The rate of death from treatment-related late effects such as subsequent cancers and cardiopulmonary conditions has decreased among childhood cancer survivors, according to researchers.

At 15 years post diagnosis, the cumulative incidence of death from any cause for survivors diagnosed in the 1970s was 10.7%, 7.9% for those diagnosed in the 1980s, and 5.8% for those diagnosed in the 1990s (P less than .001). The cumulative incidence of death due to health-related causes, which include late effects of cancer therapy, were 3.1%, 2.4%, and 1.9%, respectively (P less than .001).

Results indicate that “the strategy of reducing treatment exposures in order to decrease the frequency of late effects is translating into a significant reduction in observed late mortality and an extension of the life span of children and adolescents who are successfully treated for cancer,” wrote Dr. Gregory Armstrong of St. Jude Children’s Research Hospital, Memphis, Tenn., and colleagues (N Engl J Med. 2016 Jan 13. doi: 10.1056/NEJMoa1510795 ).

A multivariate model showed that more recent treatment eras were associated with a reduced rate of death. The adjusted relative rate per every 5 years for death due to subsequent neoplasms was 0.83 (95% CI, 0.78-0.88), for cardiac causes, 0.77 (0.68-0.86), and for pulmonary causes, 0.77 (0.66-0.89).

Reductions across treatment eras in the rate of death from health-related causes were observed among survivors of acute lymphoblastic leukemia (3.2% in the early 1970s to 2.1% in the 1990s, P less than .001), Hodgkin lymphoma (5.3% to 2.6%, P = .006), Wilms tumor (2.6% to 0.4%, P = .005), and astrocytoma (4.7% to 1.8%, P = .02).

Temporal reductions in exposure to radiotherapy and anthracyclines occurred in treatment for acute lymphoblastic leukemia, Hodgkin lymphoma, Wilms tumor, and astrocytoma. Health-related mortality reductions were observed concurrently with reduced therapeutic exposures for acute lymphoblastic leukemia and Wilms tumor. For Hodgkin lymphoma and astrocytoma, other factors such as improved screening for late effects of cancer treatment appear to account for reductions in late health-related mortality.

For certain cancers, primarily neuroblastoma, late mortality has increased in recent decades. Increased therapeutic intensity has improved 5-year survival but increased the risk of late effects.

The reduced rate of death from recurrence or progression of primary cancers is the main driver to reductions in all-cause mortality, consistent with results from previous studies.

The retrospective Childhood Cancer Survivor Study evaluated 34,033 patients diagnosed at 31 hospitals in the United States and Canada from 1970 through 1999. In total, 3,958 deaths occurred, 2,002 due to primary cancer and 1,618 due to health-related causes: 746 subsequent neoplasms, 241 cardiac causes, 137 pulmonary causes, and 494 from other causes.