Efficacy of High-Dose Chemotherapy and Three-Dimensional Conformal Radiation for Atypical Teratoid/Rhabdoid Tumor: A Report From the Children's Oncology Group Trial ACNS0333.

PURPOSE: Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive, early-childhood brain tumor without standard effective treatment. To our knowledge, we conducted the first AT/RT-specific cooperative group trial, ACNS0333, to examine the efficacy and safety of intensive postoperative chemotherapy and focal radiation to treat AT/RT. PATIENTS AND METHODS: Patients from birth to 22 years of age with AT/RT were eligible. After surgery, they received 2 courses of multiagent chemotherapy, followed by 3 courses of high-dose chemotherapy with peripheral blood stem cell rescue and involved-field radiation therapy. Timing of radiation was based on patient age and disease location and extent. Central testing of tumor and blood for SMARCB1 status was mandated. Tumor molecular subclassification was performed retrospectively. The primary analysis was event-free survival (EFS) for patients < 36 months of age compared with a cooperative groups' historical cohort. Although accrual was based on the therapeutic question, potential prognostic factors, including age, tumor location, M stage, surgical resection, order of therapy, germline status, and molecular subtype, were explored. RESULTS: Of 65 evaluable patients, 54 were < 36 months of age. ACNS0333 therapy significantly reduced the risk of EFS events in patients < 36 months of age compared with the historical cohort (P < .0005; hazard rate, 0.43; 95% CI, 0.28 to 0.66). Four-year EFS and overall survival for the entire cohort were 37% (95% CI, 25% to 49%) and 43% (95% CI, 31% to 55%), respectively. Timing of radiation did not affect survival, and 91% of relapses occurred by 2 years from enrollment. Treatment-related deaths occurred in 4 patients. CONCLUSION: The ACNS0333 regimen dramatically improved survival compared with historical therapies for patients with AT/RT. Clinical characteristics and molecular subgrouping suggest prognostic differences. ACNS0333 results lay a foundation on which to build future studies and incorporate testing of new therapeutic agents.

Cognitive profiles of neurofibromatosis type 1 patients with minor brain malformations.

Neurofibromatosis type 1 is a genetic condition associated with increased risk of abnormal brain development. The relationship between a specific type of brain malformation and a distinct cognitive sign/deficiency remains unknown. This study investigated the frequency of brain malformations in children with neurofibromatosis type 1, and the impact of those brain malformations on cognitive performance. A retrospective examination was performed of cranial magnetic resonance imaging and clinical records in 604 neurofibromatosis type 1 patients. Eighteen patients with brain malformations and intellectual evaluations were available and compared to a subset of neurofibromatosis type 1 patients (n = 20) without brain malformations. The most common brain malformations included hypothalamic hamartomas and Chiari I malformation. More complex migration disorders were also observed. Comparisons of cognitive profiles between groups revealed differences in patients with hamartomas compared with those manifesting Chiari I malformations or control subjects. As a group, those with hamartomas demonstrated below-average global intellect, whereas patients with Chiari I or no malformations performed in the average range. Disorders in cell organization, expressed as brain malformations (hamartomas or more complex defects), may comprise part of the expression of organizational and developmental defects in patients with neurofibromatosis type 1 and possibly other rat sarcoma gene-mitogen activated protein kinase pathway disorders.

MRI-negative epilepsy: protocols to optimize lesion detection.

Identification of the structural lesions that underlie pediatric epilepsy can be challenging. Careful evaluation of the gray-white matter interface is crucial, and necessitates multiplanar thin images of high resolution that can differentiate focal lesions from partial volume averaging artifacts created by the innate gyral configuration. Careful evaluation of the hippocampus and of the myelination patterns can further increase the diagnostic yield of the study. Magnetization transfer imaging can call attention to a lesion that is either very subtle or not evident on conventional sequences. Detection of cortical anomalies is best performed early in infancy, preferably before 6 months of age. If the initial magnetic resonance imaging (MRI) scan is performed between 9 and 18 months of age and is negative, a repeat scan after 2 years of age may be necessary.

Imaging of central nervous system tumors in children: advances and limitations.

Magnetic resonance technology is continually improving. Functional imaging techniques such as magnetic resonance spectroscopy, perfusion imaging, diffusion imaging, and diffusion tensor imaging are increasingly used in the diagnosis and treatment of brain tumors in children. However, estimate of tumor size remains the primary imaging endpoint in the evaluation of response to treatment, and validation across institutions and vendor platforms of magnetic resonance imaging functional parameters is necessary given the relatively uncommon occurrence of brain tumors in children. Pediatric neuroimaging can be challenging, and the optimal way to image children with tumors of the central nervous system is not uniformly applied across all centers. Application of proper scanning techniques and validation of functional imaging techniques should lead to improved care of children with central nervous system tumors.