Disease-specific Hospitalizations Among 5-Year Survivors of Hepatoblastoma: A Nordic Population-based Cohort Study.

INTRODUCTION: The long-term risk of somatic disease in hepatoblastoma survivors has not been thoroughly evaluated in previous studies. In this population-based study of 86 five-year HB survivors, we used inpatient registers to evaluate the risk for a range of somatic diseases. METHODS: In total, 86 five-year survivors of hepatoblastoma were identified in the Nordic cancer registries from 1964 to 2008 and 152,231 population comparisons were selected. Study subjects were followed in national hospital registries for somatic disease classified into 12 main diagnostic groups. Standardized hospitalization rate ratios (RRs) and absolute excess risks were calculated. RESULTS: After a median follow-up of 11 years, 35 of the 86 five-year hepatoblastoma survivors had been hospitalized with a total of 69 hospitalizations, resulting in an RR of 2.7 (95% confidence interval [CI], 2.2-3.5) and an overall absolute excess risk of 4.2 per 100 person-years. Highest risk was seen for benign neoplasms (RR=16) with 6 hospitalizations for benign neoplasms in the colon and one in rectum. CONCLUSIONS: The pattern of hospitalizations found in this first comprehensive follow-up of hepatoblastoma survivors seems reassuring. Less than 50% of the 5-year survivors had been hospitalized and often for diseases that were not severe or life-threatening.

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.

The Adult Life After Childhood Cancer in Scandinavia (ALiCCS) Study: Design and Characteristics.

BACKGROUND: During the last five decades, survival of childhood cancer has increased from 25% to 80%. At the same time, however, it has become evident that survivors experience a broad range of therapy-related late adverse health effects. The aim of the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study is to investigate long-term health consequences of past and current therapies in order to improve follow-up care of survivors and to reduce treatment-related morbidity of future patients. PROCEDURE: Childhood cancer survivors were identified through the five Nordic cancer registries and a comparison cohort was established through random selection of cancer-free individuals from the civil registration systems. A unique personal identification number was used to link between different health registries. Abstraction of treatment information for a subset of survivors allows investigation of the association between the various components of cancer therapy and late occurring comorbidity. RESULTS: The childhood cancer survivor cohort comprises 33,160 1-year survivors and the comparison cohort comprises 212,892 cancer free individuals from the general population. In the childhood cancer survivor cohort, all types of childhood cancer are represented including leukemia (21%), lymphoma (14%), central nervous system tumors (24%), sarcomas (5%), retinoblastoma (3%), and neuroblastoma (4%). Among the survivors, 22% have been followed beyond the age of 40 years. CONCLUSION: The ALiCCS study constitutes a new large resource for research on late effects of childhood cancers that include all types of childhood malignancies and has followed a large proportion of the survivors well into late adulthood.

Childhood cancer survivor cohorts in Europe.

With the advent of multimodality therapy, the overall five-year survival rate from childhood cancer has improved considerably now exceeding 80% in developed European countries. This growing cohort of survivors, with many years of life ahead of them, has raised the necessity for knowledge concerning the risks of adverse long-term sequelae of the life-saving treatments in order to provide optimal screening and care and to identify and provide adequate interventions. Childhood cancer survivor cohorts in Europe. Considerable advantages exist to study late effects in individuals treated for childhood cancer in a European context, including the complementary advantages of large population-based cancer registries and the unrivalled opportunities to study lifetime risks, together with rich and detailed hospital-based cohorts which fill many of the gaps left by the large-scale population-based studies, such as sparse treatment information. Several large national cohorts have been established within Europe to study late effects in individuals treated for childhood cancer including the Nordic Adult Life after Childhood Cancer in Scandinavia study (ALiCCS), the British Childhood Cancer Survivor Study (BCCSS), the Dutch Childhood Oncology Group (DCOG) LATER study, and the Swiss Childhood Cancer Survivor Study (SCCSS). Furthermore, there are other large cohorts, which may eventually become national in scope including the French Childhood Cancer Survivor Study (FCCSS), the French Childhood Cancer Survivor Study for Leukaemia (LEA), and the Italian Study on off-therapy Childhood Cancer Survivors (OTR). In recent years significant steps have been taken to extend these national studies into a larger pan-European context through the establishment of two large consortia - PanCareSurFup and PanCareLIFE. The purpose of this paper is to present an overview of the current large, national and pan-European studies of late effects after childhood cancer. This overview will highlight the strong cooperation across Europe, in particular the EU-funded collaborative research projects PanCareSurFup and PanCareLIFE. Overall goal. The overall goal of these large cohort studies is to provide every European childhood cancer survivor with better care and better long-term health so that they reach their full potential, and to the degree possible, enjoy the same quality of life and opportunities as their peers.

Cardiovascular disease in Adult Life after Childhood Cancer in Scandinavia: A population-based cohort study of 32,308 one-year survivors.

The lifetime risk for cardiovascular disease in a large cohort of childhood cancer survivors has not been fully assessed. In a retrospective population-based cohort study predicated on comprehensive national health registers, we identified a cohort of 32,308 one-year survivors of cancer diagnosed before the age of 20 in the five Nordic countries between the start of cancer registration in the 1940s and 1950s to 2008; 211,489 population comparison subjects were selected from national population registers. Study subjects were linked to national hospital registers, and the observed numbers of first hospital admission for cardiovascular disease among survivors were compared with the expected numbers derived from the population comparison cohort. Cardiovascular disease was diagnosed in 2,632 childhood cancer survivors (8.1%), yielding a standardized hospitalization rate ratio (RR) of 2.1 (95% CI 2.0-2.2) and an overall absolute excess risk (AER) of 324 per 100,000 person-years. At the end of follow-up 12% of the survivors were ≥ 50 years of age and 4.5% ≥ 60 years of age. Risk estimates were significantly increased throughout life, with an AER of ∼500-600 per 100,000 person-years at age ≥ 40. The highest relative risks were seen for heart failure (RR, 5.2; 95% CI 4.5-5.9), valvular dysfunction (4.6; 3.8-5.5) and cerebrovascular diseases (3.7; 3.4-4.1). Survivors of hepatic tumor, Hodgkin lymphoma and leukemia had the highest overall risks for cardiovascular disease, although each main type of childhood cancer had increased risk with different risk profiles. Nordic childhood cancer survivors are at markedly increased risk for cardiovascular disorders throughout life. These findings indicate the need for preventive interventions and continuous follow-up for this rapidly growing population.