Pediatric malignancies in neurofibromatosis type 1: A population‐based cohort study

• Published in: International journal of cancer Vol. 145; no. 11; pp. 2926 - 2932
• Main Authors: Peltonen, Sirkku, Kallionpää, Roope A., Rantanen, Matti, Uusitalo, Elina, Lähteenmäki, Päivi M., Pöyhönen, Minna, Pitkäniemi, Janne, Peltonen, Juha
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-12-2019; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adolescents; Age; astrocytoma; Brain cancer; Brain tumors; Cancer; Cancer Epidemiology; Central nervous system; Central Nervous System Neoplasms - epidemiology; Central Nervous System Neoplasms - mortality; Child; Children; Cohort analysis; Cohort Studies; Female; Finland - epidemiology; Genetic disorders; Glioma; Health risk assessment; Health risks; Humans; Incidence; Leukemia; Male; malignant peripheral nerve sheath tumor; Medical prognosis; Medical research; Mortality; Nerve Sheath Neoplasms - epidemiology; Nerve Sheath Neoplasms - mortality; Neurofibromatosis; Neurofibromatosis 1 - epidemiology; Neurofibromatosis 1 - mortality; Neurological disorders; Pediatrics; Peripheral nerves; plexiform neurofibroma; Population studies; Population-based studies; Prognosis; Recklinghausen's disease; Tumors; Young Adult; Finland; leukemia; glioma; astrocytoma; malignant peripheral nerve sheath tumor; plexiform neurofibroma
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.32187

Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome with an incidence of 1:2,000. Patients with NF1 have an increased cancer risk and mortality, but there are no population‐based cohort studies specifically investigating the risk of childhood malignancies. We used the Finnish NF1 cohort to analyze the incidence, risk and prognosis of malignancies in NF1 patients <20 years of age. Persons born in 1987–2011 were included, and 524 persons were followed through the files of the Finnish Cancer Registry from birth up to age 20 years. This amounted to 8,376 person years. Fifty‐three patients had cancer <20 years of age, yielding a standardized incidence ratio (SIR) of 35.6. The most frequent location of pediatric cancers was the central nervous system (CNS); there were 45 cases and the SIR was 115.7. Exclusion of 22 optic pathway gliomas (OPGs) gave an SIR of 59.1 for the CNS and 21.6 for all cancers. There were nine malignant peripheral nerve sheath tumors (MPNSTs); their cumulative risk was 2.7% by age 20. No cases of leukemia were observed. NF1 patients showed considerable excess mortality with a standardized mortality ratio (SMR) of 73.1. The survival of NF1 patients with CNS tumors other than OPGs did not differ from that of non‐NF1 controls (HR 0.64, 95% CI 0.23 to 1.76). In conclusion, brain tumors in childhood and MPNSTs in adolescence are malignancies of major concern in patients with NF1. The risk for myeloid malignancies may not be as high as suggested in the literature.
What's new?
Patients with neurofibromatosis type 1 (NF1) are known to have a high risk of various cancers. What has not been well‐studied, however, are the types of cancers that are most common among children with NF1, and how those cancers impact mortality. In this cohort study, the authors found that malignancies do cause increased mortality in patients under age 20. Brain tumors in childhood and malignant peripheral nerve sheath tumors (MPNSTs) in adolescence are of particular concern. On the other hand, the risk of myeloid malignancies may be lower than previously assumed.