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Junichi Soh



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

      16:45 - 18:00  |  Author(s): Junichi Soh

      • 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

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    P1.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 949)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.17-15 - Perioperative Prognostic Nutrition Index for Induction Chemoradiotherapy Followed by Surgery in Locally Advanced Non-Small Lung Cancers (ID 13055)

      16:45 - 18:00  |  Presenting Author(s): Junichi Soh

      • Abstract

      Background

      The perioperative nutritional and immunological statuses significantly associated the clinical outcome of the surgery, especially for the extended surgery. Induction chemoradiotherapy (iCRT) followed by surgery is one of treatment options for locally advanced (LA) non-small cell lung cancers (NSCLCs) although there is a risk for increasing postoperative complications. A prognostic nutritional index (PNI), calculated using serum albumin levels and peripheral lymphocyte count, has been used to predict the clinical outcome of various cancers including early stage NSCLCs but not LA-NSCLC after iCRT. In this study, we investigated the impact of PNI on clinical outcome of iCRT followed by surgery in the patients with LA-NSCLCs.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      During 1999 to 2016, 173 patients underwent iCRT followed by surgery in Okayama University Hospital. Among them, 128 patients who matched to inclusion criteria were studied. We retrospectively calculated the PNI at (1) pre-iCRT (median 5 days before administration), (2) pre-operation (Ope) (median 5 day before surgery), and (3) post-Ope (median 30 days after surgery) and reviewed the medical records.

      4c3880bb027f159e801041b1021e88e8 Result

      The median age was 62 years old (range 31 – 79) and 100 patients were male. Seventy patients were adenocarcinomas and 46 were squamous cell carcinomas. Clinical stages were IIA / IIB (n = 15), IIIA (n = 87), IIIB (n = 25), and IV (n = 1). Main regimen of iCRT was CDDP / DOC with concurrent radiotherapy (46 gray). Treatment responses were CR/PR (n = 99), SD (n = 27), and PD (n = 2). Lung resections were lobectomy (n = 109), bi-lobectomy (n = 14), and pneumonectomy (n = 5) and additional procedures were performed in 93 patients. Based on the invasiveness of surgery, we categorized into three groups: 1) highly invasive group (n = 60), 2) intermediate group (n = 33), and 3) standard group (n = 35). Pathological complete responses were present in 37 patients. The PNI were significantly decreased during treatment course [49 (24 – 71) in pre-ICRT, 44 (30 – 58) in pre-Ope, and 41 (22 – 58) in post-Ope]. Among the entire cohort, the perioperative PNI values showed some effect on overall survival. However, among the highly invasive group, the poor preoperative PNI values significantly correlated with worse overall survival.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Peri-treatment nutritional evaluation using PNI is important to predict clinical outcome of the patients who received the iCRT followed by surgery with LA-NSCLCs especially when highly invasive surgery is required.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-71 - Clinical Outcome of Induction Chemoradiotherapy Followed by Surgery for the Patients with cN2 Non-Small Cell Lung Cancer (ID 13091)

      16:45 - 18:00  |  Author(s): Junichi Soh

      • Abstract
      • Slides

      Background

      The treatment strategy for clinical N2 (cN2) non-small cell lung cancer (NSCLC) is still controversial, because its clinical outcome is unsatisfactory and cN2 NSCLC harbors various conditions. In this study, we investigated the clinical outcome of induction chemoradiotherapy (iCRT) followed by surgery in the patients with cN2 NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      During 1999 to 2016, 92 patients with cN2 NSCLC were surgically treated after iCRT in our hospital. Overall survival (OS) and relapse-free survival (RFS) were evaluated by the Kaplan-Meier method with log-rank test (univariate analyses) and by the cox proportional hazard model (multivariate analyses).

      4c3880bb027f159e801041b1021e88e8 Result

      Median follow-up was 49.3 months (range 3.0 - 216). Median age was 62 (21 - 79). Sixty-nine patients (75%) were male. Fifty-four and 38 patients were cStageIIIA and IIIB, respectively. Forty-six (50%) patients were adenocarcinoma. As for iCRT, the CDDP plus DTX regimen was applied for most of patients (96.7%), and the median radiation dose was 46Gy (36 - 60). Complete/major/minor pathological responses were exhibited in 29/36/27 patients, respectively. pCR was observed in 22 patients. The 5-year rates of OS and RFS were 64.1% and 48.1%, respectively. The patients with lower-lobe origin, cStage IIIA (UICC8th), poor radiological response (progressive or stable disease), minor pathological response, re-operation within 30days after surgery, or recurrence showed significantly worse OS than the others. In addition, the patients with lower lobe origin, cStageIIIA, multi-station N2, poor radiological response, or minor pathological response showed significantly worse RFS. The multivariate analysis revealed that the patients with lower-lobe origin tumors and multi-station N2 showed significantly worse OS [Hazard Ratio (HR) 2.55, 95% confidence interval (CI) 1.11 - 5.71, P= 0.028] and RFS (HR 2.45, 95%CI 1.34 - 4.69, P= 0.003), respectively. Adenocarcinoma, lower-lobe origin, multi-station N2, cStageIIIA, poor radiological response, and minor pathological response significantly correlated to recurrence. Among them, adenocarcinoma (odds ratio (OR) 3.27, 95%CI 1.21 – 8.89, P= 0.02), lower-lobe origin (OR 5.22, 95%CI 1.48 – 18.40, P= 0.01), and multi-station N2 (OR 3.63, 95%CI 1.32 – 9.88, P= 0.012) independently correlated to recurrence.

      8eea62084ca7e541d918e823422bd82e Conclusion

      iCRT followed by surgery may be one of the feasible treatment options for the patients with cN2-NSCLCs, especially for those which harbor non-lower lobe origin and multi-station N2 .

      6f8b794f3246b0c1e1780bb4d4d5dc53

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