Glioma, Low Grade

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    A low-grade glioma is a slow-growing cancer of the brain that begins in glial cells, which surround and support nerve cells. Learn about low-grade gliomas and find information on how we support and care for children and teens with low-grade gliomas before, during, and after treatment.

The Brain Tumor Center at Dana-Farber/Boston Children's Cancer and Blood Disorders Center cares for children with many different types of common and rare brain and spinal tumors, including astrocytomas, medulloblastomas, ependymoma, glioblastomas, and primitive neuroectodermal tumors (PNET).

Your child will receive care from some of the world’s most experienced pediatric brain tumor doctors and internationally recognized pediatric subspecialists.

Our team works closely together to develop a care plan that offers your child the highest possible quality of life after treatment, and takes the needs of your child and your family into account.

Children treated at the Brain Tumor Center have access to some of the most advanced diagnostics and therapies, including:

  • Quick and accurate diagnosis from our dedicated pediatric neuropathologist
  • Access to advanced technologies like the intraoperative MRI, which allows our neurosurgeons to see detailed images of the brain during surgery
  • Advanced pediatric radiation oncology services, including targeted radiosurgery and low-dose radiation therapy that minimize exposure to radiation
  • Outpatient and oral chemotherapy, which may minimize the number of times your child will need to visit the hospital
  • Innovative therapies offered through clinical trials at Dana-Farber, Boston Children's Hospital, and nationally
  • Specialized programs for the treatment of low- and high-grade gliomas, and medulloblastoma

Thanks to refined surgical techniques and improved chemotherapy and radiation therapy, the majority of children with brain and spinal cord tumors are now long-term survivors. However, they may face physical, social, and intellectual challenges that require specialized care.

Learn more about our Brain Tumor Center.

Information for: Patients | Healthcare Professionals

Low-Grade Gliomas

Overview

Having a tumor in the brain is always a very serious matter, and a low-grade glioma is no exception. Low-grade gliomas are a class of slow-growing, less aggressive tumors that can occur in a number of places in the brain and spinal cord. In general, low-grade gliomas have a more positive prognosis than malignant, high-grade types of brain cancer.

  • There are more 1,000 cases of pediatric low-grade gliomas each year in the United States.
  • Low-grade gliomas are the most common types of pediatric brain tumors.
  • They most commonly arise from a specific type of cell known as a glial cell, or astrocyte.
  • Astrocytes make up the supportive network of the brain, and get their name from their star-like shape.
  • Astrocytomas (tumors that begin in astrocytes) are the most common central nervous system (brain and spinal cord) tumor found in children.

As you read on, you’ll find detailed information about low-grade gliomas.

How Dana-Farber/Boston Children's Cancer and Blood Disorders Center approaches low-grade gliomas

Your child will be seen through Dana-Farber/Boston Children's Cancer and Blood Disorders Center, an integrated pediatric oncology program through Dana-Farber Cancer Institute and Boston Children’s Hospital that provides — in one specialized program — all the services of both a leading cancer center and a pediatric hospital.

Dana-Farber/Boston Children's is home to the world’s largest pediatric low-grade glioma program, the Pediatric Low-Grade Astrocytoma (PLGA) Program. Through the PLGA Program, we conduct advanced research on the genetic and molecular causes of low-grade glioma.

After treatment, your child will receive expert follow-up care through the Stop and Shop Neuro-Oncology Outcomes Clinic at Dana-Farber Cancer Institute, where he will be are able to meet with his neurosurgeon, radiation oncologist, pediatric neuro-oncologist and neurologists at the same follow-up visit.

  • Our pediatric brain tumor survivorship clinic is held weekly.
     
  • In addition to meeting with your pediatric neuro-oncologists, neurologist and neurosurgeon, your child may also see one of our endocrinologists or alternative/complementary therapy specialists.
     
  • School liaisons and psychosocial personnel from the pediatric brain tumor team are also available.
     
  • If your child needs rehabilitation, he may also meet with speech, physical and occupational therapists during and after treatments.

In-depth

We understand how overwhelming a diagnosis of a glioma can be. Right now, you probably have a lot of questions. How dangerous is this condition? What is the very best treatment? What do we do next?

We’ve tried to provide some answers to those questions here, and our experts can explain your child’s condition fully when you meet with us.

What is a low-grade glioma?

Low-grade gliomas are a class of slow-growing, less aggressive tumors of the central nervous system. They most commonly arise from a specific type of cell known as a glial cell, or astrocyte.

How are low-grade gliomas classified?

An important part of diagnosing a brain tumor involves staging and classifying the disease, which will help your child’s doctor determine treatment options and prognosis. Staging is the process of determining whether the tumor has spread and, if so, how far.

There are four major types of astrocytomas, classified based on what they look like under a microscope.

  • grade I (pilocytic astrocytoma - benign)
  • grade II (fibrillary astrocytoma)
  • grade III (anaplastic astrocytoma – refers to lack of structure in the cell)
  • grade IV (glioblastoma multiforme – the most serious kind of tumor)

Low-grade gliomas are usually either grade I or grade II.

Low-grade gliomas may also be classified according to their location in the brain. This includes:

  • cerebellar pilocytic astrocytoma (the part of the brain known as the cerebellum) cervico-medullary astrocytoma (the brainstem)
  • optic pathway glioma (the optic nerve)
  • tectal glioma (the “roof” of the brainstem) thalamic/hypothalamic astrocytoma (the parts of the brain known as the thalamus or hypothalamus)

Other types of low-grade gliomas include:

  • oligodendroglioma (very rare—account for only 2 percent of all pediatric brain tumors)
  • ganglioglioma (tumors have properties of both glial cells and neuronal cells)
  • pleomorphic xanthoastrocytoma (associated with a higher seizure rate than other low-grade gliomas)

The other two types of astrocytomas are classified as high-grade gliomas:

  • grade III or anaplastic astrocytoma
  • grade IV or glioblastoma multiforme
What causes low-grade gliomas?

As a parent, you undoubtedly want to know what may have caused your child’s tumor. It’s important to understand that low-grade gliomas most often occur with no known cause. There’s nothing that you could have done or avoided doing that would have prevented the tumor from developing.

Research has shown that there is a link between some types of low-grade gliomas and certain genetic diseases, specifically:

  • neurofibromatosis
  • tuberous sclerosis
What are the symptoms of low-grade gliomas?

The symptoms of low-grade gliomas can vary greatly depending on the size and location of the tumor and whether it has infiltrated into other areas of the brain or spine.

Due to the relative slow growth rate of low-grade gliomas, your child’s symptoms may have begun many months or years before they see the doctor. While each child may experience symptoms differently, some of the most common include:

  • change in / loss of vision due to low-grade gliomas of the visual pathway
  • weight gain or loss and/or premature puberty due to low-grade gliomas in the hormone center of the brain
  • problems with movement or bowel/bladder control due to low-grade gliomas in the spine
  • vomiting, headache, fatigue and motor control problems due to fluid build-up in and increased pressure on the brain
  • seizures, due to irritation of the normal brain cells

Keep in mind that these symptoms may resemble other, more common conditions or medical problems. If you don’t have a diagnosis and are concerned, always consult your child's physician.

Questions to ask your child’s doctor

After your child is diagnosed with a brain tumor, you may feel overwhelmed with information. It can be easy to lose track of the questions that occur to you.

Lots of parents find it helpful to jot down questions as they arise – that way, when you talk to your child’s doctors, you can be sure that all of your concerns are addressed.

If your child is old enough, you may want to suggest that she write down what she wants to ask her health care provider, too.

Some of the questions you may want to ask include:

  • What type of brain tumor does my child have?
  • Where in the brain is the tumor located? How might this affect my child?
  • Has my child’s brain tumor spread?
  • Can the tumor be treated with surgery?
  • How long will my child need to be in the hospital?
  • What are the possible short and long-term complications of treatment? How will they be addressed?
  • What is the likelihood of cure?
  • What services are available to help my child and my family cope?

FAQ

Q: What causes low-grade gliomas?

A: As a parent, you undoubtedly want to know what may have caused your child’s tumor. The vast majority of children with low-grade gliomas develop these tumors spontaneously, meaning that there is no identifiable cause. A small percentage can be associated with certain genetic syndromes.  Your doctor can easily determine if a genetic cause is associated with the development of your child’s tumor.

Q: Will my child be OK after treatment for low-grade glioma?

A: The outcome after treatment for low-grade glioma can vary significantly depending on the location of the tumor, whether or not the tumor has spread and whether the tumor can be completely removed through surgery. In general, low-grade gliomas have a more positive prognosis than malignant, high-grade types of brain cancer. Your doctor will discuss treatment options with you and your family including clinical trials and supportive care.

Q: Where will my child be treated?

A: Children treated on an outpatient basis through Dana-Farber/Boston Children's are cared for at the Jimmy Fund Clinic on the third floor of Dana Farber Cancer Institute. If your child needs to be admitted to the hospital, he will stay at Boston Children’s Hospital on the ninth floor of the Berthiaume Building.

Q: What services are available to help my child and my family cope?

A: We offer a variety of services to help you, your child and your family get through this difficult time.

Q: What kind of supportive or palliative care is available for my child?

When necessary, our Pediatric Advanced Care Team (PACT) offers supportive treatments intended to optimize the quality of life and promote healing and comfort for children with life-threatening illness. In addition, PACT can provide psychosocial support and help arrange end-of-life care when necessary.

Tests

The first step in treating your child is forming an accurate and complete diagnosis, so your child’s physician may order a number of different tests to determine the type and location of the tumor. Diagnostic procedures for a brain tumor are used to determine the exact type of tumor and whether the tumor has spread. In addition to a physical exam, a medical history and neurological exam (a test of reflexes, muscle strength, eye and mouth movement, coordination and alertness), your child may require tests such as:

  • computerized tomography scan (also called a CT or CAT scan) - a diagnostic imaging procedure that uses a combination of x-rays and computer technology to produce cross-sectional images of the body. CT scans are more detailed than general x-rays. If a low-grade glioma is suspected, your child may have a CT scan of the brain.
     
  • magnetic resonance imaging (MRI) - a diagnostic procedure that uses a combination of large magnets, radiofrequencies and a computer to produce detailed images of the brain and spine. For low-grade gliomas, an MRI of the brain is usually done. In the rare event that your child’s low-grade gliomas spread to the spine, an MRI of the spine may also be ordered.
     
  • biopsy - in many cases, a tissue sample from the tumor will be taken through a needle during a simple surgical procedure to confirm the diagnosis. However, with low-grade gliomas of the optic pathway and brain stem, surgery (including biopsy) is generally avoided, due to the very delicate structures in these areas.

After we complete all necessary tests, our experts meet to review and discuss what they have learned about your child's condition. Then we will meet with you and your family to discuss the results and outline the best treatment options.

Treatment & care

We know how difficult a diagnosis of a pediatric brain tumor can be, both for your child and for your whole family. That’s why our physicians are focused on family-centered care: From your first visit, you’ll work with a team of professionals who are committed to supporting all of your family’s physical and psychosocial needs. We’ll work with you to create a care plan that’s best for your child.

If your child has been diagnosed with a low-grade glioma, you’ll naturally be eager to know how your child’s physician will treat the tumor. 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 the disease
  • your child's tolerance for specific medications, procedures or therapies
  • how your child's doctors expects the disease to progress

There are a number of treatments we may recommend. Some of them help to treat the tumor while others are intended to address complications of the disease or side effects of the treatment.

What treatments are available for low-grade gliomas?

If your child has been diagnosed with a low-grade glioma, he may receive one or more of the following treatments:

  • surgery - usually the first step in the treatment of brain tumors. The goal is to remove as much of the tumor as possible without compromising neurological function.
  • radiation therapy - using high-energy rays (radiation) from a specialized machine to damage or kill cancer cells and shrink tumors. Due to the long-term damage that radiation can cause to the developing brain of a child, this treatment is usually only used as a last resort.
  • chemotherapy - a drug treatment that works by interfering with the cancer cell's ability to grow or reproduce. Modern treatments now include biologic (also called smart drugs) that target specific abnormal pathways required by the tumor to grow and spread. A number of these types of drugs are now in clinical trials in children with low-grade gliomas.
What is expected post-treatment for low-grade glioma?

The prognosis for a child with a low-grade glioma depends on tumor grade, location and in some cases, age of the child at diagnosis.

  • Many low-grade gliomas are first treated with surgery and then monitored for regrowth. Grade I astrocytomas, for example, are usually cured with complete surgical removal alone.
     
  • If, due to the tumor’s location, complete surgical resection is not an option (optic pathway or brain stem gliomas, thalamic/hypothalamic or cervico-medullary gliomas) or if a tumor begins to grow back after it has been removed, the doctor may recommend chemotherapy.
     
  • We usually don’t use radiation therapy unless your child’s tumor has grown after chemotherapy. Due to the potential side effects of radiation, including effects on learning and hormone function, it is best avoided if your child is young (especially under age 10).
What is chemotherapy?

Chemotherapy is systemic treatment, meaning it is introduced to the bloodstream and travels throughout the body to kill cancer cells. Different groups of chemotherapy drugs work in different ways to fight cancer cells and shrink tumors.

How is chemotherapy given?

Your child may receive chemotherapy:

  • orally, as a pill to swallow
  • intramuscularly, as an injection into the muscle or fat tissue
  • intravenously, directly to the bloodstream (intravenously or IV)
  • intrathecally, directly into the spinal fluid with a needle (intrathecally)
Does chemotherapy cause side effects?

While chemotherapy can be quite effective in treating certain cancers, the agents do not differentiate normal healthy cells from cancer cells. Because of this, your child may experience adverse side effects during treatment. Being able to anticipate these side effects can help you, your child and your care team prepare for, and, in some cases, prevent these symptoms from occurring, if possible.

How are side effects managed?

Side effects in the treatment of low-grade gliomas can arise from surgery, radiation and chemotherapy.

  • Procedures should be performed in specialized centers where experienced neurosurgeons, working in the most technologically advanced settings, can provide the most extensive resections while preserving normal brain tissue.
     
  • Radiation therapy often produces inflammation, which can temporarily exacerbate symptoms and dysfunction. To control this, inflammation steroids are sometimes necessary.

     
  • Some of the chemotherapy agents are associated with fatigue, diarrhea, constipation and headache. These side effects can be effectively managed under most circumstances with standard medical approaches.

Our Pediatric Brain Tumor Program also has access to specialists who deliver complementary or alternative medicines. These treatments, which may help control pain and side effects of therapy include the following.

  • acupuncture/acupressure
  • therapeutic touch
  • massage
  • herbs
  • dietary recommendations

Talk to your child’s physician about whether complementary or alternative medicine might be a viable option.

What about progressive or recurrent disease?

There are numerous standard and experimental treatment options for children with progressive or recurrent low-grade gliomas.

Dana-Farber Cancer Institute is one of nine institutes in the nation belonging to the Pediatric Oncology Experimental Therapeutic Investigators Consortium. The consortium is dedicated to the development of new and innovative treatments for children with newly diagnosed as well as progressive or recurrent brain tumors. We are also home to the world’s largest pediatric low-grade astrocytoma research program and the Department of Defense Neurofibromatosis Clinical Trial Consortium.

Long-term follow-up

Today, the majority of children and adolescents diagnosed with pediatric brain tumors will survive into adulthood. However, many of them will face physical, psychological, social and intellectual challenges related to their treatment and will require ongoing assessment and specialized care.

To address the needs of this growing community of brain tumor survivors, Dana-Farber/Boston Children's established the Stop & Shop Family Pediatric Neuro-Oncology Outcomes Clinic.

Today, more than 1,000 pediatric brain tumor survivors of all ages are followed by the Outcomes Clinic, a multi-disciplinary program designed to address long-term health and social issues for families and survivors of childhood brain tumors. Some of the post-treatment services provided by the Outcomes Clinic include:

  • MRI scans to monitor for tumor recurrences
  • intellectual function evaluation
  • endocrine evaluation and treatment
  • neurologic assessment
  • psychosocial care
  • hearing, vision monitoring
  • ovarian dysfunction evaluation and treatment
  • motor function evaluation and physical therapy
  • complementary medicine

As a result of treatment, children may experience changes in intellectual and motor function. Among several programs addressing these needs are the School Liaison and Back to School Programs, which provide individualized services to ease children's return to school and maximize their ability to learn. In addition to providing thorough and compassionate care, our Outcomes Clinic specialists conduct innovative survivorship research and provide continuing education for staff, patients and families

Research and Innovations

Dana-Farber/Boston Children's is a member of the Pediatric Oncology Therapeutic Experimental Investigators Consortium (POETIC), a collaborative clinical research group offering experimental therapies to patients with relapsed or refractory disease. It is also the New England Phase I Center of the Children's Oncology Group and a member of the Department of Defense Neurofibromatosis Clinical Trial Consortium.

We are home to the only dedicated pediatric low-grade glioma program, the Pediatric Low-Grade Astrocytoma (PLGA) Program. In addition to the discovery of a number of novel targets, this program has initiated a number of phase II protocols using molecular inhibitors for children with progressive/recurrent low-grade glioma.

Through the PLGA Research Program, we have pioneered strategies for analyzing the genetic and molecular characteristics of pediatric low-grade astrocytomas. In collaboration with the Broad Institute of Harvard and MIT, we have made strides towards a better understanding of these conditions. Through the program, we’ve also established a patient registry and multiple international research projects.


General Information

The PDQ childhood brain tumor treatment summaries are organized primarily according to the World Health Organization classification of nervous system tumors.[1][2] For a full description of the classification of nervous system tumors and a link to the corresponding treatment summary for each type of brain tumor, refer to the PDQ summary on Childhood Brain and Spinal Cord Tumors Treatment Overview.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2002, childhood cancer mortality has decreased by more than 50%.[3] Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)

Primary brain tumors are a diverse group of diseases that together constitute the most common solid tumor of childhood. Brain tumors are classified according to histology, but tumor location and extent of spread are important factors that affect treatment and prognosis. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in tumor diagnosis and classification.

References:

  1. Louis DN, Ohgaki H, Wiestler OD, et al., eds.: WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon, France: IARC Press, 2007.

  2. Louis DN, Ohgaki H, Wiestler OD, et al.: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114 (2): 97-109, 2007.

  3. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010.

Cellular Classification

Brain stem gliomas are classified according to their location, radiographic appearance, and histology (when obtained). Brain stem gliomas may occur in the pons, midbrain, tectum, dorsum of the medulla at the cervicomedullary junction, or in multiple regions of the brain stem. The tumor may contiguously involve the cerebellar peduncles, cerebellum, the cervical spinal cord, and/or thalamus. The majority of childhood brain stem gliomas are diffuse, fibrillary astrocytomas that involve the pons (diffuse intrinsic pontine gliomas [DIPG]), often with contiguous involvement of other brain stem sites.[1][2] The prognosis is extremely poor for these tumors. Focal pilocytic astrocytomas have a more favorable prognosis. These most frequently arise in the tectum of the midbrain, focally within the pons, or at the cervicomedullary junction where they are often exophytic, and they have a far better prognosis than diffuse intrinsic tumors.[3][4][5]

The genomic characteristics of DIPG appear to differ from those of most other pediatric high-grade gliomas and from those of adult high-grade gliomas. Approximately 80% of DIPG tumors have a mutation in a specific amino acid in one of two histone H3 genes (H3F3A or HIST1H3B).[6] These mutations are less common in non–brain stem pediatric high-grade gliomas and are uncommon in adult high-grade gliomas.[6][7] Other recurring DIPG genomic alterations include PDGFRA amplification in approximately 30% of cases, with lower rates of amplification observed for some other receptor tyrosine kinases (e.g., MET and IGF1R). DIPG tumors also commonly show deletion of the P53 gene on chromosome 17p.[8][9] The gene expression profile of DIPG similarly differs from that of non–brain stem pediatric high-grade gliomas, further supporting a distinctive biology for this subset of pediatric gliomas.[9]

Primary tumors of the brain stem are most often diagnosed based on clinical findings and on neuroimaging studies using magnetic resonance imaging.[10][11] Histologic confirmation of presumed DIPG is usually unnecessary. Biopsy or resection may be indicated for brain stem tumors that are not diffuse and intrinsic or when there is diagnostic uncertainty based on imaging findings. New approaches with stereotactic needle biopsy may make biopsy safer.[12]

References:

  1. Freeman CR, Farmer JP: Pediatric brain stem gliomas: a review. Int J Radiat Oncol Biol Phys 40 (2): 265-71, 1998.

  2. Laigle-Donadey F, Doz F, Delattre JY: Brainstem gliomas in children and adults. Curr Opin Oncol 20 (6): 662-7, 2008.

  3. Epstein F, McCleary EL: Intrinsic brain-stem tumors of childhood: surgical indications. J Neurosurg 64 (1): 11-5, 1986.

  4. Edwards MS, Wara WM, Ciricillo SF, et al.: Focal brain-stem astrocytomas causing symptoms of involvement of the facial nerve nucleus: long-term survival in six pediatric cases. J Neurosurg 80 (1): 20-5, 1994.

  5. Pollack IF, Pang D, Albright AL: The long-term outcome in children with late-onset aqueductal stenosis resulting from benign intrinsic tectal tumors. J Neurosurg 80 (4): 681-8, 1994.

  6. Wu G, Broniscer A, McEachron TA, et al.: Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44 (3): 251-3, 2012.

  7. Schwartzentruber J, Korshunov A, Liu XY, et al.: Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482 (7384): 226-31, 2012.

  8. Zarghooni M, Bartels U, Lee E, et al.: Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets. J Clin Oncol 28 (8): 1337-44, 2010.

  9. Paugh BS, Broniscer A, Qu C, et al.: Genome-wide analyses identify recurrent amplifications of receptor tyrosine kinases and cell-cycle regulatory genes in diffuse intrinsic pontine glioma. J Clin Oncol 29 (30): 3999-4006, 2011.

  10. Albright AL, Packer RJ, Zimmerman R, et al.: Magnetic resonance scans should replace biopsies for the diagnosis of diffuse brain stem gliomas: a report from the Children's Cancer Group. Neurosurgery 33 (6): 1026-9; discussion 1029-30, 1993.

  11. Liu AK, Brandon J, Foreman NK, et al.: Conventional MRI at presentation does not predict clinical response to radiation therapy in children with diffuse pontine glioma. Pediatr Radiol 39 (12): 1317-20, 2009.

  12. Cartmill M, Punt J: Diffuse brain stem glioma. A review of stereotactic biopsies. Childs Nerv Syst 15 (5): 235-7; discussion 238, 1999.

Stage Information

There is no generally applied staging system for childhood brain stem gliomas.[1] It is uncommon for these tumors to have spread outside the brain stem itself at the time of initial diagnosis. Spread of malignant brain stem tumors is usually contiguous; metastasis via the subarachnoid space has been reported in up to 30% of cases diagnosed antemortem.[2] Such dissemination may occur prior to local relapse but usually occurs simultaneously with or after local disease relapse.[3]

The less common tumors of the midbrain, especially in the tectal plate region, have been viewed separately from those of the brain stem because they are more likely to be low grade and have a greater likelihood of long-term survival (approximately 80% 5-year progression-free survival vs. <10% for tumors of the pons).[1][4][5][6][7][8] Similarly, dorsally exophytic and cervicomedullary tumors are generally low grade and have a relatively favorable prognosis. Children younger than 3 years may have a more favorable prognosis, perhaps reflecting different biologic characteristics.[9]

References:

  1. Freeman CR, Farmer JP: Pediatric brain stem gliomas: a review. Int J Radiat Oncol Biol Phys 40 (2): 265-71, 1998.

  2. Packer RJ, Allen J, Nielsen S, et al.: Brainstem glioma: clinical manifestations of meningeal gliomatosis. Ann Neurol 14 (2): 177-82, 1983.

  3. Sethi R, Allen J, Donahue B, et al.: Prospective neuraxis MRI surveillance reveals a high risk of leptomeningeal dissemination in diffuse intrinsic pontine glioma. J Neurooncol 102 (1): 121-7, 2011.

  4. Halperin EC, Wehn SM, Scott JW, et al.: Selection of a management strategy for pediatric brainstem tumors. Med Pediatr Oncol 17 (2): 117-26, 1989.

  5. Epstein F, McCleary EL: Intrinsic brain-stem tumors of childhood: surgical indications. J Neurosurg 64 (1): 11-5, 1986.

  6. Edwards MS, Wara WM, Ciricillo SF, et al.: Focal brain-stem astrocytomas causing symptoms of involvement of the facial nerve nucleus: long-term survival in six pediatric cases. J Neurosurg 80 (1): 20-5, 1994.

  7. Pollack IF, Pang D, Albright AL: The long-term outcome in children with late-onset aqueductal stenosis resulting from benign intrinsic tectal tumors. J Neurosurg 80 (4): 681-8, 1994.

  8. Mandell LR, Kadota R, Freeman C, et al.: There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy. Int J Radiat Oncol Biol Phys 43 (5): 959-64, 1999.

  9. Broniscer A, Laningham FH, Sanders RP, et al.: Young age may predict a better outcome for children with diffuse pontine glioma. Cancer 113 (3): 566-72, 2008.

Treatment Option Overview

Many of the improvements in survival in childhood cancer have been made as a result of clinical trials that have attempted to improve on the best available, accepted therapy. Clinical trials in pediatrics are designed to compare new therapy with therapy that is currently accepted as standard. This comparison may be done in a randomized study of two treatment arms or by evaluating a single new treatment and comparing the results with those that were previously obtained with existing therapy.

Because of the relative rarity of cancer in children, all patients with brain tumors should be considered for entry into a clinical trial. To determine and implement optimum treatment, treatment planning by a multidisciplinary team of cancer specialists who have experience treating childhood brain tumors is required. Radiation therapy (including 3-dimensional conformal radiation therapy) of pediatric brain tumors is technically very demanding and should be carried out in centers that have experience in that area in order to ensure optimal results.

Untreated Childhood Brain Stem Glioma

Diffuse Intrinsic Pontine Gliomas

Conventional treatment for children with diffuse intrinsic pontine glioma (DIPG) is radiation therapy to involved areas. Such treatment will result in transient benefit for most patients, but over 90% of patients will die within 18 months of diagnosis. The conventional dose of radiation therapy ranges between 54 Gy and 60 Gy given locally to the primary tumor site in single daily fractions.

Hyperfractionated (twice daily) radiation therapy techniques have been used to deliver a higher dose, and studies using doses as high as 78 Gy have been completed. Evidence demonstrates that these increased radiation therapy doses do not improve the duration or rate of survival for patients with DIPG whether given alone,[1][2] or in combination with chemotherapy.[3] Hypofractionated radiation therapy does not improve survival.[4][Level of evidence: 2A] Studies evaluating the efficacy of various radiosensitizers as a means for enhancing the therapeutic effect of this modality have been undertaken but to date have failed to show any significant improvement in outcome.[2][3][5][6][7] Radiation-induced changes may occur a few months after the completion of radiation therapy and may mimic tumor progression. When considering the efficacy of additional treatment, care needs to be taken to separate radiation-induced change from progressive disease.[8]

The utility of chemotherapy in the treatment of patients with newly diagnosed DIPG is unproven.[2][3][6][7][9][10][11]; [12][13][Level of evidence: 2A]; [14][Level of evidence: 3iiiA] Currently, no chemotherapeutic strategy—including neoadjuvant, concurrent, post-radiation survival or immunotherapy—when added to radiation therapy has led to long-term survival for children with DIPG.[15][16][17]; [18][Level of evidence: 2A] Similarly, studies utilizing high-dose, marrow-ablative chemotherapy with autologous hematopoietic stem cell rescue have been ineffective in extending survival.[19] Consonant with other brain tumors, radiation therapy is often omitted for infants with DIPG and chemotherapy-only approaches are utilized.

Focal or Low-Grade Brain Stem Gliomas

In general, maximal surgical resection should be attempted.[20][21] Patients with residual tumors may be candidates for additional therapy including 3-dimensional conformal radiation therapy approaches with or without adjuvant chemotherapy. Information about ongoing clinical trials is available from the NCI Web site.

Patients with small tectal lesions and hydrocephalus but no other neurological deficits may be treated with cerebrospinal fluid diversion alone and have follow-up with sequential neuroradiographic studies unless there is evidence of progressive disease.[20]

Neurofibromatosis

Children with neurofibromatosis type I and brain stem gliomas may have a different prognosis than other patients who have intrinsic lesions. Patients with neurofibromatosis may present with a long history of symptoms or be identified on screening tests; a period of observation may be indicated before instituting any treatment.[22] Brain stem gliomas in these children may be indolent and may require no specific treatment for years.[23]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with untreated childhood brain stem glioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Freeman CR, Krischer JP, Sanford RA, et al.: Final results of a study of escalating doses of hyperfractionated radiotherapy in brain stem tumors in children: a Pediatric Oncology Group study. Int J Radiat Oncol Biol Phys 27 (2): 197-206, 1993.

  2. Mandell LR, Kadota R, Freeman C, et al.: There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy. Int J Radiat Oncol Biol Phys 43 (5): 959-64, 1999.

  3. Allen J, Siffert J, Donahue B, et al.: A phase I/II study of carboplatin combined with hyperfractionated radiotherapy for brainstem gliomas. Cancer 86 (6): 1064-9, 1999.

  4. Negretti L, Bouchireb K, Levy-Piedbois C, et al.: Hypofractionated radiotherapy in the treatment of diffuse intrinsic pontine glioma in children: a single institution's experience. J Neurooncol 104 (3): 773-7, 2011.

  5. Freeman CR, Kepner J, Kun LE, et al.: A detrimental effect of a combined chemotherapy-radiotherapy approach in children with diffuse intrinsic brain stem gliomas? Int J Radiat Oncol Biol Phys 47 (3): 561-4, 2000.

  6. Broniscer A, Leite CC, Lanchote VL, et al.: Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study. Brainstem Glioma Cooperative Group. J Clin Oncol 18 (6): 1246-53, 2000.

  7. Doz F, Neuenschwander S, Bouffet E, et al.: Carboplatin before and during radiation therapy for the treatment of malignant brain stem tumours: a study by the Société Française d'Oncologie Pédiatrique. Eur J Cancer 38 (6): 815-9, 2002.

  8. Liu AK, Macy ME, Foreman NK: Bevacizumab as therapy for radiation necrosis in four children with pontine gliomas. Int J Radiat Oncol Biol Phys 75 (4): 1148-54, 2009.

  9. Blaney SM, Phillips PC, Packer RJ, et al.: Phase II evaluation of topotecan for pediatric central nervous system tumors. Cancer 78 (3): 527-31, 1996.

  10. Jennings MT, Sposto R, Boyett JM, et al.: Preradiation chemotherapy in primary high-risk brainstem tumors: phase II study CCG-9941 of the Children's Cancer Group. J Clin Oncol 20 (16): 3431-7, 2002.

  11. Wolff JE, Westphal S, Mölenkamp G, et al.: Treatment of paediatric pontine glioma with oral trophosphamide and etoposide. Br J Cancer 87 (9): 945-9, 2002.

  12. Korones DN, Fisher PG, Kretschmar C, et al.: Treatment of children with diffuse intrinsic brain stem glioma with radiotherapy, vincristine and oral VP-16: a Children's Oncology Group phase II study. Pediatr Blood Cancer 50 (2): 227-30, 2008.

  13. Cohen KJ, Heideman RL, Zhou T, et al.: Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children's Oncology Group. Neuro Oncol 13 (4): 410-6, 2011.

  14. Jalali R, Raut N, Arora B, et al.: Prospective evaluation of radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma. Int J Radiat Oncol Biol Phys 77 (1): 113-8, 2010.

  15. Frappaz D, Schell M, Thiesse P, et al.: Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas: final results of BSG 98 prospective trial. Neuro Oncol 10 (4): 599-607, 2008.

  16. Frazier JL, Lee J, Thomale UW, et al.: Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies. J Neurosurg Pediatr 3 (4): 259-69, 2009.

  17. Hargrave D, Bartels U, Bouffet E: Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol 7 (3): 241-8, 2006.

  18. Warren K, Bent R, Wolters PL, et al.: A phase 2 study of pegylated interferon α-2b (PEG-Intron(®)) in children with diffuse intrinsic pontine glioma. Cancer 118 (14): 3607-13, 2012.

  19. Bouffet E, Raquin M, Doz F, et al.: Radiotherapy followed by high dose busulfan and thiotepa: a prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas. Cancer 88 (3): 685-92, 2000.

  20. Vandertop WP, Hoffman HJ, Drake JM, et al.: Focal midbrain tumors in children. Neurosurgery 31 (2): 186-94, 1992.

  21. Kestle J, Townsend JJ, Brockmeyer DL, et al.: Juvenile pilocytic astrocytoma of the brainstem in children. J Neurosurg 101 (1 Suppl): 1-6, 2004.

  22. Bilaniuk LT, Molloy PT, Zimmerman RA, et al.: Neurofibromatosis type 1: brain stem tumours. Neuroradiology 39 (9): 642-53, 1997.

  23. Molloy PT, Bilaniuk LT, Vaughan SN, et al.: Brainstem tumors in patients with neurofibromatosis type 1: a distinct clinical entity. Neurology 45 (10): 1897-902, 1995.

Recurrent Childhood Brain Stem Glioma

Diffuse Intrinsic Pontine Gliomas

Given the dismal prognosis for patients with diffuse intrinsic pontine glioma, progression of the pontine lesion is anticipated generally within 1 year from initial radiation therapy. In most cases, biopsy at the time of clinical or radiologic progression is neither necessary nor recommended. To date, no salvage regimen has been shown to extend survival. Patients should be considered for entry into trials of novel therapeutic approaches because there are no standard agents that have demonstrated a clinically significant activity. Concomitant palliative care should be provided for these patients whether or not disease-directed therapy is administered.

Focal or Low-Grade Brain Stem Gliomas

At the time of recurrence, a complete evaluation to determine the extent of the relapse may be indicated for selected low-grade lesions. Biopsy or surgical resection should be considered for confirmation of relapse when other entities such as secondary tumor and treatment-related brain necrosis, which may be clinically indistinguishable from tumor recurrence, are in the differential. Other tests, such as positron-emission tomography, magnetic resonance spectroscopy, and single-photon emission computed tomography, have not yet been shown to be reliable in distinguishing necrosis from tumor recurrence in brain stem gliomas. Radiation-induced changes may occur a few months after the completion of radiation therapy and may mimic tumor progression. When considering the efficacy of additional treatment, care needs to be taken to separate radiation-induced change from progressive disease.

Treatment considerations at the time of recurrence or progression are dependent on prior treatment. Considerations include: further surgical resection, irradiation including 3-dimensional conformal radiation therapy, or chemotherapy. The need for surgical intervention must be individualized on the basis of the initial tumor type, the location within the brain stem, the length of time between initial treatment and the appearance of the mass lesion, and the clinical picture.[1]

Chemotherapy with agents such as a carboplatin and vincristine may be effective in children with recurrent low-grade exophytic gliomas.[2][3]

Treatment Options Under Clinical Evaluation

Early-phase therapeutic trials may be available for selected patients. These trials may be available via Children’s Oncology Group phase I institutions, the Pediatric Brain Tumor Consortium or other entities.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent childhood brain stem glioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Bowers DC, Krause TP, Aronson LJ, et al.: Second surgery for recurrent pilocytic astrocytoma in children. Pediatr Neurosurg 34 (5): 229-34, 2001.

  2. Packer RJ, Lange B, Ater J, et al.: Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol 11 (5): 850-6, 1993.

  3. Gururangan S, Cavazos CM, Ashley D, et al.: Phase II study of carboplatin in children with progressive low-grade gliomas. J Clin Oncol 20 (13): 2951-8, 2002.


This information is provided by the National Cancer Institute.

This information was last updated on January 23, 2013.

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