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Y. Dong



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    P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.11-007 - Relevance Between CEA Level and EGFR Mutation, Efficacy Of EGFR-TKI In Patients With Lung Adenocarcinoma (ID 910)

      09:30 - 09:30  |  Author(s): Y. Dong

      • Abstract

      Background
      EGFR-TKI has been widely used in the treatment of advanced NSCLC with positive EGFR mutation. However, tumor tissues may not always be available in patients with inoperable NSCLC. Although peripheral blood can be used to test the mutations, but the sensitivity are not satisfactory.Studies have found that the CEA level are higher in patients with positive EGFR mutation. And it also have been reported that the variation of CEA level before and after EGFR-TKI therapy was closely related with therapy efficacy. So if we use high CEA level to predict the EGFR mutation, could we get a higher sensitivity than use peripheral blood to test the mutation? Are the variation types of CEA related with the efficacy of EGFR-TKI? To solve these questions, we designed this study and hope to find a marker to predict EGFR mutation and efficacy of EGFR-TKI.

      Methods
      70 cases of newly diagnosed non-smoking adenocarcinoma of NSCLC were included in the study. We detected their EGFR mutation status, record their clinical characteristics and test CEA level. The patients with positive EGFR mutation receive EGFR-TKI treatment. The EGFR mutation status of these patients’ blood was analyzed by HRM and ARMS. Then we tested their CEA level on the third, seventh, fifteenth and thirtieth day after EGFR-TKI treatment respectively. We evaluated the efficacy on the first month and confirm it on the second month.

      Results
      44/70 cases were found with EGFR gene mutations.Including 25 cases of exon19,18 cases of L858R mutation and 1 case of exon20 mutation. EGFR mutation rate of serum CEA high-level group was significantly higher than low-level group (EGFR gene mutation rate of patients with serum CEA level <5ng/ml vs. ≥ 5ng/ml was 40.9% vs. 70.8%, p=0.017). Multivariate analysis showed that CEA high-level is independently associated with EGFR gene mutation rate. (p=0.020,OR=3.508, 95%CI：1.223-10.059).The sensitivity, positive predictive value and accuracy of high CEA level to predict EGFR mutation is 79.1%,70.8% and 67.1%.The sensitivity of HRM and ARMS is 13.9% and 51.2% respectively. 43 patients received EGFR-TKI treatment, 2 patients quit the study due to severe adverse reaction. We evaluate the efficacy and follow up their PFS.The total ORR is 41.9%, DCR is 74.4%.We divided the patients through the variation types of CEA into three groups: descending type, first increased then decreased type and ascending type. Analysis the relevance between clinical characteristics and efficacy of EGFR-TKI shows that the variation types of CEA is the only influencing factor (P=0.001). Univariate analysis of NSCLC patients who received EGFR-TKI first-line treatment shows that patients with descending type have longer PFS (P=0.001, HR 6.981, 95%CI: 2.534-19.237). Multivariate Cox proportional hazards model analyses of various factors affecting PFS shows the same result (P=0.001, HR 9.82, 95%CI: 3.322-26.031).

      Conclusion
      Patients with high CEA levels have a higher rate of EGFR mutations in NSCLC. Using high CEA level for predicting EGFR mutation is more sensitive than using peripheral blood to test EGFR mutation; the variation types of CEA could help us to predict the efficacy of EGFR-TKI for a short time (one month).

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    P2.12 - Poster Session 2 - NSCLC Early Stage (ID 205)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.12-002 - Clinical characteristics and prognosis of lung adenocarcinoma driver mutations from Chinese population (ID 1292)

      09:30 - 09:30  |  Author(s): Y. Dong

      • Abstract

      Background
      Driver gene mutation in lung adenocarcinoma varies greatly among different populations, and lacks of large sample study on Chinese population. The purpose of this study was to identify driver gene mutations or translocations, and to evaluate their association with clinicopathological features and prognosis in Chinese lung adenocarcinoma.

      Methods
      Gene mutations or translocations were detected by fluorescence quantitative PCR in tumor tissues of 762 lung adenocarcinoma patients, including mutations of EGFR, KRAS and BRAF, and translocations of ALK and RET. The correlation of gene mutations/translocations with clinicopathological features was retrospectively analyzed by Chi-square test and logistic regression. Kaplan-Meier survival curves were used to evaluate the correlation of these genes with disease-free survival(DFS) in 314 patients and overall survival(OS) in 564 patients respectively.

      Results
      In the 762 patients with lung adenocarcinoma, the positive rate of gene mutations/translocations involving EGFR, KRAS, ALK, RET and BRAF was 49.6%, 10.0%, 4.5%, 1.7%, 0.5%, respectively, among which there was no mutations of polygenes. This study showed that EGFR mutations were more common in non-smokers or light smokers, lepidic predominant invasive adenocarcinoma subtype, and patients without distant metastasis. KRAS mutations were more common in heavy smokers, mucinous invasive adenocarcinoma subtype, and early stage patients. ALK translocations were more common in patients younger than 55 years old, with solid predominant invasive adenocarcinoma subtypes. RET translocations were more common in patients younger than 52 years old, with solid predominant invasive adenocarcinoma subtypes and patients who have family history of lung cancer. BRAF mutations were more common in mucinous invasive adenocarcinoma subtype. The survival analysis showed that the median OS of EGFR-mutant group was shorter than wild-type group among stage IIIB-IV paitents without targeting therapy(P=0.019); Although KRAS gene mutations in patients with early stage was not related to disease recurrence and survival either, KRAS mutations in stage IIIA patients do contribute to shorter DFS and OS(P=0.018, 0.039); ALK translocations in each stage subgroup were not related to recurrence and survival; Patients with mutations of either EGFR, KRAS, or translocations of ALK as a group showed no significant difference in DFS and OS as compared to those without involvement of any of these genes.

      Conclusion
      The overall driver gene positive rate in this series detected by Q-PCR is 66.3%. Each type of drive gene corresponds to different clinical and pathological features. Patients with ALK or RET gene translocations are more younger, and more likely to be solid predominant invasive adenocarcinoma. EGFR-mutant group has shorter OS than wild-type group among stage IIIB-IV paitents without targeting therapy. KRAS mutations implicate poor prognosis only in patients with stage IIIA.