Hi-SMILE: Prospektive Studie zur stereotaktischen Laser Interstitial Thermal Therapy (LITT) und präklinischem Tumororganoid-basiertem Medikamentenscreening bei rezidivierenden high-grade Gliomen. Ergebnisse nach 20 Patient:innen

Recurrent high-grade glioma (glioblastoma & astrocytoma WHO 4°) 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. Fot LITT tumor volume and ablation coverage, as well as accuracy 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=20 patients (12 females, 8 males; mean age 58.3 years (+/- 11.1 years) have been enrolled. Final histological diagnoses was glioblastoma (n=14), astrocytoma WHO 4° (n=4) and radiation necrosis (n=2). N=9 patients required 2 laser catheters to cover the desired mean tumor volume of 4.0 (+/- 3.5) ml. Mean operative time was 166 minutes (+/- 45) of which a mean 90 minutes (+/- 25) were spent in the intraoperative MRI scanner. Ablation coverage was on average 228% and took on avergae 12min 55s per catheter. Laser catheters could be placed with a Euclidian distance of 1.1 mm (+/- 1.2) and a mean radial error of 0.7 mm (+/- 0.6). Treatment-related complications were two epileptic seizures and one deterioration of a preexisting neurological deficit. It was always possible to test at least 4 drugs. Most tumors revealed a high level of drug resistance with only 2 cases revealing drug sensivitivy more than 1 drug.

Surgical accuracy and ablation coverage are high in LITT for recurrent glioma. The procedure is safe and well tolerated by patients. Progression-free and overall survial will be evaluated at the end of the trial.