Brain tumours (glioma)

A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, or malignant, with cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are metastatic, and they start somewhere else in the body and move to the brain.

Brain tumors can cause many symptoms. Some of the most common are:

• Headaches, often in the morning
• Nausea and vomiting
• Changes in your ability to talk, hear, or see
• Problems with balance or walking
• Problems with thinking or memory
• Feeling weak or sleepy
• Changes in your mood or behavior
• Seizures

Doctors diagnose brain tumors by doing a neurologic exam and tests including an MRI, CT scan, and biopsy. Treatment options include watchful waiting, surgery, radiation therapy, chemotherapy, and targeted therapy. Targeted therapy uses drugs or other substances that attack cancer cells with less harm to normal cells. Many people get a combination of treatments.

NIH: National Cancer Institute

Source: MedlinePlus, U.S. National Library of Medicine

Signs and symptoms

The signs and symptoms of brain tumors are broad. People may experience symptoms regardless of whether the tumor is benign (not cancerous) or cancerous. Primary and secondary brain tumors present with similar symptoms, depending on the location, size, and rate of growth of the tumor. For example, larger tumors in the frontal lobe can cause changes in the ability to think. However, a smaller tumor in an area such as Wernicke's area (small area responsible for language comprehension) can result in a greater loss of function.

Headaches

Headaches as a result of raised intracranial pressure can be an early symptom of brain cancer. However, isolated headache without other symptoms is rare, and other symptoms including visual abnormalities may occur before headaches become common. Certain warning signs for headache exist which make the headache more likely to be associated with brain cancer. These are defined as "abnormal neurological examination, headache worsened by Valsalva maneuver, headache causing awakening from sleep, new headache in the older population, progressively worsening headache, atypical headache features, or patients who do not fulfill the strict definition of migraine". Other associated signs are headaches that are worse in the morning or that subside after vomiting.

Location-specific symptoms

The brain is divided into lobes and each lobe or area has its own function. A tumour in any of these lobes may affect the area's performance. The symptoms experienced are often linked to the location of the tumour, but each person may experience something different.

Frontal lobe: Tumours may contribute to poor reasoning, inappropriate social behavior, personality changes, poor planning, lower inhibition, and decreased production of speech (Broca's area).

Temporal lobe: Tumours in this lobe may contribute to poor memory, loss of hearing, and difficulty in language comprehension (Wernicke's area is located in this lobe).

Parietal lobe: Tumours here may result in poor interpretation of languages, difficulty with speaking, writing, drawing, naming, and recognizing, and poor spatial and visual perception.

Occipital lobe: Damage to this lobe may result in poor vision or loss of vision.

Cerebellum: Tumours in this area may cause poor balance, muscle movement, and posture.

Brain stem: Tumours on the brainstem can cause seizures, endocrine problems, respiratory changes, visual changes, headaches and partial paralysis.

Leptomeninges: Tumours that spread to the leptomeninges, the lining of the brain, may cause cranial nerve palsies such as facial paralysis, abnormalities of eye movement, abnormalities of facial sensation or swallowing difficulty, depending on which cranial nerves are involved.

Behaviour changes

A person's personality may be altered due to the tumor damaging lobes of the brain. Since the frontal, temporal, and parietal lobes control inhibition, emotions, mood, judgement, reasoning, and behavior, a tumor in those regions can cause inappropriate social behavior, temper tantrums, laughing at things which merit no laughter, and even psychological symptoms such as depression and anxiety. More research is needed into the effectiveness and safety of medication for depression in people with brain tumors.

Personality changes can have damaging effects such as unemployment, unstable relationships, and a lack of control.

Cause

A known cause of brain cancers is ionizing radiation. Approximately 4% of brain cancers in the general population are caused by CT-scan radiation. For brain cancers that follow a CT scan at lags of 2 years or more, it has been estimated that 40% are attributable to CT-scan radiation. The risk of brain cancer is dose dependent, with the relative risk increasing by 0.8 for each 100 gray of ionizing radiation received. At this dose, approximately 6391 people would have to be exposed to cause 1 case of brain cancer.

Mutations and deletions of tumor suppressor genes, such as P53, are thought to be the cause of some forms of brain tumor. Inherited conditions, such as Von Hippel–Lindau disease, tuberous sclerosis, multiple endocrine neoplasia, and neurofibromatosis type 2 carry a high risk for the development of brain tumors. People with celiac disease have a slightly increased risk of developing brain tumors. Smoking may increase the risk, but evidence of this remains unclear.

Although studies have not shown any link between cell-phone or mobile-phone radiation and the occurrence of brain tumors, the World Health Organization has classified mobile-phone radiation on the IARC scale into Group 2B – possibly carcinogenic.

The claim that cell-phone usage may cause brain cancer is likely based on epidemiological studies which observed a slight increase in glioma risk among heavy users of wireless phones. When those studies were conducted, GSM (2G) phones were in use. Modern, third-generation (3G) phones emit, on average, about 1% of the energy emitted by those GSM (2G) phones, and therefore the finding of an association between cell-phone usage and increased risk of brain cancer is not based upon current phone usage.

Treatment

A medical team generally assesses the treatment options and presents them to the person affected and their family. Various types of treatment are available depending on tumor type and location, and may be combined to produce the best chances of survival:

Surgery: complete or partial resection of the tumor with the objective of removing as many tumor cells as possible.

Radiotherapy: the most commonly used treatment for brain tumors; the tumor is irradiated with beta, X-rays or gamma rays.

Chemotherapy: a treatment option for cancer, however, it is not always used to treat brain tumors as the blood–brain barrier can prevent some drugs from reaching the cancerous cells.

A variety of experimental therapies are available through clinical trials.

Survival rates in primary brain tumors depend on the type of tumor, age, functional status of the patient, the extent of surgical removal and other factors specific to each case.

Standard care for anaplastic oligodendrogliomas and anaplastic oligoastrocytomas is surgery followed by radiotherapy. One study found a survival benefit for the addition of chemotherapy to radiotherapy after surgery, compared with radiotherapy alone.

Surgery

Surgical resection of the greatest extent of contrast enhancing tumor possible (gross total resection) is associated with increased overall and progression free survival in those with glioblastoma. Gross total resection is often required in other brain tumors. Minimally invasive techniques are becoming the dominant trend in neurosurgical oncology. The main objective of surgery is to remove as many tumor cells as possible, with complete removal being the best outcome and cytoreduction ("debulking") of the tumor may otherwise be done. Due to the infiltrative nature of glioblastomas, total resection is usually unachievable and progression after surgery usually occurs, with progression occurring about 7 months after surgery.

Many meningiomas, with the exception of some tumors located at the skull base, can be successfully removed surgically.

Most pituitary adenomas can be removed surgically, often using a minimally invasive approach through the nasal cavity and skull base (trans-nasal, trans-sphenoidal approach). Large pituitary adenomas require a craniotomy (opening of the skull) for their removal. Radiotherapy, including stereotactic approaches, is reserved for inoperable cases.

Postoperative radiotherapy and chemotherapy are integral parts of the therapeutic standard for malignant tumors.

Multiple metastatic tumors are generally treated with radiotherapy and chemotherapy rather than surgery and the prognosis in such cases is determined by the primary tumor, and is generally poor.

Radiation therapy

The goal of radiation therapy is to kill tumor cells while leaving normal brain tissue unharmed. In standard external beam radiation therapy, multiple treatments of standard-dose "fractions" of radiation are applied to the brain. This process is repeated for a total of 10 to 30 treatments, depending on the type of tumor. This additional treatment provides some patients with improved outcomes and better survival rates.

Radiosurgery is a treatment method that uses computerized calculations to focus radiation at the site of the tumor while minimizing the radiation dose to the surrounding brain. Radiosurgery may be an adjunct to other treatments, or it may represent the primary treatment technique for some tumors. Forms used include stereotactic radiosurgery, such as Gamma knife, Cyberknife or Novalis Tx radiosurgery.

Radiotherapy is the most common treatment for secondary brain tumors. The amount of radiotherapy depends on the size of the area of the brain affected by cancer. Conventional external beam "whole-brain radiotherapy treatment" (WBRT) or "whole-brain irradiation" may be suggested if there is a risk that other secondary tumors will develop in the future. Stereotactic radiotherapy is usually recommended in cases involving fewer than three small secondary brain tumors. Radiotherapy may be used following, or in some cases in place of, resection of the tumor. Forms of radiotherapy used for brain cancer include external beam radiation therapy, the most common, and brachytherapy and proton therapy, the last especially used for children.

People who receive stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) for the treatment of metastatic brain tumors have more than twice the risk of developing learning and memory problems than those treated with SRS alone. Results of a 2021 systematic review found that when using SRS as the initial treatment, survival or death related to brain metastasis was not greater than alone versus SRS with WBRT.

Postoperative conventional daily radiotherapy improves survival for adults with good functional well-being and high grade glioma compared to no postoperative radiotherapy. Hypofractionated radiation therapy has similar efficacy for survival as compared to conventional radiotherapy, particularly for individuals aged 60 and older with glioblastoma.

Chemotherapy

Patients undergoing chemotherapy are administered drugs designed to kill tumor cells. Although chemotherapy may improve overall survival in patients with the most malignant primary brain tumors, it does so in only about 20 percent of patients. Chemotherapy is often used in young children instead of radiation, as radiation may have negative effects on the developing brain. The decision to prescribe this treatment is based on a patient's overall health, type of tumor, and extent of cancer. The toxicity and many side effects of the drugs, and the uncertain outcome of chemotherapy in brain tumors puts this treatment further down the line of treatment options with surgery and radiation therapy preferred.

UCLA Neuro-Oncology publishes real-time survival data for patients with a diagnosis of glioblastoma. They are the only institution in the United States that displays how brain tumor patients are performing on current therapies. They also show a listing of chemotherapy agents used to treat high-grade glioma tumors.

Genetic mutations have significant effects on the effectiveness of chemotherapy. Gliomas with IDH1 or IDH2 mutations respond better to chemotherapy than those without the mutation. Loss of chromosome arms 1p and 19q also indicate better response to chemoradiation.

Other

A shunt may be used to relieve symptoms caused by intracranial pressure, by reducing the build-up of fluid (hydrocephalus) caused by the blockage of the free flow of cerebrospinal fluid.

For those with brain tumors, anti-seizure prophylactic (preventative) medications are not usually recommended. However, anti-epileptics are used in those with seizures.

Cerebral edema secondary to brain tumors is managed by corticosteroids. Dexamethasone is the preferred corticosteroid due to its long half-life and reduced effect on water retention (mineralcorticoid activity). Bevacizumab (an anti-VEGFA antibody) may improve cerebral edema in those that are unresponsive to steroids.

Prognosis

The prognosis of brain cancer depends on the type of cancer diagnosed. Medulloblastoma has a good prognosis with chemotherapy, radiotherapy, and surgical resection while glioblastoma has a median survival of only 15 months even with aggressive chemoradiotherapy and surgery. Brainstem gliomas have the poorest prognosis of any form of brain cancer, with most patients dying within one year, even with therapy that typically consists of radiation to the tumor along with corticosteroids. However, one type, focal brainstem gliomas in children, seems open to exceptional prognosis and long-term survival has frequently been reported.

Prognosis is also affected by presentation of genetic mutations. Certain mutations provide better prognosis than others. IDH1 and IDH2 mutations in gliomas, as well as deletion of chromosome arms 1p and 19q, generally indicate better prognosis. TP53, ATRX, EGFR, PTEN, and TERT mutations are also useful in determining prognosis.

Glioblastoma

Glioblastoma is the most aggressive (grade 4) and most common form of a malignant primary brain tumor. Even when aggressive multimodality therapy consisting of radiotherapy, chemotherapy, and surgical excision is used, median survival is only 15–18 months. Standard therapy for glioblastoma consists of maximal surgical resection of the tumor, followed by radiotherapy between two and four weeks after the surgical procedure to remove the cancer, then by chemotherapy, such as temozolomide. Most patients with glioblastoma take a corticosteroid, typically dexamethasone, during their illness to relieve symptoms. Experimental treatments include targeted therapy, gamma knife radiosurgery, boron neutron capture therapy, gene therapy, and chemowafer implants.

Oligodendrogliomas

Oligodendrogliomas are incurable but slowly progressive malignant brain tumors. They can be treated with surgical resection, chemotherapy, radiotherapy or a combination. For some suspected low-grade (grade II) tumors, only a course of watchful waiting and symptomatic therapy is opted for. These tumors show co-deletions of the p and q arms of chromosome 1 and chromosome 19 respectively (1p19q co-deletion) and have been found to be especially chemosensitive with one report claiming them to be one of the most chemosensitive tumors. A median survival of up to 16.7 years has been reported for grade II oligodendrogliomas.

Acoustic neuroma

Acoustic neuromas are non-cancerous tumors. They can be treated with surgery, radiation therapy, or observation. Early intervention with surgery or radiation is recommended to prevent progressive hearing loss.

Epidemiology

The incidence of brain tumors is higher in developed countries. This could be explained by undiagnosed tumor-related deaths in resource limited or lower income countries or by early deaths caused by other poverty-related causes that preempt a patient's life before tumors develop.

The incidence of CNS tumors in the United States, Israel, and the Nordic countries is relatively high, while Japan and Asian countries have a lower incidence.

United States

In the United States in 2015, approximately 166,039 people were living with brain or other central nervous system tumors. Over 2018, it was projected that there would be 23,880 new cases of brain tumors and 16,830 deaths in 2018 as a result, accounting for 1.4 percent of all cancers and 2.8 percent of all cancer deaths. Median age of diagnosis was 58 years old, while median age of death was 65. Diagnosis was slightly more common in males, at approximately 7.5 cases per 100 000 people, while females saw 2 fewer at 5.4. Deaths as a result of brain cancer were 5.3 per 100 000 for males, and 3.6 per 100 000 for females, making brain cancer the 10th leading cause of cancer death in the United States. Overall lifetime risk of developing brain cancer is approximated at 0.6 percent for men and women.

UK

Brain, other CNS or intracranial tumors are the ninth most common cancer in the UK (around 10,600 people were diagnosed in 2013), and it is the eighth most common cause of cancer death (around 5,200 people died in 2012). White British patients with brain tumour are 30% more likely to die within a year of diagnosis than patients from other ethnicities. The reason for this is unknown.

Children

In the United States more than 28,000 people under 20 are estimated to have a brain tumor. About 3,720 new cases of brain tumors are expected to be diagnosed in those under 15 in 2019. Higher rates were reported in 1985–1994 than in 1975–1983. There is some debate as to the reasons; one theory is that the trend is the result of improved diagnosis and reporting, since the jump occurred at the same time that MRIs became available widely, and there was no coincident jump in mortality. Central nervous system tumors make up 20–25 percent of cancers in children.

The average survival rate for all primary brain cancers in children is 74%. Brain cancer is the most common cancer in children under 19 and results in more deaths in this age group than leukemia. Younger people have worse prognoses.

The most common brain tumor types in children (0–14) are: pilocytic astrocytoma, malignant glioma, medulloblastoma, neuronal and mixed neuronal-glial tumors, and ependymoma.

In children under 2, about 70% of brain tumors are medulloblastomas, ependymomas, and low-grade gliomas. Less commonly, and seen usually in infants, are teratomas and atypical teratoid rhabdoid tumors. Germ cell tumors, including teratomas, make up just 3% of pediatric primary brain tumors, but the worldwide incidence varies significantly.

In the UK, 429 children aged 14 and under are diagnosed with a brain tumour on average each year, and 563 children and young people under the age of 19 are diagnosed.

Source: Wikipedia, The Free Encyclopedia · CC BY-SA 4.0