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.
The findings — published simultaneously in Cancer Discovery — also suggested the COVID-19 disease course may vary greatly based on a person’s 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 her presentation.
The data provide new insights into the effects of COVID-19 infection on individuals with cancer, but it is important to remember they emerged from a small retrospective case-control study conducted in a specific region in China, according to Karen L. Reckamp, MD, MS, director of the division of medical oncology and associate director for clinical research at Cedars-Sinai Cancer.
“We all have suspicions that patients with cancer might have more severe outcomes and may have higher mortality,” Reckamp — who was not involved in the study — told HemOnc Today. “These data, though intriguing and helpful, still need to be taken as somewhat hypothesis-generating. They are the best we have at the moment and they fit some of the a priori hypotheses we have, but by no means are they definitive.”
Consistent observations
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).
Individuals with cancer were significantly more likely to have a smoking history (34.28% vs. 8.58%; P < .01). Rates of hypertension (28.57% vs. 24.25%) and cardiovascular disease (11.43% vs. 7.28%) — key risk factors for COVID-19 severity — were numerically higher in the cancer population but differences did not reach statistical significance.
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 and 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.
Patients with cancer also had significantly longer median hospital length of stay (27.01 days vs. 17.75 days; P < .01).
“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.
This study is among the first that includes people with cancer and age-matched cancer-free individuals, Reckamp said. However, the population is still small and the results could be due at least in part to locally available treatments, she added.
“Considering our lack of information, these data probably are the best we have and they’re what we need to move forward with,” Reckamp told HemOnc Today. “This is certainly better than just a grouping of 20-some patients, which is what we had before, but the findings still can’t be extrapolated to a broad cancer population.
“Much of the data we are seeing are continuing to evolve,” she added. “The endpoints can change because patients are still in the hospital and undergoing treatment.”
Impact of cancer types, treatments
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.”
Reckamp, however, suggested the malignancy- and treatment-specific analyses be interpreted with caution.
“Once you start breaking results down into subgroups of cancer types or cancer treatment, you get very, very small numbers,” she told HemOnc
Today. “Their hypotheses about immunotherapy potentially being a risk factor was based on single-digit numbers.
“I primarily treat thoracic malignancies, and I am extremely interested to see the impact of immunotherapy on COVID-19 because of the potentially inflammatory response. Is it going to make outcomes worse or make them better?” she added. “I don’t think any of the data out there now really answer that question yet. There are plenty of patients receiving this therapy, so more data — based on larger populations — will continue to come out. Within a few months, even if we don’t have definitive data, hopefully we will have something that pushes the needle and helps us move forward.” – 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. Reckamp reports no 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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