Fatigue and cognitive fatigability in patients with chronic pain.

OBJECTIVES: Fatigue is common in patients with chronic pain. Still, there is a lack of studies examining objectively measurable cognitive aspects of fatigue: cognitive fatigability (CF). We aimed to investigate the presence of CF in patients with chronic pain and its relation to self-rated fatigue, attention, pain characteristics, sleep disturbance, depression, and anxiety. METHODS: Two hundred patients with chronic pain and a reference group of 36 healthy subjects underwent a comprehensive neuropsychological test battery, including measurement of CF with the Wechsler Adult Intelligence Scale-III Coding subtest, and self-assessment of trait and state fatigue. RESULTS: The patients with chronic pain did not show more CF as compared to the reference group. There was an association between CF and processing speed on a test of sustained and selective attention in the chronic pain group, while self-rated fatigue measures and pain characteristics were not associated with CF. Self-rated fatigue measures were highly correlated with self-rated pain intensity, spreading of pain, depression, anxiety, and sleep disturbance. CONCLUSIONS: The findings highlight the distinction between objective and subjective aspects of fatigue in chronic pain, and that the underlying causes of these different aspects of fatigue need to be studied further.

Late morbidity and mortality after autologous blood or marrow transplantation for lymphoma in children, adolescents and young adults-a BMTSS report.

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.

Educational attainment in survivors of childhood cancer in Denmark, Finland, and Sweden.

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.

Cognitive and mental fatigue in chronic pain: cognitive functions, emotional aspects, biomarkers and neuronal correlates-protocol for a descriptive cross-sectional study.

INTRODUCTION: Chronic pain (CP) is one of the most frequently presenting conditions in health care and many patients with CP report mental fatigue and a decline in cognitive functioning. However, the underlying mechanisms are still unknown. METHODS AND ANALYSIS: This study protocol describes a cross-sectional study aimed at investigating the presence of self-rated mental fatigue, objectively measured cognitive fatigability and executive functions and their relation to other cognitive functions, inflammatory biomarkers and brain connectivity in patients with CP. We will control for pain-related factors such as pain intensity and secondary factors such as sleep disturbances and psychological well-being. Two hundred patients 18-50 years with CP will be recruited for a neuropsychological investigation at two outpatient study centres in Sweden. The patients are compared with 36 healthy controls. Of these, 36 patients and 36 controls will undergo blood sampling for inflammatory markers, and of these, 24 female patients and 22 female controls, between 18 and 45 years, will undergo an functional MRI investigation. Primary outcomes are cognitive fatigability, executive inhibition, imaging and inflammatory markers. Secondary outcomes include self-rated fatigue, verbal fluency and working memory. The study provides an approach to study fatigue and cognitive functions in CP with objective measurements and may demonstrate new models of fatigue and cognition in CP. ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethics Review Board (Dnr 2018/424-31; 2018/1235-32; 2018/2395-32; 2019-66148; 2022-02838-02). All patients gave written informed consent to participate in the study. The study findings will be disseminated through publications in journals within the fields of pain, neuropsychology and rehabilitation. Results will be spread at relevant national and international conferences, meetings and expert forums. The results will be shared with user organisations and their members as well as relevant policymakers. TRIAL REGISTRATION NUMBER: NCT05452915.

Severe, life-threatening, and fatal chronic health conditions after allogeneic blood or marrow transplantation in childhood.

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.

Long-Term Risk of Hospitalization for Somatic Diseases Among Survivors of Childhood Acute Lymphoblastic Leukemia.

BACKGROUND: Survivors of childhood acute lymphoblastic leukemia (ALL) may be at increased long-term risk of hospitalization for somatic diseases. However, large population-based cohort studies with risk estimates for survivors successfully cured without experiencing a relapse or requiring hematopoietic stem cell transplantation (HSCT) are lacking. METHODS: Danish and Swedish patients diagnosed with ALL before age 20 years in 1982-2008 were identified in the national cancer registries. Five-year survivors and matched population comparisons without childhood cancer were followed for hospitalization for 120 somatic disease categories in the national hospital registries from 5 years postdiagnosis until 2017, and disease-specific hospitalization rate ratios (RR) were calculated. The mean cumulative count method was used to estimate the mean number of multiple and recurrent disease-specific hospitalizations per individual. RESULTS: A total of 2024 5-year survivors and 9797 population comparisons were included. The overall hospitalization rate was more than twice as high compared with comparisons (RR = 2.30, 95% confidence interval [CI] = 2.09 to 2.52). At 30 years postdiagnosis, the mean cumulative hospitalization count was 1.69 (95% CI = 1.47 to 1.90) per survivor and 0.80 (95% CI = 0.73 to 0.86) per comparison. In the subcohort without relapse or HSCT (n = 1709), the RR was 1.41 (95% CI = 1.27 to 1.58). CONCLUSIONS: Survivors of childhood ALL were at increased long-term risk for disease-specific hospitalizations; however, in survivors without relapse or HSCT, the rate was only modestly higher than in population comparisons without a childhood cancer. The absolute mean numbers of multiple and recurrent hospitalizations were generally low.

Late mortality among survivors of childhood acute lymphoblastic leukemia diagnosed during 1971-2008 in Denmark, Finland, and Sweden: A population-based cohort study.

OBJECTIVE: Investigate all-cause and cause-specific late mortality after childhood acute lymphoblastic leukemia (ALL) in a population-based Nordic cohort. METHODS: From the cancer registries of Denmark, Finland, and Sweden, we identified 3765 five-year survivors of ALL, diagnosed before age 20 during 1971-2008. For each survivor, up to five matched comparison subjects were randomly selected from the general population (n = 18,323). Causes of death were classified as relapse related, health related, and external. Late mortality was evaluated by cumulative incidences of death from 5-year survival date. Mortality hazard ratios (HR) were evaluated with Cox proportional models. RESULTS: Among the survivors, 315 deaths occurred during a median follow-up of 16 years from 5-year survival date (range 0-42). The majority were attributable to relapse (n = 224), followed by second neoplasm (n = 45). Cumulative incidence of all-cause late mortality at 15 years from diagnosis decreased gradually over treatment decades, from 14.4% (95% confidence interval [CI]: 11.6-17.2) for survivors diagnosed during 1971-1981, to 2.5% (95% CI: 1.3-3.7) for those diagnosed during 2002-2008. This was mainly attributable to a reduction in relapse-related deaths decreasing from 13.4% (95% CI: 10.7-16.1) for survivors diagnosed during 1971-1981 to 1.9% (95% CI: 0.9-2.8) for those diagnosed during 2002-2008. Health-related late mortality was low and did not change substantially across treatment decades. Compared to comparison subjects, all-cause mortality HR was 40 (95% CI: 26-61) 5-9 years from diagnosis, and 4.4 (95% CI: 3.4-5.6) ≥10 years from diagnosis. CONCLUSIONS: Survivors of ALL have higher late mortality than population comparison subjects. Among the survivors, there was a temporal reduction in risk of death from relapse, without increments in health-related death.

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.

Burden of Morbidity after Allogeneic Blood or Marrow Transplantation for Inborn Errors of Metabolism: A BMT Survivor Study Report.

Survival after blood or marrow transplantation (BMT) for inborn errors of metabolism (IEM) is excellent; however, the burden of morbidity in long-term survivors of BMT for IEM remains understudied. This study examined the risk of chronic health conditions (CHC) in ≥2-year survivors of allogeneic BMT for IEM performed between 1974 and 2014 using the BMT Survivor Study. In this retrospective cohort study, participants (or their parents; n = 154) reported demographic data and CHCs (graded using Common Terminology Criteria for Adverse Events version 5), and transplantation characteristics were obtained from institutional databases. Unaffected siblings (n = 494) served as a comparison group. Logistic regression was used to estimated the odds of severe/life-threatening CHCs compared with siblings. Cox proportional hazards regression was used to estimate factors associated with severe/life-threatening/fatal CHCs in survivors of BMT for IEM. Survivors of allogeneic BMT for IEM (leukodystrophies, 43.5%; mucopolysaccharidoses, 41.0%) were at 12.5-fold higher odds of severe/life-threatening CHCs (95% confidence interval [CI], 5.4 to 28.9) compared with their siblings. The mean 10-year post-BMT cumulative incidence of grade 3-5 CHCs was 47.5 ± 4.0%. Reduced-intensity conditioning (RIC) was associated with a 2.7-fold higher risk (95% CI, 1.2 to 6.2; P = .02) of any grade 3-5 CHC, a 6.7-fold higher risk of grade 3-5 cardiopulmonary conditions (95% CI, 1.3 to 35.4), and a 3.0-fold higher risk of severe hearing/vision deficits (95% CI, 1.4 to 6.6). Older (age >26 years) BMT survivors were significantly less likely to graduate from college (odds ratio [OR], 0.3; 95% CI, 0.1 to 0.7) or marry (OR, 0.01; 95% CI, 0.004 to 0.07) compared with their siblings. Survivors of BMT for IEM carry a significant burden of morbidities, which affects their ability to attain adult milestones. Efforts to reduce chronic health conditions in this population are needed.

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.

Does Intensive Training of Attention Influence Cognitive Fatigability in Patients With Acquired Brain Injury?

RESEARCH OBJECTIVES: Impairments in attention and the speed of information processing are central to the experience of cognitive fatigue in patients with acquired brain injury (ABI). Attention may be improved through intensive training in a rehabilitation setting. The aim of the study was to investigate the feasibility of reducing cognitive fatigability (CF) using attention training and to explore the effect of two different approaches to attention training. DESIGN: Randomised controlled study in a rehabilitation setting. PARTICIPANTS: 59 patients (age 19-59 years) with mild to moderate stroke or traumatic brain injury in the early (<4 month) phase. INTERVENTIONS: Patients were randomly assigned to intensive specific training with Attention Process Training (APT) or Activity-Based Attention Training (ABAT) for 3-5 days per week for a period of 5-6 weeks with a total of 20 h, in addition to traditional interdisciplinary rehabilitation. MAIN OUTCOME MEASURE: CF was conceptualised as performance decline in terms of an increased number of incorrect responses between the first and the last quintiles of the Paced Auditory Serial Addition Test (PASAT). A negative result was defined as fatigability. The evaluator of fatigability was blinded to treatment. RESULTS: At baseline, there were no differences between the groups in age, education, reasoning, anxiety or depression. After training, a significant treatment effect was found (p = 0.020), as the APT-group, but not the ABAT-group, had improved. However, after controlling for baseline differences regarding CF on the PASAT-f, the difference was no longer significant. CONCLUSION: The results indicate that cognitive training might be a feasible method for reducing CF through attention training and that patients with high levels of CF benefit most from attention training. The type of intervention provided, whether specific or activity-based attention training, appears to be of less importance, as there was no treatment effect after controlling for the baseline level of CF. Future studies are required to confirm the validity of the findings.

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.

Temporal changes in the probability of live birth among female survivors of childhood cancer: A population-based Adult Life After Childhood Cancer in Scandinavia (ALiCCS) study in five nordic countries.

BACKGROUND: During the past 4 decades, there has been a growing focus on preserving the fertility of patients with childhood cancer; however, no large studies have been conducted of live births across treatment decades during this period. Therefore, the authors estimated the potential birth deficit in female childhood cancer survivors and the probability of live births. METHODS: In total, 8886 women were identified in the 5 Nordic cancer registries in whom a childhood cancer had been diagnosed during 1954 through 2006. A population comparison cohort of 62,903 women was randomly selected from the central population registries matched by age and country. All women were followed for live births recorded in medical birth registries. The cumulative probability and the risk ratio (RR) with 95% confidence intervals (CIs) of a live birth were calculated by maternal age across treatment decades. RESULTS: The probability of a live birth increased with treatment decade, and, at age 30 years, the rate for survivors most recently diagnosed was close to the rate among the general population (1954-1969: RR, 0.65 [95% CI, 0.54-0.78]; 1970s: RR, 0.67 [95% CI, 0.60-0.74]; 1980s: RR, 0.69 [95% CI, 0.64-0.74]; 1990s: RR, 0.91 [95% CI, 0.87-0.95]; 2000s: RR, 0.94 [95% CI, 0.91-0.97]). CONCLUSIONS: Female childhood cancer survivors had a lower probability of a live birth than women in the general population, although, in survivors diagnosed after 1989, the probability was close to that of the general population. Because the pattern of live births differs by cancer type, continuous efforts must be made to preserve fertility, counsel survivors, and refer them rapidly to fertility treatment if necessary. LAY SUMMARY: The purpose of this study was to compare the probability of giving birth to a liveborn child in female survivors of childhood cancer with that of women in the general population. Survivors of childhood cancer had a lower probability of live births than women in the general population, although survivors diagnosed after 1989 had a probability close to that of the general population. Continuing focus on how to preserve the potential for fertility among female patients with childhood cancer during treatment is important to increase their chances of having a child.

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 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.

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.

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.

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.