Preclinical cerebral cryoablation in non-tumor bearing pigs

Irena Jankovic,Christian Bonde Pedersen,Poul Flemming Høilund-Carlsen,Ole Graumann,Louise Langhorn,Tine Schytte,Bo Halle,Willy Krone,Thomas Lund Andersen,Frantz Rom Poulsen,Bjarne Winther Kristensen

doi:10.1038/s41598-022-05889-2

Irena Jankovic, Christian Bonde Pedersen + Show 9 more

Open Access

https://doi.org/10.1038/s41598-022-05889-2

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Abstract

Patients with brain metastases, the most common intracranial tumor, have an average survival ranging from a few months to 40 months, and new treatment initiatives are needed. Cryoablation is a minimally invasive, well-tolerated, and effective procedure commonly applied for treatment of renal tumors and certain other malignancies. We aimed to examine the clinical usefulness of this procedure in a step-by-step program starting with cerebral cryoablation in healthy pigs. In four terminal and four non-terminal non-tumor bearing pigs, we studied immediate and delayed effects of cerebral cryoablation. Safety was assessed by computed tomography (CT), and clinical observation of behavior, neurological deficits, and wellbeing. Effects were assessed by histological and immuno-histochemical analyses addressing structural and metabolic changes supported by additional magnetic resonance imaging (MRI) and positron emission tomography (PET) in the non-terminal animals. Using CT-guidance, cryoablation probes were successfully inserted without complications, and ice formation could be monitored real-time with CT. No animal developed neurological deficits or signs of discomfort. Histological and immunohistochemical analyses, MRI, and PET revealed profound structural and biological damage within the lesion. MRI and PET revealed no long-term damage to healthy tissue outside the cryoablation zone. Cerebral cryoablation appears to be a feasible, safe, and controllable procedure that can be monitored successfully with CT. The net effect is a dead brain lesion without damage of either nearby or remote healthy structures. Immediate changes are local hemorrhage and edema; delayed effects are perfusion defects, immune system activation, and astrogliosis.

Highlights

IntroductionThe most common intracranial tumor, have an average survival ranging from a few months to 40 months, and new treatment initiatives are needed
Patients with brain metastases, the most common intracranial tumor, have an average survival ranging from a few months to 40 months, and new treatment initiatives are needed
In a step-by-step program, we aim to examine the applicability of cryoablation in brain metastasis

Summary

Introduction

The most common intracranial tumor, have an average survival ranging from a few months to 40 months, and new treatment initiatives are needed. Cryoablation is a minimally invasive, well-tolerated, and effective procedure commonly applied for treatment of renal tumors and certain other malignancies. We aimed to examine the clinical usefulness of this procedure in a step-by-step program starting with cerebral cryoablation in healthy pigs. Effects were assessed by histological and immunohistochemical analyses addressing structural and metabolic changes supported by additional magnetic resonance imaging (MRI) and positron emission tomography (PET) in the non-terminal animals. Brain metastases are the most common form of cerebral malignancy and can arise from a wide variety of primary tumors. Cryoablation is a procedure in which a cryoprobe is used to freeze and destroy abnormal tissue; this approach has been successfully applied in a variety of malignancies including renal cancer and primary and secondary hepatic cancers[2,3], but not yet for the treatment of secondary cerebral malignancies. We investigated the method’s feasibility, safety, and efficacy in healthy pigs, which is what we report in the present article

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