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Developing an in Vivo Preclinical Model to Assess Intratumoral Modulation Therapy for Glioblastoma

The following abstract was presented as part of London Health Research Day 2017.
 

Research Areas: Neuroscience; Advances in structural and physiological treatment of disease and therapeutic intervention (includes surgery and drugs)
First Author: Dr. Andrea Di Sebastiano
Supervisor(s): Dr. Matthew Hebb

Introduction:
Glioblastoma (GBM) is the most common primary brain cancer in adults and remains without effective treatment. Our group has been pioneering a putative new electrotherapeutic strategy, called Intratumoral Modulation Therapy (IMT), that utilizes implantable hardware to deliver chronic, titratable, targeted therapy to GBM. The aim of this proof-of-concept study was to evaluate the efficacy of IMT against GBM using a novel in vivo preclinical model.

Hypothesis:
An implantable device applying an electric current or field within a tumor may exploit the electrosensitivity of GBM cells and provide anatomically targeted, continuous, titratable therapy.

Materials and Methods:
We have developed an in vivo model of IMT using a syngeneic F98 Fischer rat GBM model. F98 tumor cells were bilaterally implanted into the caudate-putamen of 16 female Fischer rats. On postoperative day four, a seven-day course of IMT or sham conditions was initiated using an implanted electrode at the epicenter of the growing tumor. Continuous pulsed stimulation was delivered to the tumors using a sinusoidal waveform and parameters demonstrated safe in normal brain (200 kHz, +/-2V). After treatment, the brains were processed and tumor volume measured throughout the rostrocaudal extent of the tumor and also within the predicted region of the IMT treatment field.

Results:
In a cohort of 16 animals with GBM, IMT monotherapy was well-tolerated and produced significant volume reduction (range 2-61%; p<0.05) when directed at large, aggressive tumors in the living brain. Control animals implanted with therapeutic hardware but no GBM tumors exhibited no adverse behavioral or histological sequelae of IMT.

Discussion and Conclusions:
This novel proof-of-concept study demonstrates the feasibility of using an in-dwelling device to deliver efficacious and targeted therapeutic stimulation to GBM-affected regions of the brain. This data raises the intriguing prospect that innovations in IMT electrotherapy may offer new, critically-needed treatment options for GBM.