Comorbidities: 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 minimizing exposure of oncology patients to COVID-19 without compromising oncological outcome: radiation for breast cancer (Coles 2020), hematopoietic cell transplant (Dholaria 2020) and leukemia treatment (Zeidan 2020).

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

  • 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).

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).
  • In a systemic review and meta-analysis of 34 adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America (14 of 34 adult studies included only hospitalized patients), adult patients with hematologic malignancy and COVID-19 found a 34% risk of death (Vijenthira 2020), whereas pediatric patients had a 4% risk of death. Patients on systemic anticancer therapy had a similar risk of death to patients on no treatment.
  • Among 77 patients with SARS-CoV-2 who were recipients of cellular therapy (Allo, 35; Auto, 37; CAR T, 5; median time from cellular therapy, 782 days), overall survival at 30 days was 78% (Shah 2020). Mortality was largely driven by patients with active malignancy, especially relapsed leukemia, in whom the goals of care were affected by COVID-19 severity. Many patients were able to recover from COVID-19 and mount an antibody response.

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 behavior (exposure to the virus?), healthcare professional behavior (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).

References

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Dholaria B, Savani BN. How do we plan hematopoietic cell transplant and cellular therapy with the looming COVID-19 threat? Br J Haematol. 2020 Apr;189(2):239-240. PubMed: https://pubmed.gov/32180224. Full-text: 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.

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