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Radiotherapy plus concomitant temozolomide in primary gliosarcoma

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Abstract

Clinical guidelines for gliosarcoma (GSM) are poorly defined and GSM patients are usually treated in accordance with existing guidelines for glioblastoma (GBM), with maximal surgical resection followed by chemoradiation with temozolomide (TMZ). However, it is not clear yet if GSM patients profit from TMZ therapy and if O6-methylguanine–DNA–methyltransferase (MGMT) promoter methylation is crucial. We retrospectively evaluated 37 patients with histologically proven, primary GSM who had received radiation therapy since the temozolomide era (post-2005). Twenty-five patients (67.6 %) received combined chemoradiation with temozolomide, and 12 cases (32.4 %) received radiation therapy alone. Molecular markers were determined retrospectively. Survival and correlations were calculated using log-rank, univariate, and multivariate Cox proportional hazards-ratio analyses. All cases were isocitrate dehydrogenase 1 (IDH1) wildtype, MGMT promoter methylation could be observed in 33.3 % of the assessable cases (10/30) and TERT promoter mutation was seen in a high frequency of 86.7 % (26/30). The influence of TMZ therapy on overall survival (OS) was significantly improved compared with cases in which radiation therapy alone was performed (13.9 vs. 9.9 months; p = 0.045), independently of MGMT promoter methylation. The positive effect of TMZ on OS was confirmed in this study’s multivariate analyses (p = 0.04), after adjusting our results for potential confounders. In conclusion, this study demonstrates that concomitant TMZ together with radiation therapy increases GSM-patient survival independent of MGMT promoter methylation. Thus, GSM can be treated in accordance to GBM guidelines. MGMT promoter methylation was infrequent and TERT promoter mutation common without influencing the survival rates. The mechanisms of TMZ effects in GSM are still not fully understood and merit further clinical and molecular-genetic and -biological evaluation.

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Acknowledgments

We acknowledge financial support by Ruprecht-Karls-Universität Heidelberg within the funding program Open Access Publishing.

Authors’ contributions

JD, SR and AU treated the patients. SA, DB, SH, CK, and CD made the data collection. SA and CK are responsible for statistical considerations of the analysis. AvD and CK performed the neuropathologic evaluation. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Sebastian Adeberg, Denise Bernhardt, Semi Ben Harrabi, Stefan Rieken & Juergen Debus

  2. Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Sebastian Adeberg, Semi Ben Harrabi & Juergen Debus

  3. Heidelberg Ion-Beam Therapy Center (HIT), Im Neuenheimer Feld 450, 69120, Heidelberg, Germany

    Stefan Rieken & Juergen Debus

  4. Department of Neurosurgery, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Christian Diehl & Andreas Unterberg

  5. Department of Neuropathology, University Hospital of Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany

    Christian Koelsche & Andreas von Deimling

  6. Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Christian Koelsche & Andreas von Deimling

  7. Department of Radiation Oncology, Technische Universität München, Ismaninger Straße 22, 81675, Munich, Germany

    Christian Diehl

  8. Institut für Innovative Radiotherapie (iRT), Department of Radiation Sciences (DRS), Helmholtz Zentrum München, Ingostädter Landtraße 1, Neuherberg, Germany

    Christian Diehl

  9. Heidelberg Institute of Radiation Oncology (HIRO), Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Sebastian Adeberg, Denise Bernhardt, Semi Ben Harrabi, Stefan Rieken & Juergen Debus

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  1. Sebastian Adeberg
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  7. Andreas Unterberg
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  8. Andreas von Deimling
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Correspondence to Sebastian Adeberg.

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Conflicts of interest

Under a licensing agreement between DIANOVA GmbH, Hamburg, Germany, and the German Cancer Research Center, Andreas von Deimling is entitled to a share of royalties received by the German Cancer Research Center on the sales of H09 antibody. The terms of this arrangement are being managed by the German Cancer Research Center in accordance with its conflict of interest policies. The other authors have nothing to declare.

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Adeberg, S., Bernhardt, D., Harrabi, S.B. et al. Radiotherapy plus concomitant temozolomide in primary gliosarcoma. J Neurooncol 128, 341–348 (2016). https://doi.org/10.1007/s11060-016-2117-x

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  • DOI: https://doi.org/10.1007/s11060-016-2117-x

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