Prof. Dr. Mehmet Şenoğlu — Brain, Nerve and Spine Surgery
As a brain surgeon, glioblastoma is one of the most difficult diagnoses I have had to explain to my patients and their families throughout my career. The same questions fill the mind of everyone who hears this diagnosis: “What does this mean? What were the symptoms? Is there a treatment? How much life expectancy is there?” In this article, I want to explain glioblastoma through the most frequently asked questions, in language that is as clear and honest as possible while not letting go of hope. I must say at the outset: glioblastoma is a serious and challenging disease; however, treatment methods play an important role both in extending survival and in improving quality of life, and research in this field is advancing rapidly.
What Does Glioblastoma Mean? What Is Glioblastoma?
Glioblastoma is the most common and most aggressive primary brain tumor in adults, arising from the glial cells, which are the support cells of the brain. Being “primary” means it is a tumor that begins in the brain; that is, it is not a cancer that has spread to the brain from another organ (metastatic).
The most important feature of glioblastoma is that it grows by spreading with finger-like extensions into the surrounding healthy brain tissue. The tumor does not form a clear boundary around itself; for this reason, even with the most extensive surgery, a certain amount of tumor cells may be left behind at the microscopic level. This very feature explains why treatment does not end with surgery alone and why it requires a multifaceted approach.
What Does Glioblastoma Grade 4 (Stage 4) Mean?
One of the phrases people search for the most is “glioblastoma grade 4” or “stage 4 glioblastoma.” Here I would like to clarify an important point: unlike some other cancers, brain tumors are graded by the World Health Organization (WHO) from 1 to 4 not according to their degree of spread throughout the body, but according to the aggressiveness of the cells under the microscope.
In this classification, glioblastoma is always considered the highest grade, Grade 4. That is, “glioblastoma” and “grade 4” express practically the same level of aggressiveness; there is no grade 1, 2, or 3 of glioblastoma. The phrase “stage 4” is also used colloquially to describe the same situation.
What Do IDH Wild Type and IDH Mutant Mean?
The phrases “IDH wild type” and “IDH mutant,” frequently encountered in MRI or pathology reports, have in recent years become one of the most important parts of the diagnosis. According to the WHO classification updated in 2021, the term “glioblastoma” is now used specifically for IDH-wild type (no mutation in the IDH gene) Grade 4 tumors.
Tumors that were formerly called glioblastoma but are IDH-mutant are now classified as a separate group (“IDH-mutant astrocytoma, Grade 4”). The practical importance of this distinction is great: IDH-mutant tumors are generally seen in younger patients, and their course (prognosis) is markedly better than that of IDH-wild type glioblastoma. Therefore, this phrase in your report is critical information that directly affects the course of the disease and the treatment plan.
What Are the Symptoms of Glioblastoma?
The symptoms of glioblastoma vary according to which region of the brain the tumor is in and its rate of growth. Complaints that develop rapidly, generally within weeks, draw attention. The most commonly seen symptoms are:
- Headache: an unusual, increasing headache that is especially more severe in the mornings (due to increased intracranial pressure).
- Seizure (epilepsy): a seizure appearing for the first time in an adult who has never had one before can be an important warning sign.
- Nausea and vomiting: vomiting that especially accompanies a headache and may be related to increased intracranial pressure.
- Neurological losses: weakness in an arm or leg, speech impairment, vision problems, or loss of balance.
- Personality and cognitive changes: memory problems, behavioral changes, confusion, or noticeable changes in personality.
Each of these symptoms can also stem from many other, far more common and benign causes. However, especially in situations that develop rapidly, that increase progressively, or where several of the above are seen together, a doctor must be consulted.
What Causes Glioblastoma? What Are the Risk Factors?
One of the questions my patients ask most often is “Why me?” or “What caused this?”, and the honest answer is most often unsatisfying: in the great majority of glioblastoma cases, a specific, single cause cannot be found. Most patients have no significant hereditary or environmental risk factor.
A few known factors are:
- Advanced age: it is most often seen between the ages of 65 and 75; more than half of patients are over the age of 64 at the time of diagnosis. However, it can be seen at any age.
- Previously received radiation: having previously had high-dose radiotherapy to the head region is a rare risk factor.
- Some rare genetic syndromes.
Here I would also like to correct a piece of misinformation: there is no scientifically proven, definite link that cell phone use causes glioblastoma.
How Is Glioblastoma Diagnosed?
The first step in the diagnostic process is generally MRI (magnetic resonance imaging); glioblastoma shows certain typical features on an MRI. However, imaging alone does not provide a definitive diagnosis. The definitive diagnosis is made by the pathological examination of a tissue sample taken from the tumor (a biopsy or tissue removed during surgery).
Today, this examination is not limited to microscopic evaluation alone; the molecular and genetic features of the tumor (such as IDH status and MGMT methylation) are also investigated. These tests are of great importance both for the definitive diagnosis and for shaping the treatment plan according to the individual.
How Is Glioblastoma Treated?
Glioblastoma treatment is carried out not with a single method, but with a multifaceted, team-based approach. The standard treatment (known as the Stupp protocol), in which brain surgery, radiation oncology, and medical oncology work together, consists of the following steps:
1. Surgery (Operation)
If the patient’s condition is suitable, the first step is the removal of the tumor as extensively as possible, safely. The aim here is to remove as much of the tumor as possible without harming the brain’s important functions. Because the tumor has spread to the surrounding tissue, surgery alone cannot completely eliminate the disease; however, reducing the tumor burden increases the effectiveness of subsequent treatments and relieves complaints.
2. Radiotherapy and Chemotherapy
After surgery, radiotherapy is applied to target the microscopic tumor cells that may be left behind. This process is generally accompanied by temozolomide, a chemotherapy drug taken orally. After the radiotherapy is completed, temozolomide is continued in certain cycles. Here, the MGMT methylation I mentioned earlier is important; tumors carrying this feature generally respond better to temozolomide.
3. Tumor Treating Fields (TTF / Optune)
In some suitable patients, a method that uses electrical fields, aiming to prevent the division of tumor cells through electrodes placed on the head (Tumor Treating Fields), can also be added to the treatment.
Treatment in Case of Recurrence
To be honest, glioblastoma, despite appropriate treatment, most often tends to recur after a while. In this case, options such as repeat surgery, repeat radiotherapy, different chemotherapy drugs (for example, lomustine or bevacizumab), and especially participation in clinical trials (clinical studies) are evaluated. The most correct and safe way to reach new treatments is not uncontrolled methods, but such scientific studies.
How Long Is the Survival Time for Glioblastoma (Grade 4)?
This is the most frequently asked and the most difficult question to answer. Here I want to be both honest and to convey accurately what the numbers mean.
In patients receiving standard treatment, the average (median) survival time is reported to be approximately 12–15 months. The five-year survival rate, on the other hand, is low; in real-world data it is around 5–7%. These numbers are challenging, I know.
However, I must emphasize this very strongly: these numbers are averages and do not show the definite fate of any individual. Survival time varies greatly from person to person and depends on many factors: the patient’s age and general state of health, how much of the tumor could be removed with surgery, molecular features such as MGMT methylation, and the response to treatment. In younger patients who are in good general condition and whose tumor carries favorable molecular features, the course may be markedly above the average. As a doctor, I, too, do not give any of my patients a definite duration with a single number; because a statistic is an average, while the person before me is a single human being.
Is There Anyone Who Has Survived or Recovered from Glioblastoma?
The questions “Is there anyone who has survived?” and “Has anyone recovered?” are the most searched, the most hopeful, and the most fragile questions of patients and their families. The honest answer is this: glioblastoma is today a disease for which achieving a complete “cure” (permanent recovery) is very difficult, and it most often tends to recur.
That said, patients who live for a long time (long-term survivors) do exist. Examples of survival lasting for years can be seen, especially in patients who have favorable molecular features, respond well to treatment, and are in good general condition. In addition, scientific research in this field — such as immunotherapy, targeted treatments, and vaccine studies — is advancing rapidly and holds promise. So, although the picture is challenging, it is hopeless neither medically nor in human terms.
Do Herbal and Alternative Treatments Work?
I know that on the internet many “herbal treatments,” special diets, or various supplements are presented as a “miracle solution” for glioblastoma; my patients ask about these often, too. Here, as my responsibility requires, I must be very clear: there is no herbal or alternative method scientifically proven to treat glioblastoma.
The greatest danger of such methods is that they cause patients to lose valuable time by drawing them away from proven standard treatment. In addition, some herbal products and supplements can disrupt the effect of the chemotherapy or radiotherapy you are receiving or lead to serious side effects. For this reason, I earnestly ask that you definitely consult the doctor managing your treatment before using any supplement or method. It is natural to hope; however, it is very important to ground this hope on a safe and proven basis.
A Note for Patients and Their Families
Glioblastoma is a process that affects not only a patient but an entire family. As a doctor, I see very closely the burnout, fear, and sense of helplessness that the families of patients experience. I want you to know that you are not alone on this path. Establishing open communication with the treatment team, not hesitating to ask questions, receiving psychological support, and benefiting from palliative care services (care aimed at increasing quality of life and comfort) can make carrying this process easier. Paying attention to the emotional health of both the patient and their family is as valuable as the medical treatment.
In Which Symptoms Should You See a Doctor Without Delay?
If one of the following situations appears, a doctor or the nearest emergency department should be consulted without delay:
- A seizure (convulsion) appearing for the first time, never having occurred before.
- An unusual headache that increases progressively and is especially more severe in the mornings.
- Sudden and progressive loss of strength in an arm or leg, speech impairment, or loss of vision.
- Unexplained nausea and vomiting accompanying a severe headache.
- Suddenly developing personality change, confusion, or a deterioration in the state of consciousness.
Frequently Asked Questions
Below, I have gathered the most frequently asked questions about glioblastoma along with brief answers. These answers are for general information; the information that applies to your specific situation is the one given by the doctor who examines you.
What does glioblastoma mean?
Glioblastoma is the most common and most aggressive primary brain tumor in adults, arising from the glial cells, which are the support cells of the brain. It is considered Grade 4, the highest grade in the WHO classification.
Are glioblastoma grade 4 and stage 4 the same thing?
Yes, in practice they express the same situation. Glioblastoma is always a Grade 4 (Degree 4) tumor, the highest level of aggressiveness; “stage 4” is also used colloquially to describe this. There is no lower grade of glioblastoma.
How long is the survival time for glioblastoma grade 4?
With standard treatment, the average (median) survival time is reported to be approximately 12–15 months; however, this is an average. The actual duration varies greatly from person to person according to the patient’s age, general condition, the molecular features of the tumor, and the response to treatment.
Is there anyone who has survived glioblastoma; does it heal?
Glioblastoma is a disease for which achieving a complete recovery is very difficult, and it generally recurs. That said, there are examples of patients who live for a long time, especially those who have favorable molecular features and respond well to treatment, and research in this field is advancing rapidly.
What are the symptoms of glioblastoma?
The most common symptoms are a progressively increasing headache, a seizure appearing for the first time, nausea and vomiting, weakness in an arm or leg, speech and vision impairments, and personality and memory changes. The symptoms generally develop rapidly, within weeks.
What does IDH wild type mean, and why is it important?
IDH-wild type means that the tumor does not carry a mutation in the IDH gene, and in the current classification the term “glioblastoma” defines this group. IDH-mutant tumors, on the other hand, are a separate group and their course is generally better. For this reason, the IDH status is critical information in terms of treatment and prognosis.
Do herbal treatments work for glioblastoma?
There is no herbal or alternative method scientifically proven to treat glioblastoma. Such methods can cause harm by drawing patients away from standard treatment; some supplements can also disrupt the effect of the treatment. You must definitely consult your doctor before using any supplement.
How is glioblastoma treated?
The standard treatment includes surgery, in which the tumor is removed as extensively as possible safely, followed by radiotherapy and temozolomide chemotherapy. In suitable patients, tumor treating fields (TTF) may be added. In the case of recurrence, repeat surgery, different drugs, and clinical trials are evaluated.
Disclaimer (Legal Notice)
The information contained in this article has been prepared for general informational purposes only and in no way replaces a medical examination, diagnosis, or treatment. The course of glioblastoma, its treatment, and the life expectancy vary greatly from person to person according to the molecular features of the tumor, the person’s age, and general state of health, and can only be determined by a team of doctors who evaluate you. For any decision regarding diagnosis, treatment, and the process, always consult a specialist physician. If the emergency symptoms mentioned above are present, go to the nearest healthcare facility without delay.