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K. Imai



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    P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P1.04-011 - Intraoperative Diagnosis of Lymph Node Metastasis Using a Rapid-Immunohistochemical (R-IHC) Staining Method in Non-Small Cell Lung Cancer (ID 912)

      09:30 - 17:00  |  Author(s): K. Imai

      • Abstract
      • Slides

      Background:
      Nodal micrometastasis in non-small cell lung cancer (NSCLC) is associated with a poorer survival rate than node-negative disease. Furthermore, lymph node micrometastasis often cannot be detected using conventional hematoxylin and eosin staining of frozen sections; detection requires additional time-consuming immunohistochemical (IHC) analysis of paraffin-embedded tissue. We developed a novel ultrarapid immunohistochemical staining method in which an AC electric field is used to facilitate detection of tumor cells. This method allows detection of tumor cells in frozen sections in less than 20 min, and could be a useful tool for frozen diagnosis. We previously reported IHC analysis for NSCLC in detection of lymph node micrometastasis without misdiagnosis using the rapid-IHC protocol developed at our institute. This technology, which has been patented, was released in May 2014 as "Histotech-R-IHC[R]". The purpose of rapid-IHC analysis during surgery for NSCLC is the utility of intraoperative diagnosis of lymph node metastasis.

      Methods:
      Thirty-four patients with NSCLC were enrolled in the study between June 2014 and March 2015 after obtaining signed informed consent. Surgery was performed at Akita University School of Medicine and University Hospital. The patients were taken to an operating room, and the standard preparations were made for a thoracotomy and lung resection such as lobectomy with systematic/selective nodal dissection or segmentectomy. Dissected lymph nodes from each patient were used in this study. Intraoperative samples from dissected lymph nodes were sectioned, conventionally stained with HE, and immunohistochemically labeled with anti-CK (AE1/AE3) antibody using the rapid-IHC procedures, after which they were examined by a pathologist.

      Results:
      IHC analyses were completed within 20 min, and the diagnosis was made by the pathologist within about 30 min. Two patients were diagnosed as positive on the basis of conventional histological examination, and the same two patients were deemed positive on the basis of CK detection using rapid-IHC. There were no micrometastases in this study. All patients diagnosed as negative based on CK detection using rapid-IHC were pathologically N0. Twenty-one patients underwent lobectomy, and 13 patients received segmentectomy. Twenty-eight patients underwent lymph node dissection of hilar and mediastinal (ND2a) nodes, and six patients underwent lymph node dissection of hilar nodes only (ND1).

      Conclusion:
      The rapid-IHC device is useful for intraoperative diagnosis of lymph node metastasis in lung cancer surgery. We want to apply this method to the minimally invasive surgery selection such as segmentectomy and selective mediastinal lymph node dissection. Further investigation in multicenter studies will be needed to confirm the utility of this method.

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    P2.06 - Poster Session/ Screening and Early Detection (ID 219)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Screening and Early Detection
    • Presentations: 1
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      P2.06-025 - New PET/CT Criterion for Nodal Staging in Lung Cancer: Area of SUV ≥ 2.5 / Lymph Node Area (ID 61)

      09:30 - 17:00  |  Author(s): K. Imai

      • Abstract
      • Slides

      Background:
      Surgical resection is the accepted standard of care for patients with non-small cell lung cancer (NSCLC) at an early stage, patients have a favorable prognosis. Unfortunately, however, only about 25% of NSCLC patients are eligible for surgery, and once the surgical candidates are selected, mediastinal staging is mandatory because up to 50% of these patients have regional metastasis. Accurate nodal staging is crucial for determining optimal treatment strategies and optimizing prognoses. The aim of the present study was to use surgical and histological results to develop a simple noninvasive technique for improving nodal staging using routine preoperative PET/CT in patients presenting with localized and clinically resectable NSCLC.

      Methods:
      The institutional review board approved this retrospective study, and written informed consent to perform the initial and follow-up CT studies was obtained from all patients. Preoperative PET/CT findings (n=163 patients with resectable NSCLC) and pathological diagnoses after surgical resection were evaluated. Using PET/CT images, lymph node surface area (SA), the maximum standardized uptake value (SUV~max~), SA of SUV ≥2.5 (Figure) and ≥3.0 were drawn freehand and measured using caliper software. Receiver operating characteristic (ROC) curves were then used to analyze those data. Figure 1



      Results:
      Based on ROC analyses, the cut-off values for SA of SUV ≥2.5, SA of SUV ≥3.0, SUV ≥2.5 SA / node SA ratio and SUV ≥3.0 SA / node SA ratio for diagnosis of lymph node metastasis were 200 mm[2], 30 mm[2], 1.0 and 0.4. When the conventional SUV~max~ ≥2.5 was used for diagnosis, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy of nodal staging were 61.1%, 62.2%, 28.9%, 86.4%, 62.0% , respectively. SUV ≥2.5 SA / node SA ≥1.0 had the highest negative predictive value, and when a cut-off value of SUV ≥2.5 SA / node SA ≥1.0 was used for diagnosis, the sensitivity, specificity, PPV, NPV and accuracy were 61.1%, 73.4%, 36.7%, 88.2% and 70.9%, respectively.

      Conclusion:
      When diagnosing nodal staging based a lymph node SUV ≥2.5 SA / node SA ratio of ≥1.0, we achieved a higher performance level than was achieved using the conventional of SUV~max~ criterion. Furthermore, determination of this ratio from PET/CT images is a simple noninvasive procedure.

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    P3.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 214)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      P3.03-021 - Neoadjuvant Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer (NSCLC) Patients (ID 1372)

      09:30 - 17:00  |  Author(s): K. Imai

      • Abstract
      • Slides

      Background:
      Neoadjuvant chemotherapy (NAC) has gained popularity in recent years, becoming a standard treatment for locally advanced non-small cell lung cancer (NSCLC) to improve resectability and downstage nodal disease, which have clear impacts on prognosis. Potential disadvantages are increased morbidity and/or mortality after surgery and risk of progression of disease that could have been initially resected. The purpose of this study was to evaluate outcomes in a series of patients with locally advanced NSCLC receiving NAC followed by surgery.

      Methods:
      A total of 12 patients (66.7% males; median age, 71 years) affected by NSCLC in clinical stage IIA-IIIB underwent platinum-based NAC followed by surgery between 2008 and 2014. The clinical stage was IIA in 3 patients, IIIA in 8 (4 of which were IIIAN2), and IIIB in 1. Histology was adenocarcinoma in 8, squamous cell carcinoma in 3, and adenosquamous carcinoma in 1.

      Results:
      All patients received platinum-based chemotherapy (median, 4 cycles). The NAC regimen was weekly paclitaxel-carboplatin in 6 patients, pemetrexed-carboplatin in 3, paclitaxel-carboplatin-bevacizumab in 2, and gemcitabine-cisplatin in 1. Radiologic response to NAC was complete in 1 patient (8.3%), partial in 8 (66.7%) and stable disease in 3 (25.0%). Overall response rate was 75.0% (95% confidence interval, 51-100%). Grade 3 or 4 hematological toxicities were common, including neutropenia (50%) and anemia (8.3%), but were transient and manageable. Non-hematological toxicities were moderate and no treatment-related deaths were encountered. Eleven patients (91.7%) underwent complete surgical resection after induction. Surgical procedures comprised lobectomy in 10 patients, bilobectomy in 1 and pneumonectomy in 1. No severe intraoperative complications or 30-/90-day mortality were seen. At pathological evaluation, 8 patients (66.7%) showed downstaging of disease, with complete in 1 (8.3%), major in 3 (25.0%) and minor in 7 (58.3%). With a median follow-up of 12.7 months (range, 5.2-50.8 months), the 1-year relapse-free survival rate was 56.6%. Four of the 12 patients developed metastasis (at 4.7, 6.0, 8.4, and 9.2 months), and 2 patients died at 14.7 and 23.9 months.

      Conclusion:
      NAC using platinum-based chemotherapy with new-generation cytotoxic agents for locally advanced NSCLC seems justified by low morbidity and mortality, good response rates, and high resectability. Although the evidence level for induction chemotherapy is low, incorporation of chemotherapy and surgery will greatly impact strategies for future lung cancer treatment.

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