# Subsequent Primary Neoplasms and Mortality Among Survivors of Childhood Cancer in Alberta, Canada

## TL;DR

Childhood cancer survivors in Alberta face higher risks of new cancers and death compared to the general population, emphasizing the need for long-term care.

## Contribution

This study quantifies the elevated risks of subsequent cancers and mortality in modern childhood cancer survivors using a population-based cohort in Alberta.

## Key findings

- Survivors had 13.3-fold higher subsequent cancer incidence compared to the general population.
- Mortality rates were 62.5-fold higher overall among childhood cancer survivors.
- Excess deaths were mainly due to cancer recurrence, with new cancers and non-cancer causes increasing over time.

## Abstract

Children diagnosed with cancer face a higher risk of chronic health conditions and death both in the short term and long term. With improvements in treatment over the last 20 years, the risk of late effects and overall survival have changed, but there are relatively few studies examining how these risks changed over time. This study followed 2581 children diagnosed from 2001 to 2018 in Alberta, Canada, until 31 December 2018. We identified those who developed a subsquent cancer and those who died during our follow-up and compared these rates to what was expected in the general population of Alberta. Children diagnosed with cancer experienced more subsequent cancers and deaths compared to the general population; these poor outcomes differed by initial cancer type and the treatment received, and highlight the need for long-term follow-up care for survivors of childhood cancer.

Background: While research shows childhood cancer survivors experience elevated subsequent primary neoplasm (SPN) and premature mortality risks, few studies have included contemporary survivors. Methods: This study quantifies the risk of SPNs and mortality among modern survivors of childhood cancer. Utilizing a retrospective, population-based cohort of individuals diagnosed with cancer before the age of 18 in Alberta, Canada (2001–2018), we evaluated their risks of SPNs and mortality compared to the general population in Alberta, overall and after 5-year survival, using standardized mortality and incidence ratios, and absolute excess risks per 10,000 person-years. Results: Among 2581 survivors, including 1385 5-year survivors, 50 individuals developed at least one SPNs and 408 deaths were observed, with 21 SPNs and 38 deaths occurring after 5-year survival. The SPN incidence was 13.3- (95% CI: 9.8–17.5) and 10.0-fold (95% CI: 6.2–15.2) higher than expected overall and in 5-year survivors, respectively, with risks varying depending on the treatment received. For mortality, survivors experienced 62.5-fold (95% CI: 56.5–68.8) higher mortality than expected overall, equating to 233.9 (95% CI: 210.8–257.0) excess deaths per 10,000 person-years, with corresponding risks among 5-year survivors at 10.9 (95% CI: 7.7–15.0) and 43.8 (95% CI: 28.4–59.1), respectively. The excess deaths were predominantly due to recurrence/progression (89.9% overall, 66.4% in 5-year survivors), with SPNs and non-neoplastic causes contributing more excess deaths with increasing follow-up time. Risks for mortality included treatment and cancer type. Conclusions: Contemporary childhood cancer survivors in Alberta experience substantial excess SPNs and mortality, highlighting the need for long-term surveillance and tailored risk mitigation interventions.