Trends in female breast cancer incidence, mortality, and survival in Austria, with focus on age, stage, and birth cohorts (1983-2017)

Breast cancer (BC) is the most commonly diagnosed malignant disease and the leading cause of cancer death in women in Austria. We investigated overall and subgroup-specific female breast cancer rates to provide a comprehensive analysis of trends over several decades. Incidence, mortality, and survival, as well as age-, stage-, and birth cohort-specific incidence were analysed using nationwide cancer registry data on 163,694 cases of female breast cancer in Austria (1983-2017). Annual percentage changes were estimated using joinpoint regression. BC incidence underwent linear increases until 1997 and reversed with statistically non-significant declines until 2017. After initial increases in BC-specific mortality, rates were stable from 1989 through 1995 and started declining thereafter, although statistically non-significantly after 2011. Overall BC-specific survivals, as well as survivals according to the calendar period of diagnosis, increased throughout the observation period. Incidence in younger women (aged 44 and lower) showed linear increases, whereas for women aged 45 and higher mostly stable or decreasing rates were observed. Localised BC incidence increased markedly and started declining only in 2012. Distant disease-BC incidence decreased through the whole observation period and incidence of regionalised BC started declining in 2000. Birth cohort-specific incidence peaked in women born between 1935 and 1949 (ages 45-74). In conclusion, the incidence of BC in younger women is increasing, while overall female BC incidence and mortality are stable with non-significant declines. Further, increases in the incidence of early-stage BC (localised) seem disproportionately high in comparison to more modest decreases in late-stage BC incidence (regionalised and distant disease)

Anti-CD3 antibody treatment reduces scar formation in a rat model of myocardial infarction

Introduction: Antibody treatment with anti-thymocyte globulin (ATG) has been shown to be cardioprotective. We aimed to evaluate which single anti-T-cell epitope antibody alters chemokine expression at a level similar to ATG and identified CD3, which is a T-cell co-receptor mediating T-cell activation. Based on these results, the effects of anti-CD3 antibody treatment on angiogenesis and cardioprotection were tested in vitro and in vivo. Methods: Concentrations of IL-8 and MCP-1 in supernatants of human peripheral blood mononuclear cell (PBMC) cultures following distinct antibody treatments were evaluated by Enzyme-linked Immunosorbent Assay (ELISA). In vivo, anti-CD3 antibodies or vehicle were injected intravenously in rats subjected to acute myocardial infarction (AMI). Chemotaxis and angiogenesis were evaluated using tube and migration assays. Intracellular pathways were assessed using Western blot. Extracellular vesicles (EVs) were quantitatively evaluated using fluorescence-activated cell scanning, exoELISA, and nanoparticle tracking analysis. Also, microRNA profiles were determined by next-generation sequencing. Results: Only PBMC stimulation with anti-CD3 antibody led to IL-8 and MCP-1 changes in secretion, similar to ATG. In a rat model of AMI, systemic treatment with an anti-CD3 antibody markedly reduced infarct scar size (27.8% (Inter-quartile range; IQR 16.2–34.9) vs. 12.6% (IQR 8.3–27.2); p < 0.01). The secretomes of anti-CD3 treated PBMC neither induced cardioprotective pathways in cardiomyocytes nor pro-angiogenic mechanisms in human umbilical vein endothelial cell (HUVECs) in vitro. While EVs quantities remained unchanged, PBMC incubation with an anti-CD3 antibody led to alterations in EVs miRNA expression. Conclusion: Treatment with an anti-CD3 antibody led to decreased scar size in a rat model of AMI. Whereas cardioprotective and pro-angiogenetic pathways were unaltered by anti-CD3 treatment, qualitative changes in the EVs miRNA expression could be observed, which might be causal for the observed cardioprotective phenotype. We provide evidence that EVs are a potential cardioprotective treatment target. Our findings will also provide the basis for a more detailed analysis of putatively relevant miRNA candidates

Seasonal variations in the diagnosis of testicular germ cell tumors: a national cancer registry study in austria

SIMPLE SUMMARY: Seasonal variations in cancer diagnosis could already be demonstrated in prostate and breast cancer. The reasons for this observed seasonal pattern are still unclear. The health care system or other determinants such as the protective function of vitamin D3 in carcinogenesis could be assumed as one explanation. Testicular germ cell tumors are the most common developed malignancy among young men. The aim of our study was to investigate, for the first time, the seasonal variations in the clinical diagnosis of testicular germ cell tumors. We have been able to confirm that the frequency of monthly newly diagnosed cases of testicular cell tumors in Austria has a strong seasonality, with a significant reduction in the tumor incidence during the summer months and an increase during the winter months. ABSTRACT: We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend (p < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr–Sep) and an increase during the winter months (Oct–Mar) were observed (p < 0.001). Focusing on seasonality, the incidence during the months of Oct–Dec (p = 0.008) and Jan–Mar (p < 0.001) was significantly higher compared to the months of Jul–Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas (p < 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research

Catalyzing Transcriptomics Research in Cardiovascular Disease : The CardioRNA COST Action CA17129

AbstractCardiovascular disease (CVD) remains the leading cause of death worldwide and, despite continuous advances, better diagnostic and prognostic tools, as well as therapy, are needed. The human transcriptome, which is the set of all RNA produced in a cell, is much more complex than previously thought and the lack of dialogue between researchers and industrials and consensus on guidelines to generate data make it harder to compare and reproduce results. This European Cooperation in Science and Technology (COST) Action aims to accelerate the understanding of transcriptomics in CVD and further the translation of experimental data into usable applications to improve personalized medicine in this field by creating an interdisciplinary network. It aims to provide opportunities for collaboration between stakeholders from complementary backgrounds, allowing the functions of different RNAs and their interactions to be more rapidly deciphered in the cardiovascular context for translation into the clinic, thus fostering personalized medicine and meeting a current public health challenge. Thus, this Action will advance studies on cardiovascular transcriptomics, generate innovative projects, and consolidate the leadership of European research groups in the field. COST (European Cooperation in Science and Technology) is a funding organization for research and innovation networks (www.cost.eu).Abstract Cardiovascular disease (CVD) remains the leading cause of death worldwide and, despite continuous advances, better diagnostic and prognostic tools, as well as therapy, are needed. The human transcriptome, which is the set of all RNA produced in a cell, is much more complex than previously thought and the lack of dialogue between researchers and industrials and consensus on guidelines to generate data make it harder to compare and reproduce results. This European Cooperation in Science and Technology (COST) Action aims to accelerate the understanding of transcriptomics in CVD and further the translation of experimental data into usable applications to improve personalized medicine in this field by creating an interdisciplinary network. It aims to provide opportunities for collaboration between stakeholders from complementary backgrounds, allowing the functions of different RNAs and their interactions to be more rapidly deciphered in the cardiovascular context for translation into the clinic, thus fostering personalized medicine and meeting a current public health challenge. Thus, this Action will advance studies on cardiovascular transcriptomics, generate innovative projects, and consolidate the leadership of European research groups in the field. COST (European Cooperation in Science and Technology) is a funding organization for research and innovation networks (www.cost.eu)

Catalyzing Transcriptomics Research in Cardiovascular Disease : The CardioRNA COST Action CA17129

Cardiovascular disease (CVD) remains the leading cause of death worldwide and, despite continuous advances, better diagnostic and prognostic tools, as well as therapy, are needed. The human transcriptome, which is the set of all RNA produced in a cell, is much more complex than previously thought and the lack of dialogue between researchers and industrials and consensus on guidelines to generate data make it harder to compare and reproduce results. This European Cooperation in Science and Technology (COST) Action aims to accelerate the understanding of transcriptomics in CVD and further the translation of experimental data into usable applications to improve personalized medicine in this field by creating an interdisciplinary network. It aims to provide opportunities for collaboration between stakeholders from complementary backgrounds, allowing the functions of different RNAs and their interactions to be more rapidly deciphered in the cardiovascular context for translation into the clinic, thus fostering personalized medicine and meeting a current public health challenge. Thus, this Action will advance studies on cardiovascular transcriptomics, generate innovative projects, and consolidate the leadership of European research groups in the field.COST (European Cooperation in Science and Technology) is a funding organization for research and innovation networks (www.cost.eu)

Patient-derived xenografts from circulating cancer stem cells as a preclinical model for personalized pancreatic cancer research

Patient-derived xenografts (PDXs) provide biologically relevant models and potential platforms for the development of treatment strategies for precision medicine in pancreatic cancer. Furthermore, circulating epithelial tumor cells (CETCs/CTCs) are released into the bloodstream by solid tumors and a rare subpopulation—circulating cancer stem cells (cCSCs) – is considered to be responsible for recurrence and plays a key role in metastasis. For the identification of cCSCs, an innovative in vitro assay to generate tumorspheres was established in this study. The number of tumorspheres and CETCs/CTCs was analyzed perioperatively in 25 pancreatic cancer patients. Additionally, an individual in vivo chorioallantoic membrane (CAM) culture system was used to generate PDXs from these tumorspheres. While overall correlations of CETCs/CTCs with clinicopathological parameters did not reach statistical significance, a significant difference in the number of tumorspheres was observed between patient subgroups with lower and higher UICC stages. This finding underscores their potential as biomarkers, providing valuable insights into clinical decision-making and tumor progression. The application of tumorspheres on the CAM successfully established PDXs within 7 days. These xenografts closely resembled the histological features of the primary tumor. Hence, this model represents a novel and fast option for individualized testing of new therapies for PDAC

Changing geographical patterns and trends in cancer incidence in children and adolescents in Europe, 1991–2010 (Automated Childhood Cancer Information System): a population-based study

Background: A deceleration in the increase in cancer incidence in children and adolescents has been reported in several national and regional studies in Europe. Based on a large database representing 1·3 billion person-years over the period 1991–2010, we provide a consolidated report on cancer incidence trends at ages 0–19 years. Methods: We invited all population-based cancer registries operating in European countries to participate in this population-based registry study. We requested a listing of individual records of cancer cases, including sex, age, date of birth, date of cancer diagnosis, tumour sequence number, primary site, morphology, behaviour, and the most valid basis of diagnosis. We also requested population counts in each calendar year by sex and age for the registration area, from official national sources, and specific information about the covered area and registration practices. An eligible registry could become a contributor if it provided quality data for all complete calendar years in the period 1991–2010. Incidence rates and the average annual percentage change with 95% CIs were reported for all cancers and major diagnostic groups, by region and overall, separately for children (age 0–14 years) and adolescents (age 15–19 years). We examined and quantified the stability of the trends with joinpoint analyses. Findings: For the years 1991–2010, 53 registries in 19 countries contributed a total of 180 335 unique cases. We excluded 15 162 (8·4%) of 180 335 cases due to differing practices of registration, and considered the quality indicators for the 165 173 cases included to be satisfactory. The average annual age-standardised incidence was 137·5 (95% CI 136·7–138·3) per million person-years and incidence increased significantly by 0·54% (0·44–0·65) per year in children (age 0–14 years) with no change in trend. In adolescents, the combined European incidence was 176·2 (174·4–178·0) per million person-years based on all 35 138 eligible cases and increased significantly by 0·96% (0·73–1·19) per year, although recent changes in rates among adolescents suggest a deceleration in this increasing trend. We observed temporal variations in trends by age group, geographical region, and diagnostic group. The combined age-standardised incidence of leukaemia based on 48 458 cases in children was 46·9 (46·5–47·3) per million person-years and increased significantly by 0·66% (0·48–0·84) per year. The average overall incidence of leukaemia in adolescents was 23·6 (22·9–24·3) per million person-years, based on 4702 cases, and the average annual change was 0·93% (0·49–1·37). We also observed increasing incidence of lymphoma in adolescents (average annual change 1·04% [0·65–1·44], malignant CNS tumours in children (average annual change 0·49% [0·20–0·77]), and other tumours in both children (average annual change 0·56 [0·40–0·72]) and adolescents (average annual change 1·17 [0·82–1·53]). Interpretation: Improvements in the diagnosis and registration of cancers over time could partly explain the observed increase in incidence, although some changes in underlying putative risk factors cannot be excluded. Cancer incidence trends in this young population require continued monitoring at an international level. Funding: Federal Ministry of Health of the Federal German Government, the European Union's Seventh Framework Programme, and International Agency for Research on Cancer

International benchmarking of stage at diagnosis for six childhood solid tumours (the BENCHISTA project): a population-based, retrospective cohort study

Background: International variation in childhood cancer survival might be explained by differences in stage at diagnosis, among other factors. As part of the BENCHISTA project, we aimed to assess geographical variation in tumour stage at diagnosis through the application, by population-based cancer registries working with clinicians, of the international consensus Toronto Childhood Cancer Stage Guidelines. Methods: This population-based, retrospective cohort study involved 73 cancer registries from 23 European countries, Australia, Brazil, Japan, and Canada. Participating cancer registries applied the Toronto Guidelines to stage all incident cases of six childhood solid tumours—neuroblastoma, medulloblastoma, and Wilms tumour (age 0–14 years) and Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma (age ≤19 years)—diagnosed between Jan 1, 2014, and Dec 31, 2017. Eligible cancer registries were those able to assign stage according to the Toronto Guidelines; information on the staging investigations conducted was collected where available. European countries were grouped by geographical area and non-European countries were considered individually. We used χ2 tests to compare stage distribution across these geographical areas and multivariable logistic models to estimate odds ratios (ORs) for metastatic stage at diagnosis, using central Europe (Austria, Belgium, France, Germany, the Netherlands, and Switzerland) as the comparison. Sensitivity analyses were conducted to overcome potential bias from non-random missing stage information for some geographical areas and cancer types. Findings: Data from 10 937 patients with cancer (6031 [55·1%] male and 4906 [44·9%] female) were analysed. Tumour staging was complete for 93·1% (10 180 of 10 937) of patients, ranging from 88·7% (1347 of 1518 patients) with medulloblastoma to 96·5% (1083 of 1122 patients) with Ewing sarcoma. Stage distribution differed statistically by geographical area for neuroblastoma, Wilms tumour, osteosarcoma, and rhabdomyosarcoma, but not for Ewing sarcoma or medulloblastoma. After excluding patients with missing stage information and, for the sarcomas, patients aged 18–19 years, the proportions of patients with metastases detected at diagnosis were 50·3% with neuroblastoma (1435 of 2852 patients; including 1159 [40·6%] stage M and 276 [9·7%] stage MS), 35·1% with medulloblastoma (473 of 1347 patients; stages M1–M4), 32·6% with Ewing sarcoma (335 of 1028 patients), 29·0% with rhabdomyosarcoma (368 of 1267 patients), 25·5% with osteosarcoma (345 of 1353 patients), and 18·2% with Wilms tumour (384 of 2114 patients). After adjusting by age group, significant differences in the proportions of patients with metastases detected at diagnosis were found between geographical areas for neuroblastoma, Wilms tumour, osteosarcoma, and rhabdomyosarcoma. Interpretation: Assessed at a population level, the stage at diagnosis shows significant variation between geographical areas for several childhood tumours. This finding highlights the need for earlier diagnosis and standardisation of investigations for distant metastases. To enable ongoing comparisons, further cooperation efforts are required between cancer registries and clinicians regarding the sustainable and standardised use of the Toronto Guidelines at diagnosis. Funding: Children with Cancer UK and Associazione Italiana per la Ricerca sul Cancro

Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000–14 (CONCORD-3): analysis of individual data from 258 cancer registries in 61 countries

Background: Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0–14 years) and adults (aged 15–99 years) diagnosed with a haematological malignancy during 2000–14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0–24 years). Methods: We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0–14 years), adolescents (15–19 years), and young adults (20–24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. Findings: 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010–14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010–14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000–14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. Interpretation: This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group

Trends in incidence of anal cancer in Austria, 1983–2016

Summary Background Recent reports have noted increasing rates of anal cancer among high-income countries worldwide; however, little is known about these trends in Austria. Methods Data on anal cancer from 1983 to 2016 were obtained from Statistics Austria. All tumors (n = 3567) were classified into anal squamous cell carcinomas (ASCC), anal adenocarcinomas (AADC), and others (unspecified carcinoma and other specific carcinoma). Anal cancer incidence rates were calculated in 5‑year cycles and incidence average annual percentage change (AAPC) to evaluate trends by sex, histology and age group. Results The incidence rate of anal cancer was higher among females than males (relative risk, RR = 1.66, 95% confidence interval, CI: 1.55–1.79, p &lt; 0.0001). From 1983 through 2016, incident anal cancer increased significantly (0.92 per 100,000 person-years to 1.85 per 100,000 person-years, AAPC = 1.93, 95% CI: 1.52 to 2.34, p &lt; 0.0001), particularly among those 40–69 years old. From 1983 through 2016, the increasing anal cancer incidence was primarily driven by ASCC (0.47–1.20 per 100,000 person-years, AAPC = 2.23, 95% CI: 1.58 to 2.88, p &lt; 0.0001) and others (other than ASCC and AADC, AAPC = 1.78, 95% CI: 1.01–2.55), yet stable in AADC (AAPC = 0.88, 95% CI: −0.48–2.25). Conclusions Despite being a rare cancer in Austria, the increase in anal cancer incidence rate from 1983 to 2016 was substantial, particularly in ASCC. The observed rising trends reflect the need to investigate associated risk factors that have increased over time to inform preventive measures. </jats:sec