Faculty Bibliography

PURPOSE Surgery is curative therapy for pediatric low-grade gliomas (LGGs) in areas of the brain amenable to complete resection. However, LGGs located in areas where complete resection is not possible can threaten both function and life. The purpose of this study was to compare two chemotherapy regimens for LGGs in children younger than age 10 years for whom radiotherapy was felt by the practitioner to pose a high risk of neurodevelopmental injury. PATIENTS AND METHODS Previously untreated children younger than age 10 years with progressive or residual LGGs were eligible. Children were randomly assigned to receive carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and vincristine (TPCV). Children with neurofibromatosis are reported separately. Results Of 274 randomly assigned patients who met eligibility requirements, 137 received CV and 137 received TPCV. The 5-year event-free survival (EFS) and overall survival (OS) rates for all eligible patients were 45% +/- 3.2% and 86% +/- 2.2%, respectively. The 5-year EFS rates were 39% +/- 4% for CV and 52% +/- 5% for TPCV (stratified log-rank test P = .10; cure model analysis P = .007). On multivariate analysis, factors independently predictive of worse EFS and OS were younger age and tumor size greater than 3 cm(2). Tumor location in the thalamus was also associated with poor OS. CONCLUSION The difference in EFS between the regimens did not reach significance on the basis of the stratified log-rank test. The 5-year EFS was higher for TPCV on the basis of the cure model analysis. Differences in toxicity may influence physician choice of regimens.

Langerhans cell histiocytosis (LCH) encompasses a range of clinical presentations. Pure osseous involvement is referred to as eosinophilic granuloma (EG), whereas systemic involvement can either be classified as Hand-Schuller-Christian disease or Letterer-Siwe syndrome. It is estimated that of the total incidence of LCH (0.5 per 100,000 children per year in the United States), nearly 70% are categorized as EG (1). We describe a case of clinically occult calvarial eosinophilic granuloma brought to medical attention only after a traumatic event led to scalp and epidural hemorrhage at the site of the lesion. Osseous EG initially presents as a painful or tender mass, at times even mimicking osteomyelitis. Computed tomography (CT) reveals a lytic lesion with beveled edges. Magnetic resonance (MR) imaging is often non-specific, but usually demonstrates a marrow-replacing process that is T1 hypointense, T2 hyperintense, with homogenous enhancement. The complex MR imaging findings in our case provided a unique perspective regarding the presentation of EG. Once pathology established eosinophilic granuloma, skeletal survey confirmed the lesion was solitary, despite a compelling history of present illness.

The authors report the first case of a Wilms tumor (WT) with diffuse anaplasia metastatic to the brain in a 13-year-old girl with a history of neurofibromatosis Type 1. At presentation, the metastatic tumor had radiological features that suggested a meningioma. Histologically it was characterized by striking anaplasia and features similar to the patient's previously resected WT with diffuse anaplasia.

BACKGROUND: : Controversy persists regarding the optimal treatment of pediatric craniopharyngiomas. OBJECTIVE: : We performed a meta-analysis of reported series of transcranial (TC) and transsphenoidal (TS) surgery for pediatric craniopharyngiomas to determine whether comparisons between the outcomes in TS and TC approaches are valid. METHODS: : Online databases were searched for English-language articles reporting quantifiable outcome data published between 1990 and 2010 pertaining to the surgical treatment of pediatric craniopharyngiomas. Forty-eight studies describing 2955 patients having TC surgery and 13 studies describing 373 patients having TS surgery met inclusion criteria. RESULTS: : Before surgery, patients who had TC surgery had less visual loss, more frequent hydrocephalus and increased intracranial pressure, larger tumors, and more suprasellar disease. After surgery, patients in the TC group had lower rates of gross total resection (GTR), more frequent recurrence after GTR, higher neurological morbidity, more frequent diabetes insipidus, less improvement, and greater deterioration in vision. There was no difference in operative mortality, obesity/hyperphagia, or overall survival percentages. CONCLUSION: : Directly comparing outcomes after TC and TS surgery for pediatric craniopharyngiomas does not appear to be valid. Baseline differences in patients who underwent each approach create selection bias that may explain the improved rates of disease control and lower morbidity of TS resection. Although TS approaches are becoming increasingly used for smaller tumors and those primarily intrasellar, tumors more amenable to TC surgery include large tumors with significant lateral extension, those that engulf vascular structures, and those with significant peripheral calcification

BACKGROUND: Central nervous system neoplasms are the most common solid tumors in children, and more than 40% are low-grade gliomas. Variable locations, extent of resection, postoperative neurodiagnostic evaluation, and histology have confounded therapy and outcome. OBJECTIVES: To investigate disease control and survival after surgery. METHODS: A prospective natural history trial from 1991 to 1996 produced a subset of patients with low-grade gliomas managed by primary surgery and subsequent observation. Patients were evaluable if eligibility, tumor location, and extent of resection were confirmed by pathological diagnosis, preoperative and postoperative imaging, and the surgeon's report. Primary end points were overall survival (OS), progression-free survival (PFS), and postprogression survival. RESULTS: Of 726 patients enrolled, 518 were fully evaluable for analysis. The 5- and 8-year OS rates were 97% +/- 0.8% and 96% +/- 0.9%, respectively, and PFS rates were 80% +/- 1.8% and 78% +/- 2.0%. In univariate analyses, histological type, extent of residual tumor, and disease site were significantly associated with PFS and OS. In multivariate analysis, gross total resection (GTR) without residual disease was the predominant predictor of PFS. In patients with limited residual disease, 56% were free of progression at 5 years. CONCLUSION: GTR should be the goal when it can be achieved with an acceptable functional outcome. The variable rate of progression after incomplete resection highlights the need for new predictors of tumor behavior

Prognosis of diffuse intrinsic pontine gliomas (DIPGs) remains poor. Failure has been predominantly local, with leptomeningeal dissemination (LD) occurring in 4-33% of patients in pre-MRI era series. Routine craniospinal imaging after initial treatment may reveal other relapse patterns relapse. Sixteen consecutive pediatric patients with DIPG treated between 2006 and 2009 were retrospectively reviewed. Treatment regimens, recurrence patterns, survival, and pathologic diagnosis were recorded. Fourteen patients received involved-field radiotherapy to 54 Gy, and two patients received craniospinal irradiation for LD at presentation. Neuraxis MRI was performed at diagnosis and at 4 month intervals following radiotherapy. Fifteen patients have had progression of disease (median progression-free survival 5.0 +/- 1.2 months), and 13 patients have died (median survival 9.0 +/- 1.4 months). Local failure occurred in 12 patients (75%). LD occurred in nine patients (56%). LD was present at diagnosis in three patients, after initial staging and treatment in six patients, and during autopsy in two patients. Median overall survival was 12.0 +/- 3.3 months without LD and 8.0 +/- 2.1 months with LD (P = 0.059, log rank test). Median progression-free survival was 9.5 +/- 3.9 months without LD and 3.0 +/- 2.1 months with LD (P = 0.012, log rank test). The high incidence of LD probably reflects liberal use of spine MRI surveillance. All patients should undergo routine craniospinal imaging at diagnosis and follow-up. Central nervous system prophylaxis should be considered in future clinical trials