Rhabdoid Tumor of the Kidney

  • Dana-Farber / Children's Hospital Cancer Center logo

    Rhabdoid tumor of the kidney is a malignant tumor of the kidney. These tumors usually occur in children younger than 2 years. Learn about rhabdoid tumors and find information on how we support and care for children with rhabdoid tumors of the kidney before, during, and after treatment.

The Solid Tumor Center at Dana-Farber/Boston Children's Cancer and Blood Disorders Center treats children and teens with a variety of solid malignancies, including bone and soft tissue tumors, liver and kidney tumors, neuroblastomas, retinoblastomas and rare tumors. Our doctors provide unparalleled expertise in the diagnosis, treatment and management of these diseases.

Your child's care team will include pediatric oncologists, radiation oncologists, surgeons, pathologists, radiologists, and nurses with expertise in treating your child's specific type of cancer.

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 your family's needs. We consider you and your child integral parts of the care team. Our specialists will collaborate with you to customize a treatment plan that takes the needs of your child and your family into account.

As well as providing access to a range of innovative clinical trials through Dana-Farber/Boston Children's, we are New England's Phase I referral center for the Children's Oncology Group, which means we're able to offer clinical trials unavailable at other regional centers.

Your child will have access to long-term treatment and childhood cancer survivor support through Dana-Farber's David B. Perini, Jr. Quality of Life Clinic.

From diagnosis through treatment and survivorship, our team will be able to answer all of your questions about your child's care.

Find out more about our Solid Tumor Center, including the diseases we treat and our specialized programs for bone and soft tissue tumors, liver tumors, neuroblastoma, rare tumors, and retinoblastoma.

Information for: Patients | Healthcare Professionals

Rhabdoid Tumor

What is a rhabdoid tumor?

A rhabdoid tumor is a rare and highly malignant tumor of childhood, first described in 1978. These tumors were initially considered an aggressive variant of Wilms' tumor of the kidney, however, with newer diagnostic techniques these tumors are believed to represent a distinct entity.

Since that time, there have been fewer than 50 cases reported, although it is likely that some cases previously identified as medulloblastoma or as primitive neuroectodermal tumors (PNET) are in fact rhabdoid tumors. These tumors occur in young children, mean age at diagnosis of 3.5 years, with a range of 2 to 13 years. There are no reported cases in adults.

Rhabdoid tumors occur equally in males and females. The location can be supratentorial, intraventicular, and infratentorial.

As you read further below, you will find general information about rhabdoid tumors. If you would like to view summary information about brain tumors first, see the overview on brain tumors.

What are the symptoms of a rhabdoid tumor?

The symptoms depend on the location of the tumor and the age of the child. The following are the most common symptoms of a rhabdoid tumor, however each child may experience symptoms differently. Common symptoms may include:

  • seizures - can be the only presenting sign for supratentorial lesions
  • hydrocephalus - enlargement of the skull and pressure on the brain
  • raised intracranial pressure - the tumor blocks the normal flow of cerebrospinal fluid and the tumor causes increased production of fluid, resulting in headaches, morning vomiting, lethargy, and disturbances in walking
  • enlarged head size or fontanels (the soft "spot" that occurs before the bones in the head become solid) in infants

Due to the aggressiveness of these tumors, the duration of symptoms before coming to medical attention is relatively short.

The symptoms of a brain tumor may resemble other conditions or medical problems. Always consult your child's physician for a diagnosis.

How are rhabdoid tumors classified?

Rhabdoid tumors are considered mesenchymal nonmeningothelial tumors within the WHO classification. These tumors are distinct from rhabdomyosarcomas.

Immunohistochemical staining shows positivity for vimentin, cytokeratin, and epithelial membrane antigen. Neural markers are variably present. A characteristic cytogenetic abnormality has been identified, the deletion of 22q (22q11) which can aid in differentiating these tumors from other poorly differentiated malignant brain tumors.

How is a rhabdoid tumor diagnosed?

Diagnostic procedures for rhabdoid tumor may include:

  • magnetic resonance imaging (MRI) - a diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body. MRI provides greater anatomical detail than CT scan and can better distinguish between tumor, tumor-related swelling and normal tissue.
     
  • magnetic resonance spectroscopy (MRS) - a test done along with MRI at specialized facilities that can detect the presence of particular organic compounds produced by the body's metabolism within sample tissue that can identify tissue as normal or tumor, and may be able to distinguish between glial tumors and tumors of neuronal origin
What are the treatments for a rhabdoid tumor?

Specific treatment for a rhabdoid tumor will be determined by your child's physician based on:

  • 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 expect the disease to progress
  • your opinion or preference

A multidisciplinary approach, involving the neurosurgeon, pediatric oncologist, neurologist, and radiation oncologist is needed for these patients. Treatment may include (alone or in combination):

  • surgery - aggressive surgical removal followed by chemotherapy is standard treatment

     
  • radiation therapy - children over 3 years of age will receive craniospinal radiotherapy with a boost to the primary tumor. For children under 3, radiotherapy is generally deferred, however, focal radiation therapy has been incorporated into some treatment protocols designed for this age group. Radiation therapy uses high-energy rays (radiation) from a specialized machine to damage or kill cancer cells and shrink tumors.

     
  • chemotherapy - a drug treatment that works by interfering with the cancer cell's ability to grow or reproduce. Different groups of chemotherapy drugs work in different ways to fight cancer cells and shrink tumors. Often, a combination of chemotherapy drugs is used to fight a specific cancer. Certain chemotherapy drugs may be given in a specific order depending on the type of cancer it is being used to treat.

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

    Chemotherapy is systemic treatment, meaning it is introduced to the bloodstream and travels throughout the body to kill cancer cells. Chemotherapy can be given:
    • as a pill to swallow
    • as an injection into the muscle or fat tissue
    • intravenously (directly to the bloodstream; also called IV)
    • intrathecally - chemotherapy given directly into the spinal column with a needle
    Chemotherapy regimens have varied for patients with rhabdoid tumors, although none has been considered curative. Protocols have used cis-platin, VP-16, cyclophosphamide, and vincristine. Regimens for extracranial rhabdoid tumors have employed ifosfamide, doxorubicin, vincristine, and cyclophosphamide. The prognosis is very poor although objective responses have been observed but the duration is 2 to 5 months from diagnosis. Recurrent disease is managed symptomatically with consideration for palliative surgery and/or radiotherapy.

What is the latest research on rhabdoid tumors?

Dana-Farber/Boston Children's Cancer and Blood Disorders Center is conducting numerous research studies that will help clinicians better understand and treat rhabdoid tumors.


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.

Background Information About Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor

Based on present biologic understanding, atypical teratoid/rhabdoid tumor (AT/RT) is part of a larger family of rhabdoid tumors. In this summary, AT/RT refers to central nervous system (CNS) tumors only and rhabdoid tumor reflects the possibility of both CNS and non-CNS tumors. Unless noted otherwise in the text, this summary is referring to AT/RT.

Incidence

The exact incidence of childhood CNS AT/RT is difficult to determine since the tumor has been widely recognized only for the last decade. In two recent North American based prospective studies performed by the Children’s Cancer Group and the Pediatric Oncology Group for children aged 3 years or younger at diagnosis, retrospective review disclosed that approximately 10% of children had AT/RTs.[1] A Taiwanese study found that AT/RTs account for 26% of primitive or embryonal tumors in children younger than 3 years.[2] The Austrian Brain Tumor Registry, conducted between 1996 and 2006, confirmed that AT/RTs represent the sixth most common malignant brain tumor in 311 newly diagnosed children (6.1%), with a peak incidence during the first 2 years of life.[3] The incidence in older patients is unknown. In the Central Nervous System Atypical Teratoid/Rhabdoid Tumor Registry (AT/RT Registry), 12 of 42 patients (29%) were older than 36 months at the time of diagnosis.[4]

Clinical Behavior

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.[5][6] In about one-half of patients, the tumor is located in the posterior fossa, although it can occur anywhere in the CNS.[1]

Presentation

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 suggest that approximately 20% of patients present with disseminated disease.[4] 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.[7]

Prognosis

Prognostic factors that affect survival for AT/RTs are not fully delineated. Factors associated with a poor outcome include the following:

  • Germline mutation.[8]
  • Age younger than 2 years.[9]
  • Metastases at diagnosis.[9]
  • Subtotal resection.[10]

Most published information on outcomes 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][5][10][11][12] In another retrospective report, 2-year overall survival was better for patients who underwent a gross total resection than for those who had a subtotal tumor removal. However, the contribution of radiation therapy was less clear.[10] There are, however, reports of long-term survivors.[13] Notably, improved survival has been reported for those aged 3 years and older who received postoperative craniospinal irradiation and high-dose alkylator-based chemotherapy compared with those younger than 3 years with AT/RT. In this report, the incidence of leptomeningeal metastases was also higher in the infant group of patients.[14] In one prospective study of 25 children with AT/RT receiving intensive multimodal therapy, including radiation and intrathecal chemotherapy, the reported 2-year progression-free survival rate was 53%, and the overall survival rate was 70%.[15]

References:

  1. Packer RJ, Biegel JA, Blaney S, et al.: Atypical teratoid/rhabdoid tumor of the central nervous system: report on workshop. J Pediatr Hematol Oncol 24 (5): 337-42, 2002 Jun-Jul.

  2. Ho DM, Hsu CY, Wong TT, et al.: Atypical teratoid/rhabdoid tumor of the central nervous system: a comparative study with primitive neuroectodermal tumor/medulloblastoma. Acta Neuropathol 99 (5): 482-8, 2000.

  3. Woehrer A, Slavc I, Waldhoer T, et al.: Incidence of atypical teratoid/rhabdoid tumors in children: a population-based study by the Austrian Brain Tumor Registry, 1996-2006. Cancer 116 (24): 5725-32, 2010.

  4. Hilden JM, Meerbaum S, Burger P, et al.: Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry. J Clin Oncol 22 (14): 2877-84, 2004.

  5. Burger PC, Yu IT, Tihan T, et al.: Atypical teratoid/rhabdoid tumor of the central nervous system: a highly malignant tumor of infancy and childhood frequently mistaken for medulloblastoma: a Pediatric Oncology Group study. Am J Surg Pathol 22 (9): 1083-92, 1998.

  6. Lutterbach J, Liegibel J, Koch D, et al.: Atypical teratoid/rhabdoid tumors in adult patients: case report and review of the literature. J Neurooncol 52 (1): 49-56, 2001.

  7. Biegel JA, Fogelgren B, Wainwright LM, et al.: Germline INI1 mutation in a patient with a central nervous system atypical teratoid tumor and renal rhabdoid tumor. Genes Chromosomes Cancer 28 (1): 31-7, 2000.

  8. Kordes U, Gesk S, Frühwald MC, et al.: Clinical and molecular features in patients with atypical teratoid rhabdoid tumor or malignant rhabdoid tumor. Genes Chromosomes Cancer 49 (2): 176-81, 2010.

  9. Dufour C, Beaugrand A, Le Deley MC, et al.: Clinicopathologic prognostic factors in childhood atypical teratoid and rhabdoid tumor of the central nervous system: a multicenter study. Cancer 118 (15): 3812-21, 2012.

  10. Lafay-Cousin L, Hawkins C, Carret AS, et al.: Central nervous system atypical teratoid rhabdoid tumours: the Canadian Paediatric Brain Tumour Consortium experience. Eur J Cancer 48 (3): 353-9, 2012.

  11. Rorke LB, Packer RJ, Biegel JA: Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity. J Neurosurg 85 (1): 56-65, 1996.

  12. Athale UH, Duckworth J, Odame I, et al.: Childhood atypical teratoid rhabdoid tumor of the central nervous system: a meta-analysis of observational studies. J Pediatr Hematol Oncol 31 (9): 651-63, 2009.

  13. Olson TA, Bayar E, Kosnik E, et al.: Successful treatment of disseminated central nervous system malignant rhabdoid tumor. J Pediatr Hematol Oncol 17 (1): 71-5, 1995.

  14. Tekautz TM, Fuller CE, Blaney S, et al.: Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy. J Clin Oncol 23 (7): 1491-9, 2005.

  15. Chi SN, Zimmerman MA, Yao X, et al.: Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor. J Clin Oncol 27 (3): 385-9, 2009.

Cellular Classification and Tumor Biology of Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor

Childhood central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT) was first described as a discrete clinical entity in 1987 [1] because of 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.[2]

AT/RT is a rapidly growing tumor that can have an MIB-1 labeling index of 50% to 100%.[2] Immunohistochemistry for INI1 protein is useful in establishing the diagnosis of AT/RT. A loss of INI1 staining is noted in neoplastic cells, but staining is retained in non-neoplastic cells (e.g., vascular endothelial cells).[3][4][5]

Histologically, classic AT/RT is morphologically heterogeneous, typically containing sheets of large epithelioid cells with abundant eosinophilic cytoplasm and scattered rhabdoid cells, most often with accompanying components of primitive neuroectodermal cells (small round blue cells), mesenchymal cells, and/or glial cells.[6] Immunohistochemical staining for epithelial markers (cytokeratin or epithelial membrane antigen), glial fibrillary acidic protein, synaptophysin (or neurofilament), and smooth muscle (desmin) may help to identify the heterogeneity of differentiation, but will vary depending on the cellular composition.[7] Rhabdoid cells, while not present in all AT/RTs, will express vimentin, epithelial membrane antigen, and smooth muscle actin.

AT/RT is the first primary pediatric brain tumor for which a candidate tumor suppressor gene, SMARCB1 (also known as INI1 and hSNF5), has been identified.[8]SMARCB1 has been found to be abnormal in the majority of rhabdoid tumors, including CNS, renal, and extrarenal rhabdoid malignancies.[8] In published series, 76% of AT/RTs had a deletion or mutation in INI1/SMARCB1. SMARCB1 is a component of a Switch (SWI) and Sucrose non-fermenting (SNF) adenosine triphosphate-dependent chromatin-remodeling complex.[9] The exact function of the SMARCB1 gene is unknown, but it is likely that a mutation results in altered transcriptional regulation of downstream targets. Rare familial cases of rhabdoid tumors expressing SMARCB1 and lacking SMARCB1 mutations have also been associated with germline mutations of SMARCA4/BRG1, another member of the SWI/SNF chromatin-remodeling complex.[5][10]

In addition to somatic mutations, germline mutations in SMARCB1 have been reported in some AT/RT patients.[8][11] A study of 65 children with rhabdoid tumors found that 23 (35%) had germline mutations and/or deletions of SMARCB1.[3] Children with germline alterations in SMARCB1 presented at an earlier age than sporadic cases (median age approximately 5 months versus 18 months) and were more likely to present with multiple tumors.[3] One parent was found to be a carrier of the SMARCB1 germline abnormality in 7 of 22 evaluated cases showing germline alterations, with four of the carrier parents being unaffected by SMARCB1-associated cancers.[3] This indicates that AT/RT shows an autosomal dominant inheritance pattern with incomplete penetrance. Gonadal mosaicism has also been observed, as evidenced by families in which multiple siblings are affected by AT/RT and have identical SMARCB1 alterations, but both parents lack a SMARCB1 mutation/deletion.[3][4] Screening children diagnosed with AT/RT for germline SMARCB1 mutations may provide useful information for counseling families on the genetic implications of their child’s AT/RT diagnosis.[3]

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. Embryonal tumors, especially in those younger than 3 years, should undergo immunostaining for loss of SMARCB1 (INI1, hSNF5) protein expression to confirm the diagnosis.[4]

A Rhabdoid Tumor Predisposition Syndrome (RTPS), related primarily to germline SMARCB1 alterations, has been clearly defined.[8][11] This syndrome is manifested by a marked predisposition to the development of malignant rhabdoid tumors in infancy and early childhood. Up to one-third of AT/RTs are thought to arise in the setting of RTPS, and the majority of these occur within the first year of life. The most common non-CNS malignancy of RTPS is the malignant rhabdoid tumor of the kidney, which is also noted in infancy. RTPS is highly suggested in patients with synchronous occurrence of renal malignant rhabdoid tumor and AT/RT, bilateral malignant rhabdoid tumors of the kidney, or malignant rhabdoid tumors in two or more siblings.

References:

  1. Rorke LB, Packer RJ, Biegel JA: Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity. J Neurosurg 85 (1): 56-65, 1996.

  2. Kleihues P, Louis DN, Scheithauer BW, et al.: The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 61 (3): 215-25; discussion 226-9, 2002.

  3. Eaton KW, Tooke LS, Wainwright LM, et al.: Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors. Pediatr Blood Cancer 56 (1): 7-15, 2011.

  4. Bruggers CS, Bleyl SB, Pysher T, et al.: Clinicopathologic comparison of familial versus sporadic atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system. Pediatr Blood Cancer 56 (7): 1026-31, 2011.

  5. Hasselblatt M, Gesk S, Oyen F, et al.: Nonsense mutation and inactivation of SMARCA4 (BRG1) in an atypical teratoid/rhabdoid tumor showing retained SMARCB1 (INI1) expression. Am J Surg Pathol 35 (6): 933-5, 2011.

  6. Kleihues P, Cavenee WK, eds.: Pathology and Genetics of Tumours of the Nervous System. Lyon, France: International Agency for Research on Cancer, 2000.

  7. McLendon RE, Adekunle A, Rajaram V, et al.: Embryonal central nervous system neoplasms arising in infants and young children: a pediatric brain tumor consortium study. Arch Pathol Lab Med 135 (8): 984-93, 2011.

  8. Biegel JA, Tan L, Zhang F, et al.: Alterations of the hSNF5/INI1 gene in central nervous system atypical teratoid/rhabdoid tumors and renal and extrarenal rhabdoid tumors. Clin Cancer Res 8 (11): 3461-7, 2002.

  9. Biegel JA, Kalpana G, Knudsen ES, et al.: The role of INI1 and the SWI/SNF complex in the development of rhabdoid tumors: meeting summary from the workshop on childhood atypical teratoid/rhabdoid tumors. Cancer Res 62 (1): 323-8, 2002.

  10. Schneppenheim R, Frühwald MC, Gesk S, et al.: Germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in a family with rhabdoid tumor predisposition syndrome. Am J Hum Genet 86 (2): 279-84, 2010.

  11. Biegel JA, Fogelgren B, Wainwright LM, et al.: Germline INI1 mutation in a patient with a central nervous system atypical teratoid tumor and renal rhabdoid tumor. Genes Chromosomes Cancer 28 (1): 31-7, 2000.

Stage Information

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 neuraxis 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 (CNS) 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 suggest 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.[1] Chemotherapy has been the main adjuvant therapy for very young children with AT/RT. Cooperative group studies that included children younger than 36 months, demonstrated poor survival when treated with standard chemotherapeutic regimens alone.[2] 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.[3]

Intensive regimens that utilize varying combinations of high-dose chemotherapy,[4][Level of evidence: 3iA]; [5][6][Level of evidence: 3iiiDi] intrathecal chemotherapy, and radiation therapy 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.[1] 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.[1] 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.[7] All but one of the surviving patients (seven of eight) in the older group received craniospinal irradiation and intensive chemotherapy with hematopoietic stem cell transplant; only 3 of 22 of the younger patients received any form of radiation therapy, two of whom are disease free. In a Surveillance, Epidemiology, and End Results registry review, radiation therapy was associated with improved survival in children younger than 3 years.[8]

Another therapeutic approach to treating patients with AT/RT is based on the Third Intergroup Rhabdomyosarcoma (IRS-III) Study. It utilized radiation therapy, intrathecal methotrexate, cytarabine, hydrocortisone, and systemic multiagent chemotherapy. The results of small retrospective series were encouraging,[9][10] 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 were older, had a gross total resection, and had no metastatic disease at presentation.[11] Prospective cooperative group clinical trials for AT/RT are greatly needed to better understand how age and extent of therapy affect 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.

  • COG-ACNS0333 (Combination Chemotherapy, Radiation Therapy, and an Autologous Peripheral Blood Stem Cell Transplant in Treating Young Patients With AT/RT of the CNS): The Children’s Oncology Group has developed a phase III study 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.

References:

  1. Hilden JM, Meerbaum S, Burger P, et al.: Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry. J Clin Oncol 22 (14): 2877-84, 2004.

  2. Packer RJ, Biegel JA, Blaney S, et al.: Atypical teratoid/rhabdoid tumor of the central nervous system: report on workshop. J Pediatr Hematol Oncol 24 (5): 337-42, 2002 Jun-Jul.

  3. Geyer JR, Sposto R, Jennings M, et al.: Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group. J Clin Oncol 23 (30): 7621-31, 2005.

  4. Nicolaides T, Tihan T, Horn B, et al.: High-dose chemotherapy and autologous stem cell rescue for atypical teratoid/rhabdoid tumor of the central nervous system. J Neurooncol 98 (1): 117-23, 2010.

  5. Gardner SL, Asgharzadeh S, Green A, et al.: Intensive induction chemotherapy followed by high dose chemotherapy with autologous hematopoietic progenitor cell rescue in young children newly diagnosed with central nervous system atypical teratoid rhabdoid tumors. Pediatr Blood Cancer 51 (2): 235-40, 2008.

  6. Finkelstein-Shechter T, Gassas A, Mabbott D, et al.: Atypical teratoid or rhabdoid tumors: improved outcome with high-dose chemotherapy. J Pediatr Hematol Oncol 32 (5): e182-6, 2010.

  7. Tekautz TM, Fuller CE, Blaney S, et al.: Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy. J Clin Oncol 23 (7): 1491-9, 2005.

  8. Buscariollo DL, Park HS, Roberts KB, et al.: Survival outcomes in atypical teratoid rhabdoid tumor for patients undergoing radiotherapy in a Surveillance, Epidemiology, and End Results analysis. Cancer 118 (17): 4212-9, 2012.

  9. Olson TA, Bayar E, Kosnik E, et al.: Successful treatment of disseminated central nervous system malignant rhabdoid tumor. J Pediatr Hematol Oncol 17 (1): 71-5, 1995.

  10. Zimmerman MA, Goumnerova LC, Proctor M, et al.: Continuous remission of newly diagnosed and relapsed central nervous system atypical teratoid/rhabdoid tumor. J Neurooncol 72 (1): 77-84, 2005.

  11. Chi SN, Zimmerman MA, Yao X, et al.: Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor. J Clin Oncol 27 (3): 385-9, 2009.

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.

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.


This information is provided by the National Cancer Institute.

This information was last updated on January 30, 2013.

  • Email
  • Print
  • Share
  • Text
Highlight Glossary Terms
  • Make an Appointment

    • For adults:
      877-442-3324 (877-442-DFCI)
    • For children:
      888-733-4662 (888-PEDI-ONC)
    • Or complete the online form.
  • Find a Clinical Trial

  • Top Ranked

    • U.S. News and World Report Best Children's Hospital Cancer 2012-2013 logoDana-Farber/ Boston Children's Cancer and Blood Disorders Center is a top ranked pediatric cancer hospital in the U.S. News & World Report 2012-13 Best Children's Hospitals guide.