Cryo-electron tomography of biological specimens

Cryo-electron tomography (CET) is an imaging technique capable of visualizing the three-dimensional (3-D) structure of complex viruses, cells, and tissues in hydrated state. With the current resolution of 4-5 nm, CET can resolve supramolecular complexes that are responsible for many cellular functions. This paper discusses the important considerations in CET of biological specimens and identify areas where digital signal processing can make a decisive contribution. Topics discussed include the principles of electron tomography and CET, image background and feature contrasts in CET, acquisition and alignment of projection images, reconstruction of the image volume, denoising and segmentation of tomograms, and feature recognition in cellular tomograms

OA06.06 Impact of Systemic Anti-cancer Treatments on Outcomes of COVID-19 in Patients with Thoracic Cancers: CCC19 Registry Analysis

Introduction: Patients with thoracic cancers (TC) have one of the highest rates of mortality among patients with cancer and COVID-19. Data evaluating the impact of recent anti-cancer therapies on COVID-19 outcomes in patients with TC are confined to small heterogenous retrospective studies, with limited follow-up data. We analyzed data from the COVID-19 and Cancer Consortium (CCC19) (NCT04354701) to examine the impact of recent systemic therapies on the clinical outcomes of COVID-19 in patients with TC. Methods: The CCC19 registry was queried for adult patients with TC and lab-confirmed SARS-CoV-2 infection. Only patients with data quality scores of 0-4 were included in the analysis. The primary outcome was 30-day all-cause mortality. Secondary outcomes were need for oxygen supplementation, hospitalization, ICU admission, and mechanical ventilation. The outcomes were further stratified by demographics, smoking history, ECOG PS (0, 1, \u3e2), cancer status (remission, responding/stable, progressing) and type of systemic treatment \u3c3 months prior to COVID-19 (chemotherapy with or without immunotherapy, chemotherapy plus radiation, immunotherapy alone or targeted therapy). Results: From January 2020 to December 2021, 900 patients with thoracic cancer met the inclusion criteria. The median age was 70 years (IQR 62-77), 53% were female, 79% were former or current tobacco users, 56% of patients had ECOG PS of 0 or 1, and 34% of patients had active but stable or responding cancer. Fifty-three percent (N=477) of patients received at least one anti-cancer systemic therapy \u3c3 months prior to COVID-19 diagnosis. Chemotherapy with or without immunotherapy was the most prevalent treatment exposure (51%; N=242). After a median follow-up of 70 days (IQR 28-180), 30-day all-cause mortality was similar in patients who received any systemic cancer treatment versus no cancer treatment (23% and 22% respectively). Patients treated with immunotherapy and targeted therapy had the lowest mortality (15% and 18% respectively), the majority of whom were treated with palliative intent. Similar trends were also noted with secondary outcomes (Table 1). Conclusions: We report one of the largest studies evaluating the clinical outcomes of COVID-19 in the context of recent systemic anti-cancer treatments for TC. While continued caution is required when utilizing systemic treatments, delays in treatment may not be justified. The study provides reassuring data that patients receiving immunotherapy or targeted therapy even in the context of palliative treatment appear to have a lower risk for all-cause COVID-19 mortality. Further analysis exploring the prognostic factors associated with poor outcomes in patients with chemoradiation is planned

Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma

INTRODUCTION: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy. METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors. RESULTS: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35). CONCLUSIONS: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors

COVID-19 Severity and Cardiovascular Outcomes in SARS-CoV-2-Infected Patients With Cancer and Cardiovascular Disease

BACKGROUND: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. OBJECTIVES: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. METHODS: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD RESULTS: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all CONCLUSIONS: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701)