Definition of glioma
- Gliomas are a group of tumours of the central nervous system which differ according to the cells of origin in the brain (astrocytes or oligodendrocytes or both) and the grade of aggressiveness (from the least to the most aggressive: low grade glioma -> anaplastic glioma -> glioblastoma).
- Glioma can be suspected when a number of symptoms are present, such as seizures, changes in personality and behaviour, various types of neurological problems (including sight problems, difficulty in speaking, understanding what is said, loss of strength or feeling in a part of the body or gait changes), as well as symptoms associated with increased pressure in the head (headache, nausea, vomiting, and drowsiness).
- Magnetic Resonance Imaging (MRI) of the brain is the gold standard radiological test for the detection of a glioma. It also helps define the extent of the disease and indicates whether the tumour can be surgically removed safely.
- A piece of the tumour (taken either by surgical resection or by stereotactic/open biopsy in case surgical removal is not possible) must be obtained for analysis in the lab to confirm the diagnosis and get more details about the molecular characteristics of the tumour. Molecular characterisation may help define the exact subtype of glioma, gain information on the likely outcome of the diagnosis (“prognosis”) and help guide treatment decisions.
Surgery is the first treatment of choice for the majority of newly diagnosed gliomas; in fact, surgical removal as extensive as safely possible is associated with an improved outcome regardless of the subtype of glioma. After surgery, treatment differs according to the subtype of glioma.
- Low grade glioma (Grades 1 and 2)
o Radiotherapy is the standard post-operative treatment in patients whose disease characteristics suggest a high likelihood of return of the disease (called recurrence).
o Chemotherapy has a less defined role in low grade glioma. However, it can be used in patients who are not deemed eligible for surgery and/or radiotherapy or in tumours recurring after radiotherapy. Patients whose tumour shows a specific molecular characteristic (called ‘genetic loss on chromosomes 1p/19q’) appear to be particularly sensitive to chemotherapy, meaning there is more chance of chemotherapeutic benefit in these patients.
- Anaplastic glioma (Grade 3)
o Radiotherapy followed by chemotherapy is a standard post-operative treatment in anaplastic glioma.
o Radiotherapy alone may be used in anaplastic oligodendroglial tumours without genetic loss on chromosomes 1p/19q.
o Studies have shown that chemotherapy alone after surgery, and administering radiotherapy only at the time of disease progression, achieves the same results as radiotherapy applied after surgery and chemotherapy administered at the time of disease progression.
- Glioblastoma (Grade 4)
o Use of chemotherapy and radiotherapy in combination (‘concurrently’ or ‘concomittantly’) is the standard treatment after surgery in glioblastoma patients younger than 70 years as well as in older fit patients whose tumour tests positive for a specific molecular characteristic (presence of MGMT gene methylation).
o Radiotherapy alone is preferred in elderly (>70 years) patients who are not fit enough to receive concurrent chemo-radiotherapy and/or whose tumour is negative for the presence of MGMT gene methylation.
o Chemotherapy alone is the preferred treatment option in elderly unfit patients whose tumour is positive for MGMT gene methylation.
This guide for patients has been prepared by the Anticancer Fund as a service to patients, to help patients and their relatives better understand the nature of brain cancer and appreciate the best treatment choices available according to the subtype of brain cancer. We recommend that patients ask their doctors about what tests or types of treatments are needed for their type and stage of disease. The medical information described in this document is based on the clinical practice guidelines of the European Society for Medical Oncology (ESMO) for the management of brain cancer. This guide for patients has been produced in collaboration with ESMO and is disseminated with the permission of ESMO. It has been written by a medical doctor and reviewed by two oncologists from ESMO including the lead author of the clinical practice guidelines for professionals. It has also been reviewed by patient representatives from ESMO’s Cancer Patient Working Group.
Definition of glioma
Gliomas represent a group of malignancies that may arise anywhere in the central nervous system, (‘CNS’) meaning in the brain or, much less frequently, in the spinal cord (see illustration below). They are characterised by an infiltrative pattern of growth and/or a tendency for spreading locally within the CNS. Tumour spread to outside the brain usually does not occur.
Anatomy of the brain, showing the cerebrum, cerebellum, brain stem, and other parts of the brain. The upper part of the spinal cord is also represented.
Following histopathological examination, gliomas are usually named according to the type of nervous cells which they derive from (astrocytes, oligodendrocytes or ependymal cells).
The classification of gliomas follows a scale from I to IV (1 to 4), which reflects the rate of tumour growth as well as its aggressiveness. Grade I tumours, which occur mainly in childhood, are associated with the best prognosis. Grade II (low grade gliomas) represent slowly growing and infiltrative tumours with intermediate prognosis. On the other hand, grade III (anaplastic) and grade IV (glioblastoma) tumours are both considered to be high grade gliomas, as they are aggressive and generally have the least favourable prognosis. The present guide will focus on the management of low grade gliomas, anaplastic gliomas and glioblastoma. The table below provides an overview of the main types of glioma brain tumours according to the cell they derive from and the grade to which they belong.
|Cell of origin*||Name of tumour**||Grade||Comments|
|Astrocyte||Astrocytoma||I to IV||
Grades I and II are called low grade astrocytomas
Grades III and IV are called high grade astrocytomas
Grade III are also called anaplastic astrocytomas
Grade IV are also called glioblastomas
|Oligodendrocytes||Oligodendroglioma||II or III||
Grade II are called low grade oligodendrogliomas
Grade III are called high grade or anaplastic oligodendrogliomas
|Mixed (astrocyte and oligodendrocyte)||Oligoastrocytoma||II or III||
Grade II are called low grade oligoastrocytomas
Grade III are called high grade or anaplastic oligoastrocytomas
* Ependymal cells are a third type of glial cells. Rare tumours called ependymomas (grade I to III) can arise from these cells. Information on the treatment on these tumours is not covered in the current guide.
** There are many subtypes of these tumours. They are classified and named according to their specific features under the microscope and/or to their location in the brain. For instance, optic pathway gliomas are low-grade gliomas arising from astrocytes locating in the optic nerve or in the optic pathway.
Important note regarding other types of brain tumours
Secondary brain tumours, also called metastases to the brain
Cancers that initially developed in other organs of the body (e.g. in the lung or the breast), can spread to the brain. In this case, the ‘secondary’ tumour found in the brain is called metastasis as opposed to a primary brain tumour developing initially in the brain. The management of a brain metastasis is different from the management of a primary brain tumour.
Other types of primary brain tumour
Other brain tumours also exist. The most frequent other brain tumours are meningiomas which develop from the meninges and adenomas of the pituitary gland which develop from cells making the pituitary gland. Other types include ependymoma, primitive neuroectodermal tumour and medulloblastoma which are rare tumours arising mainly in children. The management of all these tumours is different from the management of gliomas and is therefore not covered in this guide.
Is glioma frequent?
Glioma is considered a rare cancer because it affects less than 6 out of 100,000 persons every year. Nevertheless, gliomas represent 80% of all tumours of the central nervous system. Gliomas can affect people of all ages including children, teenagers and young adults but are more frequent in people in their 50s and 60s. Worldwide, 3 women and 4 men out of 100,000 are diagnosed with a tumour affecting the central nervous system every year. In Europe, 5 women and 6 men out of 100,000 are affected every year. Europe has the highest rates per year. Within Europe, the highest rates are reported for Sweden and Albania (10 per 100,000), and the lowest in Cyprus and Moldova (less than 4).
On average, about one in every 150 European men and one in every 200 European women will develop a tumour of the central nervous system (of which 80% will be malignant glioma), at some point in their life.
What causes glioma?
Before addressing the risk factors that may predispose to the development of glioma, it is important to know that a risk factor increases the risk of cancer occurring, but is neither necessary nor sufficient on its own to cause cancer. A risk factor is not a cause in itself. Therefore, some people with one or more risk factors will never develop glioma and some people without any of these risk factors may nonetheless develop glioma.
Nevertheless, at the present time, it is not clear why glioma occurs, and very few risk factors have been identified. Generally speaking, gliomas are slightly more common in men than in women as well as in white rather than black populations. Recognised risk factors of gliomas are:
This is an established environmental risk factor, as documented by the observation that individuals exposed to atomic bombs and nuclear weapons testing have an increased risk of developing glioma. Individuals who have received cranial irradiation for cancer therapy during their childhood are also at increased risk of developing glioma years or even decades later.
A family history of glioma (meaning one or more cases of glioma in the same family) is associated with a 2-fold increase in the risk of developing a glioma.
A number of rare hereditary syndromes are associated with a higher risk of development of cancers in general, mainly as a result of the presence of one or multiple genetic alterations. Importantly, some of these hereditary syndromes may also carry a higher risk of glioma, such as Cowden syndrome, Turcot syndrome, Lynch syndrome, Li-Fraumeni syndrome, and neurofibromatosis type I.
Other factors have been suspected to be associated with an increased risk of glioma, but the evidence is inconsistent. This is the case with cell phone exposure, for which epidemiological studies (research into the patterns, causes and effects of specific health and disease populations) have failed so far to conclusively demonstrate an association with an increase in the risk of glioma. Evidence is also inconsistent for other factors once suspected to increase the risk of glioma such as head injury, aspartame, or exposure to pesticides.
How is glioma diagnosed ?
Signs and symptoms
Glioma can be suspected in the presence of different symptoms. Nevertheless, it is important to know that these symptoms largely depend on the type of glioma as well as on its exact location in the central nervous system.
The different lobes of the left hemisphere of the brain are represented in the illustration. The brain has two hemispheres and each lobe in each hemisphere is responsible for a multitude of functions. Therefore, the list of symptoms reported herein cannot be exhaustive. However, in an effort to generalize, the following signs and symptoms may be commonly present either alone or combined with each other both at first diagnosis or later on during the course of the disease:
These are among the most common, and often most distressing, symptoms of gliomas. Seizures are especially present in patients with slowly growing tumours such as low grade gliomas. A seizure can cause jerking or twitching of a hand, arm or leg. However, a seizure may also affect the whole body with quite violent and uncontrolled movements, possibly with losing consciousness. A seizure can be a very frightening event so it is important for carers or others witnessing a seizure not to panic. Knowing what to do when a person has a seizure can reduce fear and potential injury to the patient.
Neurological problems (known as ‘deficits’)
These largely depend on the lobe(s) of the brain that is (are) affected. Sight problems may be present if the occipital lobe (represented in blue) is involved. Difficulty in speaking or understanding what is said to you as well as loss of function (strength) or sensitivity (feeling) in a part of the body occurs when the frontal (in yellow) or parietal lobe (in red) is affected. Personality and behavioural changes such as apathy, loss of initiative, and loss of emotional control/loss of inhibition may occur if the frontal lobe (in yellow) is compromised. Finally, memory loss is often associated with involvement of the temporal (in green) lobe, while poor coordination or uncontrolled movement of the eyes can be present if the disease involves the ‘little brain’ (cerebellum). When glioma arises from the spinal cord, pain, numbness and/or weakness in the lower part of the body, and/or loss of control of the bladder or bowel may be present.
Symptoms that result from increased pressure in the brain
These symptoms are typical for high grade gliomas. They occur because the tumour grows rapidly in the brain which is contained inside the fixed space of the skull. This can result in headache, nausea, vomiting, double vision and drowsiness.
Thromboembolic events, which are the formation of clots in the blood stream, are often present in glioma patients. There are several possible reasons for this. Glioma patients often carry risk factors commonly associated with the development of thrombosis such as motor deficits and/or immobility, and, after diagnosis, treatment with chemotherapy. Symptoms associated with thrombosis largely differ according to the involved site, and their list is beyond the scope of this guide for patients.
Testing the central nervous system is the most important part of the clinical examination if a glioma is suspected or diagnosed. However, general physical examination (e.g. breast, abdomen, skin) is also important so that signs of a cancer somewhere else in the body can be excluded. With regard to neurological examination, the physician may ask a few questions, as well as perform some simple tests. Neurological examination usually includes:
- Testing your strength by asking you to squeeze the physician’s hands or push against the physician’s hand with your feet.
- Checking to see that you have normal sensation throughout the body
- Asking you to touch your nose with your finger while your eyes are shut
- Asking you to walk in a straight line
- Asking you to answer simple questions
- Asking you to follow a moving finger with your eyes
- Asking you about your hearing and sight
Radiological tests are crucial examinations which detect a glioma and define its exact location and extent. As glioma does not metastasise to distant organs, diagnostic imaging is limited to the brain.
CT-scan of the brain
This radiological test is often the first exam to be performed when a brain tumour is suspected. That is because a brain tumour usually shows up on this type of scan. The injection of contrast-medium, namely a dye that circulates in your bloodstream, before this test allows for a clearer picture of the brain. It is very important to tell your doctor if you have had previous allergic reactions to this contrast-medium.
MRI of the brain
MRI is the gold standard examination for the radiological diagnosis of glioma. As compared to CT-scan, MRI gives a much clearer picture of the brain. Similarly to CT-scan, MRI is performed following the injection of contrast medium. It is very important to tell your doctor if you have metal inside your body as this may mean you cannot have an MRI scan.
This is the laboratory examination of the tumour cells. It can be performed either on the tumour(s) removed by surgery or on biopsies coming from stereotactic procedures (see treatment options) of surgically inoperable gliomas. Importantly, histopathological examination is the only method that can definitively confirm a diagnosis of glioma. In general, the more tumour tissue is available, the more accurate the diagnosis is. However, histopathological examination can yield more precise results when carried out at experienced centres where pathologists (the medical specialists who examine your tissue after it has been removed) have particular experience of analysing brain tumours. Therefore, careful review of tumour cells by an expert neuropathologist is crucial.
What is important to know to get optimal treatment ?
Doctors will need to consider many aspects about you as the patient and your type of brain tumour in order to decide on the best treatment.
Relevant information about you
- Your age
- Your performance status, namely a measurement scale of your general condition that is influenced by the presence and severity of tumour-related symptoms
- Your personal and family medical history, including type and number of other diseases
- Results of your blood tests (e.g. white blood cells, red blood cells, platelets count, liver and kidney function).
Relevant information about your brain tumour
Histopathological examination of gliomas is the basis for guiding optimal treatment. In general, gliomas can be classified according to grade into low grade gliomas, anaplastic gliomas and glioblastoma. In addition, low grade and anaplastic gliomas can be further classified according to the type of cells they derive from, namely astrocytes, oligodendrocytes, or both. It should be noted that ependymomas, which are gliomas deriving from ependymal cells, also exist but treatment of ependymomas is not covered in the current guide.
This classification results in different treatment approaches as well as a different overall prognosis, normally based on statistics. Statistics are a tool used for comparing treatments and for describing what has happened in the past to groups of people with various tumour types. Statistics cannot predict exactly how long any individual person will live so patients should not necessarily consider statistics as a completely accurate indicator of their lifespan after diagnosis. Individual prognosis is best discussed, on a case by case basis, with brain tumour specialists. In order to provide a general idea on prognosis, we know from statistics that in general the lower the grade of the tumour, the better the prognosis. But there are exceptions to these statistics and there are even some very long term survivors of anaplastic astrocytoma and glioblastoma.
o Grade II oligodendrogliomas
o Anaplastic oligodendrogliomas (also called grade III)
o Grade II astrocytomas
o Anaplastic astrocytomas (also called grade III)
o Glioblastomas (also called grade IV)
In addition to grade and subtypes, other established prognostic factors include your age, your performance status, the possibility of resection of the tumour, your general condition and your cognitive function (a person’s mental abilities and processes). The recent advances in discovery of tumour markers (as explained below) have made it possible to predict a potentially better outcome for malignant glioma with specific tumour characteristics.
Molecular markers of the tumour
The following markers have to be taken into account for analysis by your physician because they can either provide information on the prognosis of the tumour or help guide treatment decisions.
o Genetic loss on chromosomes 1p/19q
The detection of this marker is important in order to ascertain the diagnosis of glioma with an oligodendroglial component (either pure oligodendroglioma or mixed oligoastrocytoma). Also, it identifies a tumour entity with a slower course of disease, and which shows particular sensitivity both to radiotherapy and chemotherapy.
o Mutation of the IDH gene 1 or 2
A mutation in this gene is often present both in low grade and anaplastic gliomas, where it is associated with a better survival regardless of treatment. Its presence in high grade gliomas (anaplastic gliomas or glioblastoma) suggests that these tumours developed from a previously low grade glioma. Therefore, high grade tumours with a mutation in the IDH gene generally have a better prognosis compared with high grade gliomas without IDH mutation.
o MGMT gene methylation
The presence of this marker reflects the inability of the tumour to repair the damage on the DNA produced by certain chemotherapies called ‘alkylating agents’, particularly temozolomide. Therefore, when this alteration is found in glioblastoma it suggests the tumour is more sensitive to temozolomide (see treatment options).
What are the treatment options?
Regardless of the glioma subtype, surgery (either surgical resection or stereotactic/open biopsy) represents an essential component of treatment of all newly diagnosed gliomas.
Surgical resection of the tumour is the preferred initial treatment for the majority of gliomas. Surgery is aimed to be as complete as possible. The reason for this is that maximal tumour resection has been shown to result in longer survival and allow for more effective post-operative therapies to be given. But if such radical surgery is expected to impair neurological function, it should be aimed just at removing as much tumour as is safely possible, sparing healthy tissues. In addition, surgical removal of the tumour provides a sufficient amount of tissue for both an accurate histopathological diagnosis and molecular characterisation of the tumour.
If surgery is not safely feasible, mainly due to tumour location (e.g. surgically inaccessible region or a region that carries a high risk for significant impairment of neurological function) or due to a deteriorated clinical condition, a stereotactic or open biopsy may be considered to obtain tissue for a diagnosis. A biopsy is not a treatment for the tumour but analysis of the tissue removed by biopsy will allow for planning the best treatment. A stereotactic biopsy is a less invasive way to obtain the tissue sample, while an open biopsy is surgery that uses local or general anesthesia to remove the tissue needed for the diagnosis. In experienced hands, a stereotactic biopsy provides sufficient tissue for a correct histopathological diagnosis in more than 95% of cases. However, in order to provide as much tumour tissue as possible for both diagnosis and molecular characterisation, open biopsy, may be preferred.
Radiotherapy and/or chemotherapy
Post-operative treatments mainly consist of chemotherapy and/or radiotherapy. However, their use differs according to the subtype of glioma.
Low grade glioma (WHO grade I and grade II)
Low grade gliomas comprise the histological types of astrocytoma, oligodendroglioma and oligoastrocytoma.
Post-operative radiotherapy is the standard treatment for low grade gliomas. It is usually administered in 28 sessions over 6 weeks. Nevertheless, not all patients who undergo resection of a low grade glioma should be treated with radiotherapy. That is because these patients may have a longer/slower natural history of disease even in the absence of post-operative treatment.
However, post-operative radiotherapy should always be considered in the presence of three or more of the following factors which suggest a higher likelihood of tumour recurrence:
• tumours greater than 5 cm in diameter,
• age > 40 years,
• absence of an oligodendroglial component at histopathological examination,
• tumours extending from one brain hemisphere to the other,
• presence of neurological deficits before surgery.
Temozolomide chemotherapy given orally is the preferred treatment option for patients who are not deemed eligible for surgical resection and/or radiotherapy because of tumour location and tumour dimension/appearance at MRI, respectively. Also, temozolomide can be used if/when disease recurs following radiotherapy. There is some evidence suggesting that tumours with genetic loss on chromosomes 1p/19q might be more sensitive to chemotherapy as compared to low grade gliomas without this alteration.
Anaplastic glioma (WHO grade III)
Similarly to low grade gliomas, anaplastic gliomas comprise the histological types of astrocytoma, oligodendroglioma and oligoastrocytoma. However, they differ from low grade glioma because of some histological and/or radiological characteristics which suggest a more aggressive behaviour of the tumour.
Post-operative chemotherapy of the orally administered chemotherapeutic agent temozolomide or the three-drug chemotherapy regimen called PCV (procarbazine, lomustine and vincristine) should be considered as an alternative to radiotherapy for anaplastic gliomas. Between the two regimens, temozolomide is usually preferred because of its greater tolerability and ease of administration. Genetic loss on chromosomes 1p/19q identifies the anaplastic tumours with an oligodendroglial component which are more sensitive to chemotherapy with or without radiotherapy.
Glioblastoma (WHO grade IV)
Post-operative treatment of glioblastoma may differ according to some of your characteristics (i.e. age, performance status) and histopathological/molecular features of your tumour (i.e. MGMT status of the tumour)
o Concurrent chemo-radiotherapy
The concurrent administration of chemotherapy during radiotherapy and then chemotherapy on its own for a period of time after radiotherapy is the standard post-operative treatment of patients with glioblastoma up to 70 years of age; it is also the preferred treatment approach for fit elderly patients older than 70 years whose tumour has tested positive for the presence of MGMT gene methylation.
• Chemotherapy consists of the orally administered drug called temozolomide, which acts by interfering with the mechanism of DNA replication of cancer cells. Temozolomide is administered daily from the first day of radiotherapy and for the whole duration of it. At the end of radiation, after a short treatment break (approximately 4 weeks), temozolomide is resumed at a higher dosage for at least 6 cycles (six months) of therapy. Although the addition of temozolomide to radiotherapy is beneficial for most of patients with glioblastoma, it is important to know that the greatest benefit is observed in patients whose tumour is detected positive for MGMT gene methylation testing.
• Radiotherapy is administered concurrently with temozolomide for 5 days a week for a total of 6 weeks, i.e. in 30 separate sessions.
Elderly patients older than 70 years who are not deemed eligible for concurrent chemo-radiotherapy because of deteriorated performance status and/or because their tumour has tested negative for the presence of MGMT gene methylation, are adequately treated with radiotherapy alone using a hypo-fractionated schedule. A hypo-fractioned schedule consists of administering higher daily doses of radiotherapy over a shorter period of time. Hypo-fractionated radiotherapy alone is also appropriate for elderly patients in whom no information is available on the MGMT status.
o Chemotherapy alone
Elderly patients older than 70 years who are not deemed eligible for concurrent chemo-radiotherapy, may be adequately treated with temozolomide chemotherapy, provided their tumour has tested positive for the presence of MGMT gene methylation.
Medications to relieve symptoms of a glioma
The symptoms and signs mentioned in the section about diagnosis can improve or even disappear if effective therapies are used to treat glioma successfully (see aforementioned treatment options). However, the following medications are used in order to effectively control, at least in part, tumour symptoms:
Anti-epileptic drugs are very effective medications for patients who have seizures. However, these drugs should not be used for the prevention of seizures in patients who have never experienced one. There are several types of anti-epileptic drugs. Nevertheless, only a few anti-epileptic drugs (lamotrigine, levetiracetam, pregabalin, or topiramate) offer the advantage of lack of interference with the commonly prescribed chemotherapeutic agents. Notwithstanding, clinical studies have demonstrated that temozolomide can be safely administered with any type of anti-epileptic drug.
Corticosteroids alleviate patients’ symptoms by reducing tumour-associated inflammation (called ‘oedema’), which usually forms around the tumour and contributes to symptoms by increasing intracranial pressure. Therefore, corticosteroids are indicated if oedema is detected at radiological tests, or if the responsible physician decides on starting corticosteroid treatment based on signs and symptoms of increased intracranial pressure. Unfortunately, the downside of corticosteroids is that their long-term use can be associated with some side effects (e.g. Cushingoid or moon face, condition in which fat accumulates to the sides of the face, giving it a rounded appearance, also increase in blood glucose levels which therefore should be monitored at each visit, increased risk of infection, osteoporosis, muscle weakness, impaired wound healing). For this reason, upon improvement of symptoms, the dose of corticosteroids should be gradually reduced in order to find the lowest effective dose or eventually be discontinued if symptoms resolve and/or oedema disappears as a result of effective treatment of the tumour.
Anticoagulation using coumadin derivatives (i.e. warfarin) is feasible in glioma patients experiencing thromboembolic events; however, low-molecular-weight heparin is often preferred due to a favourable safety profile.
What are the possible side effects of the treatment ?
In this section you can find the most common side effects of surgery, radiotherapy and chemotherapy. However, the following list is not exhaustive. Therefore, you should carefully discuss with your doctor the side effects potentially related to the proposed treatment(s).
Some people will have seizures within the first week of surgery, but this doesn’t mean that surgery has not been successful. Seizures after surgery can happen because of the direct stress the brain experiences during the surgical procedure. On the other hand, if seizures were one of the symptoms of disease presentation, after surgery they will likely improve or even disappear over time. However, it may take time to fully measure how successful your surgery has been in terms of seizure improvement.
There is a possibility of post-operative intracranial bleeding in cases when surgical removal of a glioma has been carried out. This bleeding causes an increase in intracranial pressure. However, only rarely this increase in pressure either within or on the brain as well as the surrounding structures has the potential to reach alarmingly high levels, thus leading to either unconsciousness or other serious complications.
If present at diagnosis, neurological deficits usually improve following surgery. However, surgical removal of tumour tissue in the brain sometimes leads to removal of healthy unaffected brain tissue as well, thus potentially causing neurological deficits. They may vary in type and severity, and can be either temporary or permanent. Symptoms gradually disappear in temporary cases within months, but where permanent damage of tissue has occurred rehabilitation may be required. In some cases, brain tissue damage can also alter personality or cause changes in mood.
To gain access to the brain tumour, a piece of the skull is temporary removed from its place, under sterile conditions. Nevertheless, bacteria may gain access to the brain during the operating procedure, and then the chances of brain infection are high. To prevent this type of infection, an intravenously administered antibiotic is given to the patient during the operating procedure. As a cut is made on the skin and a hole is made in the skull, there is always the possibility of an acquired skin or skull infection. A proper antibiotic regimen is started immediately in such cases to treat the infection.
Cerebrospinal fluid leak (also known as a ‘CSF leak’)
Surgery of the brain can cause a leak of the cerebrospinal fluid, a fluid produced by the brain. Headache, a salty taste in the throat or a watery drainage from the nose (usually from one nostril) or from the wound site are the most common symptoms. However, a cerebrospinal fluid leak may also give no symptom. A cerebrospinal fluid leak needs to be rapidly repaired since it increases the risk of bacterial infection in the brain (meningitis or abscess).
Side effects with an early onset
Side effects usually occur during or within 6 months after completion of radiotherapy. They often include nausea/vomiting, headache, a worsening of the existing neurological deficits (due to radiotherapy induced swelling, which is called ‘oedema’) and hair loss in the irradiated area as well as on the opposite side of the head where the radiotherapy beams pass through. In glioma patients, radiotherapy can also cause an increase in the risk of seizures as one of the brain’s reactions to this treatment.
Side effects with a late onset
These side effects typically occur 6 months or more from completion of radiotherapy. The most common ones include radio-necrosis (meaning death of healthy brain tissue in the previously irradiated area) which, in some instances, may lead to symptoms associated with increased pressure in the head (i.e. headache, nausea, and drowsiness), and/or neurological deficits. Late side effects may also include partial loss of short-term memory, whose occurrence strictly depends on the area of the brain which has been irradiated (i.e. temporal lobe).
The side effects of chemotherapy vary in frequency and severity based on the type of agent and/or combination regimens employed. Therefore, you are encouraged to thoroughly discuss the main side effects associated with the proposed chemotherapy regimen with your doctor.
However, in general, common side effects of chemotherapy may include: loss of appetite, fatigue, hair loss, nausea and/or vomiting, increased susceptibility to infections and bleeding. Nevertheless, it is important to note that not everyone will have side effects, or experience them to the same extent. Here, you can find some specific side effects of the most commonly administered chemotherapeutic agents for the treatment of gliomas.
This orally administered chemotherapeutic agent may cause a reduction in the number of platelets as one of its most common side effects. Platelets are cellular elements of the blood whose function is to help stop bleeding. As a consequence, the risk of bleeding may be increased during chemotherapy with temozolomide. This is the reason why the levels of platelets should be monitored and evaluated carefully at the beginning and during therapy with temozolomide.
Nausea and/or vomiting are other common side effects of temozolomide. However, they can be largely prevented with the use of anti-emetic (anti-nausea/anti-vomiting) drugs to be administered before taking temozolomide.
Finally, pneumonia due to opportunistic pathogens is a rare side effect of temozolomide. Temozolomide can weaken the immune system by lowering the level of lymphocytes, a subtype of white blood cells. This may result in a life-threatening pneumonia caused by microbes that only affect immuno-compromised patients.
Procarbazine, lomustine and vincristine (‘PCV’)
These drugs are usually administered in combination (oral administration for procarbazine and lomustine, and intravenous administration for vincristine).
Procarbazine and lomustine can often lead to a reduction in the number of white blood cells, which are elements of the blood involved in protecting the body from infections. The number of platelets might also decrease. This is why the blood counts should be monitored and evaluated carefully at the beginning and during therapy with procarbazine, lomustine and vincristine.
Vincristine can cause peripheral neuropathy, which is a progressive and often irreversible tingling, numbness and pain in the hands and feet. These side effects may have an impact on the activities of daily living and must immediately be reported to the responsible physician. It may lead to a dose reduction or interruption of vincristine, as the best interests of the patient are foremost in any treatment plan.
Nausea and/or vomiting are another common side effect of lomustine. However, they can be largely prevented with the use of anti-emetic drugs taken right before lomustine.
Should you consider clinical trials?
The prognosis for patients diagnosed with gliomas is very different from one tumour to another In all cases, but especially when the prognosis is less favourable, clinical trials should be considered. In many countries, clinical trials may be available for newly diagnosed patients as well as for patients who already received standard, first-line treatment and who may be dealing with a recurrence of their disease. As there is still unmet need for improving the effectiveness of treatments for gliomas, doctors and scientists are exploring new therapies. For instance, immunotherapies, new neurosurgical techniques, new methods of irradiation, new devices and targetted therapies have shown promise and are all being tested in clinical trials in some countries.
Promising therapies have to first be tested stringently in clinical trials before they are approved (licensed for a specific use) by regulatory bodies and then made available to patients. These clinical trials may provide an opportunity to receive a new therapy before it is generally available. On the other hand, such new therapies which are used in research studies also have some risks as, at the clinical trial stage, all of the side effects are not yet known. Because of these positive and negative aspects of clinical trials, it is very important that you thoroughly discuss the suitability of a clinical trial with your doctor.
Most of the clinical trials for gliomas are listed on the following websites:
Click here for more information on what clinical trials are and what it takes to participate.
What happens after the treatment?
Evaluating your response to treatment
MRI is the preferred imaging method for assessing treatment(s). Your first MRI should be carried out within 24-48 hours after surgery. It is in order to verify the true extent of tumour resection, to detect the presence of any residual disease and to look for any bleeding. The intervals of subsequent MRI assessments may vary depending on the type of glioma, on how it is being treated, and on the symptoms you report.
Generally speaking, the results of the MRI scan should always be viewed in relation to the neurological status of the patient and the use of corticosteroid therapy.
As for glioblastoma treated with concurrent chemo-radiotherapy a first MRI will preferably be performed 3 to 4 months after the end of radiotherapy, after 2 or 3 adjuvant temozolomide cycles. An MRI performed within 4-12 weeks after the end of treatment, may be difficult to interpret due to reactive changes in the tumour, and a possible false MRI reading of disease progression (this phenomenon is called ‘pseudoprogression’). A repeated MRI after 6-8 weeks, will help evaluate this phenomenon and disclose whether there is true progression or not. It is important to discuss MRI findings and neurological condition of the patient in a multidisciplinary tumour board, to decide on continuation of the treatment.
Follow-up with your doctors
Regular follow-up with your doctors is important in order to evaluate neurological function, seizure(s) and corticosteroid use. Corticosteroids should be tapered off as soon as possible in view of their long-term use side effects. Laboratory tests may help find out complications of symptomatic medication(s), as corticosteroids may increase blood glucose levels, and anti-epileptic drugs may alter blood cell count and liver function tests. During follow-up, MRI should be performed every 3-4 months, unless earlier or more frequent monitoring is clinically indicated.
Returning to normal life
Returning to normal life can be difficult for glioma patients, as different degrees of neurological impairment may be present. Patients become increasingly less independent as a result of direct injury of brain structures responsible for motor, sensory, cognitive, and speech functions. Also, the indirect effects of radiotherapy and chemotherapy may add to the functional deficit which patients experience. For these reasons, rehabilitation is of crucial importance for glioma patients, and emphasis should be placed on restoring or maximising independence with activities of daily living, mobility, cognition and communication.
However, though rehabilitation interventions can be applied in all stages of the disease, its goals change as the stage of illness advances. When tumour progression causes a decline in functional skills, rehabilitation assumes a supportive role, with goals adjusted to accommodate persistent physical and functional limitations. During advanced stages of illness, palliative rehabilitation can improve and maintain comfort and quality of life.
Psychological, social and peer support
Psychological stress and the social effects of the disease on patients and their families and caregivers should not be underestimated. Psychiatric difficulties should be recognised and treated with both psychotherapy and pharmacotherapy. Recognition of the social effects of having a brain tumour and adequate counselling in such circumstances are vital aspects of care for patients and their caregivers. A dedicated nurse in a neuro-oncology centre can be responsible for guiding and supporting the patient as well as the caregiver during the disease journey. Referral to other health care professionals such as psychologists, social workers, physiotherapists and speech pathologists may help the patient and caregiver alleviate the experienced burden and meet their needs.
Patient advocacy groups can help you get in touch with other patients who have brain tumours, assist you in learning more about your disease, provide helpful information, find an experienced doctor for a second opinion, identify clinical centers of expertise that run clinical trials and provide other services to help you and your family deal with the diagnosis of a brain tumour so you do not feel alone. To see whether a brain tumour patient organisation exists in your country, you can visit the website of the International Brain Tumour Alliance at http://theibta.org/brain-tumour-support-advocacy-and-information-organisations/
What if my glioma comes back?
The treatment at disease recurrence differs according to the type of initial histopathological diagnosis and clinical scenario, type and number of previous therapies. Treatment options include:
- Chemotherapy in patients with good performance status who have not received prior adjuvant chemotherapy,
- Second surgery (in particular if a period of time has elapsed since first surgical resection, or when recurrent tumour causes symptoms due to its mass effects),
- (re)-irradiation (in case of smaller tumours).
For patients progressing after prior chemotherapy, there is, as yet, no specific protocol established for a second chemotherapy regimen or targeted agents and therefore, patients should be encouraged to participate in clinical trials, if they are available (see paragraph “Should you consider clinical trials?” in the section “What are the treatment options?”). Chemotherapy with a PCV regimen or a single agent nitrosourea may achieve similar tumour control rates compared with temozolomide.
However, it should be noted that there is no agreed standard therapy when disease recurs, and clinical decision making should ideally be based on recommendations from a multidisciplinary tumour board who will review your case.
Supportive and palliative care
Medications to relieve symptoms experienced by patients with glioma are a very important part of care as already explained. However, during and after the course of active anticancer treatment, some side effects can occur and adequate supportive measures should be applied (such as anti-emetic therapy, corticosteroids, antibiotic therapy, blood transfusion, etc. depending on the type and severity of underlying side effects). This is known as supportive and palliative care. It is important for patients and carers to remember that the term ‘palliative care’ does not only apply to end-of-life care but it applies to relieving symptoms at any stage of disease, including when you are newly diagnosed. So you should not be frightened when you hear the words ‘palliative care’.
In summary, and importantly, being informed about the available therapies for a brain tumour will help you to be more actively involved in the decisions regarding your treatment. Not only that, but it can also open up the possibility of more in-depth discussions with your medical team as many questions may arise.
Do not hesitate to ask questions and to give your opinion. You, as the patient, are the primary concern and everybody is there to help you.
Standard of care
Primary brain tumor
Primary brain tumour
Cancer of the brain
Therapies by type
The following list of treatments is based on what we have found in scientific studies about cancer. More information about the listed therapies can be found under the tab THERAPIES. For registered drugs, radiotherapy and surgical interventions, approval by the authorities is given.
Synthetic products (excluding registered drugs)
Natural products (excluding registered drugs)
A clinical trial is a research study conducted with patients to evaluate whether a new treatment is safe (safety) and whether it works (efficacy). Clinical trials are performed to test the efficacy of drugs but also non-drug treatments such as radiotherapy or surgery and combinations of different treatments. Clinical trials take place in all kinds of hospitals and clinics, but mostly in academic hospitals. They are organized by researchers and doctors.
The Anticancer Fund provides a tool to search for phase III clinical trials by type of cancer and by country. For Belgium, the Netherlands, Switzerland, Luxembourg, France and the UK, the Anticancer Fund provides contacts to get more information about the phase III clinical trials currently ongoing. Discuss the possibilities of participating in one of these clinical trials with your doctor.
The list of the phase III clinical trials for primary brain cancer is available here.