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Daniel Steinfort



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    FP10 - Small Cell Lung Cancer/NET (ID 231)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP10.02 - Investigating the Immunophenotype of Small Cell Lung Cancer to Improve Immunotherapeutic Targeting (ID 1686)

      00:00 - 00:00  |  Author(s): Daniel Steinfort

      • Abstract
      • Presentation
      • Slides

      Introduction

      Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer and although most patients initially respond to platinum-based chemotherapy, resistance rapidly develops. Immunotherapy has promise in the treatment of lung cancer, however SCLC patients exhibit poor overall responses. This highlights the necessity for alternative treatment approaches. Recently, SCLC has been divided into four subtypes based on the expression of key transcription factors, ASCL1, NEUROD1, POU2F3 and YAP1. Though it has been speculated that these subtypes may respond differentially to therapeutic interventions, response to cytotoxic immune cell killing has not been investigated.

      Methods

      We have investigated the immune microenvironment (IM) profiles of human SCLC patients on freshly obtained endobronchial ultrasound biopsies. We characterized the IM through antibody panels (flow cytometry) and unbiased hierarchal clustering (single-cell sequencing). Immune cell signatures were also interrogated in publicly available human SCLC datasets. Subcutaneous transplantation studies utilizing syngeneic SCLC cell lines were performed to functionally validate the role of cytotoxic immune cell populations. Tumor growth, metastatic dissemination and the activation of CD8+ T and natural killer (NK) cells were evaluated by histology and flow cytometry.

      Results

      Transcriptomic analysis of treatment naïve human SCLC samples revealed heterogeneous immune checkpoint and cytotoxic signature profiles. We identified that immune cell infiltration scores stratified the four subtypes of SCLC, suggesting immunotherapeutic targeting may be prognostic in some patient cohorts. To functionally evaluate the role of cytotoxic immune cells in the surveillance of SCLC, we demonstrated that the absence of NK cells, but not CD8+ T cells, significantly enhanced metastatic dissemination of SCLC in vivo.

      Conclusion

      These proof-of-principle findings provide a rationale for exploiting the anti-tumor functions of NK cells in the treatment of SCLC patients. Critically, the distinct IM profiles of SCLC subtypes reveal an unappreciated level of heterogeneity that warrants further investigation in the stratification of patients for immunotherapy.

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    P09 - Health Services Research/Health Economics - Real World Outcomes (ID 121)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Health Services Research/Health Economics
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P09.18 - COVID-19 Outcomes in Patients With Thoracic Malignancies According to Gender and Ethnicity (TERAVOLT) (ID 3702)

      00:00 - 00:00  |  Author(s): Daniel Steinfort

      • Abstract
      • Slides

      Introduction

      Previously reported data on patients with thoracic malignancies who develop COVID-19 have suggested a higher mortality rate compared to the general population and to other cancer types, particularly in patients over 65 years of age or suffering from active or progressive disease. Preliminary data from other studies have suggested that gender and ethnicity may also impact patient outcomes.

      Methods

      TERAVOLT is a multi-center, international observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria include the presence of any thoracic cancer and a COVID-19 diagnosis confirmed in the laboratory with RT-PCR/serology, highly suspicious radiological and clinical findings, or suspected with symptoms and known contact with a positive person. The overarching goals of this consortium are to provide data for guidance to oncology professionals on managing patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus. Clinical outcomes including hospitalization, ICU admission, oxygen requirement and mortality were collected. The association between demographic/clinical characteristics and outcomes were measured with odds ratio with 95% confidence intervals using a logistic regression model.

      Results

      As of August 20, 2020, a total of 1,053 patients with COVID-19 and thoracic cancers from 19 countries and 130 centers have been identified, including 42% females and 84% White, 9.3% African American, 25% Hispanic. The median age of male patients was 69 compared to 66 years of age for females. While ECOG PS was similar between treatment groups, 77% of males were admitted to hospital with a mortality rate of 37% compared to 66% of females with a mortality rate of 28%. The median age of African American patients was 66 years of age compared to 68 and 69 years of age for white and Hispanic patients, respectively; 26% of African American and 25% White patients had an ECOG PS ≥2 compared to 19% of Hispanics. A similar percentage of patients were admitted to the hospital and ICU, while the mortality rate for Hispanics was 36% compared to 34% for whites and 26% for African Americans.

      Conclusion

      Similar to the general population, the mortality rate of males with thoracic cancer is higher than females. Regarding ethnicity, there is a difference in the median age of African American patients compared to Whites and Hispanics. Although the severity of COVID-19 disease, as defined by hospital admission, is similar between ethnic groups, the mortality rate in Hispanics is higher. We will present a multivariate analysis of these data according to gender and ethnicity, including the impact of cancer stage, prior cancer therapy, and COVID-19 therapy on outcomes.

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