Abstract
Detailed data describing the epidemiology of second malignant neoplasms (SMN) are needed for survivors of adolescent and young adult (AYA) cancer to inform the development of age-appropriate survivorship care guidelines. To describe the incidence, risk factors, and mortality for SMN in survivors of AYA cancer. This retrospective matched cohort study included 10 574 two-year survivors diagnosed with cancer between January 1, 1990, and December 31, 2012, at age 15 to 39 years in an integrated health care delivery system in Southern California. A comparison cohort without a history of cancer was individually matched 13:1 to survivors of AYA cancer by age, sex, and calendar year. Data analysis was completed in July 2018. Secondary malignant neoplasm risk factors of interest included age, stage, and calendar year at first cancer diagnosis; sex; race/ethnicity; radiation therapy; and chemotherapy. Diagnoses of SMN were ascertained using cancer registries from the National Cancer Institute Surveillance, Epidemiology, and End Results Program through December 31, 2014. Poisson regression was used to evaluate the association between cancer survivor status and developing SMN and risk factors for SMN, while risk of all-cause mortality by SMN status was examined in Cox regression. A total of 10 574 survivors of AYA cancer (6853 [64.8%] female; median [range] age, 33 [15-39] years; 622 with SMN) and 136 683 participants in the comparison cohort (88 513 [64.8%] female; median [range] age, 33 [15-39] years; 3437 with first cancer) were included. In survivors of AYA cancer, 20-year cumulative incidence of SMN was 12.5%. The incidence rate ratio (IRR) of developing SMN in survivors of AYA cancer was 2.6 (95% CI, 2.4-2.9) compared with the comparison cohort. Survivors of breast cancer, melanoma, and testicular cancer had substantially elevated risk for SMN of the same organ (IRR, 5.6 [95% CI, 4.6-6.8], 11.2 [95% CI, 7.3-17.2], and 16.2 [95% CI, 6.8-38.4], respectively). Among survivors of AYA cancer, older age (IRR for age 30-39 years, 1.79 [95% CI, 1.21-2.65]), female sex (IRR, 1.31 [95% CI, 1.09-1.57]), white race/ethnicity (IRR for Asian race, 0.61 [95% CI, 0.43-0.87]), advanced stage at first cancer diagnosis (IRR for stage II, 1.29 [95% CI, 1.11-1.65]), and use of radiotherapy (IRR, 1.50 [95% CI, 1.26-1.79]) were associated with increased risk of SMN. Survivors of AYA cancer who developed SMN had an all-cause mortality rate 7.2 (95% CI, 6.1-8.5) times greater than survivors without SMN. This study suggests that SMN risk is elevated in survivors of AYA cancer and varies across survivor subgroups. Survival following SMN may be significantly compromised. These data may form the basis for identifying individuals at high risk, as well as informing screening for SMN.
Highlights
Second malignant neoplasms (SMN) are among the most debilitating late effects in cancer survivors.[1,2] In survivors of childhood cancers, second malignant neoplasms (SMN) is the most common cause of non–relapserelated mortality.[3]
The incidence rate ratio (IRR) of developing SMN in survivors of AYA cancer was 2.6 compared with the comparison cohort
Melanoma, and testicular cancer had substantially elevated risk for SMN of the same organ (IRR, 5.6 [95% CI, 4.6-6.8], 11.2 [95% CI, 7.3-17.2], and 16.2 [95% CI, 6.8-38.4], respectively)
Summary
Second malignant neoplasms (SMN) are among the most debilitating late effects in cancer survivors.[1,2] In survivors of childhood cancers, SMN is the most common cause of non–relapserelated mortality.[3] In an analysis using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) data, the majority of individuals with 2 primary cancers died of their SMN rather than their initial cancer.[4] prevention and early detection of SMN are critical for prolonging life for cancer survivors.[5,6]. Extensive effort has been made to characterize SMN in survivors of childhood cancer.[7,8,9,10,11] this knowledge may not be applicable to survivors of cancers diagnosed later in life. The risk and risk factors for SMN vary across age groups because of differences in primary cancers, treatment exposures, age at exposures, exposure to other etiological factors, and background incidence,[12] necessitating age-specific approaches for managing SMN risk among cancer survivors
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