The EUROCARE-5 study revealed disparities in childhood cancer survival among European countries, giving rise to important initiatives across Europe to reduce the gap. Extending its representativeness ...through increased coverage of eastern European countries, the EUROCARE-6 study aimed to update survival progress across countries and years of diagnosis and provide new analytical perspectives on estimates of long-term survival and the cured fraction of patients with childhood cancer.
In this population-based study, we analysed 135 847 children (aged 0–14 years) diagnosed during 2000–13 and followed up to the end of 2014, recruited from 80 population-based cancer registries in 31 European countries. We calculated age-adjusted 5-year survival differences by country and over time using period analysis, for all cancers combined and for major cancer types. We applied a variant of standard mixture cure models for survival data to estimate the cure fraction of patients by childhood cancer and to estimate projected 15-year survival.
5-year survival for all childhood cancer combined in Europe in 2010–14 was 81% (95% CI 81–82), showing an increase of three percentage points compared with 2004–06. Significant progress over time was observed for almost all cancers. Survival remained stable for osteosarcomas, Ewing sarcoma, Burkitt lymphoma, non-Hodgkin lymphomas, and rhabdomyoscarcomas. For all cancers combined, inequalities still persisted among European countries (with age-adjusted 5-year survival ranging from 71% 95% CI 60–79 to 87% 77–93). The 15-year survival projection for all patients with childhood cancer diagnosed in 2010–13 was 78%. We estimated the yearly long-term mortality rate due to causes other than the diagnosed cancer to be around 2 per 1000 patients for all childhood cancer combined, but to approach zero for retinoblastoma. The cure fraction for patients with childhood cancer increased over time from 74% (95% CI 73–75) in 1998–2001 to 80% (79–81) in 2010–13. In the latter cohort, the cure fraction rate ranged from 99% (95% CI 74–100) for retinoblastoma to 60% (58–63) for CNS tumours and reached 90% (95% CI 87–93) for lymphoid leukaemia and 70% (67–73) for acute myeloid leukaemia.
Childhood cancer survival is increasing over time in Europe but there are still some differences among countries. Regular monitoring of childhood cancer survival and estimation of the cure fraction through population-based registry data are crucial for evaluating advances in paediatric cancer care.
European Commission.
Cancer survivors—people living with and beyond cancer—are a growing population with different health needs depending on prognosis and time since diagnosis. Despite being increasingly necessary, ...complete information on cancer prevalence is not systematically available in all European countries. We aimed to fill this gap by analysing population-based cancer registry data from the EUROCARE-6 study.
In this population-based study, using incidence and follow-up data up to Jan 1, 2013, from 61 cancer registries, complete and limited-duration prevalence by cancer type, sex, and age were estimated for 29 European countries and the 27 countries in the EU (EU27; represented by 22 member states that contributed registry data) using the completeness index method. We focused on 32 malignant cancers defined according to the third edition of the International Classification of Diseases for Oncology, and only the first primary tumour was considered when estimating the prevalence. Prevalence measures are expressed in terms of absolute number of prevalent cases, crude prevalence proportion (reported as percentage or cases per 100 000 resident people), and age-standardised prevalence proportion based on the European Standard Population 2013. We made projections of cancer prevalence proportions up to Jan 1, 2020, using linear regression.
In 2020, 23 711 thousand (95% CI 23 565–23 857) people (5·0% of the population) were estimated to be alive after a cancer diagnosis in Europe, and 22 347 thousand (95% CI 22 210–22 483) in EU27. Cancer survivors were more frequently female (12 818 thousand 95% CI 12 720–12 917) than male (10 892 thousand 10 785–11 000). The five leading tumours in female survivors were breast cancer, colorectal cancer, corpus uterine cancer, skin melanoma, and thyroid cancer (crude prevalence proportion from 2270 95%CI 2248–2292 per 100 000 to 301 297–305 per 100 000). Prostate cancer, colorectal cancer, urinary bladder cancer, skin melanoma, and kidney cancer were the most common tumours in male survivors (from 1714 95% CI 1686–1741 per 100 000 to 255 249–260 per 100 000). The differences in prevalence between countries were large (from 2 to 10 times depending on cancer type), in line with the demographic structure, incidence, and survival patterns. Between 2010 and 2020, the number of prevalent cases increased by 3·5% per year (41% overall), partly due to an ageing population. In 2020, 14 850 thousand (95% CI 14 681–15 018) people were estimated to be alive more than 5 years after diagnosis and 9099 thousand (8909–9288) people were estimated to be alive more than 10 years after diagnosis, representing an increasing proportion of the cancer survivor population.
Our findings are useful at the country level in Europe to support evidence-based policies to improve the quality of life, care, and rehabilitation of patients with cancer throughout the disease pathway. Future work includes estimating time to cure by stage at diagnosis in prevalent cases.
European Commission.
Cancer stem cells (CSCs) are considered a subset of the bulk tumor responsible for initiating and maintaining the disease. Several surface cellular markers have been recently used to identify CSCs. ...Among those is CD133, which is expressed by hematopoietic progenitor cells as well as embryonic stem cells and various cancers. We have recently isolated and cultured CD133 positive CD133+ cells from various cancer cell lines using a NASA developed Hydrodynamic Focusing Bioreactor (HFB) (Celdyne, Houston, TX). For comparison, another bioreactor, the rotary cell culture system (RCCS) manufactured by Synthecon (Houston, TX) was used. Both the HFB and the RCCS bioreactors simulate aspects of hypogravity. In our study, the HFB increased CD133+ cell growth from various cell lines compared to the RCCS vessel and to normal gravity control. We observed a +15-fold proliferation of the CD133+ cellular fraction with cancer cells that were cultured for 7-days at optimized conditions. The RCCS vessel instead yielded a (-)4.8-fold decrease in the CD133+cellular fraction respect to the HFB after 7-days of culture. Interestingly, we also found that the hypogravity environment of the HFB greatly sensitized the CD133+ cancer cells, which are normally resistant to chemo treatment, to become susceptible to various chemotherapeutic agents, paving the way to less toxic and more effective chemotherapeutic treatment in patients. To be able to test the efficacy of cytotoxic agents in vitro prior to their use in clinical setting on cancer cells as well as on cancer stem cells may pave the way to more effective chemotherapeutic strategies in patients. This could be an important advancement in the therapeutic options of oncologic patients, allowing for more targeted and personalized chemotherapy regimens as well as for higher response rates.
Intratumoral injections of a replication-incompetent adenovirus (Ad) expressing melanoma differentiation–associated gene-7/interleukin-24 (Ad.mda-7), a secreted cytokine displaying cancer-selective, ...apoptosis-inducing properties, profoundly inhibits prostate cancer (PC) growth in immune-incompetent animals. In contrast, Ad.mda-7 is ineffective in PCs overexpressing antiapoptotic proteins such as Bcl-2 or Bcl-xL. However, intratumoral injections of a conditionally replication-competent Ad (CRCA) in which expression of the adenoviral E1A gene is driven by the cancer-specific promoter of progression-elevated gene-3 (PEG-3) and which simultaneously expresses mda-7/interleukin (IL)-24 in the E3 region of the Ad (Ad.PEG-E1A-mda-7), a cancer terminator virus (CTV), is highly active in these cells. A major challenge for gene therapy is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles—MBs) are viable candidates for gene delivery/therapy. Here, we show that MB/Ad.mda-7 complexes targeted to DU-145 cells using US dramatically reduced tumor burden in xenografted nude mice. Additionally, US-guided MB/CTV delivery completely eradicated not only targeted DU-145/Bcl-xL-therapy-resistant tumors, but also nontargeted distant tumors (established in the opposite flank), thereby implementing a cure. These findings highlight potential therapeutic applications of this novel image-guided gene therapy technology for advanced PC patients with metastatic disease.
Co-trimoxazole reduces mortality in HIV-infected adults with tuberculosis (TB), and in vitro data suggest potential antimycobacterial activity of co-trimoxazole. We aimed to evaluate whether ...prophylaxis with co-trimoxazole is associated with a decreased risk of incident TB in Swiss HIV Cohort Study (SHCS) participants. We determined the incidence of TB per 1,000 person-years from January 1992 to December 2012. Rates were analyzed separately in participants with current or no previous antiretroviral treatment (ART) using Poisson regression adjusted for CD4 cell count, sex, region of origin, injection drug use, and age. A total of 13,431 cohort participants contributed 107,549 person-years of follow-up: 182 patients had incident TB-132 (73%) before and 50 (27%) after ART initiation. The multivariable incidence rate ratios for cumulative co-trimoxazole exposure per year for persons with no previous ART and current ART were 0.70 (95% confidence interval CI, 0.55 to 0.89) and 0.87 (95% CI, 0.74 to 1.0), respectively. Co-trimoxazole may prevent the development of TB among HIV-positive persons, especially among those with no previous ART.
Concrete used for the construction of buildings accounts for approximately 60 % of concrete production in Europe. At the same time, design approaches and materials specification are fundamental ...components of the delivery of total structural designs of concrete buildings that influence the amount and type of concrete used and procured for a building. This study investigates potential reductions on the embodied carbon of concrete framed buildings through combined improvements in structural design approaches and materials specification. Different design practices across Europe are analysed for residential and office buildings, together with effects of construction types on material efficiency of different slab structural systems and concrete mixes. Three distinct scenarios towards decarbonisation of concrete buildings are derived: a) Baseline, which accounts for conventional current building design, b) Transition, which involves achievable measures with little or no new technical development required and c) Ambitious, which involves a more optimistic view of possible interventions available over time. It was found that in the transition scenario, potential reductions of embodied carbon of the order of 40 % for the residential sector, and 29 % office sector are possible compared to the baseline. In the more ambitious scenario, these savings could be improved to 55 % and 61 %, respectively.
Introducción: Los modelos de predicción de riesgo de cirugías cardiovasculares se aplican ampliamente a la práctica médica. Sin embargo, han sido criticados por su baja calidad metodológica y escasa ...validación externa. En América Latina se agrega la limitación de que la mayoría de estos modelos fueron desarrollados en Estados Unidos o Europa, existiendo diferencias geográficas marcadas. El objetivo de este estudio es caracterizar los eventos clínicos postoperatorios de cirugías cardiovasculares con uso de bomba de circulación extracorpórea en un escenario local y evaluar la predicción de mortalidad postoperatoria del modelo predictivo EuroSCORE II. Métodos: Corte transversal en un hospital universitario urbano de Buenos Aires. Se incluyeron a pacientes ≥21 años de edad, con indicación de cirugía cardiovascular con uso de bomba. Se excluyeron a pacientes con datos clínicos incompletos respecto a las variables del EuroSCORE II o respecto a la sobrevida intrahospitalaria, con ≥95 años de edad o sometidos a trasplante cardíaco. Resultados: Se enrolaron 195 pacientes. La mortalidad postoperatoria estimada por el EuroSCORE II presentó una clara subestimación del riesgo (3,0% vs 7,7%). La discriminación (AUC = 0,82; IC95% 0,74-0,92) y la bondad del ajuste del modelo fueron adecuadas (χ2 = 7,91; p = 0,4418). Las complicaciones postoperatorias más frecuentes fueron insuficiencia cardíaca postoperatoria (35,9%), shock vasopléjico (13,3%) y shock cardiogénico (10,26%). Conclusión: El EuroSCORE II es una herramienta apropiada para discriminar entre diferentes categorías de riesgo en pacientes sometidos a cirugías cardiovasculares con uso de bomba, si bien subestima el riesgo.
Introducción: Los modelos de predicción de riesgo de cirugías cardiovasculares se aplican ampliamente a la práctica médica. Sin embargo, han sido criticados por su baja calidad metodológica y escasa ...validación externa. En América Latina se agrega la limitación de que la mayoría de estos modelos fueron desarrollados en Estados Unidos o Europa, existiendo diferencias geográficas marcadas. El objetivo de este estudio es caracterizar los eventos clínicos postoperatorios de cirugías cardiovasculares con uso de bomba de circulación extracorpórea en un escenario local y evaluar la predicción de mortalidad postoperatoria del modelo predictivo EuroSCORE II. Métodos: Corte transversal en un hospital universitario urbano de Buenos Aires. Se incluyeron a pacientes ≥21 años de edad, con indicación de cirugía cardiovascular con uso de bomba. Se excluyeron a pacientes con datos clínicos incompletos respecto a las variables del EuroSCORE II o respecto a la sobrevida intrahospitalaria, con ≥95 años de edad o sometidos a trasplante cardíaco. Resultados: Se enrolaron 195 pacientes. La mortalidad postoperatoria estimada por el EuroSCORE II presentó una clara subestimación del riesgo (3,0% vs 7,7%). La discriminación (AUC = 0,82; IC95% 0,74-0,92) y la bondad del ajuste del modelo fueron adecuadas (χ2 = 7,91; p = 0,4418). Las complicaciones postoperatorias más frecuentes fueron insuficiencia cardíaca postoperatoria (35,9%), shock vasopléjico (13,3%) y shock cardiogénico (10,26%). Conclusión: El EuroSCORE II es una herramienta apropiada para discriminar entre diferentes categorías de riesgo en pacientes sometidos a cirugías cardiovasculares con uso de bomba, si bien subestima el riesgo.
During the semi-confinement period linked to the COVID-19 pandemic, the CHUV's Child Abuse and Neglect Team observed a decrease in cases of child abuse. Has confinement made it easier for families to ...avoid violence or, on the contrary, to hide it? Within the framework of this second hypothesis, we propose that the relaxation of the measures be an opportunity for professionals to explore in families the possible occurrence of domestic abuse.
Management of lymphoid malignancies requires substantial health system resources. Total national health expenditure might influence population-based lymphoid malignancy survival. We studied the ...long-term survival of patients with 12 lymphoid malignancy types and examined whether different levels of national health expenditure might explain differences in lymphoid malignancy prognosis between European countries and regions.
For this observational, retrospective, population-based study, we analysed the EUROCARE-6 dataset of patients aged 15 or older diagnosed between 2001 and 2013 with one of 12 lymphoid malignancies defined according to International Classification of Disease for Oncology (third edition) and WHO classification, and followed up to 2014 (Jan 1, 2001–Dec 31, 2014). Countries were classified according to their mean total national health expenditure quartile in 2001–13. For each lymphoid malignancy, 5-year and 10-year age-standardised relative survival (ASRS) was calculated using the period approach. Generalised linear models indicated the effects of age at diagnosis, gender, and total national health expenditure on the relative excess risk of death (RER).
82 cancer registries (61 regional and 21 national) from 27 European countries provided data eligible for 10-year survival estimates comprising 890 730 lymphoid malignancy cases diagnosed in 2001–13. Median follow-up time was 13 years (IQR 13–14). Of the 12 lymphoid malignancies, the 10-year ASRS in Europe was highest for hairy cell leukaemia (82·6% 95% CI 78·9–86·5) and Hodgkin lymphoma (79·3% 78·6–79·9) and lowest for plasma cell neoplasms (29·5% 28·9–30·0). RER increased with age at diagnosis, particularly from 55–64 years to 75 years or older, for all lymphoid malignancies. Women had higher ASRS than men for all lymphoid malignancies, except for precursor B, T, or natural killer cell, or not-otherwise specified lymphoblastic lymphoma or leukaemia. 10-year ASRS for each lymphoid malignancy was higher (and the RER lower) in countries in the highest national health expenditure quartile than in countries in the lowest quartile, with a decreasing pattern through quartiles for many lymphoid malignancies. 10-year ASRS for non-Hodgkin lymphoma, the most representative class for lymphoid malignancies based on the number of incident cases, was 59·3% (95% CI 58·7–60·0) in the first quartile, 57·6% (55·2–58·7) in the second quartile, 55·4% (54·3–56·5) in the third quartile, and 44·7% (43·6–45·8) in the fourth quartile; with reference to the European mean, the RER was 0·80 (95% CI 0·79–0·82) in the first, 0·91 (0·90–0·93) in the second, 0·94 (0·92–0·96) in the third, and 1·45 (1·42–1·48) in the fourth quartiles.
Total national health expenditure is associated with geographical inequalities in lymphoid malignancy prognosis. Policy decisions on allocating economic resources and implementing evidence-based models of care are needed to reduce these differences.
Italian Ministry of Health, European Commission, Estonian Research Council.
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