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J. Morita



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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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      P1.02-019 - Complex Mutation of Epidermal Growth Factor Receptor (EGFR) in Patients with Non-Small Lung Cancer (ID 4672)

      14:30 - 15:45  |  Author(s): J. Morita

      • Abstract
      • Slides

      Background:
      Analysis of the epidermal growth factor receptor (EGFR) gene is currently one of the most important tests in establishment of a treatment strategy for primary lung cancer. Major mutations of exon 19 deletion and exon 20 point mutation (L858R) are particularly well known in adenocarcinomas, and tyrosine kinase inhibitors (TKIs) have provided significant benefits to patients with such mutations. Complex mutation patterns of EGFR have also been reported, but their significance is unknown.

      Methods:
      Clinicopathological features and response to treatment of non-small lung cancer (NSCLC) with complex mutation of the EGFR gene were investigated in cases treated at Kanagawa Cardiovascular and Respiratory Center from June 2014 to March 2016.

      Results:
      EGFR gene analysis was performed in 334 cases, of which 108 had EGFR mutations. These cases included 7 (6.5%) with complex mutations: two males (28.6%) and five females (71.4%) with an age of 71.0±6.0 (mean±SD) years. Five of the 7 cases underwent surgery and two were inoperable. The histological diagnoses were adenocarcinomas (n=6) and squamous cell carcinoma (n=1). The pathological stage in the surgical cases (all adenocarcinomas) were IB, IIA, and IIIA in 2, 1 and 2 cases, respectively. Both inoperable cases were clinical stage IV. The EGFR complex mutation patterns were 19 deletion and 20 T790M (n=2, with one case with acquired TKI resistance), 18 G719X and 21 L861Q (n=3), 19 deletion and 21 L858R (n=1), and 20 T790 and 21 L858R (n=1). In the five surgical cases, two (pStage IIA, 19 deletion and 20 T790M; pStage IIIA, 18 G719X and 21 L861Q) received postoperative TKI therapy because of recurrence. Both patients had a poor response to TKIs and both died. The patients in another three surgical cases are alive without receiving TKI therapy. Two inoperable cases (19 deletion and 20 T790M; 18 G719X and 21 L861Q) were treated with standard chemotherapy and TKIs, and also died. The disease-free survival period in the surgical cases was 532±319 days and the overall survival period in the case with postoperative recurrence and the inoperable cases was 810±563 days. The progression-free survival period in patients treated with TKIs was 101.5±90.6 days.

      Conclusion:
      In patients with EGFR mutation, 6.5% have complex mutations, of which 85.7% are minor-on-minor or minor-on-major mutations. Lung cancer with complex mutation of EGFR tends to have a poorer response to TKIs compared to cases with a major single mutation.

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    P3.04 - Poster Session with Presenters Present (ID 474)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Surgery
    • Presentations: 1
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      P3.04-022 - Unexpected Residual Carcinoma in the Bronchial Stump after Surgery for Lung Cancer (ID 4831)

      14:30 - 15:45  |  Author(s): J. Morita

      • Abstract
      • Slides

      Background:
      Surgery for lung cancer should result in no residual carcinoma in pulmonary vessels and the bronchial stump of the isolated lung. Intraoperative frozen diagnosis of the surgical bronchial stump is usually not scheduled unless there is a short distance between the tumor and the predetermined bronchial cutting line in postoperative chest computed tomography (CT). Rarely, unexpected microscopic residual carcinoma in the surgical bronchial stump is observed after surgery. Additional radiation therapy for the bronchial stump in such cases is controversial because of the high risk for bronchopleural fistula.

      Methods:
      From April 2000 to March 2015, 1169 consecutive patients with non-small lung cancer underwent surgeries (133 segmentectomy, 986 lobectomy, 13 bilobectomy, 37 pneumonectomy) for non-small cell lung cancer at our hospital. Among these cases, 7 (0.6%) had a bronchial stump with residual cancer cells. The clinicopathological characteristics and outcomes of these patients were investigated retrospectively.

      Results:
      Six of the 7 cases had undergone lobectomy and one received pneumonectomy. Histologically, there were 4 cases of adenocarcinoma and 3 of squamous cell carcinoma. Four cases were stage IIIA (pT1aN2M0, pT3N2M0, pT2aN2M0, pT1bN2M0), two were IIA (pT1aN1M0, pT2aN1M0), and one was IB (pT2aN0M0). All cases had lymphatic invasion microscopically. All 7 cases developed recurrence or distant metastasis. One had local recurrence at the bronchial stump and 6 had distant metastasis (2 in brain, and 1 each in lymph nodes, chest wall, ribs, and pericardium). Three cases received postoperative treatment of radiotherapy for the bronchial stump only, radiotherapy for the mediastinum and chemotherapy, and cytotoxic chemotherapy only, respectively. Bronchopleural fistula did not occur as an adverse effect. Six of the patients died due to cancer progression. The patient with lymph node metastasis is alive and under treatment with TKI therapy. In all cases, bronchial wall thickness suggesting tumor invasion was not found on a preoperative CT scan, and preoperative bronchoscopic findings showed a normal bronchial mucosa.

      Conclusion:
      In surgical cases of non-small cell lung cancer, microscopic residual cancer at the surgical bronchial stump was found at a rate of 0.6%. Such cases tended to have relapse as distant metastasis, rather than local recurrence. Preoperative evaluation of bronchial invasion is straightforward, but the postoperative treatment strategy is uncertain. In postoperative follow-up, systemic evaluation of the local region and distal organs is necessary.

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