to the increased peripheral necrosis observed in a.

View larger version (102K): [in a new window]   Figure 1b. Pathologic specimens show gross coagulation in tumor and normal kidney tissue treated with RF ablation only and with combination RF ablation-liposomal doxorubicin (Doxil) therapy. (a) Two canine transmissible venereal sarcomas: one treated with RF ablation alone (top) and the other treated with combination RF ablation-liposomal doxorubicin therapy (bottom). The combined therapy led to significant increases in overall coagulation 48 hours after treatment. Although the central white zone of RF ablation-induced coagulation (arrows) is similar in both tumors, increased peripheral necrosis (arrowheads) is observed in a red zone of the tumor treated with the combined therapy (bottom) compared with a much smaller peripheral zone in the tumor treated with RF ablation alone (top). (b) In normal kidney tissue treated with the combination therapy, a central zone of RF-induced coagulation (white arrows) is surrounded by a wide zone of peripheral necrosis (black arrows) similar to the increased peripheral necrosis observed in a.

View larger version (176K): [in a new window]   Figure 2a. Histopathologic changes observed with combination RF ablation-intravenous doxorubicin therapy. (a) Hematoxylin-eosin-stained section (magnification, x20) of canine sarcoma tissue from the center of a tumor treated with combination therapy shows a central zone of RF ablation-induced coagulation. The tumor tissue surrounding the RF ablation-induced coagulative zone is characterized by cells that have undergone classic coagulative necrosis. (b) Hematoxylin-eosin-stained section (magnification, x4) of normal rabbit liver tissue treated with combined therapy shows three distinct histopathologic zones: The white zone (zone A) represents the thermal coagulation that is observed with RF ablation alone. Zone B, the tissue undergoing coagulation necrosis and surrounding the central RF zone, has a pronounced inflammatory reaction (arrows) at its inner marginal interface. Zone C is normal untreated liver tissue.

View larger version (164K): [in a new window]   Figure 2b. Histopathologic changes observed with combination RF ablation-intravenous doxorubicin therapy. (a) Hematoxylin-eosin-stained section (magnification, x20) of canine sarcoma tissue from the center of a tumor treated with combination therapy shows a central zone of RF ablation-induced coagulation. The tumor tissue surrounding the RF ablation-induced coagulative zone is characterized by cells that have undergone classic coagulative necrosis. (b) Hematoxylin-eosin-stained section (magnification, x4) of normal rabbit liver tissue treated with combined therapy shows three distinct histopathologic zones: The white zone (zone A) represents the thermal coagulation that is observed with RF ablation alone. Zone B, the tissue undergoing coagulation necrosis and surrounding the central RF zone, has a pronounced inflammatory reaction (arrows) at its inner marginal interface. Zone C is normal untreated liver tissue.