Skeletal adverse events in childhood cancer survivors: An Adult Life after Childhood Cancer in Scandinavia cohort study.

The dynamic growth of the skeleton during childhood and adolescence renders it vulnerable to adverse effects of cancer treatment. The lifetime risk and patterns of skeletal morbidity have not been described in a population-based cohort of childhood cancer survivors. A cohort of 26 334 1-year cancer survivors diagnosed before 20 years of age was identified from the national cancer registries of Denmark, Finland, Iceland and Sweden as well as a cohort of 127 531 age- and sex-matched comparison subjects randomly selected from the national population registries in each country. The two cohorts were linked with data from the national hospital registries and the observed numbers of first-time hospital admissions for adverse skeletal outcomes among childhood cancer survivors were compared to the expected numbers derived from the comparison cohort. In total, 1987 childhood cancer survivors had at least one hospital admission with a skeletal adverse event as discharge diagnosis, yielding a rate ratio (RR) of 1.35 (95% confidence interval, 1.29-1.42). Among the survivors, we observed an increased risk for osteonecrosis with a RR of 25.9 (15.0-44.5), osteoporosis, RR 4.53 (3.28-6.27), fractures, RR 1.27 (1.20-1.34), osteochondropathies, RR 1.57 (1.28-1.92) and osteoarthrosis, RR 1.48 (1.28-1.72). The hospitalization risk for any skeletal adverse event was higher among survivors up to the age of 60 years, but the lifetime pattern was different for each type of skeletal adverse event. Understanding the different lifetime patterns and identification of high-risk groups is crucial for developing strategies to optimize skeletal health in childhood cancer survivors.

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.

Risk of digestive cancers in a cohort of 69 460 five-year survivors of childhood cancer in Europe: the PanCareSurFup study.

BACKGROUND: Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide. METHODS: The PanCareSurFup cohort includes 69 460 five-year survivors of childhood cancer from 12 countries in Europe. Risks of digestive SPNs were quantified using standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence. RESULTS: 427 digestive SPNs (214 colorectal, 62 liver, 48 stomach, 44 pancreas, 59 other) were diagnosed in 413 survivors. Wilms tumour (WT) and Hodgkin lymphoma (HL) survivors were at greatest risk (SIR 12.1; 95% CI 9.6 to 15.1; SIR 7.3; 95% CI 5.9 to 9.0, respectively). The cumulative incidence increased the most steeply with increasing age for WT survivors, reaching 7.4% by age 55% and 9.6% by age 60 years (1.0% expected based on general population rates). Regarding colorectal SPNs, WT and HL survivors were at greatest risk; both seven times that expected. By age 55 years, 2.3% of both WT (95% CI 1.4 to 3.9) and HL (95% CI 1.6 to 3.2) survivors had developed a colorectal SPN-comparable to the risk among members of the general population with at least two first-degree relatives affected. CONCLUSIONS: Colonoscopy surveillance before age 55 is recommended in many European countries for individuals with a family history of colorectal cancer, but not for WT and HL survivors despite a comparable risk profile. Clinically, serious consideration should be given to the implementation of colonoscopy surveillance while further evaluation of its benefits, harms and cost-effectiveness in WT and HL survivors is undertaken.

Hospital admission for neurologic disorders among 5-year survivors of noncentral nervous system tumors in childhood: A cohort study within the Adult Life after Childhood Cancer in Scandinavia study.

Large, comprehensive studies of the risk for neurologic disorders among long-term survivors of noncentral nervous system (CNS) childhood cancers are lacking. Thus, the aim of our study was to assess the lifetime risk of Nordic non-CNS childhood cancer survivors for neurologic disorders. We identified 15,967 5-year survivors of non-CNS childhood cancer diagnosed in Denmark, Iceland, Finland and Sweden in 1943-2008, and 151,118 matched population comparison subjects. In-patient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). A neurologic disorder was diagnosed in 755 of the survivors while 370 were expected, yielding a RR of 2.0 (95% confidence interval (CI) 1.9-2.2). The highest risks were found among survivors of neuroblastoma (4.1; 95% CI 3.2-5.3) and leukemia (2.8; 95% CI 2.4-3.2). The AER decreased from 331 (278-383) excess neurologic disorders per 100,000 person-years 5-9 years after diagnosis to 82 (46-118) ≥ 20 years after diagnosis. Epilepsy was the most common diagnosis (n = 229, 1.4% of all survivors), and significantly increased risks were seen among survivors of eight out of 12 types of childhood cancer. Survivors of neuroblastoma had remarkably high risks (RR ≥ 10) for hospitalization for paralytic syndromes and hydrocephalus, while survivors of leukemia had additional high risks for dementia and encephalopathy. In conclusion, survivors of non-CNS childhood cancer are at high risk for neurologic disorders, especially within the first decade after diagnosis. Therefore, intensive follow-up to identify those who require close management is needed.

Neurologic disorders in long-term survivors of neuroblastoma - a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) research program.

Background: Neuroblastoma is the commonest extracranial solid tumor of childhood, yet rare, and with poor survival before 1990, especially for high-risk disease; thus, information on late effects is sparse. With great advances in cancer treatment, survival has reached 80% in the Nordic countries. The aim of the study was to investigate the risk of developing neurologic disorders after neuroblastoma.Material and methods: Through population-based cancer registries of four Nordic countries we identified 654 5-year survivors of neuroblastoma (diagnosed 1959-2008) and 133,668 matched population comparisons. We grouped neurologic diagnoses from national hospital registries into 11 main diagnostic categories and 56 disease-specific sub-categories and calculated relative risks (RRs), absolute excess risks (AERs), cumulative incidence and mean cumulative count (MCC). Information on cancer treatment was available for 49% of survivors.Results: A hospital contact for a neurologic disorder was observed in 181 survivors 5 years or more from cancer diagnosis with 59 expected, yielding a RR of 3.1 (95% CI 2.7-3.6) and an AER of 16 per 1,000 person-years (95% CI 12-19). The most frequent disorders included epilepsy, paralytic syndromes, diseases of the eyes and ears and hearing loss. The cumulative incidence of any neurologic disorder was 31% in survivors 20 years after cancer diagnosis with a MCC of 0.5 unique diagnoses. All risks were highest in survivors of high-risk neuroblastoma.Conclusion: Neuroblastoma survivors represent a population with a high risk of developing neurologic disorders. Our results should contribute to improving health care planning and underscores the need for systematic follow-up care of this vulnerable group of survivors.

Suicides and deaths linked to risky health behavior in childhood cancer patients: A Nordic population-based register study.

BACKGROUND: Childhood cancer survivors have been reported to be vulnerable to psychiatric morbidities and risky health behavior. Suicides, substance abuse, accidents, and violence as causes of death can be regarded as an extreme manifestation of risky health behavior. In the current study, the authors studied the risk of suicide and other risky health behavior-related deaths among childhood cancer patients in Denmark, Finland, and Sweden. METHODS: Using linkage between national cancer, population, and cause-of-death registries, the authors investigated the causes of death in 29,285 patients diagnosed with cancer before age 20 years between 1971 and 2009 compared with a cohort of 146,282 age-matched, sex-matched, and country-matched population comparisons. Rate ratios (RRs) with 95% CIs were estimated using Poisson regression models, adjusting for demographic factors. RESULTS: The overall risk of dying of a risky health behavior was found to be increased among childhood cancer patients (RR, 1.25; 95% CI, 1.06-1.47) when compared with population comparisons. The elevated risk was statistically significant among patients with central nervous system tumors (RR, 1.49; 95% CI, 1.08-2.05) and patients diagnosed at ages 5 to 9 years and 15 to 19 years (RR, 1.50 [95% CI, 1.01-2.24] and RR, 1.31 [95% CI, 1.03-1.67], respectively). The overall risk of suicide was found to be increased (RR, 1.37; 95% CI, 1.02-1.83), and statistically significantly so when patients were diagnosed between ages 15 and 19 years (RR, 1.61; 95% CI, 1.09-2.39). CONCLUSIONS: Childhood cancer patients appear to have an increased risk of risky health behavior-related causes of death compared with the general population. The results of the current study suggest the importance of integrating psychosocial support into the follow-up care of these individuals.

Hyperthyroidism as a late effect in childhood cancer survivors - an Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study.

BACKGROUND: Hyperthyroidism is a rare disorder which may negatively affect health and quality of life. Its occurrence in childhood cancer survivors has not previously been investigated in detail. MATERIAL AND METHODS: In the hospital registers of the five Nordic countries, 32,944 childhood cancer survivors and 212,675 population comparisons were followed for the diagnosis of hyperthyroidism. Hospitalisation rates, standardised hospitalisation rate ratios and absolute excess risks were calculated with 95% confidence intervals (CI). RESULTS: Hyperthyroidism was diagnosed in 131 childhood cancer survivors, yielding an overall relative risk of 1.6 (95% CI: 1.3-1.9) compared with population comparisons. The risk was greatest 1-5 years after the diagnosis of cancer and in survivors of thyroid cancers, neuroblastomas, acute lymphoblastic leukaemia and Hodgkin lymphoma. Sixty-seven percent of survivors with hyperthyroidism had tumours located in the head, neck or upper body and half of survivors with hyperthyroidism were irradiated with 77% of them in the head and neck area. CONCLUSION: Childhood cancer survivors are at an increased risk of hyperthyroidism, potentially resulting in non-endocrine morbidity.

Survival from tumours of the central nervous system in Danish children: Is survival related to family circumstances?

Little is known about social inequalities in childhood cancer survival. We investigated the impact of family circumstances on survival from paediatric central nervous system (CNS) tumours in a nationwide, register-based cohort of Danish children. All children born between 1973 and 2006 and diagnosed with a CNS tumour before the age of 20 years (N = 1,261) were followed until 10 years from diagnosis. Using Cox proportional hazards models, the impact of various family characteristics on overall survival was estimated. Hazard ratios (HRs) for all CNS tumours combined did not show strong associations between survival and any family characteristic. Analyses by CNS tumour subtypes showed reduced survival for children with glioma when living outside of Copenhagen (HR 1.55; CI 1.03; 2.35). For embryonal CNS tumours, the number of full siblings was associated with worse survival (HR for having 3+ siblings 3.60; CI 1.52; 8.53) and a trend of better survival was observed for children with parents of younger age at child's diagnosis and poorer survival of children with parents of older age. Despite free and uniform access to health care services, some family circumstances appear to affect survival from specific CNS tumour types in Danish children. Further research is warranted to gain a more comprehensive understanding of the impact of family factors on childhood cancer survival in other populations and to elaborate underlying mechanisms and pathways of those survival inequalities observed.

Somatic late effects in 5-year survivors of neuroblastoma: a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia study.

Because of the rarity of neuroblastoma and poor survival until the 1990s, information on late effects in neuroblastoma survivors is sparse. We comprehensively reviewed the long-term risk for somatic disease in neuroblastoma survivors. We identified 721 5-year survivors of neuroblastoma in Nordic population-based cancer registries and identified late effects in national hospital registries covering the period 1977-2012. Detailed treatment information was available for 46% of the survivors. The disease-specific rates of hospitalization of survivors and of 152,231 randomly selected population comparisons were used to calculate standardized hospitalization rate ratios (SHRRs) and absolute excess risks (AERs). During 5,500 person-years of follow-up, 501 5-year survivors had a first hospital contact yielding a SHRR of 2.3 (95% CI 2.1-2.6) and a corresponding AER of 52 (95% CI 44-60) per 1,000 person-years. The highest relative risks were for diseases of blood and blood-forming organs (SHRR 3.8; 95% CI 2.7-5.4), endocrine diseases (3.6 [3.1-4.2]), circulatory system diseases (3.1 [2.5-3.8]), and diseases of the nervous system (3.0 [2.6-3.3]). Approximately 60% of the excess new hospitalizations of survivors were for diseases of the nervous system, urinary system, endocrine system, and bone and soft tissue. The relative risks and AERs were highest for the survivors most intensively treated. Survivors of neuroblastoma have a highly increased long-term risk for somatic late effects in all the main disease groups as compared to background levels. Our results are useful for counseling survivors and should contribute to improving health care planning in post-therapy clinics.

The PanCareSurFup cohort of 83,333 five-year survivors of childhood cancer: a cohort from 12 European countries.

Childhood cancer survivors face risks from a variety of late effects, including cardiac events, second cancers, and late mortality. The aim of the pan-European PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies (PanCareSurFup) Consortium was to collect data on incidence and risk factors for these late effects among childhood cancer survivors in Europe. This paper describes the methodology of the data collection for the overall PanCareSurFup cohort and the outcome-related cohorts. In PanCareSurFup 13 data providers from 12 countries delivered data to the data centre in Mainz. Data providers used a single variable list that covered all three outcomes. After validity and plausibility checks data was provided to the outcome-specific working groups. In total, we collected data on 115,596 patients diagnosed with cancer from 1940 to 2011, of whom 83,333 had survived 5 years or more. Due to the eligibility criteria and other requirements different numbers of survivors were eligible for the analysis of each of the outcomes. Thus, 1014 patients with at least one cardiac event were identified from a cohort of 39,152 5-year survivors; for second cancers 3995 survivors developed at least one second cancer from a cohort of 71,494 individuals, and from the late mortality cohort of 79,441 who had survived at least 5 years, 9247 died subsequently. Through the close cooperation of many European countries and the establishment of one central data collection and harmonising centre, the project succeeded in generating the largest cohort of children with cancer to date.

Survival From Childhood Hematological Malignancies in Denmark: Is Survival Related to Family Characteristics?

BACKGROUND: Due to diverse findings as to the role of family factors for childhood cancer survival even within Europe, we explored a nationwide, register-based cohort of Danish children with hematological malignancies. METHODS: All children born between 1973 and 2006 and diagnosed with a hematological malignancy before the age of 20 years (N = 1,819) were followed until 10 years from diagnosis. Kaplan-Meier curves and Cox proportional hazards models estimating hazard ratios (HR) and 95% confidence intervals (CI) were used to assess the impact of family characteristics on overall survival in children with hematological malignancies. RESULTS: Having siblings and increasing birth order were associated with reduced survival from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Associations with AML were strongest and statistically significant. HRs of 1.62 (CI 0.85; 3.09) and 5.76 (CI 2.01; 16.51) were observed for the fourth or later born children with ALL (N = 41) and AML (N = 9), respectively. Children with older parents showed a tendency toward inferior ALL survival, while for AML young maternal age was related to poorer survival. Based on small numbers, a trend toward poorer survival from non-Hodgkin lymphoma was observed for children having siblings and for children of younger parents. CONCLUSIONS: Further research is warranted to gain further knowledge on the impact of family factors on childhood cancer survival in other populations and to elaborate potential underlying mechanisms and pathways of those survival inequalities.

Birth order and risk of childhood cancer in the Danish birth cohort of 1973-2010.

PURPOSE: Many studies have investigated the possible association between birth order and risk of childhood cancer, although the evidence to date has been inconsistent. Birth order has been used as a marker for various in utero or childhood exposures and is relatively straightforward to assess. METHODS: Data were obtained on all children born in Denmark between 1973 and 2010, involving almost 2.5 million births and about 5,700 newly diagnosed childhood cancers before the age of 20 years. Data were analyzed using Poisson regression models. RESULTS: We failed to observe associations between birth order and risk of any childhood cancer subtype, including acute lymphoblastic leukemia; all rate ratios were close to one. Further analyses stratified by birth cohort (those born between 1973 and 1990, and those born between 1991 and 2010) also failed to show any associations. Considering stillbirths and/or controlling for birth weight and parental age in the analyses had no effect on the results. Analyses by years of birth (those born between 1973 and 1990, and those born between 1991 and 2010) did not show any changes in the overall pattern of no association. CONCLUSIONS: In this large cohort of all children born in Denmark over an almost 40-year period, we did not observe an association between birth order and the risk of childhood cancer.

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.

Genital warts and risk of cancer: a Danish study of nearly 50 000 patients with genital warts.

BACKGROUND: We conducted a large national cohort study to examine the risk of cancer among men and women with genital warts (GW). METHODS: By use of the Danish National Patient Register, we identified 16,155 men and 32,933 women who received a diagnosis of GW during 1978-2008. Standardized incidence ratios (SIRs) were computed as estimates of the relative risk of specific cancers or sites. RESULTS: A diagnosis of GW was strongly related to anal (SIR for men, 21.5; SIR for women, 7.8), vulvar (SIR, 14.8), vaginal (SIR, 5.9), cervical (SIR, 1.5), penile (SIR, 8.2), and head and neck cancer (SIR, 2.8), including subsites of head and neck cancer with confirmed HPV association (SIR for men, 3.5; SIR for women, 4.8). The risks remained elevated for >10 years following GW diagnosis. In addition, we found moderately increased SIR estimates for nonmelanoma skin cancer, smoking-related cancers, and Hodgkin and non-Hodgkin lymphoma. CONCLUSIONS: Individuals with GW have a long-term increased risk of anogenital cancers and head and neck cancers. The elevated risks of nonmelanoma skin cancers might indicate an association with HPV, while excess risks of other cancers could point to differences in other risk factors between individuals with GW and the general population.

Employment status and occupational positions of childhood cancer survivors from Denmark, Finland and Sweden: A Nordic register-based cohort study from the SALiCCS research programme.

BACKGROUND: A childhood cancer diagnosis and late effects of treatment may affect survivors' possibilities of employment or highly skilled occupations later in life. In this study, we compared the employment and occupational status of childhood cancer survivors with population comparisons and siblings. METHODS: In a cohort study based on Nordic registers, we identified 10 461 survivors of childhood cancer diagnosed before age 20 years in Denmark, Finland and Sweden since 1971. Survivors were compared with 48 928 population comparisons matched to survivors by age, sex and geographical region and 12 605 siblings of survivors. Annual outcome information on employment, unemployment, health-related unemployment and occupational position was obtained from the statistical institutes between 1980-2017 and assessed in multivariate logistic regression analyses from age 30 onwards. FINDINGS: By 30 years of age, 9.2% (95% CI, 8.6-9.9%) of survivors were unemployed for health reasons. Childhood cancer survivors had considerably higher odds of health-related unemployment at ages 30, 40 and 50 than population comparisons (ORage30, 2.57; 95% CI, 2.35-2.81) and siblings (ORage30, 2.50; 95% CI, 2.15-2.90). We observed no large difference in unemployment unrelated to health or in occupational position. Health-related unemployment was particularly pronounced among survivors of central nervous system tumours and survivors diagnosed below 15 years of age. INTERPRETATION: Survivors at risk of health-related unemployment should be offered comprehensive survivorship care and interventions for obtaining and maintaining suitable employment. FUNDING: NordForsk [76111], the Danish Childhood Cancer Foundation [2016-0293], Aarhus University [43239402], the Swedish Childhood Cancer Foundation [PR2020-0130] and [OB2019-0003], Tømrermester Jørgen Holm og Hustru Elisa F. Hansens Mindelegat [20088] and the Swiss National Science Foundation to LM [P2LUP3_175288].

Psychiatric disorders in childhood cancer survivors in Denmark, Finland, and Sweden: a register-based cohort study from the SALiCCS research programme.

BACKGROUND: A childhood cancer diagnosis and treatment-induced somatic late effects can affect the long-term mental health of survivors. We aimed to explore whether childhood cancer survivors are at higher risk of psychiatric disorders later in life than their siblings and the general population. METHODS: In this register-based cohort study (part of the Socioeconomic Consequences in Adult Life after Childhood Cancer [SALiCCS] research programme), we included 5-year survivors of childhood cancer diagnosed before 20 years of age between Jan 1, 1974 and Dec 31, 2011, in Denmark, Finland, and Sweden. In Denmark and Sweden, 94·7% of individuals were born in a Nordic country (ie, Denmark, Finland, Iceland, Norway, or Sweden); similar information was not available in Finland. Data on ethnicity were not collected. Survivors were compared with their siblings and randomly selected individuals from the general population who were matched to the survivors by year of birth, sex, and geographical region. We followed up our study population from 5 years after the childhood cancer diagnosis or corresponding calendar date for matched individuals (the index date) until Aug 11, 2017, and assessed information on hospital contacts for any and specific psychiatric disorders. For siblings, the index date was defined as 5 years from the date on which they were of the same age as their sibling survivor when diagnosed with cancer. FINDINGS: The study population included 18 621 childhood cancer survivors (9934 [53·3%] males and 8687 [46·7%] females), 24 775 siblings (12 594 [50·8%] males and 12 181 [49·2%] females), and 88 630 matched individuals (47 300 [53·4%] males and 41 330 [46·6%] females). The cumulative incidence proportion of having had a psychiatric hospital contact by 30 years of age between Jan 1, 1979, and Aug 11, 2017, was 15·9% (95% CI 15·3-16·5) for childhood cancer survivors, 14·0% (13·5-14·5) for siblings, and 12·7% (12·4-12·9) for matched individuals. Despite a small absolute difference, survivors were at higher relative risk of any psychiatric hospital contact than their siblings (1·39, 1·31-1·48) and matched individuals (hazard ratio 1·34, 95% CI 1·28-1·39). The higher risk persisted at the age of 50 years. Survivors had a higher burden of recurrent psychiatric hospital contacts and had more hospital contacts for different psychiatric disorders than their siblings and the matched individuals. INTERPRETATION: Childhood cancer survivors are at higher long-term risk of psychiatric disorders than their siblings and matched individuals from the general population. To improve mental health and the overall quality of life after childhood cancer, survivorship care should include a focus on early signs of mental health problems, especially among high-risk groups of survivors. FUNDING: NordForsk, Aarhus University, Swedish Childhood Cancer Foundation, Danish Health Foundation, and Swiss National Science Foundation.

Somatic Disease in Survivors of Childhood Malignant Bone Tumors in the Nordic Countries.

Survivors of malignant bone tumors in childhood are at risk of long-term adverse health effects. We comprehensively reviewed cases of somatic diseases that required a hospital contact in survivors of osteosarcoma and Ewing sarcoma. In a population-based cohort study, 620 five-year survivors of osteosarcoma (n = 440) or Ewing sarcoma (n = 180), diagnosed before the age of 20 years in Denmark, Finland, Iceland, and Sweden during 1943-2008, were followed in the national hospital registers. Overall rates of hospital contacts for any somatic disease and for 12 main diagnostic groups and 120 specific disease categories were compared with those in a matched comparison cohort (n = 3049) randomly selected from the national population registers. The rate of hospital contact for any somatic disease was 80% higher in survivors of malignant bone tumors than in comparisons and remained elevated up to 30 years after diagnosis. The rate of hospital contacts was higher after Ewing sarcoma (rate ratio (RR) 2.24; 95% confidence interval (CI) 1.76-2.85) than after osteosarcoma (RR 1.67; 95% CI 1.41-1.98). Elevated rates were observed for 11 main diagnostic groups, including infections, second malignant neoplasms, and diseases of the skin, bones, and circulatory, digestive, endocrine, and urinary systems. Survivors of malignant bone tumors in childhood are at increased risk of somatic diseases many years after diagnosis. This comprehensive study contributes new insight into the risk of late effects in survivors of osteosarcoma and Ewing sarcoma, which is an essential basis for optimal patient counseling and follow-up care.

Cohort Profile: The Socioeconomic Consequences in Adult Life After Childhood Cancer in Scandinavia (SALiCCS) Research Programme.

INTRODUCTION: The growing number of survivors of childhood cancer, with many years of life ahead, demonstrates the increasing clinical and public health relevance of investigating the risks of social and socioeconomic impairment after a childhood cancer diagnosis and the life-saving treatment. To enrich understanding of the mental, social and socioeconomic difficulties that childhood cancer survivors may face during their life-course, identify particularly vulnerable survivors and overcome the limitations of previous research, we initiated the Socioeconomic Consequences in Adult Life after Childhood Cancer in Scandinavia (SALiCCS) research programme. METHODS: This Nordic cross-border research programme is a collaboration between the Danish Cancer Society, the Finnish Cancer Registry and Karolinska Institutet to investigate a broad range of mental, social and socioeconomic conditions in long-term childhood cancer survivors in Denmark, Finland and Sweden. SALiCCS is based on a registry-based matched cohort design, comprising five-year survivors of cancer diagnosed at ages 0-19 years (1971-2008 in Denmark, 1971-2009 in Finland, 1971-2011 in Sweden), age-, sex- and country-matched population comparisons and sibling comparisons who were followed over time. Outcomes of interest included mental disorders, educational achievements, employment and profession, family life and the need of social security benefits. Individual-level data linkage among various national registries provided the data for the research programme. RESULTS: The SALiCCS core population comprises 21,292 five-year survivors, 103,303 population comparisons and 29,644 siblings as a second comparison group. The most common diagnoses in survivors were central nervous system tumours, leukaemias and lymphomas. DISCUSSION: SALiCCS is the largest, most comprehensive population-based research initiative in this field, based on high-quality registry data with minimal risk of bias. The findings will be informative for evidence-based survivorship care targeting not only somatic late effects but also psychosocial impairments.

Long-Term Risk of Hospitalization Among Five-Year Survivors of Childhood Leukemia in the Nordic Countries.

BACKGROUND: Adverse effects from childhood leukemia treatment may persist or present years after cure from cancer. We provide a comprehensive evaluation of subsequent hospitalization in five-year survivors of childhood acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). METHODS: In the Adult Life after Childhood Cancer in Scandinavia Study, we identified 4003 five-year survivors diagnosed with childhood leukemia 1970-2008 in Denmark, Sweden, Iceland, and Finland. Survivors and 129 828 population comparisons were followed for first-time nonpsychiatric hospitalizations for 120 disease categories in the hospital registries. Standardized hospitalization rate ratios and absolute excess rates were calculated. All statistical tests were two-sided. RESULTS: Survivors of ALL (n = 3391), AML (n = 389), and CML (n = 92) had an increased overall hospitalization rate compared with population comparisons. The rate ratio for any hospitalization was 1.95 (95% confidence interval [CI] = 1.83 to 2.07) in ALL, 3.09 (95% CI = 2.53 to 3.65) in AML, and 4.51 (95% CI = 3.03 to 6.00) in CML survivors and remained increased even 20 years from leukemia diagnosis. Corresponding absolute excess rates per 1000 person-years were 28.48 (95% CI = 24.96 to 32.00), 62.75 (95% CI = 46.00 to 79.50), and 105.31 (95% CI = 60.90 to 149.72). CONCLUSION: Leukemia survivors have an increased rate of hospitalization for medical conditions. We provide novel insight into the relative and absolute rate of hospitalization for 120 disease categories in survivors of ALL, AML, and CML, which are likely to be informative for both survivors and healthcare providers.