Primary Neurosurgery for Pediatric Low-Grade Gliomas: A Prospective Multi-Institutional Study From the Children's Oncology Group

Abstract 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

Randomized Study of Two Chemotherapy Regimens for Treatment of Low-Grade Glioma in Young Children: A Report From the Children's Oncology Group

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