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H.J. Lee



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    MA 06 - Lung Cancer Biology I (ID 660)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Biology/Pathology
    • Presentations: 1
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      MA 06.04 - Development of Next-Generation Sequencing Based Cancer Panel and Its Clinical Implications in Lung Cancer (ID 9003)

      15:45 - 17:30  |  Author(s): H.J. Lee

      • Abstract
      • Presentation
      • Slides

      Background:
      To search actionable driver mutations, various cancer panels using next-generation target sequencing technologies are rapidly developed and adopted in the treatment of lung cancer. We developed a new cancer panel to detect 313 coding gene mutations, 30 fusion and 3 exon-skipping genes including either known or potential target genes. Performance of the panel was tested on our archived lung cancer tissue bank samples.

      Method:
      Two hundreds and two samples were tested (male 118, female 84, median age 63 (30-84) years). Histologic cell types were mainly adenocarcinoma (adenocarcinoma 158, squamous cell 25, large cell 6, sarcomatous 3, small cell 1, and mixed cell types 9).

      Result:
      With our cancer panel, 139 samples (68.8%) were identified to have mutations including 88 EGFR, 23 KRAS, 8 MET mutations, 7 ALK, 6 RET, 3 ROS1, 6 rare fusions (PTEN, BRAF, MET, CBFB, EWSR1, BCR), and 18 CNV alterations. Medical records revealed that traditional single-site tests including Sanger sequencing of EGFR, KRAS mutations and either immunohistochemical stain or FISH test for ALK or RET fusion had been performed in 191 patients. Among those patients, we identified 102 pathogenic mutations (53.4%) including 80 EGFR, 14 KRAS mutations, 6 ALK, and 2 RET fusions. Conventional single-site test results matched with that of cancer panel in 139 samples (72.8%). Cancer panel detected additional mutations in 48 samples (25.1%; 38 from the single-site test negative and 10 from positive samples). In two samples, the results showed discrepancy while in the other two, mutations were detected only in single-site test. However additional tests revealed cancer panel results to be correct. Excluding 4 patients with M1 stage, 198 patients’ long-term survival were analyzed according to the mutational status. In Cox’s proportional hazard model, presence of EGFR mutation was the only prognostic marker that predicted long-term survival along with clinical variables such as age, pT-stage, and pN-stage.

      Conclusion:
      In our results, we confirmed superior accuracy of our cancer panel compared to the traditional single-site tests. Furthermore, the new cancer panel discovered novel mutations, of which significance requires future functional investigation and potential development of new target agents.

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    P2.02 - Biology/Pathology (ID 616)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.02-059 - Genomic Mutation Patterns Detected with Cancer Panel Can Predict Postoperative Prognosis in Clinical Stage I Adenocarcinoma (ID 9024)

      09:30 - 16:00  |  Author(s): H.J. Lee

      • Abstract
      • Slides

      Background:
      Recent development of cancer panels based on target sequencing technology can detect genomic mutations which are useful to choose target agents for advanced stage lung cancer. We investigated if the result of panel-detected mutation patterns can predict prognosis of early stage lung cancer.

      Method:
      Among the 350 cases whose postoperative tissues were tested with cancer panel, we selected 338 cases excluding 9 recurrent tumors and 3 cases who received neo-adjuvant treatment. The mean age was 60.7+/-11.4 years (Male 197, female 141). Adenocarcinoma (293) was the most common followed by squamous cell (26), larger cell (5) and others (14). We classified the mutations patterns into three group; SN group (n=126) where a single nucleotide mutation (EGFR, KRAS, NRAS, CTNNB1) was detected, SV group (n=117) where a structural variation (SV) (indel, fusion, splicing) was present, and NO group (n=95) where no significant mutation was found. We investigated the association of mutation patterns with various clinical variables and their impact on the prognosis.

      Result:
      The mutation was rarely found in squamous cell cancer and the SVs were more frequently found in never-smoked patients. The 5 year overall survival was 73.8+/-3.1% and the 5 year disease-free survival was 46.3+/-3.2%. The disease-free survival of SV group was inferior to that of SN group (p=0.029). When we selected only adenocarcinoma patients and stratified them by clinical stage, the SV group showed poorer disease-free survival to that of SN group in clinical stage I (p=0.017). However, when stratified by pathologic stage, there was no difference. When we investigated discrepancies between clinical and pathologic stages, up-stage from clinical stage I to pathologic N2 was more frequently found in SV group. Figure 1



      Conclusion:
      Our observation suggests that if structural variations are detected in clinical stage I adenocarcinoma, more aggressive mediastinal lymph node evaluation is mandatory and a different treatment strategy may be investigated.

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    P3.16 - Surgery (ID 732)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Surgery
    • Presentations: 1
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      P3.16-026 - Clinical Implication of Occult Lymph Node Metastasis in the Remaining Lobes After Lobectomy in Non-small Cell Lung Cancer (ID 8993)

      09:30 - 16:00  |  Author(s): H.J. Lee

      • Abstract
      • Slides

      Background:
      The presence of lymph node metastasis in the ipsilateral remaining lobe and its clinical implication after lobectomy have not been evaluated or discussed.

      Method:
      We sampled station 12 node of the remaining lobe during the surgery and completely dissected all the segmental nodes if cancer cell metastasis was either confirmed or suspicious. We retrospectively reviewed such patients and analyzed clinicopathologic characteristics.

      Result:
      Between 2010 and 2016, we found 20 cases where a complete lymph node dissections of the remaining lobes were performed (male 19, female 1, median age 55 (29-71) years). The location of primary cancer was predominantly in the RLL (RLL 17, RML 2 and LLL 1) and the surgical procedure performed were mainly bi-lobectomy (RLL and RML 11, RLL 6, RML 2, LLL 1). The site of lymph nodes in the other lobe were predominantly located in the RUL (RUL 18, RUL and RML 1, LUL 1). Clinical N-stages were N0 in 6, N1 in 9, and N2 in 15 patients. Preoperative CT and PET-CT failed to predict presence of metastasis of other lobe lymph nodes. The pathologic N-stages were N0 in 3, N1 in 4 and N2 in 13. The metastasis in the other lobe was present in 14 patients whereas, 6 were negative. Twelve out of 14 patients with positive lymph node in the other lobe had mediastinal lymph node metastasis (85.7%). The overall survival rates were 94.4% at one year and 74.4% at 2 years. However, as many as 8 patients (40%) recurred at the time of the study. Figure 1



      Conclusion:
      In conclusion, we found some patients possessed occult metastasis in N1 nodes of the remaining lobe especially in lower lobe cancers and the majority had occult N2 metastasis as well. The prognostic and clinical implication of knowing lymph node status of the remaining lobe needs further investigations.

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