Elsevier

World Neurosurgery

Volume 104, August 2017, Pages 581-588
World Neurosurgery

Original Article
A Survival Analysis with Identification of Prognostic Factors in a Series of 110 Patients with Newly Diagnosed Glioblastoma Before and After Introduction of the Stupp Regimen: A Single-Center Observational Study

https://doi.org/10.1016/j.wneu.2017.05.018Get rights and content

Background

Current treatment protocol for glioblastoma multiforme (GBM) is based on maximal safe resection followed by the Stupp protocol. In Serbia, temozolomide was introduced as adjuvant therapy in 2011. The aims of this study were to confirm the safety and efficacy on overall and progression-free survival of the Stupp protocol and evaluate the influence of prognostic factors in one of the largest series of patients with GBM treated over a 2-year period.

Methods

Between January 2010 and December 2012, 110 patients with newly diagnosed GBM underwent surgical removal at the Neurooncology Department of the Clinic Center of Serbia. Patients were divided into 2 groups according to postoperative treatment. Group A (n = 24 patients), treated before January 2011, received adjuvant standard radiation therapy and carmustine (bis-chloroethyl-nitrosourea), and group B (n = 86 patients), treated after January 2011, received postoperative treatment according to the Stupp protocol.

Results

The Stupp protocol had a significant favorable impact on overall survival at 1-year follow-up (79.1% in group B vs. 62.5% in group A; P = 0.016); no differences were noted in regard to progression-free survival. Multivariate analysis identified younger age and gross total resection of tumor as positive prognostic factors.

Conclusions

Adoption of the Stupp protocol had a favorable impact on overall, but not on progression-free, survival rate. Wider surgical resection involving the peritumoral brain zone, as confirmed by univariate and multivariate analysis, represents the most favorable prognostic factor.

Introduction

Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor, with an annual incidence of 1 per 100,000 people. Despite recent advances in medical treatment, the prognosis remains extremely poor, with median overall survival (OS) of 14.6–16.7 months from diagnosis and a 2-year survival rate of 26.5%; most patients present with recurrence and/or regrowth within 1 year from initial treatment. At the present time, standard treatment for newly diagnosed GBM consists of maximum allowed safe surgical resection followed by concomitant chemoradiotherapy as per the Stupp protocol.1, 2, 3 Stupp et al.1 measured a better OS in patients who underwent combined therapy, regardless of methylguanine-deoxyribonucleic acid methyltransferase (MGMT) status; on the contrary, patients presenting with the methylated variant exhibited an advantage in terms of progression-free survival (PFS) compared with patients with the unmethylated gene. In attempts to define the impact of demographic and surgical factors on clinical outcomes, it has been emphasized that maximal safe resection, eventual performance status, and age at surgery are positive predictive factors, independent of the Stupp protocol.4, 5, 6

Nevertheless, as per health care system bylaws in Serbia, since 2011, temozolomide (TMZ) has been administered as adjuvant chemotherapy. At the Clinic of Neurosurgery of the Clinical Center of Serbia in Belgrade, before the introduction of the Stupp regimen, patients with GBM with good performance status would have received postoperative treatment with radiotherapy (RT) followed by carmustine (bis-chloroethyl-nitrosourea [BCNU]) or lomustine (chloroethyl-cyclohexyl-nitrosourea [CCNU]) (3–6 cycles, depending on hematotoxicity). The aims of this study were to confirm the efficacy and safety of the Stupp protocol on both OS and PFS and evaluate the influence of the prognostic factors in one of the largest series of patients with GBM treated by modern surgical techniques at a single institution over a short period of time (i.e., 2 years). To our knowledge, this is the first survival analysis of patients with GBM treated in Serbia, where chronic exposure to environmental carcinogens and poor socioeconomic conditions are possible factors affecting the outcome of GBM.

Section snippets

Materials and Methods

A retrospective analysis of 110 consecutive patients with histologically confirmed GBM was performed. The cohort consisted of adult patients operated on between January 2010 and December 2012 by a surgical team of 4 neurosurgeons at the Department of Neuro-oncology of the Clinical Center of Serbia. Patient demographics, clinical preoperative features, extent of resection, postoperative treatment modalities, date of progression or reoperation, salvage chemotherapy, and date of latest follow-up

Tumor Features

In the entire cohort, 4 (3.6%) patients had involvement of the basal ganglia, 2 (1.8%) had involvement of the corpus callosum, and 2 (1.8%) had involvement of the insula. Multicentric tumors (>2 lobes involved) were present in 19 (17.3%) patients, whereas 22 (20%) patients had GBM in 2 lobes. GBM involved the temporal lobe and occipital lobe in 26 (23.6%) patients, the frontal lobe in 21 (19.1%) patients, and the parietal lobe in 12 (10.9%) cases. Finally, there were 2 rare localizations: 1 in

Discussion

TMZ is a second-generation alkylating cell cycle–nonspecific agent and has been available in Serbia since 2011 for treatment of glioblastoma. Cytotoxicity of this agent is borne through DNA methylation, which results later in the failure of mismatch repair mechanisms. A number of factors can influence the cellular response to TMZ, and MGMT is one of the most important. Compared with traditional alkylating agents, such as nitrosoureas, the effects of TMZ response in malignant glioma have been

Conclusions

Significant survival benefits have been achieved with the introduction of the Stupp protocol in the management of patients with GBM at the Clinic of Neurosurgery in Belgrade. However, in our series, the adoption of the Stupp protocol had favorable impact on OS rate but not on PFS rate. We noted that a safe and wide surgical resection involving the peritumoral brain zone permitted a longer PFS in both groups analyzed, as also confirmed by the univariate and multivariate analyses. We would like

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    Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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