Effectiveness and cost-effectiveness of The Daily Mile on childhood weight outcomes and wellbeing: a cluster randomised controlled trial.

BACKGROUND: The Daily Mile is designed to increase physical activity levels with children running or walking around school grounds for 15-min daily. It has been adopted by schools worldwide and endorsed as a solution to tackle obesity, despite no robust evidence of its benefits. We conducted a cluster randomised controlled trial to determine its clinical and cost-effectiveness. METHODS: Forty schools were randomly assigned (1:1) to either the Daily Mile intervention or control group in which only the usual school health and wellbeing activities were implemented. The primary outcome was BMI z-score (BMIz) at 12 months follow-up from baseline, with planned subgroup analysis to examine differential effects. Primary economic analysis outcome was incremental cost per Quality-Adjusted-Life-Year (QALY) gained. RESULTS: Using a constrained randomisation approach, balanced on school size, baseline BMIz and proportion of pupils eligible for free school meals, 20 schools were allocated to intervention (n = 1,153 participants) and 20 to control (n = 1,127); 3 schools withdrew (2 intervention, 1 control). At 12 months, BMIz data were available for 18 intervention schools (n = 850) and 19 control schools (n = 820 participants). Using intention-to-treat analysis the adjusted mean difference (MD) in BMIz (intervention - control) was -0.036 (95% CI: -0.085 to 0.013, p = 0.146). Pre-specified subgroup analysis showed a significant interaction with sex (p = 0.001) suggesting a moderate size benefit of The Daily Mile in girls (MD -0.097, 95% CI -0.156 to -0.037). This was consistent with the exploratory economic results that showed The Daily Mile to be highly cost-effective in girls (£2,492 per QALY), but not in boys, and overall to have a 76% chance of cost-effectiveness for the whole sample, at the commonly applied UK threshold of £20,000 per QALY. CONCLUSIONS: Overall the Daily Mile had a small but non-significant effect on BMIz, however, it had a greater effect in girls suggesting that it might be considered as a cost-effective component of a system-wide approach to childhood obesity prevention.

An exploration of the longitudinal relation between parental feeding practices and child anthropometric adiposity measures from the West Midlands Active Lifestyle and Healthy Eating in Schoolchildren (WAVES) Study.

Background: Some research suggests that parent or carer feeding practices may influence children's weight patterns, but longitudinal evidence is limited and inconsistent. Objective: The aim of this study was to investigate the relation between various parent or carer feeding practices when a child is aged 7-8 y and proxy measurements of child adiposity at age 8-9 y (weight status, waist-to-height ratio, and body fat percentage). Design: The study was a secondary analysis of data from the West Midlands Active Lifestyle and Healthy Eating in Schoolchildren (WAVES) Study comprising a diverse sample of parents and carers and their children from 54 primary schools in the West Midlands, England [n = 774 parent-child dyads (53% of the WAVES study sample)]. Information on feeding practices was collected with the use of subscales from the Comprehensive Feeding Practices Questionnaire, completed by the child's main parent or carer (self-defined). Child height, weight, bioelectrical impedance, and waist circumference were measured and converted into 3 proxy measurements of adiposity (weight status, waist-to-height ratio, and body fat percentage). Associations between these measurements and parent or carer feeding practices were examined with the use of mixed-effects logistic regression models. Results: Of the questionnaire respondents, 80% were mothers, 16% were fathers, and 4% were other carers. Median standardized subscale scores ranged from 1.7 (emotion regulation: IQR = 1.0) to 4.0 (monitoring and modeling: IQR = 1.5), and significantly different subscale scores were present between child weight statuses for emotion regulation, pressure to eat, and restriction for weight control. Logistic regression modeling showed that when baseline adiposity measures were included as covariates, all associations between parental feeding practices at age 7-8 y and measures of adiposity at age 8-9 y were attenuated. Conclusions: Observed relations between various parental feeding practices and later adiposity are mitigated by inclusion of the baseline adiposity measure. This finding lends support to the theory of reverse causation, whereby the child's size may influence parental choice of specific feeding practices rather than the child's subsequent weight status being a consequence of these feeding practices.

Effectiveness of a childhood obesity prevention programme delivered through schools, targeting 6 and 7 year olds: cluster randomised controlled trial (WAVES study).

OBJECTIVE: To assess the effectiveness of a school and family based healthy lifestyle programme (WAVES intervention) compared with usual practice, in preventing childhood obesity. DESIGN: Cluster randomised controlled trial. SETTING: UK primary schools from the West Midlands. PARTICIPANTS: 200 schools were randomly selected from all state run primary schools within 35 miles of the study centre (n=980), oversampling those with high minority ethnic populations. These schools were randomly ordered and sequentially invited to participate. 144 eligible schools were approached to achieve the target recruitment of 54 schools. After baseline measurements 1467 year 1 pupils aged 5 and 6 years (control: 28 schools, 778 pupils) were randomised, using a blocked balancing algorithm. 53 schools remained in the trial and data on 1287 (87.7%) and 1169 (79.7%) pupils were available at first follow-up (15 month) and second follow-up (30 month), respectively. INTERVENTIONS: The 12 month intervention encouraged healthy eating and physical activity, including a daily additional 30 minute school time physical activity opportunity, a six week interactive skill based programme in conjunction with Aston Villa football club, signposting of local family physical activity opportunities through mail-outs every six months, and termly school led family workshops on healthy cooking skills. MAIN OUTCOME MEASURES: The protocol defined primary outcomes, assessed blind to allocation, were between arm difference in body mass index (BMI) z score at 15 and 30 months. Secondary outcomes were further anthropometric, dietary, physical activity, and psychological measurements, and difference in BMI z score at 39 months in a subset. RESULTS: Data for primary outcome analyses were: baseline, 54 schools: 1392 pupils (732 controls); first follow-up (15 months post-baseline), 53 schools: 1249 pupils (675 controls); second follow-up (30 months post-baseline), 53 schools: 1145 pupils (621 controls). The mean BMI z score was non-significantly lower in the intervention arm compared with the control arm at 15 months (mean difference -0.075 (95% confidence interval -0.183 to 0.033, P=0.18) in the baseline adjusted models. At 30 months the mean difference was -0.027 (-0.137 to 0.083, P=0.63). There was no statistically significant difference between groups for other anthropometric, dietary, physical activity, or psychological measurements (including assessment of harm). CONCLUSIONS: The primary analyses suggest that this experiential focused intervention had no statistically significant effect on BMI z score or on preventing childhood obesity. Schools are unlikely to impact on the childhood obesity epidemic by incorporating such interventions without wider support across multiple sectors and environments. TRIAL REGISTRATION: Current Controlled Trials ISRCTN97000586.

The West Midlands ActiVe lifestyle and healthy Eating in School children (WAVES) study: a cluster randomised controlled trial testing the clinical effectiveness and cost-effectiveness of a multifaceted obesity prevention intervention programme targeted at children aged 6-7 years.

BACKGROUND: Systematic reviews suggest that school-based interventions can be effective in preventing childhood obesity, but better-designed trials are needed that consider costs, process, equity, potential harms and longer-term outcomes. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of the WAVES (West Midlands ActiVe lifestyle and healthy Eating in School children) study intervention, compared with usual practice, in preventing obesity among primary school children. DESIGN: A cluster randomised controlled trial, split across two groups, which were randomised using a blocked balancing algorithm. Schools/participants could not be blinded to trial arm. Measurement staff were blind to allocation arm as far as possible. SETTING: Primary schools, West Midlands, UK. PARTICIPANTS: Schools within a 35-mile radius of the study centre and all year 1 pupils (aged 5-6 years) were eligible. Schools with a higher proportion of pupils from minority ethnic populations were oversampled to enable subgroup analyses. INTERVENTIONS: The 12-month intervention encouraged healthy eating/physical activity (PA) by (1) helping teachers to provide 30 minutes of additional daily PA, (2) promoting 'Villa Vitality' (interactive healthy lifestyles learning, in an inspirational setting), (3) running school-based healthy cooking skills/education workshops for parents and children and (4) highlighting information to families with regard to local PA opportunities. MAIN OUTCOME MEASURES: The primary outcomes were the difference in body mass index z-scores (BMI-zs) between arms (adjusted for baseline body mass index) at 3 and 18 months post intervention (clinical outcome), and cost per quality-adjusted life-year (QALY) (cost-effectiveness outcome). The secondary outcomes were further anthropometric, dietary, PA and psychological measurements, and the difference in BMI-z between arms at 27 months post intervention in a subset of schools. RESULTS: Two groups of schools were randomised: 27 in 2011 (n = 650 pupils) [group 1 (G1)] and another 27 in 2012 (n = 817 pupils) [group 2 (G2)]. Primary outcome data were available at first follow-up (n = 1249 pupils) and second follow-up (n = 1145 pupils) from 53 schools. The mean difference (MD) in BMI-z between the control and intervention arms was -0.075 [95% confidence interval (CI) -0.183 to 0.033] and -0.027 (95% CI -0.137 to 0.083) at 3 and 18 months post intervention, respectively. The main analyses showed no evidence of between-arm differences for any secondary outcomes. Third follow-up included data on 467 pupils from 27 G1 schools, and showed a statistically significant difference in BMI-z (MD -0.20, 95% CI -0.40 to -0.01). The mean cost of the intervention was £266.35 per consented child (£155.53 per child receiving the intervention). The incremental cost-effectiveness ratio associated with the base case was £46,083 per QALY (best case £26,804 per QALY), suggesting that the intervention was not cost-effective. LIMITATIONS: The presence of baseline primary outcome imbalance between the arms, and interschool variation in fidelity of intervention delivery. CONCLUSIONS: The primary analyses show no evidence of clinical effectiveness or cost-effectiveness of the WAVES study intervention. A post hoc analysis, driven by findings at third follow-up, suggests a possible intervention effect, which could have been attenuated by baseline imbalances. There was no evidence of an intervention effect on measures of diet or PA and no evidence of harm. FUTURE WORK: A realist evidence synthesis could provide insights into contextual factors and strategies for future interventions. School-based interventions need to be integrated within a wider societal framework and supported by upstream interventions. TRIAL REGISTRATION: Current Controlled Trials ISRCTN97000586. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 8. See the NIHR Journals Library website for further project information.

Risk stratification of childhood cancer survivors necessary for evidence-based clinical long-term follow-up.

BACKGROUND: Reorganisation of clinical follow-up care in England was proposed by the National Cancer Survivorship Initiative (NCSI), based on cancer type and treatment, ranging from Level 1 (supported self-management) to Level 3 (consultant-led care). The objective of this study was to provide an investigation of the risks of serious adverse health-outcomes associated with NCSI Levels of clinical care using a large population-based cohort of childhood cancer survivors. METHODS: The British Childhood Cancer Survivor Study (BCCSS) was used to investigate risks of specific causes of death, subsequent primary neoplasms (SPNs) and non-fatal non-neoplastic outcomes by NCSI Level. RESULTS: Cumulative (excess) risks of specified adverse outcomes by 45 years from diagnosis among non-leukaemic survivors assigned to NCSI Levels 1, 2 and 3 were for: SPNs-5% (two-fold expected), 14% (four-fold expected) and 21% (eight-fold expected); non-neoplastic death-2% (two-fold expected), 4% (three-fold expected) and 8% (seven-fold expected); non-fatal non-neoplastic condition-14%, 27% and 40%, respectively. Consequently overall cumulative risks of any adverse health outcome were 21%, 45% and 69%, respectively. CONCLUSIONS: Despite its simplicity the risk stratification tool provides clear and strong discrimination between survivors assigned to different NCSI Levels in terms of long-term cumulative and excess risks of serious adverse outcomes.

Employment status and occupational level of adult survivors of childhood cancer in Great Britain: The British childhood cancer survivor study.

The British Childhood Cancer Survivor Study (BCCSS) provides the first detailed investigation of employment and occupation to be undertaken in a large population-based cohort. Previous studies have been limited by design issues such as using small numbers of survivors with specific diagnoses, and involved limited assessment of employment status and occupational level. The BCCSS includes 17,981 5-year survivors of childhood cancer. Employment status and occupational level were ascertained by questionnaire from eligible survivors (n = 14,836). Multivariate logistic regression was used to explore factors associated with employment and occupation, and to compare survivors to their demographic peers in the general population. Employment status was available for 10,257 survivors. Gender, current age, cancer type, radiotherapy, age at diagnosis and epilepsy were consistently associated with being: employed; unable to work; in managerial or non-manual occupations. Overall, survivors were less likely to be working than expected (OR (99% CI): 0.89 (0.81-0.98)), and this deficit was greatest for irradiated CNS neoplasm survivors (0.34 (0.28-0.41)). Compared to the general population, survivors were fivefold more likely to be unable to work due to illness/disability; the excess was 15-fold among CNS neoplasm survivors treated with radiotherapy. Overall survivors were less likely to be in managerial occupations than expected (0.85 (0.77-0.94)). However, bone sarcoma survivors were more likely to be in these occupations than expected (1.37 (1.01-1.85)) and also similarly for non-manual occupations (1.90 (1.37-2.62)). Survivors of retinoblastoma (1.55 (1.20-2.01)) and 'other' neoplasm group (1.62 (1.30-2.03)) were also more likely to be in non-manual occupations than expected.

Risk of Adverse Health and Social Outcomes Up to 50 Years After Wilms Tumor: The British Childhood Cancer Survivor Study.

PURPOSE: Survivors of Wilms tumor (WT) are at risk for adverse health and social outcomes but risks beyond 30 years from diagnosis remain uncertain. We investigated the risks of adverse outcomes among 5-year survivors of WT, in particular, those between 30 and 50 years from diagnosis. PATIENTS AND METHODS: The British Childhood Cancer Survivor Study includes 1,441 5-year survivors of WT. We investigated cause-specific mortality, risk of subsequent primary neoplasms (SPNs), and, for those who completed a questionnaire, the extent of smoking and drinking, educational achievement, health status, and health service use compared with the general population. RESULTS: Cumulative risk of death from all causes, excluding recurrence, increased substantially from 5.4% to 22.7% at 30 years and 50 years, respectively, after WT diagnosis-75% of excess deaths beyond 30 years from diagnosis were attributable to SPNs (50%) and cardiac diseases (25%). Digestive cancer, most frequently bowel, accounted for 41% of excess cancers beyond 30 years. CONCLUSION: Between 30 and 50 years from diagnosis, survivors of WT are at a substantially increased risk of premature mortality, and 75% of excess deaths were accounted for by SPNs and cardiac diseases. Radiotherapy exposure was a risk factor for both outcomes. The proportion of patients with WT who are exposed to radiotherapy has reduced substantially in recent decades because of initiatives such as the SIOP WT 2001 clinical trial, which sought to reduce late effects; however, the majority of current survivors, who are at least 30 years from diagnosis, received radiotherapy. Surveillance of this group should focus on SPNs, in particular, bowel and breast cancers, and cardiac conditions.

Parent and child perceptions of school-based obesity prevention in England: a qualitative study.

BACKGROUND: Schools are key settings for childhood obesity prevention, and the location for many intervention studies. This qualitative study aims to explore parent and child experiences of the WAVES study obesity prevention intervention, in order to gain understanding of the mechanisms by which the intervention results in behaviour change, and provide context to support interpretation of the main trial results. METHODS: Focus groups were held with 30 parents and 62 children (aged 6-7 years) from primary schools in the West Midlands, UK. Data analysis (conducted using NVivo 10) was guided by the Framework Approach. RESULTS: Three over-arching themes were identified: 'Impact', 'Sustainability' and 'Responsibilities', under which sub-themes were determined. Participants were supportive of the school-based intervention. Parental involvement and the influential role of the teacher were seen as key ingredients for success in promoting consistent messages and empowering some parents to make positive behavioural changes at home. Parents recognised that whilst they held the primary responsibility for obesity prevention in their children, they faced a number of barriers to healthier lifestyles, and agreed that schools have an important role to play. CONCLUSIONS: This study enabled us to better understand aspects of the WAVES study intervention programme that have the potential to initiate positive behaviour changes in families, and indicated that a combination of pathways influenced such changes. Pathways included: increasing capability through improving knowledge and skills of children and parents; increasing motivation through parental empowerment and role modelling; and the direct provision of opportunities to lead healthier lifestyles. Strategies to sustain behaviour changes, and the school role in supporting these, are important considerations.

A cluster-randomised controlled trial to assess the effectiveness and cost-effectiveness of a childhood obesity prevention programme delivered through schools, targeting 6-7 year old children: the WAVES study protocol.

BACKGROUND: There is some evidence that school-based interventions are effective in preventing childhood obesity. However, longer term outcomes, equity of effects and cost-effectiveness of interventions have not been assessed. The aim of this trial is to assess the clinical and cost-effectiveness of a multi-component intervention programme targeting the school and family environment through primary schools, in preventing obesity in 6-7 year old children, compared to usual practice. METHODS: This cluster randomised controlled trial is set in 54 primary schools within the West Midlands, UK, including a multi-ethnic, socioeconomically diverse population of children aged 6-7 years. The 12-month intervention consists of healthy diet and physical activity promotion. These include: activities to increase time spent doing physical activity within the school day, participation in the 'Villa Vitality' programme (a programme that is delivered by an iconic sporting institution (Aston Villa Football Club), which provides interactive learning opportunities for physical activity and healthy eating), healthy cooking skills workshops in school time for parents and children, and provision of information to families signposting local leisure opportunities. The primary (clinical) outcome is the difference in body mass index (BMI) z-scores between arms at 3 and 18 months post-intervention completion. Cost per Quality Adjusted Life Year (QALY) will also be assessed. The sample size estimate (1000 children split across 50 schools at follow-up) is based on 90% power to detect differences in BMI z-score of 0.25 (estimated ICC ≤ 0.04), assuming a correlation between baseline and follow-up BMI z-score of 0.9. Treatment effects will be examined using mixed model ANCOVA. Primary analysis will adjust for baseline BMI z-score, and secondary analysis will adjust for pre-specified baseline school and child level covariates. DISCUSSION: The West Midlands ActiVe lifestyle and healthy Eating in School children (WAVES) study is the first trial that will examine the cost-effectiveness and long term outcomes of a childhood obesity prevention programme in a multi-ethnic population, with a sufficient sample size to detect clinically important differences in adiposity. The intervention was developed using the Medical Research Council framework for complex interventions, and outcomes are measured objectively, together with a comprehensive process evaluation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN97000586 (registered May 2010).

Process evaluation design in a cluster randomised controlled childhood obesity prevention trial: the WAVES study.

BACKGROUND: The implementation of a complex intervention is heavily influenced by individual context. Variation in implementation and tailoring of the intervention to the particular context will occur, even in a trial setting. It is recognised that in trials, evaluating the process of implementation of a complex intervention is important, yet process evaluation methods are rarely reported. The WAVES study is a cluster randomised controlled trial to evaluate the effectiveness of an obesity prevention intervention programme targeting children aged 6-7 years, delivered by teachers in primary schools across the West Midlands, UK. The intervention promoted activities encouraging physical activity and healthy eating. This paper presents the methods used to assess implementation of the intervention. METHODS: Previous literature was used to identify the dimensions of intervention process and implementation to be assessed, including adherence, exposure, quality of delivery, participant responsiveness, context, and programme differentiation. RESULTS: Multiple methods and tools were developed to capture information on all these dimensions. These included observations, logbooks, qualitative evaluation, questionnaires and research team reflection. DISCUSSION: Data collection posed several challenges, predominantly when relying on teachers to complete paperwork, which they saw as burdensome on top of their teaching responsibilities. However, the use of multiple methods helped to ensure data on each dimension, where possible, was collected using more than one method. This also allowed for triangulation of the findings when several data sources on any one dimension were available. CONCLUSIONS: We have reported a comprehensive approach to the assessment of the implementation and processes of a complex childhood obesity prevention intervention within a cluster randomised controlled trial. These approaches can be transferred and adapted for use in other complex intervention trials. TRIAL REGISTRATION NUMBER: ISRCTN97000586.

Hypothyroidism following childhood cancer therapy-an under diagnosed complication.

To determine the prevalence of hypothyroidism amongst most adult survivors of childhood cancer in Britain using the British Childhood Cancer Survivor Study (BCCSS). The BCCSS is a population based cohort of individuals diagnosed with childhood cancer between 1940 and 1991 and who survived at least 5 years from diagnosis (n = 17,981). 10483, 71% of those survivors aged at least 16 years, returned a completed questionnaire, which asked if hypothyroidism had been diagnosed. Of the whole cohort, 7.7% reported hypothyroidism with the highest risk among patients treated for Hodgkin's disease (HD) (19.9%), CNS neoplasms (15.3%), Non-Hodgkin's lymphoma (6.2%) and leukaemia (5.2%). Survivors were more likely to develop hypothyroidism if they had received radiotherapy for HD (p = 0.0001) or a CNS neoplasm (p < 0.00005) but not leukaemia (p = 0.3). In these three patient groups, the frequency of hypothyroidism was similar in men and women. Survivors of irradiated CNS tumours reported a prevalence of hypothyroidism, which was substantially lower if discharged to primary care compared with being on hospital follow-up and which declined substantially with increased follow-up in both primary care (p = 0.004) and hospital follow-up (p = 0.023) settings. Hypothyroidism is a common finding amongst adult survivors of childhood malignancy. The substantial differences in reported hypothyroidism prevalence after irradiated CNS neoplasms suggests substantial under-diagnosis, which increased with increased follow-up, and which increased among those followed-up in primary care compared with hospital settings.

Health care use of long-term survivors of childhood cancer: the British Childhood Cancer Survivor Study.

PURPOSE: Survivors of childhood cancer are at high risk of chronic conditions, but few studies investigated whether this translates into increased health care utilization. We compared health care service utilization between childhood cancer survivors and the general British population and investigated potential risk factors. METHODS: We used data from the British Childhood Cancer Survivor Study, a population-based cohort of 17,981 individuals diagnosed with childhood cancer (1940-1991) and surviving ≥ 5 years. Frequency of talks to a doctor, hospital outpatient visits, and day-patient and inpatient hospitalizations were ascertained by questionnaire in 10,483 survivors and were compared with the General Household Survey 2002 data by using logistic regression. RESULTS: Among survivors, 16.5% had talked to a doctor in the last 2 weeks, 25.5% had attended the outpatient department of a hospital in the last 3 months, 11.9% had been hospitalized as a day patient in the last 12 months, and 9.8% had been hospitalized as an inpatient in the last 12 months. Survivors had talked slightly more often to a doctor than the general population (odds ratio [OR], 1.2; 95% CI, 1.1 to 1.3) and experienced increased hospital outpatient visits (OR, 2.5; 95% CI, 2.3 to 2.8), day-patient hospitalizations (OR, 1.4; 95% CI, 1.3 to 1.6) and inpatient hospitalizations (OR, 1.9; 95% CI, 1.7 to 2.2). Survivors of Hodgkin's lymphoma, neuroblastoma, and Wilms tumor had the highest ORs for day-patient care, whereas survivors of CNS tumors and bone sarcomas had the highest OR for outpatient and inpatient care. The OR of health care use did not vary significantly with age of survivor. CONCLUSION: We have quantified how excess morbidity experienced by survivors of childhood cancer translates into increased use of health care facilities.

Long-term risks of subsequent primary neoplasms among survivors of childhood cancer.

CONTEXT: Survivors of childhood cancer are at excess risk of developing subsequent primary neoplasms but the long-term risks are uncertain. OBJECTIVES: To investigate long-term risks of subsequent primary neoplasms in survivors of childhood cancer, to identify the types that contribute most to long-term excess risk, and to identify subgroups of survivors at substantially increased risk of particular subsequent primary neoplasms that may require specific interventions. DESIGN, SETTING, AND PARTICIPANTS: British Childhood Cancer Survivor Study--a population-based cohort of 17,981 5-year survivors of childhood cancer diagnosed with cancer at younger than 15 years between 1940 and 1991 in Great Britain, followed up through December 2006. MAIN OUTCOME MEASURES: Standardized incidence ratios (SIRs), absolute excess risks (AERs), and cumulative incidence of subsequent primary neoplasms. RESULTS: After a median follow-up time of 24.3 years (mean = 25.6 years), 1354 subsequent primary neoplasms were ascertained; the most frequently observed being central nervous system (n = 344), nonmelanoma skin cancer (n = 278), digestive (n = 105), genitourinary (n = 100), breast (n = 97), and bone (n = 94). The overall SIR was 4 times more than expected (SIR, 3.9; 95% confidence interval [CI], 3.6-4.2; AER, 16.8 per 10,000 person-years). The AER at older than 40 years was highest for digestive and genitourinary subsequent primary neoplasms (AER, 5.9 [95% CI, 2.5-9.3]; and AER, 6.0 [95%CI, 2.3-9.6] per 10,000 person-years, respectively); 36% of the total AER was attributable to these 2 subsequent primary neoplasm sites. The cumulative incidence of colorectal cancer for survivors treated with direct abdominopelvic irradiation was 1.4% (95% CI, 0.7%-2.6%) by age 50 years, comparable with the 1.2% risk in individuals with at least 2 first-degree relatives affected by colorectal cancer. CONCLUSION: Among a cohort of British childhood cancer survivors, the greatest excess risk associated with subsequent primary neoplasms at older than 40 years was for digestive and genitourinary neoplasms.

Population-based risks of CNS tumors in survivors of childhood cancer: the British Childhood Cancer Survivor Study.

PURPOSE: CNS tumors are the most common second primary neoplasm (SPN) observed after childhood cancer in Britain, but the relationship of risk to doses of previous radiotherapy and chemotherapy is uncertain. METHODS: The British Childhood Cancer Survivor Study is a national, population-based, cohort study of 17,980 individuals surviving at least 5 years after diagnosis of childhood cancer. Linkage to national, population-based cancer registries identified 247 SPNs of the CNS. Cohort and nested case-control studies were undertaken. RESULTS: There were 137 meningiomas, 73 gliomas, and 37 other CNS neoplasms included in the analysis. The risk of meningioma increased strongly, linearly, and independently with each of dose of radiation to meningeal tissue and dose of intrathecal methotrexate. Those whose meningeal tissue received 0.01 to 9.99, 10.00 to 19.99, 20.00 to 29.99, 30.00 to 39.99 and≥40 Gy had risks that were two-fold, eight-fold, 52-fold, 568-fold, and 479-fold, respectively, the risks experienced by those whose meningeal tissue was unexposed. The risk of meningioma among individuals receiving 1 to 39,40 to 69, and at least 70 mg/m2 of intrathecal methotrexate was 15-fold, 11-fold, and 36-fold, respectively, the risk experienced by those unexposed. The standardized incidence ratio for gliomas was 10.8 (95% CI, 8.5 to 13.6). The risk of glioma/primitive neuroectodermal tumors increased linearly with dose of radiation, and those who had CNS tissue exposed to at least 40 Gy experienced a risk four-fold that experienced by those who had CNS tissue unexposed. CONCLUSION: The largest-ever study, to our knowledge, of CNS tumors in survivors of childhood cancer indicates that the risk of meningioma increases rapidly with increased dose of radiation to meningeal tissue and with increased dose of intrathecal methotrexate.

Long-term cause-specific mortality among survivors of childhood cancer.

CONTEXT: Survivors of childhood cancer are at increased risk of premature mortality compared with the general population, but little is known about the long-term risks of specific causes of death, particularly beyond 25 years from diagnosis at ages when background mortality in the general population starts to increase substantially. OBJECTIVE: To investigate long-term cause-specific mortality among 5-year survivors of childhood cancer in a large-scale population-based cohort. DESIGN, SETTING, AND PATIENTS: British Childhood Cancer Survivor Study, a population-based cohort of 17,981 5-year survivors of childhood cancer diagnosed with cancer before age 15 years between 1940 and 1991 in Britain and followed up until the end of 2006. MAIN OUTCOME MEASURES: Cause-specific standardized mortality ratios (SMRs) and absolute excess risks (AERs). RESULTS: Overall, 3049 deaths were observed, which was 11 times the number expected (SMR, 10.7; 95% confidence interval [CI], 10.3-11.1). The SMR declined with follow-up but was still 3-fold higher than expected (95% CI, 2.5-3.9) 45 years from diagnosis. The AER for deaths from recurrence declined from 97 extra deaths (95% CI, 92-101) per 10,000 person-years at 5 to 14 years from diagnosis, to 8 extra deaths (95% CI, 3-22) beyond 45 years from diagnosis. In contrast, during the same periods of follow-up, the AER for deaths from second primary cancers and circulatory causes increased from 8 extra deaths (95% CI, 7-10) and 2 extra deaths (95% CI, 2-3) to 58 extra deaths (95% CI, 38-90) and 29 extra deaths (95% CI, 16-56), respectively. Beyond 45 years from diagnosis, recurrence accounted for 7% of the excess number of deaths observed while second primary cancers and circulatory deaths together accounted for 77%. CONCLUSION: Among a cohort of British survivors of childhood cancer, excess mortality from second primary cancers and circulatory diseases continued to occur beyond 25 years from diagnosis.

Extent of alcohol consumption among adult survivors of childhood cancer: the British Childhood Cancer Survivor Study.

BACKGROUND: This study aimed to identify subgroups of childhood cancer survivors at highest risk of consuming alcohol, consuming above recommended weekly levels, and consuming potentially harmful amounts and compare survivor risks with those expected from the general population. METHODS: Using the British Childhood Cancer Survivor Study, a population-based cohort of 17,981 individuals diagnosed with childhood cancer (1940-1991) and surviving>or=5 years, 14,836 were eligible for a questionnaire that ascertained drinking behavior, as previously ascertained in the 2002 General Household Survey throughout Britain. RESULTS: Of 10,389 survivors who responded, 77.2% were alcohol drinkers, 23.8% consumed over weekly recommendations, and 3.9% consumed potentially harmful amounts. Survivors were less likely than the general population to be a current drinker {odds ratio [OR; 99% confidence interval (CI)]: 0.52 (0.46-0.60)}, consume over weekly recommended levels [OR (99% CI): 0.65 (0.58-0.73)], and consume harmful amounts [OR (99% CI): 0.40 (0.32-0.49)]. Survivors of a central nervous system neoplasm or leukemia, particularly those treated with brain irradiation, were the least likely to have adverse drinking behaviors when compared with the general population. However, survivors of Hodgkin's lymphoma, non-Hodgkin's lymphoma, Wilms' tumor, bone sarcoma, and soft tissue sarcoma had adverse drinking behaviors at levels expected from the general population. CONCLUSION: Overall adverse drinking behaviors were less frequent in survivors than expected from the general population, but subgroups with adverse drinking behaviors were identified, and it is these subgroups who are most in need of intervention. IMPACT: UK clinical follow-up guidelines for childhood cancer survivors need strengthening in relation to alcohol consumption.

Risk of bladder tumours after childhood cancer: the British Childhood Cancer Survivor Study.

OBJECTIVES: To estimate the risk of a second primary tumour (SPT) of the bladder in a cohort of childhood cancer survivors, investigate factors associated with a bladder SPT developing, and compare the risk observed with that expected from the general population. PATIENTS AND METHODS: The analysis included 17981 individuals diagnosed with childhood cancer, between 1940 and 1991 in Britain, and surviving for ≥5 years. Ascertainment of a bladder SPT was primarily through the National Health Service Central Registers (NHSCR). RESULTS: From the NHSCR, 17 bladder SPTs were ascertained; this corresponded to four times (95% confidence interval 2.5-6.4) the expected number of bladder tumours. Standardized incidence ratios (SIRs) varied significantly (P < 0.05) by first primary tumour (FPT) type, follow-up period, attained age and chemotherapy. The highest SIRs were in those: with heritable retinoblastoma (31.4); treated with chemotherapy (12.0); 0-9 years of follow-up (10.8); and aged 0-19 years (9.3). The absolute excess risk (AER) for a bladder SPT was 3.7 cases/100000 survivors per year. The AER varied significantly by FPT type, follow-up period, attained age and gender. The highest AERs were in those: diagnosed with heritable retinoblastoma (34.0); 20-29 years of follow-up (14.2); aged 40-49 years (13.0); and male (5.8). Using multivariable Cox regression, FPT and chemotherapy were significantly associated with the risk of a bladder SPT developing. By the age of 55 years, 0.4% of survivors developed a bladder SPT. CONCLUSION: Although the absolute risk of a bladder tumour within childhood cancer survivors was low, the risk was four times that expected from the general population. Specific groups, e.g. survivors of heritable retinoblastoma and those treated with chemotherapy, were at the highest risk.

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

BACKGROUND: Previously from the British Childhood Cancer Survivor Study (BCCSS) it was seen that adult survivors of childhood cancer were less likely to marry than the general population. The objectives of this study were to assess the number of childhood cancer survivors from the BCCSS who were currently divorced or separated, examine factors associated with marriage dissolution and compare survivor divorce rates to population rates. PROCEDURE: The BCCSS is a population-based cohort of 18,119 individuals diagnosed with cancer aged 0-14 years between 1940 and 1991, and survived at least 5 years. 14,539 were alive, aged 16 years or over and eligible to receive a questionnaire, which ascertained marital status. RESULTS: From 8,155 survivors, who were aged at least 20 years at questionnaire completion, the proportions currently divorced and divorced or separated were 13.5% and 18.1%, respectively. Only current age, educational attainment and age at marriage were associated with divorce, and for divorce and separation status only age at marriage (P < 0.05). Overall the survivors were no different to the general population for being currently divorced (odds ratio (OR) (95% confidence intervals (95% CI)): 0.94 (0.81-1.10)). However, the survivors overall (OR (95% CI): 0.82 (0.72-0.94)), and separately for those diagnosed with non-Hodgkin lymphoma (OR (95% CI): 0.55 (0.34-0.89)) and leukaemia (OR (95% CI): 0.70 (0.52-0.95)), were less likely to be currently divorced or separated than the general population. CONCLUSIONS: It is reassuring that survivors do not experience more divorce than the general population, and that no cancer or treatment factors were shown to be associated with marriage dissolution.

Survival after second primary neoplasms of the brain or spinal cord in survivors of childhood cancer: results from the British Childhood Cancer Survivor Study.

PURPOSE: Survival after brain or spinal cord neoplasms is poor and varies by diagnostic group, age, grade, treatment and pretreatment factors, and location and size of tumor. We carried out a study to investigate survival and factors affecting survival of all diagnostic types of second primary brain or spinal cord neoplasms. PATIENTS AND METHODS: The British Childhood Cancer Survivor Study (BCCSS) is a long-term population-based follow-up study of 17,980 5-year survivors of childhood cancer. We used relative survival and multivariate Cox regression analysis to determine 5-year relative survival and factors affecting survival in second primary meningiomas and gliomas that developed in survivors included in the BCCSS. RESULTS: There were 247 second primary brain or spinal cord neoplasms, including 137 meningiomas and 73 gliomas in a young adult population. Five-year relative survival after meningiomas was similar for males (84.0%; 95% CI, 72.6% to 91.1%) and females (81.7%; 95% CI, 69.9% to 89.3%). For gliomas, 5-year relative survival was 19.5% (95% CI, 8.6% to 33.7%) for males and females. Multivariate analysis showed significant heterogeneity by decade of treatment (P = .04), grade (P = .03), and genetic risk (P = .03) for rate of mortality after a meningioma. For gliomas, survival was significantly affected by grade (P < .001). CONCLUSION: Our results indicate survival is poor after second primary glioma in this young adult population, although survival after second primary meningioma is good. Our study has clinical implications for the surveillance of childhood cancer survivors at risk of developing second primary brain tumors, in particular survivors of childhood acute lymphoblastic leukemia or childhood brain tumors.

Pregnancy outcomes among adult survivors of childhood cancer in the British Childhood Cancer Survivor Study.

PURPOSE: We used data from the first large-scale overwhelmingly population-based study (a) to quantify the risk of adverse pregnancy outcomes in survivors of childhood cancer in relation to cancer type and treatment and (b) to assess live birth rates relative to the general population. METHODS: A questionnaire, including questions inquiring about pregnancy outcomes, was completed by 10,483 survivors. A total of 7,300 pregnancies were reported. Odds ratios (OR) for live birth, miscarriage, termination, stillbirth, premature birth, and low birth weight were calculated for different types of childhood cancer and by whether initial treatment involved chemotherapy and abdominal or brain irradiation. For females, the observed number of live births was compared with that expected based on the general population of England and Wales. RESULTS: Female survivors exposed to abdominal irradiation had a significantly increased OR of delivering preterm [OR, 3.2; 95% confidence interval (95% CI), 2.1-4.7] and producing offspring with a low birth weight (OR, 1.9; 95% CI, 1.1-3.2). An increased OR of miscarriage was also associated with abdominal radiotherapy (OR, 1.4; 95% CI, 1.0-1.9). The number of live births observed from all female survivors was two thirds of that expected (O/E, 0.64; 95% CI, 0.62-0.66) and lowest among survivors treated with brain (O/E, 0.52; 95% CI, 0.48-0.56) and abdominal radiotherapy (O/E, 0.55; 95% CI, 0.50-0.61). CONCLUSION: Female survivors of childhood cancer treated with abdominal radiotherapy are at 3-fold increased risk of delivering preterm, 2-fold increased risk of low birth weight, and a small increased risk of miscarriage. Overall, female survivors produce considerably fewer offspring than expected, particularly those treated with abdominal or brain radiotherapy.