Diffuse Intrinsic Pontine Glioma (DIPG)

Other names for DIPG include diffuse midline glioma, H3 K27M-mutant, brainstem glioma, pontine glioma, diffuse (infiltrating) astrocytoma of the pons, glioblastoma of the pons

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What is DIPG?

Diffuse intrinsic pontine glioma, or DIPG, is an aggressive brain tumor. It forms in the base of the brain. DIPG begins in the brainstem. The area is called the pons.

The pons controls vital life functions including:

Balance
Breathing
Bladder control
Heart rate
Blood pressure

Nerves that control vision, hearing, speech, swallowing, and movement also pass through this part of the brain.

Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumor. It begins in the brainstem in an area called the pons. The pons controls vital life functions as well as the nerves that control vision, hearing, speech, swallowing, and movement.

About 200–300 new cases of DIPG are diagnosed every year in the United States. DIPG most often occurs in children ages 5–10 years old. But it can occur in younger children and teens. DIPG is rare in adults.

DIPG grows from glial cells. These cells make up the supportive tissue of the brain. DIPG is a diffuse tumor. This means it is not well-defined or contained. The tumor extends finger-like projections into healthy tissue.

Because of the location in the brainstem and spread-out nature of the tumor, surgery cannot safely remove DIPG.

DIPG is very hard to treat. Most children do not survive more than 2 years after diagnosis. The main treatment for DIPG is radiation therapy. Radiation temporarily improves symptoms in most patients, but it is not a cure. Families may consider clinical trials that test new treatments to see if outcomes can be improved.

Early palliative care is important. It can help families manage symptoms and promote quality of life.

Symptoms of DIPG

DIPG tumors grow quickly. Symptoms usually develop in a short period of time (often about 1 month before diagnosis). There is a rapid onset and fast progression. Signs and symptoms of DIPG may include:

Loss of balance or problems walking
Eye problems such as blurred vision, double vision, drooping eyelids, uncontrolled eye movements, not being able to fully close the eye, eyes don’t look the same direction together or appear crossed (strabismus)
Facial weakness or drooping, usually on 1 side
Drooling or problems swallowing
Weakness in the legs and arms, usually on 1 side
Irregular or jerking movements
Abnormal reflexes
In very young children, a failure to thrive

Less common symptoms may include:

Nausea and vomiting
Headache, especially in the morning and often better after vomiting
Behavioral changes, school problems, irritability, or night laughter

Triad of symptoms and nerve problems in DIPG

DIPG triad of symptoms

Children with DIPG often have a collection of 3 symptoms, knowns as the DIPG triad of symptoms. About 1/3 of patients have all 3 signs at diagnosis.

Most patients develop at least 1 of these signs:

Problems with balance and coordination (ataxia)
Weakness in the arms and legs, jerking movements, and abnormal reflexes
Facial weakness or drooping or abnormal eye movement due to problems with nerves that control the muscles and sensation of the head, face, and eyes

Problems related to cranial nerves

Cranial nerves are 12 pairs of nerves that arise in the brain. Cranial nerves 5, 6, and 7 arise in the pons. They can be affected in DIPG. Specific problems can be related to each of these nerves:

Cranial nerve 5: Loss of sensation or numbness over the face and parts of the mouth
Cranial nerve 6: Abnormal eye movements such as not being able to look to the side or crossing of the eye
Cranial nerve 7: Weakness over the face, mainly the mouth and eyelids

Problems with cranial nerves 6 and 7 are most common in DIPG. Sometimes other cranial nerves can be injured. If the tumor spreads to an area above the pons, patients can develop more eye movement problems. If the tumor spreads to an area below the pons, problems with swallowing and changes in voice can occur.

Diagnosis of DIPG

An MRI can be used to diagnose diffuse intrinsic pontine glioma.

Doctors test for DIPG with tests that include:

A physical exam and medical history help doctors learn about:
- The type and time course of symptoms
- General health
- Past illness
- Risk factors
A neurological exam measures different aspects of brain function. These include memory, vision, hearing, muscle strength, balance, coordination, and reflexes.
Imaging tests help identify the tumor, see how big the tumor is, and find out what brain areas may be affected. Magnetic resonance imaging (MRI) is the main imaging test used to diagnose DIPG.

Doctors look for key features of the tumor on the MRI to diagnose DIPG:

The tumor is in the pons.
It usually involves and expands most of the pons (intrinsic).
The tumor does not have well-defined borders. It moves into healthy tissue (diffuse).

About 10–20% of pediatric brain tumors are found in the brainstem. When a tumor develops in the brainstem, it is usually DIPG. But about 20% of brainstem tumors are low-grade astrocytomas. These are not considered DIPG.

Role of biopsy in DIPG diagnosis

Doctors sometimes use a biopsy to diagnose DIPG. In the past, a biopsy was not usually used. Reasons for not doing a biopsy include:

DIPG often has specific features on both MRI and clinical evaluation. This means it can be diagnosed without any more tests.
There is risk of harm by doing a biopsy. This is because of the tumor’s location.
A biopsy may not change treatment plans or outcomes.

With better surgical techniques and advances in understanding, biopsy has become more common for DIPG. After a biopsy, a pathologist will look at the tissue sample under a microscope to identify the specific type and grade of tumor.

The tumor will also be tested for genetic changes or markers. Understanding tumor histology and molecular features may one day offer better treatments for DIPG. These could include targeted therapy and immunotherapy.

No one knows the cause of DIPG. But scientists are learning more about gene changes linked to these tumors. Having certain genetic disorders, including neurofibromatosis type 1 (NF1), may increase the risk of a brainstem glioma.

Staging and grading of DIPG

There is no standard staging system for DIPG. Treatment is based on 2 main factors:

Whether DIPG is found only in the brainstem or if it has spread to distant areas in the brain or spinal cord (metastatic disease)
Whether DIPG is newly diagnosed or has come back after treatment (recurrent disease)

Gliomas are grouped by how they look under the microscope. The more abnormal the cells look, the higher the grade. Grade 1 and 2 tumors are low-grade gliomas. The cells look more like normal cells and grow more slowly.

Grade 3 and 4 tumors are high-grade gliomas. They are aggressive and grow quickly. These tumors can spread throughout the brain.

DIPG tumors are usually high grade. Rarely, DIPG may appear as a low-grade tumor (grade 2).

H3 K27M mutation in DIPG

About 80% of DIPG tumors have a specific mutation, or change in the DNA. This mutation is known as H3 K27M.

This finding has led to a new diagnosis called diffuse midline glioma, H3 K27M-mutant. These tumors most often occur in the pons. But they may also be found in the thalamus, spinal cord, or other sites in the midline of the brain.

Even without a biopsy, it is thought that most DIPG tumors have the H3 K27M mutation. Tumors with an H3 K27M mutation usually have a poor outcome no matter the grade or how they appear under the microscope.

Treatment of DIPG

DIPG is quite aggressive. No cure is known at this time. The standard of care is based on radiation therapy.

Much of DIPG patient care focuses on controlling symptoms and supporting quality of life. Corticosteroid medicines such as dexamethasone can help reduce some of the tumor’s symptoms. These medicines are usually used at diagnosis and at tumor progression to help manage neurologic symptoms.

A number of clinical trials are exploring therapies that may improve outcomes for patients with DIPG.

Radiation therapy

Radiation therapy is the main treatment for DIPG. In most cases, radiation provides a temporary response to slow or shrink the tumor. But radiation therapy does not provide a long-term cure. It may ease symptoms for an average of 6 months. It may extend life by an average of 3 months.

At most U.S. treatment centers, the standard guideline is local radiation therapy for 6–7 weeks.

Newer studies suggest that hypofractionated radiation therapy may offer similar benefits with less burden on the patient and family. This approach gives larger doses of radiation over a shorter time (usually 3 weeks).

Radiation up front usually helps stall disease progression for a time. Recent studies have shown that repeat radiation to the DIPG tumor can be done safely. But when the disease comes back, the tumor has become more resistant to radiation. This means radiation’s benefits are more limited. When radiation is given a second time, it is usually done over 2–3 weeks.
Chemotherapy

Chemotherapy may be used along with radiation therapy. But it has not been found to increase length of life or overall survival in DIPG. As a result, chemotherapy is generally not offered as part of standard care for DIPG.

With new insights into the underlying genetic changes in DIPG, more tumor-specific treatment protocols are being tested through clinical trials. These include different combinations of drugs and new methods of giving them.

Convection-enhanced delivery of chemotherapy

The blood-brain barrier can make chemotherapy less effective for some brain tumors. This protective barrier prevents substances in the blood from getting into the brain. This can limit how much medicine reaches a brain tumor.

Scientists are exploring new drug-delivery techniques to overcome this problem. One method is convection-enhanced delivery (CED). It involves placing a catheter into the region of the DIPG tumor. This allows the drug to reach the tumor directly in a more controlled way.
Surgery

Surgery is not used to treat DIPG due to the tumor’s location. The pons, the region of the brain where the tumor occurs, controls vital life functions. This means the tumor cannot be removed by surgery.

Surgery may be used to help treat hydrocephalus. As the pons expands due to tumor, it can block cerebrospinal fluid (CSF) around the brain and spinal cord. This can cause added pressure on the brain. A child with hydrocephalus may have a shunt placed to drain fluid from the brain.

In some cases, surgery may be used to remove parts of the bone at the base of the skull (decompression). This can relieve pressure on the brainstem and spinal cord.
Targeted therapy
Targeted therapies work by targeting specific features of the tumor such as genes and proteins. Some targeted therapies being studied as part of clinical trials for DIPG target:
- Cell surface receptors thought to be enriched or active in DIPG
- Intracellular proteins that control cell growth and survival of tumor cells
- Proteins that repair DNA damage that might be changed in DIPG, making cancer cells more resistant to radiation and chemotherapy
- Proteins that regulate gene expression related to the H3 K27M mutation
Immunotherapy

Immunotherapy is a type of treatment that uses the body’s own immune system to recognize and attack cancer cells.

Certain types of immunotherapy are being explored in patients with DIPG. These include antibodies that may activate the patient’s immune system to fight the DIPG tumor. Scientists are also studying whether a vaccine may be able to target DIPG tumor cells that have a certain type of H3 K27M mutation.

Many patients with DIPG get care through a clinical trial. Clinical trials are available:

At the time of diagnosis
After completion of radiation therapy but before the disease progresses
After tumor progression

Many times, the tumor may shrink for a while after initial radiation therapy. Symptoms improve, and patients can go home to their usual activities. This is sometimes called the “honeymoon period.”

This phase is hard to predict. Some children are almost back to normal during this time. Some children do not improve at all. Families may use the time to be together or do something special as a family. Wish-granting organizations can often help with this.

Prognosis for DIPG

DIPG has no cure at this time.

Fewer than 10% of children in the United States survive more than 2 years after diagnosis. A somewhat better outcome may be seen in very young patients (3 years old or younger) and those who have symptoms for a longer time before diagnosis.

Patients with neurofibromatosis type 1 (NF1) who have diffuse brainstem tumors may also live longer with the disease.

Long-term survival in DIPG is generally linked to atypical features or misdiagnosis (the tumor was not actually DIPG).

Support for children with DIPG

In DIPG, symptoms get worse over time. Supportive care helps maintain quality of life as much as possible for as long as possible.

Talk to your care team about problems to expect and ways to help manage them.

Common symptoms of late stage DIPG

Symptoms can worsen rapidly when DIPG comes back. But symptoms and their course and severity can vary.

Some signs and symptoms of late-stage DIPG include:

Loss of balance and motor control. This often leads to inability to walk and the need for a wheelchair.
Weakness and paralysis that gets worse, often on 1 side of the body
Problems swallowing. This may lead to aspiration pneumonia, not being able to eat normally, and requiring a feeding tube
Weight gain and face swelling or puffiness because of corticosteroid medicines such as dexamethasone
Problems speaking or communicating
Anxiety, irritability, or agitation
Depression and feelings of sadness
Fatigue or drowsiness
Sleep problems
Changes in vision
Headache
Nausea and vomiting
Constipation
Decrease in urine, urinary retention
Problems breathing
Problems with heart rate and blood pressure
Seizures
Confusion, delirium
Loss of consciousness

Medicines can help control pain, nausea and vomiting, anxiety and depression, and medical problems that develop as the tumor grows.

Art therapy, music therapy, and other complementary therapies can also help patients and families manage symptoms.

Weight gain and face swelling with DIPG

This is usually not due to the tumor itself. Weight gain, face swelling, and puffiness are mainly due to high doses of corticosteroids given to help manage symptoms of DIPG.

Brain tumors can cause fluid and pressure to build up. This pressure (hydrocephalus) causes symptoms such as headaches, nausea, weakness, and problems walking. Steroid medicines like dexamethasone decrease brain swelling and pressure. But they also have side effects, especially when given in high doses or for a long time.

Corticosteroids can increase appetite and cause patients to eat more and gain weight. These medicines can make it hard for the body to get rid of fluids, causing swelling. The body may also store fat differently. This can lead to puffy cheeks or “moon face.”

Rapid weight gain sometimes causes stretch marks on the skin. The change in appearance due to corticosteroids can be distressing to patients and families. Other side effects of steroid treatment include mood swings, irritability, and muscle weakness.

Despite the side effects, these medicines are an important part of supportive care and quality of life for many brain tumor patients. Talk to your care team about side effects and goals of care.

Read more about steroids from the American Brain Tumor Association.

Hydrocephalus causes symptoms such as headaches, nausea, weakness, and problems walking. Steroid medicines decrease brain swelling and pressure, but they also have side effects. Weight gain, face swelling, and puffiness are mainly due to high doses of corticosteroid medications. — Hydrocephalus causes symptoms such as headaches, nausea, weakness, and problems walking. Steroid medicines decrease brain swelling and pressure, but they also have side effects. Weight gain, face swelling, and puffiness are mainly due to high doses of corticosteroid medications to treat hydrocephalus.

Working with the care team

With the poor prognosis of DIPG, it is important for families to talk with their care teams about goals of therapy, palliative care, and end of life care. These conversations should begin early in the care process.

Goals of care change over the course of the disease with the changing needs of the patient and family.

A team of health care providers can help meet specific patient needs as DIPG progresses.

Palliative care or quality of life services help patients and families:

Manage pain and other symptoms
Promote quality of life
Make difficult decisions including treatment choices and end of life care

Hospice care provides medical and practical support as patients near the end of life. Rehabilitation services provide care for movement, speech, hearing, or swallowing problems. Child life, social work, spiritual care, and psychology can help with emotional and practical needs through the cancer journey for the entire family.

Questions to ask your child’s care team

What are our treatment options?
What can we expect as my child’s illness progresses?
What are the possible side effects of each treatment?
What can be done to manage side effects?
Will my child need to be in the hospital for treatment?
What options should we consider to promote quality of life for my child?
Where is the treatment available? Is it close to home or will we have to travel?

Key points about DIPG

DIPG is an aggressive brain tumor.
DIPG forms in the pons.
DIPG is hard to treat. Radiation therapy is one of the most common treatments.
Most children do not survive more than 2 years after diagnosis of DIPG.
DIPG symptoms can progress quickly. They can include loss of balance and motor skills, headaches, weight gain, and difficulty swallowing.
Early talks about palliative care can help families and care teams decide on treatment goals.

More information on DIPG

Resources to support children during serious illness

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Reviewed: May 2023

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