Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness.Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. FindingsOf 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57-76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1•84, 95% CI 1•53-2•21), male sex (1•63, 1•07-2•48), smoking status (former smoker vs never smoked: 1•60, 1•03-2•47), number of comorbidities (two vs none: 4•50, 1•33-15•28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3•89, 2•11-7•18), active cancer (progressing vs remission: 5•20, 2•77-9•77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2•93, 1•79-4•79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0•24, 0•07-0•84) or the US-Midwest (0•50, 0•28-0•90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.

Mutations in the copper/zinc superoxide dismutase (SOD1) gene produce an animal model of familial amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. To test a new therapeutic strategy for ALS, we examined the effect of caspase inhibition in transgenic mice expressing mutant human SOD1 with a substitution of glycine to alanine in position 93 (mSOD1(G93A)). Intracerebroventricular administration of zVAD-fmk, a broad caspase inhibitor, delays disease onset and mortality. Moreover, zVAD-fmk inhibits caspase-1 activity as well as caspase-1 and caspase-3 mRNA up-regulation, providing evidence for a non-cell-autonomous pathway regulating caspase expression. Caspases play an instrumental role in neurodegeneration in transgenic mSOD1(G93A) mice, which suggests that caspase inhibition may have a protective role in ALS.

Extracutaneous melanomas are poorly characterized tumors that include ocular (OM), mucosal (MM) and leptomeningeal melanomas, often lacking standardized staging and treatment guidelines. We analyzed cases of cutaneous melanoma (CM, N 5 219,890), OM (N 5 7,069) and MM (N 5 2,755) of different anatomical origins, diagnosed between 1988 and 2010, recorded in the Surveillance Epidemiology and End Results (SEER) database. Relative survival was studied in patients grouped by summary stage classification (localized, regional or distant disease) and in multivariate models adjusting for varying distribution of baseline factors. Unlike in CM, the incidence rate in MM increased exponentially with age. Five-year relative survival was significantly worse for OM (78%) and for most mucosal sites (aggregate 34%, range 3-69%) compared with CM (89%). The differences between primary sites were particularly pronounced in localized disease, with a hazard ratio of 5.7 for OM, 4.3-9.0 for external genital or oral cavity MM and 19.8-90.4 for other mucosal locations. Melanomas of the pharynx, gastrointestinal, urinary tract and vagina had poor outcomes regardless of clinical stage. In contrast to CM, there was no evidence of improved survival in OM and MM during the study period. A substantial proportion of patients with operable OM or MM underwent radical organ resections (13-88% depending on site and stage) or perioperative radiotherapy (0-66%). In conclusion, extracutaneous melanomas have a markedly worse survival than CM and aggressive locoregional management appears to be insufficient for their control. Because of poor outcomes in MM, studies of systemic therapy are warranted regardless of the extent of disease at presentation.Extracutaneous melanomas (ECMs) are rare, aggressive cancers that encompass ocular, mucosal and leptomeningeal melanomas. Ocular (OM) and mucosal melanomas (MM) have incidence of less than 1 per 100,000 person-years, making accrual into prospective studies difficult. 1 Consequently, there are no evidence-based management guidelines for these subtypes. ECMs have been reported to occur in older patients, often at an advanced stage, and to have worse prognosis. 2,3 It is possible that mechanisms of carcinogenesis in ECM differ from those in cutaneous melanoma (CM), rendering currently used targeted therapies ineffective. 4 The objective of our study was to examine incidence, survival outcomes and locoregional treatment patterns of CM, OM and MM in the United States over the past two decades using a populationbased registry. Patients and Methods Data sourceThe Surveillance Epidemiology and End Results (SEER) program collects data on cancer incidence, treatment and outcomes from 18 United States (US) registries, currently representing 28% of the total US population. The registry mandates a 98% case ascertainment rate and conducts continuous quality assurance programs to secure completeness and consistency of coding. We extracted case listings and incidence rates from the November 2012 SEER submission files, coveri...

Among 2,186 U.S. adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. Although observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through inclusive prospective controlled trials. SIgnIfICAnCe: Evaluating the potential role of COVID-19 treatments in patients with cancer in a large observational study, there was no statistically significant 30-day all-cause mortality benefit with hydroxychloroquine or high-dose corticosteroids alone or in combination; remdesivir showed potential benefit. Treatment receipt reflects clinical decision-making and suggests disparities in medication access.