Stereotaktische Laserbasierte interstitielle thermische Therapie (LITT) und präklinisches, Tumororganoid-basiertes Medikamentenscreening bei rezidivierenden hochgradigen Gliomen. Erste Erfahrungen aus der Hi-SMILE Studie.

Recurrent high-grade glioma require innovative locoregional and systemic treatment options. Laser Interstitital thermal therapy (LITT) is a stereotactic, minimally invasive surgical approach to target small and difficult to resect tumors under MR-thermometric guidance. Tumororganoids are representative tumor avatars that enable 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 in a registry. For LITT, tumor volume and ablation coverage andaccuracy of laser catheter placement are assessed. OR time, length of hospital stay and surgical complications are documented. Stereotactic frame-based biospsy and laser catheter placement are performed before laser ablation is carried out in an intraoperative MRI setting.Biopsy samples taken during LITT surgery are used for tumororganoid formation. After tumororganoid formation, ex-vivo high-throughput drug testing of up to 9 selected drugs is performed. Responses are classified as sensitive, intermediate or resistant.

So far, n=9 patients (4 females, 5 males; mean age 51.8 years) have been enrolled. Final histological diagnoses was glioblastoma (n=6), astrocytoma WHO 4° (n=2) and radiation necrosis (n=1). N=4 patients required 2 laser catheters to cover the desired mean tumor volume of 4.2 (+/- 3.2) ml. Mean operative time was 194min (+/- 38) of which a mean 103min (+/- 24) were spent in the intraoperative MRI scanner. Ablation coverage was on average 138% and took on avergae 14min 30s per catheter. Laser catheters could be placed with a Euclidian distance of 1.1 mm (+/- 0.85) and a mean radial error of 0.8 mm (+/- 0.7). Mean postoperative hospital stay was 2.1 days. One epileptic seizure occurred after surgery. It was always possible to test at leat 5 drugs. Most tumors revealed a high level of driug resistance with only 1 case revealing drug sensivitivy more than 1 drug.

In the first patients surgical accuracy an ablation coverage was high. 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.