Risk of Subsequent Neoplasms During the Fifth and Sixth Decades of Life in the Childhood Cancer Survivor Study Cohort.
OBJECTIVE
Survivors of childhood cancer have an increased risk for subsequent neoplasms (SNs), but the incidence beyond the age of 40 years and associations with therapeutic exposures have not been well described.


METHODS
Among 14,364 survivors of childhood cancer diagnosed between 1970 and 1986, 3,171 had an attained age of 40 years or older at the time of last contact. Cumulative incidence of SNs, standardized incidence ratios (SIRs), excess absolute risk of subsequent malignant neoplasms (SMNs), and relative risks (RRs) for SMNs and nonmelanoma skin cancers were calculated.


RESULTS
In total, 679 SNs were diagnosed in patients age 40 years or older. These included 196 SMNs, 419 nonmelanoma skin cancers, 21 nonmalignant meningiomas, and 43 other benign neoplasms. At age 55 years, the cumulative incidence of new SNs and SMNs occurring after age 40 years was 34.6% (95% CI, 28.7 to 40.6) and 16.3% (95% CI, 11.7 to 20.9), respectively. Survivors were twice as likely as the general population to receive a diagnosis of SMN after age 40 years (SIR, 2.2; 95% CI, 1.9 to 2.5). Among SMNs, risk was increased for breast cancer (SIR, 5.5; 95% CI, 4.5 to 6.7), renal cancer (SIR, 3.9; 95% CI, 2.0 to 7.5), soft tissue sarcoma (SIR, 2.6; 95% CI, 1.5 to 4.4), and thyroid cancer (SIR, 1.9; 95% CI, 1.0 to 3.5). Female sex (RR, 1.9; 95% CI, 1.3 to 2.6; P < .001) and therapeutic radiation exposure (RR, 2.2; 95% CI, 1.4 to 3.3; P < .001) were associated with an increased for risk for SMN in multivariable analysis.


CONCLUSIONS
Even after age 40 years, survivors of childhood cancer remain at increased risk for treatment-related SNs. These data suggest the need for life-long monitoring and should inform anticipatory guidance provided to survivors of childhood cancer.
Lucie M. Turcotte and Joseph P. Neglia, University of Minnesota Medical School, Minneapolis, MN; John A. Whitton and Wendy Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Debra L. Friedman, Vanderbilt University School of Medicine, Nashville; Gregory T. Armstrong and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Sue Hammond, Ohio State University, Columbus, OH. turc0023@umn.edu.
Lucie M
LM
Turcotte
Lucie M. Turcotte and Joseph P. Neglia, University of Minnesota Medical School, Minneapolis, MN; John A. Whitton and Wendy Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Debra L. Friedman, Vanderbilt University School of Medicine, Nashville; Gregory T. Armstrong and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Sue Hammond, Ohio State University, Columbus, OH.
John A
JA
Whitton
Lucie M. Turcotte and Joseph P. Neglia, University of Minnesota Medical School, Minneapolis, MN; John A. Whitton and Wendy Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Debra L. Friedman, Vanderbilt University School of Medicine, Nashville; Gregory T. Armstrong and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Sue Hammond, Ohio State University, Columbus, OH.
Debra L
DL
Friedman
Lucie M. Turcotte and Joseph P. Neglia, University of Minnesota Medical School, Minneapolis, MN; John A. Whitton and Wendy Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Debra L. Friedman, Vanderbilt University School of Medicine, Nashville; Gregory T. Armstrong and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Sue Hammond, Ohio State University, Columbus, OH.
Sue
S
Hammond
Lucie M. Turcotte and Joseph P. Neglia, University of Minnesota Medical School, Minneapolis, MN; John A. Whitton and Wendy Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Debra L. Friedman, Vanderbilt University School of Medicine, Nashville; Gregory T. Armstrong and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Sue Hammond, Ohio State University, Columbus, OH.
Gregory T
GT
Armstrong
Lucie M. Turcotte and Joseph P. Neglia, University of Minnesota Medical School, Minneapolis, MN; John A. Whitton and Wendy Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Debra L. Friedman, Vanderbilt University School of Medicine, Nashville; Gregory T. Armstrong and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Sue Hammond, Ohio State University, Columbus, OH.
Wendy
W
Leisenring
Lucie M. Turcotte and Joseph P. Neglia, University of Minnesota Medical School, Minneapolis, MN; John A. Whitton and Wendy Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Debra L. Friedman, Vanderbilt University School of Medicine, Nashville; Gregory T. Armstrong and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Sue Hammond, Ohio State University, Columbus, OH.
Leslie L
LL
Robison
Lucie M. Turcotte and Joseph P. Neglia, University of Minnesota Medical School, Minneapolis, MN; John A. Whitton and Wendy Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Debra L. Friedman, Vanderbilt University School of Medicine, Nashville; Gregory T. Armstrong and Leslie L. Robison, St Jude Children's Research Hospital, Memphis, TN; and Sue Hammond, Ohio State University, Columbus, OH.
Joseph P
JP
Neglia
D000293:Adolescent; D000328:Adult; D001943:Breast Neoplasms / Q000150:complications / Q000175:diagnosis; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000150:complications / Q000175:diagnosis; D008137:Longitudinal Studies; D008297:Male; D008577:Meningeal Neoplasms / Q000150:complications / Q000175:diagnosis; D008579:Meningioma / Q000150:complications / Q000175:diagnosis; D008875:Middle Aged; D015999:Multivariate Analysis; D016609:Neoplasms, Second Primary / Q000175:diagnosis* / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D012509:Sarcoma / Q000150:complications / Q000175:diagnosis; D012878:Skin Neoplasms / Q000150:complications / Q000175:diagnosis; D017741:Survivors; D013964:Thyroid Neoplasms / Q000150:complications / Q000175:diagnosis