Subsequent neoplasms after a primary tumor in individuals with neurofibromatosis type 1

Smita Bhatia, Yanjun Chen, F. Lennie Wong, Lindsey Hageman, Kandice Smith, Bruce Korf, Ashley Cannon, Daniel J. Leidy, Alejandro Paz, Joseph E. Andress, Gregory K. Friedman, Katie Metrock, Joseph P. Neglia, Michael Arnold, Lucie M. Turcotte, Peter De Blank, Wendy Leisenring, Gregory T. Armstrong, Leslie L. Robison, D. Wade ClappKevin Shannon, Jean L. Nakamura, Michael J. Fisher

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)3050-3058
Number of pages9
JournalJournal of Clinical Oncology
Volume37
Issue number32
DOIs
StatePublished - Jan 1 2019

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Neurofibromatosis 1
Neoplasms
Survivors
Alkylating Agents
Radiation
Drug Therapy

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Bhatia, S., Chen, Y., Wong, F. L., Hageman, L., Smith, K., Korf, B., ... Fisher, M. J. (2019). Subsequent neoplasms after a primary tumor in individuals with neurofibromatosis type 1. Journal of Clinical Oncology, 37(32), 3050-3058. https://doi.org/10.1200/JCO.19.00114

Subsequent neoplasms after a primary tumor in individuals with neurofibromatosis type 1. / Bhatia, Smita; Chen, Yanjun; Wong, F. Lennie; Hageman, Lindsey; Smith, Kandice; Korf, Bruce; Cannon, Ashley; Leidy, Daniel J.; Paz, Alejandro; Andress, Joseph E.; Friedman, Gregory K.; Metrock, Katie; Neglia, Joseph P.; Arnold, Michael; Turcotte, Lucie M.; De Blank, Peter; Leisenring, Wendy; Armstrong, Gregory T.; Robison, Leslie L.; Clapp, D. Wade; Shannon, Kevin; Nakamura, Jean L.; Fisher, Michael J.

In: Journal of Clinical Oncology, Vol. 37, No. 32, 01.01.2019, p. 3050-3058.

Research output: Contribution to journalArticle

Bhatia, S, Chen, Y, Wong, FL, Hageman, L, Smith, K, Korf, B, Cannon, A, Leidy, DJ, Paz, A, Andress, JE, Friedman, GK, Metrock, K, Neglia, JP, Arnold, M, Turcotte, LM, De Blank, P, Leisenring, W, Armstrong, GT, Robison, LL, Clapp, DW, Shannon, K, Nakamura, JL & Fisher, MJ 2019, 'Subsequent neoplasms after a primary tumor in individuals with neurofibromatosis type 1', Journal of Clinical Oncology, vol. 37, no. 32, pp. 3050-3058. https://doi.org/10.1200/JCO.19.00114
Bhatia, Smita ; Chen, Yanjun ; Wong, F. Lennie ; Hageman, Lindsey ; Smith, Kandice ; Korf, Bruce ; Cannon, Ashley ; Leidy, Daniel J. ; Paz, Alejandro ; Andress, Joseph E. ; Friedman, Gregory K. ; Metrock, Katie ; Neglia, Joseph P. ; Arnold, Michael ; Turcotte, Lucie M. ; De Blank, Peter ; Leisenring, Wendy ; Armstrong, Gregory T. ; Robison, Leslie L. ; Clapp, D. Wade ; Shannon, Kevin ; Nakamura, Jean L. ; Fisher, Michael J. / Subsequent neoplasms after a primary tumor in individuals with neurofibromatosis type 1. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 32. pp. 3050-3058.
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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.",
author = "Smita Bhatia and Yanjun Chen and Wong, {F. Lennie} and Lindsey Hageman and Kandice Smith and Bruce Korf and Ashley Cannon and Leidy, {Daniel J.} and Alejandro Paz and Andress, {Joseph E.} and Friedman, {Gregory K.} and Katie Metrock and Neglia, {Joseph P.} and Michael Arnold and Turcotte, {Lucie M.} and {De Blank}, Peter and Wendy Leisenring and Armstrong, {Gregory T.} and Robison, {Leslie L.} and Clapp, {D. Wade} and Kevin Shannon and Nakamura, {Jean L.} and Fisher, {Michael J.}",
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TY - JOUR

T1 - Subsequent neoplasms after a primary tumor in individuals with neurofibromatosis type 1

AU - Bhatia, Smita

AU - Chen, Yanjun

AU - Wong, F. Lennie

AU - Hageman, Lindsey

AU - Smith, Kandice

AU - Korf, Bruce

AU - Cannon, Ashley

AU - Leidy, Daniel J.

AU - Paz, Alejandro

AU - Andress, Joseph E.

AU - Friedman, Gregory K.

AU - Metrock, Katie

AU - Neglia, Joseph P.

AU - Arnold, Michael

AU - Turcotte, Lucie M.

AU - De Blank, Peter

AU - Leisenring, Wendy

AU - Armstrong, Gregory T.

AU - Robison, Leslie L.

AU - Clapp, D. Wade

AU - Shannon, Kevin

AU - Nakamura, Jean L.

AU - Fisher, Michael J.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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