Comorbidities: Cancer

Cancer

Providing continuous and safe care for cancer patients is challenging in this pandemic. Oncologic patients may be vulnerable to infection because of their underlying illness and often immunosuppressed status and may be at increased risk of developing severe complications from the virus. On the other hand, the COVID-19 triage and management may stretch an already fragile system and potentially leave uncovered some vital activities, such as treatment administration or surgeries. It is well established that suboptimal timing and delayed oncologic treatment may lead to disease progression, leading to worse survival outcomes. There are several recommendations to minimising exposure of oncology patients to COVID-19 without compromising oncological outcome: Radiation for breast cancer (Coles 2020), hematopoietic cell transplantion (Dholaria 2020) and leukemia treatment (Zeidan 2020).


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What is known about risk factors, besides general risk factors such as age, male gender and other comorbidities?

  • Compared to 519 statistically matched patients without cancer, 232 patients from Wuhan were more likely to have severe COVID-19 (64% vs 32%). An advanced tumour stage was a risk factor (odds ratio 2.60, 95% CI 1.05–6.43) (Tian 2020).
  • A systematic review of all studies until June 3 indicated that patients with hematological malignancies, especially those diagnosed recently (and likely those with myeloid malignancies), were at increased risk of death with COVID‐19 compared to the general population. The evidence that this risk is higher than for those with solid malignancies was conflicting (El-Sharkawi 2020).
  • Patients with Chronic Lymphatic Leukemia (CLL) seem to be at particular high risk of death. Of 198 CLL patients diagnosed with symptomatic COVID-19, 39% were treatment-naïve (“watch and wait”) while 61% received at least one CLL therapy. At 16 days, the overall CFR was 33%, while another 25% were still in hospital (Mato 2020).
  • In a retrospective study from Italy, including 536 patients with a diagnosis of a hematological malignancy, 198 (37%) had died. Progressive disease status, diagnosis of acute myeloid leukemia, indolent or aggressive NHL were associated with worse overall survival (Passamonti 2020).
  • In a large cohort study of 928 cancer patients with COVID-19 from the USA, Canada, and Spain, most prevalent malignancies were breast (21%) and prostate (16%). In total 121 (13%) patients had died. Independent risk factors were an ECOG status of 2 or higher and “active” cancer (Kuderer 2020).
  • SARS-CoV-2 viral load in nasopharyngeal swab specimens of 100 patients with cancer who were admitted to three New York City hospitals predicted outcome. The authors also found that patients with hematologic malignancies had higher median viral loads than patients without cancer (Westblade 2020).

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Does anti‐neoplastic treatment lead to increased risk of complications?

  • Among a total of 309 patients, cytotoxic chemotherapy administered within 35 days of a COVID-19 diagnosis was not significantly associated with a severe or critical COVID-19 event. However, patients with active hematologic or lung malignancies, lymphopenia, or baseline neutropenia had worse COVID-19 outcomes.
  • Among 423 cases of symptomatic COVID-19 patients, 40% were hospitalized and 12% died within 30 days. Age older than 65 years and treatment with immune checkpoint inhibitors were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not (Robilotti 2020).

All these studies are not controlled. A myriad of potential factors may lead to a difference in COVID-19 outcomes and risk for patients with malignancies, compared to the rest of the population (nice review: El-Sharkawi 2020). These include patient behaviour (exposure to the virus?), healthcare professional behaviour (i.e., testing patients with a history of cancer for COVID‐19 more frequently?), biological differences but also several confounders (more co-morbidities, older age in cancer patients). Continued analysis of the data is required to attain further understanding of the risk factors for cancer patients in this pandemic.

Finally, it’s not only treatment, it’s also diagnosis. Diagnostic delays may lead to an increase in the numbers of avoidable cancers (Maringe 2020). During the pandemic, a large cross-sectional study in the US has observed significant declines in several cancer types, ranging from 24.7% for pancreatic cancer to 51.8% for breast cancer, indicating that a delay in diagnosis will likely lead to presentation at more advanced stages and poorer clinical outcomes (Kaufman 2020).


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References

Coles CE, Aristei C, Bliss J, et al. International Guidelines on Radiation Therapy for Breast Cancer During the COVID-19 Pandemic. Clin Oncol (R Coll Radiol). 2020 May;32(5):279-281. PubMed: https://pubmed.gov/32241520. Full-text: https://doi.org/10.1016/j.clon.2020.03.006

Dholaria B, Savani BN. How do we plan hematopoietic cell transplant and cellular therapy with the looming COVID-19 threat? Br J Haematol. 2020 Mar 16. Fulltext: https://doi.org/10.1111/bjh.16597

El-Sharkawi D, Iyengar S. Haematological Cancers and the risk of severe COVID-19: Exploration and critical evaluation of the evidence to date. Br J Haematol. 2020 Jun 19. PubMed: https://pubmed.gov/32559308. Full-text: https://doi.org/10.1111/bjh.16956.

Kaufman HW, Chen Z, Niles J, Fesko Y. Changes in the Number of US Patients with Newly Identified Cancer Before and During the Coronavirus Disease 2019 (COVID-19) Pandemic. JAMA Netw Open 2020;3(8):e2017267. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.17267.

Kuderer NM, Choueiri TK, Shah DP, et al. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet. 2020 May 28:S0140-6736(20)31187-9. PubMed: https://pubmed.gov/32473681. Full-text: https://doi.org/10.1016/S0140-6736(20)31187-9

Lee J, Foote MB, Lumish M, et al. Chemotherapy and COVID-19 Outcomes in Patients With Cancer. J Clin Oncol 2020, August 14, 2020. Full-text: https://ascopubs.org/doi/full/10.1200/JCO.20.01307

Maringe C, Spicer J, Morris M, et al. The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study. Lancet Oncology,  published: July 20, 2020. Full-text: https://doi.org/10.1016/S1470-2045(20)30388-0.

Mato AR, Roeker LE, Lamanna N, et al. Outcomes of COVID-19 in Patients with CLL: A Multicenter, International Experience. Blood. 2020 Jul 20:blood.2020006965. PubMed: https://pubmed.gov/32688395. Full-text: https://doi.org/10.1182/blood.2020006965.

Passamonti F, Cattaneo C, Arcaini L, et al. Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study. Lancet Haematol 2020, published 13 August. Full-text: https://doi.org/10.1016/S2352-3026(20)30251-9

Robilotti EV, Babady NE, Mead PA, et al. Determinants of COVID-19 disease severity in patients with cancer. Nat Med June 24, 2020. Full-text: https://doi.org/10.1038/s41591-020-0979-0

Tian J, Yuan X, Xiao J, et al. Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, retrospective, cohort study. Lancet Oncol. 2020 May 29:S1470-2045(20)30309-0. PubMed: https://pubmed.gov/32479790. Full-text: https://doi.org/10.1016/S1470-2045(20)30309-0

Westblade LF, Brar G, Pinheiro LC, et al. SARS-CoV-2. Viral Load Predicts Mortality in Patients with and Without Cancer Who Are Hospitalized with COVID-19. Cancer Cell 2020, published 15 September. Full-text: https://doi.org/10.1016/j.ccell.2020.09.007

Zeidan AM, Poddu P, Patniak MM, et al. Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts. Lancet Hematology 2020, June 18. Full-text: https://doi.org/10.1016/S2352-3026(20)30205-2