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Wilms tumour (WT) management represents a success story in pediatric oncology. We aimed to assess, for the first time, the event-free survival (EFS) vs. overall survival (OS) in Southern and Eastern Europe (SEE) using harmonised clinical data collected by childhood cancer registries and to identify respective prognostic factors. From 1999 to 2017, data for incident WT cases aged 0–14 years from 3 nationwide (Greece, Belarus and Slovenia) and one regional (Greater Poland) SEE registries were collected following common coding. Kaplan–Meier curves were constructed, and EFS vs. OS values were derived from Cox proportional hazard models by study variables. A total of 338 WT cases (45.6% males; median age, 3.19 years; age<5 years, 75%) were included in the analyses. Bilateral were 21 tumours (6.2%). Among the 317 unilateral cases, the majority (93.7%) received International Society of Pediatric Oncology–based protocols; EFS 5-year was 85.1%, and OS 5-year 91.1%; both outcomes were significantly worse in stage IV patients or in those with high-risk/unfavourable histology. Relapse rate among high-risk/unfavourable histology cases was 2.3 times higher than among low-intermediate risk/favourable histology cases, with respective death rate 5.6 times higher. Both relapse and death rates increased significantly in patients with advanced anatomical stage and high-risk/unfavourable histology. Finally, significantly worse was the outcome in bilateral tumours (OS 5-year : 76.3%) vs. unilateral non-metastatic tumours (OS 5-year : 94.7%). Our results delineate the potential of high-quality childhood cancer registration entailing clinical data to assess predictors of WT outcome over and beyond those derived from enrolment into clinical trials. Specifically, outcomes among children with WT residing in the four participating SEE countries were comparable with those reported by major cooperative international groups, albeit somehow inferior. Despite the excellent overall prognosis, however, subgroups of patients with advanced or bilateral disease and/or high-risk histology still suffer poor outcomes. • Event-free survival (EFS) and overall survival (OS) in South-East Europe are comparable with those of major cooperative international groups. • Outcomes for patients with advanced disease, high-risk histology and bilateral tumours need to be optimised. • Better risk stratification and enhanced clinical management may be needed to improve outcomes. • Quality childhood cancer registration entailing harmonised clinical data is crucial in assessing Wilms tumour outcomes. [ABSTRACT FROM AUTHOR]

Background Despite recent therapeutic advancements, Wilms tumour (WT) presents remarkable survival variations. We explored mortality and survival patterns for children (0–14 years) with WT in 12 Southern and Eastern European (SEE) countries in comparison with the United States of America (USA). Methods A total of 3966 WT cases (0–14 years) were registered by a network of SEE childhood cancer registries (N:1723) during available registration periods circa 1990–2016 and surveillance, epidemiology, and end results program (SEER) (N:2243; 1990–2012); mortality data were provided by the respective national statistical services. Kaplan–Meier curves and Cox proportional hazards models were used to assess the role of age, sex, year of diagnosis, urbanisation and Human Development Index (HDI) on overall survival (OS). Results Persisting regional variations shape an overall 78% 5-year OS in the participating SEE countries, lagging behind the USA figure (92%, p=0.001 ) and also reflected by higher SEE mortality rates. Worth mentioning is the gradually escalating OS in SEE (hazard ratio [HR] 5-year increment :0.67, 95% confidence interval [CI]:0.60, 0.75) vs. a non-significant 10% improvement in the SEER data, which had a high starting value. OS differentials [two-fold less favourable among children aged 10–14 years, boys and those living in rural SEE areas (HR:1.37; CI:1.10–1.71) or countries with inferior HDI (2–3-fold)] were minimal in the USA. Conclusions Children with WT residing in SEE countries do not equally enjoy the substantial survival gains, especially for those living in rural areas and in lower HDI countries. Noteworthy are steep and sizeable survival gains in SEE along with the newly presented Greek data pointing to achievable survival goals in SEE despite the financial crisis. [ABSTRACT FROM AUTHOR]

Aim Neuroblastoma outcomes vary with disease characteristics, healthcare delivery and socio-economic indicators. We assessed survival patterns and prognostic factors for patients with neuroblastoma in 11 Southern and Eastern European (SEE) countries versus those in the US, including—for the first time—the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumours (NARECHEM-ST)/Greece. Methods Overall survival (OS) was calculated in 13 collaborating SEE childhood cancer registries (1829 cases, ∼1990–2016) and Surveillance, Epidemiology, and End Results (SEER), US (3072 cases, 1990–2012); Kaplan–Meier curves were used along with multivariable Cox regression models assessing the effect of age, gender, primary tumour site, histology, Human Development Index (HDI) and place of residence (urban/rural) on survival. Results The 5-year OS rates varied widely among the SEE countries (Ukraine: 45%, Poland: 81%) with the overall SEE rate (59%) being significantly lower than in SEER (77%; p < 0.001). In the common registration period within SEE (2000–2008), no temporal trend was noted as opposed to a significant increase in SEER. Age >12 months (hazard ratio [HR]: 2.8–4.7 in subsequent age groups), male gender (HR: 1.1), residence in rural areas (HR: 1.3), living in high (HR: 2.2) or medium (HR: 2.4) HDI countries and specific primary tumour location were associated with worse outcome; conversely, ganglioneuroblastoma subtype (HR: 0.28) was associated with higher survival rate. Conclusions Allowing for the disease profile, children with neuroblastoma in SEE, especially those in rural areas and lower HDI countries, fare worse than patients in the US, mainly during the early years after diagnosis; this may be attributed to presumably modifiable socio-economic and healthcare system performance differentials warranting further research. [ABSTRACT FROM AUTHOR]

The prognosis of children with neuroblastoma (NBL) can be dismal with significant variations depending on the stage and biology of the tumor. We assessed the event-free (EFS) and overall (OS) survival using harmonized data from three Southern-Eastern European (SEE) countries. Data for 520 incident NBL cases (2009-2018) were collected from Greece, Slovenia and Russia. Kaplan-Meier curves were fitted, and EFS/OS were derived from Cox proportional models by study variables including the protocol-based risk-group (low/observation, intermediate, high). Over one-third of cases were coded in the high-risk group, of which 23 children (4.4%) received treatment with anti-ganglioside 2 (GD2) mAb. Survival rates were inferior in older (OS 5-year; 1.5-4.9 years: 61%; EFS 5-year; 1.5-4.9 years: 48%) compared to children younger than 1.5 years (OS 5-year; <1.5 years: 91%; EFS 5-year; <1.5 years: 78%). Predictors of poor OS included stage 4 (hazard ratio, HR OS : 18.12, 95% confidence intervals, CI: 3.47-94.54), N-myc amplification (HR OS : 2.16, 95% CI: 1.40-3.34), no surgical excision (HR OS : 3.27, 95% CI: 1.91-5.61) and relapse/progression (HR OS : 5.46, 95% CI: 3.23-9.24). Similar unfavorable EFS was found for the same subsets of patients. By contrast, treatment with anti-GD2 antibody in high-risk patients was associated with decreased risk of death or unfavorable events (HR OS : 0.11, 95% CI: 0.02-0.79; HR EFS : 0.19, 95% CI: 0.07-0.52). Our results confirm the outstanding prognosis of the early NBL stages, especially in children <1.5 years, and the improved outcomes of the anti-GD2 treatment in high-risk patients. Ongoing high-quality clinical cancer registration is needed to ensure comparability of survival across Europe and refine our understanding of the NBL biology., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite advances in the management of nephroblastoma (Wilms' tumor, WT), the etiology of the tumor remains obscure. We aimed to compare nephroblastoma incidence rates and time trends among children (0-14 years) in 12 Southern and Eastern European (SEE) countries and the Surveillance, Epidemiology, and End Results Program (SEER), USA, in relation to the human development index (HDI)., Methods: In total 1776 WT cases were recorded in 13 SEE collaborating registries (circa 1990-2016), whereas data on 2260 cases (1990-2012) were extracted from the SEER database. Age-standardized incidence rates (AIRs) were calculated and correlated with HDI, whereas temporal trends were evaluated using Poisson regression and Joinpoint analyses., Results: The overall SEE AIR (9.2/10 6 ) was marginally higher than that of the SEER (8.3/10 6 ), whereas significant differences were noted among the 13 SEE registries which comprised mainly Caucasian populations. A statistically significant temporal increase in incidence was noted only in Belarus. Most cases (∼75%) were diagnosed before the fifth year of life, with rates steadily declining thereafter; median age at diagnosis was similar in SEE countries and SEER. A slight male preponderance in the first year of life (male:female = 1.1) was followed by a female preponderance in the older age groups (male:female = 0.7). Lastly, a statistically significant positive association between higher HDI and increasing nephroblastoma incidence was noted (regression coefficient: +3.25, 95%CI: +1.35, +5.15)., Conclusions: Variations in incidence and time trends across the examined registries, changing male-to-female patterns with advancement in age, and positive associations with the HDI imply a plausible role for environmental and genetic factors in disease etiology, and these need to be explored further., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Neuroblastoma comprises the most common neoplasm during infancy (first year of life). Our study describes incidence of neuroblastoma in Southern-Eastern Europe (SEE), including - for the first time - the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST)/Greece, compared to the US population, while controlling for human development index (HDI). Age-adjusted incidence rates (AIR) were calculated for 1,859 childhood (0-14 years) neuroblastoma cases, retrieved from 13 collaborating SEE registries (1990-2016), and were compared to those of SEER/US (N = 3,166; 1990-2012); temporal trends were assessed using Poisson regression and Joinpoint analyses. The overall AIR was significantly lower in SEE (10.1/million) compared to SEER (11.7 per million); the difference was maximum during infancy (43.7 vs. 53.3 per million, respectively), when approximately one-third of cases were diagnosed. Incidence rates of neuroblastoma at ages <1 and 1-4 years were positively associated with HDI, whereas lower median age at diagnosis was correlated with higher overall AIR. Distribution of primary site and histology was similar in SEE and SEER. Neuroblastoma was slightly more common among males compared to females (male-to-female ratio: 1.1), mainly among SEE infants. Incidence trends decreased in infants in Slovenia, Cyprus and SEER and increased in Ukraine and Belarus. The lower incidence in SEE compared to SEER, especially in infants living in low HDI countries possibly indicates a lower level of overdiagnosis in SEE. Hence, increases in incidence rates in infancy noted in some subpopulations should be carefully monitored to avoid the unnecessary costs health impacts of tumors that could potentially spontaneously regress., (© 2017 UICC.)

Aim: Childhood central nervous system (CNS) tumour registration and control programs in Southern and Eastern Europe remain thin, despite the lethal nature of the disease. Mortality/survival data were assembled to estimate the burden of malignant CNS tumours, as well as the potential role of sociodemographic survival determinants across 14 cancer registries of this region., Methods: Average age-adjusted mortality rates were calculated, whereas time trends were quantified through Poisson and Joinpoint regressions. Kaplan-Meier curves were derived for the maximum and the more recent (10 and 5 year) registration periods. Multivariate Cox regression models were used to assess demographic and disease-related determinants., Results: Variations in mortality (8-16 per million) and survival (5-year: 35-69%) were substantial among the participating registries; in most registries mortality trend was stable, whereas Bulgaria, having the highest starting rate, experienced decreasing annual mortality (-2.4%, p=0.001). A steep decrease in survival rates was evident before the second year of follow-up. After controlling for diagnostic subgroup, age, gender and diagnostic year, Greece seemed to present higher survival compared with the other contributing registries, although the follow-up period was short. Irrespective of country, however, rural residence was found to impose substantial adverse repercussions on survival (hazard ratio (HR): 1.2, 95% confidence interval (CI): 1.1-1.4)., Conclusion: Cross-country mortality and survival variations possibly reflect suboptimal levels of health care delivery and cancer control in some regions of Southern and Eastern Europe, notwithstanding questionable death certification patterns or follow-up procedures. Continuous childhood cancer registration and linkage with clinical data are prerequisite for the reduction of survival inequalities across Europe., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aim: Following completion of the first 5-year nationwide childhood (0-14 years) registration in Greece, central nervous system (CNS) tumour incidence rates are compared with those of 12 registries operating in 10 Southern-Eastern European countries., Methods: All CNS tumours, as defined by the International Classification of Childhood Cancer (ICCC-3) and registered in any period between 1983 and 2014 were collected from the collaborating cancer registries. Data were evaluated using standard International Agency for Research on Cancer (IARC) criteria. Crude and age-adjusted incidence rates (AIR) by age/gender/diagnostic subgroup were calculated, whereas time trends were assessed through Poisson and Joinpoint regression models., Results: 6062 CNS tumours were retrieved with non-malignant CNS tumours recorded in eight registries; therefore, the analyses were performed on 5191 malignant tumours. Proportion of death certificate only cases was low and morphologic verification overall high; yet five registries presented >10% unspecified neoplasms. The male/female ratio was 1.3 and incidence decreased gradually with age, apart from Turkey and Ukraine. Overall AIR for malignant tumours was 23/10(6) children, with the highest rates noted in Croatia and Serbia. A statistically significant AIR increase was noted in Bulgaria, whereas significant decreases were noted in Belarus, Croatia, Cyprus and Serbia. Although astrocytomas were overall the most common subgroup (30%) followed by embryonal tumours (26%), the latter was the predominant subgroup in six registries., Conclusion: Childhood cancer registration is expanding in Southern-Eastern Europe. The heterogeneity in registration practices and incidence patterns of CNS tumours necessitates further investigation aiming to provide clues in aetiology and direct investments into surveillance and early tumour detection., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: Within Europe, incidence and mortality rates of childhood leukemia and lymphoma are rather heterogeneous. The present study comprising data from five Southern and Eastern European Cancer Registries aims to compare time trends and examine whether sociodemographic variables, clinical parameters, and proxies of efficient care affect survival., Methods: Data spanning 1996-2010 were obtained for a total of 3,041 newly diagnosed childhood leukemia and 1,183 lymphoma cases reported by the Greek Nationwide Registry for Childhood Hematological Malignancies, Bulgarian National Cancer Registry, Moscow Region and Turkey (Antalya and Izmir) Cancer Registries. Poisson modeling for the evaluation of time trends and multivariate Cox regression analysis for the assessment of prognostic factors were performed., Results: The incidence of leukemia was increasing in all cases, with Bulgaria and Greece presenting statistically significant annual changes (+3.5, and +1.7 %, respectively), followed by marginally increasing trends in Izmir and Moscow; by contrast, there was a remarkable, statistically significant, decreasing mortality trend for leukemia. Rates for lymphoma remained flat. Greece experienced almost twofold better survival rates for both leukemia and lymphoma, probably due to its higher socioeconomic status during the study period. Overall, patients with leukemia living in rural areas had a 28 % lower prognosis (RR: 1.28, 95 % CI 1.03-1.59), pointing to effects of remoteness, when the most privileged country (Greece) was excluded from the analysis., Conclusions: The favorable mortality trends highlight the progress in Southern-Eastern European countries along their trajectory to converge with Northern-Western EU counterpart states. Socioeconomic status may act as a multipotent factor underlying the study findings.