Diffuse intrinsic pontine gliomas (DIPG)

Diffuse intrinsic pontine gliomas (DIPG) are a type of brain tumour that arises from the pons, a part of the brainstem which is located at the base of the brain. The brainstem controls vital functions such as breathing, heart rate, the sleep-wake cycle, etc. Additionally, many of the nerves that control the muscles of our face, eyes, and tongue arise from the brainstem.

Because of their location, these tumours are difficult to treat as it is impossible to remove a tumour in the brainstem without severe damage to vital functions controlled by the brainstem. Instead of surgical removal, the main treatment for DIPG is radiation therapy.

DIPGs are usually diagnosed in children aged 5 to 10, however they can be seen at any age, including in toddlers and in teenagers.

You and your child will have a dedicated, supportive care team who will help you make decisions about your child’s care and can offer other resources and supports in areas such as family support, mental health and finances.

What are the symptoms of a diffuse pontine glioma?

When the DIPG tumour presses on the brainstem and the nerves that control the muscles of the face, eyes and tongue, symptoms appear.

Patients diagnosed with DIPG present with the following symptoms:

• crossed eyes
• facial asymmetry (crooked smile)
• balance problems (ataxia)
• muscle weakness on one side of the body (hemiparesis)
• swallowing problems (dysphagia)
• speech problems (dysarthria)
• drowsiness
• hearing loss
• personality changes

Sleep problems are also frequently described, for example nighttime laughter is usually noted before other symptoms appear.

Most symptoms develop quickly, over a period of 1 to 2 weeks. Sometimes symptoms can develop over a longer time, but usually less than 3 months.

What causes a diffuse intrinsic pontine glioma?

The cause of DIPG is unknown. Research has shown that DIPGs rise from brain cells that are unable to properly develop into a mature normal brain cell. There is no way to predict that a child will get brain cancer.

There is no definite proof that there is a connection between environmental factors such as food, chemicals or radiation and the development of brain cancer in children.

Biology of DIPG

Doctors and scientists’ understanding of the biological behaviour of DIPGs has significantly improved in recent years. It is now known that most of these tumors are characterized by a mutation in a protein called histone. The main function of histone proteins is to protect the DNA.

Most recently, scientists have also learned that not all DIPGs behave the same way. Some may be dormant (inactive or not growing quickly) for a long time while others are very aggressive. Certain medication can be used to target different tumor components to slow down its growth.

How many children have diffuse intrinsic pontine gliomas?

DIPGs account for about 10% of brain tumours in children.

How are diffuse intrinsic pontine gliomas diagnosed?

Doctors and other health-care professionals use well-established diagnostic tests to see if a brain tumour is causing your child’s symptoms. These tests will include a physical examination, and brain scans such as magnetic resonance imaging (MRI). The diagnosis is usually made based on the signs and symptoms in your child, and on the results of the MRI study.

When the DIPG tumour looks typical on an MRI, a biopsy is not required to confirm the diagnosis.

How are diffuse pontine intrinsic gliomas treated?

While there are different treatments that may be recommended for your child, the main type of treatment for DIPG is radiation therapy.

The treatment team is led by a doctor called a neuro-oncologist. They take the responsibility for your child’s care and make the decisions about your child’s treatment plan.

Radiation for DIPG

DIPGs are treated with radiation therapy, which are high-energy X-rays, gamma rays, or electrons that destroy tumour cells and shrink tumours. This treatment can reduce symptoms significantly, but there may be some permanent damage to the brainstem caused by the tumour which can not be repaired by the radiation treatment.

Steroids for DIPG

Steroids, an anti-inflammatory medication, are often given to improve some of the symptoms of gliomas. Steroids decrease the swelling (edema) within and around the tumour and often cause significant improvement of the symptoms. Usually doctors start steroid treatment immediately after the initial MRI, unless your child has very mild symptoms. They will continue the steroid until there is evidence that your child gets better.

Surgery for DIPG

Surgery is not part of the standard treatment for DIPG because it is too damaging to this part of the brain and it does not improve the outcome. However, surgery may be considered if a tumour component grows outside the brainstem (exophytic component).

Biopsy of these tumors may be considered as part of diagnosis to confirm the diagnosis and sometimes to find changes that can be amenable to treatment with new drugs.

Other treatments for DIPG

There are several other types of treatment being considered. Treatments targeting molecules expressed by the tumor cells have been developed and may be offered to certain patients. The use of those “targeted agents” is dependent on the finding of an alteration in the tumor cells obtained through a biopsy. However, these treatments target only a small minority of DIPG tumours and for the large proportion there is no targeted treatment that will specifically ‘turn off’ the tumour, or stop it from growing.

Chemotherapy for DIPG

In DIPG, the effectiveness of chemotherapy is uncertain. In DIPGs, chemotherapy has not shown effective killing of the tumor cells and is not routinely offered. Although many trials have been done using chemotherapy, there is no evidence that it improves survival.

In DIPG, chemotherapy is given in one of the following circumstances:

• As part of a clinical trial to evaluate the benefits of new chemotherapy drugs or drug combinations in addition to radiation
• At a later stage when the child's tumour shows signs of progression (getting worse). The aim in this case is to try to decrease the symptoms of progression and to help improve quality of life

What is the outcome for a child with a diffuse intrinsic pontine glioma?

After diagnosis, the survival time is on average 9 to 12 months. This is because brainstem gliomas are difficult to treat. To improve the outcome, doctors have tried giving higher amounts of radiation, or using chemotherapy medications to kill the tumour cells. Research is underway to achieve better results. When the tumour recurs (grows back after initially responding to treatment), the focus of treatment is on managing symptoms to make sure the child is as comfortable as possible.

Recurrence of diffuse intrinsic pontine gliomas

Repeated radiation therapy to the tumor area has been the only treatment proven to improve symptoms and prolong the life of patients with DIPG at recurrence. Such treatment is usually offered to children who had a good response to initial treatment and at least 4 to 6 months of remission following radiotherapy. The second radiation treatment will give a lower dose, as the brainstem cannot tolerate a high dose of radiotherapy twice.

Unfortunately, no chemotherapy or high-dose chemotherapy treatment has yet shown any benefit in curing a recurrence. When a DIPG recurs, the focus of care is to manage symptoms with the fewest side effects possible. Sometimes chemotherapy drugs taken by mouth are offered.

Because of their side effects, steroids are usually avoided at the time of recurrence, except when a second radiation treatment is planned.

Surgery to place a shunt is sometimes considered when a recurrence occurs, if the child has hydrocephalus due to the blockage of the flow of cerebrospinal fluid in the brain by the growing tumour. However, a shunt is not a treatment for DIPG itself; the objective of the shunt placement is to improve the symptoms associated with hydrocephalus and improve the child's quality of life.