Pediatric cancer survivors have an increased risk of late mortality, according to research published in The Lancet.
From 15 to 40 years after diagnosis, pediatric cancer survivors had a roughly 4-fold higher risk of death than the general population, researchers found. They also found independent associations between cancer treatments and death among patients who survived at least 30 years from diagnosis.
In this retrospective study, the researchers evaluated late mortality and causes of death in 34,230 patients who were diagnosed with cancer during 1970-1999. The patients were diagnosed at 20 years of age or younger (median age, 6 years) and survived at least 5 years from diagnosis. Cancer types included leukemia, lymphoma, central nervous system tumors, Wilms’ tumor, neuroblastoma, and soft tissue or bone sarcoma.
The median follow-up from diagnosis was 29.1 years. There were 5916 deaths, of which 2009 (34.0%) were attributed to recurrence or progression of the primary cancer. Another 3061 deaths (51.2%) were attributed to subsequent neoplasms (n=1458), cardiac causes (n=504), pulmonary causes (n=238), and other health-related causes (n=861).
Compared with the general population, the pediatric cancer survivors had an 18.1-fold higher risk of death at 5-9 years from diagnosis. This fell to a 6.2-fold increased risk at 10-14 years. At all subsequent time points — from 15-19 years through 40 years — the cancer survivors had a roughly 4-fold increased risk of death (P <.001 for all time points).
When the analysis was limited to health-related causes of death, the pediatric cancer survivors had a 13.1-fold increased risk of death at 5-9 years from diagnosis. This fell to a 7.6-fold increased risk at 10-14 years and a roughly 5-fold increased risk from 15 years to 39 years. At 40 years, the cancer survivors had a 4.4-fold increased risk of death from health-related causes (P <.001 for all time points).
Pediatric cancer survivors had a higher risk of death from 9 of the 10 of leading causes of health-related death in US adults younger than 60 years, including:
- Subsequent cancer (standardized mortality ratio [SMR], 8.9; 95% CI, 8.5-9.4)
- Influenza and pneumonia (SMR, 8.5; 95% CI, 6.9-10.4)
- Sepsis (SMR, 8.1; 95% CI, 6.3-10.1)
- Kidney failure (SMR, 6.8; 95% CI, 5.0-9.0)
- Cerebrovascular disease (SMR, 5.1; 95% CI, 4.2-6.2)
- Heart disease (SMR, 4.3; 95% CI, 3.9-4.7)
- Diabetes (SMR, 1.7; 95% CI, 1.2-2.3)
- Liver disease (SMR, 1.6; 95% CI, 1.1-2.2)
- Chronic lower respiratory disease (SMR, 1.7; 95% CI, 1.1-2.6).
In a multivariable analysis of the cancer survivors, a healthy lifestyle was associated with a 20% decreased risk of health-related mortality independent of traditional cardiovascular risk factors (P =.002).
The researchers also found independent associations between cancer treatments and death among patients who survived at least 30 years from diagnosis. Cranial irradiation (per 10 Gy) was associated with an increased risk of death from subsequent neoplasms (relative rate [RR], 1.15; 95% CI, 1.09-1.22) and other health-related causes (RR, 1.24; 95% CI, 1.17-1.32).
Chest irradiation (per 10 Gy) was associated with an increased risk of death from subsequent neoplasms (RR, 1.34; 95% CI, 1.26-1.42), cardiac events (RR, 1.60; 95% CI, 1.48-1.72), pulmonary events (RR, 1.41; 95% CI, 1.22-1.62), or other health-related causes (RR, 1.21; 95% CI, 1.12-1.31).
Anthracycline chemotherapy was associated with an increased risk of death from cardiac causes (RR, 1.10; 95% CI, 1.01-1.20 per 100 mg/m² in doxorubicin equivalent dose). Alkylator chemotherapy was associated with an increased risk of death from subsequent neoplasms (RR, 1.07; 95% CI, 1.03-1.12 per 5000 mg/m² in cyclophosphamide equivalent dose).
“Despite improvements in 5-year survival, long-term survivors of childhood cancer are at four times the risk of death compared with the general, aging population,” the researchers concluded. “Continued reductions in intensity of primary cancer therapy and future research targeting interventions for modifiable lifestyle and cardiovascular risk factors in survivors could offer an opportunity to reduce morbidity and extend the lifespan for survivors.”
Dixon SB, Liu Q, Chow EJ, et al. Specific causes of excess late mortality and association with modifiable risk factors among survivors of childhood cancer: A report from the Childhood Cancer Survivor Study cohort. Lancet. Published online April 5, 2023. doi:10.1016/S0140-6736(22)02471-0