Late effects of cancer in children, teenagers and young adults: Population-based study on the burden of 183 conditions, in-patient and critical care admissions and years of life lost

Children, teenagers and young adults who survived cancer are prone to developing late effects. The burden of late effects across a large number of conditions, in-patient hospitalisation and critical care admissions have not been described using a population-based dataset. We aim to systematically quantify the cumulative burden of late effects across all cancer subtypes, treatment modalities and chemotherapy drug classes. We employed primary care records linked to hospitals, the death registry and cancer registry from 1998–2020. CTYA survivors were 25 years or younger at the time of cancer diagnosis had survived ≥5 years post-diagnosis. Year-of-birth and sex-matched community controls were used for comparison. We considered nine treatment types, nine chemotherapy classes and 183 physical and mental health late effects. Cumulative burden was estimated using mean cumulative count, which considers recurring events. Multivariable logistic regression was used to investigate the association between treatment exposures and late effects. Excess years of life lost (YLL) attributable to late effects were estimated. Among 4,063 patients diagnosed with cancer, 3,466 survived ≥ 5 years (85%); 13,517 matched controls were identified. The cumulative burden of late effects at age 35 was the highest in survivors of leukaemia (23.52 per individual [95% CI:19.85–29.33]) and lowest in survivors of germ cell tumours (CI:6.04 [5.32–6.91]). In controls, the cumulative burden was 3.99 (CI:3.93–4.08) at age 35 years. When survivors reach age 45, the cumulative burden for immunological conditions and infections was the highest (3.27 [CI:3.01–3.58]), followed by cardiovascular conditions (3.08 [CI:1.98–3.29]). Survivors who received chemotherapy and radiotherapy had the highest disease burden compared to those who received surgery only. These patients also had the highest burden of hospitalisation (by age 45: 10.43 [CI:8.27–11.95]). Survivors who received antimetabolite chemotherapy had the highest disease and hospitalisation burden, while the lowest burden is observed in those receiving antitumour antibiotics. Regression analyses revealed that survivors who received only surgery had lower odds of developing cardiovascular (adjusted odds ratio 0.73 [CI:0.56–0.94]), haematological (aOR 0.51 [CI:0.37–0.70]), immunology and infection (aOR 0.84 [CI:0.71–0.99]) and renal (aOR 0.51 [CI:0.39–0.66]) late effects. By contrast, the opposite trend was observed in survivors who received chemo-ra