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.     

Educational attainment among survivors of childhood cancer: a population-based cohort study in Denmark

We identified 2384 patients in the Danish Cancer Register in whom cancer had been diagnosed in 1960-1996 before they reached the age of 20 and compared them with 53 143 sex- and age-matched controls identified from the Register of Population Statistics. Complete education records and demographic and socioeconomic information for the period 1980-2000 were obtained for both cohorts from Statistics Denmark. The rate ratio (RR) for educational attainment was estimated by discrete-time Cox regression analyses. An overall reduction in attaining basic education was found (RR, 0.90; 95% confidence interval, 0.83-0.96). Female survivors of central nervous system (CNS) tumours showed the largest educational deficit (RR, 0.55; 95% confidence interval, 0.37-0.82). Non-CNS tumour survivors attained education as controls at most levels. When the analyses were conditioned on completion of youth education, further educational attainment was not reduced for any group of survivors. These findings confirm that only survivors of CNS tumours in childhood experience significant educational deficits. The deficit was mainly seen among persons whose tumour was diagnosed before they reached the level of secondary education.     

Gastrointestinal and liver disease in Adult Life After Childhood Cancer in Scandinavia: A population‐based cohort study

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.     

Sex ratio among offspring of childhood cancer survivors treated with radiotherapy

It has been postulated that paternal gonadal exposure would increase the sex ratio by inducing X-chromosomal dominant lethals but that maternal gonadal exposure would decrease the sex ratio by inducing recessive sex-linked lethals. We therefore evaluated the sex ratio (male-to-female ratio) of children born to survivors of childhood cancers in Denmark. Children with cancer were identified from the Danish Cancer Registry from 1943 to 1996 and their offspring from the Central Population Registry. Radiation treatments were determined from records within the Cancer Registry and gonadal radiation exposures were estimated based on the cancer being treated and the likely proximity of the radiation fields to the gonads. Overall, 1100 survivors of childhood cancer became the parents of 2130 children. The sex ratio for male (0.99) and female (1.00) cancer survivors was similar and did not differ significantly from the Danish population (1.06). Radiotherapy did not influence the sex ratio of the children of either male or female survivors, and there was no evidence for dose-related changes over categories of estimated dose to parental gonads. We saw no consistent association between the sex ratio and the interval between cancer diagnosis of the parent and birth of the child. This nationwide study provides no support for the hypothesis that radiation exposure to the gonads results in an inherited genetic effect that would be manifested by a change in the sex ratio of children born after exposure. It may be, however, that sex ratio alterations are not a good or even a valid indicator of possible genetic effects in humans.     

Molar pregnancy and childhood cancer: a population-based linkage study from Denmark

We observed a relative risk of 1.40 (95% confidence interval; 0.86-2.16) for cancers diagnosed under the age 20 in 6192 offspring of 3431 mothers with a molar pregnancy, indicating it is not a major determinant of childhood cancer.     

Long-term population-based marriage rates among adult survivors of childhood cancer in Britain

The objectives of this study were to assess the number of adult survivors of childhood cancer who ever married and the factors influencing marriage, compare observed marriages to those expected from the general population, and assess age at marriage and influencing factors. The data is based on the British Childhood Cancer Survivor Study (BCCSS), which is a population-based cohort of 18,119 individuals who were diagnosed with childhood cancer between 1940 and 91 and survived at least 5 years. Fourteen thousand five hundred thirty-nine were alive, aged at least 16 years and eligible to receive a postal questionnaire, which ascertained marriage status. Thirty-four percent of 9,954 survivors had married. Survivors with the following characteristics: males, CNS neoplasm, received radiotherapy, diagnosed with mental retardation, registered blind, low social functioning score (calculated from SF-36 health status measure), and achieved the highest level of educational attainment, were less likely to have married than the complementary survivor groups. The deficits in the proportion ever married compared to the general population were mostly between 9 and 18% among males and 7-10% among females. The largest ever married deficits were among male CNS neoplasm survivors aged 30 years or over (29-38%). Age at first marriage among survivors was related to: sex, childhood cancer type, age at diagnosis, chemotherapy, radiotherapy, mental retardation, and level of educational attainment. Regular follow-up for these survivors should address not just physical late-effects of the childhood cancer and treatment, but also psychosocial needs throughout the lifespan of the survivors to help them achieve life events as they occur in the general population.     

Life After Cancer Epidemiology (LACE) Study: A cohort of early stage breast cancer survivors (United States)

The Life After Cancer Epidemiology (LACE) Study, a cohort of 2321 early stage breast cancer survivors, was established in 2000 to examine how modifiable behavioral risk factors affect quality of life and long-term survival. Women were recruited primarily from the Kaiser Permanente Northern California Cancer Registry (KPNCAL) and the Utah cancer registry (UCR), United States. Baseline data were collected, on average, at two years post-diagnosis through self-administered questionnaires that included information on demographics, medical history, anthropometry, diet, supplements, physical activity and quality of life. The purpose of this paper is to describe the creation and baseline characteristics of the cohort. Forty-six percent of women to whom questionnaires were mailed agreed to participate. The cohort which is 80% white, was diagnosed predominantly with Stage I and II breast cancer (93%), and will have been followed for 5.6 years post-diagnosis, on average, by the end of 2004. Women reported slightly over four daily servings of fruit and vegetables, well below the suggested 5-A-Day national guidelines. Compared to women free of cancer, physical activity patterns were similar, while weight gain, especially in younger women, was higher than is typical. These data suggest that in the early years post-diagnosis, breast cancer survivors exhibit similar patterns to the general population in many health behaviors.* Address correspondence to: Bette Caan, Dr. PH, Division of Research, Kaiser Permanente Medical Program, 2000 Broadway, Oakland, CA 94612, USA. Ph.: +1-510-891-3719; Fax: +1-510-891-3761; E-mail: Bjc@dor.kaiser.org     

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

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

Health-status of adult survivors of childhood cancer: a large-scale population-based study from the British Childhood Cancer Survivor Study

The purpose of this study was to investigate the effect of childhood cancer and its treatment on self-reported health-status in 10,189 adult survivors of childhood cancer in Britain. Age- and sex-adjusted scores on the SF-36 Mental and Physical Component Summary scales (MCS, PCS, respectively) were compared between survivors and UK norms, and between subgroups of survivors, by multiple regression. Survivors had comparable scores to UK-norms on the MCS scale (difference (D) = -0.1, 99% CI: -0.5, 0.3). The difference in scores between survivors and UK-norms on the PCS scale varied by age (p(heterogeneity) < 0.001). Young survivors (16-19 years) scored similarly to UK-norms (D = 0.5, (-1.1, 2.2), whereas the age groups of 25 and older scored statistically and clinically significantly below UK-norms (all p-values < 0.0001), with Ds ranging between -2.3 (-3.5, -1.2) and -3.7 (-5.0, -2.4). Survivors of central nervous system (CNS) and bone tumors scored significantly (p-value at all ages <0.003) below UK-norms on the PCS scale. Specifically, these survivors were substantially more limited in specific daily activities such as, for example, walking a mile (40, 63%, respectively) when compared to UK-norms (16%). In conclusion, childhood cancer survivors rate their mental health broadly similarly to those in the general population. Survivors of CNS and bone tumors report their physical health-status to be importantly below population norms. Although self-reported physical health is at least as good as in the general population among young survivors, this study suggests that perceived physical health declines more rapidly over time than in the general population.     

Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): A population‐based cohort study of 32,839 one‐year survivors

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.     

Hospital-related morbidity among childhood cancer survivors in British Columbia, Canada: report of the childhood, adolescent, young adult cancer survivors (CAYACS) program

Our study examines inpatient, hospital-related morbidity in a geographically-defined cohort of long-term cancer survivors diagnosed before age 20 years in the province of British Columbia (BC), Canada. A total of 1374 survivors diagnosed from 1981 to 1995 surviving at least 5-years postdiagnosis, and a matched sample of 13,740 BC residents, were identified from population registers, and linked to provincial hospitalization records from 1986 to 2000. Logistic regression was used to assess relative risk and effect of sociodemographic, clinical, and temporal factors on risk. Approximately 41% of survivors vs. 17% of the population sample had at least one type of hospitalization-related late morbidity in the observation period (adjusted RR 4.1, 95% CI 3.7-4.5). Those at highest risk were survivors of leukemia (RR 4.8, 95% CI 4.0-5.8), central nervous system tumors (RR 4.8, 95% CI 4.0-5.8), bone and soft tissue sarcomas (RR 4.9, 95% CI 3.8-6.2), and kidney cancer (RR 4.9, 95% CI 3.4-7.0). Adjusted relative risk was elevated for all types of morbidity except pregnancy and birth complications, and highest for neoplasms (including second primary cancers) (RR 21.7, 95% CI 16.3-28.7). Morbidity was elevated for all combinations of primary treatment and highest for those with previous radiation, chemotherapy, and surgery (RR 7.1, 95% CI 5.5-9.0). Over time, morbidity for late effects other than neoplasms became more prevalent. These results suggest that survivors are at increased ongoing risk of many types of hospital-related late morbidity, implying that long-term monitoring for multiple health problems is warranted.     

Impact of insurance type on survivor-focused and general preventive health care utilization in adult survivors of childhood cancer: the Childhood Cancer Survivor Study (CCSS)

BACKGROUND:

Lack of health insurance is a key barrier to accessing care for chronic conditions and cancer screening. The influence of insurance type (private, public, none) on survivor‐focused and general preventive health care in adult survivors of childhood cancer was examined.

METHODS:

The Childhood Cancer Survivor Study is a retrospective cohort study of childhood cancer survivors diagnosed between 1970 and 1986. Among 8425 adult survivors, the relative risk (RR) and 95% confidence interval (CI) of receiving survivor‐focused and general preventive health care were estimated for uninsured (n = 1390) and publicly insured (n = 640), compared with for the privately insured (n = 6395)

RESULTS:

Uninsured survivors were less likely than those privately insured to report a cancer‐related visit (adjusted RR, 0.83; 95% CI, 0.75‐0.91) or a cancer center visit (adjusted RR, 0.83; 95% CI, 0.71‐0.98). Uninsured survivors had lower levels of utilization in all measures of care in comparison with privately insured. In contrast, publicly insured survivors were more likely to report a cancer‐related visit (adjusted RR, 1.22; 95% CI, 1.11‐1.35) or a cancer center visit (adjusted RR, 1.41; 95% CI, 1.18‐1.70) than were privately insured survivors. Although publicly insured survivors had similar utilization of general health examinations, they were less likely to report a Papanicolaou test or a dental examinations

CONCLUSIONS:

Among this large, socioeconomically diverse cohort, publicly insured survivors utilize survivor‐focused health care at rates at least as high as survivors with private insurance. Uninsured survivors have lower utilization of both survivor‐focused and general preventive health care. Cancer 2011. © 2010 American Cancer Society.