Percutaneous tumor ablation: increased necrosis with combined radio-frequency ablation and intravenous liposomal doxorubicin in a rat breast tumor model.
OBJECTIVE
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.


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 degrees 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.


CONCLUSIONS
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.
Goldberg
S Nahum
SN
Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA. sgoldber@caregroup.harvard.edu
Girnan
Geoffrey D
GD
Lukyanov
Anatoly N
AN
Ahmed
Muneeb
M
Monsky
Wayne L
WL
Gazelle
G Scott
GS
Huertas
Juan Carlos
JC
Stuart
Keith E
KE
Jacobs
Timothy
T
Torchillin
Vladimir P
VP
Halpern
Elkan F
EF
Kruskal
Jonathan B
JB
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017115:Catheter Ablation; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D007262:Infusions, Intravenous; D008081:Liposomes; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D009336:Necrosis; D009368:Neoplasm Transplantation; D011092:Polyethylene Glycols; D051381:Rats; D011916:Rats, Inbred F344; D013501:Surface-Active Agents; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008081:Liposomes; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D004317:Doxorubicin