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.

Current applications of deep-learning in neuro-oncological MRI.

PURPOSE: Magnetic Resonance Imaging (MRI) provides an essential contribution in the screening, detection, diagnosis, staging, treatment and follow-up in patients with a neurological neoplasm. Deep learning (DL), a subdomain of artificial intelligence has the potential to enhance the characterization, processing and interpretation of MRI images. The aim of this review paper is to give an overview of the current state-of-art usage of DL in MRI for neuro-oncology. METHODS: We reviewed the Pubmed database by applying a specific search strategy including the combination of MRI, DL, neuro-oncology and its corresponding search terminologies, by focussing on Medical Subject Headings (Mesh) or title/abstract appearance. The original research papers were classified based on its application, into three categories: technological innovation, diagnosis and follow-up. RESULTS: Forty-one publications were eligible for review, all were published after the year 2016. The majority (N = 22) was assigned to technological innovation, twelve had a focus on diagnosis and seven were related to patient follow-up. Applications ranged from improving the acquisition, synthetic CT generation, auto-segmentation, tumor classification, outcome prediction and response assessment. The majority of publications made use of standard (T1w, cT1w, T2w and FLAIR imaging), with only a few exceptions using more advanced MRI technologies. The majority of studies used a variation on convolution neural network (CNN) architectures. CONCLUSION: Deep learning in MRI for neuro-oncology is a novel field of research; it has potential in a broad range of applications. Remaining challenges include the accessibility of large imaging datasets, the applicability across institutes/vendors and the validation and implementation of these technologies in clinical practise.

Pharmacokinetic modeling of a novel hypoxia PET tracer [18F]HX4 in patients with non-small cell lung cancer.

BACKGROUND: [18F]HX4 is a promising new PET tracer developed to identify hypoxic areas in tumor tissue. This study analyzes [18F]HX4 kinetics and assesses the performance of simplified methods for quantification of [18F]HX4 uptake. To this end, eight patients with non-small cell lung cancer received dynamic PET scans at three different time points (0, 120, and 240 min) after injection of 426 ± 72 MBq [18F]HX4, each lasting 30 min. Several compartment models were fitted to time activity curves (TAC) derived from various areas within tumor tissue using image-derived input functions. RESULTS: Best fits were obtained using the reversible two-tissue compartment model with blood volume parameter (2T4k+VB). Simplified measures correlated well with VT estimates (tumor-to-blood ratio (TBr) R 2 = 0.96, tumor-to-muscle ratio R 2 = 0.94, standardized uptake value R 2 = 0.89). CONCLUSIONS: [18F]HX4 shows reversible kinetics in tumor tissue: 2T4k+VB. TBr based on static imaging at 2 or 4 h can be used for quantification of [18F]HX4 uptake.

Stereotactic ablative body radiotherapy combined with immunotherapy: present status and future perspectives.

Radiotherapy is along with surgery and chemotherapy one of the prime treatment modalities in cancer. It is applied in the primary, neoadjuvant as well as the adjuvant setting. Radiation techniques have rapidly evolved during the past decade enabling the delivery of high radiation doses, reducing side-effects in tumour-adjacent normal tissues. While increasing local tumour control, current and future efforts ought to deal with microscopic disease at a distance of the primary tumour, ultimately responsible for disease-progression. This review explores the possibility of bimodal treatment combining radiotherapy with immunotherapy.