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K. Shimizu



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    P1.03 - Poster Session 1 - Technology and Novel Development (ID 150)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.03-003 - Novel detection method for EGFR T790M mutation by Eprobe mediated PCR and melting curve analysis (ID 2006)

      09:30 - 16:30  |  Author(s): K. Shimizu

      • Abstract

      Background
      Figure 1Epidermal growth factor receptor (EGFR) mutation status is the primary issue on the appropriate therapy of EGFR-tyrosine kinase inhibitor (EGFR-TKI) in non-small lung cancer. The point mutation of EGFR T790M (C→T) is known to be an acquired and the most common resistance against EGFR-TKI. Highly sensitive mutation detection system has been desired considering the difficulty in　obtaining tissue specimens during disease progression. Eprobe is new fluorescence labeled probe with high affinity toward target ssDNA and works as competitive probe (Figure 1). Here we describe a novel method to identify T790M mutation using Eprobe on real-time monitoring of PCR and melting curve analysis.

      Methods
      Figure 1Eprobe was designed to bind wild type allele including T790M region with competing primer, which enriches mutant allele amplification (Figure 2). The T790M mutation was detected by melting curve analysis following real-time monitoring of PCR. We verified detection ability by genomic DNA containing wild type and mutated EGFR T790M (cell lines H1975) gene. For clinical evaluation, 338 tumor tissues from the patients with lung adenocarcinoma, of which EGFR gene mutation status had been revealed by the nucleic acid-locked nucleic acid PCR clamp (PNA-LNA PCR clamp), were assayed by Eprobe method. We compared the two methods on T790M mutation assay.

      Results
      The T790M mutant genome could be detected when it accounted for as little as 0.5% of a mixture of wild type genome by enrichment of mutation amplicon. The activating EGFR mutation (exon19 deletion, L858R, and L861Q) had been detected in 143 out of 338 samples (42.3%) but no T790M mutation was identified by PNA-LNA PCR clamp. Among 143 samples harboring activating EGFR mutation, T790M mutation was identified in 2 samples (1.4%) by Eprobe method.

      Conclusion
      The Eprobe method is sensitive for detecting EGFR T790M. Since Eprobe works in simple manner, current method is expected to apply to other gene detections.

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    P1.07 - Poster Session 1 - Surgery (ID 184)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P1.07-018 - Surgical Treatment for Super-elderly Patients ( over 85 years old ) with Lung Cancer (ID 1414)

      09:30 - 16:30  |  Author(s): K. Shimizu

      • Abstract

      Background
      It is by now widespread that surgical resection is standard curative treatment for lung cancer, however in super-elderly cancer patients (over 85 years old) there is no clear evidence of safety and efficacy of surgical approach. This study attempts to clarify the benefit of surgical treatment for them.

      Methods
      Between January 2002 and December 2012, among 1229 consecutively treated patients with primary lung cancer who underwent surgical resection, 29 patients (2.4%) were over 85 years old. Clinicopathological information on these patients was retrospectively reviewed and the surgical outcome was investigated.

      Results
      There were 21 men and 8 women, with a mean age of 86.5 years old (range, 85-91 years old). All patients were selected as operable candidates based on the results of routine staging procedures consisting of physical examination, blood chemistry, chest roentgenograms, bronchoscopy, computed tomography of the thorax, abdomen, MRI of brain, and radionuclide bone scanning. Indications for surgery included clinical stage I,II, or IIIA (except bulky N2 ) disease. The surgical procedure was lobectomy in 19 patients, sleeve lobectomy in 2 patients, segmentectomy in 1 patient, and wedge resection in 7 patients. Curative operation ratio was 75.9%. The median intraoperative blood loss and operative time were 96 ml and 165 min. There was no blood transfusion case in this series. Postoperative pathological stage was stage IA in 11 patients, IB in 8 patients, IIA in 1 patient, IIB in 5 patients, IIIA in 2 patients, IIIB in 1 patient. 25 patients (86%) were what is called limited disease. Histological diagnosis was adenocarcinoma in 14 (48.3%) patients, squamous cell carcinoma in 11(37.9%) patients, large cell neuroendocrine carcinoma (LCNEC) in 2 (6.9%) patients, large cell carcinoma in 1 (3.45%) patient, undifferentiated carcinoma in 1 (3.45%) patient. Patients presented postoperative complications in high rate. The complications recorded were delirium in 9 (31.0%) patients, respiratory failure 3 (10.3%) patients, acute renal failure in 2 (6.9%) patients, angina attack in 2 (6.9%) patients, atrial fibrillation in 1(3.5%) patient, cerebral infarction in 1 (3.5%) patient. Although surgical morbidity rate was 62.1%, surgical mortality rate was 0%. 14 patients died until now, 7 of them were recurrent death. Overall patient 1, 3, and 5 years survival rate were 100%, 68.5% and 38.6%, respectively. Postoperative hospital days were 19.5±7.51.　

      Conclusion
      Although surgical morbidity rate is high and postoperative hospital days is long, surgical results in this study are acceptable and support the value of surgical treatment in super-elderly patients with lung cancer.

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    P2.16 - Poster Session 2 - Other Thoracic Malignancies (ID 187)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Thymoma & Other Thoracic Malignancies
    • Presentations: 1
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      P2.16-001 - Diagnosis and surgical resection of solitary pulmonary nodules in patients with breast cancer (ID 1266)

      09:30 - 16:30  |  Author(s): K. Shimizu

      • Abstract

      Background
      The differential diagnosis of solitary pulmonary nodules (SPNs) in patients with breast cancer is vital but difficult using radiological features. We assessed the nature of SPNs in these patients and the role of surgery in diagnosis and treatment.

      Methods
      Thirty consecutive patients who underwent surgery for an SPN between 2002 and 2011 after curative surgery for breast cancer were retrospectively evaluated.

      Results
      Most (93%) SPNs were malignant. Pathological diagnoses in patients with SPNs were primary lung cancer (n = 20, 67%), pulmonary metastasis from breast (n = 7, 23%) or colon (n = 1, 3%) cancer, and benign conditions (n = 2, 7%). Among the 20 patients with primary lung cancer, 15 (75%) had stage IA tumors (T1aN0M0). The average disease-free interval was significantly longer in patients with primary lung cancer than in those with pulmonary metastases from breast cancer (P = 0.031). The five-year survival rates after pulmonary resection for lung metastasis from breast cancer patients and primary lung cancer patients were 100 and 61.1%, respectively.

      Conclusion
      SPNs found in patients with breast cancer have a high probability of malignancy, especially primary lung adenocarcinoma. Early resection of SPNs in patients who were diagnosed with both primary and metastatic lung cancer led to a good prognosis. We suggest that early pathological diagnosis by surgical resection should be conducted for the early diagnosis and appropriate treatment of SPNs in patients with breast cancer.