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S. Kimura



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    MO06 - NSCLC - Chemotherapy I (ID 108)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO06.02 - Monitoring EGFR T790M with plasma DNA in lung cancer patients treated with EGFR tyrosine kinase inhibitor in prospective observational study (ID 1399)

      16:20 - 16:25  |  Author(s): S. Kimura

      • Abstract
      • Presentation
      • Slides

      Background
      Detection of mutations with plasma DNA isolated from peripheral blood is an alternative method of biopsy. The gatekeeper T790M mutation of EGFR has been observed in half of patients who acquired resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI). Considering that majority of lung cancer recurrence occurs as distant metastases, determination of T790M using a non-invasive mutation detection system with plasma DNA would be useful. We recently developed a novel non-invasive, fully-automated monitoring system, MBP-QP (mutation-biased PCR and quenching probe) method, to detect T790M using plasma DNA. The detection limit was two copies of control plasmid and 0.2 ng of genomic DNA, the T790M mutation was detected in plasma DNA from 53% of lung adenocarcinoma patients who acquired resistance in the previous retrospective study. Compared with the other methods such as PNA-LNA PCR clamp, the cycleave PCR technique, and digital PCR, the MBP-QP method is simple, sensitive, and reflective of clinical course. To determine the usefulness of the MBP-QP method for monitoring T790M during treatment of EGFR-TKI, a prospective clinical study has been performed.

      Methods
      This is a prospective, multicenter observational study involving lung adenocarcinoma patients carrying EGFR activating mutations such as L858R and exon 19 deletions treated with EGFR-TKI. Primary objective was to determine whether T790M was detected with plasma DNA at the time point of progressive disease (PD), and the secondary objective was correspondence of T790M with plasma and cancer specimens. The association between detection of T790M and effect of EGFR-TKI were also investigated as the exploratory objective. Plasma DNA was isolated from the patients before treatment of EGFR-TKI, every four months during treatment, at the time of occurrence of PD, and after two courses of post-chemotherapy.

      Results
      Ninety lung adenocarcinoma patients treated with EGFR-TKI were enrolled, in whom 51% of L858R and 49% of exon 19 deletions were determined in tumor specimens before treatment. Most of the patients, 92.1%, had adenocarcinoma. 62% (55/90) was stage IV, and 29% (26/90) had postoperative recurrent disease. 43% (38/90) of the patients were treated with EGFR-TKI as the first-line therapy, and the rest of them were previously treated including 17% of the patients experienced with EGFR-TKI. T790M was detected in 23% (21/90) among the entire patients. Forty patients showed PD two years after beginning of this trial, and T790M was detected in 13 patients among the patients who acquired resistance to EGFR-TKI; the frquency of T790M positive among the patients with PD was 32.5% (13/40). Although T790M was temporarily detected during treatment of EGFR-TKI in 8 patients who were still responded to EGFR-TKI, is disappeared after that.

      Conclusion
      T790M was detected in plasma DNA isolated from lung cancer patients whose diseases were progressed. Continuous detection of T790M in plasma DNA seemed to be related with occurrence of PD.

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    P1.19 - Poster Session 1 - Imaging (ID 179)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      P1.19-004 - Evaluation of a cloud-based solution for local imaging evaluations in clinical trials for lung cancer (ID 1362)

      09:30 - 09:30  |  Author(s): S. Kimura

      • Abstract

      Background
      Background: Clinical trials for determination of anti-cancer effects of chemotherapeutic agents are key for developing new strategies for cancer treatment. In most trials, primary endpoints are provided by imaging evaluations. Regulatory authorities have been recommending an Independent Central Review (ICR) with several readers to mitigate potential biases resulting from variance between investigator sites in clinical trials. Based on recent publications promoting site -based evaluation as imaging endpoint, they currently investigate an alternative to ICR. The goal of this study is to evaluate a cloud-based paradigm implementing software solutions and services that standardize the imaging evaluations among international investigator sites.

      Methods
      Methods: Ten lung cancer patients, who received epidermal growth factor receptor-tyrosine kinase inhibitor and for which chest CT scans were available at three time points from baseline to progression, were retrospectively selected. CT scans were evaluated according to the RECIST 1.1 criteria by two oncologists (Saga University) and one radiologist (Nice University Hospital) independently, through a cloud-based software solution named LMS (Lesion Management Solutions, MEDIAN Technologies), which offers reviewing tools and lesion segmentation algorithms. Such system was hosted on the data center (Canon IT Solutions, Japan) and used by readers and data managers (Canon and MEDIAN Technologies) for de-identification, quality control and centralization of the images and their evaluations. The study compared response evaluations between readers and analyzed the reasons for discordances.

      Results
      Results: Readers with different medical training and education, working at distant locations were able to reliably perform radiological evaluations using the same cloud-based system. Between the oncologists and the radiologist, a discordance rate of 35 % (14/40 evaluations) was observed when considering RECIST overall response (CR, PR, SD, PD) at all time points. Precisely, 6 and 8 evaluations were discordant at time point 1 and 2, respectively. . Half of discordances (7/14) were explained by a difference in the selection of target lesions. There were 3 /14 discordances due to a difference in lesion segmentation. The different segmentations occurred when the lesions were adjacent to mediastinum or pleura, where limits of lesions are not very contrasted.

      Conclusion
      Conclusion: The study shows the feasibility of imaging evaluation based on cloud services for clinical studies involving multiple international sites. Centralization of data made possible the on-going monitoring of evaluations through specialized services reducing variability among sites. Analysis of discordances between readers identified areas of improvement for cloud-based services such as a consensus process for target selection at baseline and the development of segmentation tools to standardize management of measurable lesions.