/ An estimated 34,000 patients are diagnosed in the US with primary liver each year with a substantially largernumber of patients will developing liver metastasis from a broad range of primary tumor sites. Unfortunately, thevast majority of these patients are not candidates for surgical resection, which is the only reliably curativetreatment for liver tumors, yielding a five year survival rate of approximately between 10 and 20% for patientswith primary disease. The primary clinical challenge is that most tumors form deep within organs, near majorblood vessels, bile ducts, or nerves which complicate surgical removal and contraindicate other first linetreatments. Phased Algorithmically Controlled Electrotherapy (PACE) is a new minimally invasive techniquedeveloped by the Gradient Medical for the treatment of inoperable tumors which uses ultrashort high intensityelectrical pulses to destabilize the cell membrane and induce a tunable combination of necrotic and apoptoticcell death. In this proposal we investigate the feasibility of this approach for the treatment of liver tumors throughtwo specific aims: 1) Characterization of Selective Targeting with ACE protocols. 2) Development of a MultiphaseAlternating Polarity Pulse Generation System. In the proposed study Gradient Medical will design and build anovel pulse generation system which enables instantaneous electrical energy delivery between up to foursynchronized temperature sensing applicators. Feasibility of this approach will be demonstrated using abenchtop perfused liver model which enables direct visualization of the treatment zones created by the non-thermal pulsed electric field mediated cell death mechanisms. Preliminary safety and in vivo efficacy will beevaluated in an in vivo large animal liver model. The results from this feasibility study will be used to generatepreliminary treatment planning algorithms necessary for subsequent Phase II in vivo safety and efficacy studiesagainst spontaneous liver tumors in veterinary patients.
Public Health Relevance Statement: Relevance to Public Health
The vast majority of patients diagnosed with liver cancer will not be candidates for surgical treatment.
Unfortunately, these patients tend to have poor responses to standard treatments including radiation and
chemotherapy resulting in a five-year survival rate of approximately 20%. This study will investigate the feasibility
of PACE, a minimally invasive cancer therapy which uses ultrashort alternating polarity pulsed electric fields to
rapidly destroy deep seated inoperable tumors through non-thermal mechanisms.
Project Terms: | | | | 