COVID-19 outcomes more severe among individuals with cancer
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Individuals with cancer and COVID-19 infection could be two to three times more likely to die than cancer-free individuals with the novel coronavirus, according to results of a multicenter study presented at the virtual American Association for Cancer Research Annual Meeting.
People with cancer also appeared considerably more likely to experience severe outcomes from COVID-19.
Outcomes varied based on cancer type and treatment. Those with hematologic malignancies, lung cancer or any type of metastatic cancer were more likely to experience severe events, and those who underwent cancer surgery were more likely to die or experience critical symptoms.
“Individualized treatment plans need to be developed based on the tumor types and stages of patients,” HongBing Cai, MD, PhD, director of the department of gynecologic oncology at Zhongnan Hospital of Wuhan University in Wuhan, China, said during a presentation.
Self-protective isolation, strict in-hospital infection control and appropriate online medical services are recommended for all patients with cancer during the pandemic, Cai said.
However, key questions remain unanswered. These include whether all patients with early-stage cancer should postpone their treatments, as well as whether immunotherapy may aggravate the severe outcomes experienced by patients with COVID-19 and cancer.
The results that Cai presented at AACR were published simultaneously in Cancer Discovery.
The death rate associated with COVID-19 in the general population is approximately 2% to 3%.
A prior study conducted in China showed people with cancer were at higher risk than cancer-free individuals for severe events after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19.
However, because of the small number of patients, researchers concluded age was the only risk factor for illness severity. The small sample size also limited the applicability of the findings to a broader population and made it difficult to compare patients based on cancer type or treatment, according to study background.
“Asia, Europe, and Northern American have the highest incidence of cancer in the world and, at the moment of the writing of this study, the SARS-CoV-2 virus is mainly spreading in these areas,” Cai and colleagues wrote. “[Although patients with COVID-19 and cancer] may share some epidemiological features with the general population with this disease, they may also have additional clinical characteristics. Therefore, we conducted this study on patients with cancer with coexisting COVID-19 disease to evaluate the potential effect of COVID-19 on patients with cancer.”
Cai and colleagues used patient information from 14 hospitals in Hubei province in China to describe the clinical characteristics and outcomes of 641 people (339 women) with confirmed COVID-19.
The cohort — enrolled from Jan. 1 to Feb. 24 — included 105 people with cancer, as well as 536 cancer-free individuals matched by age, hospital and hospitalization time.
The cancer and cancer-free groups were balanced with regard to median age (64 years vs. 63.5 years), sex and comorbidities, although individuals with cancer were more likely to have a smoking history (34.28% vs. 8.58%; P < .01).
Those with cancer appeared more likely to experience in-hospital COVID-19 infection (19% vs. 1.49%; P < .01). They also had a higher prevalence of chest distress (14.29% vs. 6.16%; P = .02); otherwise, symptoms were similar between groups.
The outcomes analysis showed people with cancer demonstrated significantly higher risk for death (OR = 2.34; 95% CI, 1.15-4.77), ICU admission (OR = 2.84; 95% CI, 1.59-5.08) and development of at least one severe or critical symptom (OR = 2.79; 95% CI, 1.74-4.41). They also were more likely to need invasive mechanical ventilation.
Multivariable logistic regression adjusted for age, sex, smoking and comorbidities — including diabetes, hypertension, chronic obstructive pulmonary disease — continued to show patients with cancer had increased risk for development of any severe symptoms (OR = 1.99; P < .01), ICU admission (OR = 3.13; P < .01) and utilization of invasive mechanical ventilation (OR = 2.71; P = .04); however, the observed increased risk for death (OR = 2.17) no longer remained statistically significant.
“The consistency of observed odds ratios between multivariable regression model and unadjusted calculation reassures the association between cancer and severe events even in the presence of other factors such as age differences,” researchers wrote.
Lung cancer (20.9%) was the most common malignancy among the cancer cohort, followed by gastrointestinal cancer (12.3%), breast cancer (10.4%), thyroid cancer (10.4%) and hematologic malignancies (8.5%).
When researchers evaluated risks for severe conditions based on cancer type, they determined patients with blood cancers — including leukemia, lymphoma and multiple myeloma — had a relatively high death rate (33.3%; n = 3 of 9), high ICU admission rate (44.4%; n = 4 of 9), high risks for severe or critical symptoms (66.6%; n = 6 of 9) and high chance of invasive mechanical ventilation utilization (22.2%; n = 2 of 9).
Patients with lung cancer exhibited the second-highest levels of risk. For this group, investigators calculated a death rate of 18.1% (n = 4 of 22) and an ICU admission rate of 27.2% (n = 6 of 22). Half of patients (50%; n = 11 of 22) developed any severe or critical symptoms, and nearly one in five (18.1%; n = 4 of 22) required invasive mechanical ventilation.
An analysis of outcomes by cancer stage showed patients with metastatic disease had greater risk for death (OR = 5.58; 95% CI, 1.71-18.23), ICU admission (OR = 6.59; 95% CI, 2.32-18.72), development of severe conditions (OR = 5.97; 95% CI, 2.24-15.91) and use of mechanical ventilation (OR = 55.42; 95% CI, 13.21-232.47) than cancer-free individuals.
Results showed no significant difference in any of those variables between patients with nonmetastatic cancer and those without cancer.
Researchers analyzed the types of treatments patients with cancer had received within 40 days prior to COVID-19 symptom onset. The most common was chemotherapy (14.15%), followed by radiotherapy (12.26%), surgery (7.62%), immunotherapy (5.71%) and targeted therapy (3.81%). All patients treated with immunotherapy received PD-1 inhibitors for lung cancer, and all patients treated with targeted therapy received EGFR tyrosine kinase inhibitors for lung cancer.
Results showed patients who received immunotherapy had high rates of death (33.3%; n = 2 of 6) and a high chance of developing critical symptoms (66.6%; n = 4 of 6).
Those who underwent surgery had higher rates of death (25%; n = 2 of 8), ICU admission (37.5%; n = 3 of 8), severe or critical symptoms (62.5%; n = 5 of 8) and use of invasive ventilation (25%; n = 2 of 8) than those who received any other treatments aside from immunotherapy.
Patients with cancer had significantly longer median hospital length of stay (27.01 days vs. 17.75 days; P < .01).
Researchers acknowledged their study was limited to a cohort from one province in China, as well as by the absence of some potentially informative data that were not collected during the initial stage of the outbreak.
“Altogether, these findings suggest that patients with cancer are a much more vulnerable population in the current COVID-19 outbreak,” Cai and colleagues wrote. “We have discovered additional risk factors — including cancer types, cancer stage and cancer treatments — may contribute to the severity. ... We believe the information and insights provided in this study will help improve our understanding of the effects of SARS-CoV-2 in patients with cancer.” – by Mark Leiser
Reference:
Cai H, et al. Patients with cancer appear more vulnerable to SARS-COV-2: A multi-center study during the COVID-19 outbreak. Presented at: AACR Annual Meeting; April 27-28, 2020 (virtual meeting).
Dai M, et al. Cancer Discov. 2020;doi: 10.1158/2159-8290.CD-20-0422.
Disclosures: The National Natural Science Foundation of China supported this study. Cai reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
Perspective
Back to TopMartin J. Edelman, MD, and Alexander Kutikov, MD, FACS
The paper by Dai and colleagues provides the largest report to date of the outcomes of patients with cancer who are infected with the COVID-19 virus. Not surprisingly, there is increased mortality among people with cancer who develop COVID-19 compared with age-matched, cancer-free controls. This increased risk is concentrated in patients with metastatic disease and hematologic malignancies — again, not surprising because these patients frequently are immune suppressed as a consequence of their disease and/or treatment.
Interestingly, there appears to be some increased risk associated with cancer surgery, which is consistent with another report from China that documented a 20% risk for perioperative death among patients found to have a SARS-CoV-2 infection postoperatively.
A weakness of this study is that it actually presents too much data in the sense that conclusions are drawn from very small numbers of patients. For example, the statement that there seems to be an increased risk for mortality among patients receiving immunotherapy is based upon data from six patients, and the suggestion that radiotherapy is not associated with mortality comes from an evaluation of 12 patients. These conclusions should be viewed with extreme skepticism and more likely result from the nature of the patients being treated than from the therapeutic approach.
The value of any clinical report lies in its utility for clinical practice and generation of future testable hypotheses. For now, we can say that advanced malignancy likely is a significant risk for mortality from COVID-19, and that every effort should be made to isolate these patients from those who are infected. The approach of creating COVID-negative facilities, as we have done at Fox Chase, is one such strategy. Future research needs to evaluate whether there are specific treatments that may cause particular problems for infected patients. This is being pursued through several registry studies, such as those led by ASCO, NCI and ad hoc consortia.
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