Prognosis factors of survival time in patients with glioblastoma multiforme: a multivariate analysis of 340 patients

SummaryBackground. The prognosis of glioblastoma multiforme remains poor despite recent therapeutic advances. Several clinical and therapeutic factors as well as tumour characteristics have been reported as significant to survival. A more efficient determination of the prognostic factors is required to optimize individual therapeutic management. The aim of our study was to evaluate by univariate then multivariate analysis the factors that influence prognosis and particularly survival. Methods. Data of 340 patients with newly-diagnosed GBM were retrospectively analyzed. Univariate analysis of prognosis factors of survival time was performed. Factors that seemed determinant were evaluated by Kaplan–Meier survival curves. Finally, the significant factors found in univariate analysis were tested in multivariate analysis using the COX regression method. Findings. Using multivariate analysis, the following factors were found to influence survival: radiotherapy was the predominant factor followed by radical surgery, tumour location, age and chemotherapy. Patients treated with temozolomide had a markedly better survival rate than patients treated with other chemotherapies (Log-rank test P < 0.005). The values of GBM type (de novo or secondary), as well as repeated surgery and partial surgery (vs. simple biopsy) were suggested by univariate analysis but not confirmed by the COX regression method. After radical surgery, progression-free survival was correlated to overall survival (r = 0.87, P < 10e-5). Conclusions. The influence of radiotherapy on survival was greater than the influence of age, an argument supporting the proposition of radiotherapy for patients until at least age 70. In the case of recurrence, the correlation between overall survival and progression-free survival is an important factor when considering the therapeutic options. Initial radical surgery and repeated procedures dramatically influence survival. The benefit of partial surgery remains difficult to evaluate. Partial surgery could be used to decrease intracranial pressure and to minimize residual tumours in order to enable treatment by chemotherapy and radiotherapy. The value of temozolomide treatment was confirmed.

[1]  W. Hopman,et al.  Indicators of Functional Status for Primary Malignant Brain Tumour Patients , 2005, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[2]  Y Sawamura,et al.  Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression. , 1999, Neuro-oncology.

[3]  A. Verma MGMT Gene Silencing and Benefit From Temozolomide in Glioblastoma , 2006 .

[4]  Manfred Westphal,et al.  A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. , 2003, Neuro-oncology.

[5]  M Koslow,et al.  Pathways leading to glioblastoma multiforme: a molecular analysis of genetic alterations in 65 astrocytic tumors. , 1994, Journal of neurosurgery.

[6]  Z L Gokaslan,et al.  A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. , 2001, Journal of neurosurgery.

[7]  P. Kleihues,et al.  Primary and secondary glioblastomas: from concept to clinical diagnosis. , 1999, Neuro-oncology.

[8]  V. Gebski,et al.  The effect of waiting for radiotherapy for grade III/IV gliomas. , 2000, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[9]  R. Hayes,et al.  Prognostic relevance of epidermal growth factor receptor (EGF-R) and c-neu/erbB2 expression in glioblastomas (GBMs) , 1993, Journal of Neuro-Oncology.

[10]  Stefano Colella,et al.  Loss of Heterozygosity on Chromosome 10 Is More Extensive in Primary (De Novo) Than in Secondary Glioblastomas , 2000, Laboratory Investigation.

[11]  Martin J. van den Bent,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[12]  P. Lunardi,et al.  Long-Term Survival in Cerebral Glioblastoma. Case Report and Critical Review of the Literature , 1998, Tumori.

[13]  Robert C. Rostomily,et al.  The cause of death in patients with glioblastoma is multifactorial: , 1991, Journal of Neuro-Oncology.

[14]  G. Besson,et al.  [Glioblastomas: clinical study and search for prognostic factors]. , 2002, Neuro-Chirurgie.

[15]  H Stepp,et al.  Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. , 2000, Journal of neurosurgery.

[16]  Y. Yonekawa,et al.  PTEN (MMAC1) Mutations Are Frequent in Primary Glioblastomas (de novo) but not in Secondary Glioblastomas , 1998, Journal of neuropathology and experimental neurology.

[17]  D.,et al.  Regression Models and Life-Tables , 2022 .

[18]  J. Shinoda,et al.  Selection of Eligible Patients with Supratentorial Glioblastoma Multiforme for Gross Total Resection , 2001, Journal of Neuro-Oncology.

[19]  N. Rainov,et al.  Prognostic factors in malignant glioma: Influence of the overexpression of oncogene and tumor-suppressor gene products on survival , 1997, Journal of Neuro-Oncology.

[20]  E L Kaplan NON-PARAMETRIC ESTIMATION FROM INCOMPLETE OBSERVATION , 1958 .

[21]  P J Kelly,et al.  Resection, biopsy, and survival in malignant glial neoplasms. A retrospective study of clinical parameters, therapy, and outcome. , 1993, Journal of neurosurgery.

[22]  G. Maira,et al.  Glioblastoma Multiforme in the Elderly: A Therapeutic Challenge , 2005, Journal of Neuro-Oncology.

[23]  P. Wen,et al.  Treatment of patients with primary glioblastoma multiforme with standard postoperative radiotherapy and radiosurgical boost: prognostic factors and long-term outcome. , 1999, Journal of neurosurgery.

[24]  Wei Huang,et al.  Functional outcomes and survival in patients with high-grade gliomas in dominant and nondominant hemispheres. , 2005, Journal of neurosurgery.

[25]  D P Byar,et al.  Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. , 1980, The New England journal of medicine.

[26]  H. Mehdorn,et al.  Glioblastoma multiforme-report of 267 cases treated at a single institution. , 2005, Surgical neurology.

[27]  A. Obwegeser,et al.  Therapy of glioblastoma multiforme: A cumulative experience of 10 years , 2005, Acta Neurochirurgica.

[28]  F. Zanella,et al.  Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. , 2006, The Lancet. Oncology.

[29]  A. Bordron,et al.  Recombinant humanised anti-HER2/neu antibody (Herceptin®) induces cellular death of glioblastomas , 2004, British Journal of Cancer.

[30]  P. Kelly,et al.  Grading of astrocytomas: A simple and reproducible method , 1988, Cancer.

[31]  Klaus Sartor,et al.  Early Postoperative Magnetic Resonance Imaging after Resection of Malignant Glioma , 1995 .

[32]  M. Berger,et al.  The effect of extent of resection on time to tumor progression and survival in patients with glioblastoma multiforme of the cerebral hemisphere. , 1999, Surgical neurology.

[33]  R. Jena,et al.  Mathematical modelling of survival of glioblastoma patients suggests a role for radiotherapy dose escalation and predicts poorer outcome after delay to start treatment. , 2006, Clinical oncology (Royal College of Radiologists (Great Britain)).

[34]  K. Sartor,et al.  Early Postoperative Magnetic Resonance Imaging after Resection of Malignant Glioma: Objective Evaluation of Residual Tumor and Its Influence on Regrowth and Prognosis , 1995 .

[35]  P. Kleihues,et al.  Epidemiology and etiology of gliomas , 2005, Acta Neuropathologica.