Artikel
Importance of biomarkers in glioblastomas patients receiving local BCNU wafer chemotherapy
Die Bedeutung von Biomarkern von Patienten mit Glioblastom, welche mit BCNU wafern behandelt wurden
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Autoren
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Steffi Urbschat
- Universitätsklinikum des Saarlandes, Klinik für Neurochirurgie, Homburg, Deutschland
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Christoph Sippl
- Universitätsklinikum des Saarlandes, Klinik für Neurochirurgie, Homburg, Deutschland
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Jana Engelhardt
- Universitätsklinikum des Saarlandes, Klinik für Neurochirurgie, Homburg, Deutschland
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Kai Kammers
- University, Department of Biostatistics, Baltimore, United States
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Joachim Oertel
- Universitätsklinikum des Saarlandes, Klinik für Neurochirurgie, Homburg, Deutschland
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Ralf Ketter
- Universitätsklinikum des Saarlandes, Klinik für Neurochirurgie, Homburg, Deutschland
| Veröffentlicht: | 8. Mai 2019 |
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Gliederung
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Objective: To assess the influence of molecular markers with potential prognostic value to groups of patients with newly diagnosed glioblastoma patients were examined: group A with 36 patients (surgical resection plus standard combined chemoradiotherapy) and group B with 36 patients (surgical resection, standard combined chemoradiotherapy plus carmustine wafer implantation). Our aim was to determine chromosomal alterations, methylation status of MGMT, p15, and p16 (CDKN2A) in order to analyse the influence on patient survival time as well as radio- and chemotherapy responses.
Methods: Promoter hypermethylation of MGMT, p16, and p15 genes were determined by MS-PCR. Comparative genomic hybridisation (CGH) analyses were performed with isolated, labelled DNA of each tumor to detect genetic alterations.
Results: Age of onset of the disease showed a significant effect on overall survival (OS) (p<0.0001). Additional treatment with carmustine wafer (group B) compared to the control group (group A) did not result in improved OS (p=0.562). Patients with a methylated MGMT promotor showed a significant longer OS compared to those patients with unmethylated MGMT promotor (p=0.041). Subgroup analyses revealed that patients with methylated p15 showed a significant shorter OS when administered to group B rather than in group A (p=0.0332). In patients additionally treated with carmustine wafer an amplification of 4q12 showed a significant impact on a reduced OS (p=0.00835). In group B a loss of 13q was significantly associated with a longer OS (p=0.0364). If a loss of chromosome 10 occurred, patients in group B showed a significantly longer OS (p=0.0123).
Conclusion: A clinical benefit for the widespread use of additional carmustine wafer implantation could not be found. However, carmustine wafer implantation shows a significantly improved overall survival if parts of chromosome 10 or chromosome 13 are deleted. In cases of 4q12 amplification and in cases of a methylated p15 promotor, the use of carmustine wafers is especially not recommended.
