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Reduced Tumor Growth with Combined Radiofrequency Ablation and Radiation Therapy in a Rat Breast Tumor Model¹

¹ From the Minimally Invasive Tumor Therapy Laboratory, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Road, WCC 308B, Boston, MA 02215 (C.H., K.D., S.N.G.); Department of Nuclear Engineering, Massachusetts Institute of Technology, Cambridge, Mass (J.A.C., J.L.K.); Department of Radiology, Rhode Island Hospital, Providence, RI (D.E.D.); Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (S.S.); and Institute for Technology Assessment, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass (E.F.H.). From the 2003 RSNA Annual Meeting. Received February 11, 2004; revision requested April 14; revision received May 19; accepted June 28. Address correspondence to S.N.G. (e-mail: sgoldber@bidmc.harvard.edu).

View larger version (14K): [in a new window]   Figure 1a. Graphs show tumor growth patterns and end-point survival in individual animals in four tumor treatment groups: (a) no treatment (controls), (b) treatment with RF ablation alone, (c) treatment with 20-Gy radiation alone, and (d) treatment with RF ablation plus 20-Gy radiation. Sacrifice was mandated at a tumor diameter of 30 mm because of animal welfare concerns. Control tumors showed the most rapid growth. Tumors treated with either RF ablation or radiation therapy alone showed a growth trend similar to that in controls but a decreased growth rate. Tumors treated with combined RF ablation and radiation therapy initially increased in size, probably because of hyperemia and edema, which were followed by tumor involution and healing in nine (82%) of 11 animals.

View larger version (22K): [in a new window]   Figure 1b. Graphs show tumor growth patterns and end-point survival in individual animals in four tumor treatment groups: (a) no treatment (controls), (b) treatment with RF ablation alone, (c) treatment with 20-Gy radiation alone, and (d) treatment with RF ablation plus 20-Gy radiation. Sacrifice was mandated at a tumor diameter of 30 mm because of animal welfare concerns. Control tumors showed the most rapid growth. Tumors treated with either RF ablation or radiation therapy alone showed a growth trend similar to that in controls but a decreased growth rate. Tumors treated with combined RF ablation and radiation therapy initially increased in size, probably because of hyperemia and edema, which were followed by tumor involution and healing in nine (82%) of 11 animals.

View larger version (20K): [in a new window]   Figure 1c. Graphs show tumor growth patterns and end-point survival in individual animals in four tumor treatment groups: (a) no treatment (controls), (b) treatment with RF ablation alone, (c) treatment with 20-Gy radiation alone, and (d) treatment with RF ablation plus 20-Gy radiation. Sacrifice was mandated at a tumor diameter of 30 mm because of animal welfare concerns. Control tumors showed the most rapid growth. Tumors treated with either RF ablation or radiation therapy alone showed a growth trend similar to that in controls but a decreased growth rate. Tumors treated with combined RF ablation and radiation therapy initially increased in size, probably because of hyperemia and edema, which were followed by tumor involution and healing in nine (82%) of 11 animals.

View larger version (23K): [in a new window]   Figure 1d. Graphs show tumor growth patterns and end-point survival in individual animals in four tumor treatment groups: (a) no treatment (controls), (b) treatment with RF ablation alone, (c) treatment with 20-Gy radiation alone, and (d) treatment with RF ablation plus 20-Gy radiation. Sacrifice was mandated at a tumor diameter of 30 mm because of animal welfare concerns. Control tumors showed the most rapid growth. Tumors treated with either RF ablation or radiation therapy alone showed a growth trend similar to that in controls but a decreased growth rate. Tumors treated with combined RF ablation and radiation therapy initially increased in size, probably because of hyperemia and edema, which were followed by tumor involution and healing in nine (82%) of 11 animals.

View larger version (20K): [in a new window]   Figure 2. Graph shows results of Kaplan-Meier analysis of animal end-point survival after no treatment (both control groups combined), RF ablation alone, radiation therapy (XRT) alone (at total dose of 5 Gy or 20 Gy), and combined RF ablation and radiation therapy (at total dose of 5 Gy or 20 Gy). Longest end-point survival was observed with combined RF ablation and 20-Gy radiation therapy. Dose dependency of the effect of external-beam radiation therapy is also demonstrated.

View larger version (116K): [in a new window]   Figure 3. Gross tumor progression in rats treated with combined RF ablation and radiation therapy. A, Tumor (arrow) with 11-mm diameter at day 0, prior to therapy. B, At day 4, after RF ablation and 20-Gy radiation therapy, beginning of involution is evident in tumor (arrow). C, At day 7, granulation tissue (arrow) can be seen, and there are signs of hair regrowth. (All that will remain by day 25 is scar tissue.) D, Scar (arrow) on chest wall at day 120.

View larger version (85K): [in a new window]   Figure 4. Photomicrographs show histopathologic sections from tumors excised at day 7 after therapy. A, Slice from tumor treated with RF ablation alone (70°C for 5 minutes) shows typical appearance of heat-fixed tissue with rim of coagulative necrosis and peripheral areas of viable tumor. B, Slice from tumor treated with combined RF ablation and 20-Gy radiation therapy also shows an area of heat-fixed tissue. In this slice, however, marked hyperemia also is seen, with neovascular proliferation (black arrows) and edema (white arrows), and there is no evidence of viable tumor in the peripheral zone, which is composed of cellular debris. C, Slice from tumor treated with 20-Gy radiation therapy alone shows nothing but viable tumor cells. (Hematoxylin-eosin stain; original magnification, x10 [A and B] and x40 [C].)