Fractionated stereotactic radiotherapy in people with drug-resistant focal epilepsy: first-in-human experience with a healthy tissue-preserving dose-fractionation concept
ObjectiveStereotactic radiosurgery (SRS) emerges as a non-surgical treatment option for drug-resistant non-neoplastic focal epilepsy. Previous studies have reported that in about 20% of patients treated with radiotherapy, however, subsequent salvage surgery is required, among other because of sympto...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-06-01
|
| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2025.1600381/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850163867092516864 |
|---|---|
| author | Cas Stefaan Dejonckheere Attila Rácz Gustavo Renato Sarria Julian Philipp Layer Julian Philipp Layer Younèss Nour Lara Caglayan Molina Grimmer Victoria Volkenborn Fabian Kugel Thomas Müdder Tobias Baumgartner Valeri Borger Alexander Radbruch Hartmut Vatter Frank Anton Giordano Frank Anton Giordano Frank Anton Giordano Eleni Gkika Rainer Surges Davide Scafa |
| author_facet | Cas Stefaan Dejonckheere Attila Rácz Gustavo Renato Sarria Julian Philipp Layer Julian Philipp Layer Younèss Nour Lara Caglayan Molina Grimmer Victoria Volkenborn Fabian Kugel Thomas Müdder Tobias Baumgartner Valeri Borger Alexander Radbruch Hartmut Vatter Frank Anton Giordano Frank Anton Giordano Frank Anton Giordano Eleni Gkika Rainer Surges Davide Scafa |
| author_sort | Cas Stefaan Dejonckheere |
| collection | DOAJ |
| description | ObjectiveStereotactic radiosurgery (SRS) emerges as a non-surgical treatment option for drug-resistant non-neoplastic focal epilepsy. Previous studies have reported that in about 20% of patients treated with radiotherapy, however, subsequent salvage surgery is required, among other because of symptomatic radiation necrosis (RN). We propose a novel and radiobiologically substantiated dose-fractionation regimen which minimizes the RN risk while aiming to preserve efficacy and report our first-in-human experience.MethodsFrom February 2021 to April 2024, three patients (aged 42, 45, and 47 years) with different underlying etiologies were treated, including a post-hemorrhagic lesion, Rasmussen encephalitis, and focal cortical dysplasia. We applied linac-based frameless fractionated stereotactic radiotherapy (fSRT) to a total dose of 50 Gy in 10 fractions over 2 weeks. Each epileptogenic zone was defined by a multidisciplinary team, including a radiation oncologist, epileptologist, neurosurgeon, and neuroradiologist.ResultsThe irradiated volumes were 10.3, 11.3, and 16.5 cm3. After a follow-up of 12, 29, and 36 months, all three patients experienced an improvement in both seizure frequency and severity (two already during or shortly after fSRT). One patient achieved complete seizure freedom. All patients reported improvements in quality of life and regained independence or displayed functional recovery. Tolerability was excellent, with radiation-induced side effects being mild (grade 1 only) and transient. RN was not observed. One patient died 29 months after radiotherapy most likely from a ruptured aneurysm of a vertebral artery, unrelated to the treatment.SignificanceFrameless fSRT of 50 Gy in 10 fractions was feasible and might be safe and effective in selected patients with drug-resistant non-neoplastic focal epilepsy and large suspected epileptogenic zones. A prospective single-arm evaluation with structured long-term follow-up including assessment of patient-reported outcome measures is currently being conducted. |
| format | Article |
| id | doaj-art-d9dbb29dd0a14997a06deef5882b96a7 |
| institution | OA Journals |
| issn | 1664-2295 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj-art-d9dbb29dd0a14997a06deef5882b96a72025-08-20T02:22:06ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-06-011610.3389/fneur.2025.16003811600381Fractionated stereotactic radiotherapy in people with drug-resistant focal epilepsy: first-in-human experience with a healthy tissue-preserving dose-fractionation conceptCas Stefaan Dejonckheere0Attila Rácz1Gustavo Renato Sarria2Julian Philipp Layer3Julian Philipp Layer4Younèss Nour5Lara Caglayan6Molina Grimmer7Victoria Volkenborn8Fabian Kugel9Thomas Müdder10Tobias Baumgartner11Valeri Borger12Alexander Radbruch13Hartmut Vatter14Frank Anton Giordano15Frank Anton Giordano16Frank Anton Giordano17Eleni Gkika18Rainer Surges19Davide Scafa20Department of Radiation Oncology, University Hospital Bonn, Bonn, GermanyDepartment of Epileptology, University Hospital Bonn, Bonn, GermanyDepartment of Radiation Oncology, University Hospital Bonn, Bonn, GermanyDepartment of Radiation Oncology, University Hospital Bonn, Bonn, GermanyInstitute of Experimental Oncology, University Hospital Bonn, Bonn, GermanyDepartment of Radiation Oncology, University Hospital Bonn, Bonn, GermanyDepartment of Radiation Oncology, University Hospital Bonn, Bonn, GermanyDepartment of Radiation Oncology, University Hospital Bonn, Bonn, GermanyDepartment of Radiation Oncology, University Hospital Bonn, Bonn, GermanyDepartment of Radiation Oncology, University Hospital Bonn, Bonn, GermanyDepartment of Radiation Oncology, University Hospital Bonn, Bonn, GermanyDepartment of Epileptology, University Hospital Bonn, Bonn, GermanyDepartment of Neurosurgery, University Hospital Bonn, Bonn, GermanyDepartment of Neuroradiology, University Hospital Bonn, Bonn, GermanyDepartment of Neurosurgery, University Hospital Bonn, Bonn, GermanyDepartment of Radiation Oncology, University Medical Center Mannheim, Mannheim, GermanyDKFZ-Hector Cancer Institute, University Medical Center Mannheim, Mannheim, GermanyMedical Faculty Mannheim, Mannheim Institute of Intelligent Systems in Medicine (MIISM), Heidelberg University, Mannheim, GermanyDepartment of Radiation Oncology, University Hospital Bonn, Bonn, GermanyDepartment of Epileptology, University Hospital Bonn, Bonn, GermanyDepartment of Radiation Oncology, University Hospital Bonn, Bonn, GermanyObjectiveStereotactic radiosurgery (SRS) emerges as a non-surgical treatment option for drug-resistant non-neoplastic focal epilepsy. Previous studies have reported that in about 20% of patients treated with radiotherapy, however, subsequent salvage surgery is required, among other because of symptomatic radiation necrosis (RN). We propose a novel and radiobiologically substantiated dose-fractionation regimen which minimizes the RN risk while aiming to preserve efficacy and report our first-in-human experience.MethodsFrom February 2021 to April 2024, three patients (aged 42, 45, and 47 years) with different underlying etiologies were treated, including a post-hemorrhagic lesion, Rasmussen encephalitis, and focal cortical dysplasia. We applied linac-based frameless fractionated stereotactic radiotherapy (fSRT) to a total dose of 50 Gy in 10 fractions over 2 weeks. Each epileptogenic zone was defined by a multidisciplinary team, including a radiation oncologist, epileptologist, neurosurgeon, and neuroradiologist.ResultsThe irradiated volumes were 10.3, 11.3, and 16.5 cm3. After a follow-up of 12, 29, and 36 months, all three patients experienced an improvement in both seizure frequency and severity (two already during or shortly after fSRT). One patient achieved complete seizure freedom. All patients reported improvements in quality of life and regained independence or displayed functional recovery. Tolerability was excellent, with radiation-induced side effects being mild (grade 1 only) and transient. RN was not observed. One patient died 29 months after radiotherapy most likely from a ruptured aneurysm of a vertebral artery, unrelated to the treatment.SignificanceFrameless fSRT of 50 Gy in 10 fractions was feasible and might be safe and effective in selected patients with drug-resistant non-neoplastic focal epilepsy and large suspected epileptogenic zones. A prospective single-arm evaluation with structured long-term follow-up including assessment of patient-reported outcome measures is currently being conducted.https://www.frontiersin.org/articles/10.3389/fneur.2025.1600381/fullepileptic seizuresfractionated stereotactic radiotherapystereotactic radiosurgerynon-invasiveepilepsy |
| spellingShingle | Cas Stefaan Dejonckheere Attila Rácz Gustavo Renato Sarria Julian Philipp Layer Julian Philipp Layer Younèss Nour Lara Caglayan Molina Grimmer Victoria Volkenborn Fabian Kugel Thomas Müdder Tobias Baumgartner Valeri Borger Alexander Radbruch Hartmut Vatter Frank Anton Giordano Frank Anton Giordano Frank Anton Giordano Eleni Gkika Rainer Surges Davide Scafa Fractionated stereotactic radiotherapy in people with drug-resistant focal epilepsy: first-in-human experience with a healthy tissue-preserving dose-fractionation concept Frontiers in Neurology epileptic seizures fractionated stereotactic radiotherapy stereotactic radiosurgery non-invasive epilepsy |
| title | Fractionated stereotactic radiotherapy in people with drug-resistant focal epilepsy: first-in-human experience with a healthy tissue-preserving dose-fractionation concept |
| title_full | Fractionated stereotactic radiotherapy in people with drug-resistant focal epilepsy: first-in-human experience with a healthy tissue-preserving dose-fractionation concept |
| title_fullStr | Fractionated stereotactic radiotherapy in people with drug-resistant focal epilepsy: first-in-human experience with a healthy tissue-preserving dose-fractionation concept |
| title_full_unstemmed | Fractionated stereotactic radiotherapy in people with drug-resistant focal epilepsy: first-in-human experience with a healthy tissue-preserving dose-fractionation concept |
| title_short | Fractionated stereotactic radiotherapy in people with drug-resistant focal epilepsy: first-in-human experience with a healthy tissue-preserving dose-fractionation concept |
| title_sort | fractionated stereotactic radiotherapy in people with drug resistant focal epilepsy first in human experience with a healthy tissue preserving dose fractionation concept |
| topic | epileptic seizures fractionated stereotactic radiotherapy stereotactic radiosurgery non-invasive epilepsy |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2025.1600381/full |
| work_keys_str_mv | AT casstefaandejonckheere fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT attilaracz fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT gustavorenatosarria fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT julianphilipplayer fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT julianphilipplayer fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT younessnour fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT laracaglayan fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT molinagrimmer fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT victoriavolkenborn fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT fabiankugel fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT thomasmudder fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT tobiasbaumgartner fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT valeriborger fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT alexanderradbruch fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT hartmutvatter fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT frankantongiordano fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT frankantongiordano fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT frankantongiordano fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT elenigkika fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT rainersurges fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept AT davidescafa fractionatedstereotacticradiotherapyinpeoplewithdrugresistantfocalepilepsyfirstinhumanexperiencewithahealthytissuepreservingdosefractionationconcept |