Treatment for Newly Diagnosed Childhood CNS 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. However, the young age of most patients limits the extent of treatment, particularly radiation therapy.
Treatment options for newly diagnosed CNS AT/RT include the following:Surgery, Chemotherapy, and Radiation Therapy (Multimodal Therapy)
The extent of the surgical resection may affect survival. Data from the Central Nervous System Atypical Teratoid/Rhabdoid Tumor Registry (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.
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. The Children’s Cancer Group reported a 2-year event-free survival (EFS) of 14% for 28 children younger than 36 months treated with multiagent chemotherapy.
Intensive regimens that utilize varying combinations of high-dose chemotherapy,[Level of evidence: 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. 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. Of 15 evaluable children, all younger than 32 months at diagnosis, who were on a chemotherapy Head Start III protocol, 2 survived for more than 47 months.[Level of evidence: 3iA]
Radiation therapy appears to have a positive impact on survival for AT/RT patients.
- Of the 42 patients in the AT/RT Registry, 13 patients (31%) received radiation therapy in addition to chemotherapy as part of their primary therapy. The radiation field was to the primary tumor bed in nine children, and the tumor bed and the craniospinal axis in four children. Their median survival was 48 months, while the median survival of all patients on the registry was 16.75 months.
- A retrospective series of 31 patients with AT/RT from St. Jude Children's Research Hospital in which the 2-year EFS for patients older than 3 years was 78%, considerably better than 11% for patients younger than 3 years. All but one 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.
Evidence (multimodal therapy):
- The Third Intergroup Rhabdomyosarcoma Study (IRS-III) utilized radiation therapy, intrathecal methotrexate, cytarabine, hydrocortisone, and systemic multiagent chemotherapy. The results of small retrospective series were encouraging,[10,11] leading to the first prospective study of multimodality treatment in this group of patients.
- Based on the previous pilot series, a prospective multi-institutional trial was conducted for children with newly diagnosed CNS AT/RT. Treatment was divided into five phases: preirradiation, chemoradiation, consolidation, maintenance, and continuation therapy. Intrathecal chemotherapy was administered, alternating intralumbar and intraventricular routes. Radiation therapy was either focal (54 Gy) or craniospinal (36 Gy, plus primary boost), depending on the child's age and extent of disease at diagnosis.
- 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.
- Six of the eight children without progressive disease at the time of the report had received conformal radiation therapy and two children had received craniospinal radiotherapy; seven children had a gross total resection and only one child had metastatic disease (this child had persistent, stable disease 1.5 years from diagnosis).
Because AT/RT is responsive to radiation therapy, this modality is incorporated into many treatment protocols.
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
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. Information about ongoing clinical trials is available from the NCI Web site.References
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