Diffuse Intrinsic Pontine Glioma

Synonyms

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Overview

A Diffuse Intrinsic Pontine Glioma (DIPG) is a tumor located in the pons (middle) of the brain stem. The brain stem is the bottom most portion of the brain, connecting the cerebrum with the spinal cord. The majority of brain stem tumors occur in the pons (middle brain stem), are diffusely infiltrating (they grow amidst the nerves), and therefore are not able to be surgically removed. Glioma is a general name for any tumor that arises from the supportive tissue called glia, which help keep the neurons ("thinking cells") in place and functioning well. The brain stem contains all of the "wires" converging from the brain to the spinal cord as well as important structures involved in eye movements, face and throat muscle control and sensation.

Symptoms

Children with DIPG present with ataxia (clumsiness or wobbliness), weakness of a leg and/or arm, double vision, and sometimes headaches, vomiting, tilting of the head, or facial weakness. Double vision (diplopia) is the most common presenting symptom for these tumors. Symptoms are usually present for 6 months or less at time of diagnosis. Patients with focal brain stem gliomas may display some of the same symptoms, although not the usual combination of ataxia, weakness, and double vision. Duration of symptoms is often greater than 6 months before the focal brain stem tumor is diagnosed.

Causes

We don’t know what causes a diffuse pontine glioma. There is no way to predict that a child will get brain cancer and nobody is to blame if a child develops a tumor. Researchers have been studying whether environmental factors, such as radiation, food, or chemicals can cause brain cancer. At the moment, there is no definite proof that there is a connection.

Diagnosis

Diffuse pontine gliomas are located in the brainstem, at the base of the brain. They are usually diagnosed in children aged 5 to 10. They are difficult to treat because the tumor cells grow in between and around normal cells. It is impossible to remove a tumor in this area because it interferes with the functioning of this critical area of the brain.

Prognosis

DIPG often follows an inexorable course of progression, despite therapy. A large majority of children die within a year of diagnosis. Focal brain stem glioma, however, can carry an exceptional prognosis, with long-term survivals frequently reported.

Treatment

Since brain stem gliomas are relatively uncommon and require complex management, children with such tumors deserve evaluation in a comprehensive cancer center where the coordinated services of dedicated pediatric neurosurgeons, child neurologists, pediatric oncologists, radiation oncologists, neuropathologists, and neuroradiologists are available. In particular, for DIPG, because of its rarity and poor prognosis, children and their families should be encouraged to participate in clinical trials attempting to improve survival with innovative therapy.

 

Neurosurgery: Surgery to attempt tumor removal is usually not possible or advisable for DIPG. By their very nature, these tumors invade diffusely throughout the brain stem, growing between normal nerve cells. Aggressive surgery would cause severe damage to neural structures vital for arm and leg movement, eye movement, swallowing, breathing, and even consciousness.

 

Surgery with less than total removal can be performed for many focal brain stem gliomas. Such surgery often results in quality long-term survival, without administering chemotherapy or radiotherapy immediately after surgery, even when a child has residual tumor. Surgery is particularly useful for tumors that grow out (exophytic) from the brain stem.

 

Focal brain stem tumors that arise at the top back of the midbrain (tectal gliomas) should be managed conservatively, without surgical removal. Nevertheless, shunt placement or ventriculostomy for hydrocephalus (see below) is frequently necessary. These tumors have been described to be stable for many years or decades without any intervention other than shunting.

 

Radiotherapy: Conventional radiotherapy, limited to the involved area of tumor, is the mainstay of treatment for DIPG. A total radiation dosage ranging from 5400 to 6000 cGy, administered in daily fractions of 150 to 200 cGy over 6 weeks, is standard. Hyperfractionated (twice-daily) radiotherapy was used previously to deliver higher irradiation dosages, but such did not lead to improved survival. Radiosurgery (e.g., gamma knife, Cyberknife) has no role in the treatment of DIPG.

 

Chemotherapy and other drug therapies: The role of chemotherapy in DIPG remains unclear. Studies to date with chemotherapy have shown little improvement in survival, although efforts (see below) through the Children's Oncology Group (COG), Pediatric Brain Tumor Consortium (PBTC), and others are underway to explore further the use of chemotherapy and other drugs. Drugs utilized to increase the effect of radiotherapy (radiosensitizers) have thus far shown no added benefit, but promising new agents are under investigation. Immunotherapy with beta-interferon and other drugs to modify biologic response have shown disappointing results. Intensive or high-dose chemotherapy with autologous bone marrow transplant or peripheral blood stem cell rescue has not demonstrated any effectiveness in brain stem gliomas and is not recommended. Future clinical trials may incorporate medicines to interfere with cellular pathways (signal transfer inhibitors) or other approaches that alter the tumor or its environment. For more information and a listing of the most up-to date trials, the reader is encouraged to check the websites of the National Institutes of Health clinical trials registry (http://clinicaltrials.gov/), the National Childhood Cancer Foundation/COG (http://www.curesearch.org/), and the PBTC (http://www.pbtc.org/).

 In focal brain stem gliomas, chemotherapy, such as carboplatin/vincristine, procarbazine/CCNU/vincristine, or temozolomide, may be useful in children whose tumors are progressive and not surgically accessible. In children younger than age 3 years, chemotherapy may be preferable to radiotherapy because of the effects of irradiation on the developing brain.