Importance of biomarkers in glioblastomas patients receiving local BCNU wafer chemotherapy

Abstract Background 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 (surgic...

Full description

Bibliographic Details
Main Authors: Steffi Urbschat, Christoph Sippl, Jana Engelhardt, Kai Kammers, Joachim Oertel, Ralf Ketter
Format: Article
Language:English
Published: BMC 2017-05-01
Series:Molecular Cytogenetics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13039-017-0317-5
_version_ 1830453003331567616
author Steffi Urbschat
Christoph Sippl
Jana Engelhardt
Kai Kammers
Joachim Oertel
Ralf Ketter
author_facet Steffi Urbschat
Christoph Sippl
Jana Engelhardt
Kai Kammers
Joachim Oertel
Ralf Ketter
author_sort Steffi Urbschat
collection DOAJ
description Abstract Background 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. 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. The MGMT promoter methylation is a strong prognostic Biomarker for benefit from temozolomide and BCNU chemotherapy.
first_indexed 2024-12-21T09:00:11Z
format Article
id doaj.art-8dc4b34c3f82464f9d125e0a7c64eea2
institution Directory Open Access Journal
issn 1755-8166
language English
last_indexed 2024-12-21T09:00:11Z
publishDate 2017-05-01
publisher BMC
record_format Article
series Molecular Cytogenetics
spelling doaj.art-8dc4b34c3f82464f9d125e0a7c64eea22022-12-21T19:09:29ZengBMCMolecular Cytogenetics1755-81662017-05-0110111210.1186/s13039-017-0317-5Importance of biomarkers in glioblastomas patients receiving local BCNU wafer chemotherapySteffi Urbschat0Christoph Sippl1Jana Engelhardt2Kai Kammers3Joachim Oertel4Ralf Ketter5Department of Neurosurgery, Saarland UniversityDepartment of Neurosurgery, Saarland UniversityDepartment of Neurosurgery, Saarland UniversityDivision of Biostatistics and Bioinformatics, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of MedicineDepartment of Neurosurgery, Saarland UniversityDepartment of Neurosurgery, Saarland UniversityAbstract Background 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. 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. The MGMT promoter methylation is a strong prognostic Biomarker for benefit from temozolomide and BCNU chemotherapy.http://link.springer.com/article/10.1186/s13039-017-0317-5GlioblastomaCGHCarmustin waferPrognostic factorsStandard combined radiochemotherapy
spellingShingle Steffi Urbschat
Christoph Sippl
Jana Engelhardt
Kai Kammers
Joachim Oertel
Ralf Ketter
Importance of biomarkers in glioblastomas patients receiving local BCNU wafer chemotherapy
Molecular Cytogenetics
Glioblastoma
CGH
Carmustin wafer
Prognostic factors
Standard combined radiochemotherapy
title Importance of biomarkers in glioblastomas patients receiving local BCNU wafer chemotherapy
title_full Importance of biomarkers in glioblastomas patients receiving local BCNU wafer chemotherapy
title_fullStr Importance of biomarkers in glioblastomas patients receiving local BCNU wafer chemotherapy
title_full_unstemmed Importance of biomarkers in glioblastomas patients receiving local BCNU wafer chemotherapy
title_short Importance of biomarkers in glioblastomas patients receiving local BCNU wafer chemotherapy
title_sort importance of biomarkers in glioblastomas patients receiving local bcnu wafer chemotherapy
topic Glioblastoma
CGH
Carmustin wafer
Prognostic factors
Standard combined radiochemotherapy
url http://link.springer.com/article/10.1186/s13039-017-0317-5
work_keys_str_mv AT steffiurbschat importanceofbiomarkersinglioblastomaspatientsreceivinglocalbcnuwaferchemotherapy
AT christophsippl importanceofbiomarkersinglioblastomaspatientsreceivinglocalbcnuwaferchemotherapy
AT janaengelhardt importanceofbiomarkersinglioblastomaspatientsreceivinglocalbcnuwaferchemotherapy
AT kaikammers importanceofbiomarkersinglioblastomaspatientsreceivinglocalbcnuwaferchemotherapy
AT joachimoertel importanceofbiomarkersinglioblastomaspatientsreceivinglocalbcnuwaferchemotherapy
AT ralfketter importanceofbiomarkersinglioblastomaspatientsreceivinglocalbcnuwaferchemotherapy