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S. Lim



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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.10-001 - Transglutaminase 2 can be predictive of epidermal growth factor receptor tyrosine kinase inhibitor efficacy and cytotoxic chemotherapy success in non-small cell lung cancer (ID 96)

      09:30 - 09:30  |  Author(s): S. Lim

      • Abstract

      Background
      Transglutaminase 2 (TG2), a cross-linking enzyme, is involved in drug resistance and the constitutive activation of NF-κB, a pro-inflammatory transcription factor. We investigated the association of the EGFR-TKI or cytotoxic chemotherapy clinical efficacy with transglutaminase 2 and NF-ĸB expression in non-small cell lung cancer (NSCLC).

      Methods
      TG2 and NF-ĸB expression was immunohistochemically studied in 120 patients with NSCLC who received an operation. Kaplan-Meier survival analysis and Cox regression analysis were used to estimate the effect of TG2 and NF-ĸB expression on chemotherapy clinical efficacy.

      Results
      Median age of patients was 64 years (41–82). There were 102 (85%) cases of adenocarcinoma and 18 patients (15%) had other histologies. Eight patients received adjuvant chemotherapy, 29 received platinum-based doublet chemotherapy and another 29 patients received EGFR-TKI. Smoking status was as follows: 25 current, 16 former and 79 never. There were 55 patients with an EGFR mutation. TG2 median value was 50 (0 to 300) and NF-kB median value was 20 (0 to 240). Response to platinum-based doublet was as follows: Overall response rate (ORR) was 13.8% and disease control rate (DCR) was 69% (Complete response (CR) 0%, partial response (PR) 13.8%, stable disease (SD) 55.2% and progressive disease (PD) 24.1%). Responses to EGFR-TKI was as follows: ORR was 24.1% and DCR was 58.6% (CR 3.4%, PR 20.7%, SD 34.5% and PD 34.5%). Among the 88 patients who received adjuvant chemotherapy, disease-free survival (DFS) did not differ between the low and high TG2 groups. Among patients (n=29) who received palliative platinum-based doublet chemotherapy, progression free survival (PFS) was significantly longer in the low TG2 group when compared with the high TG2 group (34.0 versus 15.0 months, p = 0.003). Among those who received EGFR-TKI (n=29) (first line 7, second line 18, third line 3, fourth line 1), PFS was significantly longer in the low TG2 group when compared with high TG 2 group (11.0 versus 2.0 months, p = 0.013). In patients with EGFR wild-type mutations treated with EGFR-TKI, progression free survival was longer in patients with low TG2 expression (9.0 vs 2.0 months, p=0.013).

      Conclusion
      This study suggests that TG2 expression can be predictive of success of cytotoxic chemotherapy and EGFR-TKI for patients with non-small cell lung cancer, particularly in patients with EGFR wild-type mutations.

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    P3.12 - Poster Session 3 - NSCLC Early Stage (ID 206)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.12-012 - Clinical and prognostic implication of ALK and ROS1 rearrangement in never smoker with surgically resected lung adenocarcinoma (ID 2232)

      09:30 - 09:30  |  Author(s): S. Lim

      • Abstract

      Background
      Rearrangements of oncogenic kinase proteins, anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1), were discovered as key oncogenic molecular drivers of lung adenocarcinoma recently. The aim of this study is to evaluate the prevalence and survival outcomes of ALK and ROS fusion in never smoker patients with surgically resected lung adenocarcinoma.

      Methods
      We analyzed consecutive stage IB to IIIA never smoker lung adenocarcinoma patients who underwent curative surgery in our institution. All resected tumors underwent comprehensive molecular profiling including EGFR mutation, KRAS mutation test, and fluorescence in situ hybridization (FISH) assay for ALK rearrangement. ROS1 rearrangement was evaluated by FISH assay in all triple-negative tumors (negative for EGFR, KRAS, and ALK).

      Results
      Of 162 never-smoker patients with lung adenocarcinoma, 14 (8.6%) and 5 (3.1%) patients had ALK and ROS1 rearrangement, respectively. Proportion of ALK or ROS fusion-positive (fusion-positive) patients was 26.0% (15 out of 73) among patients who are negative for EGFR and KRAS mutation. Fusion-positive patients tend to have a shorter disease free survival (DFS) than fusion negative patients, but without statistical significance (p= 0.124). However, multivariate analysis showed significantly poorer DFS of fusion-positive patients than fusion-negative patients with adjustment for T stage and lymph node metastasis (Hazard ratio 2.26; 95% Confidence interval, 1.19-4.30; p = 0.013). The 3-year DFS rate was 47.0% in fusion-negative patients and 32.7% in fusion–positive patients. Fusion-positive patients also showed poorer DFS in stage IB to IIB subgroup. (n=123, p= 0.046) Overall survival of patients was not different according to ALK or ROS fusion status. (p= 0.535) More extrathoracic metastasis was noted in fusion-positive patients than fusion-negative patients at the first time of recurrence. (46.2% vs. 35.8%, p= 0.539) The median progression free survival on EGFR tyrosine kinase inhibitor treatment after recurrence was 0.9 months in fusion-positive patients, which was significantly shorter than 10.2 months in EGFR mutation positive and 6.4 months in wild type patients..

      Conclusion
      This study shows significantly poorer DFS of ALK or ROS fusion positive patients in Asian never smoker lung adenocarcinoma patients. Development of ALK or ROS targeted adjuvant therapies in this subset of patients is needed to improve their poor survival after curative surgery.