- Purpose of This PDQ Summary
- General Information
- Background Information About Childhood Central Nervous System Atypical Teratoid / Rhabdoid Tumor
- Cellular Classification and Tumor Biology of Childhood Central Nervous System Atypical Teratoid / Rhabdoid Tumor
- Stage Information
- Treatment for Newly Diagnosed Childhood Central Nervous System Atypical Teratoid / Rhabdoid Tumor
- Treatment for Recurrent Childhood Central Nervous System Atypical Teratoid / Rhabdoid Tumor
- Get More Information From NCI
- Changes to This Summary (08 / 04 / 2009)
- More Information
Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor Treatment (PDQ®): Treatment - Health Professional Information [NCI]
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Childhood Atypical Teratoid/Rhabdoid Tumor Treatment
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood central nervous system atypical teratoid/rhabdoid tumor. This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board.
Information about the following is included in this summary:
- Cellular classification and tumor biology.
- Diagnostic evaluation.
- Treatment options.
This summary is intended as a resource to inform and assist clinicians and other health professionals who care for pediatric cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric and Adult Treatment Editorial Boards use a formal evidence ranking system in developing their level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for reimbursement determinations.
This summary is also available in a patient version, which is written in less technical language, and in Spanish.
The National Cancer Institute provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public. The PDQ childhood brain tumor treatment summaries are organized primarily according to the 2000 World Health Organization classification of nervous system tumors.
In recent decades, dramatic improvements in survival have been achieved for children and adolescents with cancer. 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. Refer to the PDQ summary on Childhood Brain and Spinal Cord Tumors Treatment Overview for information about the general classification of childhood brain and spinal cord tumors.
|1.||Kleihues P, Cavenee WK, eds.: Pathology and Genetics of Tumours of the Nervous System. Lyon, France: International Agency for Research on Cancer, 2000.|
Background Information About Childhood Central Nervous System Atypical Teratoid / Rhabdoid Tumor
The exact incidence of childhood central nervous system atypical teratoid/rhabdoid tumor (AT/RT) is difficult to determine since the tumor has been widely recognized only for the last decade. In the Children's Cancer Group study CCG-9921, 10% of infants had AT/RT. In Pediatric Oncology Group study CCG-9233, 36 (11%) of 319 patients were identified in central review as having AT/RT. A Taiwanese study suggests an incidence of 26% in children aged younger than 3 years. The incidence in older patients is unknown. In The AT/RT Registry, 12 of 42 patients (29%) were older than 36 months at the time of diagnosis.
Childhood AT/RT is a clinically aggressive tumor that primarily occurs in children younger than 3 years but it also can occur in older children and has been reported in adults.[4,5] In about half of patients, the tumor is located in the posterior fossa, although it can occur anywhere in the central nervous system.
Signs and symptoms related to the tumor are dependent on location. Young patients with posterior fossa tumors usually present with symptoms related to hydrocephalus such as early morning headaches, vomiting, and lethargy. They may also develop ataxia or regression of motor skills. Because AT/RT grows rapidly, patients typically have a fairly short history of progressive symptoms measured in days to weeks. Data from The AT/RT Registry suggests that approximately 20% of patients present with disseminated disease. Dissemination is typically through leptomeningeal pathways seeding the spine and other areas of the brain. There are also reports of rare patients with synchronous renal rhabdoid and AT/RT.
Most published information on outcome for patients with AT/RT is based on small series and is retrospective in nature. Initial retrospective studies reported an average survival from diagnosis of only about 12 months.[1,4,7] There are, however, reports of long-term survivors.
Cellular Classification and Tumor Biology of Childhood Central Nervous System Atypical Teratoid / Rhabdoid Tumor
Childhood central nervous system atypical teratoid/rhabdoid tumor (AT/RT) was first described as a discrete clinical entity in 1987  due to its pathologic and genetic characteristics. Prior to that, it was often misclassified as a medulloblastoma, primitive neuroectodermal tumor, or choroid plexus carcinoma. The World Health Organization began classifying it as an embryonal grade IV neoplasm in 1993.
Histologically, AT/RT contains sheets of rhabdoid cells against a background of primitive neuroectodermal cells, mesenchymal cells, or epithelial cells. Immunohistochemical features help to identify the disease but vary depending on the cellular composition of the tumor. Rhabdoid cells express vimentin, epithelial membrane antigen, and smooth muscle actin. The primitive neuroectodermal cells variably express neurofilament protein, glial fibrillary acidic protein, keratin, or desmin. AT/RT is a rapidly growing tumor that can have an MIB-1 labeling index of 50% to 100%.
AT/RT is the first primary pediatric brain tumor for which a candidate tumor suppressor gene, INI1, has been identified.INI1 has been found to be abnormal in the majority of rhabdoid tumors, including central nervous system, renal, and extra renal rhabdoid malignancies. In published series, 76% of AT/RTs had a deletion or mutation in INI1. INI1 is a component of a Switch (SWI) and Sucrose non-fermenting (SNF) ATP-dependent chromatin-remodeling complex. The exact function of the INI1 gene is unknown but it is likely that a mutation results in altered transcriptional regulation of downstream targets. In addition to somatic mutations, germline mutations in INI1 have been reported in some AT/RT patients.[4,6] This appears to be more common in patients with rhabdoid tumors in two primary sites and germline screening may be an important predictor of risk to develop multiple primary tumors.
Immunohistochemical staining for INI1 has been developed and appears to be a useful tool in distinguishing AT/RT from primitive neuroectodermal tumors and other central nervous system tumors that can be confused with AT/RT.[7,8] It is now being used routinely to distinguish AT/RT from other brain tumors. This tool appears very helpful in identifying AT/RT even if the tumor does not have the classic morphologic features.
Diagnostic Evaluation of Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor
All patients with childhood AT/RT should have magnetic resonance imaging of the brain and spine at the time of diagnosis. Unless medically contraindicated, patients should also have lumbar cerebrospinal fluid inspected for evidence of tumor. Consideration should also be given to renal ultrasound to detect synchronous tumors. There is no way to reliably distinguish AT/RT from other malignant brain tumors based on clinical history or radiographic evaluation. Treatment decisions are based on age of patient and extent of disease. The extent of disease affects long term outcome.
There is no defined staging system for childhood central nervous system atypical teratoid/rhabdoid tumor (AT/RT). Patients are classified as having newly diagnosed or recurrent disease with or without neuroaxis dissemination.
Treatment for Newly Diagnosed Childhood Central Nervous System Atypical Teratoid / Rhabdoid Tumor
There is no established standard treatment for children with central nervous system atypical teratoid/rhabdoid tumor (AT/RT). Given the highly aggressive nature of the tumor, most patients have been treated with intensive multimodal therapy. The young age of the majority of patients does, however, put some limitations on the extent of treatment, particularly radiation. Surgery is necessary to obtain tissue and make the diagnosis of AT/RT. Data from The AT/RT Registry suggests that patients who have had a complete resection may have a longer median survival, although complete surgical resection is often difficult given the invasive nature of the tumor. Chemotherapy has been the main adjuvant therapy for very young children with AT/RT. Cooperative group studies that included children aged younger than 36 months, demonstrated poor survival when treated with standard chemotherapeutic regimens alone. The Children's Cancer Group reported a 2-year event free survival (EFS) of 14% for 28 children younger than 36 months treated with multiagent chemotherapy.
Intensive regimens that utilize varying combinations of high-dose chemotherapy,[Level of evidence: 3iiiDi] intrathecal chemotherapy, and radiation have led to prolonged survival for some patients. Thirteen patients in The AT/RT Registry were treated with high-dose chemotherapy with hematopoietic stem cell rescue as part of initial therapy. Four of these patients, two of whom also received radiation, were alive without progressive disease 21.5 to 90 months following diagnosis at last report. Radiation therapy appears to have an impact on survival for AT/RT patients. Of the 42 patients in The AT/RT Registry, 13 patients (31%) received radiation therapy in addition to chemotherapy as part of their primary therapy. The radiation field was to the primary tumor bed in nine children, and the tumor bed and the craniospinal axis in four children. Their median survival was 48 months, while the median survival of all patients on the registry was 16.75 months. Supporting the value of radiation therapy was a retrospective series of 31 patients with AT/RT from St. Jude Children's Research Hospital in which the 2-year EFS for patients older than 3 years was 78%, considerably better than 11% for patients younger than 3 years. All but one surviving patient (seven of eight) in the older group received craniospinal irradiation and intensive chemotherapy with hematopoietic stem cell transplant; only three of 22 of the younger patients received any form of radiation therapy, two of whom are disease-free.
Another therapeutic approach to patients with AT/RT is based on the Third Intergroup Rhabdomyosarcoma (IRS-III) Study. It utilizes radiation therapy, intrathecal methotrexate, cytarabine, hydrocortisone, and systemic multiagent chemotherapy. The results of small retrospective series were encouraging,[6,7] leading to the first prospective study of multimodality treatment in this group of patients. Results of the prospective study demonstrated a 2-year progression-free survival of 53% ± 13% and an overall survival of 70% ± 10%, with results most favorable in children who had a gross total resection and no metastatic disease at presentation. Prospective cooperative group clinical trials for AT/RT are greatly needed to better understand how age and extent of therapy impact survival.
Treatment Options Under Clinical Evaluation
The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
- The Children's Oncology Group has developed a phase III study (ACNS0333) for patients aged 0 to 21 years with AT/RT. The study uses multiagent chemotherapy, radiation, and high-dose chemotherapy with hematopoietic stem cell rescue.
Treatment for Recurrent Childhood Central Nervous System Atypical Teratoid / Rhabdoid Tumor
There is no standard treatment for recurrent childhood central nervous system atypical teratoid/rhabdoid tumor. Entry into studies of novel therapeutic approaches should be considered. Information about ongoing clinical trials is available from the NCI Web site.
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Changes to This Summary (08 / 04 / 2009)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
TREATMENT FOR NEWLY DIAGNOSED CHILDHOOD CENTRAL NERVOUS SYSTEM ATYPICAL TERATOID/RHABDOID TUMOR
Added Gardner et al. as reference 4 and level of evidence 3iiiDi.
Added text on a study of intensive multimodality treatment for children with newly diagnosed central nervous system atypical teratoid/rhabdoid tumor (cited Chi et al. as reference 8).
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ADDITIONAL PDQ SUMMARIES
- PDQ® Cancer Information Summaries: Adult Treatment
Treatment options for adult cancers.
- PDQ® Cancer Information Summaries: Pediatric Treatment
Treatment options for childhood cancers.
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Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.
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Tests or procedures that detect specific types of cancer.
- PDQ® Cancer Information Summaries: Prevention
Risk factors and methods to increase chances of preventing specific types of cancer.
- PDQ® Cancer Information Summaries: Genetics
Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.
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Information about complementary and alternative forms of treatment for patients with cancer.
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
Date Last Modified: 2009-08-04