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Diffuse intrinsic pontine glioma, or DIPG, is an aggressive brain tumor that forms in the base of the brain. DIPG begins in the brainstem, in an area called the pons. The pons controls vital life functions including balance, breathing, bladder control, heart rate, and blood pressure. Nerves that control vision, hearing, speech, swallowing, and movement also pass through this part of the brain.
There are about 200-300 new cases of DIPG every year in the United States. DIPG most often occurs in children ages 5-10 years old, but it can sometimes occur in younger children and teens. DIPG is rare in adults.
DIPG grows from glial cells, which make up the supportive tissue of the brain. It is a diffuse tumor, meaning that the tumor 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. Currently, the main treatment for DIPG is radiation therapy. Although radiation temporarily improves symptoms in most patients, it is not a cure. Families may consider clinical trials which test new treatments to see if outcomes can be improved.
Early palliative care is important to help families manage symptoms and promote quality of life.
DIPG tumors grow quickly, and symptoms usually develop in a short period of time (often about 1 month before diagnosis). There is a rapid onset and fast progression of problems. Signs and symptoms of DIPG may include:
Less common symptoms may include:
DIPG triad of symptoms
Children with DIPG often have a collection of three symptoms, knowns as the DIPG triad of symptoms. About 1/3 of patients have all three signs at diagnosis, and most patients develop at least one of these signs:
Problems related to cranial nerves
Cranial nerves are 12 pairs of nerves that arise in the brain. Cranial nerves 5, 6 and 7, which arise in the pons, can be affected in DIPG. Specific problems can be related to each of these nerves:
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 (midbrain), patients can develop additional problems with eye movements. If the tumor spreads to area below the pons (medulla), problems with swallowing, and changes in voice can occur.
Doctors test for DIPG in several ways. These tests include:
Doctors look for key features of the tumor on the MRI to diagnose DIPG:
Of pediatric brain tumors, about 10-20% are found in the brainstem. When a tumor develops in the brainstem, it is usually DIPG. However, about 20% of brainstem tumors are low-grade astrocytomas and are not considered DIPG.
A biopsy is sometimes used to diagnose DIPG. In the past, a biopsy was not usually recommended. However, it is becoming more common. Reasons for not doing a biopsy include:
With better surgical techniques and advances in the understanding of the biology of DIPG, the recommendation for a biopsy has become more common. 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 such as targeted therapy and immunotherapy.
There is no standard staging system for DIPG. Treatment recommendations are based on two main factors:
Gliomas are grouped by how they look under the microscope. The more abnormal cells look, the higher the assigned grade. Grade I and II tumors are considered low grade gliomas. The cells look more like normal cells and grow more slowly. Grade III and IV tumors are considered high grade gliomas. They are aggressive and grow quickly and can spread throughout the brain. DIPG tumors are usually high grade. More rarely DIPG may appear as a low grade tumor (grade II).
A specific mutation, or change in the DNA, is found in most (about 80%) DIPG tumors. This mutation is known as H3 K27M. It is found in tumors located deep within the middle part of the brain and spine that show diffuse or infiltrative growth. This finding has led to a new diagnosis based on pathology 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, and other sites in the midline of the brain.
Even without a biopsy, it is thought that most DIPG tumors have the H3 K27M mutation. These are aggressive tumors. Tumors that have an H3 K27M mutation usually have a poor outcome no matter the grade or how they appear under the microscope.
Unfortunately, there is no cure for DIPG at this time. Less than 10% of children survive more than 2 years after diagnosis. A somewhat better outcome may be seen in very young patients (3 years of age or younger) and patients with a longer duration of symptoms leading to diagnosis. Diffuse brainstem tumors in patients with neurofibromatosis type 1 (NF1) may also live longer with the disease. However, long-term survival in DIPG is typically thought to be associated with atypical features or misdiagnosis (the tumor was not actually DIPG).
Most patients with DIPG do not survive longer than 2 years from diagnosis. In a recent study of an international DIPG registry, the median overall survival was 11 months from diagnosis. The time to tumor progression was 7 months from diagnosis. Only 10% of patients lived more than 2 years with DIPG, and the survival rate was less than 2% at 5 years.
An abstract of the original report can be found online.
In most patients, radiation therapy helps to stop or slow the symptoms of DIPG. But this improvement is only temporary. Radiation may shrink the tumor, but it starts to grow again within months. Once DIPG comes back after initial treatment, the disease usually progresses quickly and does not respond to further treatment. Death often occurs within a few months.
DIPG can sometimes spread outside of the brainstem before treatment. About 20% of patients with DIPG have spread of disease to distant areas of the brain or spine or the meninges at diagnosis. This latter type of spread of disease is called leptomeningeal metastases. DIPG can also spread to other areas of the brain and spinal cord or the meninges as the disease progresses after treatment. About 20% of patients have spread to distant regions at tumor progression.
DIPG is a very aggressive cancer. There is no cure at this time. The current standard of care is based on radiation therapy. Much of DIPG patient care is focused on controlling symptoms and supporting quality of life as much as possible. Corticosteroid medications such as dexamethasone (Decadron®) can help reduce some of the symptoms caused by the tumor. They 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 is the main treatment for DIPG. In most cases, radiation provides a temporary response to slow or shrink the tumor. However, radiation therapy does not provide a long-term cure. It may provide a temporary easing of symptoms lasting an average of 6 months and may extend life by an average of 3 months.
At most treatment centers in the US, the standard recommendation is local radiation therapy with a dose range of 54-60 Gy for a period of 6 to 7 weeks. Newer studies suggest that hypofractionated radiation therapy may offer similar benefits with less burden on the patient and family. This hypofractionated approach gives larger doses of radiation over a shorter time (usually 3 weeks).
Radiation upfront is usually helpful in stalling disease progression for a time. Recent studies have shown that repeat radiation to the DIPG tumor can be done safely; however, when the disease recurs, the tumor has become more resistant to radiation, and the benefits of radiation are more limited. When radiation is given a second time, it is usually done over 2 to 3 weeks.
Chemotherapy may be used in addition to radiation therapy to see if better outcomes can be achieved. However, chemotherapy 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 administration.
The blood-brain barrier can limit the effectiveness of chemotherapy for some brain tumors. This protective barrier acts to prevent substances in the blood from getting into the brain. This can limit how much medicine reaches a brain tumor. New drug delivery techniques are being explored to overcome this problem. One of these methods is Convection-Enhanced Delivery (CED). It involves placing a catheter into the region of the DIPG tumor by precise surgery. This allows the drug to reach the tumor directly in a more controlled way.
Surgery is not used to treat DIPG due to the location of the tumor. The pons, the region of the brain where the tumor occurs, is responsible for vital life functions. Therefore, 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 surrounding the brain and spinal cord. This can cause increased pressure on the brain. Some children with hydrocephalus due to DIPG 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) to relieve pressure on the brainstem and spinal cord.
Targeted therapies work by acting on, or targeting, specific features of the tumor such as genes and proteins. Some targeted therapies being studied as part of clinical trials in DIPG include targeting:
Immunotherapy is a type of treatment that uses the body’s own immune system to recognize and attack cancer cells. More recently, various types of immunotherapy are being explored in patients with DIPG. These include antibodies that may activate the patient’s immune system to fight against the DIPG tumor. Scientists are also studying whether a vaccine may be able to target DIPG tumor cells that have a specific type of H3 K27M mutation.
Many patients with DIPG receive care through a clinical trial. Clinical trials are available for patients at the time of diagnosis, after completion of radiation therapy but before progression, or after tumor progression.
There is often a time after initial radiation therapy where the tumor shrinks temporarily. Symptoms improve, and patients are able to go home to their usual activities. This is sometimes known as 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.
DIPG is progressive, and symptoms get worse over time. Supportive care helps maintain quality of life as much as possible for as long as possible. Families should talk to their care team about what problems to expect and ways to help manage them.
When DIPG comes back, symptoms can progress rapidly. However, symptoms and their course and severity can vary. Some signs and symptoms of late stage DIPG include:
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.
This is a common question. However, most often, this is not due to the tumor itself. Weight gain, face swelling, and puffiness are mainly due to high doses of corticosteroid medications 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. They can make it hard for the body to get rid of fluids, causing swelling. The body may also store fat differently, leading 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 very 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. Families should talk to their care team about side effects and goals of care.
Read more about steroids from the American Brain Tumor Association.
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 is important to 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, and navigate care 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.
Reviewed: November 2019