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Monday, August 31, 2020

Which Cancer Patients are Most Susceptible to Severe Effects from COVID-19

It’s well known that COVID-19 patients with comorbidities have poorer outcomes than otherwise healthy patients. When it comes to cancer, however, the risk of death from COVID-19 also varies by tumor subtype. Research published in Lancet Oncology August 24th analyzed that risk by tumor subtype and patient demographics, looking at 1,044 patients from 60 medical centers throughout the UK.

“For the first time, we have a comprehensive analysis to determine who is more at risk of COVID-19,” Lennard Lee, DPhil, academic clinical lecturer, University of Oxford, said of the study.

As Lee and colleagues from the University of Oxford and the University of Birmingham noted in the paper, “Patients with hematological malignancies (leukemia, lymphoma, and myeloma) had a more severe COVID-19 trajectory compared with patients with solid organ tumors.” Those who recently had undergone chemotherapy faced a further, heightened risk of mortality.

Cancer patients with the least risk from COVID-19 were those with lung cancer and prostate cancer. A single variable analysis of the 1,044-patient UK Coronavirus Cancer Monitoring Project (UKCCMP) also showed a significantly lower risk of death for patients for breast cancer (0.53%) and female genital cancers (0.36%), but a significantly higher risk of death from COVID-19 among patients with prostate cancer (2.14%) and leukemia (2.3%).

As part of the study, researchers developed a chart comparing cancer types of patient with COVID-19 with the overall cancer incidence in the UK, as listed in the UK Office for National Statistics (ONS) database. It shows the average increased risk for those with leukemia was 2.82%, for myeloma 2.03%, and for lymphoma 1.63%.

When age and gender were considered, the fatality rate for those with COVID-19 and leukemia remained high, at 2.25%. Notably, under that multivariable analysis, prostate cancer was no longer associated with increased fatalities. However, breast and female genital cancers were no longer associated with reduced fatality rates. “This highlight(s) the effect of patient age and sex of case-fatality rate,” according to the researchers, co-led by Gary Middleton (University Hospitals Birmingham), Rachel Kerr (Oxford University Hospitals), and Lennard Lee (University of Oxford). 

“Using these new data, we are working fast to identify trends and correlations that will enable us to create a tiered risk assessment tool so we can more precisely define the risk to a given cancer patient and move away from a blanket ‘vulnerable’ policy for all cancer patients, in the event of a second wave of COVID-19,” Rachel Kerr, FRCP, study senior researcher, University of Oxford, said.

A review of the UKCCMP database showed that nearly 57% of the patients who had both COVID-19 and cancer were male, compared to slightly more than 51% of all cancer patients listed on the ONS database.

The study also confirmed that increased risk of morbidity and mortality for patients who are older, male (vs female), and have comorbidities, such as hypertension, chronic lung disease, diabetes, and cancer. The average age of all patients was 70. Of the 1,044 patients in the UKCCMP cohort, 319 died. For 295 of those (92.5%) the cause of death was listed as COVID-19.

While correlating COVID-19 risks for patients with specific cancer is scientifically interesting, it is the practical implication that offer the greatest value. As the study reported, “Patients with hematological malignancies were significantly more likely to require high flow oxygen, non-invasive ventilation, intensive care unit admission for ventilation and have a severe or critical disease course.” Nearly half (47.6%) had received chemotherapy within the prior four weeks, compared to nearly 30% (29.5%) of patients with other types of malignancies. Ddministration of chemotherapy was associated with a 2.09% increased risk of death during COVID-19-asociated hospitalization.

In discussing possible reasons for the linkages between recent chemotherapy for hematologic cancer and death among COVID-19 patients, the authors suggested the immunological disruption and intense myelosuppressive treatments for the cancer might allow and environment that enabled the SARS-CoV-2 virus to gain a foothold in the host, and then to progress and unleash a cytokine storm.

The overrepresentation of hematological malignancies in the UKCCMP database also may suggest increased susceptibility to viral infection, the researchers speculated. They also noted the overrepresentation of patients with “extranodal natural killer/T-cell lymphoma (ICD-10 code C86), Waldenström macroglobulinaemia (C88), and unspecified neoplasm of lymphoid, hematopoietic, and related tissue (C96). The reasons for this are unclear,” they wrote.

The researchers are careful to point out the difficulty of attributing a direct cause of death for patients with both cancer and COVID-19. Even scientific literature regarding COVID-19 and cancer shows disagreement. Some studies support this correlation and others report no correlation between chemotherapy and mortality cancer patients who have contracted COVID-19. The list of potential causes of such variations is long, and includes under- or over-representation of subgroups in the various studies, methodological differences, and early protection of some patient groups, as well as low admission rates to hospitals for patients in hospice care or nursing homes.

By correlating the type of cancer to morbidity and mortality risks, the researchers hope to enable oncologists to have better-informed risk-benefit discussions with their patients, especially since cancer management has changed during the pandemic to decrease patients’ risks of contracting COVID-19. “It is important to note that whilst cancer patients are more vulnerable, the chance of any given patient getting infected with COVID-19 remains low,” Lee emphasized.


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