Radiotherapy increased CV, overall mortality in childhood cancer survivors

Childhood cancer survivors who were treated with radiation are at a significantly increased risk for long-term cardiac mortality.

Researchers observed 4,122 five-year survivors for a median of 26 years — 3,098 were observed for at least 20 years. The cohort was selected from patients treated from 1942 to 1986 for a variety of cancers.

Of the entire cohort, 603 died before Jan. 1, 2003. Researchers said the estimated overall standardized mortality ratio was 8.3-times that expected in the general population (95% CI, 7.6-9.0) and the absolute excess risk was six deaths per 1,000 person-years. The overall standardized mortality ratio was highest five to nine years after diagnosis.

Second cancers were responsible for 11.9% of deaths; 6.4% of deaths were cardiac-related. The researchers found that patients were five-times more likely to die from cardiovascular causes and 5.8-times more likely to die of CVDs than the general population. Thirty-five years after diagnosis, estimated CV mortality was 1.7% (95% CI, 1.2%-2.8%) compared with 0.3% in the general population.

CV standardized mortality ratio increased after radiotherapy and administration of alkylating agents, vinca alkaloids, anthracyclines and antimetabolites. The adjusted RR for death was 5.0 (95% CI, 1.2-21.4) for radiotherapy and 3.6 for vinca alkaloids (95% CI, 1.0-12.9).

The 21 patients who died of cardiac disease received a mean average radiation dose to the heart of 11.1 Gy and a mean cumulative dose of anthracyclines of 132.5 mg/m². After adjusting for a variety of factors, the adjusted RR for cardiac disease was 7.4 (95% CI, 1.0-56.5) among patients treated with radiotherapy. RR increased with increasing average radiation dose received by the heart and with cumulative exposure to anthracyclines of more than 360 mg/m² of the body-surface area (RR=4.4; 95% CI, 1.3-15.3).

In an accompanying editorial, Steven E. Lipshultz, MD, of the University of Miami Sylvester Comprehensive Cancer Center, and M. Jacob Adams, MD, MPH, of the University of Rochester School of Medicine and Dentistry, N.Y., praised the researchers for not only validating previous studies of overall cardiac mortality, but also providing new data on cumulative anthracycline dose, cumulative radiation dose and the contribution of other agents.

“The results of the Tukenova et al study again highlight the need to optimize the screening of survivors of childhood cancer to detect both second cancers and [CVD],” they wrote. “The study cannot identify which specific modalities will be most useful for various treatments, but we believe that information from this cohort could help address specific associations between certain treatments and specific cardiovascular causes of death.”

Tukenova M. J Clin Oncol. 2010;doi:10.1200.JCO.2008.20.2267.

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