RESUMEN
Ependymomas account for 10% of all malignant pediatric central nervous system tumors. Standard therapy includes maximal safe surgical resection, followed by focal radiation. Despite the aggressive therapy, progression-free survival is poor. Most ependymoma relapses occur locally at the original tumor site. Extraneural presentations of ependymoma are extremely rare, and no standard of care treatment exists. We present a single-institution case series of 3 patients who experienced extraneural relapses of supratentorial ependymoma and describe their treatment and outcome. These cases of extraneural relapse highlight the possible modes of extraneural spread, including hematogenous, lymphatic, and microscopic seeding through surgical drains and shunts. In addition, they illustrate the increase in histologic grade and mutational burden that may occur at the time of relapse. These cases illustrate the role of aggressive, individualized treatment interventions using a combination of surgery, radiation, and chemotherapy.
Asunto(s)
Ependimoma , Recurrencia Local de Neoplasia , Humanos , Niño , Ependimoma/patología , Terapia CombinadaRESUMEN
Gliomas arising in the setting of neurofibromatosis type 1 (NF1) are heterogeneous, occurring from childhood through adulthood, can be histologically low-grade or high-grade, and follow an indolent or aggressive clinical course. Comprehensive profiling of genetic alterations beyond NF1 inactivation and epigenetic classification of these tumors remain limited. Through next-generation sequencing, copy number analysis, and DNA methylation profiling of gliomas from 47 NF1 patients, we identified 2 molecular subgroups of NF1-associated gliomas. The first harbored biallelic NF1 inactivation only, occurred primarily during childhood, followed a more indolent clinical course, and had a unique epigenetic signature for which we propose the terminology "pilocytic astrocytoma, arising in the setting of NF1". The second subgroup harbored additional oncogenic alterations including CDKN2A homozygous deletion and ATRX mutation, occurred primarily during adulthood, followed a more aggressive clinical course, and was epigenetically diverse, with most tumors aligning with either high-grade astrocytoma with piloid features or various subclasses of IDH-wildtype glioblastoma. Several patients were treated with small molecule MEK inhibitors that resulted in stable disease or tumor regression when used as a single agent, but only in the context of those tumors with NF1 inactivation lacking additional oncogenic alterations. Together, these findings highlight recurrently altered pathways in NF1-associated gliomas and help inform targeted therapeutic strategies for this patient population.
Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Glioma , Neurofibromatosis 1 , Adulto , Astrocitoma/genética , Neoplasias Encefálicas/genética , Glioma/genética , Glioma/patología , Homocigoto , Humanos , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/genética , Eliminación de SecuenciaRESUMEN
Neurofibromatosis type 1 (NF1)-associated primary intramedullary spinal cord ganglioglioma has only rarely been reported. Because of frequent nonresectability, they pose significant management challenges despite clinical indolence. This report describes a 4-year-old girl with NF1 who was found to have multiple discrete, infiltrative intramedullary cord masses, and biopsy demonstrated World Health Organization grade I ganglioglioma. Panel-based next-generation sequencing showed her previously identified germline NF1 mutation and a second somatic NF1 mutation. This represents the first report of multiple primary intramedullary gangliogliomas in a child with NF1 and demonstrates how biopsy with panel-based next-generation sequencing provides potential targets for MAPK/MEK/BRAF pathway inhibitor therapy.
Asunto(s)
Ganglioglioma/patología , Neurofibromatosis 1/complicaciones , Médula Espinal/patología , Preescolar , Femenino , Ganglioglioma/etiología , Humanos , PronósticoRESUMEN
Treatment-related morbidity drives research to identify targetable lesions in children with cancer. Neurotrophic tropomyosin receptor kinase (NTRK) alterations occur in ~1% of pediatric solid tumors. Early phase pediatric trials involving the NTRK inhibitor treatment for progressive NTRK-mutated cancers show promising results. The authors describe the adjuvant maintenance larotrectinib treatment after definitive surgical resection in 2 toddlers with NTRK fusion-positive malignancies (ETV6-NTRK3 fusion-positive undifferentiated embryonal sarcoma of the kidney and NACC2-NTRK2 fusion-positive anaplastic astrocytoma). Both are alive, in remission, developing normally and tolerating larotrectinib 15 months later, thus extending the NTRK inhibitor therapeutic spectrum by describing the adjuvant maintenance larotrectinib treatment in children with NTRK fusion-positive cancers associated with high recurrences.
Asunto(s)
Astrocitoma/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Quimioterapia de Mantención/métodos , Proteínas de Fusión Oncogénica/genética , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Astrocitoma/genética , Astrocitoma/patología , Quimioterapia Adyuvante , Preescolar , Femenino , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Masculino , Glicoproteínas de Membrana/genética , Proteínas de Neoplasias/genética , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/patología , Pronóstico , Receptor trkB/genética , Proteínas Represoras/genéticaRESUMEN
Lesions of the cerebellopontine angle (CPA) in young children are rare, with the most common being arachnoid cysts and epidermoid inclusion cysts. The authors report a case of an encephalocele containing heterotopic cerebellar tissue arising from the right middle cerebellar peduncle and filling the right internal acoustic canal in a 2-year-old female patient. Her initial presentation included a focal left 6th nerve palsy. Magnetic resonance imaging was suggestive of a high-grade tumor of the right CPA. The lesion was removed via a retrosigmoid approach, and histopathologic analysis revealed heterotopic atrophic cerebellar tissue. This report is the first description of a heterotopic cerebellar encephalocele within the CPA and temporal skull base of a pediatric patient.
Asunto(s)
Quistes Aracnoideos , Neoplasias Cerebelosas , Ángulo Pontocerebeloso/diagnóstico por imagen , Ángulo Pontocerebeloso/cirugía , Niño , Preescolar , Encefalocele/diagnóstico por imagen , Encefalocele/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Base del CráneoRESUMEN
Brain tumors are the most common solid tumors of childhood, and the genetic drivers and optimal therapeutic strategies for many of the different subtypes remain unknown. Here, we identify that bithalamic gliomas harbor frequent mutations in the EGFR oncogene, only rare histone H3 mutation (in contrast to their unilateral counterparts), and a distinct genome-wide DNA methylation profile compared to all other glioma subtypes studied to date. These EGFR mutations are either small in-frame insertions within exon 20 (intracellular tyrosine kinase domain) or missense mutations within exon 7 (extracellular ligand-binding domain) that occur in the absence of accompanying gene amplification. We find these EGFR mutations are oncogenic in primary astrocyte models and confer sensitivity to specific tyrosine kinase inhibitors dependent on location within the kinase domain or extracellular domain. We initiated treatment with targeted kinase inhibitors in four children whose tumors harbor EGFR mutations with encouraging results. This study identifies a promising genomically-tailored therapeutic strategy for bithalamic gliomas, a lethal and genetically distinct brain tumor of childhood.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Glioma/genética , Mutación/genética , Adolescente , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Niño , Preescolar , Epigénesis Genética/genética , Receptores ErbB/genética , Femenino , Glioma/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Inhibidores de Proteínas Quinasas/farmacologíaAsunto(s)
Quinasa de Linfoma Anaplásico/genética , Astrocitoma/genética , Neoplasias Encefálicas/genética , Glicoproteínas de Membrana/genética , Receptor trkB/genética , Astrocitoma/patología , Neoplasias Encefálicas/patología , Preescolar , Femenino , Humanos , Masculino , Proteínas de Fusión OncogénicaAsunto(s)
Predisposición Genética a la Enfermedad/genética , Glioma/patología , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/patología , Adolescente , Adulto , Niño , Preescolar , Femenino , Mutación de Línea Germinal/genética , Glioma/genética , Humanos , Masculino , Proteína p53 Supresora de Tumor/genética , Adulto JovenRESUMEN
BACKGROUND: Pediatric central nervous system (CNS) atypical teratoid rhabdoid tumors (ATRT) are highly malignant tumors characterized by SMARCB1 gene abnormalities. Despite chemoradiation responsiveness, most children die of disease. No imaging findings distinguish ATRT from other malignant brain tumors. This study sought to describe magnetic resonance spectroscopy (MRS) of childhood CNS ATRT and identify metabolite patterns for diagnosis and disease status monitoring. METHODS: Data from 7 children diagnosed with CNS ATRT from 2007 to 2010, whose imaging included MRS, were retrospectively reviewed. RESULTS: Age at diagnosis ranged from 2.5 to 54 months. Tumors were large with calcium and cysts and avid gadolinium enhancement. All were isointense on T1-weighted imaging and mildly hyperintense on T2-weighted imaging. Short-TE MRS showed prominent lactate+lipid and choline, minimal N-acetyl acetate (NAA), and rarely minimal myoinositol and low creatine peaks. Long TE showed prominent choline, minimal NAA, and rarely low lactate peaks. CONCLUSIONS: The combination of prominent choline and lactate+lipids peaks, and generally absent NAA and myoinositol peaks by MRS in this panel of ATRT expands existing information and provides a potentially distinct metabolite profile from other malignant pediatric brain tumors, including medulloblastoma. Prospective, comparative quantitative MRS of ATRT with other pediatric CNS tumors is warranted.
Asunto(s)
Neoplasias Encefálicas/metabolismo , Encéfalo/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Tumor Rabdoide/metabolismo , Teratoma/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Preescolar , Colina/metabolismo , Proteínas Cromosómicas no Histona/genética , Creatina/metabolismo , Proteínas de Unión al ADN/genética , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Inositol/metabolismo , Ácido Láctico/metabolismo , Masculino , Cuidados Preoperatorios/métodos , Estudios Retrospectivos , Tumor Rabdoide/diagnóstico , Tumor Rabdoide/genética , Proteína SMARCB1 , Teratoma/diagnóstico , Teratoma/genética , Factores de Transcripción/genéticaRESUMEN
Myxopapillary ependymoma (MPE) is a rare subtype of ependymoma in children. Though classified as a Grade I tumor, their unpredictable behavior and propensity for local and disseminated recurrence poses a therapeutic challenge. Till date no predictive molecular markers exist for such recurrence, especially with dissemination. We demonstrated that Epidermal Growth Factor Receptor (EGFR) expression was seen in relapsed MPE both at diagnosis and at recurrence and none in the nonrecurring tumors. This finding suggests EGFR could be a predictive biomarker for recurrence in MPE.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias del Sistema Nervioso Central/diagnóstico , Ependimoma/diagnóstico , Receptores ErbB/análisis , Neoplasias del Sistema Nervioso Central/patología , Ependimoma/secundario , Femenino , Humanos , Proteínas Inhibidoras de la Apoptosis/análisis , Masculino , Recurrencia Local de Neoplasia/diagnóstico , Pronóstico , Survivin , Ubiquitina-Proteína Ligasas/análisisRESUMEN
Composite pleomorphic xanthoastrocytoma-ganglioglioma (PXA-GG) is an extremely rare central nervous system neoplasm with 2 distinct but intermingled components. Whether this tumor represents a "collision tumor" of separate neoplasms or a monoclonal neoplasm with divergent evolution is poorly understood. Clinicopathologic studies and capture-based next generation sequencing were performed on extracted DNA from all available PXA-GG at 2 medical centers. Five PXA-GG were diagnosed in 1 male and 4 female patients ranging from 13 to 25 years in age. Four arose within the cerebral hemispheres; 1 presented in the cerebellar vermis. DNA was sufficient for analysis in 4 PXA components and 3 GG components. Four paired PXA and GG components harbored BRAF p.V600E hotspot mutations. The 4 sequenced PXA components demonstrated CDKN2A homozygous deletion by sequencing with loss of p16 (protein product of CDKN2A) expression by immunohistochemistry, which was intact in all assessed GG components. The PXA components also demonstrated more frequent copy number alterations relative to paired GG components. In one PXA-GG, shared chromosomal copy number alterations were identified in both components. Our findings support divergent evolution of the PXA and GG components from a common BRAF p.V600E-mutant precursor lesion, with additional acquisition of CDKN2A homozygous deletion in the PXA component as is typically seen in conventional PXA.
Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Ganglioglioma , Adolescente , Adulto , Astrocitoma/genética , Astrocitoma/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Evolución Clonal , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , ADN , Femenino , Ganglioglioma/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Homocigoto , Humanos , Masculino , Mutación/genética , Proteínas Proto-Oncogénicas B-raf/genética , Eliminación de Secuencia , Adulto JovenRESUMEN
BACKGROUND: Central nervous system (CNS) atypical teratoid/rhabdoid tumors (AT/RT) are aggressive tumors usually diagnosed in young children and characterized by SMARCB1 (INI1, hSNF5) gene abnormalities. Despite initial chemo-radiation responsiveness, most children die of progressive disease (PD). Little data regarding familial AT/RT clinical course exist. This study described and compared familial (F) versus sporadic (S) AT/RT and elucidated SMARCB1 mutations and inheritance patterns. METHODS: A retrospective chart review, pedigree, and SMARCB1 analysis were done. RESULTS: Between January 1989 and June 2009, 20 children with CNS AT/RT were diagnosed, 8-S and 12-F. Median age at diagnosis (months) of S and F patient were: 13 and 4.8, respectively. Median survival (months) was S-21, F4.5, and 8-all. Pedigree analyses showed unaffected parent carriers with multiple affected offspring. CONCLUSIONS: Children with F-AT/RT are younger, have more extensive disease, and are more likely to die from PD than children with S-AT/RT. Surgery, radiation, and chemotherapy were important in achieving long-term survival. Pedigree analysis supports autosomal dominant inheritance pattern with incomplete penetrance. Germline SMARCB1 mutation analysis is important in all patients diagnosed with AT/RT to (1) determine actual incidence of F-AT/RT, (2) determine penetrance of predisposing mutations, (3) provide appropriate genetic counseling, and (4) establish surveillance screening guidelines.
Asunto(s)
Neoplasias del Sistema Nervioso Central/patología , Predisposición Genética a la Enfermedad , Tumor Rabdoide/patología , Teratoma/patología , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/terapia , Preescolar , Proteínas Cromosómicas no Histona/genética , Proteínas de Unión al ADN/genética , Femenino , Mutación de Línea Germinal/genética , Humanos , Lactante , Masculino , Linaje , Estudios Retrospectivos , Tumor Rabdoide/genética , Tumor Rabdoide/terapia , Proteína SMARCB1 , Tasa de Supervivencia , Teratoma/genética , Teratoma/terapia , Factores de Transcripción/genética , Resultado del TratamientoRESUMEN
BACKGROUND: Altered nutrient intake and decreased exercise in response to cancer therapies and their side effects, particularly corticosteroids, may be key factors in the increased body weight and differences in physical fitness reported in survivors of childhood acute lymphoblastic leukemia (ALL). PURPOSE: To assess (1) the effect of a home-based nutrition and exercise intervention program on cardiovascular fitness, strength, and flexibility in children with ALL during maintenance therapy and (2) the feasibility of conducting and evaluating a home-based exercise and nutrition program in this patient population. DESIGN: Children ages 4 to 10 years with standard-risk ALL were randomized when starting maintenance therapy to a 12-month home-based exercise and nutrition program (n=6, 3 males/3 females) or control (n=7, 4 males/3 females) group. Assessment of anthropometrics, dietary intake, physical activity, and fitness was performed at baseline and 6 and 12 months of study. RESULTS: Although age, body size, and nutrient intakes were similar between both subject groups at 0, 6, and 12 months, exercise and nutrition program children had greater improvement in physical activity and cardiovascular fitness between 6 and 12 months than control children. CONCLUSIONS: These results suggest that a home-based exercise intervention during maintenance therapy encouraged greater physical activity and improved cardiovascular fitness in children with standard-risk ALL. Further investigation involving larger populations of children with ALL is warranted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fenómenos Fisiológicos Nutricionales Infantiles , Ejercicio Físico , Leucemia-Linfoma Linfoblástico de Células Precursoras/dietoterapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Niño , Preescolar , Terapia Combinada , Registros de Dieta , Ingestión de Alimentos , Femenino , Humanos , Masculino , Actividad Motora , Evaluación Nutricional , Aptitud Física , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Medical advances continue to improve morbidity and mortality of serious pediatric diseases, including cancer, driving research addressing diminished physical and psychological quality of life in children with these chronic conditions. Empowerment enhances resilience and positively influences health, disease, and therapy understanding. We describe the development and usability assessment of a prototype Empower Stars! mobile video game grounded in behavioral and exercise theories with the purpose of coupling physical exercise with empowerment over disease in children with cancer. METHODS: Academic faculty, health-care providers, and community video game developers collaborated in this project. The iPadAir was selected as a delivery platform for its accelerometer and gyroscope features facilitating exercise design. Unity multiplatform technology provided animation and audiovisual features for immediate player feedback. Javascript, C#, Photoshop, Flash, and SketchUp were used for coding, creating graphical assets, Sprite sheets, and printing files, respectively. 3D-printed handles and case backing were used to adapt the iPad for physical exercise. Game usability, engagement, and enjoyment were assessed via a multilevel study of children undergoing cancer chemotherapy, their parents, and pediatric cancer health-care providers. Feedback crucial for ongoing game development was analyzed. RESULTS: A prototype Empower Stars! mobile video game was developed for children 7-14 years old with cancer. Active, sedentary, educational, and empowerment-centered elements intermix for 20 min of exercise within a 30 min "one-day treatment" gameplay session involving superheroes, space exploration, metaphorical cancer challenges, life restoration on a barren planet, and innumerable star rewards. No player "dies." Usability assessment data analyses showed widespread enthusiasm for integrating exercise with empowerment over cancer and the game itself. Favorite elements included collecting star rewards and planet terraforming. Traveling in space and the Healthy Food Choice game were least liked. The need for improved gameplay instructions was expressed by all groups. The usability study provided essential feedback for converting the prototype into alpha version of Empower Stars! CONCLUSION: Adapting exercise empowerment-promoting video game technology to mobile platforms facilitates usability and widespread dissemination for children with cancer. We discuss broader therapeutic applicability in diverse chronic pediatric diseases, including obesity, asthma, cystic fibrosis, diabetes, and juvenile idiopathic arthritis.
RESUMEN
Digital health technologies for people with epilepsy (PWE) include internet-based resources and mobile apps for seizure management. Since non-pharmacological interventions, such as listening to specific Mozart's compositions, cognitive therapy, psychosocial and educational interventions were shown to reduce epileptic seizures, these modalities can be integrated into mobile software and delivered by mobile medical apps as digital therapeutics. Herein, we describe: (1) a survey study among PWE about preferences to use mobile software for seizure control, (2) a rationale for developing digital therapies for epilepsy, (3) creation of proof-of-concept mobile software intended for use as an adjunct digital therapeutic to reduce seizures, and (4) broader applications of digital therapeutics for the treatment of epilepsy and other chronic disorders. A questionnaire was used to survey PWE with respect to preferred features in a mobile app for seizure control. Results from the survey suggested that over 90% of responders would be interested in using a mobile app to manage their seizures, while 75% were interested in listening to specific music that can reduce seizures. To define digital therapeutic for the treatment of epilepsy, we designed and created a proof-of-concept mobile software providing digital content intended to reduce seizures. The rationale for all components of such digital therapeutic is described. The resulting web-based app delivered a combination of epilepsy self-care, behavioral interventions, medication reminders and the antiseizure music, such as the Mozart's sonata K.448. To improve long-term patient engagement, integration of mobile medical app with music and multimedia streaming via smartphones, tablets and computers is also discussed. This work aims toward development and regulatory clearance of software as medical device (SaMD) for seizure control, yielding the adjunct digital therapeutic for epilepsy, and subsequently a drug-device combination product together with specific antiseizure medications. Mobile medical apps, music, therapeutic video games and their combinations with prescription medications present new opportunities to integrate pharmacological and non-pharmacological interventions for PWE, as well as those living with other chronic disorders, including depression and pain.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/complicaciones , Reparación de la Incompatibilidad de ADN , Glioblastoma/genética , Adolescente , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Glioblastoma/complicaciones , Glioblastoma/terapia , Homocigoto , Humanos , Masculino , Factores de TiempoRESUMEN
PURPOSE: Although metastases to the fetus via the placenta are rare, melanoma is the most common culprit. When it occurs, maternally derived melanoma metastasis in the infant is almost invariably fatal. PATIENTS AND METHODS: This article reviews current guidelines for placental evaluation in pregnant women with metastatic melanoma and presents surveillance recommendations for their infants. Comprehensive literature reviews were performed on melanoma in pregnancy and melanoma metastasis to the placenta and fetus. The use of interferon alfa in the pediatric population was also reviewed. A comprehensive search of the MEDLINE database (1966 to 2002) was performed. Articles were reviewed and additional references were obtained from the bibliographies. Translation of non-English articles was performed, and authors of previous publications were contacted. RESULTS: Eighty-seven patients with placental or fetal metastasis were identified. Twenty-seven occurrences were attributed to melanoma (31%). The fetus was affected in six of 27 melanoma patients (22%), with five of six infants dying of disease. The use of high-dose interferon alfa adjuvant therapy in pediatric patients has not been reported. CONCLUSION: The placentas of women with known or suspected metastatic melanoma should be carefully examined grossly and histologically by pathologists. With placental involvement, fetal risk of melanoma metastasis is approximately 22%. Neonates delivered with concomitant placental involvement should be considered a high-risk population. The risk-benefit ratio of adjuvant treatment for a potentially affected infant should be carefully weighed.
Asunto(s)
Enfermedades Fetales/patología , Melanoma/congénito , Melanoma/secundario , Enfermedades Placentarias/patología , Complicaciones Neoplásicas del Embarazo/patología , Femenino , Humanos , Incidencia , Recién Nacido , Masculino , Melanoma/epidemiología , Melanoma/mortalidad , Metástasis de la Neoplasia , Neoplasias/congénito , Neoplasias/epidemiología , Neoplasias/mortalidad , Neoplasias/patología , Embarazo , Resultado del Embarazo , Riesgo , Tasa de SupervivenciaRESUMEN
PURPOSE: To assess the rate of tumor response and activity of carboplatin in stabilizing the growth of progressive low-grade gliomas. PATIENTS AND METHODS: Eligible patients received carboplatin 560 mg/m(2) intravenously every 4 weeks for 1 year after maximum tumor response or until disease progression or unacceptable toxicity. RESULTS: Between October 1993 and October 2000, 81 children (median age, 79 months; range, 6 to 204) were enrolled onto this study. Patients received a median of 11 cycles of carboplatin (range, one to 29). Median follow-up from the time of enrollment was 55 months (range, 10 to 93). The overall objective response (complete response [CR] + partial response [PR] + minor response [MR]) and disease stabilization (CR + PR + stable disease + MR) rates to carboplatin treatment were 28% (95% confidence interval [CI], 18% to 38%) and 85% (95% CI, 74% to 93%), respectively. Eleven and 14 patients suffered progressive disease on study and after stopping therapy, respectively. Toxicity was predominantly myelosuppression and included grade 3/4 neutropenia in 56 patients and grade 3/4 thrombocytopenia in 40 patients. The 3-year failure-free survival (FFS) and overall survival (OS) for all patients were 64% (95% CI, 54% to 76%) and 84% (95% CI, 76% to 93%), respectively. Patients with diencephalic tumors had inferior FFS and OS compared with those with tumor at other sites (38% v 74% for FFS, P =.011; 54% v 91% for OS, P =.004). Neurofibromatosis type 1 patients with progressive low-grade glioma had a significantly better OS (95% v 80%; P =.052). CONCLUSION: Carboplatin, in the schedule used in this study, produced disease stabilization or improvement in a majority of children with progressive low-grade glioma, with manageable toxicity. Improved treatment strategies are particularly required for patients with diencephalic tumors.