WP8 – Magnetic Resonance guided Laser Interstitial Thermal Therapy (MRgLITT) as supplementary treatment for Brain Cancer
Relevance
Magnetic Resonance guided Laser Interstitial Thermal Therapy (MRgLITT) is an emerging minimally invasive technique that provides a treatment option to patients with recurrent glioblastomas who are not candidates for traditional open surgery. So far, only a few patients have been treated in Denmark using this technique and it is therefore of particular importance to run this treatment in protocol to evaluate the benefits in respect to survival, local control and quality of life. The current literature establishes the safety and effectiveness of laser therapy of recurrent glioblastomas, but often tumor histology and genomic information for the treatment effect has not yet been explored. In this project we will investigate the feasibility of a stereotactic biopsy before LITT to explore the treatment effect in respect to the current tumor histology. An interesting possible effect of LITT is the breakdown of the blood brain barrier (BBB) and thus the likely enhanced delivery of adjuvant chemotherapy. The treatment is currently only available at Rigshospitalet and will as a part of this project be made available to all citizens in Denmark.
Background
MRgLITT is a minimally invasive neurosurgical procedure that has gained significant momentum in the last decade in the treatment of intracranial tumors and epileptic foci. In brief, LITT utilizes the heat from a stereotactically placed laser catheter to selectively ablate a lesion or a structure under real time MRI guidance. The first LITT system, Visualase Thermal Therapy System by Medtronic gained FDA approval in 2007 and was CE marked in 2018. In December 2020, the first patient with recurrent glioblastoma (GBM) was successfully treated at the Department of Neurosurgery in Copenhagen, Rigshospitalet. So far we have treated in total 11 patients although not all GBM. LITT is due to its minimally invasiveness particularly well suited for treatment of difficult to access lesions, lesions adjacent to eloquent cortex and/or cases in which standard therapies are not feasible or have failed. In neurooncology, both prospective and retrospective studies have described its use in the treatment of recurrent brain metastases, radiation necrosis, low- and high-grade gliomas, meningeomas and other tumours in children and adults. The current literature establishes the feasibility and safety of the treatment, but well-designed clinical trials are needed to fully clarify its role in neurooncology and lift this treatment to a higher standard.
Aim
In this study we will investigate 1) tumor histology in gliomas and its response to laser treatment by a pre-LITT biopsy and whole-genome sequencing, 2) the pre-LITT biopsy effect on the thermal distribution and 3) the post-LITT effect on peritumoral BBB permeability and thus the possibly enhanced delivery of therapeutic agents.
Methods
Approximately 15 brain tumour patients will be treated with MRgLITT per year. In total 40 patients in 2,5 year. A MR FET-PET brain scan and a stereotactic biopsy will be obtained prior to treatment. The biopsy will be examined using histopathologic analysis and whole-genome sequencing. After treatment patients will be systematically MRI scanned using contrast enhanced sequences to evaluate the disruption of the peritumoral blood brain barrier. The blood brain barrier permeability will be further evaluated with the biochemical markers glial-specific protein S100b and brain specific Enolase. The primary end point is local control. Secondary points are progression free survival (PFS), overall survival (OS), Karnofsky performance score (KPS). Patients will be followed with respect to complications, side effects and neurological deficits.
Expected outcome
The results of the current project are anticipated to achieve a better understanding of the effect of laser therapy on recurrent glioblastomas in respect to the current tumor histology and its effects on BBB disruption to obtain an individualized treatment for patients with brain cancer.
Silas Nielsen is a PhD student currently working for WP 8. In his PhD project, he is seeking to map the peritumoral Blood-Brain Barrier disruption after LITT with systematic Dynamic Contrast-Enhanced MRI scans and biochemical markers. The project will shed light on the physiological effects of Laser Therapy and provide a solid basis for future clinical trials that investigates the potential beneficial synergistic effects of LITT in combination with chemotherapy, immunotherapy or radiation therapy.
Silas Nielsen was portraited in April 2022 as BTC’s Monthly portrait of a young researcher.