Shift in Lung Cancer Stage at Diagnosis during the COVID-19 Pandemic in New York City

Introduction: New York City was the first place in the US to record a COVID-19 case on March 1, 2020, and soon became the epicenter of the pandemic. Because of the large number of hospitalized patients, Governor Cuomo imposed a halt on all elective care from March 22 to June 8, 2020. Such action resulted in delayed cancer screening rates, care and treatment. However, no study has quantified the effect of the “pause” on cancer stage at diagnosis, one of the best indicators of cancer prognosis. We analyze here data from the Mount Sinai Heath System cancer registry;we chose lung cancer as an example of a condition where early diagnosis can dramatically modify survival. Methods: Lung cancer cases diagnosed between January 1, 2018 and February 28, 2021 (n=1884) at the Mount Sinai Health System were identified from Mount Sinai’s cancer registry, based on ICD-10 codes of C34.x. Only analytic cases (00-22) were included, based on Commission on Cancer guidelines. For multi-tumor or multi-hospital cases, unique patients were identified by selecting the earliest date of diagnosis. The ratio of the number of monthly cases in 2020-2021 over the average number of monthly cases in 2018 and 2019 was calculated. The percent of monthly diagnoses with early (0/I/II), late (III/IV) and unknown stage over the total number of monthly diagnoses was examined and was compared to the average percent in 2018 and 2019 from the same month. Results: The number of diagnoses sharply dropped in March 2020, reaching a minimum in April (78% lower than pre-pandemic averages), and returned to near pre-pandemic levels by July 2020, began to decline again in January and February 2021 (35% lower than pre-pandemic averages) (Figure 1a). Stages 0/I/II dropped to 21.9% of total in May 2020, while stage III/IV hit 75% in April 2020. Early stage diagnoses dropped again to 23.5% of total, while late stages increased to 64.7% of total in February 2021 (Figure 1b). The percent of stage III/IV diagnoses in April of 2020 was 1.79 times greater than the pre-pandemic average, the percent of stage 0/I/II diagnoses was 50% lower. The percent of stage 0/I/II cases increased between August 2020 and January 2021, but in February 2021 it was 50% lower than pre-pandemic levels, and the percent of stage III/IV diagnoses was 1.3 times greater than pre-pandemic levels (Figure 1c). Conclusions: This descriptive analysis suggests an immediate negative impact on lung cancer diagnoses of COVID-19 restrictions, which affected screening, early detection, and drastically reduced any patient’s contact with the health system that would have prompted an early lung cancer diagnosis. The increase in late stage diagnoses during pandemic surges may reflect the fact that only sick patients with symptoms, and acute events that require immediate care were seeking hospital attention. The data suggests that we will likely observe an increase in lung cancer mortality in the next few months and years, as consequence of stage shift at diagnosis associated with the COVID-19 pandemic. Keywords: Lung cancer, Covid-19, Stage shift

Analysis of Lung Cancer Patients Receiving SARS-CoV-2 Vaccines Revealed a Minority Subset With Poor Antibody Responses Relative to Controls

Introduction: Patients with lung cancer (LC) were reported to have a high case fatality rate (30-40%) from SARS-CoV-2 infection, raising the question of whether LC patients mount a weaker antibody response to natural infection and/or vaccination, compared to healthy controls (HCs). We previously analyzed antibody responses to SARS-CoV-2 mRNA vaccination in several hundred healthy individuals, stratified by previous SARS-CoV-2 infection status. Using a validated enzyme-linked immunosorbent assay (ELISA) to the full-length spike protein (PMC8183627, PMC7235504), we found strong responses to infection and a robust neutralizing antibody response to vaccination. We compare these results to data from individuals diagnosed with LC undergoing different types of cancer treatment. Methods: This is an ongoing, prospective, control-matched longitudinal cohort study of 750 LC patients in all stages with or without previous SARS-CoV-2 infection and/or vaccination, comparing SARS-CoV-2 antibody titers at baseline (time of enrollment) and at 3-, 6-, 12- and 24-month intervals. We examine the quality, magnitude, and duration of the SARS-CoV-2 antibody titers against the full-length spike protein compared to the matched (age, tobacco history, sex and ethnicity) HC cohort. Types of Analysis and Data Reporting: ELISAs are performed in a CLIA-certified laboratory using an FDA-approved antibody assay along with other well-established, research-grade assays. We hypothesized that LC patients have a weaker antibody response to SARS-Cov-2 infection and/or vaccination due to cancer or its treatment compared to matched HCs. The non-parametric Kruskal–Wallis test was used to test this hypothesis. If confirmed, a tailored vaccination program would be necessary to ensure immune protection in patient with LC. Results: 111 LC patients have been enrolled to date;with 78 receiving at least one vaccination and 33 unvaccinated. Median age is 69, with 58% female. 39 patients were fully vaccinated (defined as 14+ days after second vaccination). Partially vaccinated (after 1st vaccine dose) LC patients had a lower median antibody level than partially vaccinated HCs (p=0.01). Fully vaccinated LC patients had substantial antibody titers but a lower median antibody level than fully vaccinated HCs (p=0.01) with a subset not raising large antibody titers. Especially important were the 30% of partially vaccinated LC patients who did not develop neutralizing antibodies. To date, there were no significant differences in median antibody levels in LC patients by gender, smoking status, age (< or > 65 years old), or treatment (with or without chemotherapy, immune checkpoint inhibitors, or targeted therapy). Conclusion: While most (∼70%+) of LC patients mounted a good antibody response to vaccination, a subgroup had significantly lower anti-spike antibody/neutralizing levels compared to controls. Further studies are required to evaluate the role of further boost vaccinations in this patient population with a particular focus on patients not producing neutralizing antibodies to further understand the lack of response. We will continue to analyze the effect of systemic anti-cancer therapies as more data becomes available. Keywords: SARS-CoV-2, lung cancer, covid-19

Risk of morbidity and mortality inCOVID-19 patients with cancer

Introduction: Morbidity and mortality of cancer patients with COVID-19 have not been examined. The goal of thisanalysis was to compare the demographics and clinical characteristics of COVID-19 cancer patients to the rest ofCOVID-19 patients and assess whether cancer is associated with morbidity or mortality. Methods: COVID-19-positive patients with an inpatient or emergency encounter at the Mount Sinai Health Systembetween 03/01/20-05/27/20 were included in the analysis. Patients were compared across cancer status(noncancer, non-solid cancers, and solid cancers) on demographics and clinical characteristics. Multivariable logisticregressions were used to model the associations of cancer status with sepsis, acute venous thromboembolism, andmortality. Results: There were 5,516 COVID-19 positive patients included, 96 (1.7%) with non-solid cancers and 325 (5.8%)with solid cancers. Those with solid cancers were significantly older (mean: 70.9 vs. 63.8 and 63.2 years) and morelikely to be non-Hispanic Black (26.5% vs. 23.9% and 22.9%) than noncancer and non-solid cancers patients. Those with cancer had significantly more additional comorbid conditions (42.7% and 49.8% ≥2 comorbidities for non-solidand solid cancers, vs. 30.4% for noncancer). Platelets (mean [noncancer]: 223.8, mean [non-solid cancer]: 182.6, mean [solid cancer]: 218.3 × 10 /μL), white blood cell count (mean [noncancer]: 8.4, mean [non-solid cancer]: 6.7, mean [solid cancer]: 8.0 × 10 /μL), hemoglobin (mean [noncancer]: 13.1, mean [non-solid cancer]: 11.2, mean [solidcancer]: 12.0 g/dL), and red blood cell count (mean [non-cancer]: 4.5, mean [non-solid cancer]: 3.7, mean [solid cancer]: 4.1 × 10 /μL) were significantly lower in cancer patients, and lowest in those with non-solid cancers. Afteradjustment and compared to noncancer patients, those with cancer had significantly higher risk of acute venousthromboembolism (OR : 1.77, 95% CI: 1.01-3.09) and sepsis (OR : 1.34, 95% CI: 1.09-1.64). There was nosignificant difference in mortality (OR : 1.02, 95% CI: 0.81-1.29). There was no significant difference in alloutcomes for solid and non-solid cancer types. Conclusion: COVID-19 patients with cancer, particularly solid tumors, are significantly older, with morecomorbidities than those without cancer. There was no statistically significant difference in mortality for COVID-19patients with cancer, but a significantly higher risk of thromboembolism and sepsis. Further research into the effectthat cancer treatments may have in inflammatory and immune responses to COVID is warranted.