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K. Mori



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    P1.08 - Poster Session 1 - Radiotherapy (ID 195)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P1.08-008 - Prognostic factors in patients with brain metastasis from non-small cell lung cancer treated with whole-brain radiotherapy (ID 830)

      09:30 - 09:30  |  Author(s): K. Mori

      • Abstract

      Background
      To evaluate the prognostic factors associated with overall survival in patients with brain metastasis from non-small cell lung cancer(NSCLC) who received whole-brain radiotherapy (WBRT).

      Methods
      From September 2002 to December 2010, 257 patients with brain metastasis from NSCLC who received WBRT. Those who had undergone craniotomy or stereotactic radiotherapy before WBRT and those with leptomeningeal metastasis were excluded. The prognostic factors evaluated for overall survival were; gender, neurological deficit, histology, epidermal growth factor receptor (EGFR) mutation status, previous cytotoxic chemotherapy, previous EGFR tyrosine kinase inhibitor (TKI) treatment, RTOG-recursive partitioning analysis (RPA) (age,Karnofsy Performance Scale [KPS], primary tumor control), and diagnosis-specific graded prognostic assessment (DS-GPA)(age, KPS, extra cranial control, number of lesions). All factors with a Pvalue < 0.05 at univariate analysis were entered into a multivariate analysis using Cox regression with confidential interval of 99%.

      Results
      At the time of analysis, 225 patients (88%) died, 14 patients (5%) were alive, and 18 patients (7%) were lost to follow-up. The median follow-up time was 16.2 months. The median survival time (MST) was 5.6 months and 1-year survival rate was 28.6%. The MST according to gender, neurological deficit, histology, EGFR mutation status, previous chemotherapy, previous EGFR-TKI treatment, RPA class, and DS-GPA were shown in Table 1. In univariate analysis, the significant prognostic factors were; gender (P=0.0002), neurological deficits (P<0.0001), histology (P<0.0001), previous chemotherapy (P=0.0463), EGFR mutation (P=0.0236), RPA class (P<0.0001) and DS-GPA (P=0.0003). In multivariate analysis, RPA class (I and II vs III,KPS>70 vs <70), histology (adenocarcinoma vs non-adenocarcinoma) and previous chemotherapy (none vs present) were found to be significant prognostic factors (Table 2).Figure 1 Figure 2

      Conclusion
      RPA class I or II (KPS>70), adenocarcinoma and no previous chemotherapy were associated with longer survival. These factors should be taken into account for decision-making in an attempt to find optimal treatment for patients with brain metastasis.

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    P2.10 - Poster Session 2 - Chemotherapy (ID 207)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.10-021 - The effect of gefitinib in patients with postoperative recurrent non-small cell lung cancer harbouring mutations of the epidermal growth factor receptor. (ID 1367)

      09:30 - 09:30  |  Author(s): K. Mori

      • Abstract

      Background
      For patients with postoperative recurrent non-small cell lung cancer (NSCLC) harbouring mutations of the epidermal growth factor receptor (EGFR), EGFR tyrosine kinase inhibitor, such as gefitinib, is frequently used in clinical practice, in accordance with the treatment for patients with stage IV NSCLC. However, it is unclear whether there is a difference in effect of gefitinib between patients with postoperative recurrent NSCLC and patients with stage IV NSCLC, harbouring EGFR mutations.

      Methods
      We reviewed consecutive patients with postoperative recurrent or stage IV (at diagnosis) NSCLC harbouring EGFR mutations, who were treated with gefitinib at the Shizuoka Cancer Center between September 2002 and March 2012. The clinical data of the patients were obtained from their medical records, and retrospectively reviewed. The baseline patient characteristics, response to gefitinib, and survival were compared between patients with postoperative recurrent NSCLC (postoperative group) and patients with stage IV NSCLC at diagnosis (stage IV group). Patients were not included if they had received other EGFR tyrosine kinase inhibitors before administration of gefitinib.

      Results
      A total of 169 patients met the eligibility criteria for this study (postoperative group; 50, stage IV group; 119). The baseline characteristics (sex, age, histology, EGFR mutations status, prior cytotoxic chemotherapy) were well balanced between both groups, with the exception of performance status (PS). Patients in postoperative group had better PS than those in stage IV group (p = 0.044). At the start of treatment with gefitinib, bone and liver metastases were more common in stage IV group (p = 0.002 and p = 0.032), and pulmonary metastases were more common in postoperative group (p = 0.004). There was no significant difference in number of metastatic sites between two groups. The response rate of gefitinib in postoperative group was similar to that in stage IV group (58 vs 61%, p = 0.685). In contrast, progression free survival (PFS) (median PFS 16.7 vs 9.8 months, p < 0.001) and overall survival (OS) (median OS 63.3 vs 23.9 months, p < 0.001) were significantly longer in postoperative group than in stage IV group. Additionally, postoperative recurrent disease, PS (0-1) and single metastatic site were independent prognostic factors in the multivariate analysis of survival.

      Conclusion
      PFS and OS were superior in patients with postoperative recurrent NSCLC harbouring EGFR mutations treated by gefitinib than in those with stage IV disease. These results suggest, postoperative recurrent disease may be considered to be a stratification factor in clinical trial for NSCLC with EGFR mutations.

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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.06-012 - Pharmacogenetic study of Japanese patients with advanced non-squamous non-small cell lung cancer treated with pemetrexed plus cisplatin (ID 1407)

      09:30 - 09:30  |  Author(s): K. Mori

      • Abstract

      Background
      Pemetrexed (PEM) inhibits multiple enzymes in the folate (F) pathway. Several studies show that genetic polymorphisms in these enzymes influence the efficacy and toxicity of PEM. We aimed to investigate the relationship between genetic polymorphisms associated with the F pathway and clinical outcomes of Japanese patients with advanced non-squamous non-small cell lung cancer (NSQ-NSCLC) treated with PEM plus cisplatin (CIS).

      Methods
      We analyzed 34 polymorphisms in 14 genes associated with the F pathway in NSQ-NSCLC patients treated with PEM plus CIS: ABCC11, ADA, ATIC, DHFR, ERCC1, FPGS, GGH, MTHFD1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, and TYMS. These polymorphisms were compared with clinical outcomes such as response, toxicity, and progression-free survival (PFS) using Pearson’s χ[2] test and the log-rank test.

      Results
      All 56 patients were Japanese, with a median age of 62 years; 57.1% were male, 96.4% had an Eastern Cooperative Oncology Group Performance Status of 0–1, 96.4% had stage IV disease, and 94.6% had adenocarcinoma. The response rate, disease control rate, and median PFS were 32.2%, 78.6%, and 4.7 months, respectively. Of the 38 polymorphisms tested, none were associated with response or toxicity, but 2 single nucleotide polymorphisms (SNPs) (in the gamma-glutamyl hydrolase [GGH 452C>T] and methionine synthase [MTR 2756A>G] genes) were significantly associated with PFS. Patients harboring the GGH-C452C variant had significantly longer PFS (5.6 vs 2.8 months; p < 0.0001) than those with the C452T or T452T variants. Further, patients harboring the MTR-A2756A variant had significantly longer PFS (5.3 vs 3.7 months; p = 0.036) than those with the A2756G variant. In addition, among patients with the GGH-C452C variant, those harboring the MTR-A2756A variant had significantly longer PFS (5.9 vs 4.3 months; p = 0.044) than those with the A2756G variant.

      Conclusion
      SNPs in GGH and MTR seem to predict differences in PFS in NSQ-NSCLC patients treated with PEM plus CIS, and a combination of these 2 SNPs may predict differences in PFS more accurately. These results should be validated in larger, adequately designed prospective studies.