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      Cancer and COVID-19: what do we really know?

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          Abstract

          The COVID-19 outbreak challenges the medical community, including creating an unprecedented competition for health-care resources. The oncology community has suddenly needed to protect a population assumed to be vulnerable from a potentially fatal infection, without jeopardising cancer treatments. Dealing with shortages and lockdowns, the immediate reaction was ruled by the general principle of risk-to-benefit ratios.1, 2, 3, 4 In The Lancet, Lennard Lee and colleagues 5 and Nicole Kuderer and colleagues 6 separately present early investigations of the largest multicentre studies to date collecting data from patients with COVID-19 who have cancer. The UK Coronavirus Cancer Monitoring Project (UKCCMP) prospectively collected data on 800 patients (median age 69 years, 449 [56%] men, and 349 [44%] women) with active cancer presenting between March 18 and April 26, 2020, with COVID-19. Patients were followed up from the date of hospital admission until the patient outcomes were met (death or discharge), and 226 (28%) patients died. Although risk of death was significantly associated with age, male sex, and comorbidities, no interaction between anticancer treatments within 4 weeks before testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 morbidity or mortality was found. 5 The US COVID-19 and Cancer Consortium (CCC19) analysed prospectively collected data between March 17 and April 16, 2020, from 928 patients (median age 66 years, 468 [50%] men, and 459 [49%] women) with current or past history of cancer who had a presumptive diagnosis of COVID-19 (888 [96%]) or positive (SARS-CoV-2) test (40 [4%]). 6 The primary endpoint was all-cause mortality within 30 days of COVID-19 diagnosis. After a median follow-up of 21 days, 121 (13%) patients died and 242 (26%) were severely ill. Increased 30-day mortality was associated with age, male sex, smoking, comorbidities, Eastern Cooperative Oncology Group performance status, active cancer, region of residence, and receipt of azithromycin plus hydroxychloroquine, but not with anticancer therapy. The urgency with which data were obtained meant short follow-up times and high proportions of missing data. The mortality rate observed by the UKCCMP was probably due to the selection of patients who were admitted to hospital, underlying the need for data from patients without cancer from a matched population. Moreover, ending the observation after discharge does not capture the full disease trajectory. Similarly, for CCC19, by limiting observation to 30 days, and with follow-up data missing for 80 (61%) of 132 patients admitted to the intensive care unit (ICU), mortality rates are likely to increase. Subsequently, both studies are missing important data, without concise definitions of viral and cancer stage and status. The main lesson that we might deduce from both studies is that standard oncological care should be offered if feasible, including chemotherapy administration. We strongly encourage the continuation of these and other projects that will add pieces to the complex COVID-19 puzzle and the disease's interactions with cancer and cancer treatments. Will COVID-19 negatively affect active oncological treatments or, on the contrary, might anticancer therapy be protective against the cytokine storm caused by SARS-CoV-2?7, 8, 9 Are disease stage and status important for these interactions? After counting the number of SARS-CoV-2 infections, hospital, and ICU admissions, and measuring mortality and acquirement of immunity, we will start measuring excess mortality, and comparing expected mortality country-wise with that during the pandemic. However, this measurement is not so simple, as data show that the lockdown influences other types of mortality. Whether the shortages of non-COVID-19-related health-care provisions will affect oncological and cardiovascular mortality is too early to predict.10, 11 Finally, we must focus on improving future research, prospectively collecting all relevant data considering the specific local background, encouraging international collaboration, and setting a clear goal to stop, contain, control, delay, and reduce the effects of this virus at every opportunity, never forgetting that we will keep fighting together on behalf of our patients with cancer. © 2020 Mark Kostich/Getty Images 2020 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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          Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

          China and the rest of the world are experiencing an outbreak of a novel betacoronavirus known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). 1 By Feb 12, 2020, the rapid spread of the virus had caused 42 747 cases and 1017 deaths in China and cases have been reported in 25 countries, including the USA, Japan, and Spain. WHO has declared 2019 novel coronavirus disease (COVID-19), caused by SARS-CoV-2, a public health emergency of international concern. In contrast to severe acute respiratory system coronavirus and Middle East respiratory syndrome coronavirus, more deaths from COVID-19 have been caused by multiple organ dysfunction syndrome rather than respiratory failure, 2 which might be attributable to the widespread distribution of angiotensin converting enzyme 2—the functional receptor for SARS-CoV-2—in multiple organs.3, 4 Patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments, such as chemotherapy or surgery.5, 6, 7, 8 Therefore, these patients might be at increased risk of COVID-19 and have a poorer prognosis. On behalf of the National Clinical Research Center for Respiratory Disease, we worked together with the National Health Commission of the People's Republic of China to establish a prospective cohort to monitor COVID-19 cases throughout China. As of the data cutoff on Jan 31, 2020, we have collected and analysed 2007 cases from 575 hospitals (appendix pp 4–9 for a full list) in 31 provincial administrative regions. All cases were diagnosed with laboratory-confirmed COVID-19 acute respiratory disease and were admitted to hospital. We excluded 417 cases because of insufficient records of previous disease history. 18 (1%; 95% CI 0·61–1·65) of 1590 COVID-19 cases had a history of cancer, which seems to be higher than the incidence of cancer in the overall Chinese population (285·83 [0·29%] per 100 000 people, according to 2015 cancer epidemiology statistics 9 ). Detailed information about the 18 patients with cancer with COVID-19 is summarised in the appendix (p 1). Lung cancer was the most frequent type (five [28%] of 18 patients). Four (25%) of 16 patients (two of the 18 patients had unknown treatment status) with cancer with COVID-19 had received chemotherapy or surgery within the past month, and the other 12 (25%) patients were cancer survivors in routine follow-up after primary resection. Compared with patients without cancer, patients with cancer were older (mean age 63·1 years [SD 12·1] vs 48·7 years [16·2]), more likely to have a history of smoking (four [22%] of 18 patients vs 107 [7%] of 1572 patients), had more polypnea (eight [47%] of 17 patients vs 323 [23%] of 1377 patients; some data were missing on polypnea), and more severe baseline CT manifestation (17 [94%] of 18 patients vs 1113 [71%] of 1572 patients), but had no significant differences in sex, other baseline symptoms, other comorbidities, or baseline severity of x-ray (appendix p 2). Most importantly, patients with cancer were observed to have a higher risk of severe events (a composite endpoint defined as the percentage of patients being admitted to the intensive care unit requiring invasive ventilation, or death) compared with patients without cancer (seven [39%] of 18 patients vs 124 [8%] of 1572 patients; Fisher's exact p=0·0003). We observed similar results when the severe events were defined both by the above objective events and physician evaluation (nine [50%] of 18 patients vs 245 [16%] of 1572 patients; Fisher's exact p=0·0008). Moreover, patients who underwent chemotherapy or surgery in the past month had a numerically higher risk (three [75%] of four patients) of clinically severe events than did those not receiving chemotherapy or surgery (six [43%] of 14 patients; figure ). These odds were further confirmed by logistic regression (odds ratio [OR] 5·34, 95% CI 1·80–16·18; p=0·0026) after adjusting for other risk factors, including age, smoking history, and other comorbidities. Cancer history represented the highest risk for severe events (appendix p 3). Among patients with cancer, older age was the only risk factor for severe events (OR 1·43, 95% CI 0·97–2·12; p=0·072). Patients with lung cancer did not have a higher probability of severe events compared with patients with other cancer types (one [20%] of five patients with lung cancer vs eight [62%] of 13 patients with other types of cancer; p=0·294). Additionally, we used a Cox regression model to evaluate the time-dependent hazards of developing severe events, and found that patients with cancer deteriorated more rapidly than those without cancer (median time to severe events 13 days [IQR 6–15] vs 43 days [20–not reached]; p<0·0001; hazard ratio 3·56, 95% CI 1·65–7·69, after adjusting for age; figure). Figure Severe events in patients without cancer, cancer survivors, and patients with cancer (A) and risks of developing severe events for patients with cancer and patients without cancer (B) ICU=intensive care unit. In this study, we analysed the risk for severe COVID-19 in patients with cancer for the first time, to our knowledge; only by nationwide analysis can we follow up patients with rare but important comorbidities, such as cancer. We found that patients with cancer might have a higher risk of COVID-19 than individuals without cancer. Additionally, we showed that patients with cancer had poorer outcomes from COVID-19, providing a timely reminder to physicians that more intensive attention should be paid to patients with cancer, in case of rapid deterioration. Therefore, we propose three major strategies for patients with cancer in this COVID-19 crisis, and in future attacks of severe infectious diseases. First, an intentional postponing of adjuvant chemotherapy or elective surgery for stable cancer should be considered in endemic areas. Second, stronger personal protection provisions should be made for patients with cancer or cancer survivors. Third, more intensive surveillance or treatment should be considered when patients with cancer are infected with SARS-CoV-2, especially in older patients or those with other comorbidities.
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            Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study

            Summary 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. Findings Of 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. Funding American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.
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              COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study

              Summary Background Individuals with cancer, particularly those who are receiving systemic anticancer treatments, have been postulated to be at increased risk of mortality from COVID-19. This conjecture has considerable effect on the treatment of patients with cancer and data from large, multicentre studies to support this assumption are scarce because of the contingencies of the pandemic. We aimed to describe the clinical and demographic characteristics and COVID-19 outcomes in patients with cancer. Methods In this prospective observational study, all patients with active cancer and presenting to our network of cancer centres were eligible for enrolment into the UK Coronavirus Cancer Monitoring Project (UKCCMP). The UKCCMP is the first COVID-19 clinical registry that enables near real-time reports to frontline doctors about the effects of COVID-19 on patients with cancer. Eligible patients tested positive for severe acute respiratory syndrome coronavirus 2 on RT-PCR assay from a nose or throat swab. We excluded patients with a radiological or clinical diagnosis of COVID-19, without a positive RT-PCR test. The primary endpoint was all-cause mortality, or discharge from hospital, as assessed by the reporting sites during the patient hospital admission. Findings From March 18, to April 26, 2020, we analysed 800 patients with a diagnosis of cancer and symptomatic COVID-19. 412 (52%) patients had a mild COVID-19 disease course. 226 (28%) patients died and risk of death was significantly associated with advancing patient age (odds ratio 9·42 [95% CI 6·56–10·02]; p<0·0001), being male (1·67 [1·19–2·34]; p=0·003), and the presence of other comorbidities such as hypertension (1·95 [1·36–2·80]; p<0·001) and cardiovascular disease (2·32 [1·47–3·64]). 281 (35%) patients had received cytotoxic chemotherapy within 4 weeks before testing positive for COVID-19. After adjusting for age, gender, and comorbidities, chemotherapy in the past 4 weeks had no significant effect on mortality from COVID-19 disease, when compared with patients with cancer who had not received recent chemotherapy (1·18 [0·81–1·72]; p=0·380). We found no significant effect on mortality for patients with immunotherapy, hormonal therapy, targeted therapy, radiotherapy use within the past 4 weeks. Interpretation Mortality from COVID-19 in cancer patients appears to be principally driven by age, gender, and comorbidities. We are not able to identify evidence that cancer patients on cytotoxic chemotherapy or other anticancer treatment are at an increased risk of mortality from COVID-19 disease compared with those not on active treatment. Funding University of Birmingham, University of Oxford.
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                Author and article information

                Contributors
                Journal
                Lancet
                Lancet
                Lancet (London, England)
                Elsevier Ltd.
                0140-6736
                1474-547X
                29 May 2020
                29 May 2020
                Affiliations
                [a ]Department of Radiation Oncology, Iridium Kankernetwerk, Wilrijk-Antwerp, Belgium
                [b ]Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk-Antwerp 2610, Belgium
                [c ]Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy
                [d ]Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
                [e ]Breast Unit, Champalimaud Clinical Centre, Champalimaud Foundation, Lisbon, Portugal
                [f ]Nova Medical School, University of Lisbon, Lisbon, Portugal
                Article
                S0140-6736(20)31240-X
                10.1016/S0140-6736(20)31240-X
                7259910
                32479827
                cbff9f1b-8a7a-4160-9c7d-2089bdab063f
                © 2020 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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