Oncologists Band Together to Battle COVID-19 Crisis

Hope S. Rugo, MD, FASCO, director of Breast Oncology and Clinical Trials Education at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center

Hope S. Rugo, MD, FASCO

In response to the COVID-19 pandemic, cancer experts are banning together in a global effort to disseminate information as quickly as possible, to sift through all available data to develop a better understanding of the virus, and to use that knowledge to modify treatment plans for their patients. To continue the fight on the frontlines, it is crucial that those who are in the thick of the battle are equipped with the necessary resources, both physically and mentally.

“This is a period of not only professional stress, but of personal stresses,” said Ruben Mesa, MD, director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, and moderator of a recent webinar on COVID-19 hosted by Physicians’ Education Resource.^®

Mesa was joined by a panel of experts including Amelia A. Langston, MD, director of the Bone Marrow Stem Cell Transplant Program at Emory University; Hope S. Rugo, MD, FASCO, a breast medical oncologist, professor of medicine, and director of Breast Oncology and Clinical Trials and Education at the University of California San Francisco (UCSF)’s Comprehensive Cancer Center; and Cardinale B. Smith, MD, PhD, a chief quality officer for cancer, a thoracic oncologist, and a palliative medicine physician at the Mount Sinai Health System.

As of April 4, 2020, the total confirmed and presumptive positive cases of COVID-19 has risen to 277,205 in the United States alone, with 6593 deaths, according to the latest update from the Centers for Disease Control and Prevention.¹ On a global scale, the World Health Organization has reported 1,056,159 confirmed cases, with 57,206 lives claimed by the virus.²

Modifying Treatment to Delay Surgery and Reduce Risk

Despite efforts made to prevent the spread of infection, COVID-19 has become a global health crisis. Patients with cancer are particularly impacted by the situation as they are at increased risk of developing severe complications from the infection. Now, in an effort to prevent their patients from viral exposure, experts are also faced with the daily challenge of modifying treatment plans accordingly.

“COVID-19 certainly has been impacting the way we have been approaching [treatment] for our patients with lung cancer. For example, in someone with an unresectable stage III lung cancer, after chemotherapy and radiation, we start durvalumab (Imfinzi) maintenance for 1 year,” said Smith. “Typically, the durvalumab is given every 2 weeks; however, ongoing trials are examining giving the agent every month instead. As such, we are now considering giving these patients durvalumab monthly to minimize the number of trips that they need to make [to the clinic] to take it.”

Smith added that some of her colleagues in multiple myeloma have been switching their patients from intravenous treatments over to oral therapies as a way to obviate risk, as well.

In breast cancer, with regard to chemotherapy and endocrine therapy, Rugo said that in the case of a patient with indolent hormone receptor—positive breast cancer, endocrine therapy can be given for the first 3 to 6 months, depending on the age of the patient.

“We don't have a lot of data in premenopausal women who have these kinds of low-risk cancers, but in postmenopausal women this can certainly be a very reasonable and acceptable standard that doesn't put the patients at greater risk,” said Rugo.

The guidelines that have recently out have suggested the use of specific endocrine therapeutic agents, such as aromatase inhibitors, rather than tamoxifen or other agents, added Rugo.

“In terms of chemotherapy, I [think we’re all in agreement] that we should be giving neoadjuvant chemotherapy in patients who are likely to receive chemotherapy anyway.” These patients include those with larger tumors, triple-negative breast cancer (TNBC), HER2-positive disease, according to Rugo. Neoadjuvant therapy can help delay the time to surgery.

On March 24, 2020, the American Society of Breast Surgeons released recommendations for the prioritization, treatment, and triage of patients with breast cancer during the pandemic. The guidance is broken down into priority categories based on patient condition.³ For example, priority A means that the patient’s condition is immediately life-threatening or clinically unstable; priority B means that the situation is noncritical but any delay in treatment beyond 6 to 8 weeks could potentially effect overall outcome; and priority C means that the condition is stable enough that services can be delayed for the duration of the viral pandemic.

With regard to priorities for breast cancer—focused medical oncology, the guidelines recommend that patients who are “priority A” with TNBC or HER2-positive breast cancer receive neoadjuvant/adjuvant chemotherapy. In those who are “priority B” with stage I or II breast cancer, the use of neoadjuvant endocrine therapy can be used to defer surgery by 6 to 12 months. Those with early-stage estrogen receptor–positive breast cancer will not substantially benefit from chemotherapy. In these patients, high level evidence indicates that 6 to 12 months of primary endocrine therapy before surgery is a safe and effective way to potentially enable the deferral of surgery. In patients considered to be “priority C,” antiresorptive therapy that is not needed urgently for hypercalcemia is recommended.

Rugo added that the suggestion to administer chemotherapy every 3 weeks rather than weekly has been a topic of debate. “I feel very mixed about that because our every-3-week regimens use more steroids and cause more immunosuppression than our weekly regimens, so I'm not on that bandwagon,” said Rugo. “Although lightweight, every-3-week regimens, such as docetaxel and cyclophosphamide, might be preferred for some patients compared with others, we generally stick with our regular regimens.”

In light of the fact that patients who are immunosuppressed appear to be particularly vulnerable to COVID-19 infection, another area of concern is immunotherapy. “There is some suggestion that there may be more toxicity for patients who are COVID positive and on immunotherapy, but I don’t believe any of us truly know what that will look like,” said Smith.

For those without infection, there is no direct evidence at this time to support changing or withholding chemotherapy or immunotherapy in patients with cancer, according to the American Society of Clinical Oncology (ASCO).⁴ Treatment decisions should be made in an individualized manner. The factors to inform such a decision include the risk of cancer recurrence if treatment is modified or delayed, the number of treatment cycles already completed, and the patient’s tolerance to the treatment.

Restarting Chemotherapy After COVID-19: How Soon Is Too Soon?

Another question that has been discussed at large in the cancer community has to do with determining how long a patient who had a COVID-19—related illness must wait before they are able to restart chemotherapy; this challenge is seemingly exacerbated by testing limitations, said Mesa.

“We’re going to have to decide how important the chemotherapy is. By our ruling, [patients] can't come back until they've screened negative twice,” said Rugo “Obviously, if someone had respiratory failure [due to the virus] and they were on a ventilator, you might wait longer than you might for someone who had an asymptomatic infection at home and was doing well. We’re going to have to individualize this [decision] based on the patient, their cancer, and the treatment itself.”

Smith added that in New York, providers are no longer screening patients to be negative before restarting treatment. “Although in the very beginning when this all started, the rule from the Department of Health was to have a 2-negative screen with a certain time interval apart before we would consider someone negative and they could remove themselves from quarantine, we no longer have that,” said Smith. “NY state is really trying to minimize testing because of the personal protective equipment issue, so I don't know that we're going to actually know [whether someone is negative].”

Smith added that right now, the arbitrary consensus has been that patients who had more mild symptoms and did not require hospitalization for their infection can be restarted on treatment 2 to 3 weeks after, while those who had more severe symptoms can restart their treatment 3 to 4 weeks after.

“But some of these patients are in the hospital for 2 weeks, so it’s really hard to know how long [we need to wait] after they leave, before they’re actually going to be okay to treat again,” stressed Rugo.

Delaying Stem Cell Transplants

In some patients who are at high-risk of infection with COVID-19, delaying a planned allogeneic stem cell transplant may a reasonable course of action, especially if the patient’s malignancy is controlled with conventional treatment, according to ASCO.

Recommendations from the European Society for Blood and Marrow Transplantation state that all non-urgent transplants should be deferred as much as possible.⁵ However, those who will need to undergo transplantation should try to minimize risk of infection through home isolation 2 weeks prior to the start of the transplant conditioning. Clinic visits should be avoided unless absolutely necessary.

Furthermore, all should be tested for the virus and the results should be negative prior to the start of conditioning, irrespective of whether upper respiratory symptoms are present. If the candidate tests positive for the virus, they should be deferred for at least 3 months per European Centre for Disease Prevention and Control guidelines. However, because of the risk from the underlying disease, that length of deferral is not always possible. As such, in patients with high-risk disease, transplant should be deferred only until they become asymptomatic and are found to be negative for the virus via 2 polymerase chain reaction tests done at least 1 week apart.

With regard to patients with standard-risk multiple myeloma who need an autologous transplant, Langston said that there is comfort in bridging these patients for a number of months before sending them to surgery; data are available to support the feasibility of this, she added.

“On the other hand, our patients with lymphoma [who are] getting autologous transplants need to go [to transplant] in some reasonable real time frame,” said Johnson. “In terms of our allogeneic transplants, we can delay them a little bit but we can't necessarily delay those a great deal because we run the risk—particularly for our patients with acute leukemias—that they're going to relapse while we're in the midst of this waiting period.”

For example, patients with leukemia who are at highest risk, such as those with FLT3-positive acute myeloid leukemia (AML), will need to undergo transplant, according to Johnson. Conversely, a patient with standard-risk AML who is in their first complete response and is doing well with their consolidation therapy could potentially receive treatment for a few months before going forward with a transplant, Johnson added.

Staff Are Caring for Patients, But Who’s Taking Care of the Staff?

As the number of COVID-19 cases continues to increase in the United States, healthcare workers have been working day and night to provide the best care possible for their patients; this means juggling more patient visits, utilizing new technology to do so, exposing themselves to infection on a daily basis, and then spending off-hours reading up about new developments and dispersing available information with their colleagues.

Exposure to long hours of caring for desperately ill patients, the weight of counseling their families, adhering to electronic documentation requirements, struggling with the loss of autonomy over daily responsibilities, and trying to keep up with a constantly evolving environment are all factors that can lead to feelings of burnout in practicing oncologists.⁶ In the midst of a pandemic, oncologists are still faced with these stressors in the clinic, but they are also faced with other COVID-related challenges on a more personal level.

For example, those with young kids have to deal with the fact that their kids are home from school for the time being, and they are going to require extra attention and help with their studies, Rugo noted.

“This is the most stressful time of all our careers. I would say on behalf of all of us, without question, we have never been through anything like this and I hope we [never go through something like this again,” said Rugo. “It’s a whole new world, and people who have elderly parents at home or who are caring for elderly parents, if they’re going to work, they risk exposing their parents; this is also a very big concern for many of my colleagues.” She added that other colleagues have also expressed concerned about their spouses who are older and have medical problems.

“I think we all need to be really supportive as a community,” stressed Rugo. “I have to say that email communications [from our leadership] and, odd as it may sound, Twitter, [has become] a big source of information and [has provided] support for all of us that may help to counteract some of the burnout [we’re experiencing].”

Smith echoed that sentiment and shared that having a 7- and 3-year-old who have been ordered to shelter in place is challenging. “It is hard to work, have a job, have to homeschool your child, and then have to worry about an elderly parent or not,” said Smith. “Throughout all this, you still want to ensure that you’re doing what's right for your patients. If I'm putting this patient off for a month, is that the right thing? What are all of the potential consequences of doing that? That struggle I real.”

She added that in terms of self-care, some are better at others at finding a way to unplug. For example, some may turn to meditation or a glass of wine after a long workday to decompress, said Smith. “Whatever that is for you, it is important that you tap into that and that you recognize when you're reaching your limit. [This is especially important, because I know for most of us, this is just the beginning,” stressed Smith. “It's predicted that we're not going to peak in New York for another approximately 40 days. The pressure that we're feeling now is only going to get worse."

The Battle Rages On, But Collaboration Saves Lives

Although this may just be the beginning of the battle against COVID-19, the oncology community has banded together to fight back.

“I must say that I have just been so inspired by how the global medical community has come together on every level; this is evident in the rapid advances, the sharing of information, and even the texts I’m receiving,” said Mesa. “I got a text this morning from a colleague who is caring for a similar patient group that I treat and he shared with me what he is seeing. Having that kind of a community to tap into is amazing.”

Rugo echoed that sentiment, saying that the way the community has come together has been very inspirational. From the staff to the clinical research coordinators to the people who clean the floors at her institution, Rugo said the collaboration and unification of everyone on the front lines has been nothing short of remarkable.

“And then there’s our patients,” said Rugo. “I can't tell you how many patients have sent me a message reminding me to take care of myself, telling me that they’re worried about me. It’s just amazing kindness and that really makes a huge difference.”

References

1. Coronavirus disease 2019 (COVID-19): cases in the U.S. Centers for Disease Control and Prevention. Updated April 4, 2020. bit.ly/33Nyb4w. Accessed April 4, 2020.
2. Coronavirus disease (COVID-19) situation dashboard. World Health Organization. Updated April 4, 2020. bit.ly/2UFWizg. Accessed April 4, 2020.
3. Recommendations for prioritization treatment and triage of breast cancer patients during the COVID-19 pandemic: executive summary. The American Society of Breast Surgeons; March 24, 2020. bit.ly/2XaWcRU. Accessed April 4, 2020.
4. COVID-19 patient care information. American Society of Clinical Oncology. Updated April 2, 2020. bit.ly/34d1Unu. Accessed April 4, 2020.
5. Coronavirus disease COVID-19: EBMT recommendations update March 23, 2020. European Society for Blood and Marrow Transplantation; March 23, 2020. bit.ly/2JDXexR. Accessed April 4, 2020.
6. Copur MS. Burnout in oncology. Oncology. 2019;33(11). bit.ly/2JDuo0p. Accessed April 4, 2020.