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Angela R. Omilian



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    OA06 - Early Stage Lung Cancer: Outcomes and Interventions (ID 902)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 202 BD
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      OA06.01 - Case-Series Study in Ever- and Never-Smoking Females and Males with NSCLC: Exposures, Tumor Factors, Biology and Survival (SWOG S0424) (ID 14526)

      13:30 - 13:40  |  Author(s): Angela R. Omilian

      • Abstract
      • Presentation
      • Slides

      Background
      Sex differences in non-small cell lung cancer (NSCLC) susceptibility, tumor biology and survival have been retrospectively reported. We conducted a prospective, case-series intergroup study (SWOG S0424) in 4 cohorts of females (F) and males (M), ever-smokers (ES) and never-smokers (NS) with newly-diagnosed stages I-III NSCLC. This is the first overall survival (OS) report. a9ded1e5ce5d75814730bb4caaf49419 Method
      Patients were accrued at US sites via SWOG/NCI-CTSU. A questionnaire of demographics and exposures (tobacco, environmental, reproductive, hormonal); stage and histology data; treatment; and OS were obtained. Tumor tissue was submitted for EGFR, RAS and p53 mutations. Nuclear and cytoplasmic estrogen receptor (ER) alpha and beta were measured (Cheng, JNCI 2017). Kaplan-Meier (KM) curves and OS modeled using Cox proportional hazards were examined. The NS cohorts remained open longer to maximize accrual. Patients were followed 5 years for OS or until death. 4c3880bb027f159e801041b1021e88e8 Result
      The accrual goal of 981 was achieved from 10/2005-3/2011. Evaluable cases were FES, n=337; MES, 383; FNS, 188; MNS, 49 (MNS under-accrued despite extension). The 4 cohorts differed significantly in demographics, tumor stage, histology, mutational profile (overall, by histology), ER expression, lifestyle factors and exposures. KM curves showed MNS/MES had overlapping OS and FNS/FES had significantly better OS. Five-year estimates were FNS, 73%; FES, 69%; MNS, 58%; MES, 52%. Markedly improved OS for females persisted after adjusting for other factors. Four multivariate OS models were constructed: all patients (model 1) and women only (model 2), each with mutations and ER expression added (models 3, 4). Model 1: better OS for females (HR 0.56, p <.001); higher BMI (continuous, HR 0.98, p=0.045); and adenocarcinoma, BAC, large cell (all vs squamous, HRs 0.84, 0.48, 0.57); worse OS for stages II and III (HRs 1.87, 3.76: each p<.001) and greater age. Model 2: worse OS if ES (HR 1.48, p=0.05), higher stages; histology and hormonal exposure variables were not significant. Model 3: better OS if EGFR mutation (HR 0.53, p=0.013), female, stage I, higher BMI or greater height; worse OS if p53 mutation, higher ER-alpha cytoplasmic or ER-beta nuclear H-scores. Model 4: worse OS if higher stage, p53 mutation or ER-alpha cytoplasmic H-score; EGFR mutation lost significance. 8eea62084ca7e541d918e823422bd82e Conclusion
      Sex, histology, mutations and exposures impacted OS, with dramatically better OS for females regardless of the analysis/model. Hormonal influences (persistent association of ER-expression with OS) were independently significant. Despite adjustments, favorable female survival could not be explained away. Randomized studies should stratify by sex and validation analyses should be conducted in targeted therapy and immunotherapy trials.

      SUPPORT: NIH/NCI grants R01CA106815, U10CA180888, U10CA180819 and UG1CA189974. 6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.09 - Pathology (Not CME Accredited Session) (ID 975)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.09-02 - Utilization of Laboratory Developed Tests for PD-L1 Evaluation is Dependent on Tumor Type (ID 13781)

      12:00 - 13:30  |  Author(s): Angela R. Omilian

      • Abstract
      • Slides

      Background

      PD-L1 expression level evaluated by immunohistochemistry plays an important role in immunotherapy for many malignancies including non-small cell carcinoma of the lung (NSCLC), adenocarcinoma of the gastroesophageal junction/stomach (GEJ-G), melanoma and etc. With the growing number of indications for the use of PD-L1 immunotherapy, it has become impracticable for laboratories to adopt and maintain the various FDA approved assays for different tumor types. Harmonization to a standard assay would alleviate the current challenges and allow testing to be uniform among laboratories. The primary objective of this study was to determine if laboratory developed tests (LDTs) utilizing available antibodies are concordant with the FDA approved assays in NSCLC, melanoma and GEJ-G, and can therefore serve as alternatives for FDA approved assays.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Multiple tissue microarray slides containing NSCLC (714 cases), melanoma (87 cases) and GEJ-G (194 cases) were stained for PD-L1 with the 22C3 pharmDx Kit, the 28-8 pharmDx Kit, and/or three LDTs (clones 22C3, 28-8 and E1L3N). PD-L1 expression on tumor cells was scored for NSCLC and malignant melanoma, whereas expression on tumor cells and immune cells was scored for GEJ-G. All TMA slides were digitally scanned and independently evaluated by three board certified pathologists (JQ, AC, and BB) who were blinded to staining conditions. Raw scores were converted to a composite score based on the range of raw scores. Composite scores were compared for level of agreement utilizing a Kappa score and interclass correlation coefficients displayed on Bland-Altman plots.

      4c3880bb027f159e801041b1021e88e8 Result

      For NSCLC, the two FDA approved assays have a high level of concordance (Kappa 0.88, 95% CI 0.85-0.90) and the two LDTs (22C3 and E1L3N) also have high level of concordance (Kappa 0.82, 95% CI 0.78-0.85); however, concordance between two FDA approved assays and the two LDTs was low. For gastric adenocarcinoma, the 22C3 FDA approved assay and 22C3 LDT has a high level of concordance (Kappa 0.90, 95% CI 0.86-0.94), but the E1L3N LDT has a low level of concordance with both the 22C3 FDA approved assay and the 22C3 LDT. For malignant melanoma, there was low concordance among two FDA approved assays and two LDTs (28-8 and E1L3N).

      8eea62084ca7e541d918e823422bd82e Conclusion

      These results suggest that although LDTs can be used for evaluating PD-L1 in tumor, the utilization of LDT is tumor type dependent. One single LDT may not be sufficient to serve as appropriate alternative for the FDA approved assays on different types of tumor.

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