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H. Makino



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    P2.24 - Poster Session 2 - Supportive Care (ID 157)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P2.24-049 - The significance of fever after the first administration of zoledronate as a prognostic factor in patients with advanced non-small cell lung cancer. (ID 2971)

      09:30 - 09:30  |  Author(s): H. Makino

      • Abstract

      Background
      Nitrogen-containing bisphosphonates(N-BPs) are usually administered to patients with advanced cancer harboring bone metastases to prevent skeletal related events(SREs). Preclinical studies have demonstrated the anticancer activity of N-BPs in vitro and in vivo. Zoledronate (ZOL) is a type of N-BP, and clinical trials of ZOL have demonstrated survival benefits in breast cancer and multiple myeloma. However, the benefit of ZOL to overall survival for lung cancer patients is still controversial. The first administration of intravenous N-BPs are occasionally induced fever, which is due to the activation of γδ T cells. γδ T cells are a small subset of T lymphocytes that play an active role in the immunosurveillance against infections and tumors as components of innate immunity. However, the significance of ZOL-induced fever is not clear in patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to estimate the prognostic value of fever after N-BP administration in advanced NSCLC patients.

      Methods
      We retrospectively reviewed 46 patients with advanced NSCLC who recerved ZOL treatment from March-2009 to March-2011 in the department of respiratory medicine in Tottori University hospital. ZOL-related fever was defined as body temprature more than 37.5℃ within 48 hours after the first administration of ZOL. Fever that persister for > 2 days, or treated with antibiotics were not defined as ZOL-related fever. Even if there were records of ZOL administration, we excluded the case with no record in terms of fever after treatment with ZOL. We analysed patients who had Eastern Cooperative Oncology Group (ECOG)-performance status (PS) ≦ 1. Clinicopathological factors such as age, gender, smoking history, disease stage, histological type, and epidermal growth factor receptor (EGFR) mutation status were analyzed using univariate and multivariate analyses, and these factors were compared between the fever group and non-fever group.P-value of < 0.05 were considered statistically significant.

      Results
      Fifteen out of 46 patients (32.6%) experienced fever after the first administration of ZOL. No significant differences in clinicopathological characteristics were seen between the two groups. The mean survival time (MST) observed in the fever group [MST 1003 vs. 471 day, hazard ratio (HR) 2.15, p=0.04] was significantly longer than the non-fever group. Univariate analyses for the probability of overall survival indicated that a positive EGFR mutation status (p=0.016), non-squamous type of cancer (p=0.02), no smoking history (p=0.001), and female gender (p=0.036) were predictors of significantly longer survival time. Comparatively, the presence of fever after ZOL administration [HR, 2.73; 95% confidence interval (CI) 1.17-6.34, p=0.020] and having no smoking history [HR, 0.13; 95%CI 0.20-0.85, p=0.033] were still significant predictors for longer survival time in multivariate analyses.

      Conclusion
      Fever after the first administration of ZOL was an independent prognostic factor in patients with advanced NSCLC.

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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.06-049 - Detection of EGFR mutation in bronchial lavage fluid after transbronchial biopsy using a novel high-speed real-time PCR system. (ID 3246)

      09:30 - 09:30  |  Author(s): H. Makino

      • Abstract

      Background
      Epidermal growth factor receptor (EGFR) mutation testing is essential to determine treatment regimens for patients with advanced non-squamous non-small cell lung cancer (non-Sq NSCLC). However, it requires at least two weeks until the results of commercialized EGFR testing are available. Therefore, we developed a novel high-speed real-time PCR system to reduce the time required for EGFR mutation detection. The reaction time of this system is only 5 minutes, and EGFR mutation status is found out within a few hours after diagnostic bronchoscopy. We tried to detect exon 19 deletion and exon 21 point mutation(L858R) in bronchial lavage fluid (BLF) after transbronchial biopsy (TBB) using this system. The aim of this study is to assess the performance of this novel high-speed real-time PCR system.

      Methods
      Seventy five consecutive patients who underwent TBB in our hospital from November 2012 to May 2013 were enrolled. Samples were obtained from BLF after TBB. DNA was extracted using QIAamp Blood Mini Kit (QIAGEN Japan, Tokyo, Japan). EGFR mutations were detected with high-speed real-time PCR system (TRUST medical, Hyogo, Japan) (Method A). Once the patient was diagnosed NSCLC with histology of TBB samples, EGFR mutation status was validated with PCR-invader method (BML, Inc. Tokyo, Japan) (Method B). We evaluated the sensitivity and concordance between (A) and (B).

      Results
      Lung cancer was histologically diagnosed in 51 patients (adenocarcinoma/squamous cell carcinoma/others=42/6/3), while not in 24 patients. Detection rate of EGFR mutation in patients with lung cancer was 29.4%(15/51) with (A) and 31.4%(16/51) with (B), respectively. Concordance rate between two methods was 94%. Discordance was found in one (6%) sample, where minor mutation of Exon19 L747-P753 deletion and insertion S was found only with (B). When (B) was used as a standard, sensitivity and specificity of (A) were 94% and 100%, respectively. Time to detect EGFR mutation by (A) and (B) were 2 hours and 18 days (6-45 days), respectively.

      Conclusion
      A novel high-speed real-time PCR system enables us to apply rapid EGFR mutation detection for clinical use.