COVID-19 and cancer

How oncology providers can protect ‘the most vulnerable’ during pandemic

As the COVID-19 pandemic began to spread across the United States, the field of oncology took unprecedented measures to protect patients and providers.

Those efforts are expected to intensify, even if federal and state restrictions intended to flatten the curve of new infections from the novel coronavirus prove successful.

“Oncologists should be ... terribly attentive to [COVID-19] because patients with any type of advanced cancer are going to be at much higher risk for bad outcomes,” Paul A. Volberding, MD, an oncologist by training who serves as professor of medicine and director of the AIDS Research Institute at University of California, San Francisco, told HemOnc Today. “The oncology community should be asking themselves ... if they are doing everything they possibly can.

“I am not an alarmist by nature, but we cannot look at what [has happened] in Italy and not be alarmed,” added Volberding, Chief Medical Editor of Infectious Disease News, a Healio publication. “The chance of a rapid increase in the burden on the U.S. health care system from this virus is very real.”

HemOnc Today spoke with several oncology and infectious disease experts about the potential impact of the pandemic on individuals with cancer, how treatment may be affected, key factors providers should consider when caring for patients with concerning symptoms, and strategies clinicians can employ to ensure their own wellness during a time of extreme stress and uncertainty.

Potentially severe consequences

When the number of COVID-19 cases in the United States began to mount in mid-March, incidence among individuals with cancer remained relatively low.

That mirrored trends observed with other respiratory viruses, according to Steven Pergam, MD, MPH, medical director of the infection prevention program at Seattle Cancer Care Alliance.

“These viruses often start in the general population,” Pergam, also a clinical and infectious disease researcher at Fred Hutchinson Cancer Research Center, told HemOnc Today. “Patients undergoing active cancer treatment tend to spend more time at home and less time out in the community, so it’s not uncommon for them to get it a little later. ... [However], we expect — and must prepare for — cases to start coming in more frequently.”

It remains undetermined whether individuals with cancer are more likely to contract COVID-19.

“The real risk is the consequences for someone with a compromised immune system who does contract it, as they could be much more severe than they would be for an average healthy person,” Andrew M. Evens, DO, MSc, associate director for clinical services and director of the lymphoma program at Rutgers Cancer Institute, as well as medical director of the oncology service line at RWJBarnabas Health, told HemOnc Today.

Concerns are greatest for patients with hematologic malignancies — specifically certain leukemias or lymphomas — as well as bone marrow transplant recipients and people actively undergoing chemotherapy, as they have the greatest immune deficits.

The magnitude of elevated risk remains unclear, however.

Preliminary data from Chinese Center for Disease Control and Prevention showed a 5.6% mortality rate among people with cancer who contracted COVID-19, compared with 0.9% for those who had no underlying conditions.

Liang and colleagues analyzed data of 2,007 patients in China hospitalized with COVID-19. Their findings appeared in February in The Lancet.

Incidence of severe events — a composite endpoint defined as death or ICU admission requiring invasive ventilation — was significantly higher among individuals with a cancer history than those without (39% vs. 8%; P = .0003).

Source: Seattle Cancer Care Alliance.

However, only 18 patients analyzed had a cancer history; some had active disease and others were longer-term survivors. Heterogeneity of the cohort, the small sample size and the fact that some of those with a cancer history also had high blood pressure, COPD or diabetes — all of which increase infection susceptibility — make the findings difficult to interpret, Pergam said.

“The message that’s very clear is that those who have comorbidities are at an increased risk from this infection,” Pergam said. “[However], we have a lot of concerns both from this paper and another one that suggest there are increased rates of major complications [among individuals with cancer], as many are double and triple hits. They not only have cancer but respiratory, cardiac or other organ dysfunction, as well.”

Despite limited data about the potential impact, oncologists with whom HemOnc Today spoke said they understand the importance of preparing as much as possible for a potential crisis unlike any other they have faced.

“The rate of spread and the magnitude of how much this is affecting us has been more significant than anybody could have imagined,” Che-Kai Tsao, MD, medical director of Ruttenberg Treatment Center at The Tisch Cancer Institute at Mount Sinai, told HemOnc Today. “As a medical oncologist, I take care of a population that is among the most vulnerable. My main concern has to be: How do we best protect our patients at a time when there is so much uncertainty?”

Individualized assessments

Many cancer centers have implemented triage and assessment strategies for patients who come to the clinic and exhibit concerning symptoms.

However, provider-patient communication can reduce the likelihood that a person who poses a threat to others walks through the door, according to Tina Tan, MD, professor of pediatrics at Northwestern University Feinberg School of Medicine and an infectious disease attending at Ann and Robert H. Lurie Children’s Hospital of Chicago.

“Practitioners need to have some type of phone line or internet set-up so patients who are concerned about any symptoms they have can call and get some direction about what to do, including whether they should go to the clinic or to the emergency room,” Tan said.

Not every person needs to seek help from a health care provider, and clear communication between clinicians and patients can convey that message, Pergam said.

Those with mild symptoms — such as a slight cough or runny nose — should be urged to stay home. They should check their temperature twice a day, and notify their physician if their symptoms worsen, if they feel winded during routine movement around their house or if they notice other changes in their physiology, Pergam said.

Those with more serious active symptoms should be urged to call the cancer center before arriving so they can be masked and assessed before entering the clinical space, Pergam said.

In those cases, thoughtful evaluations should be performed, Tsao said.

“We have to think carefully about the best way to treat our patients so we don’t unnecessarily increase their exposure,” he said. “For example, not all patients with fever have to be sent to the ED for evaluation.”

Patients with neutropenia or other high-risk features who develop a fever should be admitted if possible. However, those who are clinically stable and have no other symptoms that suggest an immediate need for medical attention may be able to monitor themselves at home, according to Tsao.

“It really depends on the other risk factors,” Tsao said. “I’d be more concerned about somebody with advanced disease who is very symptomatic than someone who is 2 years out from surgery and chemotherapy who is disease free and otherwise in good health.

“In times like this ... it is important to take a step back, evaluate the risks and benefits, and ask ourselves, ‘Can this person be observed at home so they can avoid exposure to others?’” Tsao said.

Individualized assessments are important for two other reasons, Pergam said.

“Right now, the majority of people who are presenting with symptoms do not have COVID-19. They have another respiratory virus,” he said. “That may change over time but, in the short term, there are still flu, respiratory syncytial virus, and other respiratory viruses and infections. We have to make sure we are careful and don’t miss those other possibilities.”

Also, patients with cancer who do have COVID-19 may present with different symptoms than a cancer-free individual.

“Patients with oncologic illness normally don’t present with respiratory viruses in a similar fashion,” Pergam said. “For example, not all oncology patients will present with fever, which is a common presentation for most normal hosts.”

Sore throat is a common early symptom among patients with weakened immune systems, Pergam said. Data from China also suggested about 10% of patients with confirmed COVID-19 presented with diarrhea before they developed respiratory symptoms.

“It is very important to remember there are alternate ways these patients can present,” Pergam said.

‘Low threshold for testing’

It is unlikely that effective treatments for COVID-19 will be available in time to contribute to the initial national response to the pandemic, Volberding said.

He speculated a vaccine may not be available for at least another year.

“Despite what some may have heard, vaccine development cannot be done too quickly,” he said. “There has to be development of a candidate vaccine and we have to do safety testing. Some vaccines can actually make infections worse, which would be a true disaster.”

Consequently, testing plays a key role in virus control.

In mid-March, Infectious Disease Society of America released recommendations for COVID-19 testing prioritization. The four-tiered guidance categorized the following individuals as Tier 1:

• Critically ill patients receiving ICU-level care with unexplained viral pneumonia or respiratory failure, regardless of travel history or close contact with suspected or confirmed COVID-19;
• Any person — including health care workers — with fever or signs/symptoms of a lower respiratory tract illness who had close contact with a laboratory-confirmed COVID-19 patient within 14 days of symptom onset;
• Any person — including health care workers — with fever or signs/symptoms of a lower respiratory tract illness and a history of travel within 14 days of symptom onset to geographic regions where sustained community transmission has been identified;
• Individuals with fever or signs/symptoms of a lower respiratory tract illness who also are immunosuppressed, elderly or have underlying chronic health conditions; and
• Individuals with fever or signs/symptoms of a lower respiratory tract illness who are critical to pandemic response, including health care workers, public health officials and other essential leaders.

The recommendations characterize hospitalized non-ICU patients and long-term care residents with unexplained fever and signs or symptoms of a lower respiratory tract illness as Tier 2, noting the number of COVID-19 cases in the community should be considered.

“Many of the patients we take care of are included in the higher tiers and should be tested if they have signs and symptoms,” Samuel M. Silver, MD, PhD, MACP, FRCP, professor of internal medicine and assistant dean for research at University of Michigan Medical School, and a HemOnc Today Editorial Board Member, said during an Oncology Business Review-conducted webinar intended to help clinics prepare for COVID-19 infections.

Members of the cancer care team should be attentive to — and ask their patients about — symptoms such as fever, shortness of breath, dry cough and fatigue. COVID-19 also often causes lymphopenia at presentation.

“If they have any of these symptoms, there should be an incredibly low threshold for testing,” Volberding said.

Limited availability of COVID-19 testing through mid-March made it difficult to accurately assess the scope of the virus. It also allowed people who wanted to deny the seriousness of the outbreak to point to a low number of cases, when actual numbers were much larger, Volberding said.

Pergam characterized the initial lack of sufficient testing in the United States as “a real weakness in our system.”

“I’ve heard people say, ‘If we don’t have a treatment, why does it matter if I get tested?’” Pergam said. “I’d much rather know who has COVID-19 so we can keep them in isolation as much as possible. If the test shows they don’t have coronavirus but rather rhinovirus, the flu or something else, you can focus on it differently.”

Although COVID-19 testing has increased the past few weeks, it still may not be widely available in all regions or facilities. That reality supports the importance of provider-patient communication.

Cancer centers, hospitals and other medical practices can rely on local media outlets and their own social media channels to let people in their area know whether they offer testing.

“Patients who develop symptoms and get nervous may show up in your clinic unexpectedly or in the ER to get tested, and that is dangerous,” Pergam said. “If you don’t have testing, tell people where it is available. If it is not routinely available anywhere in your community, tell them that, too. It is extremely important for patients to know they should stay home because, even if they go to the ER, they will not get tested.”

Treatment decisions

The COVID-19 pandemic has transformed the way many health care providers care for their patients.

In most subspecialties, nonessential appointments and elective surgeries have been rescheduled to minimize patients’ exposure to health care settings and reduce congestion in the clinical space.

In oncology, those decisions require careful consideration, Evens said.

“We might have discussions on truly elective therapies, but there aren’t many circumstances like that, so this has to be done very carefully and strategically,” Evens said. “The risk for exposure obviously is higher coming into the clinic than just staying home, but you have to counterbalance this with the need for treatment — especially if a person has a life-threatening cancer.”

David I. Quinn, MD, associate professor of medicine and section head of genitourinary oncology at Keck School of Medicine of USC, echoed Evens’ sentiment.

“We get questions from patients about whether they should come for their appointments. ... The answer is generally ‘yes,’” Quinn told HemOnc Today. “This is a pandemic, and we are going to have to try to cut down exposure where we can, but our patients are vulnerable and need to be looked after. We have to find a balance.”

In a paper published in March in JNCCN — Journal of National Comprehensive Cancer Network, Masumi Ueda, MD, MA, and colleagues at Seattle Cancer Care Alliance urged cancer care teams to consider several specific measures to strike that balance.

Among the options they outlined: deferring second opinion consultations, expanding hours of general hospital operations to minimize unnecessary use of ED resources, limiting the number of care team members who enter patients’ rooms, considering lower thresholds for blood transfusions, having upfront end-of-life or palliative conversations with individuals with cancer who may become infected with COVID-19, and transitioning some procedures from inpatient to outpatient settings.

Ueda and colleagues recommended patients with solid tumors continue adjuvant therapy with curative intent, despite the risk for COVID-19 infection during treatment.

Treatment delays may lead to worsening performance status for patients with metastatic disease, resulting in “loss of the window to treat,” Ueda and colleagues wrote. The effect of these delays on admission for symptom palliation — which requires inpatient resources — should be considered.

Surgical intervention should be prioritized when possible to preserve bed capacity and personal protective equipment.

“For example, several months of endocrine therapy and delay in surgery may be appropriate for some patients with early-stage hormone receptor-positive breast cancer,” Ueda and colleagues wrote. “Surgeon-to-patient phone calls have optimized shared decision-making to delay surgery.”

Cellular immunotherapies and stem cell transplantation — which provide curative treatments for many patients with aggressive hematologic malignancies — often cannot be delayed.

“To what extent we can prioritize the therapies given to individual patients to reduce the burden on our system under stress is an ongoing challenge,” Ueda and colleagues wrote. “Cancer centers should make it their mission to do all possible to continue to keep their doors open to provide care, unless there comes a time when staff and patient safety are no longer tenable.”

Debra Patt, MD, MPH, MBA, executive vice president of Texas Oncology and a panelist in Oncology Business Review’s webinar, explained how her team embraced telemedicine and delayed routine follow-up visits to reduce clinic volume and ensure appropriate spacing between patients.

“When I took off 3-month, 6-month and 12-month visits, I decreased my clinic volume by about 70%,” Patt said. “We don’t want a packed waiting room or infusion center right now because of the risks associated with people being in close proximity. If you can simply decrease the volume in your clinic, you can preserve the safety of patients on active treatment who really need it.

“Some of our surgeons also have been triaging some of their cases to an ambulatory care facility instead of routinely doing them in the hospital setting, recognizing that the hospital in my community soon will have the highest proportion of concentrated risk,” she added.

However, she agreed that delaying treatment “can be tricky” in many cases.

“If you assume someone has a 4-cm ductal carcinoma in situ and they want to consider delaying surgery, that’s probably fine. But it’s also possible that person could have a coexisting invasive ductal carcinoma in their breast, so you really need to think about each case individually,” Patt said. “Is the patient low risk because of their cancer? Are they low risk or high risk because of comorbid illness? What is the natural consequence of delaying the therapy?”

In some cases, there are other options. For example, if a patient with advanced triple-negative breast cancer learns she has a BRCA mutation and elects to have bilateral mastectomy with reconstruction, she could undergo a staged procedure in which mastectomy is performed in one interval and reconstruction is delayed, Patt said.

“In general, delaying cancer treatment is not my recommendation because the natural consequence of not treating it is that the cancer will progress and the patient will have adverse outcomes,” Patt said. “If you are considering whether it is reasonable to delay the intervention until it is safer for the patient, [the clinician] should always weigh the risks and benefits, as it is highly variable for every patient.”

‘Save your strength’

Prior studies suggested 40% of patients with cancer experience significant distress, and oncology providers should anticipate patient anxiety will increase during the pandemic.

“We should understand that all patients are anxious. Physicians are human, and we share those anxieties, as well,” Volberding said. “We should be attentive to those anxieties without being alarmists. People with cancer are already under so much pressure. We should recognize their concerns without adding to them unnecessarily.”

For example, people with cancer already are at risk for fever or respiratory problems depending on the nature of their disease and treatment.

“We should reassure patients that not every symptom they have is going to be from COVID-19,” he said.

Tan recommended oncology providers refer patients who are extremely anxious about the pandemic to medical psychologists trained to help patients cope and reduce their anxiety.

She also suggested providers reinforce the practical steps their patients can take to reduce their risk for COVID-19 infection, and also use the pandemic as a teachable moment about influenza.

“Influenza is definitely affecting — and killing — more people than COVID-19, especially in the cancer population,” she said. “If one of your patients hasn’t been vaccinated yet, they need to be. Tell them that is something proactive that they can do during an otherwise uncertain time.”

Although it is essential for individuals with cancer to follow recommendations from WHO, CDC and other health authorities to minimize their exposure, providers who care for these patients should do the same, Tan said.

“Common-sense measures probably will be most effective for everybody,” Tan said. “These include hand hygiene, cough and sneeze etiquette, not touching your face, avoiding large public gatherings and — particularly important for those who work in the medical field — not going to work when you’re sick. If you do, you could potentially expose individuals who are immunocompromised to whatever you have.”

Even if they feel fine, oncologists and other health care providers should look for opportunities to reduce time spent in the office or clinic. Those who are not actively involved in patient care should work from home if they can, and they should identify opportunities for telehealth, Pergam said.

“It feels a little draconian at times to say you must stay home, but the idea of social distancing is really important,” Pergam said. “If we don’t have a treatment and we don’t have a vaccine, the only way to prevent severe complications is to avoid getting sick. One of the best ways to flatten an epidemic curve is to prevent transmission events from happening. That said, you absolutely need a good game plan so if one person on your team develops an illness, someone else can step up, take the baton and run some of the incident command.”

Given the likelihood that health care providers — including those who care for patients with cancer — will face additional burdens that result in longer hours and elevated stress, it is essential for them to prioritize personal wellness, Pergam said.

He recommended taking breaks each day, eating healthy, drinking plenty of water and getting adequate sleep. Regular exercise — even simply taking a walk, provided you aren’t in a crowded space — also is important, Pergam said.

“These are tough times, and I think they’re going to get tougher for a while,” he said. “Physicians are people, too. The immune system is affected by how we treat ourselves. If we get sick, we can’t take care of our patients. It is very important to save your strength and be ready.” – by Mark Leiser, Jennifer Southall and John DeRosier

References:

ASCO. ASCO Annual Report 2018. Available at: https://www.qgdigitalpublishing.com/publication/?m=54077&i=612492&p=0. Accessed on March 24, 2020.

Carlson LE, et al. J Clin Oncol. 2012;doi:10.1200/JCO.2011.39.5509.

Infectious Disease Society of America. COVID-19 prioritization of diagnostic testing. Available at: www.idsociety.org/globalassets/idsa/public-health/covid-19-prioritization-of-dx-testing.pdf. Accessed on March 24, 2020.

Liang W, et al. Lancet Oncol. 2020;doi:10.1016/S1470-2045(20)30096-6.

Ueda M, et al. J Natl Compr Canc Netw. 2020;doi:10.6004/jnccn.2020.7560.

Online resources:

Several societies and organizations offer updated information and resources to help clinicians during the COVID-19 pandemic:

ASCO: www.asco.org/asco-coronavirus-information.

ASH: www.hematology.org/covid-19.

ASTRO: www.astro.org/daily-practice/COVID-19-recommendations-and-information.

Center to Advance Palliative Care: www.capc.org/toolkits/covid-19-response-resources.

For more information:

Andrew M. Evens, DO, MSc, can be reached at ae378@cinj.rutgers.edu.

Debra Patt, MD, MPH, MBA, can be reached at debra.patt@usoncology.com.

Steven Pergam, MD, MPH, can be reached at spergam@fhcrc.org.

David I. Quinn, MD, can be reached at diquinn@usc.edu.

Samuel M. Silver, MD, PhD, MACP, FRCP, can be reached at msilver@umich.edu.

Tina Tan, MD, can be reached at ttan@northwestern.edu.

Che-Kai Tsao, MD, can be reached at che-kai.tsao@mssm.edu.

Paul A. Volberding, MD, can be reached at paul.volberding@ucsf.edu.

Disclosures: Evens, Patt, Pergam, Quinn, Silver, Tan, Tsao and Volberding report no relevant financial disclosures.