| 1. |
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| 2. |
- Sällfors-Holmqvist, Anna, et al.
(author)
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Young age at diagnosis is a risk factor for negative late socio-economic effects after acute lymphoblastic leukemia in childhood.
- 2010
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In: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 55, s. 698-707
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Journal article (peer-reviewed)abstract
- BACKGROUND: The increasing number of survivors after childhood cancer requires characterization of the late complications of these diseases and their treatment. We examined a large number of possible socio-economic late effects following treatment for acute lymphoblastic leukemia (ALL) in order to identify factors leading to a poor outcome. PROCEDURE: All individuals who had been diagnosed with ALL and who were alive in January 2007 (n = 213; men = 107) were identified from a database of all patients with cancer before the age of 18 in Southern Sweden from 1970 to 1999. For each subject, 50 matched controls were identified from the Swedish Population Register. Information on marital status, children, education, employment, income, and support from the community was obtained from Statistics Sweden. RESULTS: At the ages of 25 and 30, survivors of ALL had attained a lower level of education than controls. At the age of 30, they were less often employed (70% vs. 82%, P = 0.019), less often married (19% vs. 32%, P = 0.019), and had children to a lesser extent (31% vs. 47%, P = 0.011) than controls. We identified young age at diagnosis as a risk factor for adverse outcome in the majority of the socio-economic variables studied, apart from the known risk of cranial irradiation treatment. Furthermore, female survivors had a greater risk of achieving a lower level of education than both male survivors and controls. CONCLUSIONS: Young age at diagnosis, as well as treatment with cranial irradiation, is a risk factor for socio-economic late effects after treatment for ALL in childhood. Pediatr Blood Cancer (c) 2010 Wiley-Liss, Inc.
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| 3. |
- Asdahl, Peter Haubjerg, et al.
(author)
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Gastrointestinal and liver disease in Adult Life After Childhood Cancer in Scandinavia : A population-based cohort study
- 2016
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In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 139:7, s. 1501-1511
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Journal article (peer-reviewed)abstract
- Survival after childhood cancer diagnosis has remarkably improved, but emerging evidence suggests that cancer-directed therapy may have adverse gastrointestinal late effects. We aimed to comprehensively assess the frequency of gastrointestinal and liver late effects among childhood cancer survivors and compare this frequency with the general population. Our population-based cohort study included all 1-year survivors of childhood and adolescent cancer in Denmark, Finland, Iceland, Norway and Sweden diagnosed from the 1940s and 1950s. Our outcomes of interest were hospitalization rates for gastrointestinal and liver diseases, which were ascertained from national patient registries. We calculated standardized hospitalization rate ratios (RRs) and absolute excess rates comparing hospitalizations of any gastrointestinal or liver disease and for specific disease entities between survivors and the general population. The study included 31,132 survivors and 207,041 comparison subjects. The median follow-up in the hospital registries were 10 years (range: 0-42) with 23% of the survivors being followed at least to the age of 40 years. Overall, survivors had a 60% relative excess of gastrointestinal or liver diseases [RR: 1.6, 95% confidence interval (CI): 1.6-1.7], which corresponds to an absolute excess of 360 (95% CI: 330-390) hospitalizations per 100,000 person-years. Survivors of hepatic tumors, neuroblastoma and leukemia had the highest excess of gastrointestinal and liver diseases. In addition, we observed a relative excess of several specific diseases such as esophageal stricture (RR: 13; 95% CI: 9.2-20) and liver cirrhosis (RR: 2.9; 95% CI: 2.0-4.1). Our findings provide useful information about the breadth and magnitude of late complications among childhood cancer survivors and can be used for generating hypotheses about potential exposures related to these gastrointestinal and liver late effects.
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| 4. |
- Asdahl, Peter H, et al.
(author)
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The adult life after childhood cancer in scandinavia (ALiCCS) study: Design and characteristics.
- 2015
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In: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 62:12, s. 2204-2210
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Journal article (peer-reviewed)abstract
- 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.
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| 5. |
- Bonnesen, Trine Gade, et al.
(author)
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Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS) : A population-based cohort study of 32,839 one-year survivors
- 2018
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In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 142:4, s. 702-708
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Journal article (peer-reviewed)abstract
- Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow-up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort. We included all 1-year survivors of childhood cancer treated in the five Nordic countries. A Cox proportional hazards model was used to estimate hospitalisation rate (hazard) ratios (HRs) for each liver outcome according to type of cancer. We used the risk among survivors of central nervous system tumour as internal reference. With a median follow-up time of 10 years, 659 (2%) survivors had been hospitalised at least once for a liver disease. The risk for hospitalisation for any liver disease was high after hepatic tumour (HR = 6.9) and leukaemia (HR = 1.7). The Danish sub-cohort of leukaemia treated with haematopoietic stem cell transplantation had a substantially higher risk for hospitalisation for all liver diseases combined (HR = 3.8). Viral hepatitis accounted for 286 of 659 hospitalisations corresponding to 43% of all survivors hospitalised for liver disease. The 20-year cumulative risk of viral hepatitis was 1.8% for survivors diagnosed with cancer before 1990 but only 0.3% for those diagnosed after 1990. The risk of liver disease was low but significantly increased among survivors of hepatic tumours and leukaemia. Further studies with focus on the different treatment modalities are needed to further strengthen the prevention of treatment-induced late liver complications.
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| 6. |
- Bonnesen, Trine Gade, et al.
(author)
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Long-term risk of renal and urinary tract diseases in childhood cancer survivors : A population-based cohort study
- 2016
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 64, s. 52-61
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Journal article (peer-reviewed)abstract
- Background Childhood cancer has been associated with long-term risk of urinary tract diseases, but risk patterns remain to be comprehensively investigated. We analysed the lifetime risk of urinary tract diseases in survivors of childhood cancer in the Nordic countries. Methods We identified 32,519 one-year survivors of childhood cancer diagnosed since the 1940s and 1950s in the five Nordic cancer registries and selected 211,156 population comparisons of a corresponding age, sex, and country of residence from the national population registries. To obtain information on all first-time hospitalizations for a urinary tract disease, we linked all study subjects to the national hospital registry of each country. Relative risks (RRs) and absolute excess risks (AERs) and associated 95% confidence intervals (CIs) for urinary tract diseases among cancer survivors were calculated with the appropriate morbidity rates among comparisons as reference. Results We observed 1645 childhood cancer survivors ever hospitalized for urinary tract disease yielding an RR of 2.5 (95% CI 2.4-2.7) and an AER of 229 (95% CI 210-248) per 100,000 person-years. The cumulative risk at age 60 was 22% in cancer survivors and 10% in comparisons. Infections of the urinary system and chronic kidney disease showed the highest excess risks, whereas survivors of neuroblastoma, hepatic and renal tumours experienced the highest RRs. Conclusion Survivors of childhood cancer had an excess risk of urinary tract diseases and for most diseases the risk remained elevated throughout life. The highest risks occurred following therapy of childhood abdominal tumours.
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| 7. |
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| 8. |
- de Fine Licht, Sofie, et al.
(author)
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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
- 2017
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In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 14:5
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Journal article (peer-reviewed)abstract
- 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.
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| 9. |
- Frederiksen, Line Elmerdahl, et al.
(author)
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Psychiatric disorders in childhood cancer survivors in Denmark, Finland, and Sweden : a register-based cohort study from the SALiCCS research programme
- 2022
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In: The Lancet Psychiatry. - 2215-0366 .- 2215-0374. ; 69
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Journal article (peer-reviewed)abstract
- 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.
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| 10. |
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| 11. |
- Holmqvist, Anna Sällfors, et al.
(author)
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Assessment of Late Mortality Risk after Allogeneic Blood or Marrow Transplantation Performed in Childhood
- 2018
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In: JAMA Oncology. - : American Medical Association (AMA). - 2374-2437. ; 4:12
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Journal article (peer-reviewed)abstract
- Importance: Allogeneic blood or marrow transplantation (BMT) is a curative option for malignant and nonmalignant diseases of childhood. However, little is known about trends in cause-specific late mortality in this population during the past 3 decades. Objectives: To examine cause-specific late mortality among individuals who have lived 2 years or more after allogeneic BMT performed in childhood and whether rates of late mortality have changed over time. Design, Setting, and Participants: A retrospective cohort study was conducted of individuals who lived 2 years or more after undergoing allogeneic BMT performed in childhood between January 1, 1974, and December 31, 2010. The end of follow-up was December 31, 2016. Exposure: Allogeneic BMT performed in childhood. Main Outcomes and Measures: All-cause mortality, relapse-related mortality, and non-relapse-related mortality. Data on vital status and causes of death were collected using medical records, the National Death Index Plus Program, and Accurint databases. Results: Among 1388 individuals (559 females and 829 males) who lived 2 years or more after allogeneic BMT performed in childhood, the median age at transplantation was 14.6 years (range, 0-21 years). In this cohort, there was a total of 295 deaths, yielding an overall survival rate of 79.3% at 20 years after BMT. The leading causes of death were infection and/or chronic graft-vs-host disease (121 of 244 [49.6%]), primary disease (60 of 244 [24.6%]), and subsequent malignant neoplasms (45 of 244 [18.4%]). Overall, the cohort had a 14.4-fold increased risk for death (95% CI, 12.8-16.1) compared with the general population (292 deaths observed; 20.3 deaths expected). Relative mortality remained elevated at 25 years or more after BMT (standardized mortality ratio, 2.9; 95% CI, 2.0-4.1). The absolute excess risk for death from any cause was 12.0 per 1000 person-years (95% CI, 10.5-13.5). The cumulative incidence of non-relapse-related mortality exceeded that of relapse-related mortality throughout follow-up. The 10-year cumulative incidence of late mortality decreased over time (before 1990, 18.9%; 1990-1999, 12.8%; 2000-2010, 10.9%; P =.002); this decrease remained statistically significant after adjusting for demographic and clinical factors (referent group: <1990; 1990-1999: hazard ratio, 0.64; 95% CI, 0.47-0.89; P =.007; 2000-2010: hazard ratio, 0.49; 95% CI, 0.31-0.76; P =.002; P <.001 for trend). Conclusions and Relevance: Late mortality among children undergoing allogeneic BMT has decreased during the past 3 decades. However, these patients remain at an elevated risk of late mortality even 25 years or more after transplantation when compared with the general population, necessitating lifelong follow-up.
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| 12. |
- Holmqvist, Anna Sällfors, et al.
(author)
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Late morbidity and mortality after autologous blood or marrow transplantation for lymphoma in children, adolescents and young adults—a BMTSS report
- 2024
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In: Leukemia. - 0887-6924. ; 38:3, s. 601-609
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Journal article (peer-reviewed)abstract
- We determined the risk of late morbidity and mortality after autologous blood or marrow transplantation (BMT) for lymphoma performed before age 40. The cohort included autologous BMT recipients who had survived ≥2 years after transplantation (N = 583 [HL = 59.9%; NHL = 40.1%]) and a comparison cohort (N = 1070). Participants self-reported sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life threatening] or 5 [fatal]) was assigned to the conditions using CTCAE v5.0. Logistic regression estimated the odds of grade 3–4 conditions in survivors vs. comparison subjects. Proportional subdistribution hazards models identified predictors of grade 3–5 conditions among BMT recipients. Median age at BMT was 30.0 years (range: 2.0–40.0) and median follow-up was 9.8 years (2.0–32.1). Survivors were at a 3-fold higher adjusted odds for grade 3–4 conditions (95% CI = 2.3–4.1) vs. comparison subjects. Factors associated with grade 3–5 conditions among BMT recipients included age at BMT (>30 years: adjusted hazard ratio [aHR] = 2.31; 95% CI = 1.27–4.19; reference: ≤21 years), pre-BMT radiation (aHR = 1.52; 95% CI = 1.13–2.03; reference: non-irradiated), and year of BMT (≥2000: aHR = 0.54; 95% CI = 0.34–0.85; reference: <1990). The 25 years cumulative incidence of relapse-related and non-relapse-related mortality was 18.2% and 25.9%, respectively. The high risk for late morbidity and mortality after autologous BMT for lymphoma performed at age <40 calls for long-term anticipatory risk-based follow-up.
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| 13. |
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| 14. |
- Holmqvist, Anna Sällfors, et al.
(author)
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Late Mortality after Allogeneic Bone Marrow Transplantation in Childhood for Bone Marrow Failure Syndromes and Severe Aplastic Anemia
- 2019
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In: Biology of Blood and Marrow Transplantation. - : Elsevier BV. - 1083-8791. ; 25:4, s. 749-755
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Journal article (peer-reviewed)abstract
- Children with bone marrow failure syndromes and severe aplastic anemia (SAA) are treated with allogeneic blood or marrow transplantation (BMT). However, there is a paucity of studies examining late mortality risk after allogeneic BMT performed in childhood for bone marrow failure syndromes and SAA and evaluating how this risk differs between these diseases. We investigated cause-specific late mortality in 2-year survivors of allogeneic BMT for bone marrow failure syndromes and SAA performed before age 22 years between 1974 and 2010 at 2 US transplantation centers. Vital status information was collected from medical records, the National Death Index, and Accurint databases. Overall survival was calculated using Kaplan-Meier techniques. The standardized mortality ratio (SMR) was calculated using age- sex-, and calendar-specific mortality rates from the Centers for Disease Control and Prevention. Among the 2-year survivors of bone marrow failure syndromes (n = 120) and SAA (n = 147), there were 15 and 19 deaths, respectively, yielding an overall survival of 86.4% for bone marrow failure syndromes and 93.1% for SAA at 15 years post-BMT. Compared with the general population, patients with bone marrow failure syndromes were at a higher risk for premature death (SMR, 22.7; 95% CI, 13.1 to 36.2) compared with those with SAA (SMR, 4.5; 95% CI, 2.8 to 7.0) (P <.0001). The elevated relative risk persisted at ≥15 years after BMT for both diseases. The hazard of all-cause late mortality was 2.9-fold (95% CI, 1.1 to 7.3) higher in patients with bone marrow failure syndromes compared with those with SAA. The high late mortality risk in recipients of allogeneic BMT in childhood for bone marrow failure syndromes calls for intensified life-long follow-up.
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| 15. |
- Holmqvist, Anna Sällfors, et al.
(author)
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Late mortality after autologous blood or marrow transplantation in childhood : A Blood or Marrow Transplant Survivor Study-2 report
- 2018
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 131:24, s. 2720-2729
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Journal article (peer-reviewed)abstract
- Autologous blood or marrow transplantation (BMT) is a curative option for several types of childhood cancer. However, there is little information regarding the risk of late mortality. We examined all-cause mortality, relapse-related mortality (RRM), and nonrelapse-related mortality (NRM) in 2-year survivors of autologous BMT performed before age 22 between 1980 and 2010 at 1 of 2 US transplant centers. Vital status information was collected using medical records, National Death Index, and Accurint databases. Overall survival was calculated using Kaplan-Meier techniques. Cumulative incidence of mortality used competing risk methods. Standardized mortality ratio (SMR) was calculated using age-, sex-, and calendar-specific mortality rates from Centers for Disease Control and Prevention. Cox regression analysis was used to determine predictors of all-cause late mortality. Among the 345 2-year survivors, 103 deaths were observed, yielding an overall survival of 70.3% 15 years post-BMT. The leading causes of death included primary disease (50.0%), subsequent neoplasm (21.4%), and infection (18.2%). Overall, the cohort was at a 22-fold increased risk of late mortality (SMR, 21.8; 95% CI, 17.9-26.3), compared with the general population. Mortality rates remained elevated among the 10-year survivors (SMR, 20.6; 95% CI, 9.9-37.2) but approached those of the general population ≥15 years post-BMT. The 10-year cumulative incidence of RRM (14.3%) exceeded that of NRM (10.4%). The 10-year cumulative mortality rate declined over time (<1990, 35.1%; 1990-1999, 25.6%; 2000-2010, 21.8%; P 5 .05). In conclusion, childhood autologous BMT recipients have an increased risk of late mortality, compared with the general population. The late mortality rates have declined over the past 3 decades.
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| 16. |
- Holmqvist, Anna Sällfors, et al.
(author)
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Severe, life-threatening, and fatal chronic health conditions after allogeneic blood or marrow transplantation in childhood
- 2023
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In: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 129:4, s. 624-633
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Journal article (peer-reviewed)abstract
- Background: A comprehensive assessment of morbidity after allogeneic bone marrow transplantation (BMT) performed in childhood remains understudied. Methods: Seven hundred eighty-nine allogeneic BMT recipients who had survived ≥2 years after BMT performed between 1974 and 2014 at age <22 years and 690 siblings completed a 255-item survey self-reporting sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life-threatening], or 5 [fatal]) was assigned to the conditions using Common Terminology Criteria for Adverse Events, version 5.0. For the BMT cohort, the cumulative incidence of chronic health conditions was calculated as a function of time from BMT. Proportional subdistribution hazards models were used to determine predictors of grade 3–5 conditions. Logistic regression was used to estimate the risk of grade 3–4 conditions in BMT recipients who were alive at the time of this study compared with siblings. Results: The median age at transplantation was 11.3 years (range, 0.4–22.0 years), and the median length of follow-up was 11.7 years (range, 2.0–45.3 years). The most prevalent primary diagnoses were acute lymphoblastic leukemia (30.7%), and acute myeloid leukemia/myelodysplastic syndrome (26.9%). At age 35 years, the cumulative incidence of a grade 3–4 condition was 53.8% (95% CI, 46.7%–60.3%). The adjusted odds ratio of a grade 3–4 condition was 15.1 in survivors (95% CI, 9.5–24.0) compared with siblings. The risk of a grade 3–5 condition increased with age at BMT (hazard ratio [HR], 1.03; 95% CI, 1.01–1.05) and was higher among females (HR, 1.27; 95% CI, 1.02–1.59), patients who received total body irradiation (HR, 1.71; 95% CI, 1.27–2.31), and those reporting chronic graft-versus-host disease (HR, 1.38; 95% CI, 1.09–1.74). Conclusions: Two-year survivors of allogeneic BMT in childhood have an increased risk of grade 3–4 chronic health conditions compared with siblings, suggesting the need for long-term follow-up.
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| 17. |
- Høgsholt, Stine, et al.
(author)
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Disease-specific hospitalizations among 5-year survivors of Wilms tumor : A Nordic population-based cohort study
- 2021
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In: Pediatric Blood and Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 68:5
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Journal article (peer-reviewed)abstract
- 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.
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| 18. |
- Jackmann, Natalja, 1968-
(author)
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Vitamin D, bone turnover markers and hCAP-18 in children with hemato-oncological diseases
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Children with hemato-oncological diseases may have significant skeletal morbidities. Vitamin D is essential for the maintenance of skeletal health and may also be important for immunological functions and cancer outcomes. As vitamin D deficiency is a recognized problem in children worldwide, it is important to evaluate its prevalence among children and adolescents with hemato-oncological diseases in Sweden.In this thesis, I investigated vitamin D status and its predictors, serum hCAP-18 (the pro-protein of the antimicrobial peptide LL-37 produced during neutrophil differentiation in the bone marrow), and bone turnover markers in children with hemato-oncological diseases at the time of diagnosis. Vitamin D deficiency was found in 30.9–46% of the children. Lower 25-hydroxyvitamin D level correlated with older age, seasons outside summer, a more recent calendar year of sampling, lack of vitamin D supplementation, and country of parental origin located between latitudes -45° and 45°. In preschool children with leukemia, a 25-hydroxyvitamin D level < 50 nmol/L was associated with inferior overall survival. There was no correlation between serum 25-hydroxyvitamin D and hCAP-18 neither in children with hemato-oncological diseases nor in healthy controls. Children with diseases that impair myelopoiesis presented low hCAP-18 levels, whereas those with non-hematological malignancies displayed serum hCAP-18 levels in the same range as that of healthy children.Children diagnosed with leukemia had lower levels of bone formation and resorption markers than those of children with solid tumors or bone marrow failure. Adolescents with osteosarcoma displayed high bone alkaline phosphatase levels.The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid the development of supportive treatments that reduce the adverse effects of cancer and its treatment.
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| 19. |
- Kenborg, Line, et al.
(author)
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Neurologic disorders in 4858 survivors of central nervous system tumors in childhood-an Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study
- 2019
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In: Neuro-Oncology. - : Oxford University Press (OUP). - 1523-5866 .- 1522-8517. ; 21:1, s. 125-136
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Journal article (peer-reviewed)abstract
- Background: A comprehensive overview of neurologic complications among survivors of central nervous system (CNS) tumors in childhood is lacking. We aimed to investigate the risk for these disorders in a large, population-based study with outcome measures from nationwide hospital registries. Methods: We identified 4858 five-year survivors with diagnoses of CNS tumor in childhood in Denmark, Iceland, Finland, and Sweden in 1943-2007, and 166658 matched population comparison subjects. Inpatient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). Results: A neurologic disorder was verified in 1309 survivors, while 92.4 were expected, yielding an overall RR of 14.2 (95% confidence interval [CI]: 13.3-15.1) and an AER of 20 hospitalizations per 1000 persons per year. The risks remained increased more than 20 years after diagnosis (RR: 6.3, 95% CI: 5.6-7.2; AER: 11, 9-12). The most frequent diagnoses were epilepsy (affecting 14.1% of all survivors) followed by hydrocephalus (9.5%) and paralytic syndromes (4.2%), with RRs of 28.7 (95% CI: 26.0-31.6), 243 (95% CI: 190-311), and 40.3 (95% CI: 33.1-49.2), respectively. Of these outcomes, 30%-40% were diagnosed prior to or synchronously with the CNS tumor. The survivors had highly increased RRs for infectious diseases of the CNS, disorders of cranial nerves, and degenerative diseases of the nervous system. Conclusions: Survivors of childhood CNS tumors are at markedly increased risk for neurologic disorders throughout their lives. Health care professionals must be aware of survivors who might benefit from preventive interventions and intensive follow-up.
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| 20. |
- Mogensen, Hanna, et al.
(author)
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Educational attainment in survivors of childhood cancer in Denmark, Finland, and Sweden
- 2024
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In: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 130:2, s. 260-268
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Journal article (peer-reviewed)abstract
- Background: Survivors of childhood cancer may face difficulties at school. We investigated whether childhood cancer affects attainment of upper secondary education, in a register-based cohort study from Denmark, Finland, and Sweden, where we limit bias from selection and participation.Methods: From the national cancer registers, we identified all long-term survivors of childhood cancer diagnosed aged 0–14 years in 1971–2005 (n = 7629), compared them to matched population comparisons (n = 35,411) and siblings (n = 6114), using odds ratios (OR) and 95% confidence intervals (CI).Results: Overall, 6127 survivors (80%) had attained upper secondary education by age 25, compared to 84% among comparison groups. Elevated OR for not attaining this level were mainly confined to survivors of central nervous system (CNS) tumours (ORSurv_PopComp2.05, 95%CI: 1.83–2.29). Other risk groups were survivors who had spent more time in hospital around cancer diagnosis and those who had hospital contacts in early adulthood, particularly psychiatric. Survivors of all cancer types were less likely to have attained upper secondary education without delay.Conclusions: Although survivors of childhood cancer experienced delays in their education, many had caught up by age 25. Except for survivors of CNS tumours, survivors attained upper secondary education to almost the same extent as their peers.
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| 21. |
- Norsker, Filippa Nyboe, et al.
(author)
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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
- 2020
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In: Acta Oncologica. - 0284-186X. ; 59:2, s. 134-140
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Journal article (peer-reviewed)abstract
- 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.
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| 22. |
- Norsker, Filippa Nyboe, et al.
(author)
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Risk of late health effects after soft-tissue sarcomas in childhood–a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia research programme
- 2020
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In: Acta Oncologica. - 0284-186X. ; 59:10, s. 1-11
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Journal article (peer-reviewed)abstract
- Background: In the 1960s only 1/3 of children with soft-tissue sarcomas survived, however with improved treatments survival today has reached 70%. Given the previous poor survival and the rarity of soft-tissue sarcomas, the risk of somatic late effects in a large cohort of Nordic soft-tissue sarcoma survivors has not yet been assessed. Methods: In this population-based cohort study we identified 985 five-year soft-tissue sarcoma survivors in Nordic nationwide cancer registries and late effects in national hospital registries covering the period 1964–2012. Information on tumour site and radiotherapy was available for Danish and Finnish survivors (N = 531). Using disease-specific rates of first-time hospital contacts for somatic diseases in survivors and in 4,830 matched comparisons we calculated relative rates (RR) and rate differences (RD). Results: Survivors had a RR of 1.5 (95% CI 1.4–1.7) and an absolute RD of 23.5 (17.7–29.2) for a first hospital contact per 1,000 person-years. The highest risks in both relative and absolute terms were of endocrine disorders (RR = 2.5; RD = 7.6), and diseases of the nervous system (RR = 1.9; RD = 6.6), digestive organs (RR = 1.7; RD = 5.4) and urinary system (RR = 1.7; RD = 5.6). By tumour site, excess risk was lower after extremity tumours. Irradiated survivors had a 2.6 (1.2–5.9) times higher risk than non-irradiated. Conclusions: Soft-tissue sarcoma survivors have an increased risk of somatic late effects in 5 out of 10 main diagnostic groups of diseases, and the risk remains increased up to 40 years after cancer diagnosis. Risks were slightly lower for those treated for tumours in the extremities, and radiotherapy increased the risk by more than two-fold.
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| 23. |
- Norsker, Filippa Nyboe, et al.
(author)
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Somatic late effects in 5-year survivors of neuroblastoma : a population-based cohort study within the Adult Life after Childhood Cancer in Scandinavia study
- 2018
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In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 143:12, s. 3083-3096
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Journal article (peer-reviewed)abstract
- 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.
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| 24. |
- Oskarsson, Trausti, et al.
(author)
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Skeletal adverse events in childhood cancer survivors : An Adult Life after Childhood Cancer in Scandinavia cohort study
- 2021
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In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 149:11, s. 1863-1876
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Journal article (peer-reviewed)abstract
- 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.
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| 25. |
- Pedersen, Camilla, et al.
(author)
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Somatic disease in survivors of childhood malignant bone tumors in the nordic countries
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:18
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Journal article (peer-reviewed)abstract
- 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.
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| 26. |
- Sällfors-Holmqvist, Anna, et al.
(author)
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Adult Life after Childhood Cancer in Scandinavia: Diabetes mellitus following treatment for cancer in childhood.
- 2014
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In: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 50:6, s. 1169-1175
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Journal article (peer-reviewed)abstract
- An increased risk for diabetes mellitus (DM) adds significantly to the burden of late complications in childhood cancer survivors. Complications of DM may be prevented by using appropriate screening. It is, therefore, important to better characterise the reported increased risk for DM in a large population-based setting.
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| 27. |
- Sällfors-Holmqvist, Anna, et al.
(author)
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Autoimmune diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS).
- 2015
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967.
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Journal article (peer-reviewed)abstract
- The pattern of autoimmune diseases in childhood cancer survivors has not been investigated previously. We estimated the risk for an autoimmune disease after childhood cancer in a large, population-based setting with outcome measures from comprehensive, nationwide health registries.
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| 28. |
- Sällfors-Holmqvist, Anna
(author)
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Long-term Morbidity and Socioeconomic Outcome among Nordic Childhood Cancer Survivors
- 2015
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Doctoral thesis (other academic/artistic)abstract
- Survival after childhood cancer has improved dramatically during the past four decades, resulting in a five-year survival rate of 80% in children recently treated for cancer in the Nordic countries. However, these advances in treatment and survival has come at a price, and many survivors face significant treatment-induced sequelae, most of which only become clinically apparent many years after the child has been cured. Previous studies have highlighted the need for better characterization of these late complications and their risk factors, in order to improve the basis for individual patient counselling and optimal long-term follow-up care. The main objective of the studies presented in this thesis was to investigate some of the diseases that contribute to long-term morbidity in childhood cancer survivors, as well as the late socioeconomic effects after treatment for acute lymphoblastic leukaemia (ALL) in childhood. All the studies presented in this thesis are population-based, retrospective cohort studies. Studies I and II are register-based studies of late socioeconomic effects and hospital-related morbidity, respectively, among 213 five-year survivors of ALL in the southern region of Sweden, compared to a population comparison cohort. Studies III–V included 33,160 one-year survivors of childhood cancer diagnosed between the start of cancer registration in the 1940s and 1950s up to and including 2008, identified in the national cancer registries of Denmark, Finland, Iceland, Norway and Sweden, and 212,892 comparison subjects, selected from national population registers. The study subjects in Studies III–V were linked to the national hospital registers and standardized hospitalization rate ratios and absolute excess risks of specific diseases were calculated. ALL survivors were married, had children, attained a high level of education and were employed to a lesser extent than the comparison subjects. Young age at diagnosis and cranial radiotherapy were risk factors for these negative late socioeconomic effects. Increased morbidity among ALL survivors, measured in terms of health care utilization, was primarily confined to those treated with cranial irradiation. Nordic childhood cancer survivors exhibited an increased risk of diabetes mellitus, which persisted throughout life. In addition, survivors were found to have a substantially increased risk of other endocrine disorders. The diagnoses of pituitary hypofunction, hypothyroidism and dysfunction of the gonads were the most frequent endocrine disorders found among the survivors. Childhood cancer survivors also showed an increased risk of various autoimmune diseases; increased risk ratios were seen in survivors of leukaemia, Hodgkin’s lymphoma, renal tumours and central nervous system neoplasms. The findings of these studies underscore the need for preventive interventions and prolonged follow-up of childhood cancer survivors.
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| 29. |
- Wilhelmson, Mari, et al.
(author)
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Hospitalizations in Long-term Survivors of Childhood AML Treated with Allogeneic HSCT - an Adult Life after Childhood Cancer in Scandinavia (ALiCCS) Study
- 2019
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In: 38th NOPHO Annual meeting. Aalborg, Denmark 3-7 May.
-
Conference paper (other academic/artistic)abstract
- Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is effective in treating childhood acute myeloid leukemia (AML) but the long-term disease burden may be increased. In a population-based study, the standardized hospitalization rates ratios (SHRR) and absolute excess risks for disease specific hospitalizations were evaluated in 5-year survivors of AML treated at 0-17 years of age according to the NOPHO-AML protocols in four Nordic countries during 1984-2005. In total, 229 eligible AML survivors were identified in the NOPHO-AML database and the treatment data of 196 survivors could be linked to 5-year follow-up data in national hospital registries. After a median follow-up time of 12 (range 5–28) years, 35 out of the 97 survivors treated with allo-HSCT had been hospitalized (SHRR 2.8 (95% CI 2.0– 4.0) with increased risk for hospitalizations due to cardiovascular 8.7 (3.9–19), endocrine 12 (6.7–22), pulmonary 3.0 (1.8–5.2), gastrointestinal 4.0 (2.4–6.7), infectious 3.1 (1.3–7.6), neurological 4.4 (2.1–9.2) and uro-genital system conditions 2.9 (1.3–6.4). In comparison, after a median follow-up time of 11 (range 5–28) years, 21 out of the 99 survivors treated with chemotherapy alone had been hospitalized; SHRR 1.4 (0.9–2.1). Our results indicate that hospitalization rates are significantly increased in long-term survivors of childhood AML if treated with allo-HSCT but not in survivors treated with chemotherapy only.
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| 30. |
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| 31. |
- Winther, Jeanete F., et al.
(author)
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Childhood cancer survivor cohorts in Europe
- 2015
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In: Acta Oncologica. - 1651-226X. ; 54:5, s. 655-668
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Research review (peer-reviewed)abstract
- 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.
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| 32. |
- Winther, Jeanette F., et al.
(author)
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Risk of cardiovascular disease among Nordic childhood cancer survivors with diabetes mellitus : A report from adult life after childhood cancer in Scandinavia
- 2018
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In: Cancer. - : Wiley. - 0008-543X. ; 124:22, s. 4393-4400
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Journal article (peer-reviewed)abstract
- BACKGROUND: Childhood cancer survivors have an increased risk of cardiovascular disease (CVD) and diabetes mellitus. Because diabetes is a potentially modifiable risk factor for CVD in the general population, it is important to understand how diabetes affects the risk of CVD among childhood cancer survivors. METHODS: This study examined the risk of CVD among survivors with diabetes and 142,742 population comparison subjects. From the national cancer registries of the 5 Nordic countries, 29,324 one-year survivors of cancer diagnosed before the age of 20 years between 1968 and 2008 were identified. Study subjects were linked to the national hospital registers. The cumulative incidence of CVD was determined with competing risk methods. A Cox proportional hazards model was used to estimate the effects of diabetes and cancer on the hazard of CVD. The interaction between diabetes and cancer was analyzed. RESULTS: Diabetes was diagnosed in 324 of the 29,324 one-year survivors, and CVD was diagnosed in 2108. The hazard of diabetes was 1.7 times higher among survivors than comparison subjects (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.5-1.9), whereas the HR of CVD was 3.6 (95% CI, 3.3-3.8) 1 to 15 years after the cancer diagnosis and 1.9 (95% CI, 1.8-2.0) after more than 15 years. Individuals with diabetes had a 2.4 times higher hazard of CVD (95% CI, 2.1-2.8) among both survivors and comparison subjects in comparison with individuals without diabetes. CONCLUSIONS: Childhood cancer survivors with diabetes have a markedly increased risk of CVD in comparison with survivors without diabetes. However, diabetes does not increase the risk of CVD more in survivors than the general population.
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