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Yusuke Ogoshi



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    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • 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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      P3.01-72 - Pulmonary Resection in a Prone Position for Lung Cancer Invading the Spine: Two Cases Report (ID 12700)

      12:00 - 13:30  |  Author(s): Yusuke Ogoshi

      • Abstract

      Background

      The prone position is usually not selected for pulmonary resection. The intraoperative body position is an important issue in surgery for non-small cell lung cancer (NSCLC) invading the spine because the standard intraoperative body position for vertebrectomy is a prone position, while that for pulmonary resection is a lateral decubitus position. Intraoperative changes in body position are correlated with disadvantages such as the risks of infection and nerve injury.

      We have previously reported significantly favorable clinical outcome of induction chemoradiotherapy (iCRT) followed by surgery among patients with clinical T3 or T4 locally advanced NSCLC, compared with initial surgery. iCRT can prevent cancer cell microresidues at local sites and to eradicate micrometastatic disease at distant sites.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Case 1: A 60-year-old man was found to have squamous cell carcinoma of the left lung with invasion of the adjacent chest wall and vertebral bodies from Th3 to Th5 and his clinical stage (UICC 7th edition) was diagnosed as c-stage IIIA (cT4N0M0).

      Case 2: A 63-year-old man was found to have adenocarcinoma of the right lung with invasion of the adjacent chest wall and Th3 and Th4 vertebral bodies and was diagnosed as c-stage IIIA (cT4N1M0).

      They were treated with iCRT consisting of two cycles of cisplatin plus docetaxel with concurrent radiotherapy of total 46 Gy.

      4c3880bb027f159e801041b1021e88e8 Result

      They obtained a moderate decrease in tumor size after iCRT (restaging ycT4N0M0: Case 1, ycT4N0M0: Case 2).

      The surgery was started in the prone position. After partial vertebrectomy and chest wall resection were performed using an O-arm with a navigation system, upper lobectomy with systemic lymph node dissection (sLND) was performed through the chest wall defect via the posterior approach. Firstly, all pulmonary arterial branches to upper lobe were divided. Next, after division of the posterior and anterior interlobar fissure, the upper lobe bronchus was transected. Finally, the upper pulmonary vein was divided, and sLND was performed under an excellent view.

      Pathologic examination confirmed complete resection of squamous cell carcinoma invading the vertebral bodies and a diagnosis of Ef3 and ypN0 in Case 1, and complete resection of adenocarcinoma adjacent to the vertebral bodies, which had not been infiltrated, and a diagnosis of Ef2 and ypN0 in Case 2.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Lobectomy with systemic LND in the prone position, especially after wide resection of the bony thorax, can be performed via the posterior approach without any significant difficulties in the patients with NSCLC invading the spine.

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    P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)

    • 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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      P3.13-35 - Antitumor Effect of Neratinib Targeting HER2-Altered Lung Cancer (ID 12236)

      12:00 - 13:30  |  Presenting Author(s): Yusuke Ogoshi

      • Abstract
      • Slides

      Background

      Human epidermal growth factor receptor 2 (HER2) plays an important role in the pathogenesis of various cancers. HER2 alterations have been suggested to be a therapeutic target in non-small-cell lung cancer (NSCLC), as in breast and gastric cancers. However, the benefit of HER2-targeted therapy is much less defined. The aim of the study is to investigate the antitumor effect of neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), in NSCLC cells harboring HER2 alterations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We examined the sensitivity of neratinib against normal bronchial epithelial cells BEAS-2B which ectopically overexpressing wild-type or mutant HER2. Human cDNAs encoding full-length HER2 (wild-type and its variants A775insYVMA, G776VC, G776LC, P780insGSP, V659E, G660D, and S310F) were inserted into the pIDT-SMART (C-TSC) vector, pCMViRTSC. Furthermore, we examined the antitumor activity of neratinib in several NSCLC cell lines harboring HER2 alterations in vitro and in vivo experiments, and investigated the association between their genetic alterations and sensitivity to neratinib treatment.

      4c3880bb027f159e801041b1021e88e8 Result

      BEAS-2B cells ectopically overexpressing wild-type HER2 or mutants (A775insYVMA, G776VC, G776LC, P780insGSP, V659E, G660D, and S310F) showed constitutive auto phosphorylation of HER2 and activation of downstream signaling by Western blotting. These BEAS-2B cells were sensitive to neratinib, but insensitive to erlotinib, a first generation EGFR-TKI. Neratinib significantly inhibited the growth of HER2-altered (H2170, Calu-3, and H1781) NSCLC cell lines with an average IC50 value of 0.00347µL, 0.0428µL, and 0.0119µL. Neratinib administration showed strong antitumor effect on tumor growth in mouse xenograft model using HER2-altered lung cancer cell lines.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our study strongly suggests that neratinib is a promising therapeutic option for the treatment of HER2-altered NSCLC.

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