The increased risk of malignancy following childhood cancer persists past the age of 40 years, according to an analysis of 3,171 members of the Childhood Cancer Survivor Study published online Aug. 10 in the Journal of Clinical Oncology.

Survivors “have a substantial risk of a new malignancy in the fifth and sixth decades of life in excess of what is expected among the general U.S. population … Being free of SN [subsequent neoplasms] before age 40 years does not preclude survivors from having an increased risk of future [neoplasms] … These data suggest the need for life-long monitoring and should inform anticipatory guidance provided to survivors of childhood cancer,” said the investigators, led by Dr. Lucie Turcotte, a pediatric oncologist at the University of Minnesota, Minneapolis (J Clin Oncol. 2015 Aug 10. doi: 10.1200/JCO.2015.60.9487).

The Childhood Cancer Survivor Study (CCSS) is an ongoing project to gauge the late effects of childhood cancers. Previous reports found an increased risk of malignancy in early adulthood.

The 3,171 patients in the latest analysis were diagnosed from the period of 1970-1986, and had completed at least one follow-up questionnaire after age 40.

Among them, there were 679 subsequent neoplasms (SNs) over the age of 40, including 196 subsequent malignant neoplasms (SMNs) in 180 people, as well as 419 nonmelanoma skin cancers, 21 nonmalignant meningiomas, and 43 other benign neoplasms.

At age 55 years, the cumulative incidence after the age of 40 of new SNs was 34.6% and new SMNs 16.3%.

Survivors were twice as likely as was the general population to be diagnosed with an SMN after age 40 (standardized incidence ratio [SIR] 2.2; 95% CI 1.9-2.5). Among SMNs, risk was increased for breast cancer (SIR 5.5; 95% CI 4.5-6.7), renal cancer (SIR 3.9; 95% CI 2.0-7.5), soft tissue sarcoma (SIR 2.6; 95% CI 1.5- 4.4), and thyroid cancer (SIR 1.9; 95% CI 1.0-3.5).

On multivariate analysis, female sex (relative risk [RR] 1.9; 95% CI 1.3-2.6), platinum chemotherapy (RR 2.3; CI 1.0-5.2), and therapeutic radiation exposure (RR 2.2; 95% CI 1.4-3.3) increased the risk of SMN.

“Therapeutic radiation exposure continues to place survivors at increased risk for SMNs … well into their fifth and sixth decades of life, indicating a need for ongoing monitoring of this at-risk subgroup,” the authors said.

Females and Hodgkin lymphoma survivors were at increased risk for breast cancer, driven by high-dose, chest-directed radiation as children, which was previously a central component of treatment.

Routine mammography is typically started around age 40-50, but “the risks experienced by the survivor population are unique,” and may warrant greater vigilance. “Survivors without an SN before age 40 may be particularly vulnerable because they have not had previous neoplasms that may have altered screening practices,” the investigators said.

They did not find an excess risk for subsequent head, neck, lung, colon, or female genital tract malignancies. “This contrasts with observations in previous CCSS publications showing an increased risk for these malignancies among [younger adult] survivors … It is possible that the period of highest risk for these malignancies among survivors occurs before age 40 years and that, as the incidence of these cancers increases with age in the general population, the risk beyond what is experienced by the general population is diminished,” they said.

Male survivors aged older than 40 years who were not irradiated as children did not have an increased risk of SMNs, regardless of their SN history before age 40.

The work was funded in part by the National Institutes of Health and the Children’s Cancer Research Fund. Dr. Turcotte has no disclosures.


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