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Childhood cancer survivors (CCS) require specialized follow-up throughout their lifespan to prevent or manage late effects of cancer treatment. Knowing the size and structure of the population of CCS is crucial to plan interventions. In this scoping review we reviewed studies that reported prevalence of CCS in Europe. We searched Medline, Web of Science, and Embase using permutations of terms referring to childhood, cancer, survivors, prevalence, registries, and Europe. We followed PRISMA-ScR guidelines to select studies and The Joanna Briggs Institute Prevalence Critical Appraisal Tool to evaluate their quality. From 979 unique studies published between 1989 and 2022, 12 were included. Limited-duration prevalence (LDP) for all childhood cancers, assessed in three studies using counting method, varied between 450 and 1240 persons per million. Complete prevalence (CP) of survivors of any childhood cancer except skin carcinomas, reported in three studies using observed data complemented with modelled data for the unobserved period, varied between 730 and 1110 persons per million. CP of survivors of an embryonal tumour was estimated by completeness index method in six studies. In four of them CP ranged from 48 to 95 persons per million for all embryonal tumours, while CP for those occurring in central nervous system was 43 per million in one study and CP for rhabdomyosarcoma was 17 per million in another. Information on prevalence of CCS in Europe is fragmented and inconsistent. The large variations in LDP and CP estimates were linked to differences in data availability, the selection of populations, prevalence measure, statistical method, incidence period, index date, age at diagnosis and prevalence, cancer types, sex, and, for LDP, also the length of follow-up. Standardisation of methodology and reporting are needed to systematically monitor and compare CCS prevalence in Europe and provide data to help address survivors' needs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Background: Childhood brain tumours (CBTs) are the leading cause of cancer death in children under the age of 20 years globally. Though the aetiology of CBT remains poorly understood, it is thought to be multifactorial. We aimed to synthesize potential risk factors for CBT to inform primary prevention., Methods: We conducted a systematic review and meta-analysis of epidemiological studies indexed in the PubMed, Web of Science, and Embase databases from the start of those resources through 27 July 2023. We included data from case-control or cohort studies that reported effect estimates for each risk factor around the time of conception, during pregnancy and/or during post-natal period. Random effects meta-analysis was used to estimate summary effect sizes (ES) and 95% confidence intervals (CIs). We also quantified heterogeneity (I 2 ) across studies., Findings: A total of 4040 studies were identified, of which 181 studies (85 case-control and 96 cohort studies) met our criteria for inclusion. Of all eligible studies, 50% (n = 91) were conducted in Europe, 32% (n = 57) in North America, 9% (n = 16) in Australia, 8% (n = 15) in Asia, 1% (n = 2) in South America, and none in Africa. We found associations for some modifiable risk factors including childhood domestic exposures to insecticides (ES 1.44, 95% CI 1.20-1.73) and herbicides (ES 2.38, 95% CI 1.31-4.33). Maternal domestic exposure to insecticides (ES 1.45, 95% CI 1.09-1.94), maternal consumption of cured meat (ES 1.51, 95% CI 1.05-2.17) and coffee ≥ 2 cups/day (ES 1.45, 95% 95% CI 1.07-1.95) during pregnancy, and maternal exposure to benzene (ES 2.22; 95% CI 1.01-4.88) before conception were associated with CBTs in case-control studies. Also, paternal occupational exposure to pesticides (ES 1.48, 95% CI 1.23-1.77) and benzene (ES 1.74, 95% CI 1.10-2.76) before conception and during pregnancy were associated in case-control studies and in combined analysis. On the other hand, assisted reproductive technology (ART) (ES 1.32, 95% CI 1.05-1.67), caesarean section (CS) (ES 1.12, 95% CI 1.01-1.25), paternal occupational exposure to paint before conception (ES 1.56, 95% CI 1.02-2.40) and maternal smoking > 10 cigarettes per day during pregnancy (ES 1.18, 95% CI 1.00-1.40) were associated with CBT in cohort studies. Maternal intake of vitamins and folic acid during pregnancy was inversely associated in cohort studies. Hormonal/infertility treatment, breastfeeding, child day-care attendance, maternal exposure to electric heated waterbed, tea and alcohol consumption during pregnancy were among those not associated with CBT in both case-control and cohort studies., Conclusion: Our results should be interpreted with caution, especially as most associations between risk factors and CBT were discordant between cohort and case-control studies. At present, it is premature for any CBT to define specific primary prevention guidelines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The purpose of this study was to determine factors associated with chronic fatigue (CF) in childhood cancer survivors (CCS)., Patients and Methods: Participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort, a nationwide cohort of CCS (≥5 years after diagnosis) and siblings as controls. Fatigue severity was assessed with the 'fatigue severity subscale' of the Checklist Individual Strength ('CIS-fatigue'). CF was defined as scoring ≥35 on the 'CIS-fatigue' and having fatigue symptoms for ≥6 months. Twenty-four parameters were assessed, categorized into assumed fatigue triggering, maintaining and moderating factors. Multivariable logistic regression analyses were carried out to investigate the association of these factors with CF., Results: A total of 1927 CCS participated in the study (40.7% of invited cohort), of whom 23.6% reported CF (compared with 15.6% in sibling controls, P < 0.001). The following factors were associated with CF: obesity [versus healthy weight, odds ratio (OR) 1.93; 95% confidence interval (CI) 1.30-2.87], moderate physical inactivity (versus physical active, OR 2.36; 95% CI 1.67-3.34), poor sleep (yes versus no, OR 2.03; 95% CI 1.54-2.68), (sub)clinical anxiety (yes versus no, OR 1.55; 95% CI 1.10-2.19), (sub)clinical depression (yes versus no, OR 2.07; 95% CI 1.20-3.59), pain (continuous, OR 1.49; 95% CI 1.33-1.66), self-esteem (continuous, OR 0.95; 95% CI 0.92-0.98), helplessness (continuous, OR 1.13; 95% CI 1.08-1.19), social functioning (continuous, OR 0.98; 95% CI 0.97-0.99) and female sex (versus male sex, OR 1.79; 95% CI 1.36-2.37)., Conclusion: CF is a prevalent symptom in CCS that is associated with several assumed maintaining factors, with lifestyle and psychosocial factors being the most prominent. These are modifiable factors and may therefore be beneficial to prevent or reduce CF in CCS., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This article describes the study design of the quantitative part of the VersKiK study, The primary objectives of this study are to examine the occurrence of late effects in survivors of childhood or adolescent cancer (module 1), investigate health-related vulnerabilities and medical service utilization within this survivor group (modules 1 and 3), and assess the alignment between documented follow-up care for cardiological and audiological late effects with guideline recommendations, along with evaluating the extent of adherence among paediatric cancer survivors (module 3)., Methods: This is a non-interventional retrospective observational cohort study. It is based on stochastically linked insurance claims data from approximately 150,000 statutory insured persons with information concerning around 25,000-30,000 cancer survivors recorded in the German Childhood Cancer Register (GCCR). To explore adherence to selected follow-up guidelines, intention to treat treatment data from clinical study groups for particular diagnostic entities will be additionally included., Discussion: The growing group of survivors after cancer in childhood and adolescence is representing a special population with an increasing demand for life-long healthcare services through relative high probability of late effects. Currently, there is a limited evidence in Germany on utilization of corresponding medical services and adherence to follow-up guidelines. With this study design, we are aiming to address these gaps and, consequently, suggest improvements to existing follow-up guidelines and follow-up care provision in Germany., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Despite its rarity, cancer in children and adolescents (CAC) is a major health issue worldwide. The lack of appropriate cancer registries is an obstacle for defining its incidence and survival, and informing cancer control. As in Cyprus, CAC epidemiology has not previously been comprehensively examined, we determined incidence rates and temporal trends of cancer in the 0-19 age group during 1998-2017., Methods: We established the population based Paediatric Oncology Registry of Cyprus (PORCY) for the period 1998-2017. World age standardised incidence rate per million children and adolescents per year (ASRW) were calculated and time trends were assessed using Joinpoint regression analysis. Comparisons were made with other countries using the International Incidence of Childhood Cancer, third volume., Results: For all cancers combined, for ages 0-19-years, ASRW was 203.54 (95% CI 189.49, 217.59) one of the highest rates globally. The most frequent CAC were leukaemias followed by lymphomas, specified epithelial neoplasms and central nervous system tumours, differing to what is described in most other countries. For all cancers, both combined and individual types, except thyroid carcinoma (where incidence was rising), no significant temporal variation was found., Conclusions: To inform cancer control activities, we conducted the first ever population-based epidemiological study of childhood and adolescent cancer (0-19 years) in Cyprus. The striking findings indicate high overall incidence rates that are among the world's highest, a higher frequency of lymphomas and thyroid cancer than brain tumours, and rising incidence for thyroid, but not for other, cancers. These novel findings, will help the formulation of hypotheses to provide explanation for the high rates for all CAC in Cyprus and may contribute to the global efforts for improving prevention of cancer in this age group., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The aetiology of most childhood cancers remains poorly understood. We conducted a nationwide register-based case-control study to assess the association between residential road traffic and railway noise exposure and risk of childhood cancers., Methods: We identified all cases of first cancers diagnosed in children aged 0-19 years in 1985-2013 from the Danish Cancer Registry (N = 3962) and sampled four individually matched (by sex and date of birth) controls per case (N = 14,790) using the Central Population Register. We estimated time-weighted exposure averages of residential road traffic and railway noise at the most (L den max) and least (L den min) exposed façades from birth to index-date (for additional analysis: in utero period) based on the individual address history for the respective time windows. We fitted conditional logistic regression models to estimate odds ratios (OR) and their 95% confidence intervals (CI)., Results: ORs varied by noise estimate and cancer type, with generally wide CIs mostly including 1.00. We found a tendency of higher ORs with increasing railway and road traffic noise for Hodgkin lymphoma (ORs for railway and road L den min were 1.63 (95% CI 1.00; 2.66) and 1.14 (95% CI 0.87; 1.48) per 10 dB), as well as a tendency of higher ORs with increasing railway noise for non-Hodgkin lymphoma. For embryonal CNS tumours and astrocytoma and other glioma we observed also some weak suggestions of a positive association. Analysing exposure to traffic noise in utero revealed similar patterns to those of the main analyses., Conclusions: This nationwide study with minimal risk of bias suggests no strong associations between traffic noise and risk of most childhood cancers. We found however some suggestive evidence for a positive association with Hodgkin lymphoma, non-Hodgkin lymphoma and some CNS tumours. Further research is warranted to confirm these associations in other populations and elucidate the underlying biological mechanisms., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: A childhood cancer diagnosis and treatment-induced somatic late effects can affect the long-term mental health of survivors. We aimed to explore whether childhood cancer survivors are at higher risk of psychiatric disorders later in life than their siblings and the general population., Methods: In this register-based cohort study (part of the Socioeconomic Consequences in Adult Life after Childhood Cancer [SALiCCS] research programme), we included 5-year survivors of childhood cancer diagnosed before 20 years of age between Jan 1, 1974 and Dec 31, 2011, in Denmark, Finland, and Sweden. In Denmark and Sweden, 94·7% of individuals were born in a Nordic country (ie, Denmark, Finland, Iceland, Norway, or Sweden); similar information was not available in Finland. Data on ethnicity were not collected. Survivors were compared with their siblings and randomly selected individuals from the general population who were matched to the survivors by year of birth, sex, and geographical region. We followed up our study population from 5 years after the childhood cancer diagnosis or corresponding calendar date for matched individuals (the index date) until Aug 11, 2017, and assessed information on hospital contacts for any and specific psychiatric disorders. For siblings, the index date was defined as 5 years from the date on which they were of the same age as their sibling survivor when diagnosed with cancer., Findings: The study population included 18 621 childhood cancer survivors (9934 [53·3%] males and 8687 [46·7%] females), 24 775 siblings (12 594 [50·8%] males and 12 181 [49·2%] females), and 88 630 matched individuals (47 300 [53·4%] males and 41 330 [46·6%] females). The cumulative incidence proportion of having had a psychiatric hospital contact by 30 years of age between Jan 1, 1979, and Aug 11, 2017, was 15·9% (95% CI 15·3-16·5) for childhood cancer survivors, 14·0% (13·5-14·5) for siblings, and 12·7% (12·4-12·9) for matched individuals. Despite a small absolute difference, survivors were at higher relative risk of any psychiatric hospital contact than their siblings (1·39, 1·31-1·48) and matched individuals (hazard ratio 1·34, 95% CI 1·28-1·39). The higher risk persisted at the age of 50 years. Survivors had a higher burden of recurrent psychiatric hospital contacts and had more hospital contacts for different psychiatric disorders than their siblings and the matched individuals., Interpretation: Childhood cancer survivors are at higher long-term risk of psychiatric disorders than their siblings and matched individuals from the general population. To improve mental health and the overall quality of life after childhood cancer, survivorship care should include a focus on early signs of mental health problems, especially among high-risk groups of survivors., Funding: NordForsk, Aarhus University, Swedish Childhood Cancer Foundation, Danish Health Foundation, and Swiss National Science Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Paediatric and adolescent thyroid cancer incidence rates are increasing in many countries. We determined incidence rates, temporal trends and survival from thyroid cancer diagnosed in childhood and adolescence in Cyprus during 1998-2017., Methods: Patients aged 0-19 years, diagnosed with thyroid cancer in the Pediatric Oncology Registry of Cyprus were included. Crude incidence rates, age standardized rates, time trends and overall survival were analysed. Annual rates and temporal trends were calculated using Microsoft Excel 2016 and Joinpoint regression analysis., Results: Eighty-one cases (76.5 % female, 23.5 % male) were identified. The crude rates (per 100,000 persons) were for both sexes 2.00 (95 % CI 1.61, 2.49), females 3.15 (95 % CI 2.45, 4.03) and males 0.92 (95 % CI 0.58, 1.44). The annual percentage changes of crude and standardised rates were 7.5 % (p < 0.05) and 7.6 % (p < 0.05). The annual percentage changes of crude rates were for females 5.1 % (p = 0.1), males 8.4 % (p < 0.05) and 15-19-year-olds 7.6 % (p < 0.05). The female to male rate ratio was 3.42 (95 % CI 2.06, 5.74). Papillary thyroid carcinoma represented 86.4 % of all cases. There was only one case after previous cancer therapy. The rate ratio of 2nd (2008-2017) to 1st (1998-2007) periods for metastatic (regional) stages was 3.76 (95 % CI 1.74, 8.31). Survival until 2018 was 100 %., Conclusion: This population-based study demonstrated that thyroid cancer incidence rates in 0-19-year-olds in Cyprus was among the world's highest. Increasing trends mainly affected males and females aged 15-19 years with papillary thyroid carcinoma, the dominant type. Cases after previous cancer therapy didn't contribute to increasing rates. The increase of metastatic cases suggests a true increase of thyroid cancer rather than overdiagnosis. Although prognosis is excellent with 100 % survival, the rising incidence rate is unexplained, indicating the need to identify causes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The aetiology of childhood leukaemia is largely unknown. Analyses of geographical differences may enhance aetiologic insights. The reunification of Germany in 1990 provides a unique opportunity to evaluate incidence patterns and time trends in two merging countries with substantial lifestyle, social and socioeconomic differences. With this study we provide an extensive assessment of 28-year incidence patterns and temporal trends after the German reunification., Methods: We identified all children diagnosed with a lymphoid leukaemia (LL) or acute myeloid leukaemia (AML) before the age of 15 years between 1991 and 2018 using the German Childhood Cancer Registry (N = 14,922), and evaluated the incidence pattern and temporal trends in former East Germany compared to West Germany by subtype, age at diagnosis and sex., Results: Incidence rates of LL were substantially lower (around 20 %) in Eastern Germany compared to Western Germany at the time of reunification. This was followed by a remarkable increase in Eastern Germany across both sexes and age groups until around 2000, when incidence rates reached the same levels as those in Western German federal states. Thereafter, incidence rates remained rather stable with some indications of a slightly decreasing tendency in both Eastern and Western Germany (estimated annual percentage changes (EAPC) 2005-2018: East Germany = -0.8 %; West Germany = -0.4 %), driven by the 0- to 4-year olds. Overall, AML incidence rates were stable over time in Western Germany, while EAPC for Eastern Germany indicated an increasing tendency (EAPC 1991-2018 = 1.3 %) driven by the older children, mostly during the early 2000s and in most recent years., Conclusion: The underlying mechanisms driving the childhood leukaemia rates remain inconclusive. Linkage studies including individual and clinical data would be valuable in evaluating the impact of a population's social, socioeconomic and lifestyle changes on the risk of childhood leukaemia and disease aetiology overall., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The aetiology for most solid tumours in childhood is largely unknown. The lack of evidence concerns also the relationship between socioeconomic position (SEP) and risk of childhood solid tumours other than in the central nervous system (CNS). We sought to access the association between individual and neighbourhood SEP measures and risk of childhood non-CNS solid tumours in Denmark and to evaluate whether associations varied by measure of SEP, time point of SEP assessment (during pregnancy versus before diagnosis) and tumour type., Methods: We conducted a nationwide case-control study based on Danish registry data. We identified all children born in 1980-2013 and diagnosed with a non-CNS solid tumour at ages 0-19 years (N = 1961) from the Danish Cancer Registry and sampled four individually matched controls per case using the Population Registry. We fitted conditional logistic regression models to estimate associations with register-based individual-level and neighbourhood-level SEP measures., Results: We observed a tendency of increased odd ratios (OR) in association with medium and high maternal income for most tumour types (e.g. OR for the highest income quintile and malignant bone tumours = 2.11; 95 % CI: 1.01, 4.38) and for parental education in association with higher education for some tumour types. For malignant epithelial neoplasms, higher parental education and income level were overall associated with an increased risk, e.g. OR = 1.63 (95 % CI: 1.00, 2.65) for the fourth group of maternal income during pregnancy. We found no risk pattern for neighbourhood SEP., Conclusion: This large register-study with minimal risk of bias found a tendency of slightly to moderately increased risks for most childhood non-CNS solid tumours in association with higher maternal income and parental education. Future research examining the underlying mechanisms of these socioeconomic differences in non-CNS solid tumours as well as other childhood cancer types are warranted., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Differences exist concerning when and how to perform lymph node dissection (LND) during radical prostatectomy due to lack of high-grade evidence to its safety and efficacy. We aimed to compare readmission rates between limited and extended LND during open radical prostatectomy (ORP) and robot-assisted radical prostatectomy (RARP)., Materials and Methods: We conducted a prospective trial of 3,706 eligible patients comparing ORP vs. RARP (LAPPRO). Six hundred and twenty-seven underwent concomitant LND. Data were retrieved for readmissions within 90 days from surgery from the Swedish Patient Registry. Causes for readmissions were classified according to the modified Clavien-Dindo classification system. We estimated risks for readmission stratified by type of LND and surgical approach., Results: We recorded 107 readmissions in 90 patients. The overall readmission rate was 14% (90/627). In the open group, extended LND had a higher, but not statistically significant readmission rate of 18% compared to 11% after limited LND (95%CI 0.87-3.01). In the robot-assisted group, readmissions after extended LND did not differ from limited LND (15% vs. 18%, 95%CI 0.49-1.61). RARP with limited LND showed a higher risk for any (RR 1.98, 95%CI [1.02-3.81]) as well as Clavien-Dindo grade 1 to 2 readmissions (RR 2.49, 95%CI [1.10-5.63]) compared to open approach with limited LND. Robot-assisted extended LND reduced the risk for Clavien-Dindo grade 3 to 5 complications leading to readmissions compared to the open approach by 59% (RR 0.41, 95%CI [0.19-0.87])., Conclusions: The risk for hospital readmission was similar when performing limited or extended LND during a radical prostatectomy. Robot-assisted technique for performing extended LND may decrease the risk for severe complications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Although preliminary evidence suggests that intermittent calorie restriction (ICR) exerts stronger effects on metabolic parameters, which may link obesity and major chronic diseases, compared with continuous calorie restriction (CCR), there is a lack of well-powered intervention studies., Objective: We conducted a randomized controlled trial to test whether ICR, operationalized as the "5:2 diet," has stronger effects on adipose tissue gene expression, anthropometric and body composition measures, and circulating metabolic biomarkers than CCR and a control regimen., Design: One hundred and fifty overweight and obese nonsmokers [body mass index (kg/m2) ≥25 to <40, 50% women], aged 35-65 y, were randomly assigned to an ICR group (5 d without energy restriction and 2 d with 75% energy deficit, net weekly energy deficit ∼20%), a CCR group (daily energy deficit ∼20%), or a control group (no advice to restrict energy) and participated in a 12-wk intervention phase, a 12-wk maintenance phase, and a 26-wk follow-up phase., Results: Loge relative weight change over the intervention phase was -7.1% ± 0.7% (mean ± SEM) with ICR, -5.2% ± 0.6% with CCR, and -3.3% ± 0.6% with the control regimen (Poverall < 0.001, PICR vs. CCR = 0.053). Despite slightly greater weight loss with ICR than with CCR, there were no significant differences between the groups in the expression of 82 preselected genes in adipose tissue implicated in pathways linking obesity to chronic diseases. At the final follow-up assessment (week 50), weight loss was -5.2% ± 1.2% with ICR, -4.9% ± 1.1% with CCR, and -1.7% ± 0.8% with the control regimen (Poverall = 0.01, PICR vs. CCR = 0.89). These effects were paralleled by proportional changes in visceral and subcutaneous adipose tissue volumes. There were no significant differences between ICR and CCR regarding various circulating metabolic biomarkers., Conclusion: Our results on the effects of the "5:2 diet" indicate that ICR may be equivalent but not superior to CCR for weight reduction and prevention of metabolic diseases. This trial was registered at clinicaltrials.gov as NCT02449148.