Focused Ultrasound Surgery (FUS) has potential to become a best-in-class non-invasive treatment strategy for a multitude of intracranial indications, including solid tumors. Current therapeutic options for intracranial tumors often center on surgery or stereotactic radiosurgery (SRS), with the latter in particular demonstrating good control rates with low treatment toxicitiy. However some clinical situations are less amenable to a favourable SRS response, including diffuse tumors such as glioblastoma multiforme (GBM)1, and tumors with areas of central necrosis and hypoxia2. These situations present an opportunity for FUS to be applied as an adjuvant treatment to augment the primary SRS response through radiosensitization of the target.
We hypothesize that a progressive approach, where we would first demonstrate the benefits of FUS to enhance existing treatment modalities, would be beneficial to foster acceptance and awareness of this novel disruptive technology by the neurosurgical community, for indications with long established clinical practices, such as brain tumours with surgery and radiotherapy.
We propose to demonstrate the effectiveness of FUS to improve SRS outcomes in the treatment of GBM by creating FUS-mediated combined therapies that have shown documented improvements in more traditional radiation therapy settings: hyperthermia 3 and microbubble-radiosensitization4, but have faced resistance to clinical acceptance due to past practical and technical limitations.. We believe SRS+FUS-induced hyperthermia (FUS-HT), and SRS+FUS-mediated microbubble vascular disruption (FUS-MB) will permit localized radiosensitization of the radiosurgical target. Moreover, we intend to capitalize on recent discoveries about the impact of FUS on the anti-cancer immune response5, to also investigate whether these combined treatments will positively affect intra-tumor immune cell representation.
The primary objective of the proposed research program is to determine whether a combined FUS+stereotactic radiosurgery (SRS) treatment can improve tumor growth control and animal survival in rat glioblastoma (GBM) model.
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