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Cancer

Last updated: November 5, 2020

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Overview

Individuals who are immunocompromised appear to be at higher risk for severe illness with COVID-19 (CDC, May 2020; Giannakoulis, June 2020). Here we review current clinical information related to COVID-19 in patients with cancer; for information on other immunocompromised populations, see our reviews for patients with HIV and Solid Organ Transplant/Immunosuppressive Medications.

In general, patients with cancer appear to have similar COVID-19 clinical presentations to the general population.

 

Testing and Isolation

In addition to testing patients with immune compromise who are symptomatic or who have been exposed to someone with COVID-19, IDSA recommends testing asymptomatic immunocompromised patients at the time of hospital admission or before initiation of immunosuppressive therapy or transplantation (within 48-72 hours) to detect infection early.

Studies have shown that in most patients with mild to moderate disease, SARS-CoV-2 cannot be cultured 10-12 days post symptom onset, and that in 95% of patients, SARS-CoV-2 cannot be cultured after 15 of symptoms (see Isolation & Infection Control). However, in one unpublished study, SARS-CoV-2 was cultured 20 days after symptom onset in one patient who was immunocompromised (van Kampen, June 2020). In addition, patients with immune compromise may shed viral RNA longer than other populations (Zhu, June 2020).

Given these factors, CDC guidance on discontinuation of transmission-based precautions in patients with severe immune compromise differs from that it gives the general population. Transmission-based precautions can be discontinued if at least 10-20 days have passed since symptoms first appeared AND (if symptomatic) at least 24 hours have passed since the last fever without antipyretics AND (if symptomatic) respiratory symptoms have improved. A test-based strategy can also be considered, with resolution of fever and symptoms and two consecutive negative respiratory SARS-CoV-2 RT-PCR tests at least 24 hours apart. Consultation with infection control experts is also recommended.

 

Treatment Guidance

It is unclear whether cancer patients have a higher incidence of COVID-19 than the general population: some studies have found increased incidence, while others have not (Liang, March 2020; Rogado, May 2020; Bertuzzi, August 2020). Data show increased mortality in patients with cancer and COVID-19, but it is not clear whether cancer is an independent risk factor, or if patients with cancer are more likely to have conditions associated with worse COVID-19 outcomes, such as old age, poor performance status or diabetes (Docherty, May 2020; Brar, September 2020). Data on the effect of recent cytotoxic chemotherapy, immunotherapy, etc., on mortality are also mixed (Kuderer, May 2020; Luo, August 2020; Robilotti, August 2020; Brar, September 2020; Lee, October 2020). Some data suggest patients with lung cancer and hematologic malignancy are at increased risk for severe disease (Passamonti, August 2020; Luo, October 2020), and that depending on the types of cancer, there may be an association of different rates of mortality when concurrent with COVID-19 (Lee, October 2020).

Whether or not to pause cancer therapies in patients with active COVID-19 depends on the risks and benefits of withholding the drug.

The American Society of Clinical Oncology recommends:

  • Chemotherapy: Interrupting anti-cancer treatment in patients with active COVID-19 should be based on the risk of interrupting cancer treatment versus the “poorly defined risk of adverse COVID-19 outcomes in patients receiving active cancer treatment.”
  • Checkpoint inhibitors: In patients with active COVID-19, these drugs can be dosed less frequently if it is reasonable to do so from a cancer standpoint.
  • Bone marrow/stem cell transplantation: If a patient pending a transplant develops active COVID-19 and is able to be managed on conventional treatment, it is not unreasonable to delay stem cell transplantation for up to 3 weeks and until symptoms resolve.

The American Society for Therapeutic Radiology and Oncology notes:

  • Radiation: Hypo fractionated radiation schedules can be considered if “reasonable” — meaning the cancer is not rapidly progressing and is potentially curable.

Here we review select key epidemiologic literature relating to COVID-19 in patients with solid and hematologic malignancies, focusing on the largest studies/studies with the highest level of evidence, with the most generalizable results. 

 

Key Literature

In summary: It is not clear if COVID-19 occurs at a higher incidence in patients with cancer compared to the general population. Observational studies suggest a higher risk of severe disease in this group, but whether this is due to the cancer state itself or due to comorbidities or increasing age is not clear. The management of these patients for cancer and COVID-19 does not differ from the general population.

 

COVID-19 prevalence and mortality in patients with cancer and the effect of primary tumor subtype and patient demographics: a prospective cohort study (Lee, October 2020).

Patient population:

  • 1,044 adult patients with cancer who were diagnosed with COVID-19 and enrolled in the U.K. Coronavirus Cancer Monitoring Project cohort between March 18 and May 8, 2020, compared with a parallel non-COVID-19 U.K. cancer control population from the U.K. Office for National Statistics (2017 data).
  • 9% of the patients were male, and the median age was 70 years (IQR 60–77).

Primary endpoint:

  • Effect of primary tumor subtype, age and sex on COVID-19 and the case-fatality rate during hospital admission.

Key findings:

  • 295 of 1,044 patients in the cohort (28%) died from COVID-19.
  • The all-cause case fatality rate in patients with cancer after SARS-CoV-2 infection was significantly associated with increasing age, rising from 0.10 in patients aged 40–49 years to 0.48 in those aged 80 years and older.
  • All-cause case fatality rate in patients with cancer once they had contracted COVID-19 was significantly associated with sex (35.6% of male patients vs. 23.6% of female patients; OR 1.92, p<0.0001).
  • Patients with hematological malignancies (leukemia, lymphoma and myeloma) had a more severe COVID-19 trajectory compared with patients with solid organ tumors (OR57; p<0.0043).
  • On univariable analysis there was a higher risk of death from COVID-19 in patients with prostate cancer (OR 2.14; p=0.014) and leukemia (2.03; p=0.038), and a significantly lower risk of death from COVID-19 for patients with breast cancer (0.53; p=0.049) and female genital cancers (0.36, p=0.031).
  • On multivariable correction for age and sex, compared with the rest of the UKCCMP cohort, only patients with leukemia still showed a significantly increased case fatality rate (OR 2.25; p=0.023).
  • After adjustment for potential confounding variables of age and sex, patients with hematological malignancies were significantly more likely to require high flow oxygen (OR 1.82; p=0.015), non-invasive ventilation (OR 2.10; p=0.014) and intensive care unit admission for ventilation (OR 2.73; p=0.0019) and have a severe or critical disease course (OR 1.57; p=0.0043).
  • After correction for age and sex, patients with hematological malignancies who had recent chemotherapy had an increased risk of death during COVID-19-associated hospital admission (OR 2.09; p=0.028).

Limitations:

  • Retrospective study, which could have led to bias.
  • The control group was from 2017; therapies may have changed since then.
  • The cohort consisted of patients with symptomatic cancer who seek help from cancer centers; therefore, the results may not be generalizable to all patients with cancer.
  • Performance status, ethnicity and comorbidities were not included in data collection.

Overall, after adjusting for age and sex, only hematologic malignancies (not solid tumors) were associated with an increased case fatality rate from COVID-19.

 

Mortality in patients with cancer and coronavirus disease 2019: A systematic review and pooled analysis of 52 studies (Saini, September 2020).

Patient population:

  • 18,650 patients from 52 studies of patients with both COVID-19 and cancer that reported mortality rates.

Primary endpoint:

  • Case fatality rate, defined as the rate of death among patients with cancer and COVID-19. 

Key findings:

  • 4,243 deaths were recorded.
  • The probability of death was 25.6% (95% CI, 22–29.5%; I2=48.9%).

Limitations:

  • Evaluated overall mortality rate only; did not control for potential confounders (such as comorbidities and age) or account for different types of malignancies.

Overall, in this systematic review, the mortality rate of patients with cancer and COVID-19 was high; however, it did not control for comorbidities.

 

COVID-19 Severity and Outcomes in Patients with Cancer: A Matched Cohort Study (Brar, September 2020).

Patient population:

  • Cohort of adult patients presenting to the emergency departments of 2 New York City hospitals who were diagnosed with COVID-19.
  • In this study 117 patients with active cancer were included, and for every cancer case there were 4 matched controls with COVID-19 and without a cancer diagnosis — a total of 468.
  • The median age was 71 years, and 55% were male.
  • More patients with cancer were white (47%) compared to patients without cancer (38%).
  • Comorbidities were similar between the two groups.
  • Seventy-four percent of patients with cancer were older than 65 years, and 74% of patients had 0-1
  • The most common type of cancer was genitourinary (18.8%), followed by GI (16.2%), chronic leukemia (16.2%) and breast (12.8%).
  • 45% of patients were receiving active cancer therapy, including cytotoxic or immunosuppressive treatment, and 37% of patients had received cytotoxic treatment within 90 days of their emergency department admission.

Primary endpoint:

  • Composite incident outcome of ICU admission, intubation and death.

Key findings:

  • There were 29 deaths among hospitalized patients with cancer (24.8%) compared with 100 deaths among patients without cancer (21.4%; p=.894).
  • There was no difference in death or composite outcome (death, intubation or ICU admission) among patients with versus without cancer.
  • There were no differences in composite outcome between hematologic and solid malignancies in terms of ICU admissions, intubation or death (p=.283).
  • There was no difference in outcome if patients were treated with cytotoxic therapy within 90 days of admission (p=.446).
  • In a multivariable marginal Cox model, age was a predictor of both composite outcome (HR, 1.19 [95% CI, 1.04 to 1.36]) and death (HR, 2.05 [95% CI, 1.72 to 2.42]); obesity was significant only for the composite outcome (HR, 1.85 [95% CI, 1.37 to 2.50]).

Limitations:

  • Observational study; bias is possible.
  • The cohort was heterogeneous; it is not clear the data is generalizable.
  • Not all patients had the outcome of interest occur during the study.
  • Use of a composite endpoint could limit the generalizability of the results.

Overall, in this matched cohort study, patients with and without cancer had similar outcomes for a composite endpoint of death, intubation and ICU admission.

 

Case Fatality Rate of Cancer Patients with COVID-19 in a New York Hospital System (Mehta, July 2020).

Patient population:

  • 218 patients with cancer and COVID-19 treated at Montefiore Health Systems in New York City.
  • 164 patients had solid tumors (75%) and 54 had hematologic malignancies (25%).
  • The median age was 69 years (IQR 10–92 years).

Primary endpoint:

  • To describe the clinical characteristics and outcomes of patients with cancer and COVID-19.

Key findings:

  • 61 patients (28%) died from COVID-19.
  • The mortality rate was 25% among all patients with solid tumors and occurred at higher rates in patients with lung cancers (55%), gastrointestinal cancers [colorectal (38%), pancreatic (67%), upper GI (38%)] and gynecologic malignancies (38%).
  • Rates of ICU admission and ventilator use were slightly higher for hematologic malignancies than solid tumors (26% vs. 19% and 11% vs. 10%, respectively), but did not achieve statistical significance.
  • In propensity score matching with controls, the observed case fatality rates were elevated in all age cohorts in patients with cancer and achieved statistical significance in the age groups 45–64 and in patients >75 years of age.

Limitations:

  • The study design was retrospective; bias is possible.
  • Did not control for differential treatment paradigms for COVID-19 infection and sequelae.
  • Because of limited follow-up, the full clinical course of these patients may not be included.
  • The study occurred at a single center; the findings may not be generalizable.

Overall, in this retrospective single-center study, the mortality rate in patients with COVID-19 and cancer was high.

 

Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study During the COVID-19 Outbreak (Dai, June 2020).

Patient population:

  • 105 patients at 14 hospitals in China with cancer and COVID-19; 536 patients without cancer and COVID-19.

Primary outcome:

  • To describe the clinical characteristics and outcomes of those with cancer and COVID-19 compared to those without cancer.

Key findings:

  • In 105 patients with cancer, lung cancer was the most frequent cancer type (20.95%), followed by gastrointestinal cancer (12.38%) and breast cancer (10.48%).
  • COVID-19 patients with cancer showed similar signs and symptoms upon admission as those without cancer, except for a higher prevalence of chest distress (15 [14.29%] of 105 patients vs. 36 [6.16%] of 536 patients; p=0.020.
  • Compared to COVID-19 patients without cancer, patients with cancer had higher observed death rates (OR, 2.34; p=0.03), higher rates of ICU admission (OR, 2.84; p<0.01), higher rates of having at least one severe or critical symptom (OR, 2.79; p<0.01) and higher chances of needing invasive mechanical ventilation.
  • In general, patients with cancer deteriorated more rapidly compared to those without cancer, with those with lung cancer having the worst outcomes.

Limitations:

  • Single country study; may not be generalizable to other countries.
  • Small cohort of patients with cancer.
  • The study design was retrospective; bias is possible.

Overall, in this retrospective study, patients with cancer had similar symptoms of COVID-19, but a higher mortality and adverse outcome rate.

 

Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study (Kuderer, May 2020).

Patient population:

  • 928 patients from the U.S., Canada and Spain with active or previous malignancy and confirmed SARS-CoV-2 infection included in the COVID-19 and Cancer Consortium database.
  • Median age was 66 years (IQR 57–76); 279 (30%) were >75 years.
  • The most prevalent malignancies were breast (21%) and prostate (16%).
  • 366 (39%) patients were on active anti-cancer treatment, and 396 (43%) had active cancer.

Primary endpoint:

  • All-cause mortality within 30 days of COVID-19 diagnosis.

Key findings:

  • 121 (13%) patients died.
  • Independent factors associated with increased 30-day mortality were: increased age (per 10 years; aOR 1.84, 95% CI, 1.53–2.21), male sex (1.63, 95% CI, 1.07–2.48), smoking status (former smoker vs. never smoked: 1.60, 95% CI, 1.03–2.47), number of comorbidities (two vs. none: 4.50, 95% CI, 1.33–15.28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs. 0 or 1: 3.89, 95% CI, 2.11–7.18), active cancer (progressing vs. remission: 5.20, 95% CI, 2.77–9.77) and receipt of azithromycin plus hydroxychloroquine (vs. treatment with neither: 2.93, 95% CI, 1.79–4.79; confounding by indication cannot be excluded).
  • Race and ethnicity, obesity status, cancer type, type of anti-cancer therapy and recent surgery were not associated with mortality.

Limitations:

  • There were regional differences in patient characteristics, which may have impacted the primary outcome.

Overall, in this retrospective study of patients with cancer and COVID, all-cause mortality was high and associated with various comorbidities; cancer type and type of anti-cancer therapy were not associated with mortality.

 

COVID-19 mortality in patients with cancer on chemotherapy or other anti-cancer treatments: a prospective cohort study (Lee, May 2020).

Patient population:

  • Prospective observational study of 800 patients with a diagnosis of cancer and symptomatic COVID-19 enrolled via the U.K. Coronavirus Cancer Monitoring Project registry.

Primary endpoint:

  • To describe the clinical and demographic characteristics and COVID-19 outcomes in patients with cancer.

Key findings:

  • 412 patients (52%) had mild COVID-19.
  • 226 patients (28%) died, and the risk of death was significantly associated with advancing patient age (OR 9.42; p<0.0001), being male (OR 1.67; p=0.003) and the presence of other comorbidities such as hypertension (OR 1.95; p<0.001) and cardiovascular disease (OR 2.32; p=0.0019).
  • 281 (35%) received chemotherapy 4 weeks prior to testing positive for COVID-19.
  • After adjusting for confounders, chemotherapy in the past 4 weeks had no significant effect on mortality from COVID-19 compared with not receiving chemotherapy.

Limitations:

  • The analysis is dependent on the U.K. testing policy, which is less permissive than other parts of the world; therefore, there may be an underreporting of COVID-19 cases.

Overall, in this prospective study of patients with cancer and COVID-19, chemotherapy in the last 4 weeks was not associated with increased mortality.

 

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