Postoperative radiotherapy of glioblastoma multiforme: analysis and critical assessment of different treatment strategies and predictive factors.
OBJECTIVE
Different factors influence glioblastoma patients' prognosis. The aim of this retrospective, explorative analysis was to define the role of recent treatment strategies and to examine the value of different prognostic factors.


METHODS
A total of 110 patients was analyzed. Complete resection, partial resection, and biopsy was accomplished in 69, 22, and 19 patients, respectively. 56 patients received conventionally fractionated radiotherapy with a median total dose of 60 Gy, 2 Gy daily. 54 patients received hyperfractionated accelerated radiotherapy with a median total dose of 54 Gy, 2 x 1.8 Gy daily. 20 patients had concomitant temozolomide (50-75 mg/m2/d), and 20 patients concomitant topotecan (0.5 mg/m2 as continuous venous infusion over 21 days). 37 patients received temozolomide as salvage therapy.


RESULTS
Median overall (OS) and disease-free survival (DFS) were 8.7 and 4.8 months. After complete resection, partial resection, and biopsy, OS was 9.5, 8.5, and 5.5 months, respectively. OS was 8.5, 13.8, and 8.2 months for radiotherapy alone, concomitant temozolomide, and concomitant topotecan, respectively. Hazard ratio was 0.29 (OS; p = 0.002) and 0.32 (DFS; p = 0.003) for concomitant temozolomide compared to radiotherapy alone. Topotecan led to an increased toxicity. With 9.7 months for conventionally fractionated radiotherapy and 8.1 months for hyperfractionated radiotherapy, OS differed significantly (p = 0.003, log-rank test). OS in patients with RPA (recursive partitioning analysis) score III, IV, V, and VI was 14.1, 10, 9.5, and 5.8 months (p = 0.003, log-rank test). In the univariate (p = 0.0001, log-rank test) and multivariate analysis (p = 0.002, Cox regression), salvage temozolomide led to a statistically significant survival benefit (10.6 vs. 7.7 months).


CONCLUSIONS
Concomitant topotecan or the use of hyperfractionated radiotherapy did not show to be superior in outcome in this retrospective analysis. Topotecan led to an increased toxicity. An attempt at complete resection is justified. Temozolomide should be integrated in therapy initially. As salvage therapy, temozolomide is also effective.
Department of Radiation Oncology, RWTH Aachen University Hospital, Aachen, Germany. mpiroth@ukaachen.de
Marc D
MD
Piroth
Bernd
B
Gagel
Michael
M
Pinkawa
Sven
S
Stanzel
Branka
B
Asadpour
Michael J
MJ
Eble
D000328:Adult; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000633:toxicity; D001706:Biopsy; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003399:Craniotomy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011832:Radiation Injuries / Q000209:etiology; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D016879:Salvage Therapy; D000077204:Temozolomide; D019772:Topotecan / Q000008:administration & dosage / Q000633:toxicity
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D019772:Topotecan; D000077204:Temozolomide