Monitoring the decreasing trend of testicular cancer mortality in Spain during 2005-2019 through a Bayesian approach

Purpose : To assess time trends of testicular cancer (TC) mortality in Spain for period 1985-2019 for age groups 15-74 years old through a Bayesian age-period-cohort (APC) analysis. Methods: A Bayesian age-drift model has been fitted to describe trends. Projections for 2005-2019 have been calculated by means of an autoregressive APC model. Prior precision for these parameters has been selected through evaluation of an adaptive precision parameter and 95% credible intervals (95% CRI) have been obtained for each model parameter. Results: A decrease of -2.41% (95% CRI: -3.65%; -1.13%) per year has been found for TC mortality rates in age groups 15-74 during 1985-2004, whereas mortality showed a lower annual decrease when data was restricted to age groups 15-54 (-1.18%; 95% CRI: -2.60%; -0.31%). During 2005-2019 is expected a decrease of TC mortality of 2.30% per year for men younger than 35, whereas a leveling off for TC mortality rates is expected for men older than 35. Conclusions: A Bayesian approach should be recommended to describe and project time trends for those diseases with low number of cases. Through this model it has been assessed that management of TC and advances in therapy led to decreasing trend of TC mortality during the period 1985-2004, whereas a leveling off for these trends can be considered during 2005-2019 among men older than 35.

Monitoring the decreasing trend of testicular cancer mortality in Spain during 2005-2019 through a Bayesian approach

Purpose : To assess time trends of testicular cancer (TC) mortality in Spain for period 1985-2019 for age groups 15-74 years old through a Bayesian age-period-cohort (APC) analysis. Methods: A Bayesian age-drift model has been fitted to describe trends. Projections for 2005-2019 have been calculated by means of an autoregressive APC model. Prior precision for these parameters has been selected through evaluation of an adaptive precision parameter and 95% credible intervals (95% CRI) have been obtained for each model parameter. Results: A decrease of -2.41% (95% CRI: -3.65%; -1.13%) per year has been found for TC mortality rates in age groups 15-74 during 1985-2004, whereas mortality showed a lower annual decrease when data was restricted to age groups 15-54 (-1.18%; 95% CRI: -2.60%; -0.31%). During 2005-2019 is expected a decrease of TC mortality of 2.30% per year for men younger than 35, whereas a leveling off for TC mortality rates is expected for men older than 35. Conclusions: A Bayesian approach should be recommended to describe and project time trends for those diseases with low number of cases. Through this model it has been assessed that management of TC and advances in therapy led to decreasing trend of TC mortality during the period 1985-2004, whereas a leveling off for these trends can be considered during 2005-2019 among men older than 35.

Monitoring the decreasing trend of testicular cancer mortality in Spain during 2005-2019 through a Bayesian approach

Purpose : To assess time trends of testicular cancer (TC) mortality in Spain for period 1985-2019 for age groups 15-74 years old through a Bayesian age-period-cohort (APC) analysis. Methods: A Bayesian age-drift model has been fitted to describe trends. Projections for 2005-2019 have been calculated by means of an autoregressive APC model. Prior precision for these parameters has been selected through evaluation of an adaptive precision parameter and 95% credible intervals (95% CRI) have been obtained for each model parameter. Results: A decrease of -2.41% (95% CRI: -3.65%; -1.13%) per year has been found for TC mortality rates in age groups 15-74 during 1985-2004, whereas mortality showed a lower annual decrease when data was restricted to age groups 15-54 (-1.18%; 95% CRI: -2.60%; -0.31%). During 2005-2019 is expected a decrease of TC mortality of 2.30% per year for men younger than 35, whereas a leveling off for TC mortality rates is expected for men older than 35. Conclusions: A Bayesian approach should be recommended to describe and project time trends for those diseases with low number of cases. Through this model it has been assessed that management of TC and advances in therapy led to decreasing trend of TC mortality during the period 1985-2004, whereas a leveling off for these trends can be considered during 2005-2019 among men older than 35.

Monitoring the decreasing trend of testicular cancer mortality in Spain during 2005-2019 through a Bayesian approach

Purpose : To assess time trends of testicular cancer (TC) mortality in Spain for period 1985-2019 for age groups 15-74 years old through a Bayesian age-period-cohort (APC) analysis. Methods: A Bayesian age-drift model has been fitted to describe trends. Projections for 2005-2019 have been calculated by means of an autoregressive APC model. Prior precision for these parameters has been selected through evaluation of an adaptive precision parameter and 95% credible intervals (95% CRI) have been obtained for each model parameter. Results: A decrease of -2.41% (95% CRI: -3.65%; -1.13%) per year has been found for TC mortality rates in age groups 15-74 during 1985-2004, whereas mortality showed a lower annual decrease when data was restricted to age groups 15-54 (-1.18%; 95% CRI: -2.60%; -0.31%). During 2005-2019 is expected a decrease of TC mortality of 2.30% per year for men younger than 35, whereas a leveling off for TC mortality rates is expected for men older than 35. Conclusions: A Bayesian approach should be recommended to describe and project time trends for those diseases with low number of cases. Through this model it has been assessed that management of TC and advances in therapy led to decreasing trend of TC mortality during the period 1985-2004, whereas a leveling off for these trends can be considered during 2005-2019 among men older than 35.

Epigenetic Activation of SOX11 in Lymphoid Neoplasms by Histone Modifications

Recent studies have shown aberrant expression of SOX11 in various types of aggressive B-cell neoplasms. To elucidate the molecular mechanisms leading to such deregulation, we performed a comprehensive SOX11 gene expression and epigenetic study in stem cells, normal hematopoietic cells and different lymphoid neoplasms. We observed that SOX11 expression is associated with unmethylated DNA and presence of activating histone marks (H3K9/14Ac and H3K4me3) in embryonic stem cells and some aggressive B-cell neoplasms. In contrast, adult stem cells, normal hematopoietic cells and other lymphoid neoplasms do not express SOX11. Such repression was associated with silencing histone marks H3K9me2 and H3K27me3. The SOX11 promoter of non-malignant cells was consistently unmethylated whereas lymphoid neoplasms with silenced SOX11 tended to acquire DNA hypermethylation. SOX11 silencing in cell lines was reversed by the histone deacetylase inhibitor SAHA but not by the DNA methyltransferase inhibitor AZA. These data indicate that, although DNA hypermethylation of SOX11 is frequent in lymphoid neoplasms, it seems to be functionally inert, as SOX11 is already silenced in the hematopoietic system. In contrast, the pathogenic role of SOX11 is associated with its de novo expression in some aggressive lymphoid malignancies, which is mediated by a shift from inactivating to activating histone modifications.

Survival of European patients diagnosed with lymphoid neoplasms in 2000-2002: results of the HAEMACARE project

The European Cancer Registry-based project on hematologic malignancies (HAEMACARE), setup to improve the availability and standardization of data on hematologic malignancies in Europe, used the European Cancer Registry-based project on survival and care of cancer patients (EUROCARE-4) database to produce a new grouping of hematologic neoplasma(defined by the International Classification of Diseases for Oncology, Third Edition and the 2001/2008 World Health Organization classifications) for epidemiological and public healthpurposes. We analyzed survival for lymphoid neoplasms in Europe by disease group, comparing survival between different European regions by age and sex. Design and Methods Incident neoplasms recorded between 1995 to 2002 in 48 population-based cancer registries in 20 countries participating in EUROCARE-4 were analyzed. The period approach was used to estimate 5-year relative survival rates for patients diagnosed in 2000-2002, who did not have 5years of follow up. Results: The 5-year relative survival rate was 57% overall but varied markedly between the definedgroups. Variation in survival within the groups was relatively limited across European regions and less than in previous years. Survival differences between men and women were small. The relative survival for patients with all lymphoid neoplasms decreased substantially after the age of 50. The proportion of ‘not otherwise specified’ diagnoses increased with advancing age.Conclusions: This is the first study to analyze survival of patients with lymphoid neoplasms, divided into groups characterized by similar epidemiological and clinical characteristics, providing a benchmarkfor more detailed analyses. This Europe-wide study suggests that previously noted differences in survival between regions have tended to decrease. The survival of patients with all neoplasms decreased markedly with age, while the proportion of ‘not otherwise specified’ diagnoses increased with advancing age. Thus the quality of diagnostic work-up and care decreased with age, suggesting that older patients may not be receiving optimal treatment

Neuroendocrine Tumors (NETs): A population-based study of incidence and survival in Girona province, 1994-2004

Els tumors neuroendocrins (TNEs) són un grup de neoplàsies poc freqüents i heterogènies i amb un ampli espectre d’agressivitat. Hi ha molt poca informació epidemiològica a nivell mundial, l’objectiu d’aquest estudi ha estat el de reportar-ne les dades a la província de Girona. Hem inclòs tots els codis de la ICD-O3 que codifiquen un TNE, període 1994-2002. Hem identificat 698 tumors. Es reporten les dades tant de la casuística com les taxes d’incidència i supervivència de cada TNE per separat. Els resultats són consistents amb les publicacions europees. El fet d’haver reportat la incidència i la supervivència dels TNEs a Girona contribueix a un millor coneixement d’aquestes neoplàsies.

Estudio de marcadores moleculares en neoplasias mieloproliferativas

Las neoplasias mieloproliferativas (NM) son un grupo de enfermedades clonales de la célula hematopoyética madre. Entre las NM clásicas se encuentran la policitemia vera (PV), la trombocitemia esencial (TE) y la mielofibrosis primaria (MFP). Durante muchos años el diagnóstico de estas patologías se hacía por exclusión utilizando biomarcadores de clonalidad poco específicos. En el año 2005, la descripción de la mutación JAK2V617F supuso un avance importante en el diagnóstico de estas patologías. Posteriormente, se han descrito mutaciones en otros genes como mutaciones en MPL, TET2, ASXL1, IDH1, IDH2, c-CBL, EZH2, IKZF1 y LNK, en distintas neoplasias mieloides y en porcentaje variable. Aun así, ninguno de estos genes son marcadores específicos de ninguna NM y todavía existe un porcentaje elevado de pacientes con TE y MFP sin un marcador de clonalidad conocido. Además, todos estos genes se han descrito como eventos genéticos implicados en la transformación de una NM a leucemia mieloide aguda. El objetivo de este proyecto fue estudiar varios marcadores moleculares en neoplasias mieloproliferativas Philadelphia negativas. En primer lugar, se estudió la modulación de la carga alélica JAK2V617F en pacientes con PV o TE que recibieron tratamiento citoreductor y a su vez se analizó la dinámica natural de la carga alélica en pacientes que no recibieron tratamiento. Posteriormente, se analizaron la presencia de alteraciones en los genes previamente mencionados, en distintos grupos de pacientes. En primer lugar, se analizó la presencia de mutaciones en TET2, ASXL1, IDH1, IDH2 y CBL en un grupo de pacientes JAK2 y MPL negativos, para determinar la frecuencia de alteraciones de estos genes en este grupo de pacientes y determinar su valor en el diagnóstico de estas patologías. En segundo lugar, se estudió la presencia de mutaciones en estos genes incluyendo EZH2, IKZF1 y LNK para estudiar la incidencia y el valor pronóstico de estas alteraciones en las NM que progresan a mielofibrosis.