Special Considerations in Adults and Children With Cancer
Last Updated: August 27, 2020
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials without major limitations; IIa = Other randomized trials or subgroup analyses of randomized trials; IIb = Nonrandomized trials or observational cohort studies; III = Expert opinion
People who are being treated for cancer may be at increased risk of severe COVID-19, and their outcomes are worse than individuals without cancer.1-4 A meta-analysis of 46,499 patients with COVID-19 showed that all-cause mortality (risk ratio 1.66; 95% CI, 1.33–2.07) was higher in patients with cancer, and that patients with cancer were more likely to be admitted to intensive care units (risk ratio 1.56; 95% CI, 1.31–1.87).5 The risk for immunosuppression and susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection varies between cancer types, treatments administered, and stages of therapy (e.g., patients who are actively being treated compared to those in remission). In a study that used data from the COVID-19 and Cancer Consortium Registry, cancer patients who were in remission or who had no evidence of disease were at a lower risk of death from COVID-19 than those who were receiving active treatment.6 It is unclear whether cancer survivors are at increased risk for severe COVID-19 and its complications compared to people without a history of cancer.
Many organizations have outlined recommendations for treating patients with cancer during the COVID-19 pandemic, such as:
- National Comprehensive Cancer Network (NCCN)
- American Society of Hematology
- American Society of Clinical Oncology
- Society of Surgical Oncology
- American Society for Radiation Oncology
- International Lymphoma Radiation Oncology Group
This section of the COVID-19 Treatment Guidelines complements these sources and focuses on considerations regarding testing for SARS-CoV-2, management of COVID-19 in patients with cancer, and management of cancer-directed therapies during the COVID-19 pandemic. The optimal management and therapeutic approach to COVID-19 in this population has not yet been defined.
Testing for COVID-19 in Patients With Cancer
The COVID-19 Treatment Guidelines Panel (the Panel) recommends molecular diagnostic testing for SARS-CoV-2 in patients with cancer who develop signs and symptoms of COVID-19 (AIII).
Patients with cancer who are receiving chemotherapy are at risk of developing neutropenia. The NCCN Guidelines for Hematopoietic Growth Factors categorizes cancer treatment regimens based on the risk of developing neutropenia. A retrospective study suggests that cancer patients with neutropenia have a higher mortality rate if they develop COVID-19.7 Due to the potential risk of poor clinical outcomes in the setting of neutropenia and/or during the perioperative period, the Panel recommends performing molecular diagnostic testing for SARS-CoV-2 prior to procedures that require anesthesia and before initiating cytotoxic chemotherapy and long-acting biologic therapy (BIII).8,9
General Guidance on Medical Care for Cancer Patients During the COVID-19 Pandemic
Patients with cancer frequently engage with the health care system to receive treatment and supportive care for cancer and/or treatment-related complications. Telemedicine can minimize the need for in-person services and reduce the risk of SARS-CoV-2 exposure. The Centers for Disease Control and Prevention published a framework to help clinicians decide whether a patient should receive in-person or virtual care during the COVID-19 pandemic; this framework accounts for factors such as the potential harm of delayed care and the degree of SARS-CoV-2 transmission in a patient’s community.10 Telemedicine may improve access to providers for medically or socially vulnerable populations but could worsen disparities if these populations have limited access to technology. Nosocomial transmission of SARS-CoV-2 to patients and health care workers has been reported.11-13 Principles of physical distancing and prevention strategies, including masking patients and health care workers and practicing hand hygiene, apply to all in-person interactions.14
Decisions about treatment regimens, surgery, and radiation therapy for the underlying malignancy should be made on an individual basis depending on the biology of the cancer, the need for hospitalization, the number of clinic visits required, and the anticipated degree of immunosuppression. Several key points should be considered:
- If possible, treatment delays should be avoided for curable cancers that have been shown to have worse outcomes when treatment is delayed (e.g., pediatric acute lymphoblastic leukemia).
- When deciding between equally effective treatment regimens, regimens that can be administered orally or those that require fewer infusions are preferred.15,16
- The potential risks of drug-related lung toxicity (e.g., from using bleomycin or PD1 inhibitors) must be balanced with the clinical efficacy of alternative regimens or the risk of delaying care.17
- Preventing neutropenia can decrease the risk of neutropenic fever and the need for emergency room evaluation and hospitalization during the COVID-19 pandemic. Granulocyte colony-stimulating factor (G-CSF) should be given with chemotherapy regimens that have intermediate (10% to 20%) or high (>20%) risks of febrile neutropenia.18
- Cancer treatment regimens that do not affect outcomes of COVID-19 in cancer patients may not need to be altered. In a prospective observational study, receipt of immunotherapy, hormonal therapy, or radiotherapy in the month prior to SARS-CoV-2 infection was not associated with an increased risk of mortality among cancer patients with COVID-19.19 A retrospective study from Italy evaluated the incidence of SARS-CoV-2 infection in patients with prostate cancer and found that 114 of 37,161 patients (0.3%) who were treated with therapies other than androgen deprivation therapy became infected, compared to four of 5,273 patients (0.08%) who were treated with androgen deprivation therapy (OR 4.05; 95% CI, 1.55–10.59). The viral spike proteins required for cell entry of SARS-CoV-2 are primed by TMPRSS2, an androgen-regulated gene. Whether androgen deprivation therapy protects against SARS-CoV-2 infection requires further investigation in larger cohorts.20
- Radiation therapy guidelines suggest increasing the dose per fraction and reducing the number of daily treatments in order to minimize the number of hospital visits during the COVID-19 pandemic.15,16
Blood supply shortages will likely continue during the COVID-19 pandemic due to social distancing, cancellation of blood drives, and infection among donors. Revised donor criteria have been proposed by the Food and Drug Administration to increase the number of eligible donors.21 In patients with cancer, lowering the transfusion thresholds for blood products (e.g., red blood cells, platelets) in asymptomatic patients should be considered.22,23 At this time, there is no evidence that COVID-19 can be transmitted through blood products.24,25
Cancer patients with febrile neutropenia should undergo molecular diagnostic testing for SARS-CoV-2 and evaluation for other infectious agents; they should also be given empiric antibiotics, as outlined in the NCCN Guidelines.26 Low-risk febrile neutropenia patients should be treated at home with oral antibiotics or intravenous infusions of antibiotics to limit nosocomial exposure to SARS-CoV-2. Patients with high-risk febrile neutropenia should be hospitalized per standard of care.26 Empiric antibiotics should be continued per standard of care in patients who test positive for SARS-CoV-2. Clinicians should also continuously evaluate neutropenic patients for emergent infections.
Treating COVID-19 and Managing Chemotherapy in Patients With Cancer and COVID-19
Retrospective studies suggest that patients with cancer who were admitted to the hospital with SARS-CoV-2 infection have a high case fatality rate, with higher rates observed in patients with hematologic malignancies than in those with solid tumors.27,28
Recommendations for treatment of COVID-19 are the same for cancer patients as for the general population (AIII) (see Potential Antiviral Drugs Under Evaluation for the Treatment of COVID-19 and Immunomodulators Under Evaluation for Treatment of COVID-19). Dexamethasone treatment in patients with COVID-19 who require supplemental oxygen or mechanical ventilation has been associated with a lower mortality rate.29 In cancer patients, dexamethasone is commonly used to prevent chemotherapy-induced nausea, as a part of tumor-directed therapy, and to treat inflammation associated with brain metastasis. The side effects of using dexamethasone to treat SARS-CoV-2 are not anticipated to be different between patients with or without cancer. If possible, treatments that are not currently recommended for SARS-CoV-2 infection should be administered as part of a clinical trial, since the safety and efficacy of these agents have not been well defined in patients with cancer.
The NCCN recommends discontinuing G-CSF and granulocyte-macrophage colony-stimulating factor in patients with cancer and acute SARS-CoV-2 infection who do not have bacterial or fungal infections to avoid the hypothetical risk of increasing inflammatory cytokines and pulmonary inflammation.18,30 Secondary infections (e.g., invasive pulmonary aspergillosis) have been reported in critically ill patients with COVID-19.31,32
Decisions about administering cancer-directed therapy to patients with acute COVID-19 and those who are recovering from COVID-19 should be made on a case-by-case basis; clinicians should consider the indication for chemotherapy, the goals of care, and the patient’s history of tolerance to the treatment (BIII). The optimal duration of time between resolution of infection and initiating or restarting cancer-directed therapy is unclear. Withholding treatment until COVID-19 symptoms have resolved is recommended, if possible. Prolonged viral shedding (detection of SARS-CoV-2 by molecular testing) may occur in cancer patients,2 although it is unknown how this relates to infectious virus and how it impacts outcomes. Therefore, there is no role for repeat testing in those recovering from COVID-19, and the decision to restart cancer treatments in this setting should be made on a case-by-case basis. The Panel recommends that clinicians who are treating COVID-19 in patients with cancer consult with a hematologist or oncologist before adjusting cancer-directed medications (AIII).
The use of potential antiviral or immune-based therapies to treat COVID-19 can present additional challenges in cancer patients. Clinicians should pay careful attention to potential drug-drug interactions and overlapping toxicities between drugs that are used to treat COVID-19 and cancer-directed therapies, prophylactic antimicrobials, corticosteroids, and other medications (AIII).
Several anti-neoplastic medications have known interactions with therapies that are being investigated for COVID-19.22 Tocilizumab can interact with vincristine and doxorubicin. Any COVID-19 therapy that may cause QT prolongation must be used with caution in patients treated with venetoclax, gilteritinib, and tyrosine kinase inhibitor therapy (e.g., nilotinib). Dexamethasone is commonly used as an antiemetic for cancer patients and is recommended for treatment of certain patients with COVID-19 (see Corticosteroids for more information). Dexamethasone is a weak to moderate cytochrome P450 (CYP) 3A4 inducer; therefore, interactions with any CYP3A4 substrates need to be considered. Lopinavir/ritonavir is a CYP3A4 inhibitor, and it can increase methotrexate, vincristine, or ruxolitinib concentrations. Lopinavir/ritonavir is not recommended for the treatment of COVID-19; however, patients may receive it in a clinical trial. In general, concomitant use of lopinavir/ritonavir and CYP3A4 substrates should be avoided. If lopinavir/ritonavir is used in combination with a cytotoxic drug that is also a CYP34A substrate, clinicians should monitor for toxicities of the cytotoxic drug and adjust the dose if necessary.
Special Considerations in Children
Preliminary published reports suggest that pediatric patients with cancer may have milder manifestations of COVID-19 than adult patients with cancer, although larger studies are needed.33-35 Guidance on managing children with cancer during the COVID-19 pandemic is available from an international group with input from the International Society of Paediatric Oncology, the Children's Oncology Group, St. Jude Global, and Childhood Cancer International.36 Two publications include guidance for managing specific malignancies, guidance for supportive care, and a summary of web links from expert groups that are relevant to the care of pediatric oncology patients during the COVID-19 pandemic.36,37 Special considerations for using antivirals in immunocompromised children, including those with malignancy, are available in a multicenter guidance statement.38
- Dai M, Liu D, Liu M, et al. Patients with cancer appear more vulnerable to SARS-CoV-2: a multicenter study during the COVID-19 outbreak. Cancer Discov. 2020;10(6):783-791. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32345594.
- Shah V, Ko Ko T, Zuckerman M, et al. Poor outcome and prolonged persistence of SARS-CoV-2 RNA in COVID-19 patients with haematological malignancies; King's College Hospital experience. Br J Haematol. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32526039.
- Yang K, Sheng Y, Huang C, et al. Clinical characteristics, outcomes, and risk factors for mortality in patients with cancer and COVID-19 in Hubei, China: a multicentre, retrospective, cohort study. Lancet Oncol. 2020;21(7):904-913. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32479787.
- Robilotti EV, Babady NE, Mead PA, et al. Determinants of COVID-19 disease severity in patients with cancer. Nat Med. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32581323.
- Giannakoulis VG, Papoutsi E, Siempos, II. Effect of cancer on clinical outcomes of patients with COVID-19: a meta-analysis of patient data. JCO Glob Oncol. 2020;6:799-808. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32511066.
- Kuderer NM, Choueiri TK, Shah DP, et al. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet. 2020;395(10241):1907-1918. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32473681.
- Yarza R, Bover M, Paredes D, et al. SARS-CoV-2 infection in cancer patients undergoing active treatment: analysis of clinical features and predictive factors for severe respiratory failure and death. Eur J Cancer. 2020;135:242-250. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32586724.
- American Society of Clinical Oncology. ASCO Special Report: A guide to cancer care delivery during the COVID-19 pandemic. 2020. Available at: https://www.asco.org/sites/new-www.asco.org/files/content-files/2020-ASCO-Guide-Cancer-COVID19.pdf. Accessed August 17, 2020.
- American Society of Anesthesiologists. The ASA and APSF joint statement on perioperative testing for the COVID-19 virus. 2020. Available at: https://www.asahq.org/about-asa/newsroom/news-releases/2020/06/asa-and-apsf-joint-statement-on-perioperative-testing-for-the-covid-19-virus. Accessed August 3, 2020.
- Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19): framework for healthcare systems providing non-COVID-19 clinical care during the COVID-19 pandemic. 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/framework-non-COVID-care.html. Accessed August 3, 2020.
- Wang X, Zhou Q, He Y, et al. Nosocomial outbreak of COVID-19 pneumonia in Wuhan, China. Eur Respir J. 2020;55(6). Available at: https://www.ncbi.nlm.nih.gov/pubmed/32366488.
- Luong-Nguyen M, Hermand H, Abdalla S, et al. Nosocomial infection with SARS-CoV-2 within Departments of Digestive Surgery. J Visc Surg. 2020;157(3S1):S13-S18. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32381426.
- Rivett L, Sridhar S, Sparkes D, et al. Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission. eLife. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32392129.
- Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19): how to protect yourself & others. 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html Accessed June 17, 2020.
- American Society for Radiation Oncology. COVID-19 recommendations and information: COVID-19 clinical guidance. 2020. Available at: https://www.astro.org/Daily-Practice/COVID-19-Recommendations-and-Information/Clinical-Guidance. Accessed August 3, 2020.
- Yahalom J, Dabaja BS, Ricardi U, et al. ILROG emergency guidelines for radiation therapy of hematological malignancies during the COVID-19 pandemic. Blood. 2020;135(21):1829-1832. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32275740.
- American Society of Hematology. COVID-19 and hodgkin lymphoma: frequently asked questions. 2020. Available at: https://www.hematology.org/covid-19/covid-19-and-hodgkin-lymphoma. Accessed August 3, 2020.
- National Comprehensive Cancer Network. NCCN hematopoietic growth factors: short-term recommendations specific to issues with COVID-19 (SARS-CoV-2). 2020. Available at: https://www.nccn.org/covid-19/pdf/HGF_COVID-19.pdf. Accessed: August 3, 2020.
- Lee LYW, Cazier JB, Starkey T, et al. COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. Lancet. 2020;395(10241):1919-1926. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32473682.
- Montopoli M, Zumerle S, Vettor R, et al. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Ann Oncol. 2020;31(8):1040-1045. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32387456.
- Food and Drug Administration. Coronavirus (COVID-19) update: FDA provides updated guidance to address the urgent need for blood during the pandemic. 2020. Available at: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-provides-updated-guidance-address-urgent-need-blood-during-pandemic. Accessed August 3, 2020.
- American Society of Hematology. COVID-19 resources. 2020. Available at: https://www.hematology.org/covid-19. Accessed August 3, 2020.
- American Society of Clinical Oncology. COVID-19 patient care information: cancer treatment & supportive care. 2020. Available at: https://www.asco.org/asco-coronavirus-resources/care-individuals-cancer-during-covid-19/cancer-treatment-supportive-care. Accessed August 3, 2020.
- Food and Drug Administration. COVID-19 frequently asked questions. 2020. Available at: https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-frequently-asked-questions. Accessed August 3, 2020.
- Centers for Disease Control and Prevention. Clinical questions about COVID-19: questions and answers. 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/faq.html#Transmission. Accessed August 3, 2020.
- National Comprehensive Cancer Network. Infectious disease management and considerations in cancer patients with documented or suspected COVID-19. 2020. Available at: https://www.nccn.org/covid-19/pdf/COVID_Infections.pdf. Accessed: August 3, 2020.
- Mehta V, Goel S, Kabarriti R, et al. Case fatality rate of cancer patients with COVID-19 in a New York Hospital System. Cancer Discov. 2020;10(7):935-941. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32357994.
- Meng Y, Lu W, Guo E, et al. Cancer history is an independent risk factor for mortality in hospitalized COVID-19 patients: a propensity score-matched analysis. J Hematol Oncol. 2020;13(1):75. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32522278.
- Recovery Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with COVID-19—preliminary report. N Engl J Med. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32678530.
- Nawar T, Morjaria S, Kaltsas A, et al. Granulocyte-colony stimulating factor in COVID-19: Is it stimulating more than just the bone marrow? Am J Hematol. 2020;95(8):E210-E213. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32419212.
- van Arkel ALE, Rijpstra TA, Belderbos HNA, van Wijngaarden P, Verweij PE, Bentvelsen RG. COVID-19-associated pulmonary aspergillosis. Am J Respir Crit Care Med. 2020;202(1):132-135. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32396381.
- Alanio A, Delliere S, Fodil S, Bretagne S, Megarbane B. Prevalence of putative invasive pulmonary aspergillosis in critically ill patients with COVID-19. Lancet Respir Med. 2020;8(6):e48-e49. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32445626.
- Hrusak O, Kalina T, Wolf J, et al. Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment. Eur J Cancer. 2020;132:11-16. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32305831.
- Andre N, Rouger-Gaudichon J, Brethon B, et al. COVID-19 in pediatric oncology from French pediatric oncology and hematology centers: High risk of severe forms? Pediatr Blood Cancer. 2020;67(7):e28392. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32383827.
- de Rojas T, Perez-Martinez A, Cela E, et al. COVID-19 infection in children and adolescents with cancer in Madrid. Pediatr Blood Cancer. 2020;67(7):e28397. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32383819.
- Sullivan M, Bouffet E, Rodriguez-Galindo C, et al. The COVID-19 pandemic: a rapid global response for children with cancer from SIOP, COG, SIOP-E, SIOP-PODC, IPSO, PROS, CCI, and St. Jude Global. Pediatr Blood Cancer. 2020;67(7):e28409. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32400924.
- Bouffet E, Challinor J, Sullivan M, Biondi A, Rodriguez-Galindo C, Pritchard-Jones K. Early advice on managing children with cancer during the COVID-19 pandemic and a call for sharing experiences. Pediatr Blood Cancer. 2020;67(7):e28327. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32239747.
- Chiotos K, Hayes M, Kimberlin DW, et al. Multicenter initial guidance on use of antivirals for children with COVID-19/SARS-CoV-2. J Pediatric Infect Dis Soc. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32318706.