Photo by Bill Branson
Child with cancer
Childhood cancer survivors (CCSs) who were diagnosed in the 1990s have a lower risk of subsequent malignancies than CCSs diagnosed in the 1970s, according to research published in JAMA.
The data suggest this outcome is associated with a reduction in the overall use and median dose of therapeutic radiation over time.
Past research has shown an association between therapeutic radiation and the development of subsequent neoplasms in CCSs. Studies have also linked specific chemotherapeutic agents to subsequent neoplasms.
This information has been used to modify childhood cancer treatment over time, with the hope of reducing the risk of subsequent neoplasms while maintaining or improving 5-year survival.
To assess the effects of these treatment modifications, Gregory Armstrong, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted a study of CCSs.
The researchers evaluated 23,603 five-year CCSs (mean age at diagnosis, 7.7 years) treated at pediatric hospitals in the US and Canada from 1970 through 1999, with follow-up through December 2015.
The most common initial diagnoses were acute lymphoblastic leukemia (35.1%), Hodgkin lymphoma (11.1%), and astrocytoma (9.6%).
Subsequent neoplasms, malignancies
At a mean follow-up of 20.5 years, 1639 CCSs had experienced 3115 subsequent neoplasms, including 1026 malignancies, 233 benign meningiomas, and 1856 non-melanoma skin cancers. The most common neoplasms were breast and thyroid cancers.
The 15-year cumulative incidence of subsequent neoplasms decreased by decade of diagnosis. The incidence was 2.9% for patients diagnosed in the 1970s, 2.4% for those diagnosed in the ’80s, and 1.5% for those diagnosed in the ’90s. For the 1970s vs 1980s, the P value was 0.02. For the 1970s vs 1990s and for the 1980s vs 1990s, the P value was <0.001.
The 15-year cumulative incidence of subsequent malignancies also decreased by decade of diagnosis—2.1% for the ’70s, 1.7% for the ’80s, and 1.3% for the ’90s. The P value was <0.001 for the ’70s vs the ’90s and the ’80s vs the ’90s.
Risk factors
In multivariable analyses, female CCSs had a higher rate of subsequent neoplasms (including malignancies) than males.
In addition, high doses of alkylating agents and platinum agents were associated with increased rates of subsequent malignancies.
The researchers noted that, although there was a decrease in the median cumulative dose of alkylating agents over time, the proportion of CCSs receiving these agents increased. And both the median cumulative dose of platinum agents and the proportion of CCSs receiving these agents increased from the ’70s to the ’90s.
Finally, therapeutic radiation was associated with increased rates of subsequent malignant neoplasms, meningiomas, and non-melanoma skin cancers.
This corresponded with the researchers’ findings that the proportion of individuals receiving radiation and the median dose of radiation both decreased over time.
The proportion of individuals receiving any radiation therapy was 77.7% in the ’70s, 56.7% in the ’80s, and 36.8% in the ’90s. The median dose of radiation was 30.0 Gy in the ’70s, 24.0 Gy in the ’80s, and 26.0 Gy in the ’90s.
“The most ominous late effect of pediatric cancer treatment is a second malignancy,” Dr Armstrong said. “This study shows efforts to reduce the late effects of treatment are paying off. The risk of second cancers for survivors increases with age, so it is good to see the reduction emerging early in survivorship while survivors are still young.”
