Published online before print June 13, 2003, 10.1148/radiol.2281020358
Percutaneous Tumor Ablation: Reduced Tumor Growth with Combined Radio-frequency Ablation and Liposomal Doxorubicin in a Rat Breast Tumor Model1
Giuseppe D’Ippolito, MD,
Muneeb Ahmed, MD,
Geoffrey D. Girnun, PhD,
Keith E. Stuart, MD,
Jonathan B. Kruskal, MD, PhD,
Elkan F. Halpern, PhD and
S. Nahum Goldberg, MD
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).
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Figure 1. Tumor growth following treatment with RF ablation and/or intravenous liposomal doxorubicin (Dox). Scatterplot shows mean (and final SD) tumor diameter to sacrifice at 3 cm. Statistically significant reduction in tumor growth for combined therapies compared with all other groups is seen (P < .01). Mean endpoint survival of control animals was 9 days, and survival of animals treated with doxorubicin alone or RF ablation at 70°C or 90°C alone was 16 days (for all three groups, P < .001 compared with control). For animals treated with doxorubicin and RF ablation at 70°C or 90°C, mean endpoint survival was 26 days ± 5 and 31 days ± 3, respectively (P < .01).
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Figure 2. Kaplan-Meier analysis of animal endpoint survival following treatment with RF ablation and/or intravenous liposomal doxorubicin (Doxil, Dox). With tumor growth to a diameter of 3 cm as the survival endpoint, greatest endpoint survival was observed with combined therapy with liposomal doxorubicin and RF ablation at either 70°C or 90°C. In addition, improved endpoint survival was noted with a higher (90°C) RF thermal dose compared with combined treatment with a lower (70°C) RF dose.
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Figure 3a. Pathologic documentation of the effects of RF ablation and/or intravenous liposomal doxorubicin (Doxil) therapy on R3230 rat tumor growth. A comparison of tumors 10 days after receiving no treatment (Control), doxorubicin alone, RF ablation alone (tip temperature of 70°C), and combined RF ablation and doxorubicin is presented. (a) Significant difference in gross tumor size is demonstrated when comparing tumors that received no treatment with those that received other treatments. Tumors treated with combined RF ablation and adjuvant doxorubicin are much smaller than those that received either RF ablation alone or doxorubicin alone and have not grown past their initial size. (b) Samples stained with 2% 2,3,5-triphenyl tetrazolium chloride to identify residual viable tumor demonstrate a well-demarcated coagulation zone (white arrow) where RF has been applied and irregular patchy necrosis (black arrows) in tumors treated with either doxorubicin alone or RF ablation combined with doxorubicin.
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Figure 3b. Pathologic documentation of the effects of RF ablation and/or intravenous liposomal doxorubicin (Doxil) therapy on R3230 rat tumor growth. A comparison of tumors 10 days after receiving no treatment (Control), doxorubicin alone, RF ablation alone (tip temperature of 70°C), and combined RF ablation and doxorubicin is presented. (a) Significant difference in gross tumor size is demonstrated when comparing tumors that received no treatment with those that received other treatments. Tumors treated with combined RF ablation and adjuvant doxorubicin are much smaller than those that received either RF ablation alone or doxorubicin alone and have not grown past their initial size. (b) Samples stained with 2% 2,3,5-triphenyl tetrazolium chloride to identify residual viable tumor demonstrate a well-demarcated coagulation zone (white arrow) where RF has been applied and irregular patchy necrosis (black arrows) in tumors treated with either doxorubicin alone or RF ablation combined with doxorubicin.
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Copyright © 2003 by the Radiological Society of North America.
