Dutch Oncology COVID-19 consortium:Outcome of COVID-19 in patients with cancer in a nationwide cohort study

Aim of the study: Patients with cancer might have an increased risk for severe outcome of coronavirus disease 2019 (COVID-19). To identify risk factors associated with a worse outcome of COVID-19, a nationwide registry was developed for patients with cancer and COVID-19. Methods: This observational cohort study has been designed as a quality of care registry and is executed by the Dutch Oncology COVID-19 Consortium (DOCC), a nationwide collaboration of oncology physicians in the Netherlands. A questionnaire has been developed to collect pseudonymised patient data on patients' characteristics, cancer diagnosis and treatment. All patients with COVID-19 and a cancer diagnosis or treatment in the past 5 years are eligible. Results: Between March 27th and May 4th, 442 patients were registered. For this first analysis, 351 patients were included of whom 114 patients died. In multivariable analyses, age ≥65 years (p < 0.001), male gender (p = 0.035), prior or other malignancy (p = 0.045) and active diagnosis of haematological malignancy (p = 0.046) or lung cancer (p = 0.003) were independent risk factors for a fatal outcome of COVID-19. In a subgroup analysis of patients with active malignancy, the risk for a fatal outcome was mainly determined by tumour type (haematological malignancy or lung cancer) and age (≥65 years). Conclusion: The findings in this registry indicate that patients with a haematological malignancy or lung cancer have an increased risk of a worse outcome of COVID-19. During the ongoing COVID-19 pandemic, these vulnerable patients should avoid exposure to severe acute respiratory syndrome coronavirus 2, whereas treatment adjustments and prioritising vaccination, when available, should also be considered

Improvement in population-based survival of stage IV NSCLC due to increased use of chemotherapy

This study aimed to investigate which factors were associated with the administration of chemotherapy for patients with stage IV non-small cell lung cancer (NSCLC), and their relation to survival at a population-based level. All patients with NSCLC stage IV from 2001 to 2012 were identified in the Netherlands Cancer Registry in the Eindhoven area (n=5,428). Chemotherapy use and survival were evaluated by logistic and Cox regression analyses, respectively. The proportion of patients receiving chemotherapy increased from 30% in 2001 to 48% in 2012. Higher rates were found among younger patients [multivariable odds ratio (OR64_vs._75_years): 1.8 (95%CI 1.6-2.1)], high socioeconomic status [ORhigh_vs._low: 1.8 (95%CI 1.6-2.2)], no comorbidity [OR0_vs._2: 1.5 (95%CI 1.3-1.8)], diagnosed in recent years [OR2010-2012_vs._2001-2003: 2.0 (95%CI 1.6-2.3)] and adenocarcinoma [ORsquamous_vs._adenocarcinoma: 0.8 (95%CI 0.6-0.9)]. Having liver metastasis was associated with reduced odds (ORliver_vs._brain: 0.8 (95%CI 0.7-1.0). The variation between hospitals was large, up to OR 2.0 (95%CI 1.5-2.6). Median survival increased from 18 weeks in 2001-2003 to 21 weeks in 2010-2012 (log-rank p=0.007), and was 35 weeks in patients with and 10 weeks without chemotherapy. The multivariable hazard of death reduced significantly over time [HR2001-2003_vs._2010-2012: 1.1 (95%CI 1.0-1.2), HR2004-2005_vs._2010-2012: 1.2 (95%CI 1.1-1.3)] and only remained significant for 2004-2006 after additional adjustment for chemotherapy [final multivariable model, HR2004-2006_vs._2010-2012: 1.1 (95%CI 1.0-1.2)]. Besides, prognostic factors were having chemotherapy [final multivariable model: HR 0.4 (95%CI 0.4-0.4)], female sex [HRmale_vs._female: 1.1 (95%CI 1.0-1.1)], socioeconomic status [HRintermediate_and_high_vs._low both 0.9 (95%CI 0.9-1.0)], comorbidity [HRunknown_vs._2: 1.3 (95%CI 1.2-1.5)], histology [HRother_vs._adenocarcinoma: 1.1 (95%CI 1.1-1.2)], and location of metastasis [range: 1.2 (HRlymph_nodes_vs._brain) - 1.6 (HRliver_vs._brain)]. In conclusion, population-based survival increased due to increasing administration rates of chemotherapy. The administration of chemotherapy was affected by hospital of diagnosis and both patient and tumour characteristics. Identifying patients who benefit from chemotherapy should become a key issue. What's new? The addition of chemotherapy to supportive care can improve survival in patients with metastatic (stage IV) non-small cell lung cancer (NSCLC). But certain factors, such as socioeconomic status and patient age, may dictate whether patients with advanced disease use chemotherapy. This population-based study shows that chemotherapy use in stage IV NSCLC is affected by a variety of patient and tumor characteristics. Hospital of diagnosis is also a factor, with significant differences in chemotherapy use observed among hospitals. Increasing administration rates of chemotherapy over the period 2001 to 2012 resulted in an extension of median survival by three weeks

Comorbidity in Patients With Small-Cell Lung Cancer: Trends and Prognostic Impact

The present study is the first on the trends in comorbidity among patients with small-cell lung cancer. In particular, hypertension and pulmonary, cardiac, and vascular disease have become more common. Multimorbidity and cardiac and digestive disease have affected survival in those with limited-stage disease, and cardiac and cerebrovascular disease have decreased the survival of patients with extensive disease. These data are relevant for treatment decisions and patient communication in daily clinical practice. Introduction: We evaluated the trends in the prevalence of comorbidity and its prognostic impact in a cohort of unselected patients with small-cell lung cancer (SCLC). Patients and Methods: All patients (n = 4142) diagnosed with SCLC from 1995 to 2012 were identified from the population-based Netherlands Cancer Registry in the Eindhoven region. Results: The prevalence of comorbidity increased from 55% in 1995 to 1998 to 76% in 2011 to 2012 and multimorbidity (ie, >= 2 concomitant diseases) from 23% to 51%. The prevalence of a comorbidity increased with age. Among the men, hypertension, cardiac disease, and diabetes, in particular, became more common (increased from 11% to 35%, from 19% to 36%, and from 7% to 18%, respectively). In the women, the rate of pulmonary disease, hypertension, and cardiac disease increased the most (increased from 18% to 30%, from 12% to 28%, and from 11% to 24%, respectively). Multimorbidity was associated with a slightly increased hazard of death, independent of treatment in those with limited-stage SCLC (hazard ratio [HR] for >= 2 comorbidities vs. no comorbidities, 1.2; 95% confidence interval [CI], 1.0-1.4). The prognostic effects of multimorbidity resulted from treatment in those with extensive-stage SCLC (HR for >= 2 comorbidities vs. no comorbidities, final model, 1.2; 95% CI, 1.0-1.2). The prognostic impact of the specific comorbidities varied, with digestive disease reducing the hazard and cardiac disease increasing the hazard in those with limited-stage SCLC (HR for digestive disease vs. no digestive disease, 0.7 [95% CI, 0.5-0.9], and HR for cardiac vs. no cardiac disease, 1.2 [95% CI, 1.0-1.3]). Also, cardiac and cerebrovascular disease increased the hazard in those with extensive-stage SCLC (HR 1.2 [95% CI, 1.0-1.3] and HR 1.3 [95% CI, 1.1-1.6], respectively). Conclusion: Comorbidity among patients with SCLC is very common and has been increasing. Multimorbidity was associated with a slightly increased hazard of death in those with limited-stage SCLC, independent of treatment. However, the prognostic effects in those with advanced-stage SCLC resulted from treatment. Digestive disease favorably affected survival and cardiac disease negatively affected the prognosis for those with limited-stage SCLC, and cardiac and cerebrovascular diseases had a negative prognostic effect for those with extensive-stage SCLC. With the burden of comorbidities in patients with SCLC increasing, more attention to individualized treatment approaches is needed. (C) 2015 Elsevier Inc. All rights reserved

Chloroquine could be used for the treatment of filoviral infections and other viral infections that emerge or emerged from viruses requiring an acidic pH for infectivity

Viruses from the Filoviridae family, as many other virus families, require an acidic pH for successful infection and are therefore susceptible to the actions of 4-aminoquinolines, such as chloroquine. Although the mechanisms of action of chloroquine clearly indicate that it might inhibit filoviral infections, several clinical trials that attempted to use chloroquine in the treatment of other acute viral infections - including dengue and influenza A and B - caused by low pH-dependent viruses, have reported that chloroquine had no clinical efficacy, and these results demoted chloroquine from the potential treatments for other virus families requiring low pH for infectivity. The present review is aimed at investigating whether chloroquine could combat the present Ebola virus epidemic, and also at exploring the main reasons for the reported lack of efficacy. Literature was sourced from PubMed, Scopus, Google Scholar, reference list of articles and textbooks - Fields Virology (Volumes 1and 2), the cytokine handbook, Pharmacology in Medicine: Principles and Practice, and hydroxychloroquine and chloroquine retinopathy. The present analysis concludes that (1) chloroquine might find a place in the treatment of Ebola, either as a monotherapy or in combination therapies; (2) the ineffectiveness of chloroquine, or its analogue, hydroxychloroquine, at treating infections from low pH-dependent viruses is a result of the failure to attain and sustain a steady state concentration sufficient to increase and keep the pH of the acidic organelles to approximately neutral levels; (3) to successfully treat filoviral infections - or other viral infections that emerge or emerged from low pH-dependent viruses - a steady state chloroquine plasma concentration of at least 1 µg/mL(~3.125 μM/L) or a whole blood concentration of 16 μM/L must be achieved and be sustained until the patients' viraemia becomes undetectable. These concentrations, however, do not rule out the efficacy of other, higher, steady state concentrations - although such concentrations might be accompanied by severe adverse effects or toxicities. The feasibility of the conclusion in the preceding texts has recently been supported by a subsequent study that shows that amodiaquine, a derivative of CQ, is able to protect humans infected with Ebola from death