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Joanna Chorostowska-Wynimko



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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): Joanna Chorostowska-Wynimko

      • 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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    P35 - Pathology - Genomics (ID 105)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 2
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P35.05 - The Monitoring of Mutated EGFR Levels in Liquid Biopsy from Patients on EGFR-TKIs – Early Detection of NSCLC Progression (ID 1912)

      00:00 - 00:00  |  Presenting Author(s): Joanna Chorostowska-Wynimko

      • Abstract
      • Slides

      Introduction

      Non-invasive evaluation of circulating tumor DNA (ctDNA) enables the real-time monitoring of the status and quantitate expression level of mutated EGFR gene (mEGFR) in the blood from NSCLC patients (pts) on EGFR TKIs. We evaluated the feasibility of the longitudinal analysis of mEGFR level in plasma and its effectiveness in early detection of NSCLC progression in pts treated with EGFR TKIs in the first line.

      Methods

      Peripheral blood was prospectively collected from 64 advanced, EGFR mutation-positive NSCLC pts at the time of diagnosis (baseline) and then every month during the first line EGFR-TKI treatment (erlotinib, gefitinib, afatinib) until clinical progression. The mutated EGFR ctDNA was analyzed using Cobas EGFR Mutation Test v2 (Roche, Germany). The level of mEGFR in plasma was measured as the Semi-Quantitative Index (SQI).

      Results

      At baseline, 46 out of 64 (72%) pts demonstrated the same activating EGFR mutation in liquid biopsy and tumor tissue (there were no discrepant results). In the remaining 28% pts the mEGFR ctDNA was undetectable in plasma. To date, 33 pts completed the first line EGFR TKI treatment with complete set of plasma samples analyzed for mEGFR ctDNA. The median (min-max) PFS was 10 (2-25) months. In the subgroup of long-term responders to first line EGFR TKIs (PFS≥11 months, n=14, 42%) the complete clearance of baseline mEGFR levels in plasma was observed within 1-2 months of treatment regardless the type of mutation; mEGFR ctDNA remained undetectable during the following months. This phenomenon was not observed in short-term responders (PFS<5.5 months, n=8, 24%). In 17 pts, a rapid raise to or above mEGFR baseline preceded clinical progression by 4-20 weeks, with mean SQI of mEGFR in plasma at baseline 8.59, after first month of treatment 1.69, and 6.73 upon progression. In 8 (24%) pts the T790M resistance mutation was detected upon progression in plasma ctDNA alongside with the primary activating EGFR mutation (mean SQI for T790M was 7.87). In 12 (28%) pts the plasma mEGFR levels were undetectable at diagnosis and throughout the treatment.

      Conclusion

      The dynamic changes of mEGFR ctDNA levels in plasma of NSCLC pts reflect well their response to the first line EGFR TKIs. The longitudinal monitoring of mEGFR levels in plasma allows to observe the disease progression on EGFR TKIs much earlier than conventional imaging techniques. The dynamics of mEGFR ctDNA level in plasma during the first 2 months of treatment may present a predictive value for EGFR TKI therapy. In 28% pts the plasma mEGFR level remains undetectable at diagnosis and during treatment. The study is ongoing.

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      P35.08 - RNA-Based Gene Alteration and Expression Analysis in Sq-NSCLC with known FGFR1 Amplification and Protein Expression Status (ID 1951)

      00:00 - 00:00  |  Presenting Author(s): Joanna Chorostowska-Wynimko

      • Abstract
      • Slides

      Introduction

      Gene profiling is a key to understand the squamous non-small cell lung cancer (Sq-NSCLC) biology and to discover candidate biomarker(s). It was suggested that genomic aberrations other than FGFR1 expression might affect response to FGFRi. At the moment, FGFR1 amplification, is considered a predictive biomarker for FGFR inhibitors (FGFRi) in Sq-NSCLC. However, its reliability in clinical trials was not satisfactory. We aimed to comprehensively evaluate the FGFRs aberrations in Sq-NSCLC ie assess gene expression, fusions and variants by means of Real-time PCR(RT-PCR) and next-generation sequencing (NGS) alongside the FGFR1 protein expression. In addition, other functionally important genes like MET were analyzed.

      Methods

      The FGFR1 amplification (FISH) and protein expression (IHC) were determined in 204 FFPE from Sq-NSCLC patients. Next, the RNA from 19 out of 204 tumors (stageIIA–IIIB;G2,-G3; median tumor content 30%;range:30-60%) and commercial control samples (Seraseq, Horizon) was extracted with High Pure RNA Isolation Kit(Roche). Isolate quality was assessed with the use of Bioanalyzer. The FGFR1 mRNA level was assessed by real-time PCR. Subsequently, 16 tumors and 2 control samples were sequenced and screened for gene fusions, variants and expression of 14 genes of interest (ALK, BRAF, EGFR, FGFR1-3, KRAS, MET, NRG1, NTRK1-3, RET and ROS1) using the FusionPlex Lung kit, Archer analysis software v6.0 (ArcherDx).

      Results

      RNA quality (DV200) in analyzed samples ranged from 73 to 95% (median:87%); all samples subsequently analyzed by NGS passed quality control process.

      In overall, we observed 7 low confidence fusion events in 11 samples (68.7%) and 2 different types of fusion transcripts in 4 samples. The UNC45B:BRAF fusion was the most frequent (n=8), followed by the ALK:FGFR1 (n=2); other fusions were found in individual samples only. 14 clinically significant gene fusions and oncogenic isoforms (100%) were identified in positive control sample by NGS panel. Twelve(85.7%) met all basic recommendations for the fusion detection and min.10% of reads supporting the fusion. The two remaining fusions had 3.5% of reads supporting the fusion. No gene fusions were detected in negative control.

      The gene RNA variant analysis encompassed all listed variants (n=148,AF>2%). Two pathogenic or likely pathogenic KRAS variants(c.38G>A,c.39C>T) were revealed in two samples. Two stop gained (FGFR2 (c.751C>T); ROS1 (c.5668A>T)) and one EGFR missense (c.2053C>T,drug response) variants were found simultaneously in one sample.

      The FGFR1 expression analysis by real-time PCR showed a relationship between increased expression of the FGFR1 gene at the mRNA level (cut-off: median expression > 0.16), and simultaneous presence of FGFR1 gene amplification and protein expression (two-tailed (p = 0.047) and one-tailed Fisher's test (p = 0.02)) in contrast to FGFR double negative tumors (FISH and IHC status). However, the FGFR1 expression assessed with RT-PCR and NGS were moderately correlated (r=0.61,p=0.012).

      Conclusion

      Targeted RNA-sequencing of Sq-NSCLC FFPE samples revealed new gene fusion transcripts and some clinically relevant gene variants (KRAS, EGFR). Moreover, the enhanced FGFR1 mRNA level was present in 83% (5/6) of samples double-positive for FGFR1 protein overexpression and amplification. The limited size of the study group, necessitates further research to confirm current observations.

      The research was co-financed by the NCBR and CelonPharmaS.A

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