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T. Okamoto



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    MO21 - Prognostic and Predictive Biomarkers V - EGFR (ID 98)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO21.04 - Prognostic and Therapeutic Implications of the Aromatase Expression in Lung Adenocarcinoma Harboring EGFR Mutation (ID 2242)

      10:45 - 10:50  |  Author(s): T. Okamoto

      • Abstract
      • Presentation
      • Slides

      Background
      A significantly greater proportion of females and adenocarcinoma patients is found in never-smoking NSCLC groups than in smoking NSCLC groups. Recent studies have demonstrated that estrogens may contribute to the carcinogenesis and development of lung carcinoma. In the present study, we investigate the correlation between the expression of aromatase (CYP19-1) and clinicopathologic factors and assess the prognostic significance of the aromatase expression in patients with primary lung adenocarcinoma.

      Methods
      The aromatase mRNA expression levels in the primary tumors and corresponding nonneoplastic lung specimens of 110 Japanese patients who underwent complete resection for primary lung adenocarcinoma were evaluated using quantitative RT-PCR. The relationships between the aromatase expression and clinicopathologic factors or survival were analyzed. To test the growth inhibitory effects of the aromatase inhibitor exemestane alone and in combination with the EGFR-TKI erlotinib in vitro, the cell proliferation of the lung adenocarcinoma cell lines HCC4006 and 11-18 was measured according to the WST-8 method.

      Results
      The mRNA expression level of aromatase in the carcinoma tissues was significantly higher than that in the corresponding normal lung tissues (P = 0.013). The aromatase expression in the lung adenocarcinoma tissues was not correlated with the clinicopathologic factors, including patient gender, age, smoking status, EGFR mutation status or pathologic stage. A high aromatase expression was associated with a poor prognosis in terms of both the recurrence-free survival (RFS) (P = 0.004) and overall survival (OS) (P = 0.003). A multivariate analysis showed that the aromatase expression was a significant prognostic factor, with a relative risk of 2.35 (P = 0.043) for RFS and 5.19 (P = 0.004) for OS. We further stratified the population according to gender, smoking status and EGFR mutation status. A high aromatase expression was related to a poor prognosis in femles (RFS; P = 0.008, OS; P < 0.001), never-smokers (RFS; P = 0.009, OS; P < 0.001) and patients with EGFR mutations (RFS; P = 0.005, OS; P = 0.003). A multivariate analysis showed that the aromatase expression was a significant prognostic factor, with a relative risk of 5.22 (P = 0.013) for RFS in the patients with EGFR mutations. HCC4006, harboring an EGFR mutation with a low aromatase mRNA expression, was not sensitive to exemestane alone or combination with erlotinib. In contrast, 11-18, harboring an EGFR mutation with a high aromatase mRNA expression, was sensitive to exemestane alone. In addition, cell growth was significantly inhibited by the combination of exemestane and erlotinib.

      Conclusion
      A high expression of aromatase is correlated with a poor outcome in patients with lung adenocarcinoma, especially those harboring EGFR mutations. Aromatase may be a therapeutic target in lung adenocarcinoma with a high aromatase expression and with an EGFR mutation.

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    MO22 - Advanced Disease and Outcomes (ID 103)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Surgery
    • Presentations: 1
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      MO22.07 - Local treatment of oligometastatic recurrence after surgery for non-small cell lung cancer. (ID 932)

      11:10 - 11:15  |  Author(s): T. Okamoto

      • Abstract
      • Presentation
      • Slides

      Background
      We previously reported a retrospective study indicating the prognostic impact of local treatment of postoperative oligometastases in patients with non-small cell lung cancer (NSCLC) (Yano T et al. J Surg Oncol 2010;102:852-855). However, previous studies have not been sufficient to determine the therapeutic significance of local treatment for postoperative oligometastases since the conclusions were based on retrospectively collected data and the assessment of overall survival. In the present study, we prospectively observed postoperative oligometastatic patients and investigated the effects of local treatment on progression-free survival (PFS).

      Methods
      Using a prospectively maintained database of patients with completely resected NSCLC treated between October 2007 and December 2011, we identified 52 consecutive patients with postoperative recurrence. Of these patients, 31 suffering from distant metastases alone without primary site recurrence were included in this study. In order to exclude cases of second primary carcinoma of the lungs, the criteria of Martini and Melamed, modified by Antakli et al., were used to differentiate between second primary lung cancer and pulmonary metastasis. According to the definition of ‘oligometastases’ as limited recurrence potentially controlled with local treatment, 17 patients had oligometastatic disease. The number of metastases was less than four.

      Results
      The oligometastatic sites included the lungs in five patients, the brain in four patients, bone in four patients, the lungs and brain in two patients, the adrenal glands in one patient and soft tissue in one patient. Fifteen of the 17 patients first received local treatment. Three patients (lung, adrenal gland, soft tissue) underwent surgical resection, and the remaining 12 patients received radiotherapy. The median PFS was 33 months in the oligometastatic patients who received local treatment. There were seven patients with a PFS of longer than two years. The metastatic sites in these patients varied, and the number of lesions in three patients was two or three. On the other hand, the two remaining patients first received a systemic chemotherapy of their own selection. The PFS of these two patients was five and 15 months, respectively.

      Conclusion
      Both our previous retrospective study and the present study favor a choice of local treatment in patients with postoperative oligometastatic NSCLC.

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    P2.07 - Poster Session 2 - Surgery (ID 190)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P2.07-011 - A pilot study on the effects of perioperartive administration of the neutrophil elastase inhibitor, Sivelestat, to non-small cell lung cancer patients with preoperative risk factors of acute respiratory distress syndrome after pulmonary resection (ID 1217)

      09:30 - 09:30  |  Author(s): T. Okamoto

      • Abstract

      Background
      Postoperative acute respiratory distress syndrome (ARDS) is a recognized complication of pulmonary resection. ARDS following lung resection has a miserable prognosis, with overall hospital mortality rates over 25%. Previous studies demonstrated that there were risk factors of ARDS after pulmonary resection including age, chronic obstructive pulmonary disease (COPD), interstitial pneumonia, concurrent cardiac disease, prior therapy, remaining lung perfusion, duration of operation, increased blood loss and so on. Neutrophils and neutrophil elastase (NE) are believed to play a key role in the endothelial injury and increased vascular permeability characteristic of ARDS. Sivelestat sodium hydrate is a selective NE inhibitor and has been shown to improve respiratory status in cases of ARDS. It has not been well known whether or not NE inhibitors are beneficial for prevention of ARDS after lung resection.

      Methods
      We conducted a pilot study to investigate the efficacy of perioperative administration of sivelestat sodium hydrate to prevent postoperative ARDS in 34 non-small cell lung cancer (NSCLC) patients who had the various preoperative risk factors of the incidence of ARDS after pulmonary resection in Chiba University between 2009 and 2011. They received sivelestat sodium hydrate (5mg/kg/day) intravenously for 7 days starting at the beginning of operation.

      Results
      The patient demographics were as follows: median age, 68 years of age (range 47 to 83 years), male/female ratio, 31/3, clinical stage I/II/III, 9/6/19. The histology was adenocarcinoma (n =19), squamous cell carcinoma (n=10) and others (n =5). Risk factors of ARDS included induction chemotherapy (n=3), induction chemoradiotherapy (n=17), interstitial pneumonia (n=10), COPD (n=3) and medical history of ARDS (n=1). All 34 patients underwent complete resection. The operations included 2 partial resections, 31 lobectomies, and 1 pneumonectomy. Of the 31 patients who received lobectomy, bronchial or arterial plasty was performed in 9 patients. The postoperative mortality rate was 2.9%. One patient died of heart failure on the nineth postoperative day. There was no incidence of ARDS after pulmonary resection in all patients.

      Conclusion
      Perioperative administration of sivelestat sodium hydrate can be beneficial to prevent postoperative ARDS in NSCLC patients. Prospective studies are required.