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T. Okano



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    P1.02 - Poster Session with Presenters Present (ID 454)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-082 - The Feasibility of Cell-Free DNA Sequencing for Mutation Detection in Non–Small Cell Lung Cancer Was Detemined by Tumor Volume (ID 6001)

      14:30 - 15:45  |  Author(s): T. Okano

      • Abstract
      • Slides

      Background:
      Targeted therapeutics such as tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) have recently been introduced into clinical practice for individuals with NSCLC positive for actionable mutations of EGFR or ALK fusions, respectively. Molecular profiling that is able to predict the response to such drugs has thus become an important therapeutic strategy, allowing selection of the most appropriate treatment for individual patients.

      Methods:
      Matched lung cancer tissue and serum specimens were collected from 150 patients who underwent surgery at Tokyo Medical University Hospital from January 2013 to July 2014. All tissue samples were stored at –80°C until analysis. Tumor DNA and cfDNA samples were subjected to analysis with next-generation sequencing (NGS) panels for mutation detection.

      Results:
      All tumor DNA samples were successfully sequenced with the Ion Proton platform. The median read number per amplicon was 15,632. We identified TP53 mutations in 58 cases (38.7%); EGFR mutations in 56 (37.3%); KRAS mutations in 15 (10.0%); CTNNB1 mutations in 7 (4.7%); ERBB2, PIK3CA, BRAF, and PTEN mutations in 3 each (2.0%); and ERBB4, MET, ALK, FGFR2, NRAS, AKT1, and FBXW7 mutations in 1 each (0.7%). No mutation was detected in 22.0% (33/150) of the samples. Serum cfDNA was extracted for all 150 patients, with a median yield (copy number) of 4936 (range, 572 to 373,658). A total of 149 of the 150 (99.3%) cfDNA samples were successfully sequenced with the Ion Proton platform, with sequencing failure being due to an insufficient read number per amplicon in the one unsuccessful case. The median read number per amplicon for the 149 successfully sequenced cfDNA samples was 33,982.

      Conclusion:
      These results suggested that detection of mutations in cfDNA of patients with disease at stage IA or IB or at T2a or lower is difficult, and that the feasibility of mutation detection with cfDNA may depend on the T factor rather than the N factor. Tumor volume in the cfDNA mutation–positive group was significantly greater than that in the cfDNA mutation–negative group (159.1 ± 58.0 versus 52.5 ± 9.9 cm[3], p = 0.014). The maximum tumor diameter calculated at diagnosis was also larger in the cfDNA mutation–positive group than in the cfDNA mutation–negative group (5.3 ± 0.7 versus 4.1 ± 0.3 cm, p = 0.050). These results suggested that tumor volume is a determining factor for the feasibility of mutation detection with cfDNA.

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    P1.04 - Poster Session with Presenters Present (ID 456)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Pulmonology
    • Presentations: 1
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      P1.04-015 - Clinical Application of Virtual Navigated Bronchial Intervention (ID 4996)

      14:30 - 15:45  |  Author(s): T. Okano

      • Abstract
      • Slides

      Background:
      Removal of endobronchial tumor is considered the first treatment of choice to improve respiratory status to dilate and maintain the airway. In patients with inoperable tumors we frequently regard endoscopic treatment as the first treatment of choice, but the indications and decisions regarding the method require careful consideration. We reported the indications and efficacy of virtual navigated bronchial intervention for the treatment of bronchial tumors. To select safer and precisely approach for patients with bronchial tumors, we evaluate virtual navigated bronchial intervention using a high-speed 3-dimensional (3D) image analysis system, Synapse Vincent (Fuji Photo Film Co., Ltd., Tokyo, Japan).

      Methods:
      We set out to clarify, based on retrospective evaluation of routine work-up data in our charts and patient treatment data, the efficacy of virtual navigated bronchial intervention for the treatment of different types of bronchial tumors, yet representative of the spectrum of conditions we encounter, in order to provide a guide to techniques available in interventional bronchology for obstructive lesions. All computed tomography (CT) must satisfy several conditions necessary to analyze images by Synapse Vincent. Synapse Vincent provides more information not only concerning tumor size and shape, but also whether the tumor invades surrounding tissue and the extent of airway and vessel involvement. Constructed images are displayed on a monitor, which can be utilized for deciding the simulation and interventional strategy and for navigation during interventional manipulation.

      Results:
      In these cases, Synapse Vincent was used to determine the best planning of virtual navigated bronchial intervention. The feasibility and safety of Synapse Vincent in performing useful preoperative simulation and navigation of interventional procedures lead to the safer, more precise, and less invasive for the patient, and easy to construct an image, depending on the purpose, in 5-10 minutes using Synapse Vincent. Moreover, if the lesion is in the parenchyma or sub-bronchial lumen, it helps to perform simulation with virtual skeletal subtraction to estimate potential lesion movement. By using virtual navigated system for simulation, bronchial intervention was performed with no complications safely and precisely.

      Conclusion:
      Preoperative simulation using virtual navigated bronchial intervention reduces the surgeon’s stress levels, particularly when highly skilled techniques are needed to operate on lesions. This task, including interventional simulation and navigation both pre- and during manipulation, could lead to greater safety and precision. These technological instruments should be helpful for bronchial intervention procedures, and are also excellent devices for educational training.

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    P1.08 - Poster Session with Presenters Present (ID 460)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Surgery
    • Presentations: 1
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      P1.08-034 - Prognostic Impact of EGFR Mutation in Patients with Surgically Resected Lung Adenocarcinoma; Analysis about Subtypes of EGFR Mutations (ID 6031)

      14:30 - 15:45  |  Author(s): T. Okano

      • Abstract

      Background:
      Epidermal growth factor receptor (EGFR) gene mutations have an important role for predicting the prognosis in advanced or recurrent lung cancer patients. However, the significance of EGFR mutation as a prognostic factor for survival after complete resection remains controversial. The aim of this study is to evaluate the impact of mutational status in patients with surgically resected lung adenocarcinoma.

      Methods:
      We retrospectively investigated the data of 414 patients (pts) with p-stage I-IIIA adenocarcinoma who underwent completely tumor resection in our hospital from 2009 to 2013. Overall survival (OS), disease-free survival (DFS) , and clinico-pathological factors affecting these factors were evaluated.

      Results:
      There were 202 males and 212 females (median age, 67 years). In total, 270 (65%), 66 (16%) and 78 pts (19%) had p-stageI, II and IIIA disease respectively. In all 210 pts (51%) with EGFR mutation were detected. Eighty-six pts (21%) had exon 19 deletion (19 del) and 113 pts (27%), exon 21 mutation (L858R). Among 414 pts, 131 pts (31%) had lung cancer recurrence. The median follow-up period was 38.6 months. p-stageI mutant/wild:145/125, II:24/42, and IIIA:41/37. The 3-year survival rates of p-I-II and IIIA mutant/wild were 96.8%/92.1% and 81.6%/61.8% respectively. The median survival time of p-stageIIIA mutant was 80.5 months, and those of others were not reached. The 3-year DFS of p-I-II and IIIA mutant/wild were 78.3%/69.2% and 27.1%/45.1%, respectively. There were no significant difference in OS and DFS at each p-stage despite the EGFR mutational status. Compared to the wild type, the p-IIIA mutant group had a poor DFS. conversely, compared to wild type, the p-I mutant group showed a favorable DFS. According to the subtypes of EGFR mutation, there were no significant differences among EGFR subtypes, but pts with 19del tended to have the worst DFS. In subgroup analysis of 131 pts with recurrence, 3-year survival rate of p-I-II and IIIA mutant/wild were 92.0%/75.8% and 80.8%/45.6% respectively. Pts with p-IIIA mutant showed significantly favorable OS than those of wild type (p=0.014) as well as with p-I-II wild type. Although OS was not significantly different among the subtypes of EGFR mutation, pts with 19del showed statistically better prognosis than shown by the wild type (p=0.038).

      Conclusion:
      EGFR status was an independent prognostic factor in pts with surgically resected lung adenocarcinoma. Particularly, EGFR exon 19 deletion might be the strongest predictive factor of poor DFS and good OS in resected lung adenocarcinoma.