Subsequent neoplasms (SNs), which may be benign or malignant, are defined as histologically distinct neoplasms developing at least 2 months after completion of treatment for the primary malignancy. Childhood cancer survivors have an increased risk of developing SNs that varies according to the following:
- Host factors (e.g., genetics, immune function, hormone status).
- Primary cancer therapy.
- Environmental exposures.
- Lifestyle factors.
SNs are the leading cause of nonrelapse late mortality (standardized mortality ratio, 15.2; 95% CI, 13.9–16.6). The Childhood Cancer Survivor Study (CCSS) reported the following 30-year cumulative incidence rates:
- All SNs—20.5% (95% confidence interval [CI], 19.1%–21.8%).
- SNs with malignant histologies (excluding nonmelanoma skin cancer [NMSC])—7.9% (95% CI, 7.2%–8.5%).
- NMSC—9.1% (95% CI, 8.1%–10.1%).
- Meningioma—3.1% (95% CI, 2.5%–3.8%).
This represents a sixfold increased risk of SNs among cancer survivors, compared with the general population.
The risk of SNs remains elevated for more than 30 years from diagnosis of the primary cancer. Moreover, prolonged follow-up has established that multiple SNs are common among aging childhood cancer survivors.
The development of an SN is likely multifactorial in etiology and results from a combination of influences including gene-environment and gene-gene interactions. Outcome after the diagnosis of an SN is variable, as treatment for some histological subtypes may be compromised if childhood cancer therapy included cumulative doses of agents and modalities at the threshold of tissue tolerance.
The incidence and type of SNs depend on the following:
- Primary cancer diagnosis.
- Type of therapy received.
- Presence of genetic conditions.
Unique associations with specific therapeutic exposures have resulted in the classification of SNs into the following two distinct groups:
- Chemotherapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML).
- Radiation-related solid SNs.
Therapy-Related Myelodysplastic Syndrome and Leukemia
Therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) has been reported after treatment of Hodgkin lymphoma (HL), acute lymphoblastic leukemia (ALL), and sarcomas, with the cumulative incidence approaching 2% at 15 years after therapy.[5,6,7,8]