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T. Eguchi



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    MINI 06 - Quality/Prognosis/Survival (ID 111)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      MINI06.02 - T1a Lung Adenocarcinomas: Presence of Spread of Tumor through Alveolar Spaces (STAS), Micropapillary and Solid Patterns Determines Outcomes (ID 3068)

      16:45 - 18:15  |  Author(s): T. Eguchi

      • Abstract
      • Presentation
      • Slides

      Background:
      Our previous reports highlighting the significance of presence of micropapillary (MIP) (JNCI 2013), STAS- spread of tumor through alveolar spaces (JTO 2015), and predominant solid (SOL) (Modern Pathol 2011) histological subtype as poor prognostic markers in stage I lung adenocarcinomas (ADC) are reproduced by others. In this study, we hypothesized that presence of STAS, MIP or SOL patterns (≥5%) in small stage I lung ADC (≤2 cm) is a marker of invasion and poor prognosis, and can influence the recurrence patterns based on the type of surgical resection – lobectomy (LO) versus limited resection (LR).

      Methods:
      All available tumor slides from patients with therapy-naive, surgically resected small (≤ 2cm), solitary stage I lung ADC were reviewed (1995-2011; n = 909). STAS was defined as isolated tumor cells within alveolar spaces separate from the main tumor. MIP and SOL patterns were considered present in the tumor when it comprised ≥5% of the overall tumor. Cumulative incidence of recurrence (CIR; any types, locoregional or distant) was estimated using a cumulative incidence function. Differences in CIR between groups were assessed using Gray’s method.

      Results:
      Figure 1 The association of outcomes with the presence of STAS, MIP, or SOL patterns is shown in the table. The risk of developing any types of recurrence was significantly higher in patients with both STAS and MIP positive tumors than others (P < 0.001); and the risk of developing any types of recurrence was significantly lower in patients with both STAS and SOL negative tumors than others (P < 0.001). In the LR group, STAS, MIP and SOL patterns were independent prognostic factors for any types of recurrence (HR: 4.5, 1.4, and 1.3, respectively), locoregional recurrence (HR: 5.2, 1.3, and 1.3, respectively), and distant recurrence (HR: 3.1, 1.4, and 1.2, respectively).



      Conclusion:
      Tumor STAS, presence of MIP and SOL patterns are independent risk factors of recurrence especially in the LR group of small stage I lung ADC patients. Importantly, of these factors, tumor STAS was the strongest predictor of locoregional recurrence in this group. These results suggest that the identification of STAS in small lung ADC may identify LR patients who need further management, one of which may be completion lobectomy.

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    P1.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 209)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      P1.02-029 - Long and Short-Term Predictors of Outcome in Elderly Patients (≥ 75 Years) Undergoing Lobectomy for Stage I Non-Small Cell Lung Cancer (ID 3126)

      09:30 - 17:00  |  Author(s): T. Eguchi

      • Abstract
      • Slides

      Background:
      More than 65% of patients diagnosed with non-small cell lung cancer (NSCLC) are above the age of 65 years. Half of this cohort are ≥75 years who are at higher risk following surgical resection, which is the mainstay of treatment for early-stage NSCLC. The purpose of this study is to determine the factors influencing the outcomes in patients ≥75 years who underwent lobectomy for stage I NSCLC: postoperative complications, short-term (30- and 90-day mortality) and long-term (overall survival (OS) and cancer-specific survival (CSS)). In addition to the routinely used clinical factors, we investigated the utility of lung age, the tool commonly used for smoking cessation.

      Methods:
      Patients with pathological stage I NSCLC who underwent lobectomy between 2000 and 2011, age ≥75 years at surgery with no induction therapy, and no previous lung resection were included in the study (n =435). We investigated the influence of smoking history, preoperative history of cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD), Carlson comorbidity index (CCI), serum creatinine level, lung age (calculated by height and forced expiratory volume in one second), percent predicted diffusing capacity of the lung for carbon monoxide (%DLCO), and p-stage. Outcomes studied were postoperative in-hospital complication (CTCAE grade ≥3), 30- and 90-day mortality, OS, and CSS. Complications and mortality were analyzed by chi-square tests for univariate analysis. OS and CSS were analyzed by Kaplan-Meier methods with log-rank tests for univariate analysis, and Cox proportional analysis for multivariate analysis.

      Results:
      Median chronological age was 79 years, whereas median lung age was 89 years (female gender n = 334, positive smoking history n = 391, p-stage IA/IB were 282/153). In univariate analysis, low %DLCO and CVD history were significantly associated with postoperative complications (p = 0.032 and 0.018, respectively), and only high serum creatinine level was significantly associated with 30- and 90-day mortality (p = 0.02 and 0.027, respectively). P-stage, lung age, %DLCO, and COPD history were significantly associated with poor OS (p <0.001, p <0.001, p = 0.009 and 0.008, respectively). P-stage, lung age, and COPD history were significantly associated with poor CSS (p =0.003, 0.004, and 0.046, respectively). In multivariate analysis, both p-stage and lung age were independently associated with poor OS (p <0.001 and <0.001, respectively) and poor CSS (p = 0.006 and 0.01, respectively).

      Conclusion:
      In elderly patients with stage I NSCLC undergoing lobectomy, p-stage and lung age were independent risk predictor for long-term prognosis (OS and CSS); serum creatinine level was associated with short-term mortality; and %DLCO and CVD history were associated with postoperative complications. Our observations from this large cohort are useful for treatment decision making in elderly patients with stage I NSCLC.

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    P3.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 226)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      P3.08-038 - Targetable Cancer-Associated Antigens for Immunotherapy in Malignant Pleural Mesothelioma (MPM) - Mesothelin, CA125 and WT-1 (ID 3165)

      09:30 - 17:00  |  Author(s): T. Eguchi

      • Abstract

      Background:
      Mesothelin (MSLN), CA125 (also know as mucin-16, MUC16) and WT-1 are cancer-associated antigens currently under investigation as targets for tumor-specific immunotherapy, based on published observations that antigen-specific immune responses to these antigens prolong survival. In solid malignancies, we (Clin Cancer Res 2012, 2013) and others have published the role of MSLN in promoting tumor aggressiveness. Additionally, MSLN has been demonstrated to interact with CA125 in promoting invasion and metastasis, resulting in poor clinical outcomes. In this study, we investigated the individual and correlative expressions of MSLN, CA125 and WT-1 in both epithelioid and non-epithelioid MPMs.

      Methods:
      All available H&E-stained slides from patients who were diagnosed with MPM (1989-2010) were reviewed; tumors were classified according to the WHO classification. We constructed tissue microarrays (6 tumor cores/tumor) from 273 patients (epithelioid=224; non-epithelioid, including biphasic and sarcomatoid =49). MSLN, CA125, and WT-1 immunohistochemistry were performed, and total scores for each antigen were determined by assessing the combined intensity and distribution of the antigen expression.

      Results:
      Epithelioid MPMs demonstrated positive MSLN expression in 92% of patient samples (73% high-moderate expression), CA125 expression in 72% (19% high-moderate), and WT-1 in 94% (63% high-moderate) (Fig.1A). Triple positive antigen expression was recognized in 68% of patients; co-expression of two antigens was demonstrated in 23% of epithelioid MPMs (Fig.1B). In non-epithelioid MPMs, MSLN, CA125, and WT-1 were positive in 57% (16% high-moderate), 33% (2% high-moderate), and 98% (43% high-moderate) of patient tumors, respectively. Triple and double antigen co-expression were demonstrated in 29% and 33% of non-epithelioid MPMs, respectively. Only 1% of epithelioid and 2% of non-epithelioid MPMs demonstrated absence of expression of all three antigens: MSLN, CA125, and WT-1.Figure 1



      Conclusion:
      Our observation from a large cohort of MPM patients inclusive of all histological subtypes demonstrating greater than 98% positive expression of at least one of the three cancer-associated antigens in epithelioid and non-epithelioid MPMs, with strong antigen expression and high frequency of double and triple antigen expression, provides rationale to develop targeted therapies to these cancer-associated antigens for the treatment of MPM patients We are initiaiting a phase I clinical trial (NCT02414269) of mesothelin-targeted T-cell therapy for MPM patients at our center.