Abstract
PurposeTo validate the feasibility of using peri-tumoral radiofrequency hyperthermia (RFH)-enhanced chemotherapy to obliterate hepatic tumor margins.Method and MaterialsThis study included in vitro experiments with VX2 tumor cells and in vivo validation experiments using rabbit models of liver VX2 tumors. Both in vitro and in vivo experiments received different treatments in four groups (n=6/group): (i) RFH-enhanced chemotherapy consisting of peri-tumoral injection of doxorubicin plus RFH at 42°C; (ii) RFH alone; (iii) doxorubicin alone; and (iv) saline. Therapeutic effect on cells was evaluated using different laboratory examinations. For in vivo experiments, orthotopic hepatic VX2 tumors in 24 rabbits were treated by using a multipolar radiofrequency ablation electrode, enabling simultaneous delivery of both doxorubicin and RFH within the tumor margins. Ultrasound imaging was used to follow tumor growth overtime, correlated with subsequent histopathological analysis.ResultsIn in vitro experiments, MTS assay demonstrated the lowest cell proliferation, and apoptosis analysis showed the highest apoptotic index with RFH-enhanced chemotherapy, compared with the other three groups (p<0.01). In in vivo experiments, ultrasound imaging detected the smallest relative tumor volume with RFH-enhanced chemotherapy (p<0.01). The TUNEL assay further confirmed the significantly increased apoptotic index and decreased cell proliferation in the RFH-enhanced therapy group (p<0.01).ConclusionThis study demonstrates that peri-tumoral RFH can specifically enhance the destruction of tumor margins in combination with peri-tumoral injection of a chemotherapeutic agent. This new interventional oncology technique may address the critical clinical problem of frequent marginal tumor recurrence/persistence following thermal ablation of large (>3 cm) hepatic cancers.
Highlights
Advanced ablative and embolic techniques in interventional oncology have become important tools in the multidisciplinary approach to manage patients with primary and secondary liver malignancies
This study included two components: (a) in vitro experiments to prove the principle of the new concept, “radiofrequency ablation (RFA)-mediated hyperthermia (RFH) enhancement of the tumor-killing effect of chemotherapeutic agents” on VX2 tumor cells; and (b) in vivo experiments to validate the feasibility of this new interventional oncologic technique, “Imaging-guided RFH-enhanced direct chemo-destruction of tumor margin tissues”, in rabbit models with orthotopic VX2 liver tumors using a multi-modal perfusion-thermal RFA electrode
The cells were divided into four groups (n=6/group), which were treated by (a) combination therapy consisting of doxorubicin (Doxo, 13.9 mM) with RFH at 42 ± 1°C for 20 min; (b) RFH alone; (c) Doxo alone; and (d) phosphatebuffered saline (PBS)
Summary
Advanced ablative and embolic techniques in interventional oncology have become important tools in the multidisciplinary approach to manage patients with primary and secondary liver malignancies. Image-guided percutaneous ablation techniques include ethanol ablation (EA), radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, and irreversible electrophoresis (IRE). EA is currently uncommon in clinical practice due to its high local tumor progression rate, which usually requires multiple treatment sessions [1, 2]. Embolic (non-ablative) interventional techniques primarily include chemoembolization and radioembolization. The primary limitation of chemoembolization is the frequent development of tumor resistance to chemotherapy [7], while radioembolization is often technically complex (requiring two separate angiographic procedures for vascular mapping/lung-shunt fraction calculations and treatment infusion) with high cost and uncertain future for reimbursement by major insurance payers [8]
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