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Thursday, March 19, 2020

COVID-19's Impact on Cancer Patients: Lessons From China & Italy

By Sarah LaCorte

As countries report new cases of COVID-19 and try to get ahead of the virus's reach, government and medical officials are looking to China and Italy for lessons on how to prepare. It is widely acknowledged that cancer patients are in the high-risk category because of their systemic immunosuppressive state. Although analysis is ongoing and data pools are small, there are early studies from scientists in China and Italy which could be useful to oncologists in the U.S. and beyond who are considering the next steps to protect their patients.

China

On February 14, 2020 The Lancet Oncology published a study that focused on COVID-19 infection in patients with cancer (doi: 10.1016/S1470-2045(20)30096-6). Wenhua Liang, MD, from the Department of Thoracic Oncology and Surgery, The First Affiliated Hospital of Guangzhou Medical University in China, and colleagues monitored 1,590 COVID-19 cases throughout China and selected 18 (1%) of those patients who had a history of cancer.

The authors noted that lung cancer was the most frequent type (five [28%] of 18 patients), but also studied patients with breast cancer (3 patients) and bladder cancer (2 patients).

Four (25%) of 16 patients (two of the 18 patients had unknown treatment status) with cancer with COVID-19 had received chemotherapy or surgery within the past month, and the other 12 (25%) patients were cancer survivors in routine follow-up after primary resection. The authors reported: "Four (25%) of 16 patients (two of the 18 patients had unknown treatment status) with cancer with COVID-19 had received chemotherapy or surgery within the past month, and the other 12 (25%) patients were cancer survivors in routine follow-up after primary resection."

Compared with patients without cancer, those with cancer were older (mean age 63·1 years [SD 12·1] vs. 48·7 years [16·2]), had a history of smoking (four [22%] of 18 patients vs. 107 [7%] of 1,572 patients), had more polypnea (eight [47%] of 17 patients vs. 323 [23%] of 1,377 patients; some data were missing on polypnea), and more severe baseline computed tomography manifestation (17 [94%] of 18 patients vs 1,113 [71%] of 1,572 patients). The authors reported no significant differences in sex, other baseline symptoms, comorbidities, or baseline severity of X-ray.

Patients with cancer were also more likely to have a higher risk of severe events (a composite endpoint defined as the percentage of patients being admitted to the intensive care unit requiring invasive ventilation, or death), with seven (39%) of 18 patients vs. 124 [8%] of 1,572 patients (P = .0003).

At greater risk of clinically severe results were patients who underwent chemotherapy or surgery in the past month (three [75%] of four patients), compared to those not receiving chemotherapy or surgery (six [43%] of 14 patients; figure),  after adjusting for other risk factors, including age, smoking history, and other comorbidities.

For severe events among patients with cancer, older age was the only risk factor (OR 1·43, 95% CI 0·97–2·12; p=0·072). Interestingly, authors noted that patients with lung cancer did not have a higher probability of severe events compared with patients with other cancer types (one [20%] of five patients with lung cancer vs. eight [62%] of 13 patients with other types of cancer; p=0·294). Using a Cox regression model to evaluate the time-dependent hazards of developing severe events, researchers found that patients with cancer deteriorated more rapidly than those without cancer (median time to severe events 13 days [IQR 6–15] vs. 43 days [20–not reached]; p<0·0001; hazard ratio 3·56, 95% CI 1·65–7·69, after adjusting for age).

The authors summarized that based on these results: "We found that patients with cancer might have a higher risk of COVID-19 than individuals without cancer. Additionally, we showed that patients with cancer had poorer outcomes from COVID-19, providing a timely reminder to physicians that more intensive attention should be paid to patients with cancer, in case of rapid deterioration."

Liang, et al, concluded the paper by offering three strategies for oncologists to consider for COVID-19, and future pandemics that may arise:

  1. In endemic areas, oncologists should consider an intentional postponing of adjuvant chemotherapy or elective surgery for stable cancer
  2. Stronger personal protection provisions should be made for patients with cancer or cancer survivors
  3. More intensive surveillance or treatment should be considered when patients with cancer are infected with SARS-CoV-2, especially in older patients or those with other comorbidities

Italy

Public health experts have said that Italy's experience with COVID-19 could be a sign of things to come in the U.S. While there have not yet been studies published specifically examining the correlation between cancer patients and COVID-19 impact, there have been studies on critical care utilization and hospital ICU preparedness. In this COVID-19 outbreak, the major risk for patients with cancer is the inability to receive necessary medical services (both in terms of getting to hospital and provision of normal medical care once there) because of the outbreak. Therefore, studies into hospital response in Italy may give insights into what could happen at U.S. hospitals in the coming weeks if efforts of social distancing and quarantine are not taken seriously.

A commentary published March 13, 2020, in JAMA offered insights into critical care utilization in Lombardy, where there have been 1,959 COVID-19-related deaths as of March 19, 2020 (doi:10.1001/jama.2020.4031). Study authors Giacomo Grasselli, MD, Antonio Pesenti, MD, and Maurizio Cecconi in Milan outlined the initial priorities and containment measures and forecasted ICU demand from February 21, when an emergency task force was formed by the Government of Lombardy and local health authorities to lead the response to the outbreak.

The authors noted that in Lombardy, the pre-crisis total ICU capacity was approximately 720 beds. To coordinate the critical care response to the outbreak, the COVID-19 Lombardy ICU Network identified two priorities: increase surge ICU capacity and implement measures for containment.

Authors said that because the disease was not contained earlier, and "based on the assumption that secondary transmission was already occurring… it was assumed that many new cases of COVID-19 would occur, possibly in the hundreds or thousands of individuals. Thus, assuming a 5 percent ICU admission rate, it would not have been feasible to allocate all critically ill patients to a single COVID-19 ICU. The decision was to cohort patients in 15 first-responder hub hospitals, chosen because they either had expertise in infectious disease or were part of the Venous-Venous ECMO Respiratory Failure Network (RESPIRA)."

Those identified hospitals were requested to: create cohort ICUs for COVID-19 patients; organize a triage area where patients could receive mechanical ventilation if necessary; establish local protocols for triage of patients with respiratory symptoms to quickly test them and assign them to the appropriate cohort; ensure adequate personal protective equipment for health personnel is available, considering organization of adequate supply and distribution, and personnel training; and report every positive or suspected critically ill COVID-19 patient to the regional coordinating center.

All nonurgent procedures were cancelled and another 200 ICU beds were made available and staffed in the following 10 days. In total, over the first 18 days, the network created 482 ICU beds ready for patients. By March 7, the total number of dedicated cohorted COVID-19 ICU beds was 482 (about 60% of the total preoutbreak ICU bed capacity), distributed among 55 hospitals.

However, authors noted their linear model predicted that 869 patients could require ICU admission by March 20, while their exponential model pushed that figure to 14,542.

The authors concluded their commentary with this advice: "This experience would suggest that only an ICU network can provide the initial immediate surge response to allow every patient in need for an ICU bed to receive one. Health care systems not organized in collaborative emergency networks should work toward one now."


Sarah LaCorte is associate editor.