Long-term inpatient disease burden in the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study : A cohort study of 21,297 childhood cancer survivors

Background Survivors of childhood cancer are at increased risk for a wide range of late effects. However, no large population-based studies have included the whole range of somatic diagnoses including subgroup diagnoses and all main types of childhood cancers. Therefore, we aimed to provide the most detailed overview of the long-term risk of hospitalisation in survivors of childhood cancer. Methods and findings From the national cancer registers of Denmark, Finland, Iceland, and Sweden, we identified 21,297 5-year survivors of childhood cancer diagnosed with cancer before the age of 20 years in the periods 1943-2008 in Denmark, 1971-2008 in Finland, 1955-2008 in Iceland, and 1958-2008 in Sweden. We randomly selected 152,231 population comparison individuals matched by age, sex, year, and country (or municipality in Sweden) from the national population registers. Using a cohort design, study participants were followed in the national hospital registers in Denmark, 1977-2010; Finland, 1975-2012; Iceland, 1999-2008; and Sweden, 1968-2009. Disease-specific hospitalisation rates in survivors and comparison individuals were used to calculate survivors' standardised hospitalisation rate ratios (RRs), absolute excess risks (AERs), and standardised bed day ratios (SBDRs) based on length of stay in hospital. We adjusted for sex, age, and year by indirect standardisation. During 336,554 person-years of follow-up (mean: 16 years; range: 0-42 years), childhood cancer survivors experienced 21,325 first hospitalisations for diseases in one or more of 120 disease categories (cancer recurrence not included), when 10,999 were expected, yielding an overall RR of 1.94 (95% confidence interval [95% CI] 1.91-1.97). The AER was 3,068 (2,980-3,156) per 100,000 person-years, meaning that for each additional year of follow-up, an average of 3 of 100 survivors were hospitalised for a new excess disease beyond the background rates. Approximately 50% of the excess hospitalisations were for diseases of the nervous system (19.1% of all excess hospitalisations), endocrine system (11.1%), digestive organs (10.5%), and respiratory system (10.0%). Survivors of all types of childhood cancer were at increased, persistent risk for subsequent hospitalisation, the highest risks being those of survivors of neuroblastoma (RR: 2.6 [2.4-2.8]; n = 876), hepatic tumours (RR: 2.5 [2.0-3.1]; n = 92), central nervous system tumours (RR: 2.4 [2.3-2.5]; n = 6,175), and Hodgkin lymphoma (RR: 2.4 [2.3-2.5]; n = 2,027). Survivors spent on average five times as many days in hospital as comparison individuals (SBDR: 4.96 [4.94-4.98]; n = 422,218). The analyses of bed days in hospital included new primary cancers and recurrences. Of the total 422,218 days survivors spent in hospital, 47% (197,596 bed days) were for new primary cancers and recurrences. Our study is likely to underestimate the absolute overall disease burden experienced by survivors, as less severe late effects are missed if they are treated sufficiently in the outpatient setting or in the primary health care system. Conclusions Childhood cancer survivors were at increased long-term risk for diseases requiring inpatient treatment even decades after their initial cancer. Health care providers who do not work in the area of late effects, especially those in primary health care, should be aware of this highly challenged group of patients in order to avoid or postpone hospitalisations by prevention, early detection, and appropriate treatments.Peer reviewe

Kidney disease in very long‐term survivors of Wilms tumor: A nationwide cohort study with sibling controls

Abstract Background Survival after Wilms tumor has significantly increased and focus on late effects has become increasingly important. However, knowledge about long‐term renal function in survivors of Wilms tumor is missing. Our aim was to investigate evidence of kidney disease in 20‐ or more‐year survivors of Wilms tumor in a clinical setting, with siblings as comparisons. Methods In this cross‐sectional study, we established a cohort of Danish 20‐plus‐year survivors of Wilms tumor and siblings as controls. Participants answered a comprehensive health questionnaire supplemented by measurements of estimated glomerular filtration rate (eGFR), urine albumin‐to‐creatinine ratio, and blood pressure and were categorized according to the chronic kidney disease classification. Multiple linear regression analysis, taking family membership into account, was used to describe the differences in eGFR. Logistic regression analysis was performed to describe risk factors for the development of kidney disease. Results We included 99 survivors of Wilms tumor and 38 sibling controls with a median of 37 years of follow‐up. The eGFR of Wilms tumor survivors was 13 ml/min/1.73 m2 (95% CI –20; −5) lower when compared to sibling control. Evidence of kidney disease, with risk factors as hypertension and diabetes, was found in 19% of the Wilms tumor survivors and 2% developed end‐stage renal disease. Ninety‐two percent of the Wilms tumor survivors had an eGFR >60 ml/min/1.732. Conclusion Long‐term Wilms tumor survivors have on average a significantly decreased renal function along with the increased prevalence of kidney disease and end‐stage renal disease when compared to sibling controls. Still, most survivors had kidney function within the normal range

Disease-specific hospitalizations among 5-year survivors of Wilms tumor : A Nordic population-based cohort study

Background: With modern therapy, over 90% of Wilms tumor patients can expect to become long-term survivors, and focus on morbidity and late effects become increasingly important. We provide a novel evaluation and insight to subsequent hospitalizations in 5-year survivors of Wilms tumor. Methods: As part of the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study, we identified 5-year survivors of Wilms tumor. Based on stratified random sampling, we constructed a population comparison cohort. Outcomes of interest were overall hospitalizations; hospitalizations for specific organ systems and disease-specific categories. Standardized hospitalization rate ratios (SHRR) and absolute excess risks (AER) were calculated. Results: We included 913, 5-year survivors of Wilms tumor and 152 231 population comparisons. Survivors of Wilms tumor had an increased overall risk of being hospitalized (SHRR 1.8; 95% confidence interval (CI) 1.7-2.0). The hospitalization risk was increased within all major organ systems: urinary and genital organs (SHRR 2.5; 95% CI 2.1-3.0), endocrine (SHRR 2.5; 95% CI 1.9-3.3), cardiovascular (SHRR 2.2; 95% CI 1.7-2.9), and gastrointestinal (SHRR 1.5; 95% CI 1.3-1.8). Risks for specific diseases are reported in the study. Conclusions: Survivors of Wilms tumor had higher risks than population comparisons for a wide range of diseases, with the highest risks seen for urinary, endocrine, and cardiovascular disorders. Five to 20 years after the Wilms tumor diagnosis, 43% of survivors had been hospitalized at least once versus 29% of population comparisons. The overall AER was 2.3, which translates into 0.2 extra hospitalizations in 10 years for every Wilms tumor survivor

Measuring childhood cancer late effects: evidence of a healthy survivor effect

To access publisher's full text version of this article click on the hyperlink belowGiven considerable focus on health outcomes among childhood cancer survivors, we aimed to explore whether survivor bias is apparent during long-term follow-up of childhood cancer survivors. METHODS: We identified all 1-year survivors of cancer diagnosed before 20 years of age in Denmark, Finland, Iceland, and Sweden. From the general population, we randomly sampled a comparison cohort. Study individuals were followed for hospitalizations for diseases of the gastroenterological tract, endocrine system, cardiovascular system, or urinary tract from the start of the cancer registries to 2010. We estimated cumulative incidence with death as competing risk and used threshold regression to compare the hazards of the diseases of interest at ages 20, 40, 60, and 75 years. RESULTS: Our study included 27,007 one-year survivors of childhood cancer and 165,620 individuals from the general population. The cumulative incidence of all four outcomes was higher for childhood cancer survivors during early adulthood, but for three outcomes, the cumulative incidence was higher for the general population after age 55 years. The hazard ratios (HRs) decreased for all outcomes with increasing age, and for two of the outcomes, the hazards were higher for the general population at older ages (endocrine diseases: age-specific HRs = 3.0, 1.4, 1.0, 0.87; Cardiovascular diseases: age-specific HRs = 4.1, 1.4, 0.97, 0.84). CONCLUSIONS: Our findings provide empirical evidence that survivor bias attenuates measures of association when comparing survivors with the general population. The design and analysis of studies among childhood cancer survivors, particularly as this population attains older ages, should account for survivor bias to avoid misinterpreting estimates of disease burden.Danish Council for Strategic Research Danish Child Cancer Foundatio

Hospital contacts for endocrine disorders in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): a population-based cohort study.

The pattern of endocrine disorders in long-term survivors of childhood cancer has not been investigated comprehensively. Here, we aimed to assess the lifetime risk of these disorders in Nordic survivors of childhood cancer

Standardised hospitalisation rate ratios (RRs), absolute excess risks (AERs), and the percentage (%) of total AER for main diagnostic groups and selected disease categories distinguished by AER ≥ 20.

<p>Standardised hospitalisation rate ratios (RRs), absolute excess risks (AERs), and the percentage (%) of total AER for main diagnostic groups and selected disease categories distinguished by AER ≥ 20.</p

Absolute excess risks (AERs) for hospitalisation by age (years).

<p>(A) Infections, new primary cancers, and diseases of the nervous system, circulatory system, and respiratory system. Note that follow-up for new primary cancers started at age 20 years. (B) Benign neoplasms and diseases of the endocrine system; blood and blood-forming organs; digestive system; urinary and genital system; skin and subcutaneous system; and bone, joints, and soft tissue.</p

Standardised hospitalisation rate ratios (RRs) of survivors of all types of childhood cancers.

<p>95% CI, 95% confidence interval; Obs., observed.</p

Characteristics of the study population of 21,297 5-year childhood cancer survivors in four Nordic countries.

<p>Characteristics of the study population of 21,297 5-year childhood cancer survivors in four Nordic countries.</p

Observed and expected numbers of bed days at hospital among 21,297 5-year survivors of childhood cancer and standardised bed day ratios (SBDRs).

<p>Observed and expected numbers of bed days at hospital among 21,297 5-year survivors of childhood cancer and standardised bed day ratios (SBDRs).</p