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Brief Report
November 2017

Second Primary Malignant Neoplasms and Survival in Adolescent and Young Adult Cancer Survivors

Author Affiliations
  • 1Center for Oncology Hematology Outcomes Research and Training (COHORT), Division of Hematology and Oncology, University of California, Davis, School of Medicine, Sacramento
  • 2Department of Radiation Medicine, Oregon Health and Science University, Portland
  • 3John Wayne Cancer Institute at Providence Saint John’s Health Center, Santa Monica, California
JAMA Oncol. 2017;3(11):1554-1557. doi:10.1001/jamaoncol.2017.0465
Key Points

Question  Do second primary malignant neoplasms (SPMs) have a similar detrimental impact on survival for children, adolescents and young adults (AYAs), and older adults?

Findings  In this cohort study, the impact of SPMs on survival was more pronounced in children and AYAs than older adults. Adolescents and young adults with a second Hodgkin lymphoma, sarcoma, or breast, thyroid, or testicular cancers had a greater than 2-fold increased risk of cancer-specific death than those with the same primary malignant neoplasms, but no prior cancer.

Meaning  The adverse impact of SPMs on survival is substantial for AYAs and may partially explain the relative lack of survival improvement in AYAs compared with older adults with the same cancers.


Importance  Although the increased incidence of second primary malignant neoplasms (SPMs) is a well-known late effect after cancer, few studies have compared survival after an SPM to survival of the same cancer occurring as first primary malignant neoplasm (PM) by age.

Objective  To assess the survival impact of SPMs in adolescents and young adults (AYAs) (15-39 years) compared with that of pediatric (<15 years) and older adult (≥40 years) patients with the same SPMs.

Design, Setting, and Participants  This was a population-based, retrospective cohort study of patients with cancer in 13 Surveillance, Epidemiology and End Results regions in the United States diagnosed from 1992 to 2008 and followed through 2013. Data analysis was performed between June 2016 and January 2017.

Main Outcomes and Measures  Five-year relative survival was calculated overall and for each cancer occurring as a PM or SPM by age at diagnosis. The impact of SPM status on cancer-specific death was examined using multivariable Cox proportional hazards regression.

Results  A total of 15 954 pediatric, 125 750 AYAs, and 878 370 older adult patients diagnosed as having 14 cancers occurring as a PM or SPM were included. Overall, 5-year survival after an SPM was 33.1% lower for children, 20.2% lower for AYAs, and 8.3% lower for older adults compared with a PM at the same age. For the most common SPMs in AYAs, the absolute difference in 5-year survival was 42% lower for secondary non-Hodgkin lymphoma, 19% for secondary breast carcinoma, 15% for secondary thyroid carcinoma, and 13% for secondary soft-tissue sarcoma. Survival by SPM status was significantly worse in younger vs older patients for thyroid, Hodgkin lymphoma, non-Hodgkin lymphoma, acute myeloid leukemia, soft-tissue sarcoma, and central nervous system cancer. Adolescents and young adults with secondary Hodgkin lymphoma (hazard ratio [95% CI], 3.5 [1.7-7.1]); soft-tissue sarcoma (2.8 [2.1-3.9]); breast carcinoma (2.1 [1.8-2.4]); acute myeloid leukemia (1.9 [1.5-2.4]); and central nervous system cancer (1.8 [1.2-2.8]) experienced worse survival compared with AYAs with the same PMs.

Conclusion and Relevance  The adverse impact of SPMs on survival is substantial for AYAs and may partially explain the relative lack of survival improvement in AYAs compared with other age groups. The impact of a particular SPM diagnosis on survival may inform age-specific prevention, screening, treatment, and survivorship recommendations.