Low-Grade Gliomas

What is Low-Grade Gliomas?

Tumors that exist in the central nervous system (CNS), the part of our nervous system that includes our brain and spinal cord, are grouped according to where they come from. Gliomas are one type of these tumors, and they start from glial cells. These are supportive cells within the CNS that keep neurons, the nerve cells, in place and functioning properly. Different types of glial cell tumors exist, such as astrocytomas, ependymomas, oligodendrogliomas, and mixed oligoastrocytomas, depending on which particular glial cells are involved.

In this context, we’re focusing on a specific type of gliomas known as “diffuse gliomas with lower grade pathology,” specifically grade 2 gliomas. They infiltrate or spread diffusely into surrounding brain tissue.

In 2016, the World Health Organization (WHO) updated their classification system for CNS tumors. This update was a significant change because they included molecular features — the tiny characteristics of cells that can be seen on a molecular level — alongside traditional features seen under a microscope, such as abnormal cell shapes, increased cell division, changes in cell size, new blood vessel growth, and dead tissue.

Typically, these microscopic and tissue-level features are more pronounced in high-grade gliomas, which are more aggressive, while they are minimal or absent in lower-grade tumors. Lower-grade gliomas (LGGs) typically grow more slowly than high-grade gliomas. However, over a decade or so, more than 70% of these slow-growing tumors can transform into a higher grade or become more aggressive.

Studies using MRI scans before treatment have shown that these lesions usually grow steadily, increasing in size by about 4.1 millimeters each year. People with lower-grade gliomas usually live longer than those with more aggressive types of the tumor. As such, when planning treatment, it’s important to consider various factors, such as potential side effects of chemotherapy and radiation therapy, as well as potential complications from surgery. These considerations are vital in properly managing the disease and improving the overall patient outcomes.

What Causes Low-Grade Gliomas?

We don’t yet fully understand what causes gliomas (a type of brain tumor), and it’s unclear what factors increase the risk of developing them. We do know that radiation therapy is the main environmental factor that increases the risk of all brain tumors, including low-grade gliomas.

Certain diets, environmental toxins, and specific jobs can cause random changes, or mutations, in our genes – like the TP53 gene. These mutations can sometimes lead to the development of gliomas. Inherited gene mutations can also lead to gliomas, although this happens less often.

Some people have inherited conditions that increase their risk of developing brain tumors, such as neurofibromatosis (NF), Li-Fraumeni cancer syndrome, and Lynch syndrome. However, these conditions only account for a very small number of all glioma cases.

Risk Factors and Frequency for Low-Grade Gliomas

Low-grade gliomas, a type of brain tumor, is quite rare and can be difficult to track accurately due to changing medical classification systems. The most recent information states that the occurrence of three types of low-grade gliomas, known as oligodendrogliomas, astrocytomas, and mixed gliomas are 0.25, 0.51, and 0.20 cases respectively per 100000 people each year in the United States. These kinds of brain tumors most frequently develop in younger individuals, typically between the ages of 20 and 40. Of the three types, oligodendrogliomas most commonly appear in people aged 40 to 45, while astrocytomas usually occur in the 30 to 40 age range. Low-grade gliomas also tend to be slightly more common in males.

• Low-grade gliomas are rare types of brain tumors whose occurrence rate can be hard to measure due to changing medical classification systems.
• In the United States, the yearly rate per 100,000 people is approximately 0.25 for oligodendrogliomas, 0.51 for astrocytomas, and 0.20 for mixed gliomas.
• These types of brain tumors are most common in people aged 20 to 40.
• The peak age for oligodendrogliomas is 40 to 45, while for astrocytomas it’s 30 to 40.
• Low-grade gliomas are slightly more common in males.

Signs and Symptoms of Low-Grade Gliomas

Low-grade gliomas are types of brain tumor. The symptoms of these tumors depend on their location in the brain. For instance, tumors in the front part of the brain (frontal lobe) may cause changes in behavior. Tumors in the temporal lobe can lead to receptive aphasia, a condition that affects the understanding of speech. Furthermore, tumors in the parietal lobe can have varying symptoms. However, these locations are less likely to cause obvious physical symptoms like weakness on one side of the body or difficulty with speech because these tumors tend to spread within the brain rather than destroying or compressing it. As the tumors grow in size, they can affect memory and other cognitive functions.

The most common symptoms of low-grade gliomas are headaches and seizures. This is especially true for a type of tumor called oligodendroglioma, which typically affects the outer layer of the brain (cortex). Seizures can be partial/focal or sometimes take the form of generalized tonic-clonic seizures (involving the entire body). Partial seizures may go unnoticed for some time before an actual diagnosis is made.

As the tumor grows, it can raise the pressure inside the brain. This pressure can cause headaches, changes in vision, nausea and vomiting. However, it’s crucial to remember that not all people with these types of tumors will have symptoms, especially if their tumors don’t cause any blockage or compression within the brain.

A thorough physical exam is essential to look for any signs of physical impairment or other organ involvement, particularly in individuals predisposed to these types of tumors due to their genetics. Swelling of the optic disc (papilledema) may be seen during an eye exam.

Testing for Low-Grade Gliomas

If a doctor suspects that a patient might have a brain tumor based on their medical history and initial physical examination, they will typically order certain tests to understand the condition better. Depending on the type and severity of the tumor, the results from these tests can vary. After analyzing these results, the doctor will decide whether surgery is needed to either remove the tumor or take a sample of it for further testing. The eventual outcome for the patient depends on several factors, including the type of tumor, the patient’s age, and whether they have any other health conditions.

There are several types of radiographic (imaging) tests that doctors might use in this situation. If the patient is in an emergency department, a CT (Computed Tomography) scan is usually the first test performed. This scan can help locate the tumor and determine its size and other characteristics. Another commonly used test is an MRI (Magnetic Resonance Imaging) scan, which can provide more detailed images of the brain than a CT scan. For instance, it can show whether the tumor is infiltrating surrounding tissues. Sometimes, if further information is needed, more advanced imaging techniques, such as functional MRI, diffusion MRI, perfusion MRI, MR spectroscopy, and PET (Positron Emission Tomography) scans, may be used. However, these are not done routinely.

If the doctor decides to proceed with surgery or a biopsy, they will obtain a sample of the tumor. This sample will then be examined in a lab to determine the exact type of tumor. The lab will also test for certain molecular markers to classify the tumor more precisely.

There are a few key features that the lab will be looking for when examining the tissue sample under a microscope. For instance, they might look at whether the tumor cells are multiplying rapidly (i.e., demonstrating “mitotic activity”) and how similar they are to normal cells (i.e., whether they are “well-differentiated”). The appearance of the cells can also give clues about what type of tumor it might be.

In addition to looking at the cells themselves, the lab will also test for certain genetic mutations that can help classify the tumor. For instance, a mutation in the IDH gene, which codes for an enzyme involved in the Krebs cycle, is found in over 75% of low-grade (i.e., slow-growing) brain tumors. Other common mutations include a combined loss of chromosome arms 1p and 19q, which is common in a specific type of tumor known as oligodendrogliomas, and mutations in the TP53 gene, which is common in another type of tumor known as astrocytomas.

All this information helps the doctor to make the most accurate diagnosis and to determine the best course of treatment. And in some cases, even when a tumor might initially appear to be a mix of different types (e.g., an “oligoastrocytoma”), thorough molecular testing can usually provide a more precise classification, helping to guide treatment decisions.

Treatment Options for Low-Grade Gliomas

If someone has signs and symptoms that suggest a low-grade glioma, which is a kind of brain tumor, doctors usually first consider whether surgery would be appropriate. Surgery makes the most sense in patients who have significant brain swelling or neurological problems like difficulty speaking or moving, caused by the tumor. In such cases, the decision to perform surgery is usually straightforward.

However, decision making becomes a little tricky when the tumor is found unexpectedly. For instance, an individual might go to the doctor due to a seizure or other neurological symptoms like a headache, which is being managed with medication, and the person seems otherwise healthy.

There are many factors to consider in these situations, including what the patient wants, the patient’s age, the size of the tumor, and where the tumor is located in the brain. Additional treatments like radiotherapy (a type of cancer treatment that uses high-energy rays to kill cancer cells) and chemotherapy (drug treatment that uses powerful chemicals to kill fast-growing cells in your body) might be considered for patients who are at a high risk of their tumor coming back, based on factors like their age and how much of the tumor the surgeon was able to remove.

On the other hand, in cases where the risk is low, the common approach is to monitor the situation with routine imaging tests. The decision can then be reassessed over time based on the results of these follow-up tests.

What else can Low-Grade Gliomas be?

There are several conditions that can look similar to low-grade gliomas in terms of symptoms. Therefore, doctors need to consider a long list of other possible diagnoses, which includes:

• Meningioma
• Primary CNS lymphoma
• Cerebral metastasis
• Spinal tuberculosis
• Brain abscess
• Cavernous malformation
• Cavernous sinus syndrome
• Intracranial hemorrhage
• Stroke
• Progressive multifocal leukoencephalopathy
• Acute disseminated encephalomyelitis (ADEM)

Surgical Treatment of Low-Grade Gliomas

The standard treatment for low-grade brain tumors, known as gliomas, often involves surgery. There isn’t much data from highly conclusive scientific studies on this, but the process works both for diagnosis and treatment. Surgeons can take enough tissue from the tumor to confirm the diagnosis and also perform additional tests. This surgery can also help relieve symptoms associated with the tumor such as build-up of fluid in the brain (hydrocephalus) and swelling (edema). Studies suggest that the more of the tumor that can be removed, the better the chances for survival.

If surgeons can remove 90% or more of the tumor, the 5-year survival rate is approximately 97%, compared to 76% if less than 90% of the tumor is removed. Experts generally agree that removing as much of the tumor as safely possible is the best approach, and this method also gives a more accurate diagnosis compared to a needle biopsy.

There are a variety of techniques that can help surgeons remove tumors while reducing the risk of harming healthy brain tissue. These methods include stereotactic neuro-navigation, using MRI during surgery, fluorescence-guided glioma surgery, and intraoperative functional mapping. Each technique has its strengths and role in the surgery.

An intraoperative MRI, developed in the 1990s, can give real-time imaging during the surgery, helping doctors remove more of the tumor. Trials showed that using this technique helped surgeons remove all of the tumor in 96% of cases, compared to 68% of cases when using conventional techniques.

Another technique, called 5-aminolevulinic acid (5-ALA) method, involves giving the patient a substance which turns into protoporphyrin IX (PpIX) that glows red under blue light. During surgery, it helps distinguish between the tumor and healthy brain tissue. Although this has shown good results for high-grade gliomas, it’s not as effective in detecting low-grade tumors.

Intraoperative functional mapping is a method used to minimize the risk of harm to the patient after surgery. One type of this includes awake craniotomy for functional mapping, where the surgeons are able to test the patient’s brain function during the operation. This helps them to avoid areas of the brain that are crucial for normal function.

Stereotactic neuro-navigation is a common tool used in brain surgery. It helps doctors create a 3-dimensional map of the brain using imaging like CT or MRI scans. While it can’t make real-time adjustments for swelling or changes in fluid, it is still a valuable tool for surgery planning.

It’s important to note that brain tumors can return years or even decades after initial treatment. Even in these cases, re-surgery might be a consideration if the complete removal of the tumor is possible. A careful evaluation before surgery is essential to balance the benefit of complete resection and the risk of complications.

There are potential complications of tumor removal, including seizures, a collection of blood outside the brain (epidural hematoma), brain abscess, infection of the wound, stroke, difficulties with movement or sensation, speech problems, vision loss, and changes in behavior.

After the surgery, an MRI scan is usually done within 24 to 72 hours. This is crucial for the planning of any further treatments and for assessing the patient’s condition.

What to expect with Low-Grade Gliomas

For people with low-grade gliomas (a type of brain tumor), the outcomes can vary widely. Some patients may survive for as little as two years, while others can live for more than 12 years, depending on how severe the tumor is according to the 2016 World Health Organization’s brain tumor classification.

Several factors can impact a patient’s prognosis or likely outcome:

* Age: Younger patients generally fare better than older ones. Some studies even suggest that patients below 40 are at lower risk than those above 40 years.
* Symptoms at the start: For instance, if a patient’s symptoms begin with seizures, their outlook is typically better, probably because the condition is diagnosed earlier. On the other hand, if a patient has ongoing neurological problems, their prognosis may be poorer.

The size of the tumor and the area it affects also matter. Large tumors generally lead to a worse prognosis, and if the corpus callosum (a part of the brain) is involved, that’s also a bad sign.

Molecular tests can provide a more precise estimation of a patient’s prognosis. The presence of a genetic change called a 1p/19q co-deletion generally indicates a better prognosis. One study found that patients with this deletion (in a type of tumor called oligodendrogliomas) had a median survival of 12 years, compared to 8 years for those without the deletion.

Also, if the tumor has a certain mutation in a gene called IDH, that is also associated with a better prognosis. A French study found that tumors with this mutation had an average survival of 11 years, compared to 7 years for tumors without the mutation when treated with a chemotherapy drug called temozolomide. This suggests the tumors with the mutation respond better to chemotherapy.

Possible Complications When Diagnosed with Low-Grade Gliomas

Gliomas, a type of brain tumor, tend to grow in size. Without treatment, this growth can lead to severe complications, such as brain herniation, which is when the brain is pushed against the skull or out of the skull due to pressure. This can cause a significant rise in the intracranial pressure, which is the pressure within the skull, and other downstream effects; ultimately, it could even result in death.

Radiation therapy (RT) is one of the treatments for gliomas, but it can also cause various complications. The severity of these complications depends on the length of the treatment.

Common immediate side effects of RT include:

• Fatigue
• Headache
• Nausea and vomiting
• Skin rash on the scalp and hair loss

These side effects usually start a few days after the treatment begins and normally resolve in the weeks following the end of the treatment. However, the long-term side effects, which might appear anywhere from 3 months to several years after the treatment, are more concerning. These long-term side effects include:

• Cognitive decline
• Radiation necrosis (a serious condition where brain tissue dies due to radiation)
• Optic neuropathy (damage to the optic nerve that can cause vision loss)
• Spinal cord myelopathy (nerve damage in the spinal cord)
• Hearing loss
• Cataracts
• Pituitary insufficiency (deficiency of the pituitary gland that can affect growth and hormone production)
• Radiation-induced secondary tumors

Chemotherapy, another common treatment for gliomas, can also cause a variety of side effects, including hair loss, constipation, flu-like symptoms, and central nervous system toxicity that can cause weakness, loss of balance, headache, unsteadiness, drowsiness, or dizziness. Some specific chemotherapy drugs can also cause additional side effects, such as neuropathy (nerve damage) with vincristine and a depletion of blood counts with lomustine. Other treatments used along with chemotherapy, like anti-seizure medications and steroids, can also have side effects. Notably, long-term use of steroids can also have additional side effects.

Recovery from Low-Grade Gliomas

After surgery, regular check-ups are essential to deal with any problems that might arise, like an infection at the site of the operation or other issues related to the surgery. In some cases, there might be neurological issues after a large amount of tissue has been removed. This calls for rehabilitation care.

Cancer can negatively affect the quality of life as it can harm important aspects such as physical health, social interactions, and mental well-being. The goal of rehabilitation is to help the patient regain strength physically, mentally, and socially. This is done by offering support and implementing suitable methods in all areas.

Preventing Low-Grade Gliomas

It’s very important to explain to patients about the tumor, its severity, possible complications, and treatment options. Patients with low-grade gliomas, a type of brain tumor, should be strongly encouraged to keep all follow-up appointments and maintain long-term monitoring of their condition. The treatment of this condition requires a team of various healthcare professionals, so that any problems that come up during treatment can be quickly addressed. Patients should follow all the instructions given by the healthcare team. If the necessary care isn’t available locally, a referral to a larger medical center might be necessary.

Since the patient plays a big role in managing a low-grade glioma, it’s critical to keep them updated on their condition and all available treatments in relation to their risk. This will help the patient make the best decisions to improve not only how they manage their condition, but also their overall quality of life.