Cancer patients diagnosed with COVID-19 infection: a multicenter retrospective cohort of nine Brazilian cancer centers

The infection caused by the novel coronavirus-19 (COVID-19) has emerged in December 2019 and was declared pandemic in March 2020.^[ 1 ^] The clinical presentation ranges between asymptomatic and acute respiratory syndrome and death.^[ 2 ^] Because of their systemic inflammatory status and high prevalence of associated comorbidities, cancer patients are more susceptible to infections regardless of the natural course of disease and anticancer treatments. Moreover, the heterogeneity of this population makes it difficult to identify which are the most prevalent and the important risk factors associated with outcomes during COVID-19 infection.^[ 3 ^] Early reports from China showed that comorbidities such as hypertension, diabetes, and obesity were risk factors for COVID-19 mortality. Several clinical trials have also confirmed that cancer patients are at risk for worse outcomes as well. Among patients with cancer, those with higher ECOG PS, lung or hematological neoplasms and those with recent systemic treatment, appear to have higher risk of mortality. Smoking status, number of comorbidities, and older age are also risk factors.^[ 4 5 6 7 8 9 ^] However, it is noticed that many characteristics vary between different cohorts, therefore each cancer center should better study its population.

To date, few data exist regarding COVID-19 infection in patients with cancer in South America and the associations between outcomes and risk factors should be described. This is a retrospective and multicenter analysis of cancer patients, treated in nine private oncology centers in Brazil, describing association between demographic characteristics, risk factors, and clinical outcomes.

At the data of cutoff we had 130 oncologic patients eligible for analysis. Five patients who were transferred to hospices and 17 patients without available outcomes were also excluded from the final analysis. Six patients with negative RT-PCR for SARS-CoV-2 were not included. Finally, association between risk factor and mortality was performed in 85 patients, which corresponded to hospitalized patients (Figure 1).

In this multicenter retrospective study involving cancer patients with COVID-19 infection, we found higher mortality among patients in ICU compared with those treated on the ward. The median admission time in ICU was 12 days, which was the same length time of all admission period for less serious infection. Patients in end-of-life care at the palliative unit, ICU admission, and mechanical ventilation were the most important hospitalization variables to increase mortality. The presence of coronary disease was the most important patient comorbidity to increase the risk of death. Regarding cancer characteristics, although primary lung cancer increased the risk of death, patients with metastatic disease in the lungs had an even worse outcome. The mortality rate of cancer inpatients was our primary endpoint, and it was slightly higher than other international reports, but it was similar to that observed in Brazilian cohorts.

A trial developed by the Brazilian National Cancer Institute, which included 181 hospitalized cancer patients, reported a mortality rate of 33.1%. Patients with older age, lung or bone metastasis, and two or more metastatic sites had higher risk.^[ 11 ^] The rate of patients admitted to the ICU in this cohort was 17.1%, compared to 44.7% in our study. This data could be partially explained by the different populations, including the distinct severity of the disease. Data from a single-center Brazilian hospital in São Paulo, presented at the ESMO (European Society of Medical Oncology) 2020 Congress evaluated a cohort of cancer patients diagnosed with COVID-19. Overall mortality rate was 40.95%. Of the 105 patients, 69.52% required hospitalization and 33.3% were referred to the ICU.^[ 12 ^] More recently, a broader study conducted in private practices in Brazil showed a mortality rate of 16.7% among 198 cancer patients. However, it is a cohort of patients with better prognosis, including 29% of patients with breast cancer, 35% undergoing curative treatment, and 55% of outpatients.^[ 13 ^]

Early Chinese data, in an unselected population, showed a mortality rate by 30% for patients with severe disease and more than 80% for those admitted to the ICU. Median duration of hospitalization was 12 days, also similar to our data.^[ 8 ^] Importantly, our hospitals provide cancer care at the tertiary level, with advanced diagnostic and treatment support, which can increase incidence of serious cases.

There is limited data on the incidence of COVID-19 in cancer patients. The Department of Radiation and Medical Oncology of Zhongnan Hospital of Wuhan University have published a cohort of 1,524 cancer patients, of which 12 (0.79%) had COVID-19, versus 0.37% of the general population of Wuhan during the same period of time (OR 2.31, 95% CI: 1.89-3.02).^[ 14 ^] Approximately 1,630 cancer patients are treated each month at our cancer centers. Considering that almost 8,150 patients are treated in the nine cancer centers during the study inclusion period, we can estimate that nearly 1.04% of our population had an indication for hospitalization due to COVID-19 complications during this pandemic period. The Chinese retrospective trial appeared to have a cohort of patients with a worse prognosis, 58.3% of whom had lung cancer. Other Chinese studies also shows a higher prevalence of lung cancer and a propensity to worse outcomes, particularly in patients who underwent chemotherapy in the last 14 days and those with older age.^[ 15 16 ^] Another Chinese case-control study of 232 cancer patients, conducted in nine hospitals in Wuhan, showed a higher risk of complications compared to patients without cancer. Those with ECOG>2, advanced disease, recent antitumor treatment, and elevated pro-inflammatory peptides are at increased risk for severe disease.^[ 17 ^] Unlike our study, hypertension and coronary heart disease did not lead to a higher risk and the impact of lung cancer or lung metastases was not reported.

During the course of the pandemic, retrospective trials were also developed by many countries. A consort of more than 120 centers from US, Canada and Spain have published data on cancer patients and COVID-19. Of 928 patients, the most common types of cancer were breast (21%) and prostate (16%), however, it also included outpatients; therefore, it had a mortality rate of 13%, lower than that observed in our study. Among the patients who required hospitalization, the mortality rate within 30 days of inclusion was 23%. This rate may have been lower due to distinct population or shorter followup. Among risk factors for mortality, male gender, smoking status, ECOG, and number of comorbidities were responsible for worse outcomes.^[ 9 ^]

A multicenter, prospective study involving data collection from patients with thoracic malignancies included 200 patients, of whom 66 (33%) died, whether hospitalized or at home. The risk factors were similar, including age and smoking status.^[ 4 ^] In this study, it was also noticed that patients with thoracic tumors had a lower rate of admission to the ICU, and suggest that the indication of intensive care should be better discussed in view of therapeutic advances. This was not a challenge in our cohort as none of the patients not referred to the ICU had lung cancer, two of whom had no active cancer, but advanced age. The higher mortality rate for patients in palliative care, in general with more advanced tumors and older age, was also observed in other cohorts.^[ 4 9 ^] A retrospective cohort from New York showed that, among 218 patients with a malignant diagnosis, the fatality rate was 28%, particularly higher in lung and hematological malignancies.^[ 18 ^] A single-center study from the UK Cancer Center reached a mortality rate of 22%, however, 82% of the population had mild/moderate COVID-19.^[ 19 ^]

By using a multiple linear regression model, it was possible to analyze the relationship between length of stay and clinical variables. However, only variables related to the severity of COVID-19, such as ICU admission and tracheostomy, were associated with prolonged hospitalization.

The main strengths of our study is that it is a multicenter trial, which explores different levels of hospital care. The main limitations are the retrospective design, leading to missing data, and the absence of a comparator group of patients without cancer. In addition, there is a selection bias, represented by the low rate of outpatients, not reflecting the real incidence of COVID-19 in patients treated in our cancer centers.

Several studies involving the development of vaccines against COVID-19 infection are underway. As cancer patients are generally not included in these trials, many questions may arise regarding the risks and effectiveness of this type of prevention for cancer patients. Whereas more than 17 million patients are diagnosed with cancer every year worldwide, we must always consider cancer as pandemic and assess the possibility of including such patients in prospective trials. Currently, we also know that COVID-19 pneumonia can lead to chronic symptoms, many of which coincide with symptoms of cancer or its treatment. Longer follow-up may be necessary to better clarify the real impact of the pandemic on this population.

Despite the high mortality of patients hospitalized with COVID-19, our data are compatible with other Brazilian cohorts and with other risk groups. Cancer patients must be carefully monitored in pandemic periods of infectious diseases.