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Radiochemotherapy with temozolomide for patients with glioblastoma

Prognostic factors and long-term outcome of unselected patients from a single institution

Radiochemotherapie mit Temozolomid bei unselektionierten Patienten mit Glioblastom: Prognostische Faktoren und Überleben im Rahmen einer monoinstitutionellen Serie

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Abstract

Background

The objective of this retrospective analysis was to assess long-term outcome and prognostic factors of unselected patients treated for glioblastoma (GB) at a single center with surgery, standard radiotherapy (RT), and concomitant temozolomide (TMZ). From 1999–2005, the institutional protocol included surgery and RT with TMZ. From 2005 on, adjuvant TMZ was routinely added.

Patients and Methods

Between April 1999 and September 2009, 181 patients with GB were treated with RT (60 Gy in 30 fractions) and concomitant TMZ (75 mg/m2/day throughout RT). Biopsy only had been performed in 53 patients (29.3%), 128 patients (70.7%) had undergone resection, which was complete based on postoperative MRI in 51 patients (28.2%). Adjuvant TMZ was applied in 67 of 181 patients (37%).

Results

Median overall survival (OS) and progression-free survival (PFS) were 15.0 (95% CI, 13.1–16.8) and 7.2 months (95% CI, 5.9–8.5), respectively. After complete resection, partial/subtotal resection and biopsy, median OS was 23.20, 14.75, and 7.89 months (p < 0.001), respectively. In multivariate Cox proportional hazards regression models, extent of resection (p < 0.0001), Karnofsky’s performance score (p < 0.0001) and adjuvant TMZ (p = 0.001) were significant independent prognostic factors for OS. RT with concomitant TMZ was well tolerated in the majority of patients and could be completed as scheduled in 146 patients (80.7%), while 11 patients (6.1%) discontinued RT. Another 35 patients (19.3%) interrupted concomitant chemotherapy.

Conclusion

RT with concomitant TMZ is a feasible regimen with acceptable toxicity in routine practice. Our data are compatible with a beneficial effect of adjuvant TMZ on OS and PFS.

Zusammenfassung

Hintergrund

Ziel dieser retrospektiven Analyse einer monoinstitutionellen Serie war es, Langzeitergebnisse sowie Prognosefaktoren nach Operation und simultaner Radiochemotherapie (RCT) mit Temozolomid (TMZ) zu untersuchen. Zwischen 1999 und 2005 erfolgte nach Operation eine RCT mit TMZ; seit 2005 wurde routinemäßig eine adjuvante TMZ-Chemotherapie hinzugefügt.

Patienten und Methoden

Von 04/1999 bis 9/2009, wurden 181 GB-Patienten mit einer kombinierten RCT (60 Gy in 30 Fraktionen) mit TMZ 75 mg/m2/Tag während der RT behandelt. Eine alleinige Biopsie lag bei 53 Patienten (29,3 %) vor. 128 Patienten (70,7 %) wurden reseziert; davon erreichten 51 Patienten (28,2 %) nach Maßgaben eines postoperativen MRT eine komplette Resektion. Eine adjuvante TMZ-Therapie erhielten 67 der 181 Patienten (37 %).

Ergebnisse

Das mediane Gesamtüberleben (GÜ) und das progressionsfreie Überleben (PFÜ) lag bei 15,0 (95 %-CI: 13,1–16,8 Monate) bzw. 7,2 Monaten (95 %-CI: 5,9–8,5 Monate). Nach kompletter Resektion, partieller/subtotaler Resektion bzw. Biopsie betrug das mediane GÜ 23,2 bzw. 14,75 und 7,89 Monate (p < 0,001). In der multivariaten Analyse waren Resektionsstatus (p < 0,0001), Karnofsky-Index (p < 0,0001) und adjuvante TMZ-Therapie (p = 0,001) unabhängige prognostische Faktoren. Von der Mehrzahl der Patienten wurde die kombinierte RCT gut vertragen und konnte bei 146 Patienten (80,7 %) vollständig durchgeführt werden. Bei 11 Patienten (6,1 %) wurde die RT abgebrochen. Bei weiteren 35 Patienten wurde die konkomitante Chemotherapie unterbrochen.

Schlussfolgerung

Die kombinierte RCT mit TMZ ist in der klinischen Routine ein gut verträgliches Therapieregime mit einer akzeptablen Toxizität. Die adjuvante Chemotherapie mit TMZ war mit einer Verbesserung des GÜ und PFÜ assoziiert.

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Authors and Affiliations

  1. Department of Radiotherapy and Oncology, Johann Wolfgang Goethe University, Frankfurt/Main, Germany

    Johanna Gerstein, Claus Rödel & Christian Weiss MD

  2. Department of Neurosurgery, Johann Wolfgang Goethe University, Frankfurt/Main, Germany

    Kea Franz & Volkert Seifert

  3. Dr. Senckenberg Institute of Neurooncology, Johann Wolfgang Goethe University, Frankfurt/Main, Germany

    Joachim P. Steinbach

  4. Department of Radiation Therapy and Oncology, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590, Frankfurt/Main, Germany

    Christian Weiss MD

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  1. Johanna Gerstein
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  2. Kea Franz
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  3. Joachim P. Steinbach
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  4. Volkert Seifert
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  5. Claus Rödel
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Correspondence to Christian Weiss MD.

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Gerstein, J., Franz, K., Steinbach, J.P. et al. Radiochemotherapy with temozolomide for patients with glioblastoma. Strahlenther Onkol 187, 722–728 (2011). https://doi.org/10.1007/s00066-011-2230-x

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  • DOI: https://doi.org/10.1007/s00066-011-2230-x

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