NeoTherma Oncology Inc. — Department of Health and Human Services SBIR Phase I: 102

Description

Pancreatic Ductal AdenocarcinomaPDACis the third leading cause of cancer related death in the United Statesand is characterized with dismal odds due to advanced disease at late stage diagnosisTheyear survival rate ranges fromfor patients with non resectable diseaseof patientstofor patients with resectable tumorsandltof patientsPDAClike most solid tumorsis highly hypoxicresulting from both poor oxygen delivery due to leaky and chaotic vasculature and increased oxygen consumption due to high metabolic activityThis makes drug delivery to the tumor microenvironment more difficult and often ineffectiveIn the pastyearsonly marginal improvements in complete responseCRprogression free survivalPFSoverall survivalOSand quality of lifeQoLhave occurred despite the development of a number of promising chemotherapyor chemoradiation regimensNew and improved therapeutic options are urgently needed to improve the treatment of this diseaseMild hyperthermiaHTin the range ofC has shown to improve blood flow to tumorsenhancing the delivery of therapeutics to the hypoxic tumor microenvironmentNumerous randomized clinical trials have shown to provide CRPFSOR and QoL benefits but implementation in clinical practice has been lagging due to the inability to provide safequantifiable and controlled therapeutic thermal dose through accurate temperature monitoringNTO has designed and built the VectronTTx device which can effectively deliver heat non invasively in deep tissue without causing skin burns or excessive fat heatingthe most common adverse effect encountered with current technologieswithout the need for a cooling mechanism such as a water bolus that is a frequent cause for interrupted treatments due to patient discomfortThe heating elements of the device are integrated into an applicator with magnetic resonanceMRtransmit and receive channels to allow for real time MR thermometry imagingMRTImeasurementsIn this Phase I proposalwe will develop novel MRTI methodologies that significantly improve the state of the art by accurately measuring temperature over HT treatment time scalesminutesin an abdominal environment compensating for interfering processes including field drift and motion induced field variationsWe will also develop a treatmentmodeling architecture that combines virtual modelspatient specific featuresand an artificial intelligenceAIbased architecture to create extrapolated patient specific treatment plansUpon successful completion of Phase I and validation of the developed real time MRTI monitoring techniqueswe will develop methods in Phase II for accurate measurements of temperature in fat by incorporating interleaved or hybrid fat based techniques into the field corrected MRTI sequencesIn phase IIwe will also develop and implement the infrastructure to perform personalized treatment planningThis treatment planning will be based on conventional image transformationsconventional EM solvingand AI learning of thermal sink and tissue properties Numerous clinical trials have shown that mild hyperthermia in conjunction with chemotherapy or radiation therapy is a promising strategy to treat cancerHoweveradoption in the clinic will require the ability to measure temperature in the heated regions both for safety and to verify tumor heatingNeoTherma OncologyNTOhas developed a device that can heat tumors non invasively within a Magnetic Resonance scannerMRwhich will allow the MR to be used to map temperatures inside the bodyIn this proposalNTO and the University of Utah will develop MR methods that will provide accurate and precise measurement of temperature in near real timeallowing evaluation of this device for clinical use