BASIC FACTS ABOUT EPENDYMOMA

“Where hope springs eternal”

Pediatric Brain Tumor Foundation of the United States

A Resource for Families ACKNOWLEDGEMENTS The Pediatric Brain Tumor Foundation of the United States wishes to thank Ian Pollack, MD, Department of Neurosurgery, Children’s Hospital of Pittsburgh, Pittsburgh, PA, for the scientific review of this publication.

SOURCES Statistical data in this publication was obtained from the Central Brain Tumor Registry of the United States (CBTRUS) and the World Health Organization Classification of Tumors, 2000.

DISCLAIMER The Pediatric Brain Tumor Foundation of the United States does not engage in rendering medical advice or professional medical services. Information contained in this publication is NOT intended to be a substitute for medical care and should not be used for the diagnosing or the treatment of a brain tumor or any other health problem. If you have or even suspect you have a problem concerning your health or that of someone else, you should consult with your healthcare provider. The materials provided by the Pediatric Brain Tumor Foundation of the United States are compiled based on current information at the time that they were written. Medical research concerning disease and treatments is an ongoing process. We endeavor to keep our materials current. However, you should contact your doctors and medical institutions to seek the most current information available.

COPYRIGHT Copyright© 2002 by the Pediatric Brain Tumor Foundation of the United States, Inc. The contents of this publication have been prepared for the exclusive use of the Pediatric Brain Tumor Foundation of the United States. It may not be reproduced in part or in its entirety without the written permission of the Pediatric Brain Tumor Foundation of the United States. Mission Statement Find the cause and cure of childhood brain tumors through the support of medical research; Increase public awareness about the severity and prevalence of childhood brain tumors; Aid in early detection and treatment of childhood brain tumors; Support a national database on all primary brain tumors; and Provide hope and emotional support for the thousands of children and families affected by this life-threatening disease.

Pediatric Brain Tumor Foundation of the United States 1 INTRODUCTION The news that a child has a brain tumor is nearly impossible to absorb. Naturally, when parents first receive such news, they are stunned. Gradually, the initial shock is replaced by a desire to learn more about the tumor: Exactly where is it? Which areas of the body is it affecting? What can be done about it? What lies ahead? Almost instinctively, people realize that seeking the answers to these questions will restore a sense of control. To help you in your efforts to gain understanding about your child’s illness, the Pediatric Brain Tumor Foundation of the United States (PBTFUS) has put together this booklet. It contains information about the specific type of tumor that has invaded your family’s world. We encourage you to learn as much as you can. Trust your instincts. When you have questions or concerns, voice them. Take an active part in selecting which approach will result in the best care for your child. Pediatric brain tumors require specialized treatment methods that are most often provided at comprehensive pediatric hematology/oncology centers by a multidisciplinary team of pediatric cancer specialists. This team usually includes physicians, nurses, social workers, child life specialists, psychologists and rehabilitation specialists. Such care should provide families access to education and support services. We have much to learn about childhood brain tumors. Funding research to find the cause and cure, increasing public awareness, and aiding in the early detection and treatment of childhood brain tumors are all the ways the PBTFUS fulfills its mission. Families like yours are at the heart of our mission. If you need further information or other PBTFUS publications, our Family Support Program Coordinator is on staff to take your call. Contact us at 1-800-253-6530 or e-mail: [email protected].

A FEW BASIC FACTS ABOUT BRAIN TUMORS What causes a brain tumor? The short answer is: We don’t know. Researchers believe that inherited and genetic factors may be involved. Environment may play a part. While studies have yielded valuable information, they have not provided a concrete answer about the cause of most brain tumors. The key may even lie in areas not yet investigated by science.

2 Pediatric Brain Tumor Foundation of the United States What does it mean when a tumor is classified as Grade I, Grade II, Grade III, or Grade IV? Tumors are graded to help determine the best treatment approach. The more aggressive and dangerous a tumor is, the higher the grade it is assigned. Some types of tumors, such as medulloblastoma, are always considered high grade. Grade I tumors are the most benign appearing under the microscope. Grade II is a significant step higher with cells that more easily become malignant. Malignant tumors invade and destroy healthy tissue. Grade III and IV tumors are malignant with increasing severity. Grade alone does not determine prognosis, however. Other factors, such as tumor location, can influence how easy or difficult a tumor is to treat.

What is staging? The “stage” of a cancerous tumor is based on its size and the extent to which it has metastasized, or spread, beyond the site of its origin.

EPENDYMOMA What is an ependymoma? Ependymomas arise from cells that line the ventricles (hollow areas in the nervous system that contain cerebrospinal fluid) of the brain, the central canal of the spinal cord, and the filum terminale (a thread-like structure within the lower end of the spinal cord). They are considered a type of glioma. Most appear benign under the microscope, but nonetheless can show malignant behavior because they tend to be locally invasive. Some tumors do appear malignant and these tend to have a somewhat worse prognosis.

Types of ependymoma: Ependymoma: A slowly growing tumor of children and young adults, most are benign or low-grade, but some are capable of malignant behavior.

Anaplastic Ependymoma: A higher grade malignant tumor growing more rapidly.

Sub-Ependymoma: Benign, slow growing. Myxopapillary Ependymoma: Benign, slow growing tumors of the spinal cord that occur mostly in young adults.

Pediatric Brain Tumor Foundation of the United States 3 cerebrum subarachnoid space

posterior fossa brainstem midbrain pons tentorium medulla oblongata fourth ventricle cerebellum

LOCATION: In the brain, the most common location for ependymomas is the posterior fossa and the floor of the fourth ventricle. Tumors arising in the posterior fossa often infiltrate the brain stem to involve the medulla oblongata and upper spinal cord. Seeding, or spreading, to the ventricles and subarachnoid space is not uncommon.

What are the symptoms of an ependymoma? Many symptoms associated with ependymomas are caused by increased intracranial pressure (ICP). They may vary depending on the age of the child and exact location of the tumor. In children younger than two years of age, symptoms may include vomiting, irritability, lethargy, gait disturbance, feeding problems, involuntary eye movement, and increased head size due to hydrocephalus, increased cerebrospinal fluid inside the brain. In children older than two, vomiting, headache, and gait disturbance are the most common symptoms.

How common are ependymomas in children? Ependymomas represent just over 6 % of childhood brain and CNS (Central Nervous System) tumors. Incidence rates for ependymoma are similar in children and adults; however, ependymomas are more likely to occur in infants and very young children than in older children. Ependymomas are less common in children between the ages of 5 and 14, with an average

4 Pediatric Brain Tumor Foundation of the United States incidence rate of 1.4 per million. The rate of occurrence is slightly higher in males than females. (SEER 1986-94; CBTRUS 1992-1997)

DIAGNOSIS Diagnosis is the process of finding out which disease is causing a person’s symptoms. Only after this is done can the best treatment plan be determined. In many cases, making the diagnosis of a brain tumor can be challenging because the early symptoms can mimic those of other less serious conditions. However, once a diagnosis of a brain tumor is considered, an imaging evaluation of the brain is required to confirm the suspicion. Following examination and evaluation of signs and symptoms, MRI and CT scans are useful in determining the presence of a brain or spinal cord tumor, but biopsy is the only reliable way to confirm a specific diagnosis.

MRI Suite MRI (Magnetic Resonance Imaging) An MRI scan combines high-frequency radio waves and a strong magnetic field to produce a picture of the inside of the body. No x-ray radiation is involved. Before the test begins the doctor may inject a special dye called contrast material into the patient’s vein. The dye makes it easier to see abnormal tissue. The MRI procedure usually takes from thirty minutes to an hour. To have an MRI, the patient lies on a mechanical table. The table is then moved into a large structure with a

Pediatric Brain Tumor Foundation of the United States 5 donut-shaped opening. If a “closed MRI” is used, it’s a little like going into a tunnel. In contrast, an “open MRI” is open on the top and sides. Children are never left alone during an MRI. The child is continually monitored during the procedure. Some MRI centers will allow parents to remain with their children as well. Although the scan should not cause any pain, the thumping noise that occurs in the machinery from time to time during the procedure may startle young children. An accurate scan can only be obtained if the patient is still. For this reason, a mild sedative may be used to calm a child during the scan. At times they may play music during the scan to help with relaxation.

CT (Computerized Tomography) A CT scan uses a sophisticated x-ray machine combined with a computer to create a picture of the inside of the body. Before the test begins, the doctor may inject a special dye called contrast material into the patient’s vein. The dye makes it easier to see abnormal tissue. When it is time for the scan, a technologist positions the patient on a movable padded table. The table inches slowly through a donut-shaped scanner ring, stopping about every half-inch for a picture to be taken. During the scan, the technologist watches through a glass window and talks to the patient on an intercom. The sound of motors and gears can be heard as the scanner takes the pictures. A CT scan normally takes less than an hour.

PET (Positron Emission Tomography) A PET scan provides a picture of brain activity. It may be used when trying to tell whether a CT or MRI scan is showing the return of a tumor or tissue damage caused by radiation. PET may be used in addition to CT or MRI.

SPECT (Single Photon Emission Tomography) SPECT provides information similar to the PET scan, and is more widely available.

Biopsy A biopsy is a procedure in which a sample of tumor tissue is removed so that doctors can study its characteristics. The sample can be taken through an open or surgical biopsy, or a needle biopsy. If the tumor is difficult or impossible to resect (remove) safely, a doctor may perform a needle biopsy to identify the type of tumor and determine what treatment would be most useful. If the tumor is surgically resectable, tissue removed during the resection process can be examined to confirm the diagnosis. 6 Pediatric Brain Tumor Foundation of the United States TREATMENT FOR EPENDYMOMA Treatment for an ependymoma usually begins with surgery unless the location of the tumor makes surgery too risky. The surgeon’s goal is to resect as much of the tumor as possible with minimal harm to the patient. Treatment can often be difficult because certain regions of the tumor may be responsive to a specific treatment, while other regions of the same tumor are resistant. Corticosteroids may be used to treat swelling caused by the tumor. In addition, a shunt or, more commonly, a temporary ventricular drainage procedure may be used to relieve elevated intracranial pressure (ICP) caused by hydrocephalus. Radiotherapy (RT) and chemotherapy may be used in an effort to destroy tumor cells not removed during surgery. Chemotherapy alone may be used if the child is less than 3 years of age, because radiotherapy has greater risks in young children.

Surgery To remove an ependymoma, the pediatric neurosurgeon must first gain access to the brain. This is usually done by craniotomy or craniectomy. “Cranio” means skull. “Otomy” means surgical incision. “Ectomy” means surgical removal. For a craniotomy, the surgeon creates a “bone flap” in the skull which is removed and put back in place when the operation is over. For a craniectomy, the bone is removed in pieces and not replaced. During surgery, the doctor may find that the ependymoma is blocking the cerebrospinal fluid (CSF) pathway. In some cases, removing at least a portion of the tumor will correct the problem. Sometimes, however, even when the CSF pathway is open, it does not function properly. In that case, the surgeon may insert a small plastic tube called a ventriculostomy or external ventricular drain (EVD) to avoid fluid buildup around the time of surgery. Later, a more permanent internal shunt may be inserted to keep the fluid circulating around the brain. Another way to keep the fluid from building up is to create a small hole in the floor of the third ventricle (a third ventriculostomy). Sometimes steroids are given to reduce swelling before, during, and after surgery. The brain is a complex, sensitive organ, and doctors and parents must understand the risks of brain surgery. Despite these risks, surgery may be essential to remove as much of the tumor as possible. Studies show that at least two out of every ten children who have brain surgery for a tumor may develop serious aftereffects. Examples include loss of speech, balance difficulties, hormonal disorders, or growth disorders. These

Pediatric Brain Tumor Foundation of the United States 7 problems may last for weeks, months, or longer. Speech therapy, physical therapy, or occupational therapy can help restore function to its maximum potential.

Staging Staging determines if and how much a tumor has spread beyond the site of its origin. To stage a tumor, the doctor reviews scans taken before and after surgery, and may also analyze samples of cerebrospinal fluid (CSF) obtained through a spinal tap or bone marrow obtained through a bone marrow needle biopsy. The extent of surgical removal is also used to stage a tumor. Surgeons commonly designate surgical resection as being total or near total, subtotal, partial, or biopsied only. Total resection means that there is no visible residual tumor under the operating microscope or on the postoperative MRI, although there are always some tumor cells left behind. Because of this, some surgeons refer to this as a “gross total” resection to distinguish this from the rare instances of a true total resection in which the tumor as well as margin of normal tissue are removed (which is rarely safe in the brain). Near total means a small amount (less than 10% of residual tumor left behind). Subtotal means 50%-90% tumor removal, and partial means less than 50% tumor removal. Ask your doctor to more fully explain the term being used to describe the stage of your child’s tumor.

Radiation Therapy (RT) Radiation therapy, also called radiotherapy (RT), uses x-rays to attempt to destroy tumor cells. In cases where a tumor cannot be completely resected, survival rates improve when RT is used after surgery. The side effects of RT vary from child to child and are most related to the dose received by the brain and the age of the child. Radiation effects can be temporary or permanent, occurring during radiotherapy or not until months or years later. Problems that can occur during radiation therapy include fatigue, nausea or diminished appetite, skin changes (like sunburn), hair loss, or difficulty swallowing. RT can cause low white blood cell counts (leaving the child susceptible to infection) or low levels of platelets (important for clotting and healing). Your radiation oncologist can often suggest ways to relieve some of the symptoms seen during radiotherapy.

8 Pediatric Brain Tumor Foundation of the United States Later Effects of RT include: • RT to the entire brain can cause learning problems noted several years after therapy. The effect of irradiation on learning or on memory is quite variable, but in general is more pronounced when higher doses are used in younger children. • Changes in growth can result from direct effects on spinal bone growth or more commonly from a reduction in growth hormone. Growth hormone, or GH, is an important substance produced at the base of the brain. GH is often diminished when measured a year or more after radiation therapy. In many cases, growth hormone can be replaced as a medicine. • Changes in other hormones, including thyroid hormone and sometimes the hormones responsible for sexual maturation during puberty, can be noted at or beyond the one-year post-therapy point. When hormone levels are inadequate, the hormones can be replaced with medication. • Because of the risks of radiotherapy in younger children with ependymoma, many treatment protocols try to delay the use of radiotherapy (RT) by administering multi-agent chemotherapy regimens after surgery or by focusing the radiation dose specifically to the bed of the tumor, thereby minimizing the radiation exposure of the surrounding brain.

Chemotherapy Chemotherapy is the use of a single medicine or combination of medicines to attack tumor tissue. Chemotherapy can be taken by mouth, by injection, or through an intravenous line (IV). Some therapies can be given on an outpatient basis, while others require one or more days in the hospital. An ependymoma may be treated with chemotherapy to destroy cells that remain after surgical removal of the tumor. Chemotherapy is often used if the patient is a child under three years old and the doctor wishes to delay or avoid RT. Chemotherapy may also be used for instances in which the treatment team thinks that a second attempt at surgical resection may be feasible after an initial incomplete resection, in order to render the tumor more responsive to total resection. If your child requires chemotherapy, it is helpful to keep the following two facts in mind: (1) children do not normally experience all possible side effects, and (2) there are ways to relieve or offset many of them. Among the side effects caused by chemotherapy are hair loss, skin problems, nausea, vomiting, diarrhea, constipation, changes in taste, fatigue, mouth sores, seizures, hearing loss, kidney and liver problems, and reduction of platelets, red cells, or white cells in the

Pediatric Brain Tumor Foundation of the United States 9 blood. Remember: some of these problems may not occur at all. Some may be temporary, while others may be permanent. Research is ongoing in an attempt to improve the effectiveness and reduce the negative side effects of RT and chemotherapy. If you are interested in learning about clinical trials or studies that are testing new approaches, ask your doctor, contact the National Cancer Institute at http://cancernet.nci.gov, call the PBTFUS at 1-800-253-6530 or e-mail [email protected].

PROGNOSIS AND OUTCOME The likely outcome, or prognosis, for a child with a brain tumor depends on many factors, including: • age of the child • child’s overall health • exact location of the tumor • how much the tumor has already affected the child’s ability to function • degree of metastasis, especially the extent to which the tumor has already spread when first found • degree of surgical resection • type of treatment received

Surgical removal of an ependymoma can lead to a cure, and postoperative RT increases overall survival at five years. However, even “totally” resected tumors can recur because of microscopic deposits of tumor within the normal brain surrounding the tumor bed. Recurrence usually takes place sooner following subtotal resection than after gross total resection. Prognosis is poorest for patients with high-grade ependymomas and those with tumors that cannot be safely removed surgically. Relative survival rates appear to be highest in people between the ages of 20 and 65. In people under age 19, relative survival rates for malignant ependymoma are nearly 68 percent at two years, about 48 percent at five years, and around 41 percent at ten years. Rates are significantly higher for adolescents than for children under age 5 (SEER 1973- 1996).

WHEN A TUMOR RETURNS Ependymomas that recur often do so at the primary tumor site. In addition, there is always a chance that even a benign ependymoma will spread into the meninges – the membranes covering the brain and spinal cord. If only part of the tumor is removed (as in near total, subtotal, or partial resection), recurrence is

10 Pediatric Brain Tumor Foundation of the United States more likely. If tumor progression is discovered, repeat surgery, RT or chemotherapy may be recommended.

IN THE LONG TERM: LIVING WITH EPENDYMOMA More children than ever are surviving brain tumors. Having survived, however, they and their families must often deal with long-term effects caused by the tumor or by the therapy used to treat the tumor. Among the possible issues are: • decreased levels of growth hormone • decreased levels of thyroid hormone • delayed growth • reduced ability to think and reason • impaired vision or hearing • physical disabilities • fatigue • depression • personality and attitude changes • hydrocephalus • seizures As distressing as these side effects can be, it is important to remember that untreated children have little chance of survival. The choice to do what it takes to extend life carries with it a choice to accept the risk that complications may occur. Your best defense is a good offense. Educate yourself. Seek out other people who are going through similar experiences, or who have already been down the road you are traveling. Be prepared. Don't hesitate to ask questions, express concerns, and seek more explanation when needed. Many of the problems caused by brain tumors or treatment can be offset. Hormone Replacement Therapy (HRT) is used to overcome hormone deficiencies. Physical therapy and occupational therapy are helpful to children with impaired coordination. If a child has difficulty talking, speech therapy may be useful. Specialists can address vision and hearing problems. The entire family can benefit from social support programs, including individual, couples or group counseling. For example, the Pediatric Brain Tumor Foundation of the United States offers a Family Support Program. For more information on family support groups in your area or starting a family support group, contact the Pediatric Brain Tumor Foundation of the United States at 1-800-253-6530 or e-mail: [email protected]. Even if there are no apparent complications, a child who has had a brain tumor must be monitored closely.

Pediatric Brain Tumor Foundation of the United States 11 Regular MRI or CT scans are required for several years following surgery. Your doctor may also recommend hormone evaluation and neuropsychological testing. Talk with your doctor about post-treatment monitoring of your child’s tumor. Your child may sustain late effects from the tumor itself and/or from treatments for the disease. After completing treatment, there will be concern for appropriate reintegration into school. This may require school placement and interventions to deal with the child’s particular learning needs. It is important for parents to work with educators, the medical care team, and the child to identify individual needs, which can then be addressed with an Individualized Education Plan (IEP). Ongoing interaction will help to assure that your child’s needs are addressed. Consultation with a neuropsychiatrist or neuropsychologist may be helpful in evaluating learning needs. Information is available about this process from the PBTFUS at 1-800-253-6530 or e-mail: [email protected].

CONCLUSION: HOPE FOR TODAY AND TOMORROW By now, you have probably discovered that when you are dealing with a brain tumor, you do not travel in a straight line from beginning to end. Instead, one step forward can be followed by two steps backward, followed by three steps forward, and so on. An attempt to treat one complication may create other problems, which then must be solved. Yet you also experience small triumphs along the way, and you are always aware that a major victory may be just around the corner. As you continue on this difficult journey, we encourage you to ask questions and express your concerns. At the same time, seek out people and places that give you energy and hope. Only when you are nourished can you give of yourself to those who need you. We are making progress against ependymomas. Every study and clinical trial increases our understanding of this tumor’s origin and behavior, improving our ability to destroy it. One day, we will learn how to prevent it. And with each advance, more and more children will be able to enjoy a long and productive life.

12 Pediatric Brain Tumor Foundation of the United States Pediatric Brain Tumor Foundation of the United States 302 Ridgefield Court Asheville, NC 28806 (828) 665-6891 • (828) 665-6894 (fax) (800) 253-6530 e-mail [email protected] [email protected] [email protected] websites http://www.pbtfus.org http://www.ride4kids.org

This publication made possible through a generous grant from the Janirve Foundation.