High-precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION trial).

INTRODUCTION: The standard treatment for patients with focal drug-resistant epilepsy (DRE) who are not eligible for open brain surgery is the continuation of anti-seizure medication (ASM) and neuromodulation. This treatment does not cure epilepsy but only decreases severity. The PRECISION trial offers a non-invasive, possibly curative intervention for these patients, which consist of a single stereotactic radiotherapy (SRT) treatment. Previous studies have shown promising results of SRT in this patient population. Nevertheless, this intervention is not yet available and reimbursed in the Netherlands. We hypothesize that: SRT is a superior treatment option compared to palliative standard of care, for patients with focal DRE, not eligible for open surgery, resulting in a higher reduction of seizure frequency (with 50% of the patients reaching a 75% seizure frequency reduction at 2 years follow-up). METHODS: In this waitlist-controlled phase 3 clinical trial, participants are randomly assigned in a 1:1 ratio to either receive SRT as the intervention, while the standard treatments consist of ASM continuation and neuromodulation. After 2-year follow-up, patients randomized for the standard treatment (waitlist-control group) are offered SRT. Patients aged ≥ 18 years with focal DRE and a pretreatment defined epileptogenic zone (EZ) not eligible for open surgery will be included. The intervention is a LINAC-based single fraction (24 Gy) SRT treatment. The target volume is defined as the epileptogenic zone (EZ) on all (non) invasive examinations. The seizure frequency will be monitored on a daily basis using an electronic diary and an automatic seizure detection system during the night. Potential side effects are evaluated using advanced MRI, cognitive evaluation, Common Toxicity Criteria, and patient-reported outcome questionnaires. In addition, the cost-effectiveness of the SRT treatment will be evaluated. DISCUSSION: This is the first randomized trial comparing SRT with standard of care in patients with DRE, non-eligible for open surgery. The primary objective is to determine whether SRT significantly reduces the seizure frequency 2 years after treatment. The results of this trial can influence the current clinical practice and medical cost reimbursement in the Netherlands for patients with focal DRE who are not eligible for open surgery, providing a non-invasive curative treatment option. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05182437. Registered on September 27, 2021.

Inter-observer variation of hippocampus delineation in hippocampal avoidance prophylactic cranial irradiation.

BACKGROUND: Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) techniques have been developed to reduce radiation damage to the hippocampus. An inter-observer hippocampus delineation analysis was performed and the influence of the delineation variability on dose to the hippocampus was studied. MATERIALS AND METHODS: For five patients, seven observers delineated both hippocampi on brain MRI. The intra-class correlation (ICC) with absolute agreement and the generalized conformity index (CIgen) were computed. Median surfaces over all observers' delineations were created for each patient and regional outlining differences were analysed. HA-PCI dose plans were made from the median surfaces and we investigated whether dose constraints in the hippocampus could be met for all delineations. RESULTS: The ICC for the left and right hippocampus was 0.56 and 0.69, respectively, while the CIgen ranged from 0.55 to 0.70. The posterior and anterior-medial hippocampal regions had most variation with SDs ranging from approximately 1 to 2.5 mm. The mean dose (Dmean) constraint was met for all delineations, but for the dose received by 1% of the hippocampal volume (D1%) violations were observed. CONCLUSION: The relatively low ICC and CIgen indicate that delineation variability among observers for both left and right hippocampus was large. The posterior and anterior-medial border have the largest delineation inaccuracy. The hippocampus Dmean constraint was not violated.

[Diagnosis and treatment of brain tumours]. / Diagnose en behandeling van hersentumoren.

Primary brain tumours are relatively rare, but brain metastases are a frequent complication of the most common cancers elsewhere in the body (breast, lung, melanoma). Loss of function and excitation of brain nerves i.e. sensory loss, paralysis and pain in the head-and-neck region are specific features in base of skull tumours: meningioma, glomus tumours, vestibular Schwannoma, meningeal metastases by breast cancer, melanoma, and leukaemia, melanoma. In the diagnosis and treatment of brain tumours, special attention is required for rare complications in the head and neck region.