Treatment Options Under Clinical Evaluation

There is no established standard treatment for children with central nervous system atypical teratoid/rhabdoid tumor (AT/RT). Given the highly aggressive nature of the tumor, most patients have been treated with intensive multimodal therapy. The young age of the majority of patients does, however, put some limitations on the extent of treatment, particularly radiation. Surgery is necessary to obtain tissue and make the diagnosis of AT/RT. Data from The AT/RT Registry suggests that patients who have had a complete resection may have a longer median survival, although complete surgical resection is often difficult given the invasive nature of the tumor.[1] Chemotherapy has been the main adjuvant therapy for very young children with AT/RT. Cooperative group studies that included children aged younger than 36 months, demonstrated poor survival when treated with standard chemotherapeutic regimens alone.[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, intrathecal chemotherapy, and radiation have led to prolonged survival for some patients. Thirteen patients in The AT/RT Registry were treated with high-dose chemotherapy with hematopoietic stem cell rescue as part of initial therapy.[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. Their median survival was 48 months, while the median survival of all patients on the registry was 16.75 months. Of the 14 long-term survivors in the registry, eight received radiation as part of their primary therapy, including four patients who were younger than 36 months at diagnosis. Seven of these eight surviving patients received involved-field radiation to the tumor or tumor bed and only one received craniospinal radiation. Other reports have advocated the combination of intensive chemotherapy combined with radiation therapy.

In a series of 31 patients with AT/RT from St. Jude Children's Research Hospital, the 2-year EFS for patients older than 3 years was 78%, considerably better than 11% for patients younger than 3 years.[4] All but one surviving patient (seven of eight) in the older group received craniospinal irradiation and intensive chemotherapy with transplant; only three of 22 of the younger patients received any form of irradiation, two of which are disease free. This also suggests that radiation does play an important role in survival for patients with AT/RT. Another therapeutic approach to patients with AT/RT is based on the Third Intergroup Rhabdomyosarcoma (IRS-III) Study. It utilizes radiation therapy, intrathecal methotrexate, cytarabine, hydrocortisone, and systemic multiagent chemotherapy. Three patients all showed responses to therapy and one had prolonged survival.[5] More recently another group reported success in four patients with AT/RT using IRS-III-like therapy; a prospective study using this treatment is being conducted.[6] Prospective cooperative group clinical trials for AT/RT are greatly needed to better understand how age and extent of therapy impact survival.

The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

• The Children’s Oncology Group has developed a phase III study (ACS0333) for patients aged 0-21 years with AT/RT. The study will use 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.  [PUBMED Abstract]
   
   
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.  [PUBMED Abstract]
   
   
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.  [PUBMED Abstract]
   
   
4. 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.  [PUBMED Abstract]
   
   
5. 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.  [PUBMED Abstract]
   
   
6. 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.  [PUBMED Abstract]
   
   

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