Article
Clinical and oncological course of patients with recurrent glioblastoma multiforme treated with local carmustine wafers in relation to the methylation status of the MGMT promotor – preliminary results of CARENTA – a prospective multicentre observational study
Prognostische Bedeutung des Methylierungsgrades des MGMT-Promotors für das Gesamtüberleben bei Patienten mit Erstrezidiv eines Glioblastoms, welche eine lokale Carmustin-Applikation unterlaufen – Zwischenergebnisse der CARENTA Studie
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Authors
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Pawel Gutowski
- Unfallkrankenhaus Berlin, Klinik für Neurochirurgie, Berlin, Deutschland; Brodno Masovian Hospital, Neurosurgery, Warschau, Polen
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Ullrich Meier
- Unfallkrankenhaus Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
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Johannes Lemcke
- Unfallkrankenhaus Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
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Sergej Rot
- Unfallkrankenhaus Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
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Maximillian Sitz
- Unfallkrankenhaus Berlin, Klinik für Neurochirurgie, Berlin, Deutschland
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Michael Fritsch
- Diakonie Klinikum Dietrich Bonhoeffer, Neurosurgery, Neubrandenburg, Deutschland
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Martin Kunz
- Diakonie Klinikum Dietrich Bonhoeffer, Neurosurgery, Neubrandenburg, Deutschland
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Andreas Jödicke
- Diakonie Klinikum Dietrich Bonhoeffer, Neurosurgery, Neubrandenburg, Deutschland
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Finn Ruppert
- Vivantes Klinikum Neukölln, Klinik für Neurochirurgie, Berlin, Deutschland
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Veit Rohde
- University Medical Center Göttingen, Neurosurgery, Göttingen, Deutschland
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Christian von der Brelie
- University Medical Center Göttingen, Neurosurgery, Göttingen, Deutschland
| Published: | June 4, 2021 |
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Outline
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Objective: The methylation of O6-methylguanine-DNA-methyltransferase (MGMT) is an established biomarker in IDH-wildtype glioblastoma (GBM) patients. It enhances the effectiveness of alkylating chemotherapy and by such affects the progression free survival (PFS) and overall survival (OS). Standardized therapy modalities regarding of recurrent GBM are yet to be established. The goal of this study was to investigate a beneficial use of carmustine wafers in recurrent glioblastoma in relation to the MGMT methylation promotor status.
Methods: Adult patients with the first recurrence of a GBM were included in this study. Only patients were included who underwent prior gross total resection and adjuvant chemoradiotherapy following the “Stupp” protocol. The methylation status of the MGMT promotor was evaluated by pyrosequencing of the tumor tissue after the primary resection. Study documentation resembles clinical practice. Follow-ups were performed at 3, 6 and 12 months postoperatively. Clinical parameters, quality of life data and MRI results were gathered. The primary outcome measure was the OS (measured after the date of recurrent resection and carmustine wafer implantation) in relation to the grade of methylation of the MGMT promoter. Secondary outcome measures obtained PFS after recurrent resection, the quality of life (using the Short-Form [SF] 36 health survey) and complication rates. A monitor regularly visited the study sites to ensure the quality of the data.
Results: Patient enrollment began in 2015. Four study centers participated. The target number of 60 participants was reached in 2020. The median patient age was 57 years. In 60% of the patients, histological analysis revealed an unmethylated MGMT promotor status. The mean OS after recurrent resection was 213 days (7.1 months). The mean OS of patients after carmustine wafer implantation with an unmethylated MGMT promotor status and a methylated MGMT promotor status were 207 days and 222 days, respectively. The OS showed no significant difference in the groups (Log Rank test; p=0.729). An increased rate of complications associated with the use of carmustine wafers has not been observed.
Conclusion: The therapy of recurrent GBM remains challenging. The preliminary results of our study suggest that the use of carmustine wafers might counterweigh the shorter OS in patients with unmethylated MGMT promotor.
