Adjuvant electrochemotherapy after debulking in canine bone osteosarcoma infiltration

Abstract

Osteosarcoma is a bone cancer considered rare to humans, but common in dogs. Dogs and humans share genetic homology and environmental risk factors. Improving the treatment of osteosarcoma in dogs could also be relevant to improve procedures in humans. Traditional treatments of osteosarcoma involve surgery and chemotherapy. Such treatments are commonly aggressive and not possible for many patients. Electrochemotherapy emerges as a minimally invasive, effective, and safe treatment alternative. Electrochemotherapy combines applications of high‐intensity electric fields during short periods with anti‐cancer drugs to improve its medicine cytotoxicity. Analyzing the electric field distribution, as well as electric current density, are essential to electrochemotherapy success. This paper brings the first case of a canine osteosarcoma treatment performed with bleomycin and electrochemotherapy. We performed in silico studies with finite element method software to observe the electric field distribution. In silico experiments help to verify possibilities and limitations of treating bone destruction and macro or micro tumor infiltrations around the primary tumor mass. Results show that both needle or plate electrodes are feasible to remove the tumor even with invasion into the bone. Plate electrodes perform well in treating micro infiltrations when associated with conductive gel and direct contact between electrode and bone (without soft tissues). Needle electrodes are effective in treating tumor infiltration on external cortical bone. Multiple applications are needed to cover all cranium layers with sufficient electric field intensity. Electrochemotherapy protocol with needle or plate electrodes does not present sufficient electric current density capable of affecting brain tissue, even in cases of bone destruction.

Clinical Applications and Immunological Aspects of Electroporation-Based Therapies

“…Among the different indications of ECT for cutaneous and subcutaneous primary cancer or skin metastasis, the following are included: palliative treatment of skin metastases in advanced diseases; neoadjuvant cytoreductive therapy prior to conventional treatment; organ and function sparing treatment; patients not suitable for or relapsed after treatment by surgery, radiotherapy or systemic therapy, and treatment of highly vascularized nodules due to its antivascular effect [ 42 , 73 , 74 , 75 , 76 ]. Additionally, in veterinary medicine ECT is used as an adjuvant therapy for the treatment of incompletely resected tumors, aiming to remove possible residual infiltrating cancer cells at the surgical site, when a wide safety margin resection is not possible [ 31 , 77 , 78 ]. The use of ECT in noncutaneous deep-seated and internal organ tumors is under investigation in a number of human clinical trials, with preliminary results indicating its feasibility and safety [ 42 , 72 , 79 , 80 , 81 , 82 , 83 ].…”

Eletrogeneterapia com IFN-Beta em modelo murino de melanoma

“…palliative treatment of skin metastases in advanced diseases; neoadjuvant cytoreductive therapy prior to conventional treatment; organ and function sparing treatment; patients not suitable for or relapsed after treatment by surgery, radiotherapy or systemic therapy, and treatment of highly vascularized nodules due to its antivascular effect [42,[73][74][75][76]. Additionally, in veterinary medicine ECT is used as an adjuvant therapy for the treatment of incompletely resected tumors, aiming to remove possible residual infiltrating cancer cells at the surgical site, when a wide safety margin resection is not possible [31,77,78]. The use of ECT Similar to surgical approaches as a local treatment, an adequate application of ECT must uniformly cover the whole tumor tissue and its surrounding safety margins with an appropriate electric field and sufficient drug at the moment of the delivery of electric pulses [42,89].…”