Glioblastoma: changing expectations?

Glioblastoma (GB) represents the most aggressive glioma in the adult population. Despite recent research efforts, the prognosis of patients with GB has remained dismal. Lately, the knowledge of genetic information about gliomagenesis has increased; we even have a classification of the genetic expression of the tumour. The main problem is that at the moment we do not have any therapeutical resources to help us better treat these tumours, as we can do, with others tumours like breast, lung and colorectal cancer. We have also improved on diagnostic imaging, especially with the new MRI sequences; we can now better define the characteristics of the tumour area and the surrounding brain structures, allowing us to adjust resections. Thanks to the most advanced surgery techniques, such as neuronavigation, intraoperative control of the nervous function and the tumour volume, the neurosurgeon is able to complete tumour exeresis with less morbidity. These imaging techniques allow the radiation oncologist to better contour the irradiation target volume, the structures and the organs at risk, to diminish the irradiation of apparently healthy tissue. Nowadays, knowledge of brain stem cells provides new expectations for future treatments. Novel targeted agents such as bevacizumab, imatinib, erlotinib, temsirolimus, immunotherapy, cilengitide, talampanel, etc. are helping classical chemotherapeutic agents, like temozolomide, to achieve an increase in overall survival. The main objective is to improve median overall survival, which is currently between 9 and 12 months, with a good quality of life, measured by the ability to carry out daily life activities (AU)

[S100 protein in tumours of the central nervous system]. / Proteína S100 en tumores del sistema nervioso central.

OBJECTIVE: S100 protein has been detected in glials cells. The subject of this study is to evaluate the usefulness of serum levels of S100 as tumor marker for the screening diagnosis and follow up in patients with CNS tumors. PATIENTS AND METHODS: 57 patients were studied with tumors of the CNS: 24 multiform glioblastomas (GM), 11 anaplastic astrocytomas (AA), 3 oligodedrogliomas, 1 pinealoblastoma, 3 neurinomas, 1 low grade glioma and 13 brain metastasis of other extraneural primary tumors. 25 healthy people have been taken as control group. The S100 was analyzed by an immunoradiometric assay (IRMA) with 125 Iode. The cut off value was 0.2 g/L. RESULTS: The presurgical mean serum values of S100 didn t differ of the mean values of the control group (0.08 and 0.07 g/L, respectively). In the surgical treated patients with residual tumoral or recurrent tumors, the values of S100 increases to 38.9% in GM, 57.11% in AA and 76.9% in brain metastasis. In GM the serum values are significantly higher in patients with active tumor before receiving treatment with chemotherapy, radiotherapy or radiosurgery (p < 0.05). The values decreses to normal levels after response to oncological therapies. During the follow up (mean 551 days), the global sensitivity of S100 for progression of the disease was 47.5% and specificity was 90% with a correspondence between S100 and disease s evolution of 56%. CONCLUSIONS: S100 protein is not useful in the initial diagnosis of tumoral disease but it could be of help in the follow up of the disease because it decreases with successful treatments and increases at the time when the tumor progress.

Proteína S100 en tumores del sistema nervioso central / S100 protein in tumours of the central nervous system

Objetivo. La proteína S100 se detecta en las células gliales. El propósito de este estudio es evaluar la utilidad de la S100 sérica como marcador tumoral en el diagnóstico, seguimiento y monitorización de pacientes con tumores del sistema nervioso central (SNC). Pacientes y métodos. Se han estudiado 57 pacientes con tumores del SNC: 24 glioblastomas multiformes (GM), 11 astrocitomas anaplásicos (AA), tres oligodendrogliomas, un pinealoblastoma, tres neurinomas,ungliomade bajo grado y 13 metástasis cerebrales de otros tumores primarios. Se ha analizado la S100 en 25 personas sanas que se han tomado como grupo control. La determinación de S100 se ha realizado mediante un ensayo inmunorradiométrico (IRMA) con yodo 125, y se ha tomado como valor de corte 0,2 µg/L. Resultados. Los valores medios de la concentración sérica de S100 preoperatorios no difieren de los del grupo control (0,08 y 0,07µg/L, respectivamente). En los pacientes operados con restos tumorales y en los pacientes recidivados, la S100 se eleva: 38,9 por ciento en los GM, 57,11 en los AA y 76,9 por ciento en las metástasis cerebrales de otros tumores. En los GM, los valores séricos de S100 se elevan más significativamente en los pacientes con tumorantes de recibir tratamiento con quimioterapia, radioterapia o radiocirugía (p < 0,05). Los valores se normalizan con la respuesta a las terapias. Durante el seguimiento (media de 551 días), la sensibilidad global de la S100 para la progresión de la enfermedad fue del 47,5 por ciento, con una especificidad del 90 por ciento y una concordancia de S100 con la situación de la enfermedad del orden del 56 por ciento. Conclusiones. La S100 sérica no es útil en el diagnóstico inicial del tumor, pero podría ayudar en el seguimiento de la enfermedad, ya que su concentración disminuye con los tratamientos efectivos y se eleva cuando la enfermedad progresa (AU)

Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group.

PURPOSE: To determine the antitumor efficacy and safety profile of temozolomide in patients with malignant astrocytoma at first relapse. PATIENTS AND METHODS: This open-label, multicenter, phase II trial enrolled 162 patients (intent-to-treat [ITT] population). After central histologic review, 111 patients were confirmed to have had an anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma. Chemotherapy-naive patients were treated with temozolomide 200 mg/m(2)/d. Patients previously treated with chemotherapy received temozolomide 150 mg/m(2)/d; the dose could be increased to 200 mg/m(2)/d in the absence of grade 3/4 toxicity. Therapy was administered orally on the first 5 days of a 28-day cycle. RESULTS: Progression-free survival (PFS) at 6 months, the primary protocol end point, was 46% (95% confidence interval, 38% to 54%). The median PFS was 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and 12-month survival rates were 75% and 56%, respectively. The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35% (8% complete response [CR], 27% partial response [PR]), with an additional 26% of patients with stable disease (SD). The median PFS for patients with SD was 4.4 months, with 33% progression-free at 6 months. Maintenance of progression-free status and objectively assessed response (CR/PR/SD) were both associated with health-related quality-of-life (HQL) benefits. Adverse events were mild to moderate, with hematologic side effects occurring in less than 10% of patients. CONCLUSION: Temozolomide demonstrated good single-agent activity, an acceptable safety profile, and documented HQL benefits in patients with recurrent AA.