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Page 4 of 8 Kulkarni et al. J Cancer Metastasis Treat 2021;7:31 https://dx.doi.org/10.20517/2394-4722.2021.36

[8]
symptomatic COVID-19 . The mortality was 28% amongst these patients. Patients with lung cancer had
mortality of 14%, whereas mortality of patients with gastrointestinal cancers was 19%. Mortality was
significantly associated with advanced age (OR = 9.42, 95%CI: 6.56-10.02, P < 0.0001), male sex (OR = 1.67,
95%CI: 1.19-2.34, P = 0.003), and comorbidities such as hypertension (OR = 1.95, 95%CI: 1.36-2.80, P <
0.001) and cardiovascular disease (OR = 2.32, 95%CI: 1.47-3.64). When compared to patients who did not
receive recent chemotherapy, patients who received cytotoxic chemotherapy within 4 weeks of a diagnosis
of COVID-19 (N = 281, 35%) did not appear to have a greater COVID-19 related mortality (OR = 1.18,
95%CI: 0.81-1.72, P = 0.380). Similarly, there was no significant effect on mortality associated with other
classes of cancer therapy such as immunotherapy, hormonal therapy, targeted therapy, or radiotherapy use
within 4 weeks of COVID-19 diagnosis. However, the number of patients on these therapies was low (< 10%
for each therapy). Further details specifically on patients with lung cancer were not published.

Initial results from CCC-19 included 928 patients with cancer and lab-confirmed COVID-19 accrued
through April 2020. Breast (20%) and prostate (16%) cancers were most prevalent, and thoracic
malignancies comprised 10% of the cohort . By the time of data analysis, 242 patients (26%) had met the
[7]
composite outcome of death, severe illness requiring hospitalization, and/or mechanical ventilation. Thirty-
day mortality rate was 13% (N = 121). Multivariable analysis demonstrated that independent factors
associated with increased 30-day mortality were increased age (per 10 years, OR = 1.84, 95%CI: 1.53-2.21),
male sex (OR = 1.63, 95%CI: 1.07-2.48), smoking status (former smoker vs. never smoked: OR = 1.60,
95%CI: 1.03-2.47), the number of comorbidities (two vs. none: OR = 4.50, 95%CI: 1.33-15.28), Eastern
Cooperative Oncology Group (ECOG) performance status of 2 or higher (status of 2 vs. 0 or 1: OR = 3.89,
95%CI: 2.11-7.18), active cancer (progressing vs. remission: OR = 5.20, 95%CI: 2.77-9.77), and receipt of
azithromycin plus hydroxychloroquine (vs. treatment with neither: OR = 2.93, 95%CI: 1.79-4.79). Subgroup
analysis showed that neither cancer type nor its treatment was associated with 30-day all-cause mortality;
however, due to limited statistical power, extensive analysis (e.g., comparing patients with thoracic
malignancies to others) was not feasible. The most updated analysis included 2749 patients with cancer and
COVID-19 . Twenty-nine percent (N = 810) of the patients had met the composite outcome of death,
[19]
severe illness requiring hospitalization, and/or mechanical ventilation. Overall, 30-day all-cause mortality
for the CCC-19 cohort increased to 16% (N = 433) and about 60% (N = 1637) of the patients required
hospitalization. These increases are presumably due to longer median follow-up, as opposed to a general
worsening of COVID-19. Factors associated with an increased 30-day mortality were similar. However,
none of the cancer therapies (cytotoxic chemotherapy, immunotherapy, targeted therapy, endocrine
therapies, and radiation) were independently associated with an increased risk of 30-day all-cause mortality.
In this cohort, patients with lung cancer had one of the highest mortality rates of 26% (N = 61 of 237), while
thyroid and breast cancer had the lowest mortality rate among all malignancies (3% and 8%, respectively).

Thus far, the largest dataset dedicated to lung cancer and COVID-19 is the TERAVOLT (Thoracic Cancers
International COVID-19 collaboration) global registry, which has provided a greater understanding of the
patient- and cancer-specific risk factors in patients with lung cancer suffering from COVID-19 infection .
[11]
The TERAVOLT study initially reported 200 patients with thoracic cancers and COVID-19 across 8
countries, the vast majority had non-small cell lung cancer [N = 151 (76%), 147 (74%)] had stage 4 disease
and 147 (74%) were on active systemic cancer treatment. Similar to CCC-19, the hospitalization rates were
striking (76%), and overall mortality was as high as 33%. On multivariable analysis, only smoking was
associated with increased risk of mortality (OR = 3.18, 95%CI: 1.11-9.06). More importantly, any systemic
therapy, including targeted therapies (28/147, 19%), chemotherapy (48/147, 33%), and immunotherapy
(23%) or combination chemo-immunotherapy (14%), did not affect survival in patients with COVID-19. An
updated analysis of 400 patients in TERAVOLT was presented at the American society of clinical oncology