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M. Higuchi



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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 2
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      P1.06-024 - FAM83B, a novel molecular target for lung squamous cell carcinoma. (ID 1869)

      09:30 - 16:30  |  Author(s): M. Higuchi

      • Abstract

      Background
      Recently, personalize therapy for non-small cell lung cancer (NSCLC) has been improving and significantly to extract various molecular target. However, development of molecular targeted drugs is proceeding only in lung adenocarcinoma to date, while there are few drugs for lung squamous cell carcinoma (SCC). Therefore, we tried to extract molecular targets for SCC by comprehensive gene expression analysis of clinical specimen.

      Methods
      The subjects of this study consisted of 215 patients with NSCLC who underwent complete resection since 2005 to 2011 in our hospital. They included 102 adenocarcinomas and 113 SCC. First, we tried to extract molecules specific to SCC by tissue array analysis of clinical specimen. We selected FAM83B as a candidate marker for SCC by using comprehensive gene expression analysis. Then, we examined the protein expression of FAM83B in NSCLC tissues by immunoblot and immunohistochemical analysis (IHC). The relationship between the FAM83B expression and clinic-pathological factors was statistically analyzed.

      Results
      FAM83B expression at mRNA level was significantly higher in SCC than in normal lung or adenocarcinoma (P<0.0001). Immunoblot analysis also confirmed this tendency. In IHC, FAM83B was diffusely localized in the cytoplasm and/or plasma membrane. When more than 10% positive area for FAM83B were judged as “positive”, 94.3% (107/113) of SCC and 14.7% (15/102), of adenocarcinoma were positive. If the patients were divided into two subgroups by IHC (54 high-expression patients and 53 low-expression patients), high-expression group was associated with a better disease free survival rate (P=0.042, log-rank test). Figure 1

      Conclusion
      Our results indicated that FAM83B could be a reliable diagnostic and prognostic biomarker for SCC. Biological function of FAM83B in lung cancer is not well known. Further analyses should be required to identify its clinical significance and biological function.

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      P1.06-029 - Serum nitric oxide could be a predictor for the response of bevacizumab in patients with non-small cell lung cancer (ID 2198)

      09:30 - 16:30  |  Author(s): M. Higuchi

      • Abstract

      Background
      Bevacizumab (BEV), an inhibitory monoclonal antibody to VEGF, is widely used to treat patients with non-small cell lung cancer (NSCLC), but biomarkers that predict BEV response are controversial. Reportedly, hypertension is linked to response to BEV therapy, possibly because BEV might suppress vascular nitric oxide (NO) production. However, the usefulness of serum NO (NO~s~) as a predictive biomarker for BEV therapy has not previously been shown. Here, we studied the predictive value of NO~s~ in BEV-treated patients with NSCLC.

      Methods
      Fifteen patients with advanced or recurrent NSCLC treated with BEV-based regimens were evaluated retrospectively. Blood samples were taken before treatment (Pre), and after the 1st and 2nd chemotherapy courses (Post~1~ and Post~2~, respectively). NO~s~ (NO~2~[–]/NO~3~[–]) was assayed by the Griess method. Relationships between clinical parameters (e.g., clinical responses, adverse events) were analyzed against NO~s~. This study was approved by the ethics committee of Fukushima Medical University.

      Results
      Median Pre NO~s~ was 62.7 ±42.9 μmol/L (range: 1.9–138.8 μmol/L). NO~s~ tended to decrease at Post~1~ (46.6 ± 30.8 μmol/L; P = 0.246) and Post~2~ (37.6 ± 29.4 μmol/L; P = 0.072) compared to Pre values. Post/Pre NO ratios correlated with hypertension onset (Post~1~/Pre: P = 0.316; Post~2~/Pre: P = 0.148) and clinical response (Post~1~/Pre: P = 0.389; Post~2~/Pre: P = 0.163). Decrease at Post~2~ might correlate with progression-free survival (P = 0.127). NOs level of patients with treatment responder increased at Post PD (P = 0.101).

      Conclusion
      NO~s~, could be a predictive biomarker for response to BEV in patients with NSCLC. Prospective confirmation is needed; we are conducting a prospective translational study of NOs in BEV therapy. Figure 1Figure 2

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    P3.07 - Poster Session 3 - Surgery (ID 193)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P3.07-001 - Long-term outcome and current problems of VATS versus open lobectomy for clinical stage IA non-small cell lung cancer (ID 55)

      09:30 - 16:30  |  Author(s): M. Higuchi

      • Abstract

      Background
      The oncologic efficacy of lobectomy for lung cancer by means of video-assisted thoracic surgery (VATS) compared with conventional thoracotomy has been reported, and VATS lobectomy is now considered to be one of the standard surgical procedures for lung cancer. In this study, we retrospectively evaluated the long-term prognosis and some problems after VATS lobectomy, comparing with conventional thoracotomy, for clinical stage IA non-small cell lung cancer (NSCLC) in our institution.

      Methods
      From July 2002 to June 2012, 160 patients were diagnosed as clinical stage IA NSCLC and they underwent lobectomy. Of those 160 patients, 114 patients underwent VATS lobectomy and 46 patients underwent lobectomy under conventional thoracotomy. Patients’ clinical characteristics, recurrent status and overall survival were recorded. Disease free survival (DFS) and overall survival (OS) were calculated by means of Kaplan-Meier analysis and statistical significance between the groups was analyzed by using log-rank tests. Cox proportional hazard regression was used to ascertain independent predictors of recurrence.

      Results
      Median follow-up time was 44.8 months. 5-year DFS was 88.0% in VATS group and 77.1% in thoracotomy group in clinical stage IA (p=0.1504), and 91.5% in VATS group and 93.8% in thoracotomy group in pathological stage IA (p=0.2662). 5-year OS was 94.1% in VATS group, whereas 81.8% in thoracotomy group in clinical stage IA (p=0.0268), and 94.8% in VATS group and 96.2% in thoracotomy in pathological stage IA (p=0.5545). Cox proportional hazard analysis demonstrated a lower risk of recurrent disease in patients without lymph nodes metastases in this series (p=0.0026). The accurate diagnostic rate of preoperative staging was 71.9% in VATS group and 56.5% in thoracotomy group (p=0.2611). Inconsistent factors between clinical and pathological stage were largely tumor size (12.3% and 17.4%), nodal statement (10.0% and 21.1%) and pleural involvement (15.0% and 15.8%) in VATS group and thoracotomy group, respectively. There were 27 recurrent lesions (22 cases) at the first time of recurrence after surgery in this study. Twelve lesions (11 cases) with distant metastases were detected in VATS group, whereas 8 lesions (5 cases) were occurred distant metastases in thoracotomy group. Interestingly, only one lesion with local recurrence was detected in VATS group, whereas 6 lesions (5 cases) in thoracotomy group were detected (p=0.0495).

      Conclusion
      There was no significant inferiority for DFS and OS in VATS group, and local control was also significantly better in VATS group, compared with thoracotomy group. On the other hand, the significant difference of OS between two groups in clinical stage IA and multivariate analysis for recurrence showed the insufficiency of accurate staging before surgery.