Risk of a second cancer in Canadians diagnosed with a first cancer in childhood or adolescence

Background: Second cancers are an adverse outcome experienced by childhood cancer survivors. We quantify the risk and correlates of a second cancer in Canadians diagnosed with a first cancer prior to age 20 years. Methods: Using death-linked Canadian Cancer Registry data, a population-based cohort diagnosed with a first cancer between 1992 and 2014, prior to age 20 years, were followed for occurrence of a second cancer to the end of 2014. We estimate standardized incidence ratios (SIR), absolute excess risks (AER), cumulative probabilities, and hazard ratios (HR). Findings: 22,635 people contributed 204,309.1 person-years of follow-up. Overall risk of a second cancer was 6.5 (95% CI: 5.8-7.1) times greater than expected resulting in an AER of 16.5 (14.4-18.5) cancers per 10,00 0 person-years and a 4.8% (3.8%-6.0%) cumulative probability of a second cancer at 22.6 years of follow-up. SIRs decreased with increasing age at diagnosis and time since diagnosis; were larger in more recent calendar periods of diagnosis; and varied by type of first cancer. Large SIRs in the first year after diagnosis and in those diagnosed in 2010-2014 were partly associated with changing registry practices. For the whole cohort, factors associated with the hazard of a second cancer included: being female vs. male [HR = 1.439 (95%CI: 1.179-1.760)]; being diagnosed in 2005-2014 vs. 1992-2004 [2.084 (1.598-2.719)]; having synchronous first cancers [4.814 (2.042-9.509)]; and being diagnosed with certain types of cancer. Factors varied, however, by type of first cancer. Interpretation: Risks of a second cancer are not equally distributed and can be impacted by changes in registry practice and the methods used to define second cancers. (C) 2019 Published by Elsevier Ltd.