Brain Tumor - Glioblastoma
Magnetic resonance imaging (MRI) is the gold standard non-invasive imaging approach to test whether someone has glioblastoma (Urbanska 2014; Batash 2017; Rees 2011). This test uses a magnetic field and radio waves to generate images of the brain. It can not only find tumors but also provide information that helps guide treatment decisions (NCCN 2016; Mullen 2017). Some imaging tests use a dye called gadolinium, which is injected into a patient's vein. This dye provides what is referred to as “contrast” and helps distinguish tumor tissue from normal tissue. Patients with suspected glioblastoma may have MRI scans both with and without contrast (Davis 2016; Felix 1985).
Other types of imaging tests may be used to complement MRI findings. One of these tests, called MR perfusion, can measure blood flow in tumors and requires a contrast dye (NCCN 2016; Abrigo 2018). Another imaging test called MR spectroscopy couples MRI scans with tests to determine what kinds of chemicals are present in the tumor and in the normal surrounding tissues (NCCN 2016; Mullen 2017).
A computed tomography (CT) scan is an imaging test usually reserved for patients who cannot undergo an MRI for various reasons (NCI 2018). For example, patients with pacemakers, or those with certain kinds of cardiac monitors or surgical clips are not candidates for MRI because of the magnetic fields that MRI requires (NCCN 2016). CT scans use X-rays instead of magnetic fields and are also done with and without contrast to provide detailed pictures of the brain.
Additional, more sophisticated imaging tests may be needed to distinguish glioblastomas from cancers that spread from other body parts to the brain (Kamson 2013; Fink 2013; Neska-Matuszewska 2018).
Although MRI and CT scans can provide valuable information regarding the features of glioblastoma, actual brain tissue is required for a definitive diagnosis (NCI 2018; Urbanska 2014). During a procedure called a biopsy, a small sample of the brain tumor tissue is removed for further analyses under a microscope (NCI 2018; NCCN 2016). The tumor tissue from a biopsy is analyzed by a doctor called a pathologist. In addition to confirming glioblastoma, the pathologist may also request a molecular analysis of the tumor (Davis 2016).
Some tumors are biopsied during a surgical procedure (NCI 2018; NCCN 2016). For those patients, the tumor may be removed at the same time. For brain tumors located in parts of the brain that are difficult to reach or in areas that are vital for survival, a stereotactic biopsy is preferred. This method uses fine computer-guided instruments and produces less trauma. However, about 2% of stereotactic biopsies result in hemorrhages that impair brain functioning (DeAngelis 2012; NCCN 2016).
Biomarker-Guided Treatment Decisions
Temozolomide (Temodar), a type of drug called an alkylating agent, causes damage to the DNA of cancer cells. The MGMT gene encodes a DNA repair protein (NCI 2018). When the MGMT protein is abundant in cancer cells, the cells can repair the damage caused by temozolomide and survive.
In some glioblastomas, the MGMT gene is inactivated in a process called DNA methylation (NCCN 2016). These tumors have very little or no MGMT protein available to repair the damage caused by temozolomide. As a result, these tumors tend to respond well to temozolomide (Thomas 2017).
Temozolomide usually has to be given in high doses, and prolonged administration may lead to side effects, which may be more severe in older patients (Lee 2017; Saito 2014; Straube 2017). Testing a patient’s tumor for MGMT methylation has become a valuable biomarker to predict their response to temozolomide, and can help them and their doctors decide whether they are good candidates (Fernandes 2017; Snyder 2017; Seystahl 2016). Patients without MGMT methylation might be better candidates for other therapies, such as radiation therapy instead (Malmstrom 2012; NCCN 2016; Thon 2013; Hau 2016).
Another part of the diagnostic process involves gathering information on a patient's prognosis, which is an estimation of the likely course of his or her disease. A small group of prognostic factors associated with improved patient outcomes have been identified for patients with glioblastoma (Theeler 2015):
- Age 50 or less (Lacroix 2001)
- A score of 70 or more on an assessment tool for functional impairment called the Karnofsky Performance Scale (KPS) Index (lower scores indicate greater levels of impairment) (Lacroix 2001)
- A tumor not located in an “eloquent” brain location, including areas involved in speech, vision, movement, the thalamus, basal ganglia, and internal capsule (Theeler 2015; Awad 2017)
- A tumor that can be completely or almost completely removed in surgery (Lacroix 2001; Li, Suki 2016)
- Molecular features of the tumor, such as MGMT methylation or mutations in a gene called IDH1 (Theeler 2015; NCCN 2016; Chen 2017)