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Radiotherapy plus Concomitant Temozolomide in Primary Gliosarcoma

Sebastian Adeberg MD 1,2, Denise Bernhardt MD 1, Semi Ben Harrabi MD 1,2, Christian Diehl MD 4, Christian Koelsche MD 5, Stefan Rieken MD 1,3, Wolfgang Wick MD 6, Juergen Debus MD PhD 1,2,3 1 University Hospital of Heidelberg, Department of Radiation Oncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany 2 Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany 3 Heidelberg Ion-Beam Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany 4 University Hospital of Heidelberg, Department of Neurosurgery, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany 5 University Hospital of Heidelberg, Department of Neuropathology, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany, and Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany 6 University Hospital of Heidelberg, Department of Neurooncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany


Background
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 chemo-radiation with temozolomide (TMZ). It is not, however, clear yet if GSM patients profit from TMZ therapy.
Materials and Methods
We retrospectively evaluated 39 patients with histologically proven, primary GSM who had received radiation therapy since the temozolomide era (post-2005). Twenty-seven patients (69.2%) received combined chemo-radiation with temozolomide, and 12 cases (30.8%) received radiation therapy alone. Survival and correlations were calculated using log-rank, univariate, and multivariate Cox proportional hazards-ratio analyses.
Result
The influence of TMZ therapy on progression-free survival did not reach statistical significance, even though a tendency toward increased survival could be observed (10.6 vs. 7.6 months; p = 0.69). In cases in which concomitant TMZ was administered during radiation therapy overall survival (OS) was significantly higher compared with cases in which radiation therapy alone was performed (14.5 vs. 9.9 months; p = 0.036). This positive effect of TMZ on OS was confirmed in this study’s multivariate analyses (p = 0.02), after adjusting our results for potential confounders.
Conclusion
This study demonstrates that concomitant TMZ together with radiation therapy increases GSM-patient survival. Thus, GSM should be treated in accordance to GBM guidlines. The mechanisms of this are still not fully understood and merit further clinical and molecular-genetic and -biological evaluation.

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