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1.
Cancer Control ; 28: 10732748211045275, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34623943

RESUMO

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has overwhelmed the capacity of healthcare systems worldwide. Cancer patients, in particular, are vulnerable and oncology departments drastically needed to modify their care systems and established new priorities. We evaluated the impact of SARS-CoV-2 on the activity of a single cancer center. METHODS: We performed a retrospective analysis of (i) volumes of oncological activities (2020 vs 2019), (ii) patients' perception rate of the preventive measures, (iii) patients' SARS-CoV-2 infections, clinical signs thereof, and (iv) new diagnoses made during the SARS-CoV-2 pandemic. RESULTS: As compared with a similar time frame in 2019, the overall activity in total numbers of outpatient chemotherapy administrations and specialist visits was not statistically different (P = .961 and P = .252), while inpatient admissions decreased for both medical oncology and thoracic oncology (18% (P = .0018) and 44% (P < .0001), respectively). Cancer diagnosis plummeted (-34%), but no stage shift could be demonstrated.Acceptance and adoption of hygienic measures was high, as measured by a targeted questionnaire (>85%). However, only 46.2% of responding patients regarded telemedicine, although widely deployed, as an efficient surrogate to a consultation.Thirty-three patients developed SARS-CoV-2, 27 were hospitalized, and 11 died within this time frame. These infected patients were younger, current smokers, and suffered more comorbidities. CONCLUSIONS: This retrospective cohort analysis adds to the evidence that continuation of active cancer therapy and specialist visits is feasible and safe with the implementation of telemedicine. These data further confirm the impact of SARS-CoV-2 on cancer care management, cancer diagnosis, and impact of infection on cancer patients.


Assuntos
COVID-19/epidemiologia , Institutos de Câncer/organização & administração , Institutos de Câncer/estatística & dados numéricos , Neoplasias/epidemiologia , Neoplasias/terapia , Fatores Etários , Comorbidade , Ciclopentanos , Humanos , Controle de Infecções/organização & administração , Neoplasias/diagnóstico , Neoplasias/mortalidade , Compostos de Organossilício , Pandemias , Percepção , Estudos Retrospectivos , SARS-CoV-2
2.
Sci Rep ; 11(1): 20073, 2021 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625642

RESUMO

Kidney transplantation recipients (KTR) with coronavirus disease 2019 (COVID-19) are at higher risk of death than general population. However, mortality risk factors in KTR are still not clearly identified. Our objective was to systematically analyze published evidence for risk factors associated with mortality in COVID-19 KTR. Electronic databases were searched for eligible studies on 1 August 2021. All prospective and retrospective studies of COVID-19 in KTR were considered eligible without language restriction. Since data in case reports and series could potentially be subsets of larger studies, only studies with ≥ 50 patients were included. Random-effects model meta-analysis was used to calculate weighted mean difference (WMD) and pooled odds ratio (OR) of factors associated with mortality. From a total 1,137 articles retrieved, 13 were included in the systematic review and meta-analysis comprising 4,440 KTR. Compared with survivors, non-survivors were significantly older (WMD 10.5 years, 95% CI 9.3-11.8). KTR of deceased donor were at higher risk of death (OR 1.73, 95% CI 1.10-2.74). Comorbidities including diabetes mellitus, cardiovascular disease, and active cancer significantly increased mortality risk. KTR with dyspnea (OR 5.68, 95% CI 2.11-15.33) and pneumonia (OR 10.64, 95% CI 3.37-33.55) at presentation were at higher mortality risk, while diarrhea decreased the risk (OR 0.61, 95% CI 0.47-0.78). Acute kidney injury was associated with mortality (OR 3.24, 95% CI 1.36-7.70). Inflammatory markers were significantly higher in the non-survivors, including C-reactive protein, procalcitonin, and interleukine-6. A number of COVID-19 mortality risk factors were identified from KTR patient characteristics, presenting symptoms, and laboratory investigations. KTR with these risk factors should receive more intensive monitoring and early therapeutic interventions to optimize health outcomes.


Assuntos
Injúria Renal Aguda/epidemiologia , COVID-19/epidemiologia , Transplante de Rim , Injúria Renal Aguda/mortalidade , COVID-19/mortalidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Comorbidade , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/mortalidade , Humanos , Transplante de Rim/efeitos adversos , Neoplasias/epidemiologia , Neoplasias/mortalidade , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Transplantados
3.
Anticancer Res ; 41(10): 5107-5116, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593461

RESUMO

BACKGROUND/AIM: We evaluated local control and toxicity in patients receiving radiotherapy associated with immune check point inhibitors and analyzed which oligometastatic disease setting benefits the most from local ablation in terms of advantage in overall survival. PATIENTS AND METHODS: We retrospectively identified 60 oligoprogressive patients treated with a PD-1 inhibitor in association with radiotherapy on the site of progression (119 lesions). RESULTS: After a median follow-up of 11.7 months (range=1-39 months), we observed complete response (CR) in 45/119, partial response (RP) in 42/119, and stable disease (SD) in 30/119 patients. Nine radionecrotic events occurred. Two patients experienced grade 3 toxicities and 32 patients reported grade 2 toxicities. The number of radiologically evident metastatic organs in patients who received concomitant PD-1 inhibitors and radiotherapy showed a significant increase in survival (respectively, 73% after 12 months and 47% after 24 months) in patients with 0-3 metastatic organs compared to those with more than 3 organ sites involved (p<0.0001). CONCLUSION: Radiotherapy associated with PD-1 inhibitors is overall safe and efficacious. Patients eligible for intensification of local treatments should have less or equal to 3 metastatic organ sites.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Recidiva Local de Neoplasia/mortalidade , Neoplasias/mortalidade , Radiocirurgia/mortalidade , Terapia Combinada , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Neoplasias/patologia , Neoplasias/terapia , Prognóstico , Hipofracionamento da Dose de Radiação , Estudos Retrospectivos , Taxa de Sobrevida , Testes de Toxicidade
4.
Medicine (Baltimore) ; 100(39): e27370, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596152

RESUMO

ABSTRACT: This study aimed to evaluate the impact of cancer-related mortality on life expectancy in Feicheng City.We extracted the death records and population data of Feicheng City from 2013 to 2018 through the Feicheng Center for Disease Control and Prevention. The mortality, premature mortality, cause-eliminated life expectancy, potential years of life lost (PYLL), average potential years of life lost (APYLL), annual change percentage (APC), and other indicators of cancer were calculated. The age-standardized rates were calculated using the sixth national census (2010).From 2013 to 2018, the mortality rate of cancer in Feicheng City was 221.55/100,000, and the standardized mortality rate was 166.37/100,000. The standardized mortality rate increased from 2013 to 2014 and then decreased annually. The premature mortality of cancer was 8.98% and showed a downward trend (APC = -2.47%, t = -3.10, P = .04). From 2013 to 2018, the average life expectancy of residents in Feicheng City was 78.63 years. Eliminating the impact of cancer, life expectancy could increase by 3.72 years. The rate of life loss caused by cancer in men was higher than that in women. The total life loss caused by cancer deaths was 126,870.50 person-years, the potential life loss rate was 22.51‰, and the average potential life loss was 13.30 years. The standardized potential years of life lost rate showed a downward trend (APC = -2.96%, t = -3.72, P = .02), and APYLL decreased by 1.98% annually (t = -5.44, P = .01). The top 5 malignant tumors in APYLL were leukemia, breast cancer, brain tumor, liver cancer, and ovarian cancer.Lung cancer, esophageal cancer, female breast cancer, and childhood leukemia have a great impact on the life expectancy of residents in Feicheng City. Effective measures need to be taken to reduce the disease burden of malignant tumors.


Assuntos
Mortalidade Prematura , Neoplasias/mortalidade , China , Efeitos Psicossociais da Doença , Feminino , Humanos , Expectativa de Vida , Masculino , Distribuição por Sexo
5.
Lancet Oncol ; 22(10): 1427-1437, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34487693

RESUMO

BACKGROUND: The COVID-19 pandemic has strained health system capacity worldwide due to a surge of hospital admissions, while mitigation measures have simultaneously reduced patients' access to health care, affecting the diagnosis and treatment of other diseases such as cancer. We estimated the impact of delayed diagnosis on cancer outcomes in Chile using a novel modelling approach to inform policies and planning to mitigate the forthcoming cancer-related health impacts of the pandemic in Chile. METHODS: We developed a microsimulation model of five cancers in Chile (breast, cervix, colorectal, prostate, and stomach) for which reliable data were available, which simulates cancer incidence and progression in a nationally representative virtual population, as well as stage-specific cancer detection and survival probabilities. We calibrated the model to empirical data on monthly detected cases, as well as stage at diagnosis and 5-year net survival. We accounted for the impact of COVID-19 on excess mortality and cancer detection by month during the pandemic, and projected diagnosed cancer cases and outcomes of stage at diagnosis and survival up to 2030. For comparison, we simulated a no COVID-19 scenario in which the impacts of COVID-19 on excess mortality and cancer detection were removed. FINDINGS: Our modelling showed a sharp decrease in the number of diagnosed cancer cases during the COVID-19 pandemic, with a large projected short-term increase in future diagnosed cases. Due to the projected backlog in diagnosis, we estimated that in 2021 there will be an extra 3198 cases (95% uncertainty interval [UI] 1356-5017) diagnosed among the five modelled cancers, an increase of nearly 14% compared with the no COVID-19 scenario, falling to a projected 10% increase in 2022 with 2674 extra cases (1318-4032) diagnosed. As a result of delayed diagnosis, we found a worse stage distribution for detected cancers in 2020-22, which is estimated to lead to 3542 excess cancer deaths (95% UI 2236-4816) in 2022-30, compared with the no COVID-19 scenario, among the five modelled cancers, most of which (3299 deaths, 2151-4431) are projected to occur before 2025. INTERPRETATION: In addition to a large projected surge in diagnosed cancer cases, we found that delays in diagnosis will result in worse cancer stage at presentation, leading to worse survival outcomes. These findings can help to inform surge capacity planning and highlight the importance of ensuring appropriate health system capacity levels to detect and care for the increased cancer cases in the coming years, while maintaining the timeliness and quality of cancer care. Potential delays in treatment and adverse impacts on quality of care, which were not considered in this model, are likely to contribute to even more excess deaths from cancer than projected. FUNDING: Harvard TH Chan School of Public Health. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.


Assuntos
COVID-19 , Neoplasias/diagnóstico , Neoplasias/mortalidade , Chile , Simulação por Computador , Diagnóstico Tardio/mortalidade , Feminino , Humanos , Masculino , Modelos Estatísticos , SARS-CoV-2
6.
Int J Equity Health ; 20(1): 216, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34579732

RESUMO

BACKGROUND: The small-area deprivation indices are varied across countries due to different social context and data availability. Due to lack of chronic disease-related social deprivation index (SDI) in Hong Kong, China, this study aimed to develop a new SDI and examine its association with cancer mortality. METHODS: A total of 14 socio-economic variables of 154 large Tertiary Planning Unit groups (LTPUGs) in Hong Kong were obtained from 2016 population by-census. LTPUG-specific all-cause and chronic condition-related mortality and chronic condition inpatient episodes were calculated as health outcomes. Association of socio-economic variables with health outcomes was estimated for variable selection. Candidates for SDI were constructed with selected socio-economic variables and tested for criterion validity using health outcomes. Ecological association between the selected SDI and cancer mortality were examined using zero-inflated negative binomial regression. RESULTS: A chronic disease-related SDI constructed by six area-level socio-economic variables was selected based on its criterion validity with health outcomes in Hong Kong. It was found that social deprivation was associated with higher cancer mortality during 2011-2016 (most deprived areas: incidence relative risk [IRR] = 1.40, 95% confidence interval [CI]: 1.27-1.55; second most deprived areas: IRR = 1.34, 95%CI: 1.21-1.48; least deprived areas as reference), and the cancer mortality gap became larger in more recent years. Excess cancer death related to social deprivation was found to have increased through 2011-2016. CONCLUSIONS: Our newly developed SDI is a valid and routinely available measurement of social deprivation in small areas and is useful in resource allocation and policy-making for public health purpose in communities. There is a potential large improvement in cancer mortality by offering relevant policies and interventions to reduce health-related deprivation. Further studies can be done to design strategies to reduce the expanding health inequalities between more and less deprived areas.


Assuntos
Disparidades nos Níveis de Saúde , Neoplasias , Áreas de Pobreza , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Indicadores Básicos de Saúde , Hong Kong/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Neoplasias/mortalidade , Análise de Pequenas Áreas , Adulto Jovem
7.
Eur J Endocrinol ; 185(5): 681-689, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34478404

RESUMO

Background: Insulin-like growth factor 1 (IGF1) is an important growth factor modulating development, homeostasis, and aging. However, whether and how circulating IGF1 concentrations influence early death risk in the general population remains largely unknown. Methods: We included 380 997 participants who had serum IGF1 measurement and no history of cancer, cardiovascular disease (CVD), or diabetes at baseline from UK Biobank, a prospective cohort study initiated in 2006-2010. Restricted cubic splines and Cox proportional hazards regression models were used to assess the association between baseline IGF-1 concentrations and all-cause and cause-specific mortality. Results: Over a median follow-up of 8.8 years, 10 753 of the participants died, including 6110 from cancer and 1949 from CVD. Dose-response analysis showed a U-shaped relationship between IGF1 levels and mortality. Compared to the fifth decile of IGF1, the lowest decile was associated with 39% (95% CI: 29-50%), 20% (95% CI: 8-34%), and 39% (95% CI: 14-68%) higher risk of all-cause, cancer, and CVD mortality, respectively, while the highest decile was associated with 17% (95% CI: 7-28%) and 38% (95% CI: 11-71%) higher risk of all-cause and CVD mortality, respectively. The results remained stable in detailed stratified and sensitivity analyses. Conclusions: Our findings indicate that both low and high concentrations of serum IGF1 are associated with increased risk of mortality in the general population. Our study provides a basis for future interrogation of underlying mechanisms of IGF1 in early death occurrence and possible implications for mitigating the risk.


Assuntos
Fator de Crescimento Insulin-Like I/análise , Mortalidade/tendências , Idoso , Biomarcadores , Doenças Cardiovasculares/mortalidade , Causas de Morte , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Fatores de Risco , Reino Unido/epidemiologia
8.
Eur J Epidemiol ; 36(10): 1005-1014, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34591201

RESUMO

Reported associations between vitamin K1 and both all-cause and cause-specific mortality are conflicting. The 56,048 participants from the Danish Diet, Cancer, and Health prospective cohort study, with a median [IQR] age of 56 [52-60] years at entry and of whom 47.6% male, were followed for 23 years, with 14,083 reported deaths. Of these, 5015 deaths were CVD-related, and 6342 deaths were cancer-related. Intake of vitamin K1 (phylloquinone) was estimated from a food-frequency questionnaire (FFQ), and its relationship with mortality outcomes was investigated using Cox proportional hazards models. A moderate to high (87-192 µg/d) intake of vitamin K1 was associated with a lower risk of all-cause [HR (95%CI) for quintile 5 vs quintile 1: 0.76 (0.72, 0.79)], cardiovascular disease (CVD)-related [quintile 5 vs quintile 1: 0.72 (0.66, 0.79)], and cancer-related mortality [quintile 5 vs quintile 1: 0.80 (0.75, 0.86)], after adjusting for demographic and lifestyle confounders. The association between vitamin K1 intake and cardiovascular disease-related mortality was present in all subpopulations (categorised according to sex, smoking status, diabetes status, and hypertension status), while the association with cancer-related mortality was only present in current/former smokers (p for interaction = 0.002). These findings suggest that promoting adequate intakes of foods rich in vitamin K1 may help to reduce all-cause, CVD-related, and cancer-related mortality at the population level.


Assuntos
Doenças Cardiovasculares/mortalidade , Mortalidade , Neoplasias/mortalidade , Vitamina K/administração & dosagem , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , Causas de Morte , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/metabolismo , Neoplasias/prevenção & controle , Avaliação Nutricional , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Vitamina K 1/administração & dosagem , Vitamina K 2/administração & dosagem
9.
Nat Commun ; 12(1): 5606, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556668

RESUMO

Immune checkpoint therapy (ICT) provides substantial clinical benefits to cancer patients, but a large proportion of cancers do not respond to ICT. To date, the genomic underpinnings of primary resistance to ICT remain elusive. Here, we performed immunogenomic analysis of data from TCGA and clinical trials of anti-PD-1/PD-L1 therapy, with a particular focus on homozygous deletion of 9p21.3 (9p21 loss), one of the most frequent genomic defects occurring in ~13% of all cancers. We demonstrate that 9p21 loss confers "cold" tumor-immune phenotypes, characterized by reduced abundance of tumor-infiltrating leukocytes (TILs), particularly, T/B/NK cells, altered spatial TILs patterns, diminished immune cell trafficking/activation, decreased rate of PD-L1 positivity, along with activation of immunosuppressive signaling. Notably, patients with 9p21 loss exhibited significantly lower response rates to ICT and worse outcomes, which were corroborated in eight ICT trials of >1,000 patients. Further, 9p21 loss synergizes with PD-L1/TMB for patient stratification. A "response score" was derived by incorporating 9p21 loss, PD-L1 expression and TMB levels in pre-treatment tumors, which outperforms PD-L1, TMB, and their combination in identifying patients with high likelihood of achieving sustained response from otherwise non-responders. Moreover, we describe potential druggable targets in 9p21-loss tumors, which could be exploited to design rational therapeutic interventions.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 9/genética , Resistencia a Medicamentos Antineoplásicos/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Microambiente Tumoral/imunologia , Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Resistencia a Medicamentos Antineoplásicos/genética , Homozigoto , Humanos , Tolerância Imunológica , Imunoterapia , Linfócitos do Interstício Tumoral/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/mortalidade , Prognóstico , Transdução de Sinais/imunologia
10.
Cancer Treat Rev ; 100: 102296, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34571378

RESUMO

BACKGROUND: Survivors of childhood, adolescent and young adult (CAYA) cancer may develop treatment-induced chronic liver disease. Surveillance guidelines can improve survivors' health outcomes. However, current recommendations vary, leading to uncertainty about optimal screening. The International Late Effects of Childhood Cancer Guideline Harmonization Group has developed recommendations for the surveillance of late hepatotoxicity after CAYA cancer. METHODS: Evidence-based methods based on the GRADE framework were used in guideline development. A multidisciplinary guideline panel performed systematic literature reviews, developed evidence summaries, appraised the evidence, and formulated recommendations on the basis of evidence, clinical judgement, and consideration of benefits versus the harms of the surveillance while allowing for flexibility in implementation across different health care systems. RESULTS: The guideline strongly recommends a physical examination and measurement of serum liver enzyme concentrations (ALT, AST, gGT, ALP) once at entry into long-term follow-up for survivors treated with radiotherapy potentially exposing the liver (moderate- to high-quality evidence). For survivors treated with busulfan, thioguanine, mercaptopurine, methotrexate, dactinomycin, hematopoietic stem cell transplantation (HSCT), or hepatic surgery, or with a history of chronic viral hepatitis or sinusoidal obstruction syndrome, similar surveillance for late hepatotoxicity once at entry into LTFU is reasonable (low-quality evidence/expert opinion, moderate recommendation). For survivors who have undergone HSCT and/or received multiple red blood cell transfusions, surveillance for iron overload with serum ferritin is strongly recommended once at long-term follow-up entry. CONCLUSIONS: These evidence-based, internationally-harmonized recommendations for the surveillance of late hepatic toxicity in cancer survivors can inform clinical care and guide future research of health outcomes for CAYA cancer survivors.


Assuntos
Sobreviventes de Câncer , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Neoplasias/terapia , Lesões por Radiação/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Humanos , Programas de Rastreamento/métodos , Neoplasias/mortalidade , Lesões por Radiação/etiologia
11.
BMC Cancer ; 21(1): 907, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493242

RESUMO

BACKGROUND: Cancer mortality in the U.S. has fallen in recent decades; however, individuals with lower levels of education experienced a smaller decline than more highly educated individuals. This analysis aimed to measure the influence of education lower than a high school diploma, on cancer amenable mortality among Non-Hispanic Whites (NHW) and Non-Hispanic Blacks (NHB) in the U.S. from 1989 to 2018. METHODS: We analyzed data from 8.2 million death certificates of men and women who died from cancer between 1989 and 2018. We examined 5-year and calendar period intervals, as well as annual percent changes (APC). APC was adjusted for each combination of sex, educational level, and race categories (8 models) to separate the general trend from the effects of age. RESULTS: Our study demonstrated an increasing mortality gap between the least and the most educated NHW and NHB males and females who died from all cancers combined and for most other cancer types included in this study. The gap between the least and the most educated was broader among NHW males and females than among NHB males and females, respectively, for most malignancies. CONCLUSIONS: In summary, we reported an increasing gap in the age-adjusted cancer mortality among the most and the least educated NHW and NHB between 25 and 74 years of age. We demonstrated that although NHB exhibited the greatest age-adjusted mortality rates for most cancer locations, the gap between the most and the least educated was shown for NHW.


Assuntos
Afro-Americanos/estatística & dados numéricos , Escolaridade , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Hispano-Americanos/estatística & dados numéricos , Neoplasias/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/patologia , Prognóstico , Taxa de Sobrevida , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto Jovem
12.
BMC Cancer ; 21(1): 1053, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563154

RESUMO

BACKGROUND: Over the past decades, approaches for diagnosing and treating cancer have seen significant improvement. However, the variability of patient and tumor characteristics has limited progress on methods for prognosis prediction. The development of high-throughput omics technologies now provides multiple approaches for characterizing tumors. Although a large number of published studies have focused on integration of multi-omics data and use of pathway-level models for cancer prognosis prediction, there still exists a gap of knowledge regarding the prognostic landscape across multi-omics data for multiple cancer types using both gene-level and pathway-level predictors. METHODS: In this study, we systematically evaluated three often available types of omics data (gene expression, copy number variation and somatic point mutation) covering both DNA-level and RNA-level features. We evaluated the landscape of predictive performance of these three omics modalities for 33 cancer types in the TCGA using a Lasso or Group Lasso-penalized Cox model and either gene or pathway level predictors. RESULTS: We constructed the prognostic landscape using three types of omics data for 33 cancer types on both the gene and pathway levels. Based on this landscape, we found that predictive performance is cancer type dependent and we also highlighted the cancer types and omics modalities that support the most accurate prognostic models. In general, models estimated on gene expression data provide the best predictive performance on either gene or pathway level and adding copy number variation or somatic point mutation data to gene expression data does not improve predictive performance, with some exceptional cohorts including low grade glioma and thyroid cancer. In general, pathway-level models have better interpretative performance, higher stability and smaller model size across multiple cancer types and omics data types relative to gene-level models. CONCLUSIONS: Based on this landscape and comprehensively comparison, models estimated on gene expression data provide the best predictive performance on either gene or pathway level. Pathway-level models have better interpretative performance, higher stability and smaller model size relative to gene-level models.


Assuntos
Variações do Número de Cópias de DNA , Perfilação da Expressão Gênica/métodos , Expressão Gênica , Neoplasias/genética , Mutação Puntual , Estudos de Coortes , Bases de Dados Genéticas , Humanos , Neoplasias/mortalidade , Neoplasias/patologia , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais
13.
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
14.
Nat Commun ; 12(1): 5311, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493724

RESUMO

Although some effective therapies have been available for cancer, it still poses a great threat to human health and life due to its drug resistance and low response in patients. Here, we develop a ferroptosis-based therapy by combining iron nanoparticles and cancer-specific gene interference. The expression of two iron metabolic genes (FPN and LCN2) was selectively knocked down in cancer cells by Cas13a or microRNA controlled by a NF-κB-specific promoter. Cells were simultaneously treated by iron nanoparticles. As a result, a significant ferroptosis was induced in a wide variety of cancer cells. However, the same treatment had little effect on normal cells. By transferring genes with adeno-associated virus and iron nanoparticles, the significant tumor growth inhibition and durable cure were obtained in mice with the therapy. In this work, we thus show a cancer therapy based on gene interference-enhanced ferroptosis.


Assuntos
Proteínas de Transporte de Cátions/antagonistas & inibidores , Ferroptose/genética , Ferro/metabolismo , Lipocalina-2/antagonistas & inibidores , Neoplasias/terapia , Interferência de RNA , Espécies Reativas de Oxigênio/agonistas , Animais , Proteínas Associadas a CRISPR/genética , Proteínas Associadas a CRISPR/metabolismo , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Linhagem Celular Tumoral , Dependovirus/genética , Dependovirus/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Lipocalina-2/genética , Lipocalina-2/metabolismo , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Nanopartículas/administração & dosagem , Nanopartículas/química , Neoplasias/genética , Neoplasias/mortalidade , Neoplasias/patologia , Regiões Promotoras Genéticas , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Baço/metabolismo , Baço/patologia , Análise de Sobrevida , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Lancet Oncol ; 22(10): 1416-1426, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34454651

RESUMO

BACKGROUND: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. METHODS: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. FINDINGS: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8-8·8]; p<0·0001) and upper-middle-income (1·6 [1·2-2·2]; p=0·0024) country status; age 15-18 years (1·6 [1·1-2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8-3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm3 (1·8 [1·3-2·4]; p=0·0001), and intensive treatment (1·8 [1·3-2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3-0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3-0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3-2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1-2·3]; p=0·020). INTERPRETATION: In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness. FUNDING: American Lebanese Syrian Associated Charities and the National Cancer Institute.


Assuntos
COVID-19 , Neoplasias , Adolescente , COVID-19/mortalidade , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias/mortalidade , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença
16.
Eur J Endocrinol ; 185(5): K15-K19, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34403360

RESUMO

Objective: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) has variable clinical course. Overall mortality is increased but reasons for this remain largely unknown. Our objective was to assess the causes of death and factors contributing to increased mortality. Design: A follow-up study of the Finnish APECED cohort in 1970-2019. Methods: In 33 deceased patients with APECED, causes of death and clinical course preceding the death were analyzed using national registry data, death certificates, autopsy reports, and patient records. Results: Most common causes leading to death were infections (24%), oral and esophageal malignancies (15%; median age at death 36.7 years; median survival 1.5 years), and diseases of the circulatory system (18%). Adrenal crisis was an independent cause of death in two patients. In addition, in four patients, the adrenal crisis was a complicating factor during a fatal infection. Other APECED manifestations leading to death were hypoparathyroidism, diabetes, and hepatitis. Other causes of death included accidents (12%), alcohol-related causes, and amyotrophic lateral sclerosis. Challenges in overall, and especially in the endocrine, care contributed to deaths related to carcinomas and adrenal crisis. Age at death and year of death correlated (r = 0.345, P = 0.045), suggesting improved longevity. Conclusions: Infections, malignancies, and diseases of the circulatory system are the most common primary causes of death in patients with APECED. Adrenal crisis is an independent cause of death but more often a contributing factor in fatal infections. Despite the high overall mortality and the demanding care, our results suggest improved patient survival in recent years.


Assuntos
Atenção à Saúde/estatística & dados numéricos , Endocrinologia , Poliendocrinopatias Autoimunes/mortalidade , Poliendocrinopatias Autoimunes/terapia , Acidentes/estatística & dados numéricos , Adolescente , Adulto , Idoso , Alcoolismo/complicações , Alcoolismo/mortalidade , Autopsia , Causas de Morte , Criança , Estudos de Coortes , Feminino , Finlândia/epidemiologia , Seguimentos , Humanos , Infecções/epidemiologia , Infecções/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Neoplasias/mortalidade , Sistema de Registros , Análise de Sobrevida , Adulto Jovem
17.
BMC Cancer ; 21(1): 912, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380458

RESUMO

BACKGROUND: Intake time of diet has recently been demonstrated to be associated with the internal clock and circadian pattern. However, whether and how the intake time of minerals would influence the natural course of cancer was largely unknown. METHODS: This study aimed to assess the association of mineral intake at different periods with cancer and all-cause mortality. A total of 27,455 participants aged 18-85 years old in the National Health and Nutrition Examination Survey were recruited. The main exposures were the mineral intakes in the morning, afternoon and evening, which were categorized into quintiles, respectively. The main outcomes were mortality of cancer and all causes. RESULTS: During the 178,182 person-years of follow-up, 2680 deaths, including 601 deaths due to cancer, were documented. After adjusting for potential confounders, compared to the participants who were in the lowest quintile(quintile-1) of mineral intakes at dinner, the participants in the highest quintile intake(quintile-5) of dietary potassium, calcium and magnesium had lower mortality risks of cancer (HRpotassium = 0.72, 95% CI:0.55-0.94, P for trend = 0.023; HRcalcium = 0.74, 95% CI:0.57-0.98, P for trend = 0.05; HRmagnesium = 0.75, 95% CI:0.56-0.99, P for trend = 0.037) and all-cause (HRpotassium = 0.83, 95% CI:0.73-0.94, P for trend = 0.012; HRcalcium = 0.87, 95% CI:0.76-0.99, P for trend = 0.025; HRmagnesium = 0.85, 95% CI:0.74-0.97, P for trend = 0.011; HRcopper = 0.80, 95%CI: 0.68-0.94, P for trend = 0.012). Further, equivalently replacing 10% of dietary potassium, calcium and magnesium consumed in the morning with those in the evening were associated with lower mortality risk of cancer (HRpotassium = 0.94, 95%CI:0.91-0.97; HRcalcium = 0.95, 95%CI:0.92-0.98; HRmagnesium = 0.95, 95%CI: 0.92-0.98). CONCLUSIONS: This study demonstrated that the optimal intake time of potassium, calcium and magnesium for reducing the risk of cancer and all-cause mortality was in the evening.


Assuntos
Suplementos Nutricionais , Refeições , Minerais/administração & dosagem , Neoplasias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Feminino , História do Século XXI , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/história , Neoplasias/mortalidade , Inquéritos Nutricionais , Estado Nutricional , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos/epidemiologia
18.
BMC Cancer ; 21(1): 916, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388968

RESUMO

BACKGROUND: Acute Limb Ischemia (ALI) carries a high morbidity and mortality rate that is compounded in the cancer patient. Though it is a relatively uncommon event, it is of extremely high adverse impact and carries poor awareness among clinicians. METHODS: Retrospective review of electronic medical records was performed of cancer patients presenting with acute limb ischemia (ALI) to the tertiary cancer center's urgent care center or as inpatient between January 1, 2014 and January 1, 2020. RESULTS: Out of the 29 cancer patients with ALI, 12 (41%) died within 3 month and 9 (31%) patients died within 1 months of ALI diagnosis. 65% had long term adverse outcome after ALI - 31% with death in 1 month, 2 (7%) with an amputation, 5 (17%) with lifestyle-limiting claudication, and 3 (10%) with subsequent wound ulceration or gangrene. Patients not eligible for standard of care (12 patients, 41%) (RR 2.33 95% CI [1.27-4.27], p <  0.01) and heparin administration ≥6 h from presentation (19 patients, 65%) (RR 2.81 [1.07-7.38], p = 0.04) were at increased risk of adverse outcome. Atypical/confounded presentation of ALI (13 patients, 45%) (RR 1.84 95% CI [1.03-3.29], p = 0.04), pulse exam not documented (12 patients, 41.4%) (RR 1.95 [95% CI [1.14-3.32], p = 0.01), and patients with services other than a vascular specialist initially consulted (8 patients, 27.6%) (RR 1.91 95% CI [1.27-2.87], p <  0.01) were significant risk factors for heparin administered ≥6 h from presentation. CONCLUSIONS: ALI is devastating in cancer patients, with a high number presenting with atypical/confounded signs and symptoms which delays treatment. Heparin administered ≥6 h from presentation is associated with adverse outcome.


Assuntos
Extremidades/irrigação sanguínea , Extremidades/patologia , Isquemia/epidemiologia , Neoplasias/epidemiologia , Doença Aguda , Idoso , Feminino , Humanos , Isquemia/etiologia , Isquemia/mortalidade , Masculino , Pessoa de Meia-Idade , Morbidade , Mortalidade , Neoplasias/complicações , Neoplasias/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Centros de Atenção Terciária
19.
BMC Cancer ; 21(1): 963, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34452598

RESUMO

BACKGROUND: Receiving a cancer diagnosis may trigger immediate fatal non-cancer health outcomes in addition to dying of cancer itself. We aim to investigate the full pattern of non-cancer deaths in patients within a year of a cancer diagnosis. METHODS: Patients diagnosed with cancer between 1990 and 2016 were identified from the SEER program. Standardized mortality ratios (SMRs) were calculated to characterize the relative risks of non-cancer deaths compared with the general population. RESULTS: Among 7,366,229 patients, 241,575 non-cancer deaths (15.9%) were recorded in the first year following a cancer diagnosis. The relative risk of non-cancer deaths was 2.34-fold (95% confidence interval (CI): 2.33-2.35) that of the general population. The majority of non-cancer deaths were caused by cardiovascular diseases (21.8%), followed by infectious diseases (7.2%). Significant elevations in mortality risks were observed for nearly all non-cancer causes, particularly in infectious diseases (SMR: 5.08; 95% CI: 5.03-5.13). Patients with liver cancer (SMR: 12.29; 95% CI: 12.06-12.53) were at the highest risk of early non-cancer deaths. The risks of non-cancer deaths were highest within the first month after diagnosis, and decreased rapidly thereafter. CONCLUSIONS: Risks of non-cancer deaths vary by the types of causes and anatomic sites of cancer. Our data underscore the importance of close observation and early multidisciplinary care for noncancer conditions in patients who have recently received a cancer diagnosis.


Assuntos
Doenças Cardiovasculares/mortalidade , Causas de Morte , Doenças Transmissíveis/mortalidade , Neoplasias/diagnóstico , Neoplasias/mortalidade , Programa de SEER/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
20.
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
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