Diffuse intrinsic pontine glioma (DIPG) is a type of brain tumor found in the pons, part of the brainstem on the lower back of the brain, near the top of the spinal cord. DIPG primarily affects children, with most diagnoses occurring between 5 and 7 years of age. DIPG makes up 10-15% of all brain tumors in children, with about 100-150 new diagnoses per year in the United States and about 300 per year in all of North America and Europe. Unlike many other pediatric cancers, there has been little progress in improving treatments and cure rates for DIPG over the last few decades. Unfortunately, fewer than 10% of children with DIPG survive two years from diagnosis.
What Causes DIPG?
Researchers do not know yet exactly what causes DIPG. Like most cancers, DIPG occurs when something goes during the process of cell reproduction. Cells use DNA, the building blocks of genes, in order to carry out various functions, including making more cells. Sometimes pieces of DNA become damaged or are copied incorrectly. Scientists call this a mutation. Usually, cells with mutations in their DNA either repair the mutation or die (a process called apoptosis). Sometimes, though, cells with mutations can’t be repaired and don’t die like they are supposed to. In certain cases, these mutated cells begin to divide quickly, which may cause a person to develop cancer. It is likely that more than one mutation is involved in DIPG, and also that not every patient with DIPG has the same mutations. Sometimes different cells in the same tumor may have different mutations, making it very difficult to pinpoint the cause of the disease.
So far, there is no evidence that DIPG is caused by any environmental factor, such as exposure to chemicals or radiation. There is also no evidence yet that specific inherited genetic variations contribute to DIPG. Researchers are working hard to understand the causes of DIPG, which should help them to design better treatments for the disease.
Because of their location in the brainstem, DIPGs causes pressure on the cranial nerves that originate in the pons as they grow. These nerves control muscles used to move the eyes and the face and to chew and swallow. The symptoms of DIPG include double vision, difficulty in controlling eye and eyelid movement and facial expression, and difficulty chewing and swallowing. Pressure on other nerves may cause weakness in the arms and the legs and difficulty speaking and walking. The tumor itself and a related condition called hydrocephalus (the build-up of fluid in the brain) increase pressure inside the skull, which can cause headaches (especially in the morning), nausea and vomiting, and fatigue. Because DIPGs grow quickly, symptoms usually get worse quickly.
If your doctor suspects a brain tumor, he or she will conduct a physical examination and will order tests to collect more information. Brain tumors are usually diagnosed using imaging, including computerized tomography (also called CT or CAT scans), magnetic resonance imaging (MRI), and/or magnetic resonance spectroscopy (MRS).
A CT scan uses x-rays to create a series of images of vertical and horizontal sections of the brain (often referred to as slices). A CT scan measures differences in density between tumor tissue and normal brain tissue as well as the mass effect of the tumor (changes in the brain because the tumor is taking up space inside the skull). Dyes are often injected intravenously during a CT scan. Tumor tissue absorbs more dye than healthy tissue, which makes the tumor show up more clearly on the scan.
MRI uses large magnets to create detailed images of the body’s soft tissues. MRIs help doctors distinguish among tumor tissue, swelling related to the tumor, and normal tissue. Intravenous dyes are also used with MRI to create more contrast between the tumor and healthy tissue.
MRS scans are sometimes used when the diagnosis of DIPG is uncertain. MRS can detect the presence of specific molecules produced by normal and tumor tissue. DIPG is very difficult to treat, and there is no cure for DIPG so far.
- The name diffuse intrinsic pontine glioma describes how the tumor grows, where it is found, and what kinds of cells give rise to the tumor.
- Pontine describes where the tumor is located. It is found in a part of the brain called the pons, near where the spinal cord meets the brain. The pons is responsible for a number of important bodily functions, like breathing, sleeping, bladder control, and balance. Because these functions are vital to survival, the pressure from the growing tumor is very dangerous.
- Glioma is a general term for tumors originating in glial cells. Glial cells are found throughout the brain. They make up the white matter of the brain that surrounds and supports the neurons (cells that carry messages in the brain). Gliomas can form in different areas of the brain. DIPG occurs in glial cells in the pons.
Forms of Treatment
Radiation therapy (x-rays directed at the tumor) is the best available accepted treatment. The radiation kills some of the cancer cells, shrinking the tumor and reducing pressure on the brainstem. This can greatly improve how the child feels and functions for a few months, and 75-85% of patients show some improvement in symptoms after radiation therapy. Because even carefully aimed radiation therapy causes some damage to the healthy brain tissue surrounding the tumor, there is a limit to how much radiation therapy can be given to each patient. Unfortunately, the cancer almost always grows back after a few months. In clinical trials, researchers have used drugs called radiosensitizers, which should make cancer cells more likely to die when treated with radiation, to try to make radiation therapy more effective. These clinical trials have not shown any benefit to patients so far.
Current chemotherapy is generally not effective against DIPG. Most cancer-killing drugs are not able to get into the tumor at all, which seems to be protected by the high pressure inside the pons and by the blood-brain barrier, which prevents most drugs given orally or intravenously from reaching the brain.
A series of clinical trials have tested various chemotherapy drugs and combinations of drugs before or along with radiation therapy, but so far, no trial has shown that chemotherapy extends life. Trials of newer molecularly targeted agents and anti-angiogenic agents (drugs that should prevent tumors from forming new blood vessels to feed their growth) have also so far failed to show any significant benefit to patients. Researchers are studying drugs that may be able to pass through the blood-brain barrier and are also investigating ways to inject chemotherapy drugs directly into the tumor. Work to discover new drugs also continues. As researchers learn more about the causes and biological mechanisms of DIPG, they may be able to design more effective chemotherapies to fight these tumors.
DIPG grows in a way that makes surgical removal (often called “resection”) impossible. The cancer tissue spreads into healthy tissue, and the edges of the tumor are not well defined. Surgeons cannot remove the tumor because there is no way to avoid cutting out healthy brain tissue which is necessary for survival.
Radiation therapy and chemotherapy can cause side effects. Radiation therapy often causes inflammation in the brain, which can temporarily make symptoms worse. Steroids are used to control inflammation when necessary.
Some chemotherapy drugs can cause side effects such as diarrhea, constipation, fatigue, and headache. Usually these side effects can be controlled with additional medications.
Specialized Pediatric Brain Tumor Centers
DIPGs are relatively rare, and the diagnosis and treatment of DIPG is complex and involves multiple specialists. The experts working with the DIPG Registry recommend that patients and families receive a definitive diagnosis and care at comprehensive, experienced pediatric medical centers with dedicated pediatric neuro-oncologists, neurologists, neuroradiologists, and neurosurgeons. Such centers usually offer multidisciplinary clinics, which allow patients to see multiple specialists during a single visit. This facilitates the close coordination of care. Most specialized pediatric neuro-oncology programs also offer support services such as neuropsychological consultation and school intervention professionals. These centers usually participate in collaborative clinical research groups such as the Children’s Oncology Group or the Pediatric Brain Tumor Consortium, which sponsor clinical trials of experimental treatments.
Sometimes, children with DIPG and their families can travel to a hospital with a specialized brain tumor program for diagnosis and expert advice but receive ongoing care at a hospital closer to home.
It is not possible to treat DIPG by removing tumors surgically, but surgical biopsies to remove small amounts of tumor tissue for diagnostic testing are sometimes performed. Most diagnoses of DIPG are made from imaging scans such as MRI. Because of the risks of the procedure, surgical biopsy has usually only been performed when it has not been possible to confirm a diagnosis based on imaging. In the United States and Canada, most doctors do not generally recommend biopsy, and few patients undergo the procedure. However, recent research has shown that advanced stereotactic surgical techniques greatly reduce the risks of surgical biopsy, which can sometimes yield useful diagnostic information and influence treatment decisions. Stereotactic surgical biopsy has now become a routine part of the diagnostic process at some European centers.
As researchers learn more about the genetics and biology of DIPG, they may discover that there are, in fact, important differences between different patients’ tumors. These differences could help physicians target future therapies to the right patients. In this case, surgical biopsy could become an important tool in treating the disease in the future. Tumor tissue left over from surgical biopsy, as well as tumor tissue donated by families after children with DIPG have died, can be very helpful to researchers studying DIPG.
Reassurance / Relapse
Although 75- 85% of patients show some improvement in their symptoms after radiation therapy, DIPGs almost always begin to grow again (called recurrence, relapse, or progression). Clinical trials have reported that the median time between radiation therapy treatment and progression is 5-8.8 months.
Patients whose tumors begin to grow again may be eligible for Pilot, Phase I, or Phase II clinical trials. These clinical trials use experimental drugs or other experimental therapeutic approaches to try to slow or stop the growth of the tumor. Unfortunately, clinical trials have not shown any significant benefit from these experimental therapies so far. However, researchers are always working to develop new potential therapies for DIPGs. By participating in clinical trials, patients and families can help researchers learn more about DIPG and perhaps help future patients.
Unfortunately, DIPGs that progress usually grow quickly and affect important parts of the brain. Clinical trials have reported that the median time from tumor progression to death is usually very short, between 1 and 4.5 months. During this time, doctors focus on controlling symptoms and helping children to feel as comfortable as possible.
Source: DIPG Registry (www.dipgregistry.org)