About Diffuse Intrinsic Pontine Glioma (DIPG)

What is DIPG?

Diffuse Intrinsic Pontine Glioma (DIPG) is an aggressive, malignant brain tumour almost exclusively affecting children between the ages of 4 and 11. It originates in the pons, a critical part of the brainstem controlling vital functions like breathing, swallowing, facial expressions and balance. The brain stem is the bottom most portion of the brain, connecting the cerebrum with the spinal cord. These tumours are diffuse, meaning they spread throughout the pons amidst the nerves and cannot be surgically removed due to their location and the risk of damaging healthy tissue.

There is currently no cure.

DIPG is thought to be responsible for 80% of all brain tumour death that occurs in children. Like most brain tumours, the cause of pontine gliomas is unknown.

A giagram of DIPG in the PONS area of the brain

Breaking down the acronym

DIPG It is a type of Diffuse Midline Glioma (DMG), a primary central nervous system tumour. This means they begin in the brain or spinal cord.

Diffuse: means that the tumour is not well-contained or localised. Instead, it infiltrates and spreads throughout the surrounding tissue, with cancer cells intermingling with healthy cells.

Intrinsic: means the tumour originates from within the pons area of the brainstem, growing throughout it cannot be removed

Pontine: Pontine indicates the location of the tumour is in the pons, a part of the brainstem that controls vital for life functions such as breathing, sleep, bladder control, and balance.

Glioma: is a broad term used for tumours that arise from glial cells. These cells are found throughout the brain, forming the white matter that surrounds and supports the neurons responsible for transmitting signals.

Signs and Symptoms of DIPG

The signs of a DIPG vary as the pons and surrounding structures (where DIPGs are located) are responsible for a variety of different body functions. Nearly all will be emergency presentations.

A child with a DIPG may display:

Abnormal alignment of the eyes or/and double vision (diplopia).
Weakness of facial muscles or facial asymmetry (one side of the face appearing different from the other).
Arm and leg weakness.
Unstable balance and co-ordination.
Difficulties walking and speaking.
Difficulty swallowing/unusual drooling.
General tiredness.
Changes in normal 'mood', unusually emotional.
In a relatively small number of cases, growth of a DIPG might block the drainage of cerebrospinal fluid (the fluid which surrounds and nourishes the brain), causing a build-up of pressure in the head. This is known as hydrocephalus which is very common in other types of brain tumours. Hydrocephalus can cause symptoms such as headache (especially in the morning), nausea and fatigue. Hydrocephalus can be deadly and requires surgical intervention.

Not all cases of DIPG are identical and a child might show a combination of these symptoms.

Who Does DIPG Affect?

DIPG almost exclusively affects children aged 4 to 11. Approximately 40 children per year develop DIPG in the UK, representing 10-15% of all childhood brain tumours.

It is not hereditary and occurs equally among boys and girls.

Diagnosis and Tests

Some tests will need to be carried out to find out as much as possible about the type, position and size of the tumour. This will help to decide the best treatment for your child.

CT Scan: Often the initial imaging test ordered at your local hospital, a CT (computed tomography) scan uses X-rays to create detailed cross-sectional pictures of the body's internal structures. During the scan, your child will lie on a table attached to the doughnut-shaped CT scanner.

MRI Scan: Magnetic resonance imaging (MRI) is regularly employed to diagnose and monitor the tumour’s response to treatment. This advanced imaging technique relies on strong magnetic fields and radio waves to generate highly detailed images of the brain and spinal cord. Your child will lie inside a tube-like scanner during the procedure.

Biopsy: As part of some clinical trials biopsy is becoming mandatory, it may be performed to obtain a tumour sample for diagnostic confirmation and in-depth tumour analysis. This involves sequencing and profiling the tumour to identify specific mutations like the H3 K27M mutation, which can guide personalised treatment strategies. Incorporating biopsies into DIPG treatment planning is becoming increasingly common.

These diagnostic tests play a crucial role in establishing an accurate diagnosis and tailoring the most appropriate therapeutic approach for your child's specific condition.

What is the H3 K27M Mutation?

When a child is suspected of having DIPG, doctors typically perform an MRI scan. In the past imaging alone has been used to diagnose, and is a strong indication of DIPG. To confirm diagnosis fully and understand the specific characteristics, or the tumour 'biology', doctors may take a small sample of the tumour tissue through a biopsy.

After the biopsy, the tumour tissue will be tested for the presence of the H3 K27M mutation. Finding this mutation in the tumour cells can confirm the diagnosis of DIPG, or DMG if located in other midline structures. This mutation is now considered the hallmark of DIPG disease.

In addition to confirming the diagnosis, identifying the H3 K27M mutation can also provide information about how the tumour might behave and how it might respond to treatment.

In simple terms, research has shown the presence of the H3 K27M mutation as a known molecular driver of the disease and is commonly associated with a less favourable diagnosis relative to gliomas that do not harbour this mutation, such as H3 wildtype. It is a key factor in the development of DIPG and unfortunately currently 'undruggable' making DIPG very difficult to treat and often resistant to any current therapies.

In more detail H3 K27M is a specific mutation in one of the genes that encode for proteins called histone H3. This mutation is almost exclusively found in (around 80%) of DIPG’s. Gliomas that contain the H3 K27M mutation undergo a specific change in histone H3 proteins that prevents methylation at a specific site, and results in H3 K27M trimethyl loss (H3 K27me3-loss). This leads to a cascade of changes in the epigenetic landscape that drives tumorigenesis. Precisely, the mutation is a substitution of lysine for methionine at position 27 of histone 3.

The H3 K27M mutation may also be called H3 K28M or H3 K27-altered (H3 is also sometimes referred to as histone H3, H3F3A, HIST1H3B, HIST1H3C, H3.3 or H3.1).

The mutation has become a diagnostic marker for DIPG, and other Diffuse Midline Glioma tumours (DMG’s) located in ‘midline’ regions of the central nervous system such as the brainstem and thalamus.

H3 K27M-mutant DMG is a World Health Organization (WHO) classification Grade IV brain tumour.

Whilst H3 K27M can be found in tumour locations throughout the central nervous system and across age groups, the mutation has a higher incidence in midline locations and in relatively young patients.

Testing for the H3 K27M mutation is often performed at diagnosis via methods that include immunohistochemistry (IHC) staining and gene sequencing.

Standard Treatment

Treatment Options:

Radiotherapy: The 'standard of care' treatment for DIPG is radiotherapy, which is usually administered over 3 to 6 weeks depending on the type of radiotherapy that is deemed best for your child (with a daily dose given Monday to Friday up to 54 Gy fractions). This is considered 'palliative' radiotherapy to manage symptoms and is not curative.

Steroids (Dexamethasone): Your child might also be given steroids (Dexamethasone) during this period to help reduce some of the swelling and inflammation caused by the tumour and radiation treatment. These unfortunately have some very unpleasant side effects, they do not prevent tumour growth but are necessary to alleviate symptoms. They should ideally be weaned as soon as possible and can impact some treatments so always discuss with your treating oncologist.

Shunt or ETV Surgery: If hydrocephalus (a build-up of fluid on the brain) is found in diagnostic scans or subsequent scans it can usually be treated using a shunt, a thin tube that's surgically implanted in the brain and drains away the excess fluid. An endoscopic third ventriculostomy (ETV) can sometimes be used as an alternative to shunt surgery. During this procedure, a hole is made in the floor of the brain to allow the trapped CSF to escape to the surface, where it can be absorbed.

Challenges:

If your child is diagnosed with a DIPG, having surgery to remove the tumour is not a viable option due to the dangers of operating on critical areas of the brain.

Based on the findings of numerous research studies, no single chemotherapy drug has been shown to be effective in treating DIPG, so your child should be unlikely to receive an oral chemotherapy treatment, unless as part of a clinical trial.

Palliative Care

All DIPG children are essentially considered in palliative care, so do not be alarmed if this is referred to soon after diagnosis of your child.

Palliative care is specialised medical care that focuses on providing relief from pain and other symptoms of DIPG. It also can help your child to cope with side effects from radiotherapy. It involves psychological, social and spiritual support for your child and your family. This is called a holistic approach, because it deals with your child as a "whole" person, not just the DIPG or symptoms.

The people providing your child’s care should ask you about your wishes and preferences and take these into account as they work with you throughout the disease course to plan your care, including if you would like to care for your child in a hospice, or at home.

Different health and social care professionals may be involved in your child’s end of life care, depending on their needs. For example, hospital doctors and nurses, your GP, community nurses, hospice staff and counsellors may all be involved, as well as social care staff, chaplains (of all faiths or none), physiotherapists, occupational therapists or complementary therapists.
If you would like your child cared for at home, your GP has overall responsibility for their care with the support of Community Nurses. They should also support your family, carers or other people who are important to you.

You have the right to express your wishes about where you would like to receive care and where your child wants to die. You can receive end of life care at home, in a care home, hospice or be cared for in hospital, depending on your needs and preference.

Prognosis and Progression

Current Prognosis

The prognosis for children with DIPG remains incredibly poor, as there has been a lack of medical advancements to improve survival rates or provide a cure. Only 10% of children diagnosed with DIPG survive beyond 2 years, and a mere 1% manage to reach the 5-year survival mark. The median survival time is 9 months from the time of diagnosis.

Despite ongoing research efforts, the outlook for DIPG patients has remained largely unchanged, underscoring the urgent need for breakthroughs in this devastating childhood cancer.

Progression

While radiation therapy provides initial respite, 75-85% of patients experiencing some symptomatic improvement, the relief is tragically short-lived. DIPGs invariably recur, a process known as relapse or progression, typically within 5 to 8.8 months after completing radiation treatment, as reported in research studies.

At this stage, any further treatment is primarily supportive and palliative, focused on alleviating the symptoms that manifest as the aggressive tumour rapidly regrows, affecting critical areas of the brain. The median time from tumour progression to death is alarmingly brief, ranging from just 1 to 4.5 months, according to clinical data.

Disease progression can also be known to occur more than once, and treatment options will differ depending on the prior treatments received. In some cases, there could be a second round of radiation therapy offered called re-irradiation. Re-irradiation can be performed with fewer treatments than initial radiation therapy and usually occurs at least 6 months or more after the initial radiation treatment ended.

Despite the dire statistics surrounding average survival rates, it is crucial to recognise that every child's journey with DIPG is unique. If your child has been diagnosed with a DIPG, focusing on their wellbeing and quality of life is by far the most important thing.

Depending on the individual profile of the disease some experience more severe symptoms than others.
Some children can lead a reasonably full life and then exhibit a very rapid decline...for others it happens more gradually. Research has indicated some subsets of disease to be more aggressive but generally no two journeys will be the same to the final outcome.

End-Stage Symptoms

The following can be tough to take in and you might find it distressing, so please only read when you are ready to do so. Sadly, in the 'progression' stages of DIPG disease for most children everything will become a struggle. It is difficult to detail here and indeed predict to prospective parents the severity, but all normal function of your child will become affected. We're sorry to say that most children will become completely paralysed, after an initial phase of perhaps only one-side weakness, they will be unable eventually to speak or swallow. The inability to eat may involve the placing of an NG (naso-gastric) tube for feed to be administered. There is the possibility of aspirating food into the lungs with a failing swallowing mechanism. As the body eventually gets 'shut down' the stomach may stop absorbing any feed altogether. Children can also lose their sight, hearing and are unable to control their bowels. They become unable to hold up their head unsupported and with swallowing affected they will not be able to control the secretions that will collect and move to their lungs. You may be taught techniques used on cystic fibrosis patients to loosen these and need to employ suction to their throat, to make them more comfortable. Children may experience seizures in late stages which require drug intervention, blood pressure and heart rate can be affected. Children may appear to become sleepier or completely asleep the whole time until they eventually pass away. In many ways it can be like going back to a 'baby like ' state, which is clearly extremely distressing for parents, to see. Their child will be completely aware of their own decline. These children know exactly what they want to do and say and yet their bodies fail them in the cruellest way possible.

Are you the parent of a newly diagnosed child?

DIPG is a devastating diagnosis with no current cure. Understanding its nature, symptoms, and progression can help parents and caregivers manage the disease and seek out the best possible care and treatment options for their child.

If you are the parent of a recently diagnosed child, we aim to support you through this tough time. We can help connect you with the right experts quickly, providing the most up-to-date research and evidence-based guidance on treatment options. We can also connect you with other families who understand what you're going through.

Sharing symptoms, coping mechanisms, and experiences can be a powerful source of strength.

Visit our family support section

parent holding hand of child recieving hospital treatment

Help Fund Research

Despite the heartbreaking realities of DIPG, there's a flicker of hope. Ongoing research strives to unravel this disease and discover new, effective treatments. However, this vital work needs significant funding and resources.

You can directly impact the fight against DIPG. By donating, you fuel groundbreaking research, clinical trials exploring innovative therapies, and the search for answers – hope – for future families facing this devastating diagnosis.

Every contribution, big or small, translates into tangible progress. It brings us closer to a future where no child succumbs to DIPG.

Join our mission – a mission fuelled by your compassion and the power of scientific discovery. Together, we can rewrite the story of DIPG. Donate now and be a part of the solution that will save young lives.