Mario Sekerija

Childhood central nervous system tumours: Incidence and time trends in 13 Southern and Eastern European cancer registries

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.

Childhood central nervous system tumour mortality and survival in Southern and Eastern Europe (1983-2014 ): Gaps persist across 14 cancer registries.

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.

Incidence and mortality trends of gastric and colorectal cancers in Croatia, 1988-2008

Aim To estimate the incidence and mortality trends of gastric and colorectal cancers in Croatia between 1988 and 2008. Methods Incidence data for the period 1988-2008 were obtained from the Croatian National Cancer Registry. The number of deaths from gastric and colorectal cancers was obtained from the World Health Organization mortality database. Joinpoint regression analysis was used to describe changes in trends by sex. Results Gastric cancer incidence rates declined steadily during the study period, with estimated annual percent change (EAPC) of -3.2% for men and -2.8% for women. Mortality rates in men decreased, with EAPC of -5.0% from 1988-1995 and -2.5% from 1995-2008. Mortality rates in women decreased, with EAPC of -3.2% throughout the study period. For colorectal cancer in men, joinpoint analysis revealed increasing trends of both incidence (EAPC 2.9%) and mortality (EAPC 2.1%).In women, the increase in incidence was not significant, but mortality in the last 15 years showed a significant increase of 1.1%. Conclusion The incidence and mortality trends of gastric cancer in Croatia are similar to other European countries, while the still increasing colorectal cancer mortality calls for more efficient prevention and treatment.

Neuroblastoma among children in Southern and Eastern European cancer registries: Variations in incidence and temporal trends compared to US: Incidence variation in neuroblastoma

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.

Malignant central nervous system tumors among adolescents and young adults (15‐39 years old) in 14 Southern‐Eastern European registries and the US Surveillance, Epidemiology, and End Results program: Mortality and survival patterns

Unique features and worse outcomes have been reported for cancers among adolescents and young adults (AYAs; 15‐39 years old). The aim of this study was to explore the mortality and survival patterns of malignant central nervous system (CNS) tumors among AYAs in Southern‐Eastern Europe (SEE) in comparison with the US Surveillance, Epidemiology, and End Results (SEER) program.

Mortality and survival patterns of childhood lymphomas: geographic and age-specific patterns in Southern-Eastern European and SEER/US registration data.

Childhood (0‐14 years) lymphomas, nowadays, present a highly curable malignancy compared with other types of cancer. We used readily available cancer registration data to assess mortality and survival disparities among children residing in Southern‐Eastern European (SEE) countries and those in the United States. Average age‐standardized mortality rates and time trends of Hodgkin (HL) and non‐Hodgkin (NHL; including Burkitt [BL]) lymphomas in 14 SEE cancer registries (1990‐2014) and the Surveillance, Epidemiology, and End Results Program (SEER, United States; 1990‐2012) were calculated. Survival patterns in a total of 8918 cases distinguishing also BL were assessed through Kaplan‐Meier curves and multivariate Cox regression models. Variable, rather decreasing, mortality trends were noted among SEE. Rates were overall higher than that in SEER (1.02/106), which presented a sizeable (−4.8%, P = .0001) annual change. Additionally, remarkable survival improvements were manifested in SEER (10 years: 96%, 86%, and 90% for HL, NHL, and BL, respectively), whereas diverse, still lower, rates were noted in SEE. Non‐HL was associated with a poorer outcome and an amphi‐directional age‐specific pattern; specifically, prognosis was inferior in children younger than 5 years than in those who are 10 to 14 years old from SEE (hazard ratio 1.58, 95% confidence interval 1.28‐1.96) and superior in children who are 5 to 9 years old from SEER/United States (hazard ratio 0.63, 95% confidence interval 0.46‐0.88) than in those who are 10 to 14 years old. In conclusion, higher SEE lymphoma mortality rates than those in SEER, but overall decreasing trends, were found. Despite significant survival gains among developed countries, there are still substantial geographic, disease subtype‐specific, and age‐specific outcome disparities pointing to persisting gaps in the implementation of new treatment modalities and indicating further research needs.

Cervical HPV type-specific pre-vaccination prevalence and age distribution in Croatia

The main etiological factor of precancerous lesion and invasive cervical cancer are oncogenic human papillomaviruses types (HPVs). The objective of this study was to establish the distribution of the most common HPVs in different cervical lesions and cancer prior to the implementation of organized population-based cervical screening and HPV vaccination in Croatia. In this study, 4,432 cervical specimens, collected through a 16-year period, were tested for the presence of HPV-DNA by polymerase chain reaction (PCR) with three sets of broad-spectrum primers and type-specific primers for most common low-risk (LR) types (HPV-6, 11) and the most common high-risk (HR) types (HPV-16, 18, 31, 33, 45, 52, 58). Additional 35 archival formalin-fixed, paraffin embedded tissue of cervical cancer specimens were analyzed using LiPA25 assay. The highest age-specific HPV-prevalence was in the group 18–24 years, which decreased continuously with age (P<0.0001) regardless of the cytological diagnosis. The prevalence of HR-HPV types significantly increased (P<0.0001) with the severity of cervical lesions. HPV-16 was the most common type found with a prevalence (with or without another HPV-type) of 6.9% in normal cytology, 15.5% in atypical squamous cells of undetermined significance, 14.4% in low-grade squamous intraepithelial lesions, 33.3% in high-grade squamous intraepithelial lesions, and 60.9% in cervical cancer specimens (P<0.0001). This study provides comprehensive and extensive data on the distribution of the most common HPV types among Croatian women, which will enable to predict and to monitor the impact of HPV-vaccination and to design effective screening strategies in Croatia.

Trends in incidence of lung cancer in Croatia from 2001 to 2013: gender and regional differences

Aim To provide an overview of the lung cancer incidence trends in the City of Zagreb (Zagreb), Split-Dalmatia County (SDC), and Croatia in the period from 2001 to 2013. Method Incidence data were obtained from the Croatian National Cancer Registry. For calculating incidence rates per 100 000 population, we used population estimates for the period 2001-2013 from the Croatian Bureau of Statistics. Age-standardized rates of lung cancer incidence were calculated by the direct standardization method using the European Standard Population. To describe incidence trends, we used joinpoint regression analysis. Results Joinpoint analysis showed a statistically significant decrease in lung cancer incidence in men in all regions, with an annual percentage change (APC) of -2.2% for Croatia, 1.9% for Zagreb, and -2.0% for SDC. In women, joinpoint analysis showed a statistically significant increase in the incidence for Croatia, with APC of 1.4%, a statistically significant increase of 1.0% for Zagreb, and no significant change in trend for SDC. In both genders, joinpoint analysis showed a significant decrease in age-standardized incidence rates of lung cancer, with APC of -1.3% for Croatia, -1.1% for Zagreb, and -1.6% for SDC. Conclusion There was an increase in female lung cancer incidence rate and a decrease in male lung cancer incidence rate in Croatia in 2001-20013 period, with similar patterns observed in all the investigated regions. These results highlight the importance of smoking prevention and cessation policies, especially among women and young people.