Nonrandomized comparison of neurofibromatosis type 1 and non–neurofibromatosis type 1 children who received carboplatin and vincristine for progressive low‐grade glioma: A report from the Children's Oncology Group

Abstract

Purpose To evaluate tumor response, event-free survival (EFS), overall survival (OS), and toxicity of chemotherapy, children with NF1 and progressive low-grade gliomas (LGG) were enrolled on COG A9952 protocol and treated with carboplatin and vincristine (CV). Patients and Methods Non-NF1 patients were randomized to CV versus thioguanine, procarbazine, CCNU, vincristine (TPCV) on COG A9952. NF1 patients were assigned CV only. NF1 and non-NF1 patients, who were treated with CV, were compared on baseline characteristics, toxicity, tumor response, EFS, and OS. Results A total of 127 eligible patients with NF1 were non-randomly assigned to CV: 42 (33%) NF1 patients had events and 6 (4.7%) died. The 5-year EFS for the CV-NF1 group was 69% ± 4% versus 39% ± 4% for the CV-non-NF1 group (P<0.001). In univariate analysis, NF1 children had significantly higher tumor response rate and superior EFS and OS compared to CV-treated children without NF1. NF1 and non-NF1 patients differed significantly in amount of residual tumor, extent of resection, tumor location, and pathology. After multivariate analysis, NF1 was independently associated with better EFS (p < 0.001), but not with OS. NF1 patients also had decreased risk of grade 3 or 4 toxicities compared to non-NF1 patients. Three second malignant neoplasms (SMNs) occurred in NF1 patients receiving CV (CV-NF1), at a median of 7.8 years (range 7.3 to 9.4 years) after enrollment, but none in the non-NF1 group. Conclusions Children with NF1 tolerated CV well and had tumor response rate and EFS that were superior to children without NF1.

Treatment burden and long‐term health deficits of patients with low‐grade gliomas or glioneuronal tumors diagnosed during the first year of life

“…In our cohort, up to 6 tumor‐directed surgeries per patient and up to 13 systemic therapy regimens per patient were required. An NF1 status predicted fewer surgeries, and this was consistent with the more benign course of glioma in these patients; however, tumors not completely resectable at diagnosis and those in the HT/OP (commonly found in infants) resulted in increased chemotherapy/systemic therapy . Common LGG regimens (eg, carboplatin/vincristine and vinblastine) involve weekly hospital attendance over months and disrupt daily lives and family routines.…”

Neurofibromatosis type 1 and optic pathway glioma: Molecular interplay and therapeutic insights

“…One hundred twenty‐seven patients with NF1 received only CV and were not randomized to the other arm due to concern of alkylator‐induced carcinogenesis. The 5‐year event‐free survival (EFS) rate was 70% for NF1‐related gliomas, compared with 39% of those without NF1 who were treated with CV . Another study (HIT‐LGG‐1996), conducted by the International Society of Pediatric Oncology, included 108 children with NF1.…”

“…The 5-year event-free survival (EFS) rate was 70% for NF1-related gliomas, compared with 39% of those without NF1 who were treated with CV. 37 Another study (HIT-LGG-1996), conducted by the International Society of Pediatric Oncology, included 108 children with NF1. Forty-three of these children were initially observed and 55 received therapy with CV.…”

Favorable prognosis in pediatric brainstem low‐grade glioma: Report from the German SIOP‐LGG 2004 cohort

“…Still, the prognostic risk‐factors determining natural biology are not fully understood . The prognostic impact of young age or germline mutation of neurofibromatosis type 1 (NF1) or of tumor‐related criteria like dissemination has been defined consistently . However, the role of LGG location within the central nervous system (CNS) remains controversial, and this applies in particular to the caudal brainstem where 5–10% of pediatric LGG are found.…”