Comparison of Cancer Prevalence in Patients With Neurofibromatosis Type 1 at an Academic Cancer Center vs in the General Population From 1985 to 2020

Abstract

IMPORTANCE Neurofibromatosis type 1 (NF1) is a complex genetic disorder that is associated with not only neurofibromas, but also an increased susceptibility to other neoplasms. OBJECTIVE To evaluate the prevalence of neoplasia and outcomes among patients with NF1. DESIGN, SETTING, AND PARTICIPANTS This cohort study was conducted among patients with NF1 at a single academic cancer center from 1985 to 2020 with median (range) follow-up of 2.9 years (36 days to 30.5 years). Of 2427 patients evaluated for NF1, 1607 patients who met the National Institutes of Health consensus criteria for NF1 were included. This group was compared with estimates from Surveillance, Epidemiology, and End Results (SEER) Cancer Statistics Review 1975 to 2015 and SEER participants database unless otherwise specified. Data were analyzed from August 2018 to March 2020. MAIN OUTCOMES AND MEASURES Disease-specific survival (DSS) was measured from diagnosis date to date of neoplasm-specific death or censorship and calculated using the Kaplan-Meier method. Survival curves were compared using the log-rank test. Deaths from disease were considered a DSS end point; other deaths were considered censored observations. Secondary outcome measures were comparisons of (1) overall survival of patients with NF1 with neurofibroma neoplasms vs those without nonneurofibroma neoplasms, (2) neoplasm prevalence in the NF1 group vs general population estimates, and (3) age at diagnosis in the NF1 group vs general population estimates for the most common neoplasms in the NF1 group. RESULTS Among 1607 patients with NF1, the median (range) age at initial visit was 19 years (1 month to 83 years) and 840 (52.3%) were female patients. Among 666 patients who developed other neoplasms in addition to neurofibromas (41.4%), 295 patients (18.4%) developed glioma and 243 patients (15.1%) developed malignant peripheral nerve sheath tumor (MPNST), the most common neoplasms. Patients with NF1, compared with the general population, developed several neoplasms at a younger mean (SD) age (low-grade glioma: 12.98 [11.

Current Understanding of Neurofibromatosis Type 1, 2, and Schwannomatosis

“…It has been shown that NF1 patients have decreased life expectancy of 15 years compared to the general population [ 12 ]. Malignant tumors and vascular disease have been significantly associated with the death of NF1 patients aged <40 years [ 13 ].…”

Melanoma uveal en un paciente con neurofibromatosis

“…El 50% de los pacientes llega a sufrir metástasis a los 5 años del diagnóstico primario, principalmente en el hígado, por lo que es fundamental su detección y tratamiento oportuno. En casos como el actual, por el antecedente de neurofibromatosis, se presentan tasas más altas de neoplasias, asociadas a disminución de la esperanza de vida [2]. La radioterapia es el tratamiento local más apropiado para pacientes con neoplasias de pequeño tamaño, que no presentan afectación extraocular, con el objetivo de preservar el globo ocular.…”

“…La edad media de afectación es de 62 años [1]. La neurofibromatosis es un trastorno autosómico dominante, dicha afectación se asocia al desarrollo más temprano y frecuente de neoplasias, dentro de las que se puede mencionar el melanoma, quienes presentan una esperanza de vida de hasta 15 años menos que la población en general [2]. Se presenta el caso de un paciente masculino de 55 años de edad con con melanoma uveal y antecedente de neurofibromatosis.…”

Genotype–Phenotype Correlation of Novel NF1 Gene Variants Detected by NGS in Patients with Neurofibromatosis Type 1

“…50% of neurofibromatosis type 1 cases are hereditary, the rest of them are due to de novo NF1 mutations. Neurofibromatosis type 1 is a multisystem disease and patients are at high risk of cancer [3,4]. The life span of individuals with NF1 is generally short and mortality is higher in younger individuals (<40 years) compared to the general population.…”