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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 (pin vivo experiments, ultrasound imaging detected the smallest relative tumor volume with RFH-enhanced chemotherapy (pConclusionThis 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.

PurposeTo evaluate the treatment effect of radiofrequency-induced hyperthermia (RFH) combined with intra-tumoral chemotherapy for rabbit VX2 liver tumors and explore the underlying mechanism that drives local hyperthermia-enhanced chemotherapy.Materials and MethodsVX2 cell lines and rabbits with liver VX2 tumors were randomly allocated to four treatment groups including: (1) combination therapy of Doxorubicin (DOX) plus hyperthermia/RFH (n=6); (2) DOX only; (3) hyperthermia/RFH only (n=6); and (4) phosphate-buffered saline-treated control (n=6). Cell viability and doxorubicin uptake by VX2 tumor cells were assayed using flow cytometry and fluorescence microscopy 24 h after treatments. Western blot was used to evaluate the expression level of heat shock protein 70 (HSP70) in tumor cells and tissues. For the harvested VX2 tumors, fluorescence microscopy was used to evaluate the distribution and penetration of doxorubicin in tumor tissues and HSP70 expression was analyzed by Western blot and immunohistochemistry.ResultsRFH enhanced the chemotherapeutic effect of doxorubicin in VX2 cells and rabbit liver VX2 tumors resulting in higher apoptosis and lower cell viability. Flowcytometry of VX2 cells showed more apoptotic cells in combination therapy of hyperthermia and DOX, compared with other three groups in-vitro experiments (45.80 ± 1.27% vs 20.66 ± 0.71%, vs 15.16 ± 0.81% and 0.62 ± 0.06%, respectively, pConclusionsRFH/hyperthermia enhanced the chemotherapeutic effect of DOX in VX2 tumors by promoting the uptake of DOX and the expression HSP70 in tumors.