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Abstract
Circulating biomarkers in blood may provide an interesting alternative to risky tissue biopsies in the diagnosis and follow-up of glioblastoma patients. We have assessed MGMT methylation status in blood and tissue samples from unresected glioblastoma patients who had been included in the randomized GENOM-009 trial. Paired blood and tissue samples were assessed by methylation-specific PCR (MSP) and pyrosequencing (PYR). After establishing the minimum PYR cut-off that could yield a significant difference in overall survival, we assessed the sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the analyses. Methylation could be detected in cfDNA by both MSP and PYR but with low concordance with results in tissue. Sensitivity was low for both methods (31% and 38%, respectively), while specificity was higher for MSP in blood than for PYR in plasma (96% vs 76%) and NPV was similar (56 vs 57%). Concordance of results in tissue by MSP and PYR was 84.3% (P < 0.001) and correlated with outcome. We conclude that detection of cfDNA in the blood of glioblastoma patients can be an alternative when tumor tissue is not available but methods for the detection of cfDNA in blood must improve before it can replace analysis in tumor tissue.
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1 Medical Oncology Service, Catalan Institute of Oncology Badalona, Hospital Germans Trias i Pujol, Applied Research Group in Oncology (B-ARGO Group), Badalona, Spain
2 Pathology Service, University Hospital Germans Trias i Pujol, Badalona, Spain
3 Statistical Unit, Applied Research Group in Oncology (B-ARGO Group), Institut Investigació Germans Trias i Pujol (IGTP), Badalona, Spain
4 Medical Oncology Service, Hospital Provincial de Castellón, Castellón, Spain
5 Medical Oncology Service, Catalan Institute of Oncology l’Hospitalet de LLobregat, Bellvitge Biomedical Research Institute (IDIBELL) l’Hospitalet de Llobregat, Barcelona, Spain
6 Medical Oncology Service, University Hospital 12 de Octubre, Madrid, Spain
7 Neurosurgery Service, Hospital Germans Trias i Pujol, Badalona, Spain
8 Medical Oncology Service, University Hospital General de Valencia, Valencia, Spain
9 Medical Oncology Service, University Hospital Virgen de las Nieves, Granada, Spain
10 Medical Oncology Service, Hospital Miguel Servet, Zaragoza, Spain