Helen Dana

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.

Optic pathway glioma in children: 10 years of experience in a single institution

ABSTRACT Optic pathway glioma (OPG) is a rare brain tumor that occurs more commonly during early childhood and is frequently associated with neurofibromatosis type 1 (NF1). In this study, our aim was to describe the characteristics, management, and outcome of patients with OPG. We retrospectively analyzed the clinical charts of all children diagnosed with OPG at our institution from 2003 to 2013. Twenty children (11 boys and 9 girls, median age: 5 and 3/12 years; NF1: 15/20) were diagnosed with OPG. The diagnosis was based on magnetic resonance imaging (MRI) findings. A biopsy was useful in 3 patients. The main reason for seeking medical advice was decreased vision (7/20 patients), whereas in 10/20 patients, the diagnosis was established during the routine follow-up for their NF1. Fifteen patients demonstrated MRI findings of optic nerve involvement and/or chiasmal tumor, whereas in 5 children, postchiasmal structures were also involved. Sixteen patients (16/20) received carboplatin-based regimens, whereas 4/20 patients were only under close observation. Six patients showed deterioration of visual acuity and/or imaging findings at the end of treatment and/or during their follow-up. Three of them (3/6) underwent tumor resection, whereas 1 (1/6) received radiation treatment. None of our patients had total blindness from both eyes. Half of our patients were diagnosed during follow-up for their NF1, the incidence of which was high in our group. Our data suggest that chemotherapy helps in the preservation of vision in the majority of children.

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.

A Novel Karyotype in Acute Myeloid Leukemia with Basophilia

Acute basophilic leukemia is a distinct entity of Acute Myeloid Leukemia (AML) with primary differentiation to basophils. Increased basophil count has been described in AML cases with translocation t(6;9)(p23;q34) or other chromosomal abnormalities. We describe a 15-year old female teenager with AML and excess peripheral blood and bone marrow basophils. Her white blood cell count at diagnosis was 15.4 G/L with 53% basophils and 17% blasts. The bone marrow cytogenetics analysis did not reveal any of the usual abnormalities. The karyotype showed two closely related leukemic clones: the first (16 metaphases), with a total of 48 chromosomes, had an extra chromosome 8 with deletion of the long arm and an additional 21 (48,XX, +del(8)(q24.2q24.3), t21[16]), while the second clone (2 metaphases), with a total of 47 chromosomes, did not contain the extra 21 chromosome (47, sl, −21[2]). In summary, in this case of AML-M2 with excess basophils, there is a novel chromosomal abnormality, not previously reported in this entity.

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.

Immune response to influenza vaccination in children with cancer

ABSTRACT The aim of this study was to evaluate the ability of influenza immunization to evoke a protective immune response among children with cancer. We evaluated 75 children with cancer who received influenza vaccination. Hemagglutination Inhibition Antibody titers were determined before and after vaccination. The protective rates after vaccination were 79% for H1N1, 75% for H3N2 and 59% for influenza B virus whereas the seroconversion rates were 54%, 44% and 43% respectively. The differences pre- and post-vaccination were significant regardless the method which was used: seroprotection changes, seroconversion and geometric mean titers analyses. Variables such as the pre-vaccination antibody titers, the time when the responses were measured after the vaccination, the age and the type of malignancy as well as the absolute lymphocyte count were found to be correlated with the immune response but the findings were different for each vaccine subunit. In conclusion, influenza vaccination provides protection in a remarkable proportion of pediatric cancer patients whereas this protection is more obvious against H1N1 and H3N2 compared to influenza B. The immune response after vaccination is significant and seems to be influenced by a variety of factors.

Cerebellar Glioblastoma in a Child

returned to school eventually. She received adjuvant chemotherapy (Temodal) and radiotherapy to the brain. At 15 months she developed local recurrence in the original tumour bed and disease progression with metastatic nodules anteriorly to the brain stem and in the lateral ventricles. The tumour recurrence at the original site was excised. Immunostaining of this sample showed loss of PTEN expression (with positive vascular internal control), a strong EGFR expression (with Hirsh index: 240) and a focal positivity for PDL1 (10%). She received further radiotherapy (brain and spine this time) and chemotherapy with Avastin initially while awaiting the results of immunostaining, and after the results she was started on erlotinib. She developed further disease progression while receiving Avastin, seen on an MR scan 2 months after the second surgery. Erlotinib did not influence the disease. Eventually she succumbed, 20 months after the initial diagnosis.

Lymphoblastic Lymphoma in Children and Adolescents: Introduction

Lymphoblastic lymphomas (LBL), like acute lymphoblastic leukemia (ALL), comprise of high-grade neoplasms arising from precursor lymphocytes of B- or T-cell lineage. In the great majority, they are of T-cell lineage (more than 75 %) and localize to the mediastinum (more than 80 %), whereas the less frequent B-cell lineage lymphomas have various primary sites. Mediastinal, bone marrow, and CNS involvements are more common in T-LBL, whereas skin, lymph node, and bone involvements are observed most frequently in B-LBL [1]. The incidence of LBL remains relatively constant across ages for both males and females.

Lymphomas in Children and Adolescents: Introduction

Hodgkin and non-Hodgkin lymphomas account for approximately 13 % of cancers in children and adolescents younger than 20 years of age and are the third most common childhood malignancies following leukemia and CNS tumors.