Pia Susan Zeiner, Martina Kinzig, Iris Divé, Gabriele D. Maurer, Katharina Johanna Filipski, Patrick Nikolaus Harter, Christian Senft, Roy Oliver Bähr, Elke Hattingen, Joachim Peter Steinbach, Fritz Sörgel, Martin Voß, Eike Steidl, Michael Wilfried Ronellenfitsch
- (1) Background: The phase 2 Regorafenib in Relapsed Glioblastoma (REGOMA) trial indicated a survival benefit for patients with first recurrence of a glioblastoma when treated with the multikinase inhibitor regorafenib (REG) instead of lomustine. The aim of this retrospective study was to investigate REG penetration to cerebrospinal fluid (CSF), treatment efficacy, and effects on magnetic resonance imaging (MRI) in patients with recurrent high-grade gliomas.
(2) Methods: Patients were characterized by histology, adverse events, steroid treatment, overall survival (OS), and MRI growth pattern. REG and its two active metabolites were quantified by liquid chromatography/tandem mass spectrometry in patients’ serum and CSF.
(3) Results: 21 patients mainly with IDH-wildtype glioblastomas who had been treated with REG were retrospectively identified. Thirteen CFS samples collected from 3 patients of the cohort were available for pharmacokinetic testing. CSF levels of REG and its metabolites were significantly lower than in serum. Follow-up MRI was available in 19 patients and showed progressive disease (PD) in all but 2 patients. Two distinct MRI patterns were identified: 7 patients showed classic PD with progression of contrast enhancing lesions, whereas 11 patients showed a T2-dominant MRI pattern characterized by a marked reduction of contrast enhancement. Median OS was significantly better in patients with a T2-dominant growth pattern (10 vs. 27 weeks respectively, p = 0.003). Diffusion restrictions were observed in 13 patients.
(4) Conclusion: REG and its metabolites were detectable in CSF. A distinct MRI pattern that might be associated with an improved OS was observed in half of the patient cohort. Treatment response in the total cohort was poor.
Metadaten| Author: | Pia Susan ZeinerORCiD, Martina Kinzig, Iris DivéGND, Gabriele D. MaurerORCiDGND, Katharina Johanna FilipskiGND, Patrick Nikolaus HarterORCiDGND, Christian SenftORCiDGND, Roy Oliver Bähr, Elke HattingenORCiDGND, Joachim Peter SteinbachORCiDGND, Fritz Sörgel, Martin VoßORCiDGND, Eike SteidlORCiDGND, Michael Wilfried RonellenfitschORCiDGND |
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| URN: | urn:nbn:de:hebis:30:3-518275 |
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| DOI: | https://doi.org/10.3390/jcm8122031 |
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| ISSN: | 2077-0383 |
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| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/31766326 |
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| Parent Title (English): | Journal of Clinical Medicine |
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| Publisher: | MDPI |
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| Place of publication: | Basel |
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| Document Type: | Article |
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| Language: | English |
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| Year of Completion: | 2019 |
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| Date of first Publication: | 2019/11/21 |
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| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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| Release Date: | 2020/02/05 |
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| Tag: | MRI patterns of gliomas; glioblastoma; malignant glioma; regorafenib; regorafenib csf concentration |
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| Volume: | 8 |
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| Issue: | 12, Art. 2031 |
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| Page Number: | 14 |
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| First Page: | 1 |
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| Last Page: | 14 |
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| Note: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
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| HeBIS-PPN: | 460971476 |
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| Institutes: | Medizin / Medizin |
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| Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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| Sammlungen: | Universitätspublikationen |
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| Open-Access-Publikationsfonds: | Medizin |
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| Licence (German): |  Creative Commons - Namensnennung 4.0 |
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Creative Commons - Namensnennung 4.0