Sektionstage Frühjahr 2025 der Deutschen Gesellschaft für Neurochirurgie

Prof. Dr. med.

Prof. Dr.

Prof. Dr. rer. nat.

Hi-SMILE: Stereotactic Laser Interstitial Thermal Therapy (LITT) and preclinicaltumororganoid-based drugscreening in recurrent high-grade glioma – Updated study dataLaserinduzierte interstitielle Thermaltherapie (LITT) und präklinisches Medikamentenscreening bei high-grade Gliom-Rezidiven

Innovationen

SFN02

Laser interstitial thermal therapy (LITT) is a stereotactic approach to target small, difficult to resect tumors under MR-thermometric guidance. Tumororganoids (TOs) are representative tumor avatars enabling ex-vivo drug-testing even from small tissue samples provided by stereotactic biopsies. The Hi-SMILE study is an ongoing trial to evaluate safety and efficacy of LITT and feasibility of preclinical tumororganoid-based drug screening in n=30 patients with recurrent high-grade glioma.Patients are prospectively enrolled. Tumor volume, ablation coverage and accuracy of laser catheter placement are assessed. OR time, length of hospital-stay and complications are documented. Biopsy samples are used for TO formation. Ex-vivo drug-testing of up to 9 selected drugs is performed. Responses are classified as sensitive, intermediate or resistant.So far, n=18patients (mean age 59.2 years) have been enrolled. Final histological diagnoses were glioblastoma (n=13), astrocytoma WHO 4° (n=3) and radiation necrosis (n=2). N=8 patients (44%) required 2 catheters to cover the desired mean tumor volume of 4.4 ml. Mean surgical time was 170 minutes, with 91 minutes spent in the intraoperative MRI scanner. Laserablation was active for a mean 19:59 minutes per patient. Postoperative hospital stay was 3.1 days. Two epileptic seizure occurred after surgery. A median of n=9 biopsy samples ere available to perform TO formation. It was not possible to form TOs in cases of histologically proven radiation necrosis. It was always possible to test at least 4 drugs. Chemosensitivity was diverse between tumor entities and between cases of the same entity. Most tumors revealed a high level of drug resistance with only 2 cases revealing drug sensitivity more than 1 drug. Impact on Quality of Life, neurological status, progression free and over survival are still being investigated.Surgical accuracy was high and ablation coverage supramarginal. LITT seems to be a safe and well-tolerated procedure. Progression free and overall survival need to be evaluated at the end of the trial. Tumororganoid-based drug-screening is feasible with tissue from stereotactic biopsies, however its impact on clinical decision-making is yet unclear.

Laserinduzierte interstitielle Thermaltherapie (LITT) und präklinisches Medikamentenscreening bei high-grade Gliom-Rezidiven

Sektion Funktionelle Neurochirurgie:

Abstractvortrag

Met-SMILE: Stereotactic minimally invasive laser interstitial thermal therapy and integrative molecular and fuctional diagnostics in cerebral breast cancer metastases – Study protocol

Freie Themen

SFN04

Prolonged overall survival in breast cancer patients has led to a steady increase in the total incidence of cerebral metastases of more than 30% depending on the molecular subtype. Surgical resection is warranted in superficial and safe to access symptomatic and/or space occupying lesions. Moreover, radiation represents another loco-regional therapeutic pillar in case of high number or difficult to access lesions. Despite these options, survival of breast cancer patients with brain metastases remains poor. In addition, the biology between extra- and intracranial disease can display a high discordance underlining the unmet clinical need to retrieve relevant diagnostic information from brain metastasis.Within the proposed theranostic concept, 30 patients will be prospectively identified, treated, followed and assessed for functional status, quality of life, burden of therapy as well as surgical aspects and complications. Tissue samples taken during the stereotactic biopsy will undergo histopathological analysis as well as further comprehensive molecular characterization and preclinical tumor-organoid-based drug screening for up to 10 selected targeted medications. Molecular characterization of the cerebral metastasis will be performed from tissue samples in an established genomic diagnostic platform by whole-genome and transcriptome sequencing and will be complemented by longitudinal liquid biopsies to identify and prioritize actionable alterations and biomarkers.Surgical treatment data, complications, impact on functional status, quality of life as well as therapeutic burden will be document from baseline to 3 months post surgery. Progression-free and overall survival will be followed for up to 36 months. In case molecular characterization in conjunction with preclinical drug screening suggest an effective treatment option, patients will be offered – whenever attainable - treatment within independent clinical trials, as optimized sequence within the indication (on label) or outside the indication (off-label).This innovative combination will enable a unique opportunity of a safe localized treatment of cerebral metastases and offer the option to retrieve relevant diagnostic and functional information for personalized systemic treatments for remaining tumor cells.In case this concept is deemed successful it harbors the prospect to serve as a pioneer for other tumor entities as well.

The LITTability Study - Evaluation of the Applicability of LITT in a Real-World Cohort of Glioma PatientsDie LITTability Studie - Analyse der Anwendbarkeit von LITT in einer Kohorte von echten GliompatientInnen

Laser-interstitial thermal therapy (LITT) is a minimally invasive technique used in neurosurgery for ablation of epileptic foci and malignant lesions, especially for glioma located in regions that pose high surgical risk. Current research mainly focuses on maximizing the safety on the procedure and proofing the non-inferiority compared to open resection of glioma. However, data regarding the current applicability in real-time cohorts are lacking. The goal of this study is to evaluate the real-world applicability of LITT in glioma patients, specifically focusing on those who had undergone stereotactic biopsy, and to define limiting factors.For this retrospective study, we analyzed n=207 glioma patients from a monocentric stereotactic surgery database over a 5-year period (2018 – 2022). Clinical, histopathological and radiological data was assessed. To define a lesion suitable for LITT a two-step approach was used. In a first step, predefined selection criteria were applied consisting of a Karnofsky Performance Score of 70 or higher, an ASA Score of 3 or less, MRI compatibility, and glioma presenting as a single or bifocal lesion. In a second step, the LITT simulation was performed with additional criteria consisting of at least 90% possible ablation volume, a safe trajectory with avoidance of vessels, and optimal lesion accessibility without brainstem involvement.Out of 207 patients, 137 cases met initial preselection criteria, while 36 cases (17.4%) were ultimately deemed suitable for LITT post-simulation. Common exclusion factors included multifocal lesions, irregular lesion shape, and size constraints. Among suitable cases, 94.4% had unifocal lesions, and ablation through the preexisting stereotactic burr hole was feasible in 66.7% of cases. For 44.4% of cases, only a single catheter was needed, with the number of ablation points varying from one to twelve per trajectory. The average lesion diameter for LITT-suitable cases was 26.4 mm.Even though LITT offers a promising alternative for glioma not suitable for open resection, the current application is limited. Main reasons were due to lesion morphology and size. Enhancing LITT applicability could involve addressing constraints posed by lesion geometry and volume. Prospective studies comparing LITT with conventional resection could better define the subset of glioma patients who may benefit most, advancing the potential for LITT in clinical neurosurgical practice.

Die LITTability Studie - Analyse der Anwendbarkeit von LITT in einer Kohorte von echten GliompatientInnen

Hörsaal West

FNCH 3

LITT

Sektion Funktionelle Neurochirurgie

FNCH 3
LITT

Appointment

Chairs

Programme

FNCH 3LITT

Appointment

Chairs

Programme

FNCH 3
LITT