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Kulkarni et al. J Cancer Metastasis Treat 2021;7:31 https://dx.doi.org/10.20517/2394-4722.2021.36 Page 5 of 8

[20]
(ASCO) Annual Meeting 2020 . Hospitalization rates (78%) and overall mortality were similar (35%) to the
previously published data. However, in the updated analysis, patients with age > 65 (OR = 1.70, 95%CI: 1.09-
2.63, P = 0.018), presence of comorbidities, ECOG PS ≥ 1 (OR = 2.14, 95%CI: 1.11-4.11, P < 0.001), use of
steroids (equivalent of prednisone > 10 mg/day) (OR = 1.49, 95%CI: 1.00-2.23, P = 0.052) and
anticoagulation prior to COVID-19 diagnosis were associated with increased risk of death. As opposed to
earlier analysis, prior administration of chemotherapy (alone or with immunotherapy) within 3 months of
COVID-19 diagnosis (OR = 1.71, 95%CI: 1.12-2.63, P = 0.025) was associated with increased risk of death.
Whereas receipt of immunotherapy or targeted therapy did not increase risk for mortality. In a sub-group
analysis, patients with rare thoracic malignancies (small cell lung cancer, mesothelioma) appeared to have
[21]
mortality of 40% . Furthermore, TERAVOLT recently presented updated analysis from 1053 patients at
the 2020 World Conference on Lung Cancer meeting . The overall mortality was similar to that in the
[22]
previous studies (33%). On multivariate analysis, male sex, older age, worse performance status, and four or
more metastatic sites were associated with increased risk of death. Race and ethnicity did not seem to affect
the risk of death. Full results of this data are awaiting publication. Table 2 summarizes the factors associated
with severe COVID-19 and or mortality across all the studies.

CONCLUSIONS
Metanalyses of independent studies have consistently shown high mortality in patients with cancer and
COVID-19. For instance, in a metanalyses study of 2922 patients across 18 studies, the pooled 30‐day
mortality rate was 30% in hospitalized patients where as it was about 15% among patients who were treated
either in hospital or outpatient setting . In another metanalysis of 15 studies among 3019 patients, the
[23]
mortality rate was 22.4% . In both studies a higher mortality was associated with older age and male
[24]
gender. In comparison to other cancers, patients with lung cancer and COVID-19 particularly have a
disproportionately higher mortality ranging from 11% to 40%. Amongst all studies, clinical factors
consistently associated with increased risk of severe COVID-19 or death in lung cancer patients include
advancing age, and comorbidities such as hypertension or smoking history. In the largest studies to date in
lung cancer population, use of cytotoxic chemotherapy (alone or in combination with immunotherapy) has
shown increased risk for mortality . In contrast, none of the other studies or metanalyses reported this
[20]
[25]
association with the caveat that most of these studies were across all cancers. Reassuringly, use of
immunotherapy or targeted therapy was not convincingly associated with increased mortality in any
studies. While these data may be limited by short follow-up time, it suggests that providers should not
withhold or delaying lung cancer treatment significantly due to the risk of COVID-19. The pandemic has
resulted in substantial challenges to cancer care delivery leading to significant delays in screening and
diagnosis, systemic therapy, and curative intent surgery. The long-term impact of this delay has yet to be
determined. National and international societies like ASCO, National comprehensive cancer network and
European society of medical oncology have issued guidelines for lung cancer care during the COVID-19
pandemic based on risk stratification, comorbidities, and stage of cancer [26-28] . While COVID-19 infection is
potentially disproportionately life-threatening for patients with lung cancer, the risks in delaying cancer care
can likewise result in devastating outcomes. As we evolve and adapt to emerging data, we encourage
institutions to continue to approach the treatment of patients with lung cancer in an individualized,
multidisciplinary approach. While highly effective vaccines are currently being rolled out, and bring hope to
patients and providers alike, it is projected that several more months will pass before high-risk patients such
as those with lung cancer will have access to the vaccine. Therefore, ongoing mitigation efforts like mask or
face covering, physical distancing, and optimizing virtual care will continue to be fundamental in the fight
against the COVID-19 pandemic and its devastating impact on patients with cancer.