Two bullets in the gun: combining immunotherapy with chemotherapy to defeat neuroblastoma by targeting adrenergic-mesenchymal plasticity

Neuroblastoma (NB) is a childhood tumor that originates in the peripheral sympathetic nervous system and is responsible for 15% of cancer-related deaths in the pediatric population. Despite intensive multimodal treatment, many patients with high-risk NB relapse and develop a therapy-resistant tumor. One of the phenomena related to therapeutic resistance is intratumor heterogeneity resulting from the adaptation of tumor cells in response to different selective environmental pressures. The transcriptional and epigenetic profiling of NB tissue has recently revealed the existence of two distinct cellular identities in the NB, termed adrenergic (ADRN) and mesenchymal (MES), which can spontaneously interconvert through epigenetic regulation. This phenomenon, known as tumor plasticity, has a major impact on cancer pathogenesis. The aim of this review is to describe the peculiarities of these two cell states, and how their plasticity affects the response to current therapeutic treatments, with special focus on the immunogenic potential of MES cells. Furthermore, we will discuss the opportunity to combine immunotherapy with chemotherapy to counteract NB phenotypic interconversion

Recuperación funcional en pacientes mayores de 85 años ingresados en una unidad de media estancia de Madrid

Fundamento: las unidades de media estancia componen un nivel asistencial geriátrico, destinado a restablecer la funcionalidad en pacientes ancianos con deterioro reciente potencialmente reversible. Objetivo: evaluar la ganancia funcional en pacientes mayores de 85 años ingresados, durante el año 2021, en la unidad de media estancia del Hospital Guadarrama, de la Comunidad de Madrid, España. Métodos: estudio observacional descriptivo y retrospectivo, realizado en la institución y periodo de tiempo declarados en el objetivo. La población de estudio estuvo conformada por 181 pacientes ingresados por ortogeriatría, deterioro funcional y daño cerebral adquirido. Se evaluaron las variables: edad, sexo, deterioro cognitivo (mediante cuestionario de Pfeiffer), comorbilidades (por índice de Charlson), valoración funcional (índice de Barthel), ganancia funcional, estancia y destino al alta. Resultados: la edad promedio fue de 89,6±3,1 años, con 133 (73 %) mujeres. No existieron diferencias significativas en la ganancia funcional por procesos, con ganancias funcionales similares para ortogeriatría y deterioro funcional, 24,1±21,5 y 24,2±21,7 respectivamente. Se comprobaron diferencias significativas en el índice de Barthel al ingreso (p< 0,001) y al alta (p= 0,003), índice de Charlson (p< 0,001) y Pfeiffer (p= 0,001). La eficiencia de la rehabilitación fue mayor de 0,5 en los tres procesos, sin diferencias significativas entre ellos. El 69,1 % de los pacientes regresaron a su domicilio. Conclusiones: los pacientes octogenarios se benefician del ingreso en unidades de media estancia. El tratamiento rehabilitador mejora la funcionalidad global, reduce la dependencia del paciente así como la institucionalización del mismo

Alkylphenolic compounds and risk of breast and prostate cancer in the MCC-Spain study

[EN] Background: Alkylphenolic compounds are chemicals with endocrine disrupting properties that have been widely used in industry with important changes in their usage over time. Few epidemiologic studies have evaluated the effect of alkylphenolic compounds on human health. Objectives: We investigated whether occupational exposure to alkylphenolic compounds is associated with breast and prostate cancer. Methods: We carried out a population-based case–control study including 1513 incident cases of breast cancer, 1095 of prostate cancer, and 3055 controls, frequency matched by sex, age and region. Occupational exposure to alkylphenolic compounds was estimated using a recently developed job exposure matrix, which considered different scenarios of exposure and different subtypes of alkylphenolic compounds. Results: History of occupational exposure to alkylphenolic compounds was modestly associated with breast cancer (OR = 1.23; 95% CI = 1.01–1.48). Within the different scenarios, the occupational use of domestic tensioactives was positively associated with breast cancer (OR = 1.28; 95% CI = 1.02–1.60), while occupational exposure in other scenarios showed mostly a suggestion of a similar positive associations. Exposure to nonylphenol ethoxylates was positively associated with breast cancer (OR = 1.21; 95% CI = 1.00–1.47), while exposure to other compounds was uncommon. In general, we did not observe associations between alkylphenolic compounds and prostate cancer, except for a positive association among men occupationally exposed to cosmetic, hair and personal hygiene products. Conclusions: Our findings suggest a modest association between breast cancer risk and occupational exposure to alkylphenolic compounds, and no associations between these compounds and prostate cancer risk. These findings warrant further corroboration in other studiesS

Childhood and Adolescent Central Nervous System Tumours in Spain : Incidence and Survival over 20 Years: A Historical Baseline for Current Assessment

This work is part of the PITTI project, which was funded by the Carlos III Institute of Health (Health Research Fund/Fondo de Investigación Sanitaria) (ISCIII2006_PI061742); RTICC RD 06/0020/1021; RTICC RD06/0020/0089.The Spanish Childhood Cancer Registry (RETI-SEHOP) is supported by collaboration between Spain's Ministry of Health, the Spanish Society of Paediatric Haematology and Oncology (SEHOP), and the University of Valencia, for whose support we are most grateful. We should also like to thank the Enriqueta Villavecchia Foundation and the Federación Española de Padres de Niños con Cáncer, as well as all the cancer registry staff who work so unstintingly to enable data to be collected on childhood cancer in Spain.Background: Central nervous system (CNS) neoplasms are highly frequent solid tumours in children and adolescents. While some studies have shown a rise in their incidence in Europe, others have not. Survival remains limited. We addressed two questions about these tumours in Spain: (1) Is incidence increasing? and (2) Has survival improved? Methods: This population-based study included 1635 children and 328 adolescents from 11 population-based cancer registries with International Classification of Childhood Cancer Group III tumours, incident in 1983-2007. Age-specific and age-standardised (world population) incidence rates (ASRws) were calculated. Incidence time trends were characterised using annual percent change (APC) obtained with Joinpoint. Cases from 1991 to 2005 (1171) were included in Kaplan-Meier survival analyses, and the results were evaluated with log-rank and log-rank for trend tests. Children's survival was age-standardised using: (1) the age distribution of cases and the corresponding trends assessed with Joinpoint; and (2) European weights for comparison with Europe. Results: ASRw 1983-2007: children: 32.7 cases/10; adolescents: 23.5 cases/10. The overall incidence of all tumours increased across 1983-2007 in children and adolescents. Considering change points, the APCs were: (1) children: 1983-1993, 4.3%^ (1.1; 7.7); 1993-2007, −0.2% (−1.9; 1.6); (2) adolescents: 1983-2004: 2.9%^ (0.9; 4.9); 2004-2007: −7.7% (−40; 41.9). For malignant tumours, the trends were not significant. 5-year survival was 65% (1991-2005), with no significant trends (except for non-malignant tumours). Conclusions: CNS tumour incidence in Spain was found to be similar to that in Europe. Rises in incidence may be mostly attributable to changes in the registration of non-malignant tumours. The overall malignant CNS tumour trend was compatible with reports for Southern Europe. Survival was lower than in Europe, without improvement over time. We provide a baseline for assessing current paediatric oncology achievements and incidence in respect of childhood and adolescent CNS tumours

Incidence and time trends of childhood hematological neoplasms : a 36-year population-based study in the southern European context, 1983-2018

Altres ajuts: Josep Carreras Leukaemia Research Institute (Grant No. FIJC1100)Background: Hematological neoplasms (HNs) are the first and most common childhood cancers globally. Currently, there is a lack of updated population-based data on the incidence of these cancers in the Spanish pediatric population. This study aimed to describe the incidence and incidence trends of HNs in children (0-14 years) in Spain using data from the Spanish Network of Cancer Registries and to compare the results with other southern European countries. Methods: Data were extracted from 15 Spanish population-based cancer registries between 1983 and 2018. Cases were coded according to the International Classification of Diseases for Oncology, third edition, first revision, and grouped according to the International Classification of Childhood Cancer, third edition. Crude rates (CRs), age-specific rates, and age-standardized incidence rates using the 2013 European population (ASR) were calculated and expressed as cases per 1,000,000 child-years. Incidence trends and annual percentage changes (APCs) were estimated. Results: A total of 4,747 HNs were recorded (59.5% boys). Age distribution [n (%)] was as follows: <1 year, 266 (5.6%); 1-4 years, 1,726 (36.4%); 5-9 years, 1,442 (30.4%); and 10-14 years, 1,313 (27.6%). Leukemias were the most common group, with a CR and an ASR of 44.0 (95%CI: 42.5; 45.5) and 44.1 (95%CI: 42.6; 45.7), respectively. The CR and ASR of lymphomas were 20.1 (95%CI: 19.1; 21.1) and 20.0 (95%CI: 19.0; 21.1), respectively. The comparable incidence rates between our results and those of other southern European countries were similar for lymphomas, while some differences were observed for leukemias. From 1988 to 2016, the trend in leukemia incidence was stable for both sexes, with an APC of 0.0 (95%CI: −0.5; 0.7), whereas a constant overall increase was observed for lymphoma in both sexes, with an APC of 1.0 (95%CI: 0.4; 1.6). Conclusion: Leukemias are the most common HNs in children, and their incidence has remained stable since 1988, whereas the incidence of lymphomas has increased every year. Lymphoma incidence is like that of other southern European countries, while leukemia incidence is similar only to that of southwestern European countries. Collaborative cancer registry projects allow for assessing epidemiological indicators for cancers such as HNs, which helps health authorities and clinicians provide more knowledge about these malignancies

Predicting ovarian-cancer burden in Catalonia by 2030: an age-period-cohort modelling

Ovarian cancer is the most lethal gynaecological cancer in very-high-human-developmentindex regions. Ovarian cancer incidence and mortality rates are estimated to globally rise by 2035; although incidence and mortality rates depend on the region and prevalence of the associated risk factors. The aim of this study is to assess changes in incidence and mortality of ovarian cancer in Catalonia by 2030. Bayesian autoregressive age-period-cohort models were used to predict the burden of OC incidence and mortality rates for the 2015-2030 period. Incidence and mortality rates of ovarian cancer are expected to decline in Catalonia by 2030 in women ≥ 45 years of age. A decrease in ovarian-cancer risk was observed with increasing year of birth; with a rebound in women born in the 1980s. A decrease in mortality was observed for the period of diagnosis and period of death. Nevertheless; ovarian-cancer mortality remains higher among older women compared to other age groups. Our study summarizes the most plausible scenario for ovarian-cancer changes in terms of incidence and mortality in Catalonia by 2030; which may be of interest from a public health perspective for policy implementation

Cancer Survival in Adults in Spain : A Population-Based Study of the Spanish Network of Cancer Registries (REDECAN)

The assessment of cancer survival at the population level is essential for monitoring progress in cancer control. We aimed to assess cancer survival and its trends in adults in Spain. Individual records of 601,250 adults with primary cancer diagnosed during 2002-2013 and followed up to 2015 were included from 13 population-based cancer registries. We estimated net survival up to five years after diagnosis and analyzed absolute changes between 2002-2007 and 2008-2013. Estimates were age-standardized. Analyses were performed for 29 cancer groups, by age and sex. Overall, age-standardized five-year net survival was higher in women (61.7%, 95% CI 61.4-62.1%) than in men (55.3%, 95% CI 55.0-55.6%), and ranged by cancer from 7.2% (pancreas) to 89.6% (prostate) in men, and from 10.0% (pancreas) to 93.1% (thyroid) in women in the last period. Survival declined with age, showing different patterns by cancer. Between both periods, age-standardized five-year net survival increased overall by 3.3% (95% CI 3.0-3.7%) in men and 2.5% (95% CI 2.0-3.0%) in women, and for most cancer groups. Improvements were greater in patients younger than 75 years than in older patients. Chronic myeloid leukemia and myeloma showed the largest increases. Among the most common malignancies, the greatest absolute increases in survival were observed for colon (5.0%, 95% CI 4.0-6.0%) and rectal cancers (4.5%, 95% CI 3.2-5.9%). Survival improved even for some cancers with poor prognosis (pancreas, esophagus, lung, liver, and brain cancer). Further investigation of possible sociodemographic inequalities is warranted. This study contributes to the evaluation of cancer control and health services' effectivenes

Cancer Survival in Adults in Spain: A Population-Based Study of the Spanish Network of Cancer Registries (REDECAN)

The assessment of cancer survival at the population level is essential for monitoring progress in cancer control. We aimed to assess cancer survival and its trends in adults in Spain. Individual records of 601,250 adults with primary cancer diagnosed during 2002–2013 and followed up to 2015 were included from 13 population-based cancer registries. We estimated net survival up to five years after diagnosis and analyzed absolute changes between 2002–2007 and 2008–2013. Estimates were age-standardized. Analyses were performed for 29 cancer groups, by age and sex. Overall, age-standardized five-year net survival was higher in women (61.7%, 95% CI 61.4–62.1%) than in men (55.3%, 95% CI 55.0–55.6%), and ranged by cancer from 7.2% (pancreas) to 89.6% (prostate) in men, and from 10.0% (pancreas) to 93.1% (thyroid) in women in the last period. Survival declined with age, showing different patterns by cancer. Between both periods, age-standardized five-year net survival increased overall by 3.3% (95% CI 3.0–3.7%) in men and 2.5% (95% CI 2.0–3.0%) in women, and for most cancer groups. Improvements were greater in patients younger than 75 years than in older patients. Chronic myeloid leukemia and myeloma showed the largest increases. Among the most common malignancies, the greatest absolute increases in survival were observed for colon (5.0%, 95% CI 4.0–6.0%) and rectal cancers (4.5%, 95% CI 3.2–5.9%). Survival improved even for some cancers with poor prognosis (pancreas, esophagus, lung, liver, and brain cancer). Further investigation of possible sociodemographic inequalities is warranted. This study contributes to the evaluation of cancer control and health services’ effectiveness

Incidence and survival of lymphoid neoplasms in Spain, 2002-2013: A population-based study from the Spanish Network of Cancer Registries (REDECAN).

The aim of this study was to describe incidence, incidence trends and survival patterns of lymphoid neoplasms (LNs) and its subtypes in Spain in the period 2002-2013 using data from the Spanish Network of Cancer Registries (REDECAN). Data were extracted from 13 Spanish population-based cancer registries. LNs incident cases were codified using the International Classification of Diseases for Oncology, third edition (ICD-O-3) and grouped according to the WHO 2008 classification. Age-standardized incidence rates to the 2013 European standard population (ASIRe) were obtained. Poisson regression models were used to analyze trends in incidence rates and estimate the annual percentage change (APC) for each subtype. The number of cases in Spain for 2023 was estimated by applying the estimated age-specific rates for the year 2023 to the 2023 Spanish population. Observed survival (OS) was estimated by the Kaplan-Meier method and net survival (NS) by the Pohar-Perme method. Sex- and age-specific estimates of 5-year NS were calculated, as well as its changes according to two periods of diagnosis (2002-2007 and 2008-2013). LNs accounted for 69% (n=39,156) of all hematological malignancies (n=56,751) diagnosed during the period of study. Median age at diagnosis was 67 years (interquartile range (IQR) = 52-77). The overall ASIRe was 34.23 (95% confidence interval (CI): 33.89, 34.57) and showed a marked male predominance in almost all subtypes (global sex ratio = 1.45). During the study period, incidence trends of LNs remained stable (APC: 0.3; 95% CI: -0.1, 0.6), nevertheless some subtypes showed statistically significant variations, such as LNs NOS category (APC: -5.6; 95% CI: -6.8, -4.3). Around 17,926 new cases of LNs will be diagnosed in 2023 in Spain. Survival rates differed considerably across age-groups, while they were similar between men and women. Five- year NS was 62.81% (95% CI: 62.1, 63.52) for all LNs, and varied widely across LNs subtypes, ranging from 39.21% to 90.25%. NS for all LNs improved from the first period of diagnosis to the second one, being 61.57% (95% CI: 60.56, 62.61) in 2002-2007 and 64.17% (95% CI: 63.29, 65.07) in 2008-2013. This study presents the first complete and extensive population-based analysis of LNs incidence and survival in Spain. These population-based data provide relevant information to better understand the epidemiology of LNs in Southern Europe and it features some useful points for public health authorities and clinicians. However, additional improvements regarding the registration of these hematological neoplasms can be implemented

Peripheral and lung resident memory T cell responses against SARS-CoV-2

Resident memory T cells (T) positioned within the respiratory tract are probably required to limit SARS-CoV-2 spread and COVID-19. Importantly, T are mostly non-recirculating, which reduces the window of opportunity to examine these cells in the blood as they move to the lung parenchyma. Here, we identify circulating virus-specific T cell responses during acute infection with functional, migratory and apoptotic patterns modulated by viral proteins and associated with clinical outcome. Disease severity is associated predominantly with IFNγ and IL-4 responses, increased responses against S peptides and apoptosis, whereas non-hospitalized patients have increased IL-12p70 levels, degranulation in response to N peptides and SARS-CoV-2-specific CCR7 + T cells secreting IL-10. In convalescent patients, lung-T are frequently detected even 10 months after initial infection, in which contemporaneous blood does not reflect tissue-resident profiles. Our study highlights a balanced anti-inflammatory antiviral response associated with a better outcome and persisting T cells as important for future protection against SARS-CoV-2 infection. Lung resident memory T (T) cells are important for protection from viral infection in the lungs. Here the authors use paired lung biopsy material and blood to characterize T cell responses in patients with COVID-19 over time and find persistence of antiviral lung T cells that might be important to limit reinfectio