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S. Song



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    MO10 - Molecular Pathology II (ID 127)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
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      MO10.01 - Integrative and comparative genomic analysis of East-Asian lung squamous cell carcinomas (ID 2667)

      16:15 - 17:45  |  Author(s): S. Song

      • Abstract
      • Presentation
      • Slides

      Background
      Lung squamous cell carcinoma (SqCC) is the second most prevalent type of lung cancer. Currently, no targeted-therapeutics are approved for treatment of this cancer, largely due to a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SqCC, we probed somatic genome alterations of lung SqCC cases from Korean patients.

      Methods
      We performed whole-exome sequencing of DNA from 104 lung SqCC samples from Korean patients and matched normal DNA. In addition, copy number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated.

      Results
      This cancer cohort is characterized by a very high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of cigarette-smoke exposure. Seven genes demonstrated statistical enrichment for mutation (TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2 and PIK3CA). Comparative analysis between Korean and North American lung SqCC demonstrated similar spectrum of alterations in these two populations, in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SqCC.

      Conclusion
      These findings provide new steps towards the identification of genomic target candidates for precision medicine in lung SqCC, a disease with a significant unmet medical need.

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    P2.18 - Poster Session 2 - Pathology (ID 176)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P2.18-012 - Bronchial washing/brushing samples are comparable to biopsy samples for EGFR mutation testing in non-small cell lung cancer (ID 2611)

      09:30 - 16:30  |  Author(s): S. Song

      • Abstract

      Background
      Bronchial washings/brushings (BW/B) are often used for early screening and cytological diagnosis of lung cancer. We examined the possibility of EGFR testing on cytology samples, as compared to bronchial biopsy sample.

      Methods
      116 BW/B samples with non-squamous histology were submitted to our department for EGFR mutation testing at Chonnam National University Hospital within 8-month period. Biopsy samples was concurrently submitted for histologic diagnosis. We used the PNA clamping method for EFGR mutation test.

      Results
      Histologic diagnosis were 103 cases of adenocarcinomas and 13 cases of NSCLC, not otherwise specified (NOS). Each sample was assessed by a pathologist for adequacy and DNA content. At BW/B samples, 22 cases showed exon 19 deletion, 13 exon 21 mutation, 79 were wild type and 2 failed. The EGFR mutation rate using BW/B sample was 30.2%. At bronchial biopsy samples, 23 cases showed exon 19 deletion, 13 exon 21 mutation, 72 were wild type and 12 failed. The EGFR mutation rate using bronchial biopsy sample was 31.0%. Mutation detection cases were nearly identical in both samples. But, in only one case, exon 21 mutation was detected in biopsy sample, not in BW/B sample. The median DNA content for BW/B samples compared to biopsy samples were 3.7ug and 3.2ug. The failure rate for cytology samples was lower than biopsy samples.

      Conclusion
      BW/B samples are superior to bronchial biopsy samples in terms of DNA quantity and rate of failure. Moreover, in case of inadequate biopsy sample, BW/B samples were a substitute material for EGFR mutation test.

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    P3.10 - Poster Session 3 - Chemotherapy (ID 210)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 2
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      P3.10-014 - Efficacy and Safety of docetaxel plus oxaliplatin as a first-line chemotherapy in patients with advanced or metastatic Non-small-cell Lung Cancer (ID 1285)

      09:30 - 16:30  |  Author(s): S. Song

      • Abstract

      Background
      Platinum doublets are standard first-line treatment of stage IV non-small-cell lung cancer (NSCLC) without targetable driver mutations such as EGFR or ALK. Oxaliplatin is known to be more potent than cisplatin, requiring fewer DNA adducts to provide equivalent cytotoxicity. The objective of this study is to evaluate the efficacy and safety of oxaliplatin combined with docetaxel as a first line treatment of stage IV NSCLC.

      Methods
      This is prospective, single-center, phase II trial. Patients with chemotherapy-naive NSCLC received docetaxel 60mg/㎡ (day 1) and oxaliplatin 70mg/㎡ (day 2) every 3 weeks for up to 6 cycles. The primary endpoint was objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Treatment response was evaluated according to RECIST version 1.1.

      Results
      Thirty three patients were enrolled and response evaluation is available in 30 patients at the present time. There were 10 partial responses, 16 stable diseases. ORR was 33.3% and disease control rate was 86.7%. Median PFS was 127 days (95% confidence interval, 59~195) and median OS was 394 days (95% confidence interval, 264~524). Grade 3-4 toxicities occurred in 45% of patients, and the most common hematologic toxicity was neutropenia. There were two cases of hyperglycemia and sepsis.

      Conclusion
      This study suggests that the combination of oxaliplatin and docetaxel is effective in patients with NSCLC, with reasonable toxicities. (ClinicalTrials.gov Identifier: NCT01243775)

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      P3.10-031 - Comparative Study Between Belotecan/Cisplatin and Etoposide/Cisplatin (COMBAT) in Patients with Previously Untreated, Extensive Stage Small Cell Lung Cancer (ID 1896)

      09:30 - 16:30  |  Author(s): S. Song

      • Abstract

      Background
      Belotecan (camtobell™) is a topoisomerase I inhibitor, and effective in small cell lung cancer (SCLC). The objective of this study is to compare the efficacy and safety of belotecan+cisplatin (BP) and etoposide+cisplatin (EP) in first line setting.

      Methods
      This is a multicenter, randomized, prospective controlled trial to prove non-inferiority of BP compared to standard EP regimen. The primary endpoint is overall response rate (ORR), and secondary endpoints are toxicity, overall survival (OS) and progression-free survival (PFS). BP was administrated by belotecan 0.5 mg/㎡ for 4 days combined with cisplatin 60 mg/㎡ only for first day. Treatment response was evaluated according to version 1.0 of Response Evaluation Criteria in Solid Tumors.

      Results
      A total of 147 (BP: 71, EP: 76) patients were randomly assigned and received study drug at least once. In BP arm, there were 1 complete response, 41 partial responses (PR), 17 stable diseases (SD), and there were 35 PR and 28 SD in EP arm. Non-inferiority of BP compared to the EP arm was confirmed by the ORR (BP: 59.2%, EP: 46.1%, 90% confidence interval -0.3 to 26.5, meeting the predefined non-inferiority criterion). Median OS (BP: 360, EP: 305 days, p=0.21) and PFS (BP: 190, EP: 172 days, p=0.37) were not significantly different. The mean relative dose intensity was significantly different (BP: 0.79, EP: 0.86, p<0.01). The frequency of grade ≥ 3 anemia (BP: 34.3%, EP: 13.0%, p<0.01) and thrombocytopenia (BP: 54.3%, EP: 16.9%, p=<0.01) were higher in BP arm.

      Conclusion
      In extensive stage SCLC, ORR of BP was not inferior to EP and there was no difference of survival. But anemia and thrombocytopenia were more frequent in BP arm. (ClinicalTrials.gov number, NCT00826644)