Secondary sarcomas in childhood cancer survivors: a report from the Childhood Cancer Survivor Study.
BACKGROUND
Childhood cancer survivors are at increased risk for the development of secondary sarcomas. Exposure to radiation therapy is a known risk factor for the development of these sarcomas. Other risk factors for secondary sarcomas have not been well described for childhood cancer survivors. We analyzed a large cohort of childhood cancer survivors to determine the true incidence of secondary sarcomas and to examine factors associated with the risk of developing secondary sarcomas.


METHODS
The history of secondary sarcomas in 14,372 participants in the Childhood Cancer Survivor Study was determined from self-reports in three questionnaires. Risk of secondary sarcoma was evaluated by use of standardized incidence ratios (SIRs) and excess absolute risks (EARs) as calculated by use of data from the Surveillance, Epidemiology, and End Results Program. Cox regression models were used to estimate hazard ratios of developing subsequent sarcomas. Hazard ratios were reported as relative risks (RRs).


RESULTS
We identified 108 patients with sarcomas that were diagnosed a median of 11 years after the diagnosis of childhood cancer. The risk of sarcoma was more than ninefold higher among childhood cancer survivors than among the general population (SIR = 9.02, 95% confidence interval [CI] = 7.44 to 10.93). The excess absolute risk of secondary sarcoma was 32.5 per 100,000 person-years (95% CI = 26.1 to 40.3 per 100,000 person-years). Higher standardized incidence ratios and excess absolute risks were associated with young age at primary diagnosis, primary sarcoma diagnosis, and a family history of cancer. In a multivariable model, increased risk of secondary sarcoma was associated with radiation therapy (RR = 3.1, 95% CI = 1.5 to 6.2), with a primary diagnosis of sarcoma (RR = 10.1, 95% CI = 4.7 to 21.8), with a history of other secondary neoplasms (RR = 2.2, 95% CI = 1.1 to 4.5), and with treatment with higher doses of anthracyclines (RR = 2.3, 95% CI = 1.2 to 4.3) or alkylating agents (RR = 2.2, 95% CI = 1.1 to 4.6).


CONCLUSIONS
Childhood cancer survivors appear to be at increased risk for secondary sarcomas compared with general population rates.
Henderson
Tara O
TO
Department of Pediatrics, Section of Hematology-Oncology, Pritzker School of Medicine, University of Chicago, 5841 South Maryland Ave., MC 4060, Chicago, IL 60637, USA. thenderson@uchicago.edu
Whitton
John
J
Stovall
Marilyn
M
Mertens
Ann C
AC
Mitby
Pauline
P
Friedman
Debra
D
Strong
Louise C
LC
Hammond
Sue
S
Neglia
Joseph P
JP
Meadows
Anna T
AT
Robison
Leslie
L
Diller
Lisa
L
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D018943:Anthracyclines / Q000009:adverse effects; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000453:epidemiology* / Q000209:etiology*; D016017:Odds Ratio; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D018426:SEER Program; D012509:Sarcoma / Q000453:epidemiology*; D011795:Surveys and Questionnaires; D017741:Survivors / Q000706:statistics & numerical data*; D014481:United States / Q000453:epidemiology
D018943:Anthracyclines; D018906:Antineoplastic Agents, Alkylating