Abstract

Abstract Malignant gliomas are devastating intracranial tumors with dismal prognoses that impose unique therapeutic challenges. Treatment options include surgical resection, radiation, and chemotherapy, but efficacy is limited and carries associated morbidity. Promise persists for newer modalities, such as immune-based platforms, but obstacles include limited therapeutic access due to the blood-brain barrier (BBB) and the highly immunosuppressive tumor microenvironment. Laser interstitial thermal therapy (LITT) is a minimally invasive surgical intervention permitting thermal ablation of intracranial tumors. During LITT, a laser probe is stereotactically placed in the lesion through a skull burr hole. Real-time MRI is used to calculate thermal dosage zones to monitor ablation progress. LITT is not only cytoreductive but also opens the BBB and induces a powerful hyperthermia-driven anti-tumor immune response; it thus may synergize with other emerging therapies. Spontaneous canine glioma offers a matchless, optimally recapitulative appropriately sized tumor model, providing a unique opportunity to investigate and optimize the LITT platform. We adapted a commercially available LITT system (Monteris Medical) for application in canines with intracranial lesions. Initially, canine cadavers were used to optimize LITT procedures; we then performed LITT in live dogs. Our approach consists of 1. obtaining volumetric MRI studies for trajectory planning, 2. fixing canine patients to the surgical bed, 3. registering anatomic landmarks (Brainlab) to a volume rendered image, 4. using an integrated instrument holder (Varioguide, Brainlab) to guide drilling of 4.5 mm skull burr holes for placement of self-tapping titanium “mini-bolts” (Monteris Medical), and 5. introducing the laser through the mini-bolts for ablation in the MRI suite. This method allows for rigid stereotaxy, successful neuronavigation, and a minimally invasive approach. We have successfully performed LITT on four canine patients with intracranial gliomas. Future studies will explore immunologic mechanisms underlying the post-LITT anti-tumor response as well as combination therapeutic platforms, including nanoparticles and stereotactic radiotherapy.

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