Format

Send to

Choose Destination
J Clin Oncol. 2019 Sep 18:JCO1900114. doi: 10.1200/JCO.19.00114. [Epub ahead of print]

Subsequent Neoplasms After a Primary Tumor in Individuals With Neurofibromatosis Type 1.

Author information

1
University of Alabama at Birmingham, Birmingham, AL.
2
City of Hope, Duarte, CA.
3
The Children's Hospital of Philadelphia, Philadelphia, PA.
4
University of Minnesota, Minneapolis, MN.
5
Nationwide Children's Hospital, Columbus, OH.
6
Cincinnati Children's Hospital, Cincinnati, OH.
7
Fred Hutchinson Cancer Research Center, Seattle, WA.
8
St Jude Children's Research Hospital, Memphis, TN.
9
Indiana University, Indianapolis, IN.
10
University of California, San Francisco, San Francisco, CA.

Abstract

PURPOSE:

Fundamental gaps in knowledge regarding the risk of subsequent neoplasms (SNs) in children with pathogenic neurofibromatosis type 1 (NF1) variants exposed to radiation and/or alkylator chemotherapy have limited the use of these agents.

METHODS:

We addressed these gaps by determining the SN risk in 167 NF1-affected versus 1,541 non-NF1-affected 5-year childhood cancer survivors from the Childhood Cancer Survivor Study and 176 nonoverlapping NF1-affected individuals with primary tumors from University of Alabama at Birmingham and Children's Hospital of Philadelphia exposed to radiation and/or chemotherapy. Proportional subdistribution hazards multivariable regression analysis was used to examine risk factors, adjusting for type and age at primary tumor diagnosis and therapeutic exposures.

RESULTS:

In the Childhood Cancer Survivor Study cohort, the 20-year cumulative incidence of SNs in NF1 childhood cancer survivors was 7.3%, compared with 2.9% in the non-NF1 childhood cancer survivors (P = .003), yielding a 2.4-fold higher risk of SN (95% CI, 1.3 to 4.3; P = .005) in the NF1-affected individuals. In the University of Alabama at Birmingham and Children's Hospital of Philadelphia cohort, among NF1-affected individuals with a primary tumor, the risk of SNs was 2.8-fold higher in patients with irradiated NF1 (95% CI, 1.3 to 6.0; P = .009). In contrast, the risk of SNs was not significantly elevated after exposure to alkylating agents (hazard ratio, 1.27; 95% CI, 0.3 to 3.0; P = .9).

CONCLUSION:

Children with NF1 who develop a primary tumor are at increased risk of SN when compared with non-NF1 childhood cancer survivors. Among NF1-affected children with a primary tumor, therapeutic radiation, but not alkylating agents, confer an increased risk of SNs. These findings can inform evidence-based clinical management of primary tumors in NF1-affected children.

PMID:
31532722
DOI:
10.1200/JCO.19.00114

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center