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1.
Health Qual Life Outcomes ; 19(1): 213, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488798

RESUMO

BACKGROUND: Although physical activity (PA) and sedentary time in cancer survivors (CSs) were associated with health-related quality of life (HRQOL), it was not clear whether their associations were similar among CSs with different number of comorbid chronic diseases (CCDs). This study aimed to investigate the associations between PA, sedentary time and HRQOL in CSs with different number of CCDs. METHODS: A cross-sectional study was conducted among 1546 CSs between June and September 2018 in Shanghai, China. Data were collected with a self-reported questionnaire including sociodemographic characteristics, CCDs, PA, sedentary time and HRQOL. International Physical Activity Questionnaire and Cancer Quality of Life Questionnaire-Core30 were respectively used to measure PA and HRQOL of CSs. Associations of PA and sedentary time with HRQOL among CSs with different number of CCDs were evaluated by using logistic regression, adjusted for confounding factors. RESULTS: About seventy-five percent CSs had at least one CCD. Approximately three fifths CSs had high PA level and < 4 h/day sedentary time. Moderate PA level and high PA level were shown to be associated with better HRQOL among all participants. In CSs with ≤ 2 CCDs, high PA level was significantly associated with higher scores of physical function and lower scores of nausea and vomiting, appetite loss. However, there was a positive association between high PA level and constipation score among CSs with ≥ 3 CCDs. CSs with shorter sedentary time had better HRQOL in those with CCDs. CONCLUSIONS: High PA level and long sedentary time have significant association with worse HRQOL of CSs with ≥ 3 CCDs, while high PA level is positively associated with HRQOL in CSs with ≤ 2 CCDs. Our findings may support further studies of the causal association between PA, sedentary times and HRQOL to provide targeted proposal to improve the HRQOL of CSs according to their number of CCDs.


Assuntos
Sobreviventes de Câncer/psicologia , Exercício Físico/fisiologia , Neoplasias/mortalidade , Qualidade de Vida/psicologia , Comportamento Sedentário , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Exercício Físico/psicologia , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Inquéritos e Questionários , Terapêutica
2.
BMC Infect Dis ; 21(1): 760, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34353293

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread around the world. This retrospective study aims to analyze the clinical features of COVID-19 patients with cancer and identify death outcome related risk factors. METHODS: From February 10th to April 15th, 2020, 103 COVID-19 patients with cancer were enrolled. Difference analyses were performed between severe and non-severe patients. A propensity score matching (PSM) analysis was performed, including 103 COVID-19 patients with cancer and 206 matched non-cancer COVID-19 patients. Next, we identified death related risk factors and developed a nomogram for predicting the probability. RESULTS: In 103 COVID-19 patients with cancer, the main cancer categories were breast cancer, lung cancer and bladder cancer. Compared to non-severe patients, severe patients had a higher median age, and a higher proportion of smokers, diabetes, heart disease and dyspnea. In addition, most of the laboratory results between two groups were significantly different. PSM analysis found that the proportion of dyspnea was much higher in COVID-19 patients with cancer. The severity incidence in two groups were similar, while a much higher mortality was found in COVID-19 patients with cancer compared to that in COVID-19 patients without cancer (11.7% vs. 4.4%, P = 0.028). Furthermore, we found that neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were related to death outcome. And a nomogram based on the factors was developed. CONCLUSION: In COVID-19 patients with cancer, the clinical features and laboratory results between severe group and non-severe group were significantly different. NLR and CRP were the risk factors that could predict death outcome.


Assuntos
COVID-19 , Neoplasias , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , COVID-19/complicações , COVID-19/mortalidade , Feminino , Humanos , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/mortalidade , Neutrófilos/citologia , Nomogramas , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
3.
Lancet Oncol ; 22(9): 1221-1229, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34363761

RESUMO

BACKGROUND: Despite advances in cancer genomics, radiotherapy is still prescribed on the basis of an empirical one-size-fits-all paradigm. Previously, we proposed a novel algorithm using the genomic-adjusted radiation dose (GARD) model to personalise prescription of radiation dose on the basis of the biological effect of a given physical dose of radiation, calculated using individual tumour genomics. We hypothesise that GARD will reveal interpatient heterogeneity associated with opportunities to improve outcomes compared with physical dose of radiotherapy alone. We aimed to test this hypothesis and investigate the GARD-based radiotherapy dosing paradigm. METHODS: We did a pooled, pan-cancer analysis of 11 previously published clinical cohorts of unique patients with seven different types of cancer, which are all available cohorts with the data required to calculate GARD, together with clinical outcome. The included cancers were breast cancer, head and neck cancer, non-small-cell lung cancer, pancreatic cancer, endometrial cancer, melanoma, and glioma. Our dataset comprised 1615 unique patients, of whom 1298 (982 with radiotherapy, 316 without radiotherapy) were assessed for time to first recurrence and 677 patients (424 with radiotherapy and 253 without radiotherapy) were assessed for overall survival. We analysed two clinical outcomes of interest: time to first recurrence and overall survival. We used Cox regression, stratified by cohort, to test the association between GARD and outcome with separate models using dose of radiation and sham-GARD (ie, patients treated without radiotherapy, but modelled as having a standard-of-care dose of radiotherapy) for comparison. We did interaction tests between GARD and treatment (with or without radiotherapy) using the Wald statistic. FINDINGS: Pooled analysis of all available data showed that GARD as a continuous variable is associated with time to first recurrence (hazard ratio [HR] 0·98 [95% CI 0·97-0·99]; p=0·0017) and overall survival (0·97 [0·95-0·99]; p=0·0007). The interaction test showed the effect of GARD on overall survival depends on whether or not that patient received radiotherapy (Wald statistic p=0·011). The interaction test for GARD and radiotherapy was not significant for time to first recurrence (Wald statistic p=0·22). The HR for physical dose of radiation was 0·99 (95% CI 0·97-1·01; p=0·53) for time to first recurrence and 1·00 (0·96-1·04; p=0·95) for overall survival. The HR for sham-GARD was 1·00 (0·97-1·03; p=1·00) for time to first recurrence and 1·00 (0·98-1·02; p=0·87) for overall survival. INTERPRETATION: The biological effect of radiotherapy, as quantified by GARD, is significantly associated with time to first recurrence and overall survival for patients with cancer treated with radiation. It is predictive of radiotherapy benefit, and physical dose of radiation is not. We propose integration of genomics into radiation dosing decisions, using a GARD-based framework, as the new paradigm for personalising radiotherapy prescription dose. FUNDING: None. VIDEO ABSTRACT.


Assuntos
Neoplasias/radioterapia , Genômica por Radiação/métodos , Dosagem Radioterapêutica , Bases de Dados Factuais , Humanos , Neoplasias/genética , Neoplasias/mortalidade , Medicina de Precisão , Recidiva , Taxa de Sobrevida
4.
JCO Glob Oncol ; 7: 1286-1305, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34406802

RESUMO

PURPOSE: There are scarce data to aid in prognostication of the outcome of critically ill cancer patients with COVID-19. In this systematic review and meta-analysis, we investigated the mortality of critically ill cancer patients with COVID-19. METHODS: We searched online databases and manually searched for studies in English that reported on outcomes of adult cancer patients with COVID-19 admitted to an intensive care unit (ICU) or those with severe COVID-19 between December 2019 and October 2020. Risk of bias was assessed by the Modified Newcastle-Ottawa Scale. The primary outcome was all-cause mortality. We also determined the odds of death for cancer patients versus noncancer patients, as also outcomes by cancer subtypes, presence of recent anticancer therapy, and presence of one or more comorbidities. Random-effects modeling was used. RESULTS: In 28 studies (1,276 patients), pooled mortality in cancer patients with COVID-19 admitted to an ICU was 60.2% (95% CI, 53.6 to 6.7; I2 = 80.27%), with four studies (7,259 patients) showing higher odds of dying in cancer versus noncancer patients (odds ratio 1.924; 95% CI, 1.596 to 2.320). In four studies (106 patients) of patients with cancer and severe COVID-19, pooled mortality was 59.4% (95% CI, -39.4 to 77.5; I2 = 72.28%); in one study, presence of hematologic malignancy was associated with significantly higher mortality compared with nonhematologic cancers (odds ratio 1.878; 95% CI, 1.171 to 3.012). Risk of bias was low. CONCLUSION: Most studies were reported before the results of trials suggesting the benefit of dexamethasone and tocilizumab, potentially overestimating mortality. The observed mortality of 60% in cancer patients with COVID-19 admitted to the ICU is not prohibitively high, and admission to the ICU should be considered for selected patients (registered with PROSPERO, CRD42020207209).


Assuntos
COVID-19 , Neoplasias , Adulto , COVID-19/complicações , Hospitalização , Humanos , Unidades de Terapia Intensiva , Neoplasias/complicações , Neoplasias/mortalidade , Neoplasias/terapia , SARS-CoV-2
5.
Medicine (Baltimore) ; 100(30): e26789, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397730

RESUMO

BACKGROUND: Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2), a newly discovered member of the B7 family, is overexpressed in numerous tumors. However, the prognostic impact of HHLA2 in human cancers remains controversial. Thus, we performed this meta-analysis to explore the prognostic value of HHLA2 in Chinese patients with solid tumors. METHODS: PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, and WanFang databases were systematically searched for eligible studies that evaluated the impact of HHLA2 on overall survival (OS) in patients with cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to evaluate the association between HHLA2 expression and OS in solid tumors. Odds ratios (ORs) and 95% CIs were pooled to assess the correlation between HHLA2 expression and clinicopathological characteristics in solid tumors. RESULTS: A total of 12 studies, including 15 cohorts and 1747 patients, were included in this meta-analysis. We found that high HHLA2 expression was significantly associated with shorter OS (HR = 1.65, 95% CI: 1.12-2.43). Subgroup analysis by cancer type demonstrated that high HHLA2 expression was associated with poor OS in patients with clear cell renal cell carcinoma (HR = 3.42, 95% CI: 2.39-4.91), gastric cancer (HR = 2.03, 95% CI: 1.31-3.16), intrahepatic cholangiocarcinoma (HR = 1.77, 95% CI: 1.24-2.53), lung cancer (HR = 2.14, 95% CI: 1.33-3.44) and other cancer types (HR = 2.08, 95% CI: 1.34-3.24), but not in patients with epithelial ovarian cancer (HR = 0.52, 95% CI: 0.08-3.56). Nevertheless, high HHLA2 expression was associated with better OS in patients with pancreatic ductal adenocarcinoma (HR = 0.45, 95% CI: 0.32-0.64). Furthermore, high HHLA2 expression was associated with old age (OR = 1.30, 95% CI: 1.03-1.63), lymph node metastasis (OR = 1.99, 95% CI: 1.41-2.81), and vascular invasion (OR = 1.69, 95% CI: 1.18-2.42). CONCLUSIONS: HHLA2 may serve as a potential prognostic biomarker for solid tumors in Chinese population, by predict the prognosis of cancer patients based on their tumor types.


Assuntos
Imunoglobulinas/metabolismo , Neoplasias/metabolismo , Humanos , Neoplasias/diagnóstico , Neoplasias/mortalidade , Prognóstico
6.
Vaccimonitor (La Habana, Print) ; 30(2)mayo.-ago. 2021. tab, graf
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1252325

RESUMO

El uso de anticuerpos monoclonales en la lucha contra el cáncer se convierte cada día más en la terapia de elección. Para la introducción de anticuerpos monoclonales en mercados internacionales de alta demanda y con elevados requerimientos de calidad se requiere su producción a gran escala. El incremento de la presencia de dímeros en el producto final afecta su calidad y, por tanto, la eficiencia y eficacia del proceso. El objetivo del presente trabajo fue obtener un modelo matemático que permita relacionar el porcentaje de dímeros con las variables de operación de mayor influencia. Se realizó el ajuste de un modelo de regresión lineal múltiple usando el programa Statgraphics Centurion XVII versión 17.2.00. El modelo se validó con lotes de producción, logrando errores relativos inferiores al 20 por ciento. Las variables significativas obtenidas fueron: masa de IgG en el sobrenadante; masa de IgG en el producto de salida del paso de captura de proteína A; pH en el producto de salida del paso de captura de proteína A; pH del producto ajustado y conductividad de salida en la membrana de intercambio aniónico. El modelo permitió encontrar un intervalo de trabajo de las variables de mayor influencia en la formación de dímeros para reducirlos hasta valores inferiores al 3 por ciento(AU)


The use of monoclonal antibodies in the fight against cancer is becoming more and more the selected therapy. The introduction of monoclonal antibodies highly demanded in international markets, with high quality requirements needs the production of monoclonal antibodies on a large scale. The increase of dimers in the final product affects its quality, therefore, the efficiency and effectiveness of the process. The objective of this work was to obtain a mathematical model to relate the percentage of dimers with the most influential operating variables. A multiple linear regression model was obtained using Statgraphics Centurion XVII version 17.2.00 software. The model was validated with new production data with a mean error of validation below 20 percent. The significant variables were: supernatant IgG mass; IgG mass in the effluent from Protein A capture column; pH of the effluent from Protein A capture column; pH of the adjusted product and conductivity of the effluent from anionic exchange membrane. A working interval for each of the influential variables were established, in order to reduce dimers below 3 percent(AU)


Assuntos
Humanos , Computação Matemática , Análise de Dados , Anticorpos Monoclonais/imunologia , Neoplasias/mortalidade , Cuba
7.
Nat Commun ; 12(1): 4172, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234141

RESUMO

Cell-free DNA (cfDNA) is attractive for many applications, including detecting cancer, identifying the tissue of origin, and monitoring. A fundamental task underlying these applications is SNV calling from cfDNA, which is hindered by the very low tumor content. Thus sensitive and accurate detection of low-frequency mutations (<5%) remains challenging for existing SNV callers. Here we present cfSNV, a method incorporating multi-layer error suppression and hierarchical mutation calling, to address this challenge. Furthermore, by leveraging cfDNA's comprehensive coverage of tumor clonal landscape, cfSNV can profile mutations in subclones. In both simulated and real patient data, cfSNV outperforms existing tools in sensitivity while maintaining high precision. cfSNV enhances the clinical utilities of cfDNA by improving mutation detection performance in medium-depth sequencing data, therefore making Whole-Exome Sequencing a viable option. As an example, we demonstrate that the tumor mutation profile from cfDNA WES data can provide an effective biomarker to predict immunotherapy outcomes.


Assuntos
DNA Tumoral Circulante/genética , Análise Mutacional de DNA/métodos , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias/genética , Sequenciamento Completo do Exoma/métodos , Adulto , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Biópsia , DNA Tumoral Circulante/sangue , Simulação por Computador , Conjuntos de Dados como Assunto , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Polimorfismo de Nucleotídeo Único , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Intervalo Livre de Progressão , Sensibilidade e Especificidade
8.
Int J Biol Sci ; 17(9): 2348-2355, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239361

RESUMO

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to more than 150 million infections and about 3.1 million deaths up to date. Currently, drugs screened are urgently aiming to block the infection of SARS-CoV-2. Here, we explored the interaction networks of kinase and COVID-19 crosstalk, and identified phosphoinositide 3-kinase (PI3K)/AKT pathway as the most important kinase signal pathway involving COVID-19. Further, we found a PI3K/AKT signal pathway inhibitor capivasertib restricted the entry of SARS-CoV-2 into cells under non-cytotoxic concentrations. Lastly, the signal axis PI3K/AKT/FYVE finger-containing phosphoinositide kinase (PIKfyve)/PtdIns(3,5)P2 was revealed to play a key role during the cellular entry of viruses including SARS-CoV-2, possibly providing potential antiviral targets. Altogether, our study suggests that the PI3K/AKT kinase inhibitor drugs may be a promising anti-SARS-CoV-2 strategy for clinical application, especially for managing cancer patients with COVID-19 in the pandemic era.


Assuntos
COVID-19/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos , Animais , COVID-19/enzimologia , Chlorocebus aethiops , Simulação por Computador , Humanos , Neoplasias/enzimologia , Neoplasias/mortalidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirimidinas/farmacologia , Pirróis/farmacologia , Receptor Cross-Talk , Células Vero
9.
Int J Mol Sci ; 22(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34298996

RESUMO

Regulator of Chromatin Condensation 1 (RCC1) is the only known guanine nucleotide exchange factor that acts on the Ras-like G protein Ran and plays a key role in cell cycle regulation. Although there is growing evidence to support the relationship between RCC1 and cancer, detailed pancancer analyses have not yet been performed. In this genome database study, based on The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases, the potential role of RCC1 in 33 tumors' entities was explored. The results show that RCC1 is highly expressed in most human malignant neoplasms in contrast to healthy tissues. RCC1 expression is closely related to the prognosis of a broad variety of tumor patients. Enrichment analysis showed that some tumor-related pathways such as "cell cycle" and "RNA transport" were involved in the functional mechanism of RCC1. In particular, the conducted analysis reveals the relation of RCC1 to multiple immune checkpoint genes and suggests that the regulation of RCC1 is closely related to tumor infiltration of cancer-associated fibroblasts and CD8+ T cells. Coherent data demonstrate the association of RCC1 with the tumor mutation burden and microsatellite instability in various tumors. These findings provide new insights into the role of RCC1 in oncogenesis and tumor immunology in various tumors and indicate its potential as marker for therapy prognosis and targeted treatment strategies.


Assuntos
Proteínas de Ciclo Celular/genética , Cromatina/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Fatores de Troca do Nucleotídeo Guanina/genética , Neoplasias/metabolismo , Proteínas Nucleares/genética , Big Data , Linfócitos T CD8-Positivos/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Carcinogênese/genética , Carcinogênese/imunologia , Ciclo Celular/genética , Ciclo Celular/imunologia , Proteínas de Ciclo Celular/metabolismo , Cromatina/genética , Metilação de DNA , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica/imunologia , Ontologia Genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Proteínas de Checkpoint Imunológico/genética , Estimativa de Kaplan-Meier , Instabilidade de Microssatélites , Neoplasias/genética , Neoplasias/mortalidade , Neoplasias/patologia , Proteínas Nucleares/metabolismo , Fosforilação , Prognóstico , Mapas de Interação de Proteínas , Transcriptoma
10.
Nucleic Acids Res ; 49(13): 7437-7456, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34197623

RESUMO

Despite its prominence, the mechanisms through which the tumor suppressor p53 regulates most genes remain unclear. Recently, the regulatory factor X 7 (RFX7) emerged as a suppressor of lymphoid neoplasms, but its regulation and target genes mediating tumor suppression remain unknown. Here, we identify a novel p53-RFX7 signaling axis. Integrative analysis of the RFX7 DNA binding landscape and the RFX7-regulated transcriptome in three distinct cell systems reveals that RFX7 directly controls multiple established tumor suppressors, including PDCD4, PIK3IP1, MXD4, and PNRC1, across cell types and is the missing link for their activation in response to p53 and stress. RFX7 target gene expression correlates with cell differentiation and better prognosis in numerous cancer types. Interestingly, we find that RFX7 sensitizes cells to Doxorubicin by promoting apoptosis. Together, our work establishes RFX7's role as a ubiquitous regulator of cell growth and fate determination and a key node in the p53 transcriptional program.


Assuntos
Regulação da Expressão Gênica , Redes Reguladoras de Genes , Genes Supressores de Tumor , Fatores de Transcrição de Fator Regulador X/metabolismo , Estresse Fisiológico/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Antibióticos Antineoplásicos/farmacologia , Apoptose , Diferenciação Celular/genética , Linhagem Celular Tumoral , DNA/metabolismo , Doxorrubicina/farmacologia , Humanos , Camundongos , Neoplasias/genética , Neoplasias/mortalidade , Prognóstico , Regiões Promotoras Genéticas , Fatores de Transcrição de Fator Regulador X/fisiologia , Transdução de Sinais , Transativadores/metabolismo , Transcriptoma
11.
Biomed Pharmacother ; 139: 111719, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34233389

RESUMO

Poly(rC)-binding protein 2 (PCBP2) is an RNA-binding protein that is characterized by its ability to interact with poly(C) with high affinity in a sequence-specific manner. PCBP2 contains three K homology domains, which are consensus RNA-binding domains that play a role in recognizing and combining with RNA and DNA. The specific structure and localization of PCBP2 lay the foundation for its multiple roles in transcriptional, posttranscriptional, and translational processes, even in iron metabolism. Numerous studies have indicated that PCBP2 expression is increased in many cancer types. PCBP2 is considered as an oncogene that promotes tumorigenesis, development of cancer cells, and metastasis. Here, we summarized the current evidence regarding PCBP2 in the proliferation, migration, invasion of cancer cells, and drug resistance, aiming to clarify the molecular mechanisms of PCBP2 in cancer. Results from this review suggest that an in-depth study of PCBP2 in cancer may provide novel biomarkers for prognostic or therapeutic purposes.


Assuntos
Neoplasias/metabolismo , Proteínas de Ligação a RNA , Animais , Expressão Gênica , Humanos , Neoplasias/genética , Neoplasias/mortalidade , Prognóstico , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
12.
Cancer Epidemiol Biomarkers Prev ; 30(9): 1615-1619, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34233917

RESUMO

BACKGROUND: Most studies investigating the impact of coronavirus infectious disease-19 (COVID-19) on mortality among patients with cancer were performed in a hospital setting, and the evidence is thus based on a selected and frail subset of patients. This study evaluates the excess mortality during the first wave of COVID-19 in a nationwide, prevalent cancer cohort in Belgium. METHODS: Mortality was studied among almost 240,000 patients with cancer diagnosed between 2013 and 2018 and alive on January 1, 2020. The observed number of deaths in the months January to June 2020 was compared with the expected number of deaths applying the monthly mortality rates observed in the cancer cohort during the previous years. A comparison using the excess mortality rates from the general population was performed. RESULTS: An excess number of deaths of about 400 was observed in the month of April, coinciding with a peak of COVID-19 diagnoses in Belgium and corresponding to a 33% rise in mortality. A comparable number of excess deaths was estimated if the COVID-19 excess mortality rates from the general Belgian population were applied to the cancer cohort, stratified by age and sex. CONCLUSIONS: A considerable excess mortality in the Belgian cancer cohort was observed during the initial peak of COVID-19 in Belgium. The pattern of excess mortality was, however, not markedly different from that observed in the general population. IMPACT: These results suggest that the susceptibility of prevalent cancer patients to COVID-19-induced mortality during the first wave of the pandemic was comparable with the general population.


Assuntos
COVID-19/epidemiologia , Neoplasias/mortalidade , SARS-CoV-2 , Bélgica/epidemiologia , Estudos de Coortes , Humanos
13.
Cancer Epidemiol ; 73: 101950, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34214767

RESUMO

BACKGROUND: Childhood cancer survival currently exceeds 80 % five years after diagnosis in high-income countries. In this study, we aimed to describe long-term trends and to investigate socioeconomic and spatial disparities in childhood cancer survival. METHODS: The study included 28,073 cases recorded in the French National Registry of Childhood Cancers from 2000 to 2015. Contextual census data (deprivation indices, population density, spatial accessibility to general practitioners) were allocated to each case based on the residence at diagnosis. Overall survival (OS) and conditional 10-year OS for 5-year survivors were estimated for all cancers combined and by diagnostic group and subgroup. Comparisons were conducted by sex, age at diagnosis, period of diagnosis, and contextual indicators. Hazard ratios for death were estimated using Cox models. RESULTS: All cancers combined, the OS reached 82.8 % [95 % CI: 82.4-83.3] at 5 years and 80.8 % [95 % CI: 80.3-81.3] at 10 years. Conditional 10-year OS of 5-year survivors reached 97.5 % [95 % CI: 97.3-97.7] and was higher than 95 % for all subgroups except osteosarcomas and most subgroups of the central nervous system. In addition to disparities by sex, age at diagnosis, and period of diagnosis, we observed a slight decrease in survival for cases living in the most deprived areas at diagnosis, not consistent across diagnostic groups. CONCLUSION: Our results confirm the high 5-year survival for childhood cancer and show an excellent 10-year conditional survival of 5-year survivors. Additional individual data are needed to clarify the factors underlying the slight decrease in childhood cancer survival observed in the most deprived areas.


Assuntos
Sobreviventes de Câncer , Neoplasias , Sobreviventes de Câncer/estatística & dados numéricos , Criança , Estudos de Coortes , Feminino , França/epidemiologia , Humanos , Masculino , Neoplasias/mortalidade , Sistema de Registros , Fatores Socioeconômicos , Taxa de Sobrevida
14.
BMC Infect Dis ; 21(1): 636, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215207

RESUMO

BACKGROUND: This study aimed to investigate the epidemiology, microbiology, and risk factors associated with mortality and multi-drug resistance bacterial bloodstream infections (BSIs) among adult cancer patients in Shiraz, Iran. We also report a four-year trend of antimicrobial resistance patterns of BSIs. METHODS: We conducted a retrospective study at a referral oncology hospital from July 2015 to August 2019, which included all adults with confirmed BSI. RESULTS: 2393 blood cultures tested during the four-year study period; 414 positive cultures were included. The mean age of our patients was 47.57 ± 17.46 years old. Central Line-Associated BSI (CLABSI) was more common in solid tumors than patients with hematological malignancies. Gram-negative (GN) bacteria were more detected (63.3%, 262) than gram-positive bacteria (36.7%, 152). Escherichia coli was the most common gram-negative organism (123/262, 47%), followed by Pseudomonas spp. (82/262, 31%) and Klebsiella pneumoniae (38/262, 14.5%). Coagulase-negative staphylococci (CoNS) was the most frequently isolated pathogen among gram-positive bacteria (83/152, 54.6%). Acinetobacter spp., Pseudomonas spp., E. coli, and K. pneumoniae were the most common Extended-Spectrum Beta-Lactamase (ESBL) producers (100, 96.2, 66.7%, and 60.7, respectively). Acinetobacter spp., Pseudomonas spp., Enterobacter spp., E. coli, and K. pneumoniae were the most common carbapenem-resistant (CR) isolates (77.8, 70.7, 33.3, 24.4, and 13.2%, respectively). Out of 257 Enterobacterales and non-fermenter gram-negative BSIs, 39.3% (101/257) were carbapenem-resistant. Although the incidence of multi-drug resistance (MDR) gram-negative BSI increased annually during 2015-2018, the mortality rate of gram-negative BSI remains unchanged at about 20% (p-value = 0.55); however, the mortality rate was significantly greater (35.4%) in those with resistant gram-positive BSI (p-value = 0.001). The overall mortality rate was 21.5%. Early (7-day mortality) and late mortality rate (30-day mortality) were 10 and 3.4%, respectively. CONCLUSIONS: The emergence of MDR gram-negative BSI is a significant healthcare problem in oncology centers. The high proportion of the most frequently isolated pathogens were CR and ESBL-producing Enterobacterales and Pseudomonas spp. We have few effective choices against MDRGN BSI, especially in high-risk cancer patients, which necessitate newer treatment options.


Assuntos
Bacteriemia/complicações , Bactérias/patogenicidade , Farmacorresistência Bacteriana , Resistência a Múltiplos Medicamentos , Neoplasias/mortalidade , Sepse/complicações , Bacteriemia/microbiologia , Bactérias/isolamento & purificação , Terapia Combinada , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/etiologia , Neoplasias/patologia , Estudos Retrospectivos , Fatores de Risco , Sepse/microbiologia
15.
Mayo Clin Proc ; 96(7): 1758-1769, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34218856

RESUMO

OBJECTIVE: To investigate the joint associations of amounts of alcohol consumed and drinking habits with the risks of all-cause mortality and cause-specific mortality. PATIENTS AND METHODS: A total of 316,627 healthy current drinkers, with baseline measurements between March 13, 2006, and October 1, 2010, were included in this study. We newly created a drinking habit score (DHS) according to regular drinking (frequency of alcohol intake ≥3 times/wk) and whether consuming alcohol with meals (yes). RESULTS: During a median follow-up of 8.9 years, we documented 8652 incident cases of all-cause death, including 1702 cases of cardiovascular disease death, 4960 cases of cancer death, and 1990 cases of other-cause death. After adjustment confounders and amount of alcohol consumed, higher DHS was significantly associated with a lower risk of all-cause mortality, cardiovascular disease mortality, cancer mortality, or other-cause mortality (Ptrend<.001, Ptrend=.03, Ptrend<.001, and Ptrend<.001, respectively). We observed that the amount of alcohol consumed have different relationships with the risks of all-cause mortality and cause-specific mortality among participants with distinct drinking habits, grouped by DHS. For example, in the joint analyses, a J-shaped association between the amount of alcohol consumed and all-cause mortality was observed in participants with unfavorable DHS (Pquadratictrend=.02) while the association appeared to be U-shaped in participants with favorable DHS (Pquadratictrend=.003), with lower risks in those consuming greater than or equal to 50 g/wk and less than 300 g/wk. CONCLUSION: Our results indicate that alcohol consumption levels have different relationships with the risk of mortality among current drinkers, depending on their drinking habits.


Assuntos
Consumo de Bebidas Alcoólicas , Doenças Cardiovasculares/mortalidade , Etanol , Neoplasias/mortalidade , Medição de Risco , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Causas de Morte , Depressores do Sistema Nervoso Central/metabolismo , Depressores do Sistema Nervoso Central/farmacologia , Correlação de Dados , Etanol/metabolismo , Etanol/farmacologia , Feminino , Seguimentos , Hormese , Humanos , Masculino , Refeições , Pessoa de Meia-Idade , Mortalidade , Fatores de Proteção , Fatores de Risco , Estados Unidos/epidemiologia
16.
Isr Med Assoc J ; 23(7): 426-431, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34251125

RESUMO

BACKGROUND: Decisions on medication treatment in children dying from cancer are often complex and may result in polypharmacy and increased medication burden. There is no information on medication burden in pediatric cancer patients at the end of life (EOL). OBJECTIVES: To characterize medication burden during the last hospitalization in children dying from cancer. METHODS: We performed a retrospective cohort study based on medical records of 90 children who died from cancer in hospital between 01 January 2010 and 30 December 2018. Demographic and clinical information were collected for the last hospitalization. We compared medication burden (number of medication orders) at hospitalization and at time of death and examined whether changes in medication burden were associated with clinical and demographic parameters. RESULTS: Median medication burden was higher in leukemia/lymphoma patients (6 orders) compared to solid (4 orders) or CNS tumor patients (4 orders, P = 0.006). Overall, the median number of prescriptions per patient did not change until death (P = 0.42), while there was a significant reduction for some medication subgroups (chemotherapy [P = 0.035], steroids [P = 0.010]).Patients dying in the ICU (n=15) had a higher medication burden at death (6 orders) than patients dying on wards (3 orders, P = 0.001). There was a trend for a reduction in medication burden in patients with "Do not resuscitate" (DNR) orders (P = 0.055). CONCLUSIONS: Polypharmacy is ubiquitous among pediatric oncology patients at EOL. Disease type and DNR status may affect medication burden and deprescribing during the last hospitalization.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias , Cuidados Paliativos , Polimedicação , Esteroides/uso terapêutico , Assistência Terminal , Criança , Procedimentos Clínicos/estatística & dados numéricos , Demografia , Feminino , Pesquisa sobre Serviços de Saúde , Hospitalização/estatística & dados numéricos , Humanos , Israel/epidemiologia , Masculino , Estadiamento de Neoplasias , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neoplasias/patologia , Cuidados Paliativos/métodos , Cuidados Paliativos/estatística & dados numéricos , Ordens quanto à Conduta (Ética Médica) , Assistência Terminal/métodos , Assistência Terminal/estatística & dados numéricos
18.
Nat Commun ; 12(1): 4423, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285218

RESUMO

The Cancer Genome Atlas (TCGA) is one of the largest biorepositories of digital histology. Deep learning (DL) models have been trained on TCGA to predict numerous features directly from histology, including survival, gene expression patterns, and driver mutations. However, we demonstrate that these features vary substantially across tissue submitting sites in TCGA for over 3,000 patients with six cancer subtypes. Additionally, we show that histologic image differences between submitting sites can easily be identified with DL. Site detection remains possible despite commonly used color normalization and augmentation methods, and we quantify the image characteristics constituting this site-specific digital histology signature. We demonstrate that these site-specific signatures lead to biased accuracy for prediction of features including survival, genomic mutations, and tumor stage. Furthermore, ethnicity can also be inferred from site-specific signatures, which must be accounted for to ensure equitable application of DL. These site-specific signatures can lead to overoptimistic estimates of model performance, and we propose a quadratic programming method that abrogates this bias by ensuring models are not trained and validated on samples from the same site.


Assuntos
Biomarcadores Tumorais/análise , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Neoplasias/patologia , Manejo de Espécimes/métodos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Análise Mutacional de DNA/métodos , Confiabilidade dos Dados , Perfilação da Expressão Gênica/métodos , Humanos , Mutação , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/mortalidade , Medição de Risco/métodos
19.
Eur J Cancer ; 153: 123-132, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34153714

RESUMO

BACKGROUND: Changes in the management of patients with cancer and delays in treatment delivery during the COVID-19 pandemic may impact the use of hospital resources and cancer mortality. PATIENTS AND METHODS: Patient flows, patient pathways and use of hospital resources during the pandemic were simulated using a discrete event simulation model and patient-level data from a large French comprehensive cancer centre's discharge database, considering two scenarios of delays: massive return of patients from November 2020 (early-return) or March 2021 (late-return). Expected additional cancer deaths at 5 years and mortality rate were estimated using individual hazard ratios based on literature. RESULTS: The number of patients requiring hospital care during the simulation period was 13,000. In both scenarios, 6-8% of patients were estimated to present a delay of >2 months. The overall additional cancer deaths at 5 years were estimated at 88 in early-return and 145 in late-return scenario, with increased additional deaths estimated for sarcomas, gynaecological, liver, head and neck, breast cancer and acute leukaemia. This represents a relative additional cancer mortality rate at 5 years of 4.4 and 6.8% for patients expected in year 2020, 0.5 and 1.3% in 2021 and 0.5 and 0.5% in 2022 for each scenario, respectively. CONCLUSIONS: Pandemic-related diagnostic and treatment delays in patients with cancer are expected to impact patient survival. In the perspective of recurrent pandemics or alternative events requiring an intensive use of limited hospital resources, patients should be informed not to postpone care, and medical resources for patients with cancer should be sanctuarised.


Assuntos
COVID-19/epidemiologia , Neoplasias/mortalidade , Neoplasias/terapia , COVID-19/mortalidade , COVID-19/virologia , Simulação por Computador , Atenção à Saúde/organização & administração , Administração Hospitalar , Hospitais , Humanos , Neoplasias/patologia , Pandemias , Modelos de Riscos Proporcionais , SARS-CoV-2/isolamento & purificação
20.
Cancer Treat Res Commun ; 28: 100418, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34118790

RESUMO

Patients with cancer are a vulnerable population during the COVID-19 pandemic due to underlying immunosuppression, pre-existing comorbidities, and poor nutrition. There is a lack of data describing the disease course of cancer patients with COVID-19 disease. Therefore, we analyzed data from cancer patients with COVID-19 who were admitted to our hospital. Cancer patients were categorized into two groups as survivors and non-survivors of COVID-19. Among 68 cancer patients with COVID-19, 27% of patients were admitted to ICU, and 37% of the patients died. The median age was 72, and non-survivors were older than survivors (p = 0.001). Non-survivors had higher comorbidity scores, late-stage cancer, and worse ECOG performance status than survivors (all p values<0.005). Non-survivors also had significantly lower lymphocyte count and albumin level but higher lactate dehydrogenase, C-reactive protein, fibrinogen, troponin, and ferritin levels than survivors. On multivariable analysis, increased age and mechanical ventilation were associated with increased odds of death. We report no association between anti-cancer treatments and mortality from COVID-19 disease. In summary, cancer patients have higher mortality of COVID-19 infection than the general population. In addition to generally known risk factors, the high mortality rate in cancer patients with COVID-19 is associated with several cancer-specific factors.


Assuntos
COVID-19/epidemiologia , COVID-19/etiologia , Neoplasias/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , COVID-19/terapia , Comorbidade , Feminino , Hospitais/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/mortalidade , Neoplasias/terapia , Respiração Artificial , Estudos Retrospectivos , Provedores de Redes de Segurança/estatística & dados numéricos , Estados Unidos/epidemiologia , Adulto Jovem
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