Influence of Oncotherapy and Clinical Parameters on Survival of Glioblastoma Patients: A Single Center Experience.

BACKGROUND: Routine administration of temozolomide (TMZ) in the treatment protocol of glioblastoma in the last few years resulted in improving survival parameters of these patients but efficacy of supplementary bevacizumab (BVC) monotherapy has not been evidently proven. In this study, the effectiveness of different postoperative therapy for glioblastoma patients treated in our institute was evaluated. In addition, the prognostic value of clinical parameters on survival was also analyzed. METHODS: Accordance of clinical parameters (age, gender, tumor localization, size, side, Karnofsky performance score, and extension of tumor removal), postoperative treatment (radiotherapy [RT], RT + TMZ, RT + TMZ + BVC), and survival data were tested by 104 patients operated on glioblastoma in the Department of Neurosurgery, University of Debrecen between 2002 and 2012. RESULTS: Concurrent chemo-RT resulted in significant longer overall survival (OS) than RT alone (PRTvs.RT + TMZ = 0.0219) and BVC treatment after progression during TMZ also elongated survival significantly (PRT vs. RT + TMZ + BVC < 0.0001; PRT + TMZvs.RT + TMZ + BVC = 0.0022), respectively. Clinical parameters showed no significant influence on OS in comparison with different methods of postoperative oncotherapy. CONCLUSIONS: Both TMZ and BVC had a beneficial effect on glioblastoma patients' survival, but tested clinical parameters showed no evident accordance with final outcome. Although neurosurgery has an indispensable role in resecting space occupying tumors and providing good postoperative performance score patients for oncotherapy, the survival of glioblastoma patients depends rather on radio- and chemo-sensitivity than tested clinical parameters.

Differences in Extracellular Matrix Composition and its Role in Invasion in Primary and Secondary Intracerebral Malignancies.

BACKGROUND/AIM: The most common malignant primary brain tumor is glioblastoma which infiltrates the peritumoral brain, while secondary brain metastases are well demarcated malignancies. Previous research has proved the pivotal role of the changes in the extracellular matrix (ECM) in cancer cell invasion. MATERIALS AND METHODS: The mRNA expression of 40 ECM molecules was determined using qRT-PCR in 54 fresh-frozen glioblastoma and brain metastasis samples. Seventy-two samples were used to determine the levels of 20 ECM proteins. RESULTS: The mRNA and protein expression pattern of the studied tumors differs greatly. Linear discriminant analysis of mRNA expression identified samples based on their mRNA expression profile with 92.3% probability and highlighted the role of some molecules as their level greatly influenced sample identification. CONCLUSION: Different tumor types with different invasiveness differ in the composition of their ECM and this can be used to identify samples. Furthermore, some ECM molecules greatly contribute to tumor invasiveness and could be targets of anti-invasive oncotherapy.

[The role of extracellular matrix components in the invasion of intracranial malignancies]. / Az extracelluláris mátrix komponensek tumorinvázióban betöltött szerepe intrakraniális daganatokban.

The usual local recurrence of primary brain tumors is mainly due to the infiltration of adjacent brain parenchyma by the glioma cells. This invasive feature of the tumors makes total surgical excision impossible and also decreases the efficacy of focal radiotherapy. Interestingly, intracerebral metastases originating from many anaplastic tumors of other organs perform very moderate peritumoral infiltration, therefore radical resection can be routinely achieved and focal irradiation, even stereotactic radiotherapy, provides good tumor control. Differences in the effectiveness of treatment between the two tumor types derive from the remarkably different extent of peritumoral infiltration. Thus significant molecular biological research has been dealing with the infiltrative activity of various brain tumors and many attempts were made to develop anti-invasive drugs for oncotherapy. This review summarizes the results of these studies, describing cellular and molecular events of brain tumor invasion and according potential oncotherapeutic possibilities.

Brevican, neurocan, tenascin-C and versican are mainly responsible for the invasiveness of low-grade astrocytoma.

The extent of tumor removal determines the effectiveness of postoperative oncotherapy. This is especially true for primary brain tumors, where peritumoral invasion usually makes radical resection impossible. The aim of the study was to determinate the specific expression pattern of invasion related molecules of different intracranial tumors and to identify molecules that are principally responsible for the peritumoral invasiveness of grade II astrocytoma mRNA expression of 26 extracellular matrix (ECM) molecules was determined in tissue samples from grade II astrocytoma, schwannoma, intracerebral metastases of non-small cell lung cancer and normal brain. Immunohistochemical staining for brevican, neurocan, tenascin-C and versican was also performed for each tumor group. Comparing astrocytoma to metastasis, schwannoma and normal brain; and metastasis and schwannoma to normal brain, 22, 17, 20, 21, and 19 molecules, respectively, were found to be significantly overexpressed at the mRNA level. Cluster analysis of mRNA expression showed a specific gene expression pattern for each histological group. Four molecules of 26 were found to be associated to astrocytoma. Immunohistochemical staining confirmed the results of the mRNA analysis at the protein level. Tumors of different origin have a specific invasive phenotype that can evidently determinate on gene expression level. This characteristic expression pattern of the invasion-related molecules might help to screen exact targets for anti-invasion drugs. In case of low-grade astrocytoma. brevican, neurocan, tenascin-C and versican were found to correlate principally with the invasive phenotype of low-grade astrocytoma, thus these molecules can potentially serve as targets for anti-invasion therapy in the future.