Prognostic factors of CNS tumours in Neurofibromatosis 1 (NF1): a retrospective study of 104 patients.

In addition to multiple peripheral neurofibromas, Neurofibromatosis 1 (NF1) predisposes to CNS tumours. Most of them are pilocytic astrocytomas, arise in children and are located in the optic pathways or in the brainstem. The majority are indolent, but factors predictive of poor prognosis have yet to be identified. Furthermore, the incidence and natural history of gliomas of a higher grade, arising in adults or involving other locations are largely unknown in NF1. In order to address these issues, we performed a retrospective study of 104 patients followed in seven French centres between 1982 and 2000. Inclusion criteria were a diagnosis of NF1, according to the National Institutes of Health criteria, and the presence of a CNS tumour, regardless of type, location or age of onset. The series included 88 children (age range 3 months to 17 years) and 16 adults (age range 19-52 years). The median follow-up was 5.6 years. One hundred and twenty-seven CNS tumours were observed in the 104 patients. Eighty-four (66%) were optic pathway tumours (OPT) and 43 (34%) extra-optic pathway tumours (extra-OPT) (brainstem: n = 21; other locations: n = 22). Twenty-one patients (20%) had multiple CNS tumours. OPT were symptomatic in 50 patients and extra-OPT in 19. Main clinical findings at presentation included visual loss (n = 29; 58%) and precocious puberty (n = 5; 10%) for OPT, increased intracranial pressure (n = 9; 48%) for extra-OPT. Fourteen out of the 27 symptomatic tumours with histology were pilocytic astrocytomas. The overall survival rate was 90% at 5 years (95% confidence interval 82-95%). Extra-optic location, tumour diagnosis in adulthood and symptomatic tumours were independent factors associated with shorter survival time (P < 0.05, Cox model). Radiotherapy for OPT was associated with vascular complications (ischaemic strokes) and growth hormone deficiency in 32 and 46% of patients, respectively. In conclusion, mortality is high in extra-OPT, particularly in adults, whereas OPT are only exceptionally life-threatening. Radiotherapy of OPT is associated with an important morbidity in NF1.