Not all Glioblastoma multiforme (GBM, grade IV WHO) manifest the same clinical course. Different prognostic classes may arise from different morphologic and genetic profiles. The observation of oligodendroglial foci within GBM samples and their correlation with genetic alterations may predict a better prognosis. 450 patients affected by histologically proven supratentorial cerebral GBM were treated at our institutions from January 2000 to December 2006: all patients received at least subtotal surgical removal, followed by the same standard radio-chemotherapy adjuvant treatment. In a subgroup of 36 patients (8.0%) an oligodendroglial component was observed. Molecular assessment of these cases was performed and LOH for 1p, 19q and 10q, EGFR amplification and TP53 gene expression was determined. Median age of this subgroup was 52.1 years (range: 29-78 years) vs 62.4 years in the entire GBM population. Chromosome analysis resulted as follows: LOH 1p and/or 19q in 27 cases (75.0%), LOH of 10q in 21 cases (58.1%), EGFR amplification in 14 cases (39%) and TP53 mutation in eight patients (22.2%). OS was of 20.9 months while it was 13.6 months in the entire GBM population. Progression free survival (PFS) was 10.3 months and 7.6 months the entire group. Two-year survival was of 55%. The presence of an oligodendroglial component in GBM appears to be an important prognostic factor to which better prognosis can be related. LOH 1p and 19q was significantly associated with GBM with oligodendroglial component.
Malignant gliomas are the most common primary brain tumors in adults. In the past 10 years significant advances in the treatment of this entity have been made, mainly owing to a better understanding of molecular pathways and biological behavior of the oncogenetic process. This review treats the proven effective and promising approaches with chemotherapy. The standard care for glioblastoma is surgery and concomitant radio- and chemotherapy with temozolomide (TMZ), followed by adjuvant treatment with TMZ. It has been demonstrated to be the most effective treatment protocol. This standardized care allows the application and study of new types of treatment mainly in recurrences and nonresponding patients. Many different approaches have been investigated: the combination of cytotoxic and cytostatic agents as well as molecular targeted therapies have given some encouraging results. Further intensified regimens with TMZ and the local postsurgical application of slow-release polymers loaded with carmustine remain to be defined. The characterization of molecular markers thus becomes particularly important for the stratification of patients raising the possibility to individualize treatment.
With the increasing number of cancer survivors, we can observe a population that will present a higher risk of developing secondary long-term toxicities related to adjuvant chemo and radiotherapy regimens. Among these, children surviving from acute lymphoblastic leukemia (ALL) that were treated with prophylactic cranial irradiation represent a group of patients at a high risk of developing secondary brain tumors. Radiation-induced intracranial tumors have been documented since 1950, and today, more than one-hundred cases have been described. We report our experience with two young patients who were hospitalized for low grade gliomas and had a positive anamnesis for ALL and consequent radiotherapy.
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