About 1,658,370 new cancer cases are expected to be diagnosed in 2015 and 589,430 Americans are expected to die of cancer, correlating to about 1,600 deaths per day in the US. Sarcomas of the retroperitoneal space and extremities are most often difficult to treat and often recur and metastasize despite patients' undergoing extensive and radical surgery and radiation therapy, with poor outcomes. Particularly, retroperitoneal sarcomas are often detected quite late as they grow to a large size before they become symptomatic. Although not as common as breast or prostate cancer, sarcoma, by virtue of typically affecting younger patients, has a disproportionately large negative impact on society. Because sarcomas are often aggressive and nonresponsive to common therapies, there remains a critical unmet need for effective therapeutic options. Hyperthermia as an adjunct to radiation has shown improved sarcoma response. Minimally invasive procedures are often suggested due to patient characteristics and tumor location. Minimally invasive procedures result in less morbidity, shorter recovery time, less wound infection rates and decreased post-operative pain compared to open/invasive surgery. Initial success of any minimally invasive procedure depends on demonstration of safety and treatment outcome in animal models of cancer that are of comparable size to human patients. Such successes in large animal study lead to safer human trials. Primary objective of this proposed research is to assess the treatment efficacy of a 3D spatially-registered real-time image-guided needle/catheter based ultrasound (CBUS) therapy in an induced tumor grown in a genetically engineered oncogenic pig, specifically soft tissue sarcomas of the extremity and retroperitoneum, two clinically relevan sites mimicking human disease. Free-hand ultrasound (US) imaging spatially-registered with electromagnetic tracking system will be used to generate a 3D registered volume to assist accurate therapy device placement. Our proposed CBUS therapeutic technology can provide a minimally-invasive technique for volumetric ablation treatment of tumors with accurate directional targeting and potential for more thorough treatment, protection of critical non-targeted tissue, accessibility to a larger number of anatomical sites, and faster procedure times. Presently no large animal model of cancer is available to conduct these efficacy studies specifically for minimally invasive procedures. Currently, all the minimal invasive devices in the clinic or currently under investigation have never been tested in human scale large animal tumor models. We propose to induce tumor growth in genetically engineered oncogenic pigs and assess the treatment efficacy of 3D spatially-registered image-guided CBUS thermal therapy. Success of the proposed work will be beneficial for validation testing of other energy based modalities including high-intensity focused US, cryo-ablation and microwave thermal therapy. The validation test results from a large animal tumor model will ensure greater safety and permit treatment response evaluation prior to first-in-human clinical studies.
About 1,658,370 new cancer cases are expected to be diagnosed in 2015 and about 589,430 Americans are expected to die of cancer. Often the majority of these cancer patients are not suitable for conventional surgical procedures and hence a minimally invasive procedure is recommended or essential. The treatment efficacy of any minimally invasive procedure should be validated in an animal model of cancer so that safe clinical trials can be conducted. Unfortunately, at present there is no human-scale animal model available to conduct these safety and efficacy studies specifically for minimally invasive procedures. The primary objective of our proposed research is to assess the treatment efficacy of 3D spatially-registered real-time image-guided needle/catheter based ultrasound (CBUS) thermal therapy in an induced tumor grown in genetically engineered oncogenic pigs, specifically soft tissue sarcomas of the extremity and retroperitoneum, two clinically relevant sites mimicking human disease.. The development of the tumor model in a large animal that is comparable in both scale and physiology to human patients is beneficial to validate many minimally invasive modalities in addition to CBUS, such as high-intensity focused ultrasound, cryo-ablation and microwave thermal therapy. The validation test results from a large animal tumor model will ensure greater safety and permit treatment response evaluation before launching a first-in-human clinical study.
| Overgaard, Nana H; Principe, Daniel R; Schachtschneider, Kyle M et al. (2018) Genetically Induced Tumors in the Oncopig Model Invoke an Antitumor Immune Response Dominated by Cytotoxic CD8?+ T Cells and Differentiated ?? T Cells Alongside a Regulatory Response Mediated by FOXP3+ T Cells and Immunoregulatory Molecules. Front Immunol 9:1301 |
| Misra, Santosh K; Ghoshal, Goutam; Gartia, Manas R et al. (2015) Trimodal Therapy: Combining Hyperthermia with Repurposed Bexarotene and Ultrasound for Treating Liver Cancer. ACS Nano 9:10695-10718 |
