Risk factors associated with secondary sarcomas in childhood cancer survivors: a report from the childhood cancer survivor study.
OBJECTIVE
Childhood cancer survivors have an increased risk of secondary sarcomas. To better identify those at risk, the relationship between therapeutic dose of chemotherapy and radiation and secondary sarcoma should be quantified.


METHODS
We conducted a nested case-control study of secondary sarcomas (105 cases, 422 matched controls) in a cohort of 14,372 childhood cancer survivors. Radiation dose at the second malignant neoplasm (SMN) site and use of chemotherapy were estimated from detailed review of medical records. Odds ratios (ORs) and 95% confidence intervals were estimated by conditional logistic regression. Excess odds ratio (EOR) was modeled as a function of radiation dose, chemotherapy, and host factors.


RESULTS
Sarcomas occurred a median of 11.8 years (range, 5.3-31.3 years) from original diagnosis. Any exposure to radiation was associated with increased risk of secondary sarcoma (OR = 4.1, 95% CI = 1.8-9.5). A dose-response relation was observed, with elevated risks at doses between 10 and 29.9 Gy (OR = 15.6, 95% CI = 4.5-53.9), 30-49.9 Gy (OR = 16.0, 95% CI 3.8-67.8) and >50 Gy (OR = 114.1, 95% CI 13.5-964.8). Anthracycline exposure was associated with sarcoma risk (OR = 3.5, 95% CI = 1.6-7.7) adjusting for radiation dose, other chemotherapy, and primary cancer. Adjusting for treatment, survivors with a first diagnosis of Hodgkin lymphoma (OR = 10.7, 95% CI = 3.1-37.4) or primary sarcoma (OR = 8.4, 95% CI = 3.2-22.3) were more likely to develop a sarcoma.


CONCLUSIONS
Of the risk factors evaluated, radiation exposure was the most important for secondary sarcoma development in childhood cancer survivors; anthracycline chemotherapy exposure was also associated with increased risk.
Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA. thenderson@peds.bsd.uchicago.edu
Tara O
TO
Henderson
Preetha
P
Rajaraman
Marilyn
M
Stovall
Louis S
LS
Constine
Aliza
A
Olive
Susan A
SA
Smith
Ann
A
Mertens
Anna
A
Meadows
Joseph P
JP
Neglia
Sue
S
Hammond
John
J
Whitton
Peter D
PD
Inskip
Leslie L
LL
Robison
Lisa
L
Diller
D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000209:etiology*; D016017:Odds Ratio; D012307:Risk Factors; D012509:Sarcoma / Q000209:etiology*; D017741:Survivors; D055815:Young Adult
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic