Late mortality from other diseases following childhood cancer in Australia and the impact of intensity of treatment

Abstract

Background People who receive treatment for cancer during childhood often experience subsequent complications of therapy, known as late effects, which can lead to an increased risk of death. Procedure Using deidentified population‐based data from the Australian Childhood Cancer Registry for children aged 0‐14 diagnosed with cancer during the period 1983‐2011 and who survived for a minimum of 5 years, we examined disease‐related deaths (other than cancer recurrence or second primary cancers) that occurred up to 31 December 2016. Risk of death relative to the general population was approximated using standardised mortality ratios (SMRs). Treatment received was stratified according to the intensity of treatment rating, version 3 (ITR‐3). Results During the study period, 82 noncancer disease‐related deaths were recorded among 13 432 childhood cancer survivors, four times higher than expected (SMR = 4.43, 95% CI = 3.57‐5.50). A clear link to treatment intensity was observed, with the relative risk of noncancer disease‐related mortality being twice as high for children who underwent ‘most intensive’ treatment (SMR = 5.94, 95% CI = 3.69‐9.55) compared to the ‘least intensive’ treatment group (SMR = 2.98, 95% CI = 1.42‐6.24; Ptrend = .01). Thirty‐year cumulative mortality from noncancer disease‐related deaths was estimated at 1.4% (95% CI = 1.1‐1.9) after adjusting for competing causes of death such as cancer, accidents, or injuries. Conclusions Although childhood cancer survivors are at increased relative risk of death from noncancer diseases, particularly those who undergo more intensive treatment, the cumulative mortality within 30 years of diagnosis remains small. Knowledge of late effects can guide surveillance of survivors and treatment modification, without wanting to compromise the high rates of survival.

Long‐term childhood cancer survival in Australia using period estimation

“…10 In addition, 5-year survivors of childhood cancer have been shown to experience more than a four-fold increased risk of non-cancer disease-related death compared to other people matched by age and sex, with a higher risk among patients who received more intensive treatment. 3 Current literature on population-based long-term survival following childhood cancer is limited. Ten-year observed survival for all patients combined has been estimated at 82% in Canada (2013-2017, for ages 0-14), 11 81% in France (2000-2015, for ages 0-14) 12 and 80% in the Netherlands (2010-2015, for ages 0-17), 13 compared to the 85% relative survival reported here for Australia (2014-2018, for ages 0-14).…”

“…It has also been associated with worse health‐related quality of life among parents of survivors 10 . In addition, 5‐year survivors of childhood cancer have been shown to experience more than a four‐fold increased risk of non‐cancer disease‐related death compared to other people matched by age and sex, with a higher risk among patients who received more intensive treatment 3 …”

“…1 Nonetheless, 5-year survivors of childhood cancer are known to be at continuing risk of late effects from treatment, including conditions that may be life-threatening. 2,3 In the current study, we assess longer term relative survival for childhood cancer in Australia, using a statistical method designed to produce the most contemporary results possible.…”