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S. Masuda



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    P1.03 - Chemotherapy/Targeted Therapy (ID 689)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
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      P1.03-009 - A Lung Adenocarcinoma with a STRN-ALK Rearrangement Was Poorly Responsive to Alectinib Treatment (ID 9197)

      09:30 - 16:00  |  Author(s): S. Masuda

      • Abstract

      Background:
      Patients with advanced-stage non-small cell lung cancer (NSCLC) can receive benefits from treatment with anaplastic lymphoma kinase (ALK) inhibitors, if the tumor harbors a rearrangement of the ALK-encoding gene. Alectinib, a second-generation ALK inhibitor, is generally an effective therapy for ALK-rearranged NSCLC, but not all patients are responsive to Alectinib treatment. The aim of the present study was to assess the clinical and genetic characteristics of ALK-positive lung adenocarcinoma (ADC) that showed poor response to Alectinib treatment.

      Method:
      Patients with ALK-rearranged NSCLC, who received Alectinib treatment at Nihon University Itabashi Hospital (Tokyo, Japan) between 2015 and 2017, were included in the study. Demographic and clinical data including year, sex, stage, smoking history, treatment response, and survival were collected. Pleural effusion from a poorly responsive patient was further examined for secondary ALK mutations and ALK fusion partners. Secondary ALK mutations were analyzed using Sanger sequencing, and ALK fusion partners were identified by RNA sequencing. Furthermore, p-glycoprotein (p-gp)/ATP binding cassette subfamily B member 1 (ABCB1) mRNA levels were quantified by quantitative RT-PCR. The study was approved by the institutional review board.

      Result:
      Five patients (three men and two women; median age, 51 years) with adenocarcinoma were studied. Two patients received first-line treatment, two received second-line treatment, and one received fourth-line treatment. Four patients achieved partial response, and one patient did not respond to the treatment. The median progression-free survival (PFS) rate was 204 days. In the poorly responsive patient, PFS rate was 92 days, which was much shorter than previously reported. No secondary gatekeeper mutations in the ALK tyrosine kinase domain was detected in carcinoma cells obtained from pleural effusion of one poorly responsive patient. However, Striatin (STRN)/ALK, a rare fusion of the aggressive rearranged ALK, was identified, it was confirmed that one end of STRN exon3 was fused with the beginning of ALK exon 20. ABCB1 overexpression was also detected.

      Conclusion:
      A rare ALK rearrangement, STRN/ALK, and overexpression of the multidrug-resistant ABCB1 are possible candidates for predictive factors for poor response to Alectinib treatment.

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    P2.02 - Biology/Pathology (ID 616)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.02-057 - Expression of MGAT4a and MGAT5 Are Correlated with Poorer Outcome in Advanced Lung Adenocarcinoma (ID 8714)

      09:30 - 16:00  |  Author(s): S. Masuda

      • Abstract

      Background:
      Protein glycosylation is a post-translational modification that is altered in cancer. However, it is yet unclear if there is a correlation between different glycosylation patterns of N-glycan and clinicopathological features. Therefore, we aimed to investigate differing glycosylation in advanced non-small cell lung cancer tissues by lectin expression assays and N-acetylglucosaminyltransferase gene expression analysis.

      Method:
      Formalin-fixed and paraffin-embedded biopsy specimens were obtained from 62 patients with lung adenocarcinoma (ADC) (2009-2011) who were diagnosed at Nihon University Itabashi Hospital. Tumor cells were excised and collected by laser microdissection, and each solubilized glycoprotein and mRNA was extracted. Expression levels of 44 lectins were analyzed by lectin array using a lectin chip. mRNA expression levels of mannosyl (beta-1,4-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase (MGAT3), mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase, isozyme A (MGAT4a), mannosyl (alpha-1,6-)-glycoprotein beta-1,6-N-acetyl-glucosaminyltransferase (MGAT5), fucosyltransferase (FUT)7, and FUT8 were analyzed by qRT-PCR.

      Result:
      Expression levels of Datura stramonium lectin (DSA), Solanum tuberosum lectin (STL), and Aspergillus oryzae lectin (AOL) were significantly higher in drug-resistant ADCs than drug-sensitive ADCs (P = 0.036, 0.0005, and 0.035, respectively). qRT-PCR showed that overexpression of MGAT4a and MGAT5 was detected in 7/62 (11.3%) and 3/62 (4.8%) of ADCs, respectively. The prognosis of patients with MGAT4a and/or MGAT5 positive ADC was worse than those with negative ADC (P = 0.018, log-rank).

      Conclusion:
      The results of the study suggested different glycosylation of N-glycan in lung ADC tissues. MGAT4a and/or MGAT5 overexpression, in particular, may correlate with a poorer response to standard chemotherapy and poorer outcome in advanced lung ADCs.

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    P2.15 - SCLC/Neuroendocrine Tumors (ID 716)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      P2.15-015 - Negativity for Thyroid Transcription Factor 1 Was Correlated with Less Neuroendocrine Differentiation in Small Cell Lung Cancers (ID 9180)

      09:30 - 16:00  |  Author(s): S. Masuda

      • Abstract

      Background:
      The biological and clinical significance of thyroid transcription factor 1 (TTF-1) remains unclear in small cell lung cancer (SCLC). The purpose of this study was to clarify the clinicopathological characteristics of TTF-1-negative SCLC.

      Method:
      We retrospectively studied the associations between survival and the expression of TTF-1, and examined the association between the expression of TTF-1 and neuroendocrine markers (Synaptophysin, Chromogranin, and CD56), neuroendocrine cell-specific transcription factor (ASCL1, BRN2), and NF1B, which is an oncogene for SCLC. Formalin fixing and paraffin embedding (FFPE) and clinical data in SCLC patients were collected and used. The study was approved by the institutional review board.

      Result:
      Thirty-five patients were examined. Eleven patients were negative for TTF-1, and twenty-four patients were positive for TTF-1. The analysis demonstrated that overall survival was not statistically significant between patients with TTF-1-negative and those with TTF-1-positive SCLC. However, frequency of negativity of Synaptophysin and Chromogranin was greater in patients with TTF-1-negative SCLC than in those with TTF-1-positive SCLC based on immunohistochemical expression, and the difference was statistically significant. mRNA expression of ASCL1, NF1B, and serum ProGRP were significantly lower in patients with TTF-1-negative SCLC than in those with TTF-1-positive SCLC. We showed that TTF-1-negative SCLC showed less neuroendocrine differentiation. It is suspected that TTF-1-positive and -negative SCLC have different biological characteristics.

      Conclusion:
      TTF-1-negative SCLC was different in terms of aspects of neuroendocrine differentiation (negativity of Synaptophysin and Chromogranin, lower expression of ASCL1 and NF1B) compared to TTF-1-positive SCLC.

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    P3.03 - Chemotherapy/Targeted Therapy (ID 719)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
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      P3.03-011 - A Report of BRAF V600E Positive Lung Adenocarcinoma Patient Who Respond Well to Pemetrexed (ID 8806)

      09:30 - 16:00  |  Author(s): S. Masuda

      • Abstract

      Background:
      BRAF mutations is one of the important driver oncogene in non-small cell lung cancer (NSCLC), and are known to give the petients worse prognosis as same as KRAS mutations. However, we experienced that a patient with BRAF V600E positive lung adenocarcinoma was responsive to pemetrexed treatment. The patient has been followed for over 7 years without recurrence and metastasis.

      Method:
      Here, we introduce a pemetrexed well respond patient with BRAF mutation positive lung adenocarcinoma. Clinical presentation, radiological features, histopathologic findings and genetic findings of the patient are reported.

      Result:
      A 64 years-old never smoker female who complained bloody sputum visited our hospital. Chest X ray examination showed protrusion of the right first aortic arches. Transbronchial lung biopsy was performed and primary lung adenocarcinoma was diagnosed. Brain metastasis was suspected by magnetic resonance imaging. The patient was initially given combined chemotherapy with CDDP+VNR and Radiation therapy (60Gy). But after six months, tumor progression was found. Therapeutic agent was changed to 600mg single pemetrexed as outpatient chemotherapy for 14 months. Computed tomography showed reduction of tumor mass. Then, the patient has been still followed without any anti-cancer treatment. It passed for 7 years after diagnosis. The oncogenic driver mutations of the present patient were investigated in another study. Immunohistochemistry and DNA sequencing analysis showed the existence of BRAF mutation V600E in the present case.

      Conclusion:
      BRAF mutation in NSCLC was reported not associated with enhanced chemosensitivity. However, pemetrexed was effective to the present BRAF V600E positive lung adenocarcinoma patient.