Diffuse Intrinsic Pontine Glioma (DIPG)

The symptoms of diffuse intrinsic pontine glioma (DIPG) usually develop very rapidly prior to diagnosis, reflecting the fast growth of these tumors. Most patients start experiencing symptoms less than three months — and often less than three weeks — before diagnosis. The most common symptoms include:

• rapidly developing problems controlling eye movements, facial expressions, speech, chewing, and swallowing
• weakness in the arms and legs
• problems with walking and coordination

For a long time, little was understood about DIPGs because clinicians feared they could not be safely biopsied. However, recent and ongoing research at Dana-Farber/Boston Children's Cancer and Blood Disorders Center has led to important discoveries, allowing us to learn more about certain genetic mutations that may cause DIPGs.

The first step in treating your child is forming an accurate and complete diagnosis. Diffuse intrinsic pontine glioma (DIPG) is most commonly diagnosed from imaging studies.

Your child’s doctor will perform a complete medical and physical examination. In addition, your child’s physician may order some of the following imaging tests:

• computerized tomography scan 
• magnetic resonance imaging (MRI)
• magnetic resonance spectroscopy (MRS)
• biopsy

There are four stages of gliomas, according to how the cells look under a microscope. Ordered from least severe to most severe, they are:

Low grade:

• pilocytic (grade I)
• fibrillary (grade II)

High grade:

• anaplastic (grade III)
• glioblastoma multiforme (grade IV)

When DIPGs are biopsied, they are usually grade III or grade IV. Occasionally they are grade II, but, because of their location in the brain, they are still considered malignant. These are very aggressive tumors and grow by invading normal brain tissue.

Your child’s physician will determine a specific course of treatment based on several factors, including:

• your child's age, overall health, and medical history
• type, location, and size of the tumor
• extent of your child’s disease
• your child's tolerance for specific medications, procedures, or therapies

A number of treatments may be recommended. Some of them help to treat the tumor while others are intended to address complications of the disease or side effects of the treatment. Treatment for DIPG may include radiation therapy.

Radiation therapy

Radiation is the traditional therapy for newly diagnosed DIPGs, using high-energy rays (radiation) from a specialized machine to damage or kill cancer cells and shrink tumors. Conventional limited-field radiation produces responses in more than 90 percent of children with DIPGs. These responses are short-lived, however, lasting about six to nine months on average. Several trials to increase the dose of radiation therapy have been performed and none have improved survival.

Experimental chemotherapy

Biologic therapy and chemotherapy, in combination with radiation therapy, are actively being investigated as a treatment for DPG. Several trials evaluating new agents are either underway or have been recently completed. With a biopsy of the tumor at diagnosis, the selection of drugs targeted to your child’s tumor can be determined. Multiple clinical trials have demonstrated that routine chemotherapy does not increase survival rates for this condition.

Surgery

Complete surgical removal is not an option in the treatment of these tumors, because of their location in the brainstem. Surgery in this part of the brain can cause severe neurological damage and affect the body’s most vital functions and only biopsies can be performed safely.

Children and adolescents with DIPGs are treated at Dana-Farber/Boston Children's Cancer and Blood Disorders Center through our Glioma Program, one of the world’s largest pediatric glioma treatment programs. Our brain tumor specialists have extensive expertise in treating many types of gliomas, including DIPGs.

Clinical and basic scientists at both Dana-Farber Cancer Institute and Boston Children’s Hospital are conducting numerous research studies to help clinicians better understand and treat DIPGs, leading a national phase II clinical trial on the genetics of diffuse intrinsic pontine glioma. Using advanced surgical techniques, a surgical biopsy of the tumor was performed on participating patients. Samples were then analyzed at the Broad Institute, Dana-Farber Cancer Institute, and Harvard Medical School as well as with collaborators at McGill University in Montreal, Canada, in order to understand the unique molecular characteristics of each tumor. Dana-Farber/Boston Children’s researchers are using initial findings from that study to develop a follow-up DIPG clinical trial. This new trial will tailor treatments to the specific genetic mutations within each individual patient’s tumor, which hopefully will improve outcomes for children with DIPG.

For many children with rare or hard-to-treat conditions, clinical trials may provide new options.