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69. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Mexikanischen und Kolumbianischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

03.06. - 06.06.2018, Münster

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Clinical impact of TERT promoter mutation detection in cell-free DNA of patients with IDH wild-type glioblastomas – a pilot prospective study

Meeting Abstract

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  • Dietmar Krex - Universitätsklinikum Carl Gustav Carus, Klinik für Neurochirurgie, Dresden, Deutschland
  • Tareq Juratli - Universitätsklinikum Carl Gustav Carus, Klinik für Neurochirurgie, Dresden, Deutschland
  • Mazen Juratli - Universitätsklinikum Frankfurt, Klinik für Allgemien- und Viszeralchirurgie, Frankfurt am Main, Deutschland
  • Meriem Makina - Universitätsklinikum Carl Gustav Carus, Klinik für Neurochirurgie, Dresden, Deutschland
  • Gabriele Schackert - Universitätsklinikum Carl Gustav Carus, Klinik für Neurochirurgie, Dresden, Deutschland
  • Tim Lautenschlaeger - Indiana University School of Medicine, Department of Radiation Oncology, Indianapolis, IN, Vereinigte Staaten
  • Christian Thiede - Universitätsklinikum Carl Gustav Carus, Medizinische Klinik I, Dresden, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 69. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Mexikanischen und Kolumbianischen Gesellschaft für Neurochirurgie. Münster, 03.-06.06.2018. Düsseldorf: German Medical Science GMS Publishing House; 2018. DocV303

doi: 10.3205/18dgnc323, urn:nbn:de:0183-18dgnc3237

Veröffentlicht: 18. Juni 2018

© 2018 Krex et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

Gliederung

Text

Objective: Detection ofcirculatingcell-free tumor-derivedDNA(cfDNA) has been shown to be of clinical value in monitoring cancer treatment. We conducted a pilot study on the feasibility of detecting TERT promoter TERTp-mutant cfDNA in CSF and plasma in glioblastoma patients and its potential clinical implications.

Methods: Matched plasma and CSF samples were collected before tumor resection in 39 patients. The collected cfDNA and matched tumorDNAsamples were analyzed for hotspot mutations in the TERTp region (C228 and C250). Logistic regression analysis was performed to evaluate the clinical impact of the variant allele frequency (VAF) of TERTp-mutant cfDNA in predicting patients’ survival.

Results: 25 patients had a TERTp-mutant glioblastoma. The matched TERTp-CSF-derived cfDNA was successfully detected with 100% specificity and 92% sensitivity (n=23). The median VAF of the CSF-cfDNA was 20.3% (0.08%-70.3%). In the plasma, the sensitivity was far lower (12%). There was a statistically significant linear relationship between the CSF-VAFs and PFS (R2=0.1615; p=0.0418). Strikingly, in the multivariate analysis, the median TERTp-VAF for CSF-cfDNA was the best predictor for PFS (p=0.007, HR=4.1, 95%CI: 1.4–11.3) and OS (p=0.013, HR=4.7, 95%CI: 1.3–15.8). In contrast, none of the other included established clinical parameters (i.e. age, tumor volume, MGMT-promoter methylation) appear to be an independent prognostic factor.

Conclusion: We propose that the detection and accurate quantification of TERTp-mutant CSF-cfDNA in glioblastoma patients is feasible with a high sensitivity and specificity. Additionally, although generated using a small cohort, our findings indicate that pre-resection CSF-derived cfDNA might be an important prognostic marker associated with survival.