Artikel
Complete but not partial resection of glioblastoma promotes survival in the era of radiotherapy with concomitant and adjuvant temozolomide
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Autoren
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Friedrich-Wilhelm Kreth
- Neurochirurgische Klinik, Klinikum der Universität München
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Niklas Thon
- Neurochirurgische Klinik, Klinikum der Universität München
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Bettina Hentschel
- Institut für Medizinische Informatik, Statistik und Epidemiologie der Universität Leipzig
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Torsten Pietsch
- Zentrum für Pathologie Institut für Neuropathologie, Universitätsklinikum Bonn
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Michael Weller
- Klinik für Neurologie des Universitätsspitals Zürich, Schweiz
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Jörg-Christian Tonn
- Neurochirurgische Klinik, Klinikum der Universität München
| Veröffentlicht: | 21. Mai 2013 |
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Gliederung
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Objective: Resection followed by radiotherapy (RT) plus concomitant and adjuvant temozolomide (TMZ) is considered standard of care for glioblastoma. Treatment, however, is highly variable and the benefit of partial resection remains unclear. This multicenter observational study was conducted to assess both current treatment strategies and prognostic factors, including the extent of resection and MGMT promoter methylation in patients with newly-diagnosed glioblastoma.
Method: Histology, MGMT promoter methylation status and all clinical data were centrally analysed. Survival analyses were performed with the Kaplan-Meier method. Endpoints were overall survival (OS) and progression-free survival (PFS). Prognostic factors were assessed with proportional hazards models.
Results: Between 2004 and 2009, a total of 345 patients were included. Postoperative MRI revealed 36.2% complete and 42.9% partial resections. 20.9% underwent biopsy. Surgery-related morbidity was lower after biopsy (1.4% vs. 12.1%, p=0.007). 64.3% of patients received RT+TMZ, 20.0% RT, 4.3% TMZ, and 11.3% best supportive care. Patients <60years and KPS>80 were more likely to receive open tumor resection and RT+TMZ (p<0.01). Overall median PFS and OS were 6.4 months (95%-CI 5.7-7.1) and 12.8 months (95%-CI 11.2-14.4). Median OS (PFS) was as high as 33.2 (15.0) months for patients with MGMT-methylated tumors after complete resection followed by RT+TMZ to as low as 3.0 (2.4) months for biopsied patients receiving best supportive care only. Favorable prognostic factors for OS were a methylated MGMT promoter (RR=0.44; p<0.001), RT+TMZ treatment (RR=0.18, p<0.001), age <60 years (RR=0.52; p<0.001), a KPS>80 (RR=0.55; p<0.001) and complete resection (RR=0.60; p=0.003). Incomplete resection was as good as biopsy only, in all patients as well as in a large subgroup of 222 patients receiving RT+TMZ. MGMT-methylation and complete resection continued to be of independent prognostic importance.
Conclusions: Our study confirms superior over all survival in case of MGMT promoter methylation, RT+TMZ treatment and complete resection. Incomplete resection does not significantly improve OS as compared to biopsy.
