title: Does Thermosensitive Liposomal Vinorelbine Improve End-Point Survival after Percutaneous Radiofrequency Ablation of Liver Tumors in a Mouse Model?
abstract: Purpose To investigate the role of thermosensitive liposome-encapsulated vinorelbine (Thermo-Vin) in combined radiofrequency (RF) ablation of liver tumors. Materials and Methods Approval from the institutional animal care and use committee was obtained before this study. First, the anticancer efficacy of Thermo-Vin was assessed in vitro (H22 cells) for 72 hours at 37°C or 42°C. Next, 203 H22 liver adenocarcinomas were implanted in 191 mice for in vivo study. Tumors were randomized into seven groups: (a) no treatment, (b) treatment with RF ablation alone, (c) treatment with RF ablation followed by free vinorelbine (Free-Vin) at 30 minutes, (d) treatment with RF ablation followed by empty liposomes (Empty-Lip+RF), (e) treatment with RF ablation followed by Thermo-Vin (5 mg/kg), (f) treatment with RF ablation followed by Thermo-Vin (10 mg/kg), and (g) treatment with RF ablation followed by Thermo-Vin (20 mg/kg). Tumor destruction areas and pathologic changes were compared for different groups at 24 and 72 hours after treatment. Kaplan-Meier analysis was used to compare end-point survival (tumor < 30 mm in diameter). Additionally, the effect of initial tumor size on long-term outcome was analyzed. Results In vitro, both Free-Vin and Thermo-Vin dramatically inhibited H22 cell viability at 24 hours. Likewise, in vivo, 10 mg/kg Thermo-Vin+RF ablation increased tumor destruction compared with RF ablation (P = .001). Intratumoral vinorelbine accumulation with Thermo-Vin+RF increased 15-fold compared with Free-Vin alone. Thermo-Vin substantially increased apoptosis at the coagulation margin and suppressed cellular proliferation in the residual tumor (P < .001). The Thermo-Vin+RF study arm also had better survival than the arm treated with RF ablation alone (mean, 37.6 days ± 20.1 vs 23.4 days ± 5.0; P = .001), the arm treated with Free-Vin+RF (23.3 days ± 1.2, P = .002), or the arm treated with Empty-Lip+RF (20.8 days ± 0.4, P < .001) in animals with medium-sized (10-12-mm) tumors. No significant difference in end-point survival was noted in the treatment arms with large or small tumors. Conclusion Thermo-Vin can effectively increase tumor destruction and improve animal survival. End-point survival is most affected in animals with medium-sized tumors, suggesting that combination therapy should be tailored to tumor size and the expected volume of ablation of the device used. (©) RSNA, 2016 Online supplemental material is available for this article.
authors.affiliation: From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound (S.W., J.C.L., K.Y., W.Y.) and Department of Biobank (H.B.H.), Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, Beijing 100142, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China (X.G.M., W.G.); Division of Image-guided Therapy, Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel (S.N.G.); and Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Mass (S.N.G., M.A.).
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.affiliation: From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound (S.W., J.C.L., K.Y., W.Y.) and Department of Biobank (H.B.H.), Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, Beijing 100142, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China (X.G.M., W.G.); Division of Image-guided Therapy, Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel (S.N.G.); and Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Mass (S.N.G., M.A.).
authors.forename: Xing-Guo
authors.initials: XG
authors.lastname: Mei
authors.affiliation: From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound (S.W., J.C.L., K.Y., W.Y.) and Department of Biobank (H.B.H.), Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, Beijing 100142, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China (X.G.M., W.G.); Division of Image-guided Therapy, Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel (S.N.G.); and Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Mass (S.N.G., M.A.).
authors.forename: S Nahum
authors.initials: SN
authors.lastname: Goldberg
authors.affiliation: From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound (S.W., J.C.L., K.Y., W.Y.) and Department of Biobank (H.B.H.), Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, Beijing 100142, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China (X.G.M., W.G.); Division of Image-guided Therapy, Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel (S.N.G.); and Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Mass (S.N.G., M.A.).
authors.forename: Muneeb
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound (S.W., J.C.L., K.Y., W.Y.) and Department of Biobank (H.B.H.), Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, Beijing 100142, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China (X.G.M., W.G.); Division of Image-guided Therapy, Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel (S.N.G.); and Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Mass (S.N.G., M.A.).
authors.forename: Jung-Chieh
authors.initials: JC
authors.lastname: Lee
authors.affiliation: From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound (S.W., J.C.L., K.Y., W.Y.) and Department of Biobank (H.B.H.), Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, Beijing 100142, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China (X.G.M., W.G.); Division of Image-guided Therapy, Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel (S.N.G.); and Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Mass (S.N.G., M.A.).
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound (S.W., J.C.L., K.Y., W.Y.) and Department of Biobank (H.B.H.), Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, Beijing 100142, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China (X.G.M., W.G.); Division of Image-guided Therapy, Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel (S.N.G.); and Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Mass (S.N.G., M.A.).
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Han
authors.affiliation: From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound (S.W., J.C.L., K.Y., W.Y.) and Department of Biobank (H.B.H.), Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, Beijing 100142, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China (X.G.M., W.G.); Division of Image-guided Therapy, Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel (S.N.G.); and Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Mass (S.N.G., M.A.).
authors.forename: Kun
authors.initials: K
authors.lastname: Yan
authors.affiliation: From the Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound (S.W., J.C.L., K.Y., W.Y.) and Department of Biobank (H.B.H.), Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, Beijing 100142, China; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China (X.G.M., W.G.); Division of Image-guided Therapy, Department of Radiology, Hadassah Hebrew University Medical Center, Jerusalem, Israel (S.N.G.); and Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Mass (S.N.G., M.A.).
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D017115:Catheter Ablation / Q000379:methods; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006358:Hot Temperature; D008081:Liposomes; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D014747:Vinblastine; D000077235:Vinorelbine