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J. Pankowski



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    OA07 - Lymph Node Metastases and Other Prognostic Factors for Local Spread (ID 376)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Surgery
    • Presentations: 1
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      OA07.03 - Prognostic Significance of Micrometastases in Mediastinal Lymph Nodes of Patients With Radically Resected Non-Small Cell Lung Cancer (ID 5060)

      14:20 - 15:50  |  Author(s): J. Pankowski

      • Abstract
      • Presentation
      • Slides

      Background:
      Recurrence occurs in 30-50 % of patients operated for early stage non-small cell lung cancer (NSCLC), what suggests the existence of occult metastases at the time of surgery. Preoperative detection of occult micrometastases in mediastinal lymph nodes could contribute to better selection of patients apropriate for surgery. This retrospective study was undertaken to determine the prognostic significance of preoperatively detected mediastinal lymph node (LN) micrometastases in patients treated with radical surgical resection for stage I and II NSCLC.

      Methods:
      From January 2007 to December 2010, 82 patients with stage I and 67 patients with stage II NSCLC underwent transcervical extended mediastinal lymphadenectomy (TEMLA) and subsequent radical pulmonary resection. A total of 4841 mediastinal lymph nodes resected during TEMLA procedure and determined as metastases-free by hematoxylin and eosin staining were labelled to detect occult micrometastases (dual immunohistochemical staining with AE1/AE3 and BerEP4 antibodies).

      Results:
      Micrometastases were detected in mediastinal LN of 16 patients (9,7%). 11 patients had only one LN station affected (68,8%). Subcarinal LN were most frequently affected station (11 patients, 68,8%). There was significant correlation between the presence of micrometastases and tumor size. 5-year total survival was significantly better for stage I (64,1%, p=0.0001) and stage II (44,4%, p<0.05) patients without micrometastases comparing to those with micrometastases (18,8%). By multivariate analysis, only the presence of micrometastases was demonstrated to be a significant prognostic factor for 5-year total survival.

      Conclusion:
      Presence of micrometastases in mediastinal LN of patients with radically resected stage I and II NSCL is associated with significantly reduced 5-year total survival. Preoprative detection of micrometastases with immunohistochemical staining of mediastinal LN resected during TEMLA procedure improves staging and may contribute to better patient selection for curative surgery.

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    P2.03b - Poster Session with Presenters Present (ID 465)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P2.03b-011 - Screening for ALK Abnormalities in Central Nervous System Metastases of Non-Small-Cell Lung Cancer (ID 5146)

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

      • Abstract
      • Slides

      Background:
      Anaplastic lymphoma kinase (ALK) gene rearrangement was reported in 3-7% of primary non-small-cell lung cancer (NSCLC) and its presence is commonly associated with adenocarcinoma (AD) type and non-smoking history. ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, alectinib and ceritinib showed efficiency in patients with primary NSCLC harboring ALK gene rearrangement. Moreover, response to ALK TKIs was observed in central nervous system (CNS) metastatic lesions of NSCLC. Till date there is limited data ALK rearrangement incidence in CNS metastases of NSCLC, which could be considered as a regiment for targeted treatment. For this reason we undertook the present retrospective study to determine the frequency of ALK abnormalities in CNS metastases of NSCLC.

      Methods:
      The studied group included 145 patients (45 females, 100 males, median age 60 years ±8) with CNS metastases of NSCLC. The studied group was heterogeneous in terms of histology (80 adenocarcinoma, 29 squamous-cell carcinoma, 22 large-cell carcinoma, 14 not otherwise specific) and smoking status. ALK abnormalities were screened in sections obtained from formalin fixed paraffin embedded (FFPE) tissue samples. NSCLC using immunohistochemical (IHC) automated staining (BenchMark GX, Ventana, USA) and fluorescence in situ hybridization (FISH) technique (Abbot Molecular, USA).

      Results:
      ALK abnormalities were detected in 4.8% (7/145) of CNS metastases of NSCLC. ALK abnormalities were observed in AD and squamous-cell carcinoma (SqCC) patients (7.5%; 6/80 vs. 3.4%; 1/29, respectively). Analysis of clinical and demographic factors indicated that expression of abnormal ALK was significantly more frequently observed (p=0.0002; χ[2]=16.783) in former-smokers. Comparison of IHC and FISH results showed some discrepancies, which were caused by unspecific staining of macrophages and glial/nerve cells, which constitute the background of CNS tissues.

      Conclusion:
      In this retrospective study we evaluated the expression of ALK abnormal protein and ALK gene rearrangement in extremely unique material which are CNS metastatic lesions of NSCLC. The frequency of ALK abnormalities in this material could be higher or comparable to frequency of ALK gene rearrangement in primary NSCLC tumors. However, the comparison of IHC and FISH results showed discrepancies that arose from unspecific background, which was made by cells with nonmalignant origin. For this reason assessment of ALK gene rearrangement in CNS tissues require additional standardizations.

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