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*[http://www.cancer.gov/clinicaltrials National Cancer Institute Clinical Trials] If you have trouble obtaining information online you can call an NCI information specialist through a LiveHelp online text chat or by calling 1-800-4-CANCER. This is the National Cancer Institute's Physicians Query database, it has over 5,000 active cancer clinical trials. It provides summaries about clinical trials conducted by NCI-sponsored researchers, the pharmaceutical industry, and some international groups. This data is also from National Library of Medicine (NLM. It ists current information about clinical research studies. This is a major site, that many website on Pediatric Cancer link to. The Physicians Data Query (PDQ) database at NCI maintains a Clinical Trials Registry, which is used by the [ClinicalTrials.gov] website. This database is the world's most comprehensive cancer clinical trials registry. The registry contains more than 5,000 abstracts of clinical trial protocols that are open/active and approved for patient accrual (accepting patients). It includes trials for cancer treatment, genetics, diagnosis, supportive care, screening, and prevention. In addition, the registry contains more than 16,000 abstracts of clinical trial protocols that have been completed or are closed to patient accrual.

from the National Library of Medicine (NLM) lists current information about clinical research studies. This is a major site, that many website on Pediatric Cancer link to. The Physicians Data Query (PDQ) database at NCI maintains a Clinical Trials Registry, which is used by the [ClinicalTrials.gov] website. This database is the world's most comprehensive cancer clinical trials registry. The registry contains more than 5,000 abstracts of clinical trial protocols that are open/active and approved for patient accrual (accepting patients). It includes trials for cancer treatment, genetics, diagnosis, supportive care, screening, and prevention. In addition, the registry contains more than 16,000 abstracts of clinical trial protocols that have been completed or are closed to patient accrual.


PDQ includes most clinical trials sponsored by NCI. It also contains many clinical trials sponsored by pharmaceutical
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Revision as of 07:03, 29 May 2007

Atypical Teratoid Rhabdoid Tumors (AT/RT)

It has been estimated that 3% of Pediatric Central Nervous System (CNS) Cancer cases in the United States cases or 3 children per 1,000,000 will be diagnosised with AT/RT each year. There are 2,500 to 3,000 Pediatric CNS cancers each year. This 3% AT/RT percentage may increase as there is better differentiation between PNET/medulloblastoma tumors and AT/RTs. This 3% statistic implies around 30 new AT/RT cases per year. It is a rare disease, but very aggressive with a high mortality. A recent survey of 36 AT/RT patients at St. Jude Children's Hospital from 1984 to 2003 showed the survival rate for children under 3 is < 10%, for older children the survival rate is usually over 70% (See: Figure 1). Because AT/RT occurs mainly in younger children, the overall survival rate is around 20%. The mean survival time from diagnosis is 11 months. It should be noted that the tumor incidence is increasing by about 2.7% per year.

Approximately 30 children per 1,0000,000 will be affected by a CNS tumor (See Table D6) in the United States each year. Around 17% of all Pediatric Cancers involve the CNS; it is the most common childhood solid tumour. This are approximately 2500-3000 new pediatric brain tumors each year in the US. The survival rate is around 60%. Pediatric Brain cancer is the second leading cause of childhood death, just after Leukemia.

What is the history of atypical teratoid rhabdoid Tumors of the central nervous system?

Atypical teratoid rhaboid tumors of the central nervous system (CNS) were first described by Rorke and her associates at the Children’s Hospital of Philadelphia in 1987. Early literature called these tumors both atypical teratoid rhaboid tumors or malignant rabdoid tumors (MRT) of the CNS. By 1995 AT/RTs had become regarded as an aggressive, newly defined, biologically unique class of primarily Brain and Spinal tumors predominately affecting infants and young children. In January 2001, the National Cancer Institute and the Office of Rare Diseases hosted a Workshop on Childhood Atypical Teratoid/Rhabdoid Tumors of the Central Nervous System. Twenty-two participants from 14 different institutions came together to discuss the biology, treatments and new strategies for these tumors. The consensus paper on the biology of the tumor was published in Clinical Research. Given the rare nature of this tumor, there have only been a less than fifty (50) AT/RT papers in the literature since it was initially reported.

  • Lefkowitz JB (1988). "Atypical teratoid tumors of infancy: definition of an entity". Ann Neurol (22): 448–489. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  • Rorke LB (1995). "Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood". J Neurooncol 1995 (24): 21–8. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)Link is to Abstract. Paper reviews 32 AT/RT cases, mean survival time 6.5 months.
  • Beigel J (2002). "The role of INI and the SWI/SNF complex in the development of rhabdoid tumors: Meeting Summary from the workshop on childhood atypical teratoid rhabdoid tumors". Cancer Research 2002 (63:): 323–328. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)

What is the pathology of AT/RT tumors?

The pathology of the tumor is highly technical only relevant to the new brain tumor parent to show the difficulty in pathologically diagnosis to highlight the basic science research that is underway to understand this tumor. The technical information is included for those that have a background and interest in this. For all others- skip to the next section.

Technical Information

Histology

Histology is the way the tumor looks under the microscope. The tumor’s architecture is jumbled small and large cells. The tissue of this tumor contains many different types of cells including the presence of rhabdoid cells, large spindled cell, epithelial and mesencymal components and focal areas resembling a primative neruectodermal tumor. As much as 70% of the tumor may be made up of PNET (Primitive Neuroectodermal Tumor) cells. Ultrastructure characteristic whorls of intermediate filaments in the rhabdoid tumors (as with rhabdoid tumors in any area of the body). Ho and associates reported a previously unrecognized component of sickled shaped embracing cells that were present in all eleven cases atypical teratoid/rhadboid tumors that were reviewed.

Immunohistochemistry

Cytogenetic Studies

Cytogenetics is the study of the tumor’s genetic make-up. A technique called fluoresecene in situ hybridization (FISH) has been gaining attention in the literature because it may be able to help locate a mutation or abnormality that may be allowing tumor growth. Also, this technique has been shown to be useful in identifying some tumors and distinguishing two histologically similar tumors from each other (such as AT/RTs and PNETs). In particular, medulloblastmas/PNETs may possibly be differentiated cytogenetically from AT/RTs as chromosomal deletions of 17p are relatively common with medulloblastoma and abnormalities of 22q11.2 are not seen. On the other hand, chromosomal 22 deletions are very comomon in AT/RTs.

In importance of the hSNF5/INI1 gene located on chromosomal band 22q11.2 is highlighted in the summary paper form the Workshop on Childhood Atypical Teratoid Rhabdoid Tumors as the mutation’s presence is sufficient to change the diagnosis from a medulloblastoma or PNET to the more aggressive AT/RT classification. However, it should be noted that this mutation is not present in 100% of cases. Therefore, if the mutation is not present in an otherwise classic AT/RT immunohistochemical and morphologic pattern then the diagnosis remains an AT/RT.

  • Bruch LA (2001). "A role for flouresence is situ hybidization detection of chromosomal 22q dosage in distinguishing atypical teratoid/rhabdoid tumors from medulloblastoma.central primitive neurectodermal tumors". Hum Pathol (32): 156–162. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)This paper reports a comparasion of 8 AT/RT, 12 MB/PNETs and 4 central nervous system PNETs using fluoresecene in situ bybridization (FISH). None of the MB/PNET had a deletion of 22q, whereas 75% of the AT/RTs had deletion of 22q. The authors highlight the diagnositic potential of this technique in assisting in making the correct diagnosis.
  • Morley E. (2001). [www.sas.upenn.edu/~emorley "FISH as a Diagnostic Tool on Childhood Cancer"]. {{cite journal}}: Check |url= value (help); Cite journal requires |journal= (help)This paper discussing the utilization of fluoresecene in situ bybridization (FISH) as a diagnostic tool has a very good introduction into childhood cancer and brain tumors.
  • Hauser P. (2000). "A case of central nervous system atypical teratoid.rhabdoid tumor (Hungarian)". Magy Onkol 2000 (in Hungarian) (44): 285–288. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)Abstract reviewed on medline as article is in Hungarian.
  • Oka H (1999). "Clinicopathologic characteristics of atypical teratoid/rhabdoid tumor". Neurol Med Chir (Tokyo) (in English?) (39): 510–7. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: unrecognized language (link)A meta-anaylsis of 133 cases (15 new and 118 from the literature) which reviews the distingishing clinicopathologic features of this tumor.
  • Ho DM (2000). "Atypical teratoid/rhabdoid tumors of the central nervous system: a compariative study with primitive neurectodermal tumors/medulloblastoma". Acta Neuropathol (Berl) (in English?) (99:): 482–8. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link) CS1 maint: unrecognized language (link)A comparison of 11 AT/RTs and 121 PNET/medulloblastomas through histopathologic and immunohistochemical studies.


What other type of tumors can AT/RT tumors be mistaken for?

The critical step in treatment planning is an accurate pathologic diagnosis. Atypical teratoid rhaboid tumors are very rare tumors which may be mistaken for medulloblastomas, primitive neurectodermal tumors, choroid plexus carcinomas or germ cell tumors. Atypical teratoid rhaboid tumors may have areas that are identical to other CNS neoplasms as rhabdoid characteristics are not the sole component of these tumors. The rhabdoid aspect may be located only in focal areas or less pronounced.

It is important to consider AT/RT, particularly when a medulloblastoma or PNET diagnosis is entertained in the child under the age of one as these children are at the highest risk. Cytogenetic studies can assist in differentiating MB/PNETs from AT/RTs. Germ cell markers in tumor tissues and serum can guide an accurate diagnosis of germ cell tumors as AT/RTs lack these markers.

Misclassification of the tumor’s pathology can lead to errors in treatment and prognosis. On study revealed an 8.8% major disagreement in neuropathologic cases. Thus, the American Cancer Society and the American Society of Clinical Pathologist recommend a second opinion on all cancer diagnoses.

  • Beigel JA (1999). "Cytogenetics and molecular genetics of childhood brain tumors". Neuro-oncol (1:): 139–51.{{cite journal}}: CS1 maint: extra punctuation (link)This is a review article of cytogentetic and molecular genetic changes which have been idenfied in childhood brain tumors to date
  • Burger PC (1998). "Atypical teratoid rhaboid tumors of the central nervous system: a highly malignant tumor of infancy and childhood frequently mistaken for medulloblatoma: a Pediatric Oncology Group Study". Am J Surg Pathol 1998 (22:): 1083–92. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)This is a review of 55 patients diagnosed with AT/RTs to define this disease both clinically and pathologically.
  • Cuesta MT (2001). "Atypical rhabdoid/teratoid tumors: a presentation of three cases and a review of the literature". Rev Neurol 2001 (32:): 618–624. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)This paper reports the clinical, radiological,cytohistopathological and immunohistopathological aspects of three cases of AT/RTs.

How are AT/RT related to other rhabdoid tumors of the body?

Malignant rhabdoid tumors were first described as a variant of Wilms tumors of the kidney in 1978. Later rhaboid tumors outside the kidney were reported in many tissues including the liver, soft tissue, and central nervous system. Although the cell of origin is not know, cytogenetic studies have suggested a common genetic basis for rhabdoid tumors regardless of location with abnormalities in chromosome 22 commonly occurring. Regardless of location, all rhabdoid tumors are highly aggressive and tend to occur in children less than two years of age.

It should be noted that there have been reported cases of a child having both atypical teratoid rhaboid tumors in the brain as well as rhabdoid tumors of the kidney. Weeks and associates reported on 111 renal rhabdoid cases of which 13.5% also had a central nervous system malignancy. It has been hypothesized that a germline INI mutation may predispose a child to these tumors. There have been some references in the literature alluding to a new diagnosis called rhabdoid predispostion syndrome related to the gene hSNF5/INI1.

  • Weeks DA (1989). "Rhabdoid tumors of the kidney: a report of 111 cases form the National Wilms Tumor Study Pathology Center". Am J Surg Path (13:): 439–458. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)
  • Beigel JA (2000). "Germ-line INI1 mutations in a patient with a central nervous system atypical teratoid tumor and renal rhabdoid tumor". Genes Chromosomes Cancer (1:): 31–7. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)A case report of a infant that developed both tumors that were identical in histoligic and immunophenotypic features.

What is the cause of the AT/RT tumors?

The cause is unknown.

Technical Information (Genetic)

However, genetic similarities have been found within these tumors. In particular the chromosomal 22 deletion is very common in AT/RTs. This Chromosome 22 area contains the NSNF5/INI gene that appears to function as a classic tumor suppressor gene. This mutation is viewed as the “first hit” which predisposes these children to malignancies. INI1/hSNF5, a component of the chromatin remodeling SWI/SNF complex, is a critical tumor suppressor biallelically inactivated in rhabdoid tumors. Identification of INI1 as a tumor suppressor has facilitated accurate diagnosis of rhabdoid tumors.

The rate of transcription for SWI/SNF and HDAC complexes seem to be regulated by the INI1 gene. The SWI/SNF complex plays a role in chromatin remodeling. AT/RT is the first pediatric brain tumor for which a candidate tumor suppressor gene has been identified. A mutation or deletion in the INI1/hSNF5 gene occurs in the majority of AT/RT tumors. Around 90% of AT/RT cases involve 22 deletion. This is mainly point mutations on the hSNF5/INI1 gene (i.e., one can diagnosis AT/RT without a chromsome 22 deletion elsewhere). The hSNF5/INI1 gene regulates 15 or so proteins in the chromintin structure. In addition, the OPN gene has a higher expression in AT/RT tumors. It is increasingly believed that the reason that 100% of the AT/RT cancers are not associated with the hSNF5/INI1 gene is that there 14 additional proteins in the chromintin structure that are controlled by other genes. There are also some emerging mouse models of the AT/RT cancer as well as experimental cell lines derived from tumors. Despite these advances, the function of the gene is not yet understood. At the present time, there is not enough known about the function of INI1, either as an independent modulator of gene expression or through its association with the SWI/SNF complex, to be able to use specific targeted biological agents for treatment. Prospective clinical and biologic trials are greatly needed to understand the efficacy of therapeutic interventions, as well as the role of the gene.

  • Huret, J. (2002). "Rhabdoid predispostion syndrome". Atlas of Genetics and Cytogenetics in Oncology and Haematology. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)The Atlas of Genetics and Cytogenetics in Oncology and Haematology is a peer reviewed on-line journal and database in free access on internet devoted to genes, cytogenetics, and clinical entities in cancer, and cancer-prone diseases. This particular article was last updated in 2002 and references five (5) papers.


  • Jaclyn A. Biegel, (November, 2002). "Alterations of the hSNF5/INI1 Gene in Central Nervous System Atypical Teratoid/Rhabdoid Tumors and Renal and Extrarenal Rhabdoid Tumors". Clinical Cancer Research. 8: 3461–3467. doi:10.1038/modpathol.3800270. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: date and year (link) CS1 maint: extra punctuation (link)The study was designed to compare the types of INI1 alterations among tumors from diverse anatomical sites and identify mutation hot spots. Fluorescence in situ hybridization and PCR-based microsatellite, heteroduplex, and sequence analysis were used to characterize chromosome 22 deletions and INI1 mutations among 100 primary rhabdoid tumors. Deletions and/or mutations of INI1 were detected in 75 patients, including 42 children with atypical teratoid/rhabdoid tumors of the brain or spinal cord and 6 children with a brain and a renal or soft-tissue tumor. Nineteen tumors arose in the kidney (in one child, bilaterally) and eight tumors were extra-renal. Homozygous deletions detected by fluorescence in situ hybridization were most often seen in CNS and extra-renal rhabdoid tumors, whereas truncating mutations were detected in a high percentage of CNS and kidney tumors.
  • Huret, Jean-Loop (March, 1999). "SMARCB1 (SW1/SNF related, matrix associated, actin dependent regulator of chromatin B1)". Atlas of Genetics and Cytogenetics in Oncology and Haematology. {{cite journal}}: Check date values in: |date= (help)CS1 maint: date and year (link)The Atlas of Genetics and Cytogenetics in Oncology and Haematology is a peer reviewed on-line journal and database in free access on internet devoted to genes, cytogenetics, and clinical entities in cancer, and cancer-prone diseases. This particular article was last updated in 1999 and references seven (7)genetic papers on INI1/hSNF5.


  • Chung-Lan Kao (March 18, 2005). "Increased expression of osteopontin gene in atypical teratoid/rhabdoid tumor of the central nervous system". Modern Pathology (2005) (18): 769–778. doi:10.1038/modpathol.3800270. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: date and year (link)The osteopontin gene was found specifically upregulated in atypical teratoid/rhabdoid tumor cells. This specificity was confirmed by immunohistochemistry in pathological sections of tissues from atypical teratoid/rhabdoid tumor patients. Even though the role of osteopontin in the cytopathogenesis of atypical teratoid/rhabdoid tumor still needs to be determined, our data support that overexpressed osteopontin is a potential diagnostic marker for atypical teratoid/rhabdoid tumor.
  • Morley E. (2002). [www.sas.upenn.edu/~emorley "FISH as a Diagnostic Tool on Childhood Cancer"]. {{cite journal}}: Check |url= value (help); Cite journal requires |journal= (help)This paper discussing the utilization of fluoresecene in situ bybridization (FISH) as a diagnostic tool has a very good introduction into childhood cancer and brain tumors.

How common are AT/RTs?

In 2000 approximately 2.76 children per 100,000 will be affected by a CNS tumor in the United States each year. This rate has been increasing and by 2005 was 3.0 children per 100,000. This is approximately 2,500-3,000 pediatric brain tumors occuring each year in the US. It has been estimated that 3% of these pediatric brain tumors are AT/RTs although this percentage may increase as there is better differentiation between PNET/medulloblastoma tumors and AT/RTs. Finally, it should be noted that the tumor incidence is increasing by about 2.7% per year.

The CNS Cancer survival rate in children is approximately 60% (See Table 11.2 Survival Rate. However, this rate varies with the age of onset (younger has higher mortality) and cancer type. A 2005 survey See Figure 1 of AR/TR patients at St. Jude Children's Hospital showed a 11% survival rate for patients < 3 years old and an over 70% survival rate for patients > 3 years old. This is based on 37 AT/RT patients treated at Saint Jude's from 1984 to 2003.

  • Morley E. (2001). [www.sas.upenn.edu/~emorley "FISH as a Diagnostic Tool on Childhood Cancer"]. {{cite journal}}: Check |url= value (help); Cite journal requires |journal= (help)This paper discussing the utilization of fluoresecene in situ bybridization (FISH) as a diagnostic tool has a very good introduction to childhood cancer and brain tumors.

How do AT/RT tumors look on radiologic exam?

  • Location

AT/RTs can occur at any sites within the Central Nervous System (CNS), however approximately 60% are located in the posterior fossa area/Cerebellum area.

  • Appearance

The tumors’ appearance on CT and MRI are nonspecific tending towards large size, calcifications, necrosis (tissue death),and hemorrhage (bleeding).

Technical Information- CT Scans- The increased cellularity of the tumor may make the appearance on an uncontrasted CT to have increased attenuation. Solid parts of the tumor often enhance with contrast MRI Scans- Finding on T1 and T2 weighted images are variable. Pre-contrast T2 weighted images may show an iso-signal or slightly hyper-signal. Solid components of the tumor may enhance with contrast but do not always. MRI studies appear to be more able to pick up metastatic foci in other intracranial locations as well as intraspinal locations.

  • Follow-up

Preoperative and followup studies are needed to detect metastatic disease.

  • D. M.-T. Ho (2000). "Atypical teratoid/rhabdoid tumor of the central nervous system: a comparative study with primitive neuroectodermal tumor/medulloblastoma - Abstract". Acta Neuropathologica (99): 482–488. doi:10.1007/s004010051149. {{cite journal}}: More than one of |number= and |issue= specified (help); Text "May, 2000" ignored (help)Abstract, must purchase article. Eleven atypical teratoid/rhabdoid tumors (AT/¶RT) and 121 primitive neuroectodermal tumors/medulloblastomas (PNET/MB) were included in this study for evaluation of the histopathological features of AT/RT and comparison between AT/RT and PNET/MB. Histopathological studies of AT/RT showed that in addition to the commonly recognized components, i.e., rhabdoid cells, small (PNET/MB) cells, spindle cells and epithelial components, there was a previously unrecognized component, sickle-shaped embracing cells, which were present in all cases and could be useful as a histological marker of this tumor. Immunohistochemical studies showed divergent differentiation of the tumor cells and among the 16 antibodies studied, vimentin, neuron-specific enolase, epithelial membrane antigen and glial fibrillary acidic protein were most commonly reactive. The frequency of AT/RT expressed as a ratio of AT/RT to PNET/MB was 1 : 11 in general and increased to 1 : 3.8 among patients younger than 3 years old.
  • Yoon CS (2000). "Primarly malignant rhabdoid tumors of the brain: CT and MRI findings". Yonsei Med J 2000 (4:): 8–16. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)A restrospective evaluation of the radiologic appearance of 5 tumors.
  • Zuccoli G (1999). "Cental nervous system atypical teratodi/rhabdoid tumors of infancy CT and MR finding". Clinical Imaging 1999 (23:): 356–60. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)
  • Howelett DC. (1997). "Imaging and patholoigc features of primary malignant rhabdoid tumors of the brain and spine". Neuroradiaology 1997 (39:): 719–23. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)A description of two cases.

What are the clinical features of AT/RT?

Age

This is a tumor primarily of young children and infants. A Pediatric Oncology Group study reported the average age at diagnosis to be 17 months. The ASCO study of the 188 documented AT/RT cases prior to 2004 showed 173 cases < 5 years and 15 cases > 5 years. It should be noted that children older than three have been diagnosed with this tumor. In addition, a med-line search revealed four adults between the ages of 20 and 30 whose brain tumors have been classifed as atypical/teratoid rhabdoid tumors.

  • Burger PC (1998). "Atypical teratoid rhaboid tumors of the central nervous system: a highly malignant tumor of infancy and childhood frequently mistaken for medulloblatoma: a Pediatric Oncology Group Study". Am J Surg Pathol 1998 (22:): 1083–92. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)This is a review of 55 patients diagnosed with AT/RTs to define this disease both clinically and pathologically.
  • Chang HK (2001). "Classical malignant rhabodid tumors of central nervous system in 9-year-old Korean". Yonsei Med J 2001 (in English?) (42:): 142–146. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link) CS1 maint: unrecognized language (link)
  • Ashraf R (1997). "Implantation metstasis of primary malignant rhabdoid tumors of the brain in an adult (one case report)". Med Pediatr Oncol (28:): 223–7. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)
  • Arrazola J (2000). "Primary malignant rhabdoid tumour of the brain in an adult". Neuroradiology 2000 (42:): 363–7. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)
  • Lutterbach J. (2001). "Atypical teratodi/rhabdoid tumors in adult patients: case report and a review of the literature". J Neurooncol 2001 (52:): 49–56. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)
  • Sugita Y (1999). "Pineal malignant rhabdoid tumor with chondroid formation in an adult". Path Int 1999 (49:): 1114–8. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)

Presentation

The clinical presentation depends on the locations of the tumor. Since many of the tumors occur in the posterior fossa they present like other posterior fossa tumors- headache, vomitting, lethargy , and ataxia (unsteady gait). There is a case report by Tamiya and associates of a 7 month old child with a primarily spinal tumor that presented with progressive paraplegia and abnormal feeling in the legs.

  • Tamiya t. (2000). "Spinal atypical teratoid/rhabdoid tumor in an infant". Pediatr Neurosurg 2000 (32:): 145–9. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)

Location

The tumors can be located anywhere within the CNS including the spinal cord. Approximately 60% will be in the posterior fossa/cerebellar area. The ASCO study by Dr. Kieran showed 52% posterior fossa (PF); 39% sPNET (supratentorial primitive neuroectodermal tumors); 5% pineal; 2% spinal, and 2% multi-focal.

Male to Female Ratio

As with other CNS tumors, slightly more males are affected than females (ratio 1.6:1). Mark Kieran's summary of the 188 documented AT/RT cases (all prior to 2004) showed a 1.4:1 male to female ratio.

  • Morley E. (2001). [www.sas.upenn.edu/~emorley "FISH as a Diagnostic Tool on Childhood Cancer"]. {{cite journal}}: Check |url= value (help); Cite journal requires |journal= (help)This paper discussing the utilization of fluoresecene in situ bybridization (FISH) as a diagnostic tool has a very good introduction into childhood cancer and brain tumors. Alas, the URL link is broken.

Diagnostic Workup

The initial diagnosis of tumor is made with a radiographic study (MRI or CT-). If CT was performed first, a MRI is usually performed as the images are often more detailed and may reveal previously undetected metastatic tumors in other locations of the brain. In addition, a MRI of the spine is usually performed. The AT/RT tumor often spread to the spine. Examination of the cerebral spinal fluid is important as 1/3 of these patients will have intracranial dissemination with involvement of the CSF (cerebral spinal fluid). Lu reported the most consistent finding were large tumor cells, eccentricity of the nuclei and prominent nucleoli.

  • Lu L. (2000). "CSF cytology of atypical teratoid/rhaboid tumors of the brain in a two-year-old girl: a case report". Diagn Cytopathol 2000 (23:): 329–32. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)

Metastasis

Spread is noted in approximately 1/3 of the AT/RT cases at the time of diagnosis and tumors can occur anywhere throughout the Central Nervous System (CNS). In the ASCO study by Dr. Kieran of the 188 documented AT/RT cases prior to 2004; he found 30% of the cases had mets (metastasis) at diagnosis. Metastatic spread to the Meninges (leptomenigeal spread sometimes referred to as sugar coating) is very common both initially and with relapse. Average survival times decline when there is metastasis.

One case of metastatic disease to the abdomen via ventriculoperitoneal shunt has been reported with AT/RT . It should be noted that metastatic dissemination via this mechanism has been reported with other brain tumors including germinomas, medulloblastomas, astrocytomas, glioblastomas, endymomas and endodermal sinus tumors. Guler and Sugita separately reported cases of lung metastasis without a shunt.

  • Rickett CH (1998). "Abdominal metastases of pediatric brain tumors via ventriculo-peritoneal shunts". Childs Nerv Syst. 1998 (14:): 10–4.{{cite journal}}: CS1 maint: extra punctuation (link)A review of the literature which discusses the clinical aspects of 35 cases.
  • Newton HB (1992). "Extraneural metastases of infratentorial glioblastoma multiforme to the peritoneal cavity". Cancer (69:): 2149–53. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)Two cases reported with spread to the abdomen.
  • Cranston PE (1992). "Metastatic pineoblastoma via a ventriculoperitoneal shunt: CT demonstration". Comput Med Imaging Graph (16:): 349–51. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)A single case is reviewed.
  • Pallini R. (1991). "Bone metastasis associated with shunt-related peritoneal deposits from a pineal germinoma Case report and review of the literature". Acta Neurochir (Wien). 1991 (109:): 78–83. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)A case report of a 15 year old boy with metastatic spread by the blood and the shunt detected two months after surgery. There is a review of the literature.
  • Iwamuro Y. (2002). "Intrathecal and intraperitoneal germinomas occurring 20 years after total removal of a pineal teratoma. Case report". J Neurosurg. 2002 (96:): 364–7. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)
  • Altundage OO (2002). "Pineal germ cell tumor metastasis via ventriculoperitoneal shunt". Am J Clin Oncol. 2002 (25:): 104–5. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)
  • Thambidorai DR. (2001). "Spermatic cord metastasis from a medulloblastoma". Pediatr Surg Int. 2001 (17:): 654–6. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)
  • Fiorillo A. (2001). "Shunt-related abdominal metastases in an infant with medulloblastoma: long-term remission by systemic chemotherapy and surgery". J Neurooncol. 2001 (52:): 273–6. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)
  • Kornoes DN. (1999). "A 4-year-old girl with a ventriculperitoneal shunt metastasis of a central nervous system atypical teratoid/rhabdoid tumor". Med Tediat Oncol 1999 (32:): 389–91. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)
  • Guler, E. (2001). "Extraneural metastasis in a child with atypical teratoid rhabdoid tumors of the central nervous system". J Neurooncology 2001 (54:): 53–56. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)

Prognosis

As of 2006 the prognosis for AT/RT remains very poor. Although there are some indications that an IRSIII-based therapy can produce long-term survival (60 to 72 months):

  • Two year survival- less than 20%
  • Average survival postoperatively- 11 months
  • Longest reported survival reported in the literature- Hilden and associates reported a child who was still free from disease at 46 months from diagnosis. Olson and associates reported a child who was disease free at 5 years from diagnosis. In 2003 Hirth reported a case who had been disease free for over six years. More recently (2005) Zimmerman at DFCI (Dana Farber Cancer Institute) reports 50-to-72 month survial rates on four patients using an IRSIII based protocol. In addition, Philadelphia Children's Hospital is using this DFCI 02-294 protcol (see Kieran presentation). Zimmerman is expected to update this study in soon. A small German study had a 94% survival rate at two years (Peters).
  • Cancer treatments in long-term survivors usually cause a series of negative effects on physical well being, fertility, and cognition.
  • Based on a retrospective survey from 36 AT/RT St. Jude Children's Hospital patients from 1984 to 2004 a <10% survival rate in children under 3 was found, but a 70% survival rate in older children. The survival rates by age are shown in Figure 1. in this reference. The full Saint Jude article citation (Atypical Teratoid/Rhabdoid Tumors (ATRT)) is shown below:
  • Based on a retrospective Register at the Cleveland Children's hospital on 42 AT/RT patients. Median survival time is 16.25 months. The survival rate is currently around 33%. 25% of these cases did not show the mutation in the INI1/hSNF5 gene. The full article citation (CNS AT/RT Tumor: Results of Therapy in Children Enrolled in a Registry) is shown below.
  • COG CNS Committee Studies 2003-2007 by Ian Pollack See: Slide No. 30-32 on protocol ACNS033 in Study Management of MO Infant Medulloblastomas (P9934). This P9934 study is the first prospective study; it is also a Phase III AT/RT study. It is expected to make a preliminary report in 2007. The DFCI 02-294 protocol and the ACNS033 should be compared as to their respective outcomes.
  • Increasingly it is recommended that a genetic analysis be performed on the brain tumor, especially to find if a deletion in the INI1/hSNF5 gene is involved (appears to account for over 80% of the cases). The correct diagnosis of the tumour is critical to any protocol. Studies have shown that 8% to over 50% of AT/RT tumors are diagnosed incorrectly.

CITATIONS

  • Meyers, SP (May, 2006). "Primary intracranial atypical teratoid/rhabdoid tumors of infancy and childhood: MRI features and patient outcomes". AJNR Am J Neuroradiol. 2006. 27 ((5)): 962–71. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: date and year (link)Abstract Only: Patients ranged in age from 4 months to 15 years (median age, 2.9 years). Primary AT/RTs were intra-axial in 94% of patients. The single primary extra-axial lesion was located in the cerebellopontine angle cistern. AT/RTs were infratentorial in 47%, supratentorial in 41%, and both infra- and supratentorial in 12%. A germ-line mutation of the hSNF5/INI1 tumor-suppressor gene was responsible for the simultaneous occurrence of an intracranial AT/RT and a malignant renal rhabdoid tumor in a 4-month-old patient. Mean tumor sizes were 3.6 x 3.8 x 3.9 cm. On short TR images, AT/RTs typically had heterogeneous intermediate signal intensity, as well as zones of low (54%), high (8%), or both low and high (31%) signal intensity from cystic and/or necrotic regions, hemorrhage, or both, respectively. On long TR/long TE images, solid portions of AT/RTs typically had heterogeneous intermediate-to-slightly-high signal intensity with additional zones of high (54%) or both high and low signal intensity (38%), secondary to cystic and/or necrotic regions, edema, prior hemorrhage, and/or calcifications. AT/RT had isointense and/or slightly hyperintense signal intensity relative to gray matter on fluid-attenuated inversion-recovery (FLAIR) and long TR/long TE images, and showed restricted diffusion. All except 1 AT/RT showed contrast enhancement. The fraction of tumor volume showing enhancement was greater than two thirds in 58%, between one third and two thirds in 33%, and less than one third in 9%. Disseminated tumor in the leptomeninges was seen with MR imaging in 24% of patients at diagnosis/initial staging and occurred in another 35% from 4 months to 2.8 years (mean, 1.1 years) after surgery and earlier imaging examinations with negative findings. The overall 1-year and 5-year survival probabilities were 71% and 28%, respectively. Patients with MR imaging evidence of disseminated leptomeningeal tumor had a median survival rate of 16 months compared with 149 months for those without disseminated tumor (P < .004, logrank test). CONCLUSION: AT/RTs are typically intra-axial lesions, which can be infra- and/or supratentorial. The unenhanced and enhanced MR imaging features of AT/RT are often variable secondary to cystic/necrotic changes, hemorrhage, and/or calcifications. Poor prognosis is associated with MR imaging evidence of disseminated leptomeningeal tumor.
  • Biegel JA (Jan, 2006). "Molecular genetics of atypical teratoid/rhabdoid tumor" (PDF). Neurosurg Focus. 15 (20(1)). Retrieved May 27, 2007. {{cite journal}}: Check date values in: |date= (help)CS1 maint: date and year (link)The most common AT/RTlocations are the kidney and central nervous system. Although RTs can also arise in most soft-tissue sites. Rhabdoid tumors in all anatomical locations have a similar molecular origin. Mutation or deletion of both copies of the hSNF5/INI1 gene that maps to chromosome band 22q11.2 is observed in approximately 70% of primary tumors. An additional 20 to 25% of tumors have reduced expression at the RNA or protein level, indicative of a loss-of-function event. The INI1 protein is a component of the SWI/SNF chromatin remodeling complex. The complex is recruited to promoters of a large variety of genes involved in cell signaling, growth, and differentiation. This review summarizes what is currently known regarding the molecular genetics of RTs.

small. There was significant toxicity with increased incidences of mucositis and infection (48-42%). This regimen appears effective but there is significant toxicity.



  • Burger, PC (1998). "Atypical teratoid rhaboid tumors of the central nervous system: a highly malignant tumor of infancy and childhood frequently mistaken for medulloblatoma: a Pediatric Oncology Group Study". Am J Surg Pathol 1998. 22:: 1083–92. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)This is a review of 55 patients diagnosed with AT/RTs to define this disease both clinically and pathologically.
  • Olson, TA (1995). "Sucessful treatment of disseminated central nervous system malignant rhabdoid tumors". J Pediatr Hematol Oncol. 17: 71–75. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)This paper presents three new cases and a review of 18 cases in the literature.
  • Sugita, Y (1999). "Pineal malignant rhabdoid tumor with chondroid formation in an adult". Path Int. 49:: 1114–8. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)

What are the treatment options for AT/RT?

Surgical option

Surgery plays a critical role in obtaining tissue to make an accurate diagnosis. Surgery alone is not curative. In addition, 30% of the AT/RT tumors are located supratentorially and there is a predilection for the cerebello-pontine angle which makes surgical resection difficult. Unfortunately 1/3 or more children will have disseminated disease at the time of diagnosis. Total or near-total resections are often not possible. A range new treatments are emerging for Brain Tumors.

Chemotherapy options

Approximately 50% of the AT/RT tumors will transiently respond. Chemotherapy by itself is rarely curative.

There is no standard treatment for AT/RT. Various chemotherapeutic agents have been used against AT/RTs which are also used against other CNS tumors including cisplatinum, carboplatinum, cyclophosphamide, vincristine and eptoposide. More recently (2005) Zimmerman at DFCI (Dana Farber Cancer Institute) reports 50-to-72 month survial rates on four patients using an IRSIII based protocol. Zimmerman is expected to update this study soon. The Philadelphia Children's Hospital is using this new DFCI 02-294 protcol (see Dr. Kieran ASCO presentation). In addition, the COG CNS Committee Studies 2003-2007 by Ian Pollack See: Slide No. 30-32 on protocol ACNS033 in Study Management of MO Infant Medulloblastomas (P9934). This P9934 study is the first prospective study; it is also a Phase III AT/RT study. It is expected to make a preliminary report in 2007. The DFCI 02-294 and the ACNS033 chemotherapy protocols should be compared as to their respective outcomes.

There has been at least one report in the literature of malignant rhabdoid tumors of the CNS being treated in as a high-grade intracranial sarcoma. These three cases were treated with surgery, chemotherapy, radiotherapy and triple intrathecal chemotherapy similar to the Intergroup Rhadbdomyoscarcoma Study III guidelines.

One of the difficulties with brain and spinal tumors is that there is a blood brain barrier that needs to be crossed so that the drug can get to the tumor. One mechanism to deliver the drug is through a device called an Ommaya reservoir. This is a device which shares some similarities to a shunt in which a tube a surgically placed in the fluid surrounding the brain and a bulb shaped reservoir attached to the tubing is placed under the skin of the scalp. When the child is to receive intrathecal chemotherapy, the drug is administered into this bulb reservoir. At other times intrathecal chemotherapeutic agents are delivered through a lumbar puncture (spinal tap).

A current Pediatric Brain Tumor Consortium Protocol uses intrathecal mafosfamide, a pre-activated cyclophosphamide derivative, in addition to other modalities to try to effect this tumor.

  • High dose chemotherapy with stem cell rescue

This therapy uses chemotherapy at doses high enough to completely suppress the bone marrow. Prior to instituting this therapy, the child has a central line placed and stem cells are gathered. After therapy these cells are given back to the child to regrow the bone marrow. Stem cell resue with Chemotherapy has declined over the history of chemotherapy protocols.

Radiation options

The dose and volume of radiation had not been standardized, however, radiation does appear to improve survival. The use of radiation has been limited in children younger than three because of the risk of severe neurocognitive deficits. There are protocols using conformal, local radiation in the young child to try to cure this tumor (see clinical trial information).

Conformal radiation uses several fields that beam intersects at the tumor location. In this way, the normal brain tissue receives less radiation and hopefully is at less impact on cognitive function.

In 2002 this type of therapy was only offered in Massachusetts General Hospital in Boston and Loma Linda, California. The Northeast Proton Therapy Center claims that proton beam therapy offers “some theoretical advantages over other types of sterotactic radiosurgery because it uses the quantum wave properties of protons to reduce the doses to the surronding tissue beyond the target to a theoretical minimum of zero. It is also advantagous in the treatment of unusually shaped brain tumors.” An overview articlenotes that it provides better effective treatment with fewer side effects in pediatric cases. Since 2003 three or four more proton therapy centers have opened in the United States.

Chromatin re-modeling agents

This protocol is till in pre-clinical evaluation. Information on HDAC inhibitors, a new class of anticancer agents targeted directly at chromatin remodeling, was presented on the Workshop on Atypical Teratoid Rhabdoid Tumors of the CNS. These agents have been used in acute promyelocytic leukemia and have been found to affect the HDAC-mediated transcriptional repression. The participants in the workshop concluded that there was too little understanding of the INI1 deficiency to predict whether HDAC inhibitors will be effective against AT/RTs. Although, there are some laboratory results that indicate it is effective against certain AT/RT cell lines.

How does one find clinical trials?

Atypical teratoid rhabdoid tumors are rare and there is no therapy that has been proven to deliver long term survival, nor is there a set of standard protocols. Thus, most children with with AT/RTs are enrolled in clinical trials to try to find an effective cure. A clinical trial is not an treatment standard. Currently, there is no one place to find all the clinical trials which may be open to a child.

General Clinical Trial Information

  • Clinical Trials: Advanced Search is arguably, the best place to find information on pediatric cancer trials. Hit the links for Find a Treatment or enter a key word such as infant. At this time there are a few possible clinical trials listed for the newly diagnosed patient. There are other progressive pediatric brain tumor protocols that are not listed on this site.
  • National Library of Medicine listing of Medical Trials This database produced by NIH Registry now lists 4,000 primarily NIH-supported clinical studies on many conditions, and more will be added. All trials on PDQ are listed in this database. It provides summaries about clinical trials for a wide range of conditions—most of the trials listed are sponsored by NIH
  • National Cancer Institute Clinical Trials If you have trouble obtaining information online you can call an NCI information specialist through a LiveHelp online text chat or by calling 1-800-4-CANCER. This is the National Cancer Institute's Physicians Query database, it has over 5,000 active cancer clinical trials. It provides summaries about clinical trials conducted by NCI-sponsored researchers, the pharmaceutical industry, and some international groups. This data is also from National Library of Medicine (NLM. It ists current information about clinical research studies. This is a major site, that many website on Pediatric Cancer link to. The Physicians Data Query (PDQ) database at NCI maintains a Clinical Trials Registry, which is used by the [ClinicalTrials.gov] website. This database is the world's most comprehensive cancer clinical trials registry. The registry contains more than 5,000 abstracts of clinical trial protocols that are open/active and approved for patient accrual (accepting patients). It includes trials for cancer treatment, genetics, diagnosis, supportive care, screening, and prevention. In addition, the registry contains more than 16,000 abstracts of clinical trial protocols that have been completed or are closed to patient accrual.

PDQ includes most clinical trials sponsored by NCI. It also contains many clinical trials sponsored by pharmaceutical companies, medical centers, and other groups from around the world. It includes all cancer clinical trials that are registered under requirements specified by Section 113 of the Food and Drug Administration Modernization Act of 1997 (phase II and higher drug treatment trials) and requirements of the International Committee of Medical Journal Editors (phase II and higher trials that have a comparison or control group). The registration of clinical trials in PDQ is strongly encouraged, but it is strictly voluntary. PDQ and NIH's ClinicalTrials.gov database regularly exchange clinical trial information. Cancer trials registered in PDQ will automatically be registered in ClinicalTrials.gov and vice versa.

Protocol abstracts in PDQ are written in two formats, the health professional abstract (uses technical terminology) and the patient abstract (uses non-technical language). However, some trials (obtained from ClinicalTrials.gov) contain the same text in both the patient and health professional abstracts.

  • The American Cancer Society (ACS) has a free service to Find a Cancer Clinical Trial. This American Cancer Society Clinical Trials Matching Service is a free, confidential program that helps patients, families and health care workers find clinical trials most appropriate to a patient's medical and personal situation. You can also call the ACS directly at 1-800-303-5691.
  • Coalition of Cancer Cooperative Groups Maintains a web site that helps a patient find a relevant clinical trial (Trial Check). They are a network of cancer clinical trials specialists interested in expanding access to clinical trials. Members include cancer centers, academic medical centers, community hospitals, physician practices, and patient advocate groups.
  • Cancerbackup Search Engine allows one to search for cancer research trials available to UK and European patients. The databases involved include the NCRN (National Cancer Research Network), Cancer Research UK and the EORTC (European Organisation for Research and Treatment of Cancer). Trials run by the pharmaceutical industry are also included. USA clinical trials are shown on the NCI website.
  • Medline Plus - Clinical Trials US National Library of Medicine maintains the Medline Plus site. It has a lot of background articles, but points to the PDQ/Clinical Trials.Gov database.
  • CenterWatchprovides clinical research information for patients, firms, and research institutions around the world. It was founded in 1994 to provide information services to the clinical trials industry. They provide a list of IRB approved clinical trials being conducted internationally. They also list promising therapies newly approved by the FDA (Food and Drug Administration). One can search for trials by medical specialty.

Hospital/Academic Centers Clinical Trials

  • Oncolink Abrahamson Cancer Center of the University of Penn.

Industry Clinical Trials

  • IFPMA Clinical Trials Portal. The International Federation of Pharmaceutical Manufacturers & Associations (IFPMA)created this portal in 2005. It includes the [ClinicalTrials.gov] site.



  • Head Start Chemotherapy Protocol. This chemotherapy protocol is for children <10 years old with newly diagnosed high grade primary brain tumors with intent to eliminate irradiation and shorten the treatment time to 6 months. The therapy consists of 3-5 cycles of intensive chemotherapy followed by a single myeloblative chemotherapy with stem cell rescue. Dr. Jonathan Finlay of New York University Medical Center is the contact person although run at a few hospitals in the county(contact information is listed on the site).
  • Phase I Pilot Study of Intensive Chemotherapy with Peripheral Blood Stem Cell Rescue in Infants with Malignant Brain or Spinal Cord Tumors

http://www.virtualtrials.com/trialdetails.cfm?id=60500391 http://www.cancer.umn.edu/page/advtherapies_pedbrainlist1.html This is a uses cisplatinum, cycophosphamide, vincristine and etoposide followed by carboplatinum and thiopeta and then stem cell rescue. There are to be three cycles of carboplatinum and thiopeta with stem cell rescue.

Other useful references to understand clinical trials are:

This page helps explain the reason for and the types of clinical trials (phase 1,2 and 3). It also gives guidelines in how to evaluate the sponsor of a trial to help parents understand how they can insure the highest quality (such as independent per review).

This is an archived hour-long lecture on the clinical trial process by Larry Kun, MD on 4/01.

  • Clinical Trial Results summarizes the results of clinical trials. It includes cancer trials, but appears to have a cardiology focus.
  • What is the Clinical Study Results Database is a central, widely accessible, web-based repository for clinical study results in a reader-friendly, standardized format.

What will the Clinical Study Results Database contain? The database will contain the results from all “hypothesis-testing” clinical studies (mainly phase III and IV studies) completed since October 1, 2002, for drug products that are approved in the United States. This will include both published articles and unpublished study summaries. The Website will provide a link to the most current FDA-approved prescribing information for the drug in question, where available, or will otherwise direct users to consult the FDA-approved prescribing information.

  • The Cancer Trials Support Unit (CTSU) is a pilot project sponsored by the National Cancer Institute (NCI) for the support of a national network of physicians to participate in NCI-sponsored Phase III cancer treatment trials.

National Institute of Dental and Craniofacial Research (NIDCR) Clinical Trials Information about effective preventive, diagnostic, and treatment approaches for craniofacial, oral, and dental diseases and disorders.


Office for Human Research Protections (OHRP) The Office of Human Research Protections supports, strengthens, and provides leadership to the nation's system for protecting volunteers in research that is conducted or supported by the U.S. Department of Health and Human Services (HHS).

Rare Diseases Clinical Trials List of rare diseases clinical trials from the National Library of Medicine's ClinicalTrials.gov.

Are there options in alternative or complementary medicine?

Especially because the prognosis for this tumor is dismal, many parents may consider alternative medicine. Before committing to an alternative therapy a parent might want to review information on quackwatch site. Other sites to investigate are:

What are the risk for siblings and other members of the family?

Atypical teratoid rhabdoid tumors are very rare tumors and absolute risk to siblings is not reported in the literature. However, there have been some reports of AT/RTs presenting in two members of the same family, or one family member with a AT/RT and another with a renal rhabdoid tumor or other CNS tumor. These are thought to arise from Germ-line genetic mutations.

  • Proust, F. (1999). "Simultaneous presentation of atypical teratoid rhabdoid tumors in siblings". J Neurooncol (43:): 63–70. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)Two sisters were diagnosed with AT/RTs 15 days apart. This case report stated there were no karyotypic anomalies noted.
  • Beigel, JA. (2000). "Germ-line INI1 mutations in a patient with a central nervous system atypical teratoid tumor and renal rhabdoid tumor". Genes Chromosomes Cancer (1:): 31–7. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)A case report of a infant that developed both AT/RT and renal rhabdoid tumors that were identical in histoligic and immunophenotypic features.
  • Huret, J. "Rhabdoid predispostion syndrome". Atlas of Genetics and Cytogenetics in Oncology and Haematology. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)The Atlas of Genetics and Cytogenetics in Oncology and Haematology is a peer reviewed on-line journal and database in free access on internet devoted to genes, cytogenetics, and clinical entities in cancer, and cancer-prone diseases. This particular article was last updated in 2002 and references five (5) papers.


  • Sevent, N. (1999). "Constituitonal mutations of the hSNF/INI1 gene predispose to a variety of cancers". Am J Hum Genet (65:): 1343–1348. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)Three siblings had a mutation of the SMARCB1 gene and one had a plexus carcinoma and two had a AT/RT. Although the mother had a normal DNA it appears that the mutation was inherited from the mother due to a mutation during oogenesis.


  • Taylor, MD. (2000). "Familial posterior fossa brain tumors of infancy secondary to germline mutation of the hSNF5 gene". Am J Hum Genet (66:): 1403–1406. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)This article reviews a family that has had multiple generations of posterior fossa tumors including rhabdoid tumors and choroid plexus carcinoma. There seemed to be a germ-line mutation (SMARCB1) seen in both affected and some unaffected family members.
  • Fernandez, C. (2002). "Congenital disseminated malignant rhabdoid tumor and cerbellar tumor mimicking medulloblastoma in monozygotic twins: pathologic and molecular diagnosis". Am J Surg Pathol (26:): 266–70. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: extra punctuation (link)This is the first case report of monozygotic twin both with brain tumors having similar genertic alterations of both tumors. The authors suggest a common genetic pathway.

What resources are there for parents and families dealing with atypical teratoid rhaboid tumors?

Deciphering the different websites and organizations can be an overwhelming task to a new parent, relative or friend to this field. Although not an exhaustive list, some of the better resources regarding rhabdoid, pediatric brain tumors and childhood cancer are listed below. This should provide a solid foundation and starting place for finding information.

Rhabdoid Resources

Rhabdoid Kids and Angels Home Page- http://www.geocities.com/Hollywood/2587/michael/rhabdoidkids.htm A site maintained by a child’s grandfather since 1998. On this site there is a listing of kids fighting this tumor including pictures, email addresses and many personal websites. There also is a similar angel page. There is also a discussion board regarding rhabdoid tumors.

Emily’s Rhabdoid Page

A web site dedicated to Emily who died of an AT/RT in 2000. The journal is complete from initial symptoms to the end of life. There is a variety of other interesting information including:

Rhabdoid Registry

The Childhood Oncology Group Registry started as an official registry run by Dr. Joanne Hilden, Dr. Jackie Biegel, and Jan Watterson in 1995 at Saint Paul's Hospital. They are very interested in hearing from any rhabdoid parent whose child is not already listed in their registry. The registry, which will be made available to medical professionals, hopes to document as many rhabdoid cases as possible, an important step in finding the most effective treatment for rhabdoid. The registry started at Children’s Hospital in St. Paul. The main center for registry data collection is now at the Cleveland Clinic Foundation due to Dr. Hilden’s relocation to Chair of the Department of Pediatric Hematology/Oncology.

If your child is diagnosed with rhabdoid one should consider adding his case to the registry. Dr. Hilden can be contacted at 216-444-8407. The Rhabdoid Registry now operates at Cleveland Clinic. This AT/RT Registry is still run by Dr. Joanne Hilden, Chair of Pediatric Hematology/Oncology. It provides a voluntary, free, confidential, central database of information and outcomes on Central Nervous System Atypical Teratoid/Rhabdoid tumors.

  • Contact:

Joanne M. Hilden, M.D. (Principal Investigator) Chair, Department of Pediatric Hematology/Oncology/Desk S20 Medical Director, Pediatric Palliative Care Cleveland Clinic Children's Hospital 9500 Euclid Avenue Cleveland OH 44195 Phone: 216-444-8407 Fax: 216-444-5925 E-Mail: hildenj@ccf.org

Workshop on Childhood Atypical Teratoid Rhadoid Tumors of the CNS

This is a listing of the abstract on and participants in a major AT/RT workshop held in January 2001 by the National Cancer Institute and the Office of Rare Disease Abstract. The citation (paper is online) is provided below:

Pediatric Cancer List Servs

List serves provide a way to communicate to other parents who are dealing with similar experiences. Three of the most common list serves are:

This group has over 800 members and is open to persons interested in childhood brain tumors. Pediatric Brain Tumor Yahoogroup- http://health.groups.yahoo.com/group/Pediatricbraintumors/

  • This group has over 100 members and is open to all persons interested in childhood brain tumors.

- Association of Online Cancer Resources- Ped Onc Listserv http://listserv.acor.org/archives/ped-onc.html A listserv for parents dealing with all types of childhood cancer.

Pediatric Brain Tumor Books

  • Palliative Care for Infants, Children, and Adolescents: A Practical Handbookby Kathleen M. Foley (Foreword), Brian S. Carter (Editor), Marcia Levetown (Editor); The Johns Hopkins University Press (June 24, 2004) A comprehensive look at pediatric palliative care. It should be a reference textbook that serves as a 'bible' in this area. The book is organized in a way that allows readers from different disciplines to quickly find and peruse chapters relevant to their practice. Given the high mortality rate in AT/RT, pallative care is often necessary.
  • Hospice Care for Children (Hardcover) by Ann Armstrong-Dailey (Editor), Sarah Zarbock (Editor);Oxford University Press, USA; 2 edition (September 24, 2001) Children with life-threatening and terminal illnesses--and their families-- require a unique kind of care to meet a wide variety of needs. This book, the first edition of which won the 1993 Pediatric Nursing Book of the Year Award, provides an authoritative source for the many people involved in caring for dying children

Pediatric Brain Tumor Organizations

This organization began as a support group for Egleston Hospital in Atlanta and still has a very big focus on local support to brain tumor parents in the area. There is a newsletter. In May 2002, this organization held a Tools for Living Symposium that was open to all across the country.

This foundation is headquartered in Maryland features a newsletter three times a year, a basic science grant, a biannual family retreat weekend, and a childhood cancer ombudsman program. One of the best features of the website is the article section which has a couple dozen articles of interest to brain tumor parents- none on AT/RTs in particular at this time.

This foundation is based in New York and is a member of the North American Brain Tumor Coalition. The website is easy to use and has practical information such as hospital stays, Parent-to-Parent Support, support group listings (national and internet), links to sites that list clinical trials. They list a willingness to assist in sorting out clinical trial information if one calls (Phone: 212-448-9494 Fax: 212-448-1022 Toll-free: 866-228-HOPE )

This organizations featured events are the Rides for Kids that raise public awareness through the motorcycle community. They founded PBTF in 1991. Since 1984 they have raised more than $34M for research and family support. Since 2001 they have issued $1M/Year in small Research grants, which often seed subsequent research. This organization most unique feature is the informed parent internet series which held live 4 times a year and the various subjects are archived on the internet. This organization deals with family support and funds a variety of research projects and conferences. It is a member of the North American Brain Tumor Coalition.

We can is a parent support network based out of Los Angeles which offers a veteran parent program, sibs programs, lectures and other events.

Childhood Cancer Organizations and Resources

Phone: 1-800-366-2223 Candlelighter Childhood Cancer Foundation was founded in 1970 by parents who desired an organization to educate, support, and advocate for kids with cancer, their families and the professions who help them. There is a message board, on line newletters, and resources.

Phone: 703-836-4412 Hope Street Kids was founded by Representative Deborah Pryce (Ohio) and her husband after their daughter died from neuroblastoma in 1999. Possibly the best aspect of this website is the parent guide which organizes questions to consider regarding procedures, treatments, and clinical trials.

This site is a one-stop shopping place for parents of kids with cancer and it has just about everything that a parent would want to know generally about childhood cancer- venous access, blood counts, assistance information, etc.

This is a relatively new organization which was started to raise awareness of infant cancers by a mom who lost her child to a brain tumor in 2000. It was first called Sebastian's Baby Cancer Foundation, but changed its name in 2002 to America's Baby Cancer Foundation.

Hospital Groups which treat Childhood Cancer

In 1999, the National Cancer Institute funded a nine institution consortium with the “primary objective to rapidly conduct novel phase I and II clinical evaluations of new therapeutic drugs, intrathecal agents, delivery technologies, biological therapies, and radiation treatment strategies in children age 0 – 21 years of age with primary CNS tumors.” Institutional contacts and summary of research protocols are available on the site.

There are 238 Children’s Onocology Group institutions located in almost every state and province in North America and several others around the world. The COG is the US government financed integration of four pediatric brain tumor organizations in 2000. Their Website is called CureSearch. They tend to focus on Phase III and IV clinical studies. The attempt is to pool information together to gain better insight into effective strategies to manage childhood cancer.

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