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

Abstract

Use of RF ablation combined with liposomal doxorubicin facilitates increased tissue coagulation and interstitial doxorubicin accumulation in multiple tissues and tumor types and may be useful for treatment of large tumors and achieving an ablative margin within the untreated tissue surrounding RF ablation-treated tumors.

Liposomal Doxorubicin Increases Radiofrequency Ablation–induced Tumor Destruction by Increasing Cellular Oxidative and Nitrative Stress and Accelerating Apoptotic Pathways

“…Tumors were harvested at nine time points (three to six animals per time point and treatment): 2 and 30 minutes and 1, 2, 4, 8, 12, 24, and 72 hours after treatment ablation and intravenous administration of liposomal doxorubicin. Tissues undergoing combined treatment also exhibited increased tumor necrosis in animal models ( 16,17 ) and patients ( 14 ) in the transient hyperthermic zone of red coagulation surrounding the zone of white coagulation (ie, heat-induced tumor death) ( 18 ). Although combined therapies have demonstrated increased tumor destruction, particularly in the periphery of the ablation zone, to our knowledge, the underlying mechanisms that cause increased tumor destruction have not been suffi ciently explored.…”

Ultrasound ablation enhances drug accumulation and survival in mammary carcinoma models

“…Enhancement of nanoparticle accumulation in thermally ablated tumors has previously been demonstrated with minimally invasive RF thermal ablation (4-6). Previous work with Doxil and RF ablation in a canine sarcoma model suggested that accumulation is dramatically enhanced within a peripheral ring of hyperthermia about the central ablated region (4). Using MRgFUS, a noninvasive and conformal method of ablative thermal therapy, we found that enhancement is not dependent upon physical damage due to the introduction of a catheter or RF probe.…”

“…At 20 and 48 lethality in regions of sublethal hyperthermia (11). Hyperthermia enhances local accumulation of nanoparticles due to enhanced blood flow, changes in the effective pore size of vasculature, and release of inflammatory and vasodilatory substances from ablated mast cells or endothelial cells (4)(5)(6)(16)(17)(18)(19)(20). While ultrasoundinduced mild hyperthermia alone can enhance the accumulation of nanotherapeutics, the accumulation has been shown to be dependent on the tumor phenotype (21).…”

“…Thus, there are multiple motivations and precedents for combining systemic and local therapies; for example, radiation therapy combined with neoadjuvant chemotherapy reduces risk of local recurrence in breast-conserving surgery (1,2). Furthermore, the efficacy of radiofrequency (RF) ablation is improved by preablation thermosensitization (3) and coadministration of ablation and chemotherapy (4)(5)(6), suggesting that combining ablation with drug therapy may also increase coagulation diameter and reduce recurrence using MRgFUS. The purpose of this study is to determine whether a practical ablation strategy in which the tumor margin is incompletely treated to preserve sensitive surrounding tissue can be locally curative in mammary carcinoma.…”

Chemoradionuclide Therapy with186Re-labeled Liposomal Doxorubicin in Combination with Radiofrequency Ablation for Effective Treatment of Head and Neck Cancer in a Nude Rat Tumor Xenograft Model

“…A major drawback of RF ablation is the inability to completely destroy the tumor ( 18 ). To overcome this problem, RF ablation has been used in combination with liposomal doxorubicin (19)(20)(21) and other therapies (22)(23)(24)(25), resulting in larger volumes of tumor destruction.…”