IMPORTANC E Survivors of childhood cancer (CCSs) face risk of developing subsequent tumors. Solid benign tumors may be cancer precursors; benign tumors and cancers may share etiologic factors. However, comprehensive data on the risk for solid benign tumors are lacking. OBJECT; VE To quantify the incidence of and treatment-related risk factors for histologically confirmed solid nonskin benign tumors among CCSs. DESIGN, SETTING, AND PARTICIPANTS This record linkage study involves the Dutch Childhood Oncology Group-Long-Term Effects After Childhood Cancer (DCOG-LATER) cohort of 6165 individuals diagnosed with childhood cancer at younger than 18 years from January], 1963, through December 31, 2001, in 7 Dutch pediatric centers and who survived at least 5 years after the diagnosis. Study groups eligible for record linkage from 1990 onward included 5843 CCSs (94.8%) and 883 siblings. Benign tumors were identified from the population-based Dutch histopathology and cytopathology registry (PALGA). Follow-up was completed on May 1, 2015. Data were analyzed from January 1, 1990, through May 1, 2015. MAIN OUTCOMES AND MEASURES Cumulative incidence of any subsequent benign tumor for cohort strata and multivariable Cox proportional hazards regression models (hazard ratios [HRs]) were used to evaluate potential risk factors for 8 major benign tumor subtypes. RESULTS Of the 5843 eligible CC5s (55.9% male), 542 (9.3%) developed a histologically confirmed subsequent benign tumor after a median follow-up of 22.7 years (range, 5.0-52.2 years). Among women, abdominopelvic radiotherapy inferred dose-dependent increased risks for uterine leiomyoma (n = 43) for doses of less than 20 Gy (HR, 1.9; 95% CI, 0.5-7.0), 20 to less than 30 Gy (HR, 3.4; 95% CI, 1.1-10.4), and at least 30 Gy (HR, 5.4; 95% CI, 2.4-12.4) compared with no abdominopelvic radiotherapy (P =.002 for trend). High-dose radiotherapy to the trunk was not associated with breast fibroadenoma (n = 45). Of 23 osseous and/or chondromatous neoplasms, 16 occurred among leukemia survivors, including llafter total body irradiation (HR, 37.4; 95% CI, 14.8-94.7). Nerve sheath tumors (n = 55) were associated with radiotherapy (HR at 31years of age, 2.9; 95% CI, 1.5-5.5) and a crude indicator of neurofibromatosis type lor 2 status (HR, 5.6; 95% CI, 2.3-13.7). Subsequent risk for benign tumors was higher than the risks for subsequent nonskin solid malignant neoplasms and for benign tumors among siblings. CONCLUSIONS AND RELEVANCE This record linkage study uses a unique resource for valid and complete outcome assessment and shows that CCSs have an approximately 2-fold risk of developing subsequent benign tumors compared with siblings. Site-specific new findings, including for uterine leiomyoma, osteochondroma, and nervous system tumors, are important to enable early diagnosis; this information will be the first step for future surveillance guidelines that include some benign tumors in CCSs and will provide leads for in-depth etiologic studies.

Background Heart failure is one of the most important late effects after treatment for cancer in childhood. The goals of this study were to evaluate the risk of heart failure, temporal changes by treatment periods, and the risk factors for heart failure in childhood cancer survivors ( CCS ). Methods and Results The DCOG‐LATER (Dutch Childhood Oncology Group–Long‐Term Effects After Childhood Cancer) cohort includes 6,165 5‐year CCS diagnosed between 1963 and 2002. Details on prior cancer diagnosis and treatment were collected for this nationwide cohort. Cause‐specific cumulative incidences and risk factors of heart failure were obtained. Cardiac follow‐up was complete for 5,845 CCS (94.8%). After a median follow‐up of 19.8 years and at a median attained age of 27.3 years, 116 survivors developed symptomatic heart failure. The cumulative incidence of developing heart failure 40 years after childhood cancer diagnosis was 4.4% (3.4%–5.5%) among all CCS. The cumulative incidence of heart failure grade ≥3 among survivors treated in the more recent treatment periods was higher compared with survivors treated earlier (Gray test, P =0.05). Mortality due to heart failure decreased in the more recent treatment periods (Gray test, P =0.02). In multivariable analysis, survivors treated with a higher dose of mitoxantrone or cyclophosphamide had a higher risk of heart failure than survivors who were exposed to lower doses. Conclusions CCS treated with mitoxantrone, cyclophosphamide, anthracyclines, or radiotherapy involving the heart are at a high risk for severe, life‐threatening or fatal heart failure at a young age. Although mortality decreased, the incidence of severe or life‐threatening heart failure increased with more recent treatment periods.

BACKGROUND:Pediatric cranial radiotherapy (CrRT) markedly increases risk of meningiomas. We studied meningioma risk factors with emphasis on independent and joint effects of CrRT dose, exposed cranial volume, exposure age, and chemotherapy.METHODS:The Dutch Cancer Oncology Group-Long-Term Effects after Childhood Cancer (DCOG-LATER) cohort includes 5-year childhood cancer survivors (CCSs) whose cancers were diagnosed in 1963-2001. Histologically confirmed benign meningiomas were identified from the population-based Dutch Pathology Registry (PALGA; 1990-2015). We calculated cumulative meningioma incidence and used multivariable Cox regression and linear excess relative risk (ERR) modeling.RESULTS:Among 5843 CCSs (median follow-up: 23.3 y, range: 5.0-52.2 y), 97 developed a benign meningioma, including 80 after full- and 14 after partial-volume CrRT. Compared with CrRT doses of 1-19 Gy, no CrRT was associated with a low meningioma risk (hazard ratio [HR] = 0.04, 95% CI: 0.01-0.15), while increased risks were observed for CrRT doses of 20-39 Gy (HR = 1.66, 95% CI: 0.83-3.33) and 40+ Gy (HR = 2.81, 95% CI: 1.30-6.08). CCSs whose cancers were diagnosed before age 5 versus 10-17 years showed significantly increased risks (HR = 2.38, 95% CI: 1.39-4.07). In this dose-adjusted model, volume was not significantly associated with increased risk (HR full vs partial = 1.66, 95% CI: 0.86-3.22). Overall, the ERR/Gy was 0.30 (95% CI: 0.03-unknown). Dose effects did not vary significantly according to exposure age or CrRT volume. Cumulative incidence after any CrRT was 12.4% (95% CI: 9.8%-15.2%) 40 years after primary cancer diagnosis. Among chemotherapy agents (including methotrexate and cisplatin), only carboplatin (HR = 3.55, 95% CI: 1.62-7.78) appeared associated with meningioma risk. However, we saw no carboplatin dose-response and all 9 exposed cases had high-dose CrRT.CONCLUSION:After CrRT 1 in 8 survivors developed late meningioma by age 40 years, associated with radiation dose and exposure age, relevant for future treatment protocols and awareness among survivors and physicians.

Purpose Intensive therapies in pediatric malignancies increased survival rates but also occurrence of treatment-related morbidities. Therefore, supportive care fulfills an increasingly important role. In planning development of guidelines with incorporation of shared decision making, we noticed that little is known about the needs and preferences of patients and their parents. Our goals were therefore to investigate (1) which supportive care topics patients and parents regard as most important and (2) the preferred role they wish to fulfill in decision making. Methods This qualitative study consisted of three focus groups (two traditional, one online) with patients and parents of two Dutch pediatric oncology centers. Data were transcribed as simple verbatim and analyzed using thematic analysis. Results Eleven adolescent patients and 18 parents shared detailed views on various aspects of supportive care. Themes of major importance were communication between patient and physician (commitment, accessibility, proactive attitude of physicians), well-timed provision of information, and the suitability and accessibility of psychosocial care. In contrast to prioritized supportive care topics by medical professionals, somatic issues (e.g., febrile neutropenia) were infrequently addressed. Patients and parents preferred to be actively involved in decision making in selected topics, such as choice of analgesics and anti-emetics, but not in, e.g., choice of antibiotics. Conclusions Children with cancer and parents were provided a valuable insight into their views regarding supportive care and shared decision making. These results have important implications towards improving supportive care, both in selecting topics for guideline development and incorporating preferences of patients and parents herein.

BACKGROUND:Anthracyclines are frequently used chemotherapeutic agents for childhood cancer that can cause cardiotoxicity during and after treatment. Although several medical interventions in adults with symptomatic or asymptomatic cardiac dysfunction due to other causes are beneficial, it is not known if the same treatments are effective for childhood cancer patients and survivors with anthracycline-induced cardiotoxicity. This review is an update of a previously published Cochrane review.OBJECTIVES:To compare the effect of medical interventions on anthracycline-induced cardiotoxicity in childhood cancer patients or survivors with the effect of placebo, other medical interventions, or no treatment.SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2015, Issue 8), MEDLINE/PubMed (1949 to September 2015), and EMBASE/Ovid (1980 to September 2015) for potentially relevant articles. In addition, we searched reference lists of relevant articles, conference proceedings of the International Society for Paediatric Oncology (SIOP), the American Society of Clinical Oncology (ASCO), the American Society of Hematology (ASH), the International Conference on Long-Term Complications of Treatment of Children & Adolescents for Cancer, and the European Symposium on Late Complications from Childhood Cancer (from 2005 to 2015), and ongoing trial databases (the ISRCTN Register, the National Institutes of Health (NIH) Register, and the trials register of the World Health Organization (WHO); all searched in September 2015).SELECTION CRITERIA:Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing the effectiveness of medical interventions to treat anthracycline-induced cardiotoxicity with either placebo, other medical interventions, or no treatment.DATA COLLECTION AND ANALYSIS:Two review authors independently performed the study selection. One review author performed the data extraction and 'Risk of bias' assessments, which another review author checked. We performed analyses according to the guidelines in the Cochrane Handbook for Systematic Reviews of Interventions.MAIN RESULTS:In the original version of the review we identified two RCTs; in this update we identified no additional studies. One trial (135 participants) compared enalapril with placebo in childhood cancer survivors with asymptomatic anthracycline-induced cardiac dysfunction. The other trial (68 participants) compared a two-week treatment of phosphocreatine with a control treatment (vitamin C, adenosine triphosphate, vitamin E, oral coenzyme Q10) in leukaemia patients with anthracycline-induced cardiotoxicity. Both studies had methodological limitations.The RCT on enalapril showed no statistically significant differences in overall survival, mortality due to heart failure, development of clinical heart failure, and quality of life between treatment and control groups. A post-hoc analysis showed a decrease (that is improvement) in one measure of cardiac function (left ventricular end-systolic wall stress (LVESWS): -8.62% change) compared with placebo (+1.66% change) in the first year of treatment (P = 0.036), but not afterwards. Participants treated with enalapril had a higher risk of dizziness or hypotension (risk ratio 7.17, 95% confidence interval 1.71 to 30.17) and fatigue (Fisher's exact test, P = 0.013).The RCT on phosphocreatine found no differences in overall survival, mortality due to heart failure, echocardiographic cardiac function, and adverse events between treatment and control groups.AUTHORS' CONCLUSIONS:Only one trial evaluated the effect of enalapril in childhood cancer survivors with asymptomatic cardiac dysfunction. Although there is some evidence that enalapril temporarily improves one parameter of cardiac function (LVESWS), it is unclear whether it improves clinical outcomes. Enalapril was associated with a higher risk of dizziness or hypotension and fatigue. Clinicians should weigh the possible benefits with the known side effects of enalapril in childhood cancer survivors with asymptomatic anthracycline-induced cardiotoxicity.Only one trial evaluated the effect of phosphocreatine in childhood cancer patients with anthracycline-induced cardiotoxicity. Limited data with a high risk of bias showed no significant difference between phosphocreatine and control treatments on echocardiographic function and clinical outcomes.We did not identify any RCTs or CCTs studying other medical interventions for symptomatic or asymptomatic cardiotoxicity in childhood cancer patients or survivors.High-quality studies should be performed.

Objective: Anthracyclines are successfully used in cancer treatment, but their use is limited by their cardiotoxic side effects. Several risk factors for anthracycline-associated cardiomyopathy (AACM) are known, yet the occurrence of AACM in the absence of these known risk factors suggests that other factors must play a role. The purpose of this study was to evaluate whether a genetic predisposition for dilated cardiomyopathy (DCM) could be a potential risk factor for AACM.Methods: A hospital-based registry of 162 DCM families and two hospital-based registries of patients with cancer treated with systemic cancer therapy (n> 6000) were reviewed focusing on AACM. Selected patients with AACM/DCM families with possible AACM (n= 21) were analysed for mutations in cardiomyopathy-associated genes and presymptomatic cardiological evaluation of first-degree relatives was performed.Results: We identified five DCM families with AACM and one patient with AACM with a family member with a possible early sign of mild DCM. Pathogenic MYH7 mutations were identified in two of these six families. The MYH7 c. 1633G> A (p. Asp545Asn) and c. 2863G> A (p. Asp955Asn) mutations (one double mutant allele) were identified in a DCM family with AACM. The MYH7 c. 4125T> A (p. Tyr1375X) mutation was identified in one patient with AACM.Conclusions: This study further extends the hypothesis that a genetic predisposition to DCM could be a potential risk factor for AACM.

BACKGROUND:The metabolic syndrome (MS) might increase the risk of cardiovascular disease in testicular cancer (TC) survivors. We investigated its prevalence, development, vascular implications, and the role of gonadal function.METHODS:TC survivors treated with chemotherapy and follow-up ≥3 years (N = 370, study I) were retrospectively evaluated for the development of cardiovascular risk factors. A subgroup followed 3-20 years (N = 173, study II) was compared with controls (N = 1085) for MS prevalence and evaluated for vascular function.RESULTS:In TC survivors (study I), 24% developed overweight, 24% hypercholesterolemia, and 30% hypertension, after median follow-up of 1.7, 0.9, and 5.1 years, respectively. At the median follow-up of 5 years (study II), 25% of survivors have the MS {odds ratio (OR) 2.2, [95% confidence interval (CI) 1.5-3.3] compared with controls}. Survivors with MS have features of inflammation and prothrombotic state, increased carotid artery intima-media thickness. Survivors with testosterone levels <15 nmol/l (22%) have an increased risk of the MS (OR 4.1, 95% CI 1.8-9.3).CONCLUSIONS:The current data suggest that the MS occurs at earlier age in TC survivors treated with chemotherapy compared with controls and is accompanied by early signs of atherosclerosis. As low testosterone may have a causal role, it is a target for interventions.

PURPOSE:To evaluate the presence of vascular damage in long-term childhood cancer survivors (CCS) and sibling controls, and to evaluate the association between vascular damage parameters and cancer treatment and influence of cardiovascular risk factors.PATIENTS AND METHODS:Vascular assessment was performed in 277 adult CCSs (median age at diagnosis, 9 years; range, 0 to 20 years; median current age, 28 years; range, 18 to 48 years) treated with potentially cardiovascular toxic anticancer treatment (ie, anthracyclines, platinum, and/or radiotherapy [RT]). Measurements included carotid- and femoral-wall intima-media thickness (IMT), flow-mediated vasodilatation of the brachial artery by ultrasound, assessment of endothelial and inflammatory marker proteins (including tissue-type plasminogen activator [t-PA], plasminogen activator inhibitor type 1 [PAI-I]), and cardiovascular risk factors. CCS assessments were compared with those of 130 sibling controls (median age, 26 years; range, 18 to 51 years).RESULTS:At a median of 18 years (range, 5 to 31 years) after treatment, carotid and femoral IMTs in CCSs were not different from those of controls. However, CCSs who received RT as part of their treatment regimen had increased carotid and femoral IMTs and higher t-PA and PAI-I levels, indicating vascular damage and persistent endothelial activation. Patients treated with RT to the neck or chest also had greater femoral IMT. Greater IMT was associated with presence of cardiovascular risk factors (eg, hypertension and overweight).CONCLUSION:After potentially cardiovascular toxic anticancer treatment, CCSs who received RT showed signs of endothelial damage and an unfavorable cardiovascular risk profile compared with controls. CCSs treated with localized RT had increased IMT outside the primary irradiation field. These abnormalities are probably involved in the pathogenesis of cardiovascular morbidity in CCSs.

Blaauwbroek R, Barf HA, Berendsen AJ, Groenier KH, Kremer, Tissing WJE, Postma A. Nazorg huisarts voor volwassen overlevenden van kinderkanker. Huisarts Wet 2012;55(8):342-5.

BackgroundThe Late Effects of Childhood Cancer task force of the Dutch Childhood Oncology Group (DCOG LATER) developed a guideline for follow-up of asymptomatic cardiac dysfunction in childhood cancer survivors (CCS). In this paper, we present the methods, available evidence and final recommendations of our guideline.Materials and methodsA multidisciplinary working group specified clinical questions that should be answered to get to recommendations for the guideline. We carried out short or extensive evidence summaries and determined methodological quality of studies and levels of evidence in order to answer all clinical questions. When evidence was lacking for CCS, we carefully extrapolated evidence from other populations. Final recommendations were based on evidence and consensus.ResultsThere was high-level evidence for the increased risk of cardiac dysfunction in CCS and its main risk factors. Evidence was lacking regarding the prognosis, diagnosis and treatment of cardiac dysfunction in CCS. We recommended echocardiographic screening for asymptomatic cardiac dysfunction in CCS treated with cardiotoxic treatments and counseling about potential advantages and disadvantages of our screening recommendations.ConclusionThe DCOG LATER guideline recommends risk-based screening for asymptomatic cardiac dysfunction in CCS, but it should be noted that recommendations are not completely supported by evidence in CCS.

Aim: To assess systolic and diastolic function in adult childhood-cancer survivors (CCS) after treatment entailing potential cardiovascular toxicity.Methods: The study cohort consisted of 277 adult CCS (median age 28 [range 18-48] years), who had been treated with anthracyclines, platinum, and/or radiotherapy between 1976 and 1999, along with 130 healthy sibling controls. The assessments included echocardiography, baroreflex sensitivity measurement, and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP). Echocardiography measurements were shortening fraction (SF) (abnormal <29%) for systolic function and tissue velocity imaging of early diastole (TVI Et) (abnormal < 8.00) cm/sec for diastolic function; systolic function was also assessed by the wall motion score index (WMSI).Results: At 18 (5-31) years post-treatment, the prevalence of both impaired SF and abnormal WMSI was increased in CCS compared to controls (p = 0.003 and p < 0.001, respectively). CCS also had an increased prevalence of diastolic dysfunction compared to the controls (12% versus 1%, p < 0.001). Abnormal SF and/or abnormal diastolic function were found in 43% of CCS. NT-proBNP was higher in CCS and was associated to increased WMSI. Baroreflex sensitivity was lower in CCS and was associated with diastolic dysfunction. Systolic as well as diastolic dysfunction was associated with cumulative dose of anthracyclines and mediastinal irradiation.Conclusion: After treatment with potential cardiovascular toxic therapies, the risk of systolic and diastolic dysfunction in CCS is considerable. Since these abnormalities, in particular diastolic dysfunction, are age related, the observed effects might be considered a sign of precocious cardiac ageing. (C) 2011 Elsevier Ltd. All rights reserved.

Evaluation of body mass index (BMI) at final height (FH) and annual BMI increase in adult childhood cancer survivors (CCS) after treatment with anthracyclines, platinum, and/or radiotherapy.

To facilitate family doctor-driven follow-up for adult childhood cancer survivors, we developed a survivor care plan (SCP) for adult survivors and their family doctors.

BackgroundSurvival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately the improved prognosis has resulted in the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood cancer. However, among long-term childhood cancer survivors the risk of hepatic late adverse effects is largely unknown. To make informed decisions about future cancer treatment and follow-up policies it is important to know the risk of, and associated risk factors for, hepatic late adverse effects.ObjectivesTo evaluate the existing evidence on the association between antineoplastic treatment for childhood cancer and hepatic late adverse effects.Search strategyWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 2), MEDLINE (1966 to June 2009) and EMBASE (1980 to June 2009). In addition, we searched reference lists of relevant articles and conference proceedings.Selection criteriaAll studies except case reports, case series and studies including less than 10 patients that examined the association between antineoplastic treatment for childhood cancer (aged 18 years or less at diagnosis) and hepatic late adverse effects (one year or more after the end of treatment).Data collection and analysisTwo review authors independently performed the study selection, risk of bias assessment and data extraction.Main resultsWe identified 20 cohort studies investigating hepatic late adverse effects after antineoplastic treatment for childhood cancer. All studies had methodological limitations. The prevalence of hepatic late adverse effects varied widely, between 0% and 84.2%. Selecting studies where the outcome of hepatic late adverse effects was well defined as alanine aminotransferase (ALT) above the upper limit of normal resulted in five studies. In this subgroup the prevalence of hepatic late adverse effects ranged from 8.0% to 52.8%, with follow-up durations varying from one to 27 years after the end of treatment. A more stringent selection process using the outcome definition of ALT as above twice the upper limit of normal resulted in three studies, with a prevalence ranging from 7.9% to 44.8%. Chronic viral hepatitis was identified as a risk factor for hepatic late adverse effects in univariate analyses. It is unclear which specific antineoplastic treatments increase the risk of hepatic late adverse effectsAuthors' conclusionsThe prevalence of hepatic late adverse effects ranged from 7.9% to 52.8% when selecting studies with an adequate outcome definition. It has not been established which childhood cancer treatments result in hepatic late adverse effects. There is a suggestion that chronic viral hepatitis increases the risk of hepatic late adverse effects. More well-designed studies are needed to reliably evaluate the prevalence of, and risk factors for, hepatic late adverse effects after antineoplastic treatment for childhood cancer.

Department of Cardiology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and Department of Pediatric Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Blaauwbroek R, Postma A, Kamps WA, Meyboom-de Jong B. Nazorg voor volwassenen die als kind kanker hebben gehad. De rol van de huisarts. Huisarts Wet 2009;52(9):430-3.

Long-term cardiovascular morbidity is increasingly observed in chemotherapy-treated testicular cancer survivors, but little is known of early sub-clinical changes in cardiac function. We prospectively evaluated cardiac function in testicular cancer patients by echocardiography. Systolic (Wall Motion Score Index) and diastolic (E/A-ratio and Tissue Velocity Imaging (TVI)) parameters, and serum levels of N-Terminal pro-Brain Natriuretic Peptide (NT-proBNP) were assessed before the start of chemotherapy and 1 year later. Echocardiography data were compared with an age-matched group of healthy controls. Forty-two patients treated with bleomycin, etoposide and cisplatin were evaluated (median age 27 years, range 18–50). Systolic function and E/A-ratio did not change, whereas the median TVI decreased (12.0 vs 10.0 cms −1 ; P =0.002). Median levels of NT-proBNP increased (5 vs 18 pmoll −1 , P =0.034). Compared with controls, TVI before the start of chemotherapy was not significantly different. In conclusion, we found that at a median of 10 months after cisplatin-based treatment for testicular cancer, TVI decreased significantly, indicating a deterioration of diastolic cardiac function. Serum levels of NT-proBNP increased. The prognostic significance of these changes for future cardiovascular morbidity is not clear.

Background Since 75% of children with cancer will become long-term survivors, late eff ects of treatment are an ever increasing issue for patients.Paediatric oncologists generally agree that cancer survivors should be followed up for the remainder of their lives, but they might not be the most suitable health-care providers to follow up survivors into late adulthood.We designed a 3-year study to assess whether shared-care by paediatric oncologists and family doctors in the long-term follow-up of survivors of childhood cancers is feasible, whether a shared-care model is compatible with collection of data needed for registration of late eff ects, and how a shared-care model is assessed by survivors and family doctors. MethodsIn 2004 and 2005, adult survivors of childhood cancers were randomly chosen from eligible patients diagnosed with childhood cancer (excluding CNS tumours) or Langerhans-cell histiocytosis between January, 1968, and December, 1997, and recalled to the long-term follow-up (LTFU) clinic at the University Medical Centre Groningen, Groningen, Netherlands, where they underwent physical and clinical assessments by an on-site family doctor (visit 1).At this visit, assessments were done according to guidelines of the UK Children's Cancer Study Group Late Eff ects Group, and late eff ects were graded by use of Common Terminology Criteria for Adverse Events (version 3).Follow-up assessments were done 1 year later in 2005 and 2006 by local family doctors (visit 2), who were asked to return data to the LTFU clinic.At this visit, the local family doctors were asked to complete a three-item questionnaire and patients were asked to complete a seven-item questionnaire about their satisfaction with the shared-care model.At the next consultation, which was planned for the end of the study (visit 3), the on-site family doctor advised patients about future follow-up on the basis of their individual risk of late eff ects.Main endpoints were numbers of participants, satisfaction ratings, and proportions of local family doctors who returned data that they obtained at visit 2 to the LTFU clinic.Findings 133 individuals were chosen at random from 210 enrolled adult survivors.123 of 133 (92%) randomly selected survivors and 115 of 117 (98%) of their family doctors agreed to participate in the share-care programme.103 of 115 (90%) family doctors returned data to the LTFU clinic at visit 2. 89 of 101 (88%) of survivors were satisfi ed with this shared-care model, as were 94 of 115 (82%) family doctors; 18 of 115 (16%) family doctors had no views either way; and three of 115 (3%) family doctors were dissatisfi ed.Interpretation Shared-care by paediatric oncologists and family doctors is feasible for long-term follow-up of adult survivors of childhood cancers.

BACKGROUND:Obesity is a well-known problem in children with acute lymphoblastic leukemia (ALL), and it might be the result of an excess in energy intake, reduced energy expenditure, or both. The aim of this study is to describe energy intake and physical activity during treatment for ALL with intermittent dexamethasone (DEXA).METHODS:Body mass index (BMI), energy intake, and physical activity were measured in 16 ALL patients on maintenance treatment and in 17 healthy controls. ALL patients were measured during ("on DEXA") and in between ("off DEXA") DEXA treatments.RESULTS:In patients, the mean increase in BMI z-score was 1.4 +/- 1.1. Energy intake on DEXA was higher (2,125.9 +/- 476.0 vs 1,775.1 +/- 426.1 kcal/24 h, p < 0.05) and energy intake off DEXA was lower (1,305.0 +/- 249.4 vs 1,775.1 +/- 426.1 kcal/24 h, p < 0.05), compared to healthy controls. Physical activity on DEXA was lower compared to healthy controls (30.0 +/- 3.9 vs 40.0 +/- 6.0 kcal kg(-1) 24 h(-1), p < 0.001 and 7,303.1 +/- 4,622.9 vs 13,927.2 +/- 3,822.7 steps, p < 0.05). Physical activity off DEXA was not different compared to healthy controls.CONCLUSION:Weight gain in patients on ALL treatment might be owing to increased energy intake and decreased physical activity during treatment with DEXA.

10032 Background: In childhood cancer survivors (CCS), cardiac dysfunction has been mainly characterized by systolic dysfunction (SysDfx). However, both SysDfx and diastolic dysfunction (DiasDfx) are considered to be risk factors (RF) in development of clinical heart failure. Therefore, we aimed to assess the prevalence and treatment-related RF of SysDfx and DiasDfx after potential cardiovascular-toxic childhood cancer treatment (CCT). Methods: A cross-sectional single centre cardiovascular cohort study was performed in 277 CCS treated between 1976–1999 with anthracyclines (A, N=199; median (range) dose 183 (50–600) mg/m2), platinum (N=22) and/or radiotherapy (RT, N=175; chestRT, N=69; neckRT, N=67). Median age at diagnosis was 9 (0–20)-y, current age 28 (18–48)-y and follow-up (FU) 18 (5–31)-y post-treatment. Cardiac assessment included echocardiography and assessment of N-terminal pro-brain natriuretic peptide (NTproBNP). Results were compared with those of 130 age- and sex-matched sibling controls. By multivariate logistic regression, we studied the influence of CCT on the main outcome measures SysDfx (wall motion score index >1.00) and DiasDfx (E/A-ratio <1.00 and/or mean Tissue Velocity Imaging of early diastole <8.00cm/s). We adjusted for age at diagnosis, sex, current age, hypertension and BMI. Results: Clinical heart failure was found in 15 (5%) CCS. Compared with controls, CCS had a higher prevalence of SysDfx (13% vs. 2%; p<0.001) and DiasDfx (15% vs. 2%; p<0.001). In 26/40 (65%) CCS with DiasDfx no SysDfx was found. Overall, 68 (25%) CCS vs. 4 (3%) controls (p<0.001) had SysDfx and/or DiasDfx and CCS had a higher NTproBNP (47 (11–4758) vs. 34 (11–257) ng/L; p<0.001). SysDfx was associated with A-dose (by 100mg/m2; OR (95%CI) 1.4 (1.1–1.8)), not with chestRT (OR 1.1 (0.5- 2.6)). DiasDfx was associated with hypertension (OR 6.1 (2.4–15.7)), A-dose (by 100mg/m2; OR 1.4 (1.1–1.8)), chestRT (OR 3.5 (1.3–9.0)) and neckRT (OR 2.7 (1.1–7.1)). Conclusion: At median 18-y FU, 25% of CCS treated with potential cardiovascular-toxic CCT had evidence of SysDfx and/or DiasDfx. For DiasDfx, anthracycline-dose and chest-/neckRT were identified as RF. DiasDfx may be of prognostic significance in development of clinical heart failure and needs to be explored as potential intervention target. No significant financial relationships to disclose.