Long-term survival in glioblastoma Professor Dr Michael Weller and Dr Caroline Happold Zurich, Switzerland, for the EORTC 1419 study team
GLIOBLASTOMAS are malignant primary brain tumors and range amongst the most lethal cancer types in adults. They account for almost 50% of all brain tumors in adults, affecting three out of 100,000 patients per year, mostly in the later period of life. Glioblastomas invade the brain by infiltration, thus leading to significant destruction of healthy tissue and consequently neurological symptoms, including considerable loss of quality of life. This aggressive tumor also leads to a significantly shortened survival, and unfortunately, almost half of the patients diagnosed with glioblastoma pass away in the first year of diagnosis. The use of a multimodal therapeutic approach, involving surgery, radiotherapy and a variety of chemotherapeutic agents aims at prolonging overall survival, but often only increases life span for a few additional months. Yet, a small percentage of up to 5% of all patients suffering from glioblastoma may survive for more than five years. These are often, but not exclusively, younger patients with gross total tumor resection, whose tumors exhibit some prognostically favorable molecular features, such as mutations of isocitrate dehydrogenase (IDH) or methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter. This subgroup of patients is referred to as long-term survivors. However, other determinants of long-term survival have yet to be identified. To determine a maximum of factors that might influence long-term survival in glioblastoma patients is the goal of a large international multicenter study generously supported with USD $2,000,000 by the Brain Tumor Funders’ Collaborative, a strategic partnership among private philanthropic and advocacy organizations in the US and Canada composed of five members: 20
Brain Tumour
Above: Prof Dr Michael Weller, Department of
Above: Dr Caroline Happold, Department of
Neurology, University Hospital Zurich, Switzerland
Neurology, University Hospital Zurich, Switzerland
American Brain Tumor Association Brain Tumour Foundation of Canada n Children’s Brain Tumor Foundation n James S. McDonnell Foundation n Sontag Foundation
To date, more than 150 patients, alive and deceased, have been registered to the EORTC database, and the long-term survivors identified so far are overall of younger age, with a median age below 50 years. More than half of all patients were alive at the time of registration. Therefore, assessment of the total numbers of chemotherapeutic courses, surgeries at recurrence, or overall radiation doses in the course of the disease, as well as follow-up imaging data - which is collected in a separate platform and analyzed for tumor growth and recurrence pattern by different imaging tools - are still ongoing. All registered patients receive a mandatory central review of the pathological diagnosis, confirming the histology on one hand, and allowing for further molecular analysis and biomarker information on the other hand. In the currently analyzed tissue sample set, MGMT promoter methylation already emerges as a significant parameter, with most of the investigated tumor samples exhibiting methylated MGMT promoter. The analysis of other molecular markers is ongoing. In a second step, the acquired information is later compared to a
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The study is conducted under the lead of the Brain Tumor Group of the European Organisation for Research and Treatment of Cancer (EORTC) in Brussels, Belgium, and the Brain Tumor Center at the University Hospital Zurich, Switzerland. A consortium of more than 20 sites in Europe, the United States and Australia is currently registering patients with a survival of more than five years from glioblastoma diagnosis to a large comprehensive database, collecting clinical disease characteristics including all information on tumor therapy and follow-up, as well as imaging data. First results of the clinical and histological analysis have recently been presented at the annual meeting of the Society for Neuro-Oncology (SNO), and several additional sites have asked to participate in this study since then, underlining the relevance and interest in the attempt to understand the course of this disease.