@article{fffb36d7dfa0474b81ec3bfc921ad473,
title = "High-precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION trial)",
abstract = "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.",
keywords = "Cognition, Epilepsy, MRI, Radiosurgery, Stereotactic radiation therapy (SRT)",
author = "Zegers, {C. M.L.} and A. Swinnen and C. Roumen and Hoffmann, {A. L.} and Troost, {E. G.C.} and {van Asch}, {C. J.J.} and L. Brandts and I. Compter and Dieleman, {E. M.T.} and Dijkstra, {J. B.} and M. Granzier and M. Hendriks and P. Hofman and Houben, {R. M.A.} and B. Ramaekers and Ronner, {H. E.} and Rouhl, {R. P.W.} and {van der Salm}, S. and Santegoeds, {R. G.C.} and Verhoeff, {J. J.} and Wagner, {G. L.} and J. Zwemmer and Schijns, {O. E.M.G.} and Colon, {A. J.} and Eekers, {D. B.P.}",
note = "Funding Information: The authors acknowledge financial support from Zorginstituut Nederland and ZonMW and thank the epilepsy surgery workgroup (AWEC) Academic Centre of Epileptology Kempenhaeghe/MUMC+, Heeze/Maastricht and expertise center for epilepsy and sleep medicine (SEIN), UMC Utrecht SEIN Epilepsy Surgery Working Group (USWEC), and Epilepsy Surgery Working Group Amsterdam University Medical Center (AUMC) colleagues for their contribution for this trial, including Esther Decabooter, Claudia Offermann, Evelien van de Peet, and Marlies Granzier from the Maastro clinic. Many thanks to Jan Bostr\u00F6m from the University Hospital of Bonn, for sharing his knowledge and advice. Lastly, we acknowledge the patient representatives of the Dutch patients with Epilepsy, Casper Baas, and Laura M\u2019Rabet of EpilepsieNL for their constructive feedback. Funding Information: This study is funded by the ZorgInstituut Nederland and ZonMw (projectnumber: 2021038373). The funding body approved the study design but is not involved in the data collection, analysis, and writing the manuscript. Funding Information: The authors acknowledge financial support from Zorginstituut Nederland and ZonMW and thank the epilepsy surgery workgroup (AWEC) Academic Centre of Epileptology Kempenhaeghe/MUMC+, Heeze/Maastricht and expertise center for epilepsy and sleep medicine (SEIN), UMC Utrecht SEIN Epilepsy Surgery Working Group (USWEC), and Epilepsy Surgery Working Group Amsterdam University Medical Center (AUMC) colleagues for their contribution for this trial, including Esther Decabooter, Claudia Offermann, Evelien van de Peet, and Marlies Granzier from the Maastro clinic. Many thanks to Jan Bostr\u00F6m from the University Hospital of Bonn, for sharing his knowledge and advice. Lastly, we acknowledge the patient representatives of the Dutch patients with Epilepsy, Casper Baas, and Laura M\u2019Rabet of EpilepsieNL for their constructive feedback. This prospective clinical trial is registered in the ClinicalTrials.gov trial registry (NCT05182437). The public disclosure and publication policy is defined in the clinical trial agreement with the participating sites. The clinical trial agreement prevails. The results of this study will be disclosed unreservedly. All parties concerned will justify their actions in this regard. We aim to publish the results of this study in peer-reviewed (inter)national scientific journals. Also, negative results will be published. The principal investigator shall have the right to publish, present, or otherwise publicly disclose the results of and disseminate information of this study. Publication will be prepared in collaboration with the involved departments of the MUMC + and Kempenhaeghe. All results will also be presented to the colleagues of the three regional Dutch multidisciplinary epilepsy surgery conferences. Publisher Copyright: {\textcopyright} The Author(s) 2024.",
year = "2024",
month = dec,
day = "1",
doi = "10.1186/s13063-024-08168-9",
language = "English",
volume = "25",
journal = "Trials",
issn = "1745-6215",
publisher = "BioMed Central Ltd",
number = "1",
}