Isolated limb perfusion with biochemotherapy and oncolytic virotherapy combines with radiotherapy and surgery to overcome treatment resistance in an animal model of extremity soft tissue sarcoma.
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Date
2016-09-15Author
Wilkinson, MJ
Smith, HG
Pencavel, TD
Mansfield, DC
Kyula-Currie, J
Khan, AA
McEntee, G
Roulstone, V
Hayes, AJ
Harrington, KJ
Type
Journal Article
Metadata
Show full item recordAbstract
The management of locally advanced or recurrent extremity sarcoma often necessitates multimodal therapy to preserve a limb, of which isolated limb perfusion (ILP) is a key component. However, with standard chemotherapeutic agents used in ILP, the duration of response is limited. Novel agents or treatment combinations are urgently needed to improve outcomes. Previous work in an animal model has demonstrated the efficacy of oncolytic virotherapy when delivered by ILP and, in this study, we report further improvements from combining ILP-delivered oncolytic virotherapy with radiation and surgical resection. In vitro, the combination of radiation with an oncolytic vaccinia virus (GLV-1h68) and melphalan demonstrated increased cytotoxicity in a panel of sarcoma cell lines. The effects were mediated through activation of the intrinsic apoptotic pathway. In vivo, combinations of radiation, oncolytic virotherapy and standard ILP resulted in delayed tumour growth and prolonged survival when compared with standard ILP alone. However, local disease control could only be secured when such treatment was combined with surgical resection, the timing of which was crucial in determining outcome. Combinations of oncolytic virotherapy with surgical resection and radiation have direct clinical relevance in extremity sarcoma and represent an exciting prospect for improving outcomes in this pathology.
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Subject
Extremities
Cell Line, Tumor
Animals
Humans
Rats
Sarcoma
Disease Models, Animal
Recurrence
Melphalan
Antineoplastic Agents
Combined Modality Therapy
Radiotherapy
Tumor Burden
Transduction, Genetic
Apoptosis
Genetic Vectors
Male
Chemotherapy, Cancer, Regional Perfusion
Oncolytic Virotherapy
Oncolytic Viruses
Caspase 3
Proton Therapy
Research team
Sarcoma and Melanoma Surgery
Targeted Therapy
Language
eng
Date accepted
2016-04-15
License start date
2016-09
Citation
International journal of cancer, 2016, 139 (6), pp. 1414 - 1422
Publisher
WILEY