Treatment Option Overview

Key Points for This Section

There are different types of treatment for patients with childhood central nervous system germ cell tumors.
Children with childhood central nervous system germ cell tumors should have their treatment planned by a team of health care providers who are experts in treating cancer in children.
Some cancer treatments cause side effects months or years after treatment has ended.
Four types of standard treatment are used:
New types of treatment are being tested in clinical trials.
Patients may want to think about taking part in a clinical trial.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Follow-up tests may be needed.

There are different types of treatment for patients with childhood central nervous system germ cell tumors.

Different types of treatment are available for children with childhood central nervous system germ cell tumors. Some treatments are standard (the currently used treatment), and some are being tested inclinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

Because cancer in children is rare, taking part in a clinical trial should be considered. Some clinical trials are open only to patients who have not started treatment.

Children with childhood central nervous system germ cell tumors should have their treatment planned by a team of health care providers who are experts in treating cancer in children.

Treatment will be overseen by a pediatric oncologist and/or a radiation oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other pediatric health care providers who are experts in treating children with childhood central nervous system germ cell tumors and who specialize in certain areas of medicine. These may include the following specialists:

Some cancer treatments cause side effects months or years after treatment has ended.

Some cancer treatments cause side effects that continue or appear months or years after cancer treatment has ended. These are called late effects. Late effects of cancer treatment may include:

Physical problems.
Changes in mood, feelings, thinking, learning, or memory.
Second cancers (new types of cancer).

Some late effects may be treated or controlled. It is important to talk with your child's doctors about the possible late effects caused by some treatments. (See the PDQ summary on Late Effects of Treatment for Childhood Cancer for more information).

Four types of standard treatment are used:

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type of thetumor being treated.

Radiation therapy to the brain can affect growth and development in young children. Certain ways of giving radiation therapy can lessen the damage to healthy brain tissue. For children younger than 3 years, chemotherapy may be given instead. This can delay or reduce the need for radiation therapy.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into avein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Surgery

Whether surgery to remove the tumor can be done depends on where the tumor is in the brain. Surgery to remove the tumor may cause severe, long-term side effects.

Surgery may be done to remove teratomas and may be used for germ cell tumors that come back. Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

High-dose chemotherapy with stem cell rescue

High-dose chemotherapy with stem cell rescue is a way of giving high doses of chemotherapy and replacing blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through aninfusion. These reinfused stem cells grow into (and restore) the body’s blood cells.

New types of treatment are being tested in clinical trials.

Information about clinical trials is available from the NCI Web site.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your child's condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Children whose cancer affected their pituitary gland at diagnosis will usually need to have their bloodhormone levels checked. If the blood hormone level is low, replacement hormone medicine is given. Children who had a high tumor marker level (alpha-fetoprotein or beta-human chorionic gonadotropin) at diagnosis, usually need to have their blood tumor marker level checked. If the tumor marker level increases after initial treatment, the tumor may have recurred.

General Information About Childhood Central Nervous System (CNS) Germ Cell Tumors

Anatomy
Diagnosis

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.

Anatomy

Central nervous system (CNS) germ cell tumors (GCTs) may arise from the pineal and/or suprasellar regions as solitary or multiple lesions. Pineal region tumors are twice as frequent as suprasellar tumors, but approximately 5% to 10% of patients have both suprasellar and pineal gland involvement at the time of diagnosis.[4] Involvement of both sites is most commonly seen in pure germinomas. Males have a higher incidence of GCT than females, with males having a preponderance of pineal region primaries. Other areas that may be involved, though rare, include the basal ganglia, ventricles, thalamus, cerebral hemispheres, and the medulla.[5,6]

Diagnosis

Radiographic characteristics of CNS GCTs cannot reliably differentiate germinomas from nongerminomatous germ cell tumors (NGGCTs) or from other CNS tumors. The diagnosis of GCTs is based on clinical symptoms and signs, tumor markers, neuroimaging, and cytological cerebrospinal fluid (CSF) and histological confirmation. Patients with intracranial GCTs often present with pituitary dysfunction including diabetes insipidus (DI), with an increased presence in patients with tumors involving the suprasellar region. Two-thirds to 90% of patients with a GCT of the suprasellar region present with DI.[7,8] Patients with tumors in the pineal region may also present with DI without imaging evidence of third ventricular and suprasellar involvement. Visual loss, growth hormone deficiency, precocious puberty (suprasellar tumors), and Parinaud syndrome (pineal tumors) are also common.[8] Nonspecific symptoms such as enuresis, anorexia, and psychiatric complaints can lead to delays in diagnosis, whereas signs of increased intracranial pressure or visual changes tend to result in earlier diagnosis.[9]

Appropriate staging is crucial since patients with metastatic disease should receive different total radiation doses and more extended radiation fields. All patients with a suspected CNS GCT should have the following tests:

Magnetic resonance imaging (MRI) of brain and spine with gadolinium.
Alpha-fetoprotein (AFP) and beta subunit human chorionic gonadotropin (beta-HCG) in both serum and CSF. If pre-operative lumbar CSF can be obtained safely and tumor markers are elevated, this may obviate the need for upfront surgery. Lumbar CSF is preferred and is more sensitive than serum markers for beta-HCG.[10] In cases where the patient presents with hydrocephalus requiring CSF diversion, CSF tumor markers can be obtained by ventricular CSF sampling at the time of surgery.
CSF cytology.
Evaluation of pituitary/hypothalamic function.
Visual field examinations for suprasellar or hypothalamic tumors.
Baseline neuropsychologic examination.

Diagnosis of GCTs often requires a tumor biopsy, except in cases with characteristic increased tumor markers in the serum and/or CSF. When the tumor markers are negative or mildly elevated but below diagnostic criteria, or if there is any noncharacteristic finding, a tumor biopsy should be done.

References

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.
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. [PUBMED Abstract]
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. [PUBMED Abstract]
Weksberg DC, Shibamoto Y, Paulino AC: Bifocal intracranial germinoma: a retrospective analysis of treatment outcomes in 20 patients and review of the literature. Int J Radiat Oncol Biol Phys 82 (4): 1341-51, 2012. [PUBMED Abstract]
Goodwin TL, Sainani K, Fisher PG: Incidence patterns of central nervous system germ cell tumors: a SEER Study. J Pediatr Hematol Oncol 31 (8): 541-4, 2009. [PUBMED Abstract]
Villano JL, Propp JM, Porter KR, et al.: Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries. Neuro Oncol 10 (2): 121-30, 2008. [PUBMED Abstract]
Afzal S, Wherrett D, Bartels U, et al.: Challenges in management of patients with intracranial germ cell tumor and diabetes insipidus treated with cisplatin and/or ifosfamide based chemotherapy. J Neurooncol 97 (3): 393-9, 2010. [PUBMED Abstract]
Hoffman HJ, Otsubo H, Hendrick EB, et al.: Intracranial germ-cell tumors in children. J Neurosurg 74 (4): 545-51, 1991. [PUBMED Abstract]
Crawford JR, Santi MR, Vezina G, et al.: CNS germ cell tumor (CNSGCT) of childhood: presentation and delayed diagnosis. Neurology 68 (20): 1668-73, 2007. [PUBMED Abstract]
Allen J, Chacko J, Donahue B, et al.: Diagnostic sensitivity of serum and lumbar CSF bHCG in newly diagnosed CNS germinoma. Pediatr Blood Cancer 59 (7): 1180-2, 2012. [PUBMED Abstract]