Brief overview
- Prognosis: Glioblastoma is not curable. The prognosis depends, for example, on the health of the patient and the stage of the tumor. Survival time varies from a few months to several years.
- Symptoms: Headaches especially at night and in the morning, nausea and vomiting, speech disorders or epileptic seizures, coma
- Diagnosis: Physical, neurological and neuropsychological examinations, magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET).
- Treatment: surgery, chemotherapy and radiotherapy.
What is glioblastoma?
Most often, the tumor forms in one cerebral hemisphere and quickly grows across the bar into the other cerebral hemisphere. Its shape then resembles a butterfly, which is why it is sometimes descriptively called a “butterfly glioma”.
Primary and secondary glioblastoma
The tumor cells of glioblastoma are derived from special cells of the central nervous system called glial cells. They perform many important functions. For example, they hold the nerve cells in position and supply them with nutrients. Depending on the exact origin, a distinction is made between a primary and a secondary form of tumor:
- Secondary glioblastoma: It develops from a brain tumor of lower WHO grade. In this case, the glioblastoma is the final stage of a tumor disease with a longer course. The peak age of those affected is between the ages of 40 and 60.
“IDH-mutated”, by the way, stands for a punctual change in a specific gene, more precisely of the enzyme isocitrate dehydrogenase-1 or -2 gene. This enzyme is involved in cell metabolism. Physicians specifically look for an IDH mutation in all brain tumors in order to classify them accordingly.
Frequency of glioblastoma
To date, no recognized preventive or early detection measures are available.
Glioblastoma: Special variants
In rare cases, special variants of glioblastoma are distinguished: gliosarcoma, giant cell glioblastoma, and epithelioid glioblastoma. They have characteristically altered tissue properties – but diagnosis, therapy and prognosis are the same for all variants. The same applies to glioblastomas in children.
Life expectancy and quality of life are also subject to individual factors. The tumor cells do not have the same characteristics in every affected person. Some can be treated better than others. If the tumor shrinks quickly under therapy, the prognosis for glioblastoma is better than in other cases.
As a result, affected individuals influence the course of glioblastoma themselves to a certain extent: they accept a shorter lifespan if this improves their quality of life with the glioblastoma.
How does a glioblastoma manifest itself?
As with almost all diseases of the brain, the symptoms of glioblastoma depend primarily on the exact location of the proliferating tissue. Thus, depending on the brain region, completely different symptoms appear.
The headache typically occurs during the night or in the early morning hours and improves during the day. Unlike ordinary headaches, they return with increasing severity over time. Medications often remain ineffective.
If the glioblastoma grows, the intracranial pressure increases. Affected people therefore often feel nauseous, especially in the morning. Some have to throw up. If the pressure continues to rise, those affected often appear tired or sleepy. In extreme cases, a glioblastoma causes comatose states.
How does a glioblastoma develop?
Just like other cells in the body, they renew themselves regularly. In the process, errors occur in a glioblastoma that lead to uncontrolled cell growth and eventually to a tumor.
Risk factors for glioblastoma
Why glioblastoma develops is still poorly understood. However, there are a number of factors that increase the risk of developing glioblastoma:
Hereditary disease patterns: Glioblastomas usually occur sporadically, meaning they are not hereditary in most cases. However, there are a number of genetic disorders in which brain tumors generally develop more frequently:
- Neurofibromatosis (NF): rare, hereditary disease associated with benign tumors in the nervous system.
- Turcot syndrome: hereditary disease associated with a large number of polyps in the intestine
- Lynch syndrome: leads to a hereditary accumulation of cancers of the digestive organs
- Li-Fraumeni syndrome: very rare disease caused by a germline mutation of a tumor suppressor gene; occurs early in life and is associated with a number of different tumors
However, IARC – the World Health Organization’s International Agency for Research on Cancer – has listed radiofrequency fields as a possible carcinogen since 2011. A new assessment is planned, especially since studies conducted after 2011 have so far not confirmed the initial indications.
What examinations are performed for glioblastoma?
The doctors’ goal is to classify the brain tumor as accurately as possible – in other words, to determine at what stage it is, where exactly it is located, and what individual characteristics the tumor tissue has. This is the prerequisite for planning the optimal treatment.
Medical history
To take the patient’s medical history, the doctor first asks in detail about the symptoms and the course of the disease over time, as well as about any underlying or previous diseases.
The KPS is a largely subjective assessment, although results of physical examinations and laboratory values are also included in the consideration.
The KPS ranges from zero to one hundred percent, with 30 percent indicating severe disability status and 90 percent reflecting minimal symptoms with normal activity. Depending on the KPS, the treating medical team plans the next course of action according to the individual’s physical condition.
Neurological examination
Experts refer to this as a so-called standardized test battery, which is intended to shed light on many cognitive abilities as close to real life as possible. The physician uses the following tests, for example:
Montreal Cognitive Assessment (MoCa): The MoCa is also an appropriate test to assess deficits due to brain tumor disease. It takes about ten minutes and makes it possible to detect mild cognitive impairment.
Imaging procedures
Often, the symptoms appear suddenly and indicate quite clearly a pathological event in the brain. As a result, the physician promptly arranges for an imaging examination.
- Computed tomography (CT): If an MRI is not possible for certain reasons (for example, in the case of pacemaker wearers), doctors perform a CT scan as an alternative imaging procedure (also with contrast medium).
Biopsy
If a brain tumor is easily accessible, doctors remove it surgically (resection). Under certain circumstances, this is not possible, for example if the person affected is severely weakened anyway. In this case, doctors selectively remove a tissue sample (stereotactic biopsy).
The tumor tissue is then examined in the laboratory by specialists called pathologists. Only then can the tissue characteristics be precisely determined and a glioblastoma finally classified.
O-6-methylguanine-DNA methyltransferase (MGMT) is an important DNA repair enzyme. This means that it repairs damage to the genetic material. The MGMT promoter is the corresponding section of the genome that stores that information (blueprint) of the MGMT repair enzyme.
How is glioblastoma treated?
The treatment of choice for glioblastoma is radical surgery (resection). This is usually followed by radiation and chemotherapy. In some circumstances, doctors may use what are called tumor therapy fields (TTF).
The exact treatment depends on the age of the patient and his or her physical condition. In addition, the exact tissue characteristics of the tumor play a role.
Glioblastoma surgery
Doctors try to remove the tumor tissue as completely as possible and to spare healthy tissue. For this purpose, for example, various image recordings are made during the operation. This enables surgeons to orient themselves more easily in the brain (neuronavigation). If resection is not possible, doctors at least take a tissue sample.
Radiation and chemotherapy
In most cases, those affected receive chemotherapy with the active ingredient temozolomide at the same time. This is radiochemotherapy, which usually lasts six weeks. Radiation is administered in several sessions. Temozolomide is taken daily. Radiochemotherapy is usually followed by chemotherapy alone for several months.
Adjusted glioblastoma treatment
In elderly individuals, radiotherapy sessions may be reduced (hypofractionated radiotherapy). If the individual is not in good physical condition, physicians are more likely to perform chemotherapy alone (MGMT methylated) or radiation alone (MGMT unmethylated).
Tumor therapy fields
For TTFields treatment, the doctor sticks special ceramic gel pads onto the shaved scalp, creating a kind of hood. Alternating electric fields then build up across these pads. This prevents the tumor cells from dividing further and instead, at best, from dying.
In addition to TTFields treatment, individuals with the disease continue to take the drug temozolomide.
Cost coverage TTFields
Since May 2020, statutory health insurers have covered treatment with TTFields for people with newly diagnosed glioblastoma. The prerequisite is that the tumor does not grow again (early) after radiochemotherapy has been completed. To rule this out, doctors arrange for a magnetic resonance imaging (MRI) of the head beforehand.
(Still) No standard therapy
According to current medical guidelines, treatment with tumor therapy fields is not (yet) to be considered standard therapy for glioblastoma. For this, further independent studies are first necessary. These should, among other things, confirm the promising results of the pivotal study.
In a statement, experts from the Institute for Quality and Efficiency in Health Care (IQWiG) positively assessed the additional benefit of the combined therapy. The Federal Joint Committee (G-BA) followed this assessment and included the treatment option in the benefits catalog of the statutory health insurers.
Possible side effects
Overall, TTFields treatment is considered to be well tolerated. The most common side effects recorded in the pivotal study were skin irritations caused by the pads (redness, rarely itching or blisters).
In a statement, the IQWiG experts also point out that it is possible that some patients may feel restricted in their daily lives by the prolonged daily use of the wired pads.
If a tumor returns after a completed therapy or if the glioblastoma grows under an ongoing treatment, the medical team decides individually on a renewed operation, radiation therapy or chemotherapy. In the latter case, other substances are used in addition to temozolomide, for example the cytostatic drug lomustine (CCNU) or the antibody bevacizumab.
Alleviating the symptoms of the disease
Since glioblastoma has a very poor prognosis, the disease is difficult to cope with for many affected persons and their relatives. Psychotherapy, pastoral care or self-help groups may provide support here.
