Childhood cancer survivors at earlier risk for aging-related disease

Those who had cancer as children are more likely to develop certain aging-associated diseases earlier, a recent study found.

In a simulation modeling study, researchers used data from the Childhood Cancer Survivor Study and U.S. national databases to estimate lifetime risk for eight types of cancer and cardiovascular conditions in those who had cancer as children versus the general population. Long-term outcomes for five-year survivors diagnosed between 1970 and 1999 were projected based on treatment exposures and age-related risks and compared with age-, sex-, and calendar year-matched people from the general population with only age-related risk. Risks were stratified by radiation exposure. The study results were published March 20 by JAMA Oncology.

The health conditions included in the study were breast cancer, colorectal cancer, glial tumors, sarcomas, heart failure, coronary heart disease/myocardial infarction, stroke, and valvular disease. Twenty percent of the general population developed at least one of these health conditions by age 65.0 years, while five-year survivors had reached this threshold at age 47.3 years, for a 17.7-year (95% uncertainty interval [UI], 14.0-year to 21.0-year) acceleration in disease onset. Fifty-five percent of survivors were projected to develop at least one of the eight conditions by age 65 years, for a 2.7-fold (95% UI, 2.2-fold to 3.5-fold) higher relative risk and a 34.2% (95% UI, 28.3% to 42.5%) absolute excess risk versus the general population. Risk was higher in those who had received radiation therapy as children (earlier onset by 22.0 years [95% UI, 18.0 to 25.0 years]; 37.3% excess risk [95% UI, 31.6% to 44.7%]), but risk was still elevated in survivors who had not undergone radiation (earlier onset by 13.5 years [95% UI, 10.0 to 16.0]; 31.0% excess risk [95% UI, 23.9% to 40.3%]). At age 40 years, childhood cancer survivors had a 6.2-fold higher risk (95% UI, 4.8-fold to 9.4-fold) versus the general population for developing a new condition within 10 years.

The researchers noted that the Childhood Cancer Survivor Study includes mostly White, non-Hispanic patients and does not include any patients diagnosed after 1999, among other limitations. They concluded that their study indicates considerably accelerated aging among childhood cancer survivors in terms of chronic health conditions, with projected development 10 to 20 years earlier than expected and risks up to three times higher versus the general population. “Our findings underscore the importance of prioritizing cancer and [cardiovascular disease] prevention and screening for survivors decades earlier than for the general population, regardless of diagnosis or prior radiation exposure,” they wrote.

An accompanying editorial pointed out additional limitations to the study, including lack of inclusion of modifiable or cardiovascular risk factors and lack of clarity regarding the choice to assess these particular eight conditions and radiation therapy as the only treatment to potentially accelerate aging. However, the editorialists agreed that the study provides evidence for premature occurrence of and higher risk for chronic health conditions in survivors of childhood cancer diagnosed between 1970 and 1999 and reinforces the need for earlier preventive strategies.

In related news, the American Heart Association released a scientific statement last week on cardiovascular toxicity in patients treated for childhood cancer. The statement, which was published March 19 by Circulation, addresses the cardiotoxicity of anthracycline therapy and radiotherapy, potential cardiac complications of novel new treatments such as small-molecule therapy and immunotherapies, and cardiometabolic considerations, as well as information on surveillance and survivorship, exercise and rehabilitation, and clinical management of cardiotoxicity.