Cancer management: A challenge in the time of COVID-19
The COVID-19 pandemic has, and continues to have, a significant effect on the lives of individuals worldwide. Published reports suggest an elevated risk of COVID-19 among patients with cancer. As such, oncologists globally have had to adapt their management of cancer patients to minimize the risk of infection, while ensuring optimal care for this population.
Are patients with cancer at higher risk of COVID-19?
Multiple studies have alluded to an increased risk of COVID-19 and more severe outcomes among patients with cancer. [Cancer Discov 2020;doi:10.1158/2159-8290.CD-20-0422; Cancer Discov 2020;doi:10.1158/2159-8290.CD-20-0516] Additionally, European Society for Medical Oncology (ESMO)-published guidelines suggest an elevated risk of SARS-CoV-2 asymptomatic infections among patients with cancer. [ESMO, https://www.esmo.org/guidelines/cancer-patient-management-during-the-covid-19-pandemic, accessed 29/04/2020]
According to the Report of the WHO-China Joint Mission on Coronavirus Disease published in late February 2020, the case fatality rate for patients with cancer is 7.6 percent. This is higher than the overall 3.8 percent and 1.4 percent among those without comorbidities but lower than that of patients who also have diabetes (9.2 percent), hypertension (8.4 percent), or chronic respiratory disease (8.0 percent). [https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf, accessed 06/05/2020]
“[E]arly reports suggest a substantial increased risk of death associated with COVID-19 infection among patients with cancer, perhaps highest among those older than 60 years and those with pulmonary compromise,” noted Professor Deborah Schrag from the Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, US, and co-authors, in a JAMA viewpoint. [JAMA 2020;doi:10.1001/jama.2020.6236]
Patients at particular risk include current or recent (within the past 3 months) chemotherapy recipients, extensive radiotherapy recipients, immunocompromised patients (eg, those with leukocytopaenia, low immunoglobulin levels, or those on immunosuppressive drugs such as steroids and antibodies), individuals who have undergone stem cell or bone marrow transplants in the past 6 months, and those whose cancer affects the immune system, regardless of necessity of treatment (eg, chronic leukaemia, lymphoma, or myeloma). [ESMO, https://www.esmo.org/guidelines/cancer-patient-management-during-the-covid-19-pandemic, accessed 04/05/2020]
General management guidelines
The guidelines for cancer management differ between patients who are off treatment (ie, patients who have completed treatment or whose disease is under control) and those who are currently undergoing treatment. [ESMO, https://www.esmo.org/guidelines/cancer-patient-management-during-the-covid-19-pandemic, accessed 04/05/2020]
In general, all patients should be given proper medical education. They should be advised to avoid crowded areas or contact with friends or relatives who exhibit COVID-19 symptoms or who reside in endemic zones, and to socially distance themselves. They should also be educated on proper handwashing techniques and to wear personal protective equipment (PPE) during hospital visits.
For patients who are currently undergoing treatment, hospital visits should be minimized without compromising patient safety or care. Conversely, patients with lung cancer or those who have previously undergone lung surgery, older patients, and those with comorbidities should receive additional surveillance.
Patients on oral treatment should be provided with at least a three-course supply of medication to minimize hospital visits, with blood testing for monitoring purposes done at laboratories close to the patient’s home. Telemedicine services should be utilized where possible and follow-up visits delayed.
Procedures to avoid infection should be initiated. Specific areas should be available to assess for COVID-19 symptoms or early detection of individuals with infection and staffed with trained personnel who are attired in PPE. Individuals who meet criteria for highly communicable diseases that require isolation (eg, COVID-19) should be examined in private examination rooms, tested, and transferred to areas specifically for COVID-19.
Telemedicine options are preferred for communication between professionals and with patients. The benefits and risks of cancer treatment during the pandemic require discussion. This would include the option of temporarily switching to oral instead of intravenous (IV) treatments where possible, and other measures that would reduce contact, prioritizing adjuvant therapies in patients with resected high-risk disease, and having shorter or hypofractionated radiotherapy regimens.
A tiered approach to management
ESMO suggests a three-tiered approach to managing patients with cancer during the COVID-19 pandemic (tier 1: high priority, tier 2: medium priority, and tier 3: low priority). These tiers are defined as per Cancer Care Ontario, Huntsman Cancer Institute, and Magnitude of Clinical Benefit Scale (MCBS) criteria.
Patients deemed high priority have clinically unstable or immediately life-threatening conditions, or would derive significant benefits (eg, overall survival, quality of life) with intervention. Patients deemed medium priority are currently not critical. However, delaying intervention for >6 weeks could impact their outcomes. Patients deemed low priority are considered stable to the point that intervention could be delayed during the pandemic.
Who should undergo SARS-CoV-2 testing?
Patients who present with symptoms suspect for COVID-19 (eg, fever, breathing difficulties, anosmia or dysgeusia, sore throat) should be sent for confirmatory testing.
In addition, all patients who are scheduled for surgery, chemotherapy, radiotherapy, or immunotherapy should be sent for reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 testing before each treatment cycle, if possible. Cancer survivors or those undergoing follow-up care who present with symptoms suggestive of COVID-19 should also undergo RT-PCR SARS-CoV-2 testing. These patients should also undergo serology testing if possible, to identify previous COVID-19 infection.
According to the American Society of Clinical Oncology (ASCO), once testing becomes more accessible, asymptomatic patients scheduled for immunosuppressive cancer therapy or those at an increased risk of developing COVID-19 complications should be tested before treatment initiation. This will not only help protect patients and healthcare workers, but also help in decision-making, in particular whether treatment can be delayed. [ASCO, https://www.asco.org/asco-coronavirus-information/care-individuals-cancer-during-covid-19, accessed 06/05/2020]
Weighing the risks against the benefits
“[D]uring the COVID-19 pandemic, the benefit/risk ratio of cancer treatment may need to be reconsidered in certain patients,” said the ESMO guideline authors.
“Although some patients are willing to undergo treatments for small benefits, the pendulum of risk related to immunosuppression and exposure at a healthcare facility tip the risk-benefit ratio away from treatment,” said Schrag and co-authors.
However, according to an editorial published in Lancet Oncology, the decisions on cancer care are “inconsistent, and not evidence-based” with multidisciplinary teams having to make “best guesses” on a patient-by-patient basis. [Lancet Oncol 2020;21:603]
“In general, … any decisions to postpone, discontinue, or modify necessary systemic cancer therapy should consider the overall goals of treatment, risks of cancer progression if treatment is postponed or interrupted, patient tolerance of treatment, and the patient’s general medical condition. Each decision requires an individualized risk/benefit assessment,” noted the ASCO guideline authors.
While evidence is limited, ASCO recommends cessation of cancer therapy in patients with active COVID-19 “as continuation of treatment may lead to further immunosuppression and risk for serious complications.” [ASCO, https://www.asco.org/asco-coronavirus-information/care-individuals-cancer-during-covid-19, accessed 08/05/2020] Ideally, treatment should be discontinued until the patient tests negative for SARS-CoV-2. However, this decision would need to be weighed in patients with rapidly progressing disease or if the risk-benefit ratio favours treatment continuation. Both the US Centers for Disease Control and Prevention (CDC) and UK National Institute for Health and Care Excellence (NICE) have published guidelines on cancer treatment decisions during the COVID-19 pandemic. [CDC, https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-hospitalized-patients.html; NICE, https://www.nice.org.uk/guidance/ng161, accessed 08/05/2020]
Neoadjuvant therapy, where possible, should be considered in place of surgery, or surgery delayed. However, the risk of delaying surgery, the need for patient–physician contact, the burden on the healthcare system, and the immunosuppressive properties of certain neoadjuvant therapies need to be weighed. Radiotherapy for symptom control can be delayed. Hypofractionated radiotherapy should be considered where possible. While ceasing or withholding critical immunotherapy is not advisable, the decision should be individualized. [ASCO, https://www.asco.org/asco-coronavirus-information/care-individuals-cancer-during-covid-19, accessed 11/05/2020]
Global registries: An international collaborative effort to improve care
“The oncology community has united to share strategies, formulate guidance, collect data, and design and execute treatment protocols,” said Schrag. This is evident in the emergence of several global registries.
In early April, the American Society of Hematology (ASH) launched a registry to collect data on patients with COVID-19 who were previously or are currently being treated for haematologic malignancies. [ASH, https://www.ashresearchcollaborative.org/covid-19-registry, accessed 11/05/2020]
The ASH Research Collaborative’s (RC) Data Hub COVID-19 Registry for Hematologic Malignancy is open to healthcare providers (HCPs) worldwide. Using an online data collection tool, HCPs can submit de-identified data of their patients with haematologic malignancies who have tested positive for COVID-19. The data will be analysed and clinical practice and patient outcomes reported in aggregate form to provide near real-time data summaries for physicians on the frontline of the outbreak.
Similarly, ESMO launched the ESMO Co-CARE registry to collect data on treatment measures, specifically, the effect of the SARS-CoV-2 infection on patients with cancer and suspected or confirmed COVID-19. [ESMO, https://www.esmo.org/covid-19-and-cancer/collaborating-on-registries-studies-and-surveys/esmo-cocare-registry, accessed 11/05/2020]
“It is wonderful to see oncologists come together to build a registry on these patients with an intent to rapidly share these data to help guide management,” said Dr Urvi Shah from the Memorial Sloan Kettering Cancer Center, New York, US. [JAMA Oncol 2020;doi:10.1001/jamaoncol.2020.1848]