Cancer and COVID-19 – Authors' reply
Authors: Nicole M Kuderer, Elizabeth Wulff-Burchfield, Samuel M Rubinstein, Petros Grivas, Jeremy L Warner
Journal: The Lancet (2020)

We thank Dimitrios Moris and col­leagues and Alexandre Malek and colleagues for their insightful commentary about the CCC19 study findings.1Kuderer NM Choueiri TK Shah DP et al.Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study.Lancet. 2020; 395: 1907-1918Summary Full Text Full Text PDF PubMed Scopus (1276) Google Scholar We value the opportunity to further characterise mortality outcomes beyond our initial report.1Kuderer NM Choueiri TK Shah DP et al.Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study.Lancet. 2020; 395: 1907-1918Summary Full Text Full Text PDF PubMed Scopus (1276) Google Scholar With a median of 30 days (IQR 21–90) follow-up, as of Aug 21, 2020, 30-day all-cause mortality increased to 20% (154 of 754 patients who either died within 30 days or had at least 30 days of follow-up). Planned time-to-event analyses will refine these estimates. 121 (79%) deaths were attributed to respiratory failure (appendix). In our cohort,1Kuderer NM Choueiri TK Shah DP et al.Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study.Lancet. 2020; 395: 1907-1918Summary Full Text Full Text PDF PubMed Scopus (1276) Google Scholar the category of respiratory failure encompasses deaths from any respiratory failure syndrome. Although respiratory failure caused by cancer, its therapies, or other comorbidities could confound the cause of death attribution, this is unavoidable. Diagnostic procedures are challenging with COVID-19, autopsies are rare, and Vital Statistics Reporting Guidance specifically directs medical certifiers to list COVID-19 as the underlying cause of death, with the most immediate cause of death (eg, respiratory failure) listed first.2Centers for Disease Control and PreventionGuidance for certifying deaths due to coronavirus disease 2019 (COVID-19).https://www.cdc.gov/nchs/data/nvss/vsrg/vsrg03-508.pdfDate: April, 2020Date accessed: August 22, 2020Google Scholar Because this method might overestimate COVID-19-related deaths, we reported all-cause mortality. We share Moris and colleagues' concerns regarding the potential increase of cancer mortality caused by delays in cancer screening, diag­nosis, and care delivery because of severe acute respiratory syndrome coronavirus 2—a concern already borne out in some early analyses.3London JW Fazio-Eynullayeva E Palchuk MB Sankey P McNair C Effects of the COVID-19 pandemic on cancer-related patient encounters.JCO Clin Cancer Inform. 2020; 4: 657-665Crossref Scopus (210) Google Scholar The prospect of widening existing racial and socioeconomic disparities in cancer outcomes is of real concern and central to forthcoming analyses of our cohort. Malek and colleagues discuss import­ant limitations in applying the results to patients with haematological malignancies. The small number of patients with specific haematological malignancies in the CCC19 cohort required the broad categorisation with non-exclusive categories, resulting in apparent numerical discrepancies. Only 53 (26%) patients with haema­tological malig­nancies were in remission, limiting the conclusions in this subgroup (appendix). Subsequent studies have shown a high risk of severe COVID-19 outcomes for patients with haema­tological malignancies.4Williamson EJ Walker AJ Bhaskaran K et al.OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients.medRxiv. 2020; 584 (preprint).: 430-436Google Scholar, 5Passamonti F Cattaneo C Arcaini L et al.Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study.Lancet Haematol. 2020; 7: e737-e745Summary Full Text Full Text PDF PubMed Scopus (415) Google Scholar Despite a larger sample size, these analyses still do not have the power to identify, at the granular level, associations between the clinical status of the haematological malignancy, therapeutic modalities, and outcomes. The CCC19 cohort now includes more than 900 patients with haematological malignancies, and further analyses are underway. Regarding laboratory data, 449 (48%) patients presented with mild COVID-19, most of whom had no available base­line laboratory data. Additionally, our sample size only allowed the interroga­tion of the reported clinical variables (which were established a priori) in multivariable modelling. We agree that examining the independent prognostic value of laboratory parameters is vital; we will soon present a larger analysis addressing this. Although we firmly support robust methods and highlight limitations, it is imperative to deliver timely and valuable information to the community. NMK reports personal fees from G1 Therapeutics, Invitae, Beyond Spring, Spectrum, Bristol-Myers Squibb, Janssen, and Total Health. EW-B reports stock and other ownership interests by an immediate family member in Nektar, Immunomedics; and a consulting or advisory role in Astellas Scientific and Medical Affairs and Exelixis. PG reports consulting for AstraZeneca, Bayer, Bristol-Myers Squibb, Clovis Oncology, Driver, EMD Serono, Exelixis, Foundation Medicine, GlaxoSmithKline, Genentech, Genzyme, Heron Therapeutics, Janssen, Merck, Mirati Therapeutics, Pfizer, Roche, Seattle Genetics, and QED Therapeutics; participation in an educational programme for Bristol-Myers Squibb; and institutional research funding from AstraZeneca, Bavarian Nordic, Bayer, Bristol-Myers Squibb, Clovis Oncology, Debiopharm, Genentech, Immunomedics, Kure It Cancer Research, Merck, Mirati Therapeutics, Oncogenex, Pfizer, QED Therapeutics, and GlaxoSmithKline. JLW reports personal fees from Westat and International Business Machines Watson Health; and stock ownership in HemOnc.org. SMR declares no competing interests. Download .pdf (.14 MB) Help with pdf files Supplementary appendix Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort studyAmong 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. Full-Text PDF Cancer and COVID-19Nicole Kuderer and colleagues1 identified several independent prognostic factors to be conferring an increased risk of 30-day all-cause mortality: increased age, male sex, being a former smoker, multiple medical comorbidities, high Eastern Cooperative Oncology Group performance status score (≥2), and an active cancer. However, haematological malignancies, instead of increasing 30-day all-cause mor­tality, were associated with severe clinical outcomes, intensive care unit admissions, and meeting composite severe illness endpoints. Full-Text PDF Cancer and COVID-19We read, with great interest, about the outcomes in a cohort of patients with cancer and COVID-19 by Nicole Kuderer and colleagues.1 The authors showed that among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general and cancer-specific risk factors, with a mortality of 13·3%. Full-Text PDF