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X. Chen



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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.01-002 - TP53 Mutations Predict for Poor Survival in ALK Rearrangement Lung Adenocarcinoma Patients Treated with Crizotinib (ID 8241)

      09:30 - 16:00  |  Author(s): X. Chen

      • Abstract
      • Slides

      Background:
      Advanced non-small-cell lung cancer patients who harbor anaplastic lymphoma kinase (ALK) rearrangement are sensitive to an ALK inhibitor (Crizotinib), but not all ALK-positive patients benefit equally from crizotinib treatment. We analyze the impact of TP53 mutations on response to crizotinib in patients with ALK rearrangement non-small cell lung cancer (NSCLC).

      Method:
      66 ALK rearrangement NSCLC patients receiving crizotinib were analyzed. 21 cases were detected successfully by the next generation sequencing validation FFPE before crizotinib. TP53 mutations were evaluated in 8 patients in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).

      Result:
      TP53 mutations were observed in 2 (25.00%), 1 (12.50%), 1 (12.50%) and 4 (50.00%) patients in exons 5, 6, 7 and 8, respectively. The majority of patients were male (75.00%, 6/8), less than 60 years old (62.50%, 5/8) and never smokers (75.00%, 6/8). ORR and DCR for crizotinib in the entire case series were 61.90% and 71.43%, respectively. Statistically significant difference was observed in terms of PFS and OS between TP53 gene wild group and mutation group patients (P=0.038, P=0.021, respectively).

      Conclusion:
      TP53 mutations reduce responsiveness to crizotinib and worsen prognosis in ALK rearrangement NSCLC patients.

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    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 2
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      P1.02-045 - PIK3CA Mutations in Chinese Patients with Non-Small-Cell Lung Cancer (ID 8264)

      09:30 - 16:00  |  Author(s): X. Chen

      • Abstract
      • Slides

      Background:
      PIK3CA mutation represents a clinical subset of diverse carcinomas. We explored the status of PIK3CA mutation and evaluated its genetic variability and prognosis in patients with lung adenocarcinoma. The aim of this study is to investigate mutations and prognosis of non-small-cell lung cancer(NSCLC) harboring PIK3CA mutations.

      Method:
      A total of 517 patients with NSCLC were recruited between July 2012 and December 2014. The status of PIK3CA mutation and other genes were detected by reverse transcription polymerase chain reaction(RT-PCR) or next generation sequencing.

      Result:
      PIK3CA gene mutation was detected in 3.09% (16/517) NSCLC patients, including H1047R (4 patients), E545A (2 patients), E453K (2 patients), H1065Y (2 patients), E545K (1 patient), E39K (1 patient), E542K (1 patient), C420R (1 patient), K111E (1 patient) and E545K plus L781F (1 patient), and median overall survival (OS) for these patients was 23.0 months. Among them, 12 patients with co-occurring mutations had a median OS of 28.0 months, and median OS of the 4 patients without complex mutations was 21.0 months. No statistically significant difference was found between the two groups (P=0.06). Briefly, patients with (n=5) or without (n=11) co-occurring EGFR mutations had a median OS of 28.5 months and 21.0 months repectively (P=0.45); patients with (n=4) or without (n=12) co-occurring TP53 mutations had a median OS of 30.6 months and 21.0 months repectively (P=0.51).

      Conclusion:
      There is no significant difference of molecular features in PIK3CA gene mutations in NSCLC. Patients with complex mutations benefited more from therapy than those with single mutations.

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      P1.02-059 - Molecular Characteristics of SMARCA4 Mutations Detection in Chinese Non-Small Cell Lung Cancer Patients (ID 8309)

      09:30 - 16:00  |  Author(s): X. Chen

      • Abstract
      • Slides

      Background:
      The SMARCA4 gene encodes an ATP-dependent helicase BRG1 and it belongs to SWI/SNF (switching defective/sucrose nonfermenting) complex. According to previous researches, SMARCA4 is one of the most broadly mutated subunits, developing an understanding of the mechanisms by which mutation of SMARCA4 drives cancer. The aim of this study is to investigate mutations and prognosis of NSCLC harboring SMARCA4 mutations.

      Method:
      A total of 1190 patients with non-small-cell lung cancer were recruited between July 2012 and December 2014. The status of SMARCA4 mutation and other genes were detected by next generation sequencing.

      Result:
      SMARCA4 gene mutation was detected in 0.84% (10/1190) NSCLC patients, including R370P (1 patient), N519Kfs*15 (1 patient), Q464K (1 patient), Q1440* (2 patients), E959* (1 patient), I1400M (1 patient), E882K (1 patient), D656H (1 patient) and A379T plus A39T (1 patient), and median overall survival (OS) for these patients was 17.9 months. Among them, all patients were RB1 gene with co-occurring mutations. Briefly, patients with (n=5) or without (n=5) co-occurring EGFR mutations had a median OS of 22.1 months and 14.7 months repectively (P=0.79); patients with (n=6) or without (n=4) co-occurring TP53 mutations had a median OS of 26.2 months and 16.3 months repectively (P=0.43); patients with (n=2) or without (n=8) co-occurring HER2 mutations had a median OS of 28.9 months and 14.7 months repectively (P=0.28);patients with (n=2)or without (n=9) co-occurring STK11 mutations had a median OS of 14.2 months and 26.2 months repectively (P=0.04);patients with (n=2) or without (n=8) co-occurring DNMT3A mutations had a median OS of 16.3 months and 26.2 months repectively (P=0.34); patients with (n=2) or without (n=8) co-occurring TERT mutations had a median OS of 22.1 months and 14.7 months repectively (P=0.88).

      Conclusion:
      mTOR pathway may play a poor prognosis in SMARCA4 gene mutation non-small cell lung cancer. HDAC inhibitor treatment may displayed moderated efficacy in patients with SMARCA4 gene mutations. Further research on SMARCA4 gene mutation is required. Maybe a panel of biomarkers will be necessary in the future.

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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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      P2.02-007 - Molecular Spectrum of STK11 Gene Mutations in Patients with Non-Small-Cell Lung Cancer in Chinese Patients (ID 8289)

      09:30 - 16:00  |  Author(s): X. Chen

      • Abstract
      • Slides

      Background:
      STK11 is commonly mutated in non-small cell lung cancer (NSCLC). In light of recent experimental data showing that specific STK11 mutantion can acquire oncogenic activities due to the synthesis of a short STK11 isoform, The aim of this study is to investigate whether this new classification of STK11 mutants can help refine its role as a prognostic marker.

      Method:
      A total of 879 patients with NSCLC were recruited between July 2012 and December 2014. The status of STK11 mutation and other genes were detected by the next generation sequencing (NGS).

      Result:
      STK11 gene mutation rate was 0.91% (8/879) in NSCLC, including p.K269fs*18 (1 patient), p.K329stop (1 patient), c.464 plus 1G>T (1 patient), p.D194E (1 patient), p.D176V (1 patient), p.D53Tfs*11 (1 patient), p.D194A (1 patient) and p.Y118* (1 patient), and median overall survival (OS) for these patients was 22.2 months. Among them, all patients were STK11 gene with co-occurring mutations. Briefly, patients with (n=2) or without (n=6) co-occurring EGFR mutations had a median OS of 29.0 months and 22.2 months repectively (P=0.73); patients with (n=5) or without (n=3) co-occurring TP53 mutations had a median OS of 29.0 months and 22.2 months repectively (P=0.95); patients with (n=3) or without (n=5) co-occurring KRAS mutations had a median OS of not reached so far and 13.8 months repectively (P=0.02); patients with (n=2) or without (n=6) co-occurring SMARCA4 mutations had a median OS of 14.0 months and 37.0 months repectively (P=0.11); patients with (n=3) or without (n=5) co-occurring KEAP1 mutations had a median OS of not reached so far and 14.6 months repectively (P=0.20).

      Conclusion:
      STK11 mutations represent a distinct subset of NSCLC. NGS showed that STK11 mutations commonly co-existed with other driver genes. Our results show that STK11 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through STK11 inhibition might offer new opportunities.

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    P3.01 - Advanced NSCLC (ID 621)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.01-008 - Association between Icotinib Efficacy and Circulating Tumor Cell Levels in Advanced Non-Small Cell Lung Cancer (ID 8253)

      09:30 - 16:00  |  Author(s): X. Chen

      • Abstract
      • Slides

      Background:
      Advanced non-small cell lung cancer(NSCLC) studies indicated a potential association between chemotherapy efficacy and circulating tumor cells (CTC) counts in peripheral blood. The icotinib efficacy and circulating tumor cells (CTC) counts in non-small cell lung cancer remain unknown. The aim is to investigate association between the icotinib efficacy and CTC counts in advanced NSCLC patients.

      Method:
      A total of 74 advanced NSCLC patients consented to provide 5ml of peripheral blood before systematic therapy, and divided into two groups (those with high CTC counts and those with low CTC counts) based on the patients′ median CTC counts. All the patients were treated with icotinib, and the icotinib efficacy and prognoses were compared.

      Result:
      The treatment efficacies were 46.88% (15/32) and 23.81% (10/42) for the low CTC group and the high CTC group, respectively. The median overall survival was 22.0 months (95%CI: 19.6-28.7 months) for the low CTC group and 18.3 months (95% CI: 15.3-25.4 months) for the high CTC group. The median progression-free survival was 11.6 months (95% CI: 8.7-15.6 months) and 7.2 months (95% CI: 3.4-8.7 months) for the low group and the high CTC group, respectively.

      Conclusion:
      The CTC counts can be used as a important biomarker for therapy monitoring the icotinib effect on patients with advanced NSCLC. Efficacy and prognosis of icotinib and CTC counts were considered important, and the CTC counts could be used to predict the efficacy of icotinib and prognosis of advanced NSCLC. The change in CTC count levels can be used as a biomarker for evaluating the prognosis of patients with advanced NSCLC.

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