TY - JOUR
T1 - Chemotherapy and risk of subsequent malignant neoplasms in the childhood cancer survivor study cohort
AU - Turcotte, Lucie M.
AU - Liu, Qi
AU - Yasui, Yutaka
AU - Henderson, Tara O.
AU - Gibson, Todd M.
AU - Leisenring, Wendy
AU - Arnold, Michael A.
AU - Howell, Rebecca M.
AU - Green, Daniel M.
AU - Armstrong, Gregory T.
AU - Robison, Leslie L.
AU - Neglia, Joseph P.
N1 - Publisher Copyright:
© 2019 by American Society of Clinical Oncology.
PY - 2019
Y1 - 2019
N2 - PURPOSE Therapeutic radiation in childhood cancer has decreased over time with a concomitant increase in chemotherapy. Limited data exist on chemotherapy-associated subsequent malignant neoplasm (SMN) risk. PATIENTS AND METHODS SMNs occurring . 5 years from diagnosis, excluding nonmelanoma skin cancers, were evaluated in survivors diagnosed when they were , 21 years old, from 1970 to 1999 in the Childhood Cancer Survivor Study (median age at diagnosis, 7.0 years; median age at last follow-up, 31.8 years). Thirty-year SMN cumulative incidence and standardized incidence ratios (SIRs) were estimated by treatment: Chemotherapy-only (n = 7,448), chemotherapy plus radiation (n = 10,485), radiation only (n = 2,063), or neither (n = 2,158). Multivariable models were used to assess chemotherapy-associated SMN risk, including doseresponse relationships. RESULTS Of 1,498 SMNs among 1,344 survivors, 229 occurred among 206 survivors treated with chemotherapy only. Thirty-year SMN cumulative incidence was 3.9%, 9.0%, 10.8%, and 3.4% for the chemotherapy-only, chemotherapy plus radiation, radiation-only, or neither-treatment groups, respectively. Chemotherapy-only survivors had a 2.8-fold increased SMN risk compared with the general population (95% CI, 2.5 to 3.2), with SIRs increased for subsequent leukemia/lymphoma (1.9; 95% CI, 1.3 to 2.7), breast cancer (4.6; 95% CI, 3.5 to 6.0), soft-tissue sarcoma (3.4; 95% CI, 1.9 to 5.7), thyroid cancer (3.8; 95% CI, 2.7 to 5.1), and melanoma (2.3; 95% CI, 1.5 to 3.5). SMN rate was associated with . 750 mg/m2 platinum (relative rate [RR] 2.7; 95% CI, 1.1 to 6.5), and a dose response was observed between alkylating agents and SMN rate (RR, 1.2/5,000 mg/m2; 95% CI, 1.1 to 1.3). A linear dose response was also demonstrated between anthracyclines and breast cancer rate (RR, 1.3/100 mg/m2; 95% CI, 1.2 to 1.6). CONCLUSION Childhood cancer survivors treated with chemotherapy only, particularly higher cumulative doses of platinum and alkylating agents, face increased SMN risk. Linear dose responses were seen between alkylating agents and SMN rates and between anthracyclines and breast cancer rates. Limiting cumulative doses and consideration of alternate chemotherapies may reduce SMN risk.
AB - PURPOSE Therapeutic radiation in childhood cancer has decreased over time with a concomitant increase in chemotherapy. Limited data exist on chemotherapy-associated subsequent malignant neoplasm (SMN) risk. PATIENTS AND METHODS SMNs occurring . 5 years from diagnosis, excluding nonmelanoma skin cancers, were evaluated in survivors diagnosed when they were , 21 years old, from 1970 to 1999 in the Childhood Cancer Survivor Study (median age at diagnosis, 7.0 years; median age at last follow-up, 31.8 years). Thirty-year SMN cumulative incidence and standardized incidence ratios (SIRs) were estimated by treatment: Chemotherapy-only (n = 7,448), chemotherapy plus radiation (n = 10,485), radiation only (n = 2,063), or neither (n = 2,158). Multivariable models were used to assess chemotherapy-associated SMN risk, including doseresponse relationships. RESULTS Of 1,498 SMNs among 1,344 survivors, 229 occurred among 206 survivors treated with chemotherapy only. Thirty-year SMN cumulative incidence was 3.9%, 9.0%, 10.8%, and 3.4% for the chemotherapy-only, chemotherapy plus radiation, radiation-only, or neither-treatment groups, respectively. Chemotherapy-only survivors had a 2.8-fold increased SMN risk compared with the general population (95% CI, 2.5 to 3.2), with SIRs increased for subsequent leukemia/lymphoma (1.9; 95% CI, 1.3 to 2.7), breast cancer (4.6; 95% CI, 3.5 to 6.0), soft-tissue sarcoma (3.4; 95% CI, 1.9 to 5.7), thyroid cancer (3.8; 95% CI, 2.7 to 5.1), and melanoma (2.3; 95% CI, 1.5 to 3.5). SMN rate was associated with . 750 mg/m2 platinum (relative rate [RR] 2.7; 95% CI, 1.1 to 6.5), and a dose response was observed between alkylating agents and SMN rate (RR, 1.2/5,000 mg/m2; 95% CI, 1.1 to 1.3). A linear dose response was also demonstrated between anthracyclines and breast cancer rate (RR, 1.3/100 mg/m2; 95% CI, 1.2 to 1.6). CONCLUSION Childhood cancer survivors treated with chemotherapy only, particularly higher cumulative doses of platinum and alkylating agents, face increased SMN risk. Linear dose responses were seen between alkylating agents and SMN rates and between anthracyclines and breast cancer rates. Limiting cumulative doses and consideration of alternate chemotherapies may reduce SMN risk.
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U2 - 10.1200/JCO.19.00129
DO - 10.1200/JCO.19.00129
M3 - Article
C2 - 31622130
AN - SCOPUS:85075812756
SN - 0732-183X
VL - 37
SP - 3310
EP - 3319
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 34
ER -