Percutaneous tumor ablation: Increased necrosis with combined radio-frequency ablation and intratumoral doxorubicin injection in a rat breast tumor model

PURPOSE: To determine whether a combination of intratumoral doxorubicin inj ection and radio-frequency (RF) ablation increases tumor destruction compar ed with RF ablation alone in an animal tumor model. MATERIALS AND METHODS: R3230 mammary adenocarcinoma 1.2-1.5-cm-diameter nod ules (n = 110) were implanted subcutaneously in 84 female Fischer rats. For initial experiments (n = 46), tumors were treated with (a) conventional, m onopolar RF (250 mA +/-: 25 [SD] at 70 degreesC +/- 1 for 5 minutes) ablati on alone; (b) direct intratumoral doxorubicin injection (volume, 250 muL to tal dose, 0.5 mg) alone; (c) combined therapy (doxorubicin injection immedi ately followed by RF ablation); (d) RF ablation and injection of 250 muL 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 doxorub icin administration (2 days before to 2 days after RF ablation; n = 24 more tumors) were varied. Pathologic examination, including staining for mitoch ondrial enzyme activity and perfusion, was performed, and the resultant tum or 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 w ater (P = .52), while intratumoral doxorubicin injection alone produced onl y 2.0-3.0 mm of coagulation (P < .001). Increased coagulation was observed only with combined doxorubicin injection and RF therapy (P < .001). Coagula tion was dependent on concentration and timing of doxorubicin administratio n, with greatest coagulation (11.5 mm +/- 1.1) observed for doxorubicin adm inistered within 30 minutes of RF ablation. CONCLUSION: Adjuvant intratumoral doxorubicin injection increases coagulati on in solid tumors compared with RF ablation alone. Increased tumor destruc tion is also seen when doxorubicin is administered after RF ablation, which suggests that RF ablation may sensitize tumors to chemotherapy. Such combi nation therapies may, therefore, offer improved methods for ablating solid tumors.