Image-Guided Peri-Tumoral Radiofrequency Hyperthermia-Enhanced Direct Chemo-Destruction of Hepatic Tumor Margins

Minjiang Chen; Feng Zhang; Jingjing Song; Qiaoyou Weng; Peicheng Li; Qiang Li; Kun Qian; Hongxiu Ji; Sean Pietrini; Jiansong Ji; Xiaoming Yang

doi:10.3389/fonc.2021.593996

Image-Guided Peri-Tumoral Radiofrequency Hyperthermia-Enhanced Direct Chemo-Destruction of Hepatic Tumor Margins

Front Oncol. 2021 Jun 21:11:593996. doi: 10.3389/fonc.2021.593996. eCollection 2021.

Authors

Minjiang Chen^{1

2}, Feng Zhang¹, Jingjing Song^{1

2}, Qiaoyou Weng^{1

2}, Peicheng Li¹, Qiang Li¹, Kun Qian¹, Hongxiu Ji^{1

3}, Sean Pietrini¹, Jiansong Ji², Xiaoming Yang¹

Affiliations

¹ Image-Guided Bio-Molecular Interventions Research & Division of Interventional Radiology, Department of Radiology, University of Washington School of Medicine, Seattle, WA, United States.
² Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Department of Radiology, Zhejiang University Lishui Hospital, Lishui, China.
³ Department of Pathology, Overlake Medical Center and Incyte Diagnostics, Bellevue, WA, United States.

Abstract

Purpose: To validate the feasibility of using peri-tumoral radiofrequency hyperthermia (RFH)-enhanced chemotherapy to obliterate hepatic tumor margins.

Method and materials: This 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.

Results: In 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).

Conclusion: This 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.

Keywords: chemotherapy; image-guided interventional oncology; liver malignancies; peri-tumoral injection; radiofrequency hyperthermia.

Grants and funding

R01 EB028095/EB/NIBIB NIH HHS/United States