Virtual Library

Start Your Search

Kei Namba



Author of

  • +

    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.13-13 - Potent Anti-Tumor Effect of Ganetespib in Acquired EGFR-TKI Resistance NSCLC Cells (ID 12652)

      16:45 - 18:00  |  Author(s): Kei Namba

      • Abstract

      Background

      Non-small cell lung cancer (NCSLC) harboring epidermal growth factor receptor (EGFR) mutation shows favorable response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, almost all these patients eventually acquire resistance to EGFR-TKIs, and novel therapeutic strategies to overcome the acquired resistance have been required. The 90-kDa heat shock protein (HSP90) is a chaperon protein expressed at high levels in cancer cells and involved in folding or stabilization of client proteins essential for cancer cell growth and survival. Ganetespib (STA-9090) is one of the second-generation HSP90 inhibitors with potent anti-tumor effect on NSCLC cells. In this study, we evaluated the anti-tumor effect of ganetespib in EGFR-TKI sensitive and acquired resistance NSCLC cell lines.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We treated 4 EGFR-mutant NSCLC cell lines (HCC827, HCC4006, HCC4011 and PC-9), and 5 experimentally established EGFR-TKI (gefitinib) resistance cell lines with ganetespib. The EGFR-TKI resistant mechanism consisted of EGFR T790M second mutation, MET amplification, epithelial-to-mesenchymal transition (EMT) and cancer stem cell-like properties. We determined cell proliferation by MTS assay and calculated the IC50 values. We also performed Western blotting to investigate downstream signaling pathway alterations.

      4c3880bb027f159e801041b1021e88e8 Result

      The IC50 values in parental NSCLC cell lines ranged from 1.3nM to 15nM, and those in acquired EGFR-TKI resistance NSCLC cell lines ranged from 0.87nM to 25nM, which suggests potent anti-tumor effect of ganetespib. In addition, this effect was observed regardless of the resistant mechanisms, including EMT. Ganetespib effectively suppressed the expression of downstream pathway molecules in all examined cell lines including acquired EGFR-TKI resistance NSCLC cell lines. Also, ganetespib effectively induced apoptosis in parental and acquired EGFR-TKI resistance NSCLC cell lines with EGFR T790M mutation or MET amplification.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Ganetespib exhibited potent anti-tumor effect in acquired EGFR-TKI resistance NSCLC cell lines regardless of the resistant mechanisms, suggesting that ganetespib could be a promising therapeutic option in the treatment of NSCLC with acquired EGFR-TKI resistance.

      6f8b794f3246b0c1e1780bb4d4d5dc53

  • +

    P1.14 - Thymoma/Other Thoracic Malignancies (Not CME Accredited Session) (ID 946)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.14-29 - Surgical Treatment for Metastatic Lung Tumors from Various Sarcomas (ID 12551)

      16:45 - 18:00  |  Author(s): Kei Namba

      • Abstract
      • Slides

      Background

      Sarcomas are known to be one of the aggressive malignant tumors. They often develop multiple pulmonary metastasis, and thus systemic therapy is a treatment of choice for metastatic lung tumors. However, effective chemotherapeutic treatments have not yet been established. Surgical resection for metastatic lung tumors is a therapeutic option to control the disease, although it is not a curative therapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Between January 2006 and April 2018, 396 pulmonary resections were performed for 219 sarcoma patients with metastatic lung tumors in Okayama University Hospital. Among them, 129 sarcoma patients who underwent pulmonary metastasectomy between January 2006 and December 2014 were retrospectively reviewed. In total, 229 pulmonary resections were performed. We analyzed the following factors: age, sex, site of primary lesion, histology, operative procedures, size of the largest lesions resected, maximum number of the resected tumors, postoperative complications, and survival rate.

      4c3880bb027f159e801041b1021e88e8 Result

      In total, 939 metastatic nodules were resected. Average number of tumors per intervention was 4.1 (range 1-19). These sarcoma patients consisted of 31 males and 98 females, and their average age was 53.6 years (range 14-80 years). Leiomyosarcoma was the most common histological subtype (n = 72, 55.8%) and uterus was the most common location of the primary disease (n = 55, 42.6%). Operative procedures were composed of 173 partial resections, 31 segmentectomies with or without partial resections, 24 lobectomies with or without partial resections, and 1 basal segmental auto-transplantation after pneumonectomy. The postoperative complications were limited, showing that pulmonary metastasectomies for sarcomas are acceptable. Overall 3-year survival after the first pulmonary metastasectomy was 49.5%, and multivariate analysis revealed that the survival was significantly better for the group with disease-free interval of more than 2 years or the size of the largest resected lesion less than 30 mm.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Surgical resections for metastatic lung tumors from various sarcomas were performed without major complications, indicating the acceptable feasibility. If disease-free interval is more than 2 years and the size of the largest resected lesion is less than 30 mm, patients may maximally benefit from surgical resection.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      P1.14-30 - Prognostic Factors for Sarcoma Patients with Lung Metastasis Who Underwent Extended Pulmonary Resection (ID 12710)

      16:45 - 18:00  |  Author(s): Kei Namba

      • Abstract
      • Slides

      Background

      Since the effects of chemotherapy and molecular targeting agents for sarcoma with lung metastasis are limited, pulmonary metastasectomy can become one of the treatment options for the control of disease. Partial resection is the first choice of surgical procedure for lung metastasis to preserve pulmonary function. As for the tumors which occur at hilum or are too large for partial resection, the extended resection such as segmentectomy or lobectomy is occasionally required while the clinical impact of these procedures is unknown. In this study, we examined preoperative prognostic factors of sarcoma patients who underwent segmentectomy or lobectomy for lung metastasis.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      During January 2006 to December 2014, a total of 129 patients underwent pulmonary resection for lung metastasis of sarcoma at Okayama University Hospital. Among them, 40 patients (31%) underwent segmentectomy or lobectomy. The 3-year survival rate was evaluated by univariate (KaplanMeier method) and multivariate (Cox proportional hazard model) analyses with log-rank test.

      4c3880bb027f159e801041b1021e88e8 Result

      Among 40 patients, the median age was 55 years old (range, 17 to 76). Thirty-five patients (88%) were female. Thirty patients (75%) harbored two or more distant metastatic lesions at initial diagnosis and 21 patients (52.5%) suffered from bilateral lung metastasis at the first lung metastasectomy. Median maximum diameter of the maximum lung tumor and median number of the lung metastasis was 30 mm (range, 8 to 110) and 3 (range, 1 to 19), respectively. Eight patients (20%) had two years or more disease-free interval at the first lung resection. The 3-year survival rate was 36.8% in the entire cohort. The univariate analyses revealed that the 3-year survival rate was significantly better in the patients with smaller size of lung metastasis (50.5% in the tumors with maximum diameter ≤ 30mm vs 20.7% in those > 30mm, P < 0.01), unilateral lung metastasis (45.6% vs 29.5% for bilateral, P < 0.05), and the absence of metastatic lesion at initial diagnosis (50.9% vs 28.1% for the presence, P < 0.05). Smaller numbers of lung metastasis and longer disease-free interval showed favorable prognosis with marginal significance (P < 0.1). The multivariate analysis with the above five factors revealed that unilateral lung metastasis at the first pulmonary metasetasectomy was an independent favorable prognostic factor (HR 2.41, 95%CI 1.09 to 5.32, P < 0.05).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Extended pulmonary resection such as segmentectomy or lobectomy may be considered for the patients with sarcoma lung metastasis especially when the tumors are unilateral.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P3.CR - Case Reports (Not CME Accredited Session) (ID 984)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
    • +

      P3.CR-07 - Comprehensive Genomic Profiles for a Mediastinal Tumor Suspected of Synovial Sarcoma: A Case Report (ID 12832)

      12:00 - 13:30  |  Author(s): Kei Namba

      • Abstract
      • Slides

      Background

      Synovial sarcoma (SS) is an aggressive malignant tumor and accounts for 5 to 10% of all types of soft tissue sarcomas. SS commonly occurs in the deep tissue adjacent to the joints or tendons in the limbs while SS rarely occurs in the mediastinum. Most of SS harbor t(X;18)(p11.2;q11.2), which leads to chimeric fusion of SYT with one of the SSX genes. Furthermore, somatic mutations of cancer-related genes such as PIKC3A, TERT, CDH1, and PTEN have also been reported in the SS even though the frequencies of these genetic alterations were not high. Recently, the comprehensive genomic profile (CGP) using the next-generation sequencing (NGS) is widely used for better understanding of tumorigenesis and it can also provide clinically actionable information to guide treatment decisions for patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In this study, the clinical and histological records of an anterior mediastinal tumor suspected of SS were reviewed, and a reverse transcript polymerase chain reaction (RT-PCR) assay and NGS using a high sensitivity amplicon-based targeted sequencing method incorporating molecular barcodes (a panel designed for hotspots of 47 cancer-related genes) were performed to identify the genetic alterations.

      4c3880bb027f159e801041b1021e88e8 Result

      A 78 years old woman was referred to our hospital because of approximately 9 cm anterior mediastinal tumor. A positron emission tomography showed the high fluorine-18-fluorodeoxyglucose uptake. The patient underwent median sternotomy and resection of the tumor combined with wedge resection of the left upper lobe of lung. Histological examination revealed a monomorphic spindle cell growth and immunohistochemical stains (AE1/AE3, CAM5.2, CD34, CD99, Desmin, Nestin, a-SMA, CDK4, CD56, c-kit, EMA, and S-100) were negative, so the tumor was suspected of SS. We performed a RT-PCR assay for SYT-SXX fusion, however, it was not detected. NGS analysis revealed the presence of hotspot mutations in 4 cancer-related genes (PIK3CA, CDKN2A, PTEN, and MAP2K4). Because the tumor was completely resected, an adjuvant therapy had not been planned and the scheduled medical checkup has been performed. Fortunately, the patient is alive without any recurrence for 5 years.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The genetic features of a mediastinal tumor suspected of SS, without SYT-SSX fusion, were evaluated by CGP analysis. In case of the rare tumor especially when it occurs in the unusual location and the histological and molecular assessments are not conclusive, a CGP assay may be helpful to reveal the genetic feature of the tumor and to determine the effective targeted drugs.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.