Natural history and management of low-grade glioma in NF-1 children

Abstract

Pediatric neurofibromatosis type 1 (NF-1) patients are prone to developing low-grade glioma (LGG). The HIT-LGG study 1996 aimed to observe the natural history of pediatric LGG and to postpone irradiation in younger children by using carboplatinum and vincristine in case non-surgical treatment was required. A total of 109 of 1,044 (10.4%) protocol patients had a genetic NF-1 trait [57 female patients; median age 5.1 years (range 1-15.4 years)]. Eighty-three patients (76%) suffered from an optic pathway tumor. Neuroimaging only allowed diagnosis in 67 patients. Histology revealed pilocytic astrocytoma WHO grade I in 38 of 42 biopsied patients. Sixty-five (60%) patients received non-surgical treatment, either chemotherapy (n = 55) or irradiation (n = 10). The overall survival rate of 96% after a median observation time of 5.25 years contrasts with an event free survival rate (EFS) of 0.24 at 5 years. Progressive LGG were observed even in children older than 11 years. Chiasmatic/postchiasmatic localization was a univariate risk factor for progressive disease. In the chemotherapy group, we observed a 5-year progression-free survival (PFS) rate of 0.73. Similarly, the PFS rate in the irradiation group was 0.78. Multivariate analysis revealed surgical intervention and localization within the optic pathway as factors that increased the risk of tumor progression. In this large prospective multinational study, LGG in NF-1 patients did progress in 75% of patients. Chemotherapy yielded acceptable PFS. The biological factors determining progression remain poorly understood.

Tectal Lesions in Children: A Long-Term Follow-Up Volumetric Tumor Growth Analysis in Surgical and Nonsurgical Cases

“…This asseveration is different than that reported by Griessenauer et al [9], who suggested that the non-NF patients in their series had larger tumor volumes than those with NF, who had more indolent courses. However, many recent publications have proposed that NF-1-associated brain tumors, including ‘unidentified bright objects', have higher rates of progression than previously thought, even to the point of requiring surgical intervention with progression rates ranging from 30 to 75% [14,15,16]. …”

MAPK pathway activation in pilocytic astrocytoma

“…Roughly 15% of NF1 patients have PAs, particularly in the optic pathway [47], and optic pathway gliomas are considered one of the diagnostic criteria for the syndrome [48]. Conversely, about a third of tumors in the optic pathway are PAs [49] and roughly 10% of all PAs are NF1-associated, suggesting that PA patients, particularly with optic pathway tumors, should be examined for clinical signs of NF1 [50]. Mutation screening of NF1 can be difficult, since the gene comprises 58 exons spread over nearly 300 kb of chromosome 17 and the types of mutations observed can be complex.…”

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

“…Of all NF1–OPGs found routinely, vision loss or other symptoms are found in 30–50% of affected children . Precious puberty is occasionally seen, where it is often secondary to tumor infiltration of the hypothalamus . Initially symptomatic children are more likely to require treatment than are those with incidentally identified tumors .…”