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.

Clinical implementation of standardized neurocognitive assessment before and after radiation to the brain.

Background: Radiotherapy induced impairment of cognitive function can lead to a reduced quality of life. The aim of this study was to describe the implementation and compliance of standardized neurocognitive assessment. In addition, the first results of cognitive changes for patients receiving a radiation dose to the brain are described. Materials and methods: Patients that received radiation dose to the brain (neuro, head and neck and prophylactic cranial irradiation between April-2019 and Dec-2021 were included. Three neuro cognitive tests were performed a verbal learning and memory test, the Hopkins Verbal Learning Test; a verbal fluency test, the Controlled Oral Word Association Test and a speed and cognitive flexibility test, the Trail Making Test A&B. Tests were performed before the start of radiation, 6 months (6 m) and 1 year (1y) after irradiation. The Reliable Change Index (RCI) between baseline and follow-up was calculated using reference data from literature. Results: 644 patients performed the neurocognitive tests at baseline, 346 at 6 months and 205 at 1y after RT, with compliance rates of 90.4%, 85.6%, and 75.3%, respectively. Reasons for non-compliance were: 1. Patient did not attend appointment (49%), 2. Patient was unable to perform the test due to illness (12%), 3. Patient refused the test (8 %), 4. Various causes, (31%). A semi-automated analysis was developed to evaluate the test results. In total, 26% of patients showed a significant decline in at least one of variables at 1y and 11% on at least 2 variables at 1y. However, an increase in cognitive performance was observed in 49% (≥1 variable) and 22% (≥2 variables). Conclusion: Standardized neurocognitive testing within the radiotherapy clinic was successfully implemented, with a high patient compliance. A semi-automatic method to evaluate cognitive changes after treatment was defined. Data collection is ongoing, long term follow-up (up to 5 years after treatment) and dose-effect analysis will be performed.

Incidence of clinically relevant psychiatric symptoms during glioblastoma treatment: an exploratory study.

PURPOSE: In addition to neurological symptoms glioblastoma (GBM) patients can experience psychiatric complaints, which are often hard to recognize and difficult to treat. Research on psychiatric symptoms during glioblastoma treatment is limited, but can have significant impact on quality of life, treatment processes and even survival. The aim of this study is to explore the incidence of clinically relevant psychiatric symptoms, during glioblastoma treatment and active surveillance. METHODS: Medical records of 302 GBM patients were reviewed from diagnostic surgery until discontinuation of treatment or active surveillance. Clinical relevance was defined as psychiatric symptoms that interfered with the oncological treatment and required referral to a psychiatrist. "Referred" versus "non-referred" GBM patients were compared using the Pearson Chi-Square test, Fisher's Exact Test or Mann Whitney-U test. RESULTS: Psychiatric symptoms occurred in 11.5% of patients during glioblastoma treatment or active surveillance, most often mood or behavioral symptoms, followed by psychotic symptoms. Referral occurred mainly during concomitant chemoradiation or adjuvant chemotherapy (64.3%). In 28.6% of patients psychiatric symptoms were thought to be attributive to medication. Treatment was discontinued in 17.9% of patients and temporarily interrupted in 3.6%. Possible risk factors included male gender, history of psychiatric disorder, postoperative delirium, non-frontal tumor location, anti-epileptic drug use at baseline and corticosteroid initiation during treatment. CONCLUSION: The found incidence of 11.5% and the high number of patients discontinuing treatment due to psychiatric symptoms justify more research in this, to date, understudied topic in scientific literature. Further prospective studies are needed to identify risk factors and unravel possible effects on survival.

A comparison study between single- and dual-energy CT density extraction methods for neurological proton monte carlo treatment planning.

Monte Carlo proton dose calculations requires mass densities calculated from the patient CT image. This work investigates the impact of different single-energy CT (SECT) and dual-energy CT (DECT) to density conversion methods in proton dose distributions for brain tumours.Material and methods: Head CT scans for four patients were acquired in SECT and DECT acquisition modes. Commercial software was used to reconstruct DirectDensity™ images in Relative Electron Densities (RED, [Formula: see text]) and to obtain DECT-based pseudo-monoenergetic images (PMI). PMI and SECT images were converted to RED using piecewise linear interpolations calibrated on a head-sized phantom, these fits were referred to as "PMI2RED" and "CT2RED". Two DECT-based calibration methods ("Hünemohr-15it" and "Saito-15it") were also investigated. [Formula: see text] images were converted to mass-densities ([Formula: see text]) to investigate [Formula: see text]differences and one representative patient case was used to make a proton treatment plan. Using CT2RED as reference method, dose distribution differences in the target and in five organs-at-risk (OARs) were quantified.Results: In the phantom study, Saito-15it and Hünemohr-15it produced the lowest [Formula: see text]root-mean-square error (0.7%) and DirectDensity™ the highest error (2.7%). The proton plan evaluated in the Saito-15it and Hünemohr-15it datasets showed the largest relative differences compared to initial CT2RED plan down to -6% of the prescribed dose. Compared to CT2RED, average range differences were calculated: -0.1 ± 0.3 mm for PMI2RED; -0.8 ± 0.4 mm for Hünemohr-15it, and -1.2 ± 0.4 mm for Saito-15it.Conclusion: Given the wide choice of available conversion methods, studies investigating the density accuracy for proton dose calculations are necessary. However, there is still a gap between performing accuracy studies in reference [Formula: see text]phantoms and applying these methods in human CT images. For this treatment case, the PMI2RED method was equivalent to the conventional CT2RED method in terms of dose distribution, CTV coverage and OAR sparing, whereas Hünemohr-15it and Saito-15it presented the largest differences.