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X. Yang



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    O13 - Limited Resections (ID 101)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Surgery
    • Presentations: 1
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      O13.07 - Preoperative Predictive Factors of Nodal Metastasis in Patients with cT1 Lung Cancer (ID 3493)

      10:30 - 12:00  |  Author(s): X. Yang

      • Abstract
      • Presentation
      • Slides

      Background
      Lung cancer with small nodules(≤3cm) have less tendency of local regional lymph node metastasis. We investigate the value of preoperative clinicopathological characteristics in predict regional lymph node metastasis of cT1 lung cancer patients.

      Methods
      A retrospective review of database identified 384 patients with cT1N0M0 lung cancer, diagnosed by CT/PET-CT/MRI and pathologically confirmed as primary lung cancer. All the patients underwent surgery (include sublobar resection, lobectomy and pnemonectomy) and systemic mediastinal lymphadenctomy, and receive no preoperative chemotherapy or radiotherapy. The correlation between clinicopathological factors and the nodal status was analyzed by logistic regression model.

      Results
      The prevalence of lymph node metastasis is 69/384 (18.0%) . Univariate analysis identified tumour size, elevated CEA level and Standar uptake value(SUV)≥2.5 affect nodal status. Shown in Table1. In multivariate analysis, only tumour size (≤1cm vs >1-≤2cm vs >2-≤3cm，P=0.000) was found to be independent predictors of nodal metastasis. Shown in Table 2.Figure 1Figure 2

      Conclusion
      Tumour size is the only predictive factor of nodal metastasis for patients with cT1 lung cancer. Futher invastigation is recommend in omission of mediastinal lymphadenctomy in cT1 patients with tumour size of <2cm and SUVmax<2.5.

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    O20 - Staging and Advanced Disease (ID 102)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Surgery
    • Presentations: 1
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      O20.03 - Lobe-specific lymphadenectomy protocol for non-small cell lung cancer presenting as a solitary pulmonary nodule (ID 1763)

      16:15 - 17:45  |  Author(s): X. Yang

      • Abstract
      • Presentation
      • Slides

      Background
      We sought to establish an acceptable lobe-specific mediastinal lymphadenectomy protocol for non-small cell lung cancer (NSCLC) presenting as solitary pulmonary nodules (SPN) .

      Methods
      We retrospectively analyzed 415 patients pathologically diagnosed as NSCLC undergone lobectomy, bilobectomy or pneumonectomy with systematic lymphadenectomy from March 2004 to June 2011 in our hospital. All of the patients enrolled were considered SPN preoperatively. Information about primary tumor location, lymph node metastasis, and other baseline data were collected. Stepwise logistic regressions using N1 and lobe-specific regional mediastinal lymph nodes’ conditions as covariates were used to figure out the key lymph node station that indicated non-regional mediastinal lymph nodes metastases (NRM).

      Results
      As for the location of the primary tumor, 121 cases were in right upper lung (RUL), 42 in right middle lung (RML), 77 in right lower lung (RLL), 107 in left upper lung (LUL), and 68 in left lower lung (LLL). Stepwise regression showed that #2(OR (odds ratio) = 28.250, 95%CI (confidence interval): 1.756-454.422, P=0.018), N1 (OR=24.000, 95%CI: 3.346-172.121, P=0.002) and N1 (OR=21.667, 95%CI: 3.266-143.736, P=0.001) was the key lymph node station for RUL, LUL and RLL, respectively. None of the covariates show statistical significant for LLL.Patients with tumors >2 cm rarely had NRM without primary regional mediastinal involvement. Figure 1 Figure. Malignant cells’ residue when the key station shows negative metastasis

      Conclusion
      With rigid consideration, lobe-specific lymphadenectomy is feasible in practice. This protocol could be established when the lobe-specific key nodes show negative under intraoperative frozen section, especially for those NSCLCs presented as SPN smaller than 2 cm preoperatively. Table. Protocols for lobe-specific mediastinal lymphadenectomy for SPN

      Tumor locations
      RUL LUL RLL LLL RML
      Superior mediastinum^4 ◎ ◎ ○[b] ◎ ◎
      Inferior mediastinum ○[a] ○[b] ◎ ◎ ◎
      Note: ◎: Complete regional lymphadenectomy is warranted; ○: Lymph nodes dissection could be omitted considerably. [a]: when #2 shows negative in intraoperative frozen section; [b]: when #10, 11 shows negative in intraoperative frozen section; ^4: #1-4 in RUL, #4-7 in LUL

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    P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.11-044 - Progression-free survival is a poor surrogate endpoint for overall survival in the first line EGFR-TKI treatment in advanced non-small-cell lung cancer with EGFR mutation (ID 2969)

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

      • Abstract

      Background
      （Although epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs), gefitinib and erlotinib have shown antitumor activity in patients with non-small cell lung cancer (NSCLC) , it is unclear if progrssion-free survival（PFS）could be a good surrogate endpoint for overall survival(OS) in the clinical trials of first-line EGFR-TKIs treatment in patients with advanced NSCLC, especially with activating EGFR mutation.）

      Methods
      A PubMed search identified 12 randomized trials comparing first-line EGFR-TKIs treatment with chemotherapy in patients with advanced NSCLC. A total of 1816 patients were enrolled and EGFR mutation status was known in 554 patients. Linear regression analysis was carried out to estimate the correlation of PFS, response rate (RR), and survival post-progression (SPP) with OS

      Results
      PFS, RR and PPS were all strongly associated with OS（r=0.942, 0.982 and 0.895, respectively, P< 0.01） for all trials. But in trials enolled patients with EGFR mutation, PFS and RR were poor correlate with OS (r =-0.121 and 0.131, respectively, P< 0.01), while PPS strongly associated with OS (r =0.849, P<0.01 ）PFS, RR and PPS were all strongly associated with OS（r=0.942, 0.982 and 0.895, respectively, P< 0.01） for all trials. But in trials enolled patients with EGFR mutation, PFS and RR were poor correlate with OS (r =-0.121 and 0.131, respectively, P< 0.01), while PPS strongly associated with OS (r =0.849, P<0.01 ）

      Conclusion
      Our findings indicate that PFS is a poor surrogate endpoint for OS in the first line EGFR-TKI treatment in advanced EGFR mutation NSCLC. Further studies are needed to search for appropriate surrogate endpoint for OS.

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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-043 - CYP1A1*2A Polymorphism is correlate with EGFR Exon 19 Mutation and is an Independent Prognostic indicator for the Advanced Lung Cancer Patients Treated with EGFR-TKI (ID 3053)

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

      • Abstract

      Background
      The EGFR mutated status becomes a very important factor for NSCLC patients considering of the treatment, but the mechanism of the mutation is still unknown.Our study aimed to detect the correlations among EGFR mutations and polymorphisms of EGFR and CYP1A1 genes and their associations with clinical outcome of NSCLC patients treated with EGFR-TKI.

      Methods
      We evaluated the EGFR mutations, the genotypes for EGFR Intron1 (CA) n, R497K and CYP1A1 *2A, *2C polymorphisms in 70 Chinese patients with NSCLC. Genetic polymorphisms were correlated to EGFR mutations. As to subgroup of 36 patients who accepted the EGFR-TKI treatment and had systemic 5 years follow up data, the associations among the somatic EGFR mutations, the genomic polymorphisms of EGFR and CYP1A1 and clinical outcome of the EGFR-TKI were analyzed.

      Results
      The data show that EGFR Intron1 (CA) n and CYP1A1*2A, *2C polymorphisms were correlated with EGFR mutations (P=0.006, P=0.001, and P=0.008, respectively) and all the three polymorphisms were also associated with EGFR 19 exon delection (P=0.007, P=0.033, and P=0.006, respectively); whereas the multivariate analysis demonstrated that only CYP1A1*2A polymorphism was associated with EGFR somatic mutations (P=0.021). For 36 patients treated with EGFR-TKI, the EGFR mutation and CYP1A1*2A polymorphism showed correlation with clinical response of EGFR-TKI(P=0.001, and P=0.011, respectively); However, the multivariate analysis confirmed that the EGFR mutation is still the most effective predictive factor (P=0.006) ; Either the log-rank test and Cox regression analysis demonstrated that the CYP1A1*2A polymorphism is independent prognostic factor for patients’ overall survival treated with EGFR-TKI( P=0.000 for both statistical analysis).

      Conclusion
      The results demonstrate that the CYP1A1*2A polymorphism is correlated with EGFR somatic mutation; for advanced NSCLC patients with EGFR-TKI therapy, the EGFR mutation status is still most effective predictor for clinical response of EGFR-TKI, whereas the CYP1A1*2A polymorphism is an independent prognostic factor. The inner mechanisms deserve thorough study.

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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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      P2.12-016 - Predict foctors of lymphatics metastasis or early distant and regional failure after complete resection in cT1 lung adenocarcinoma (ID 2116)

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

      • Abstract

      Background
      cT1 lung cancer presented as solitary pulmonary nodule(SPN) tends to be stage I disease. Nevertheless, early recurrences were observed in these patients. The purpose of this study is to identify clinicopathological factors associated with early failure in cT1 adenocarcinoma after complete resection.

      Methods
      Between Jan.2006 and Jun.2012, 419 cases of lung adenocarcinoma presented as SPN underwent completely resection in our hospital. Of which, we identify 216 cases that follow-up for more than 1-year and assigned to three group according to pN status and recurrence. Group A, 49 cases with pathological diagnosis of lymphatic metastasis; Group B, 23 pN0 cases with early recurrence; Group C, 144 pN0 cases have no recurrence or metastasis; Group D, combine Group A and B. All the pN0 patients in this study have not received adjuvant therapy. Chi-square test is used to analyze each factors’ difference. Multivariate logistic regression analysis was used to identify independent factors.

      Results
      Incidents of preoperative elevated CEA, Poorly differentiated of cancer cells, vascular invasion in Group A, B and D were significantly higher than those of Group C. Besides, tumor size >2cm were frequently observed in Group A(p＜0.001). And more males in group D than in group C. See Table-1. Tumor size, cancer cell differentiation and vascular invasion identified as independent factors by multivariate logistic analysis. . Figure 1

      Conclusion
      cT1pN0 Stage I lung adeocarinoma patients with male, preoperative elevated CEA, poorly differentiated cancer cells, vascular invasion were associated with early failure. Adjuvant therapy in patients with these factors need further study.

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    P2.19 - Poster Session 2 - Imaging (ID 180)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      P2.19-009 - A Prediction Model to Estimate the Probability of Malignancy of Solitary Pulmonary Nodules Intergrating PET-CT and Clinical Data. (ID 1278)

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

      • Abstract

      Background
      Most solitary pulmonary nodules(SPN) discovered by CT scan are benign. 18F-FDG PET has been reported better differentiated benign from malignant pulmonary nodules. Three previous developed clinical prediction models (Mayo model,VA model and Peking University model) are based on CT scan. We intergrating PET-CT and Clinical Data to increase accuracy in estimate the probability of malignancy of SPN.

      Methods
      From January 2009 to December 2012, 365 consecutive patients diagnosed SPN by PET-CT have been identified and reviewed. Clinical data were collected retrospectively. The data set was split into two groups: training set (305 patients) and testing set (60 patients). Independent factors associated with benign and malignancies were identified using training set by logistic regression analysis, and a prediction model has been established. Patients from the testing set were then used to validate the predictive value of this model, and compared accuracy with Mayo model and Peking University model.

      Results
      Logistic analysis showed three clinical characteristics(gender,age, smoking data) and six radiological characteristics(diameter, upper lobe,speculation, lobulation, pleural tail, FDG uptake) were independent predictors for malignancy. The area under the evaluated receiver operating characteristics curve was 0.854±0.043. Compared to Mayo model,VA model and Peking University model, this PET-CT based model showed better predictive value. Figure 1

      Conclusion
      Our PET-CT based clinical prediction model has better accuracy in estimate the pretest probability of malignancy in patients with SPNs.

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    P3.19 - Poster Session 3 - Imaging (ID 181)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      P3.19-012 - Comparison of three models to estimate the probability of malignancy in Chinese patients with solitary pulmonary nodules (ID 1951)

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

      • Abstract

      Background
      A solitary pulmonary nodule (SPN) is radiologically defined as an intraparenchymal lung lesion that is < 3 cm in diameter and is not associated with atelectasis or adenopathy. The diagnosis of SPN is challenging. A prediction model would facilitates this task. Until now, three SPN prediction models have been developed, which are Mayo model, VA model and Peking University (PU) model. We compared the accuracy of three models in Chinese patients with SPN.

      Methods
      From July 2003 to December 2011, 154 surgical patients with an SPN measuring 3-30mm from Guangdong Lung Cancer Institute were included in this study. Data on gender, age, cancer history, smoking, nodule size, spiculation, calcification, border and final pathological diagnosis were collected retrospectively . Each patient’s final diagnosis was compared with probability calculated by MAYO model, VA model and PU model. The accuracy of each model was assessed by area under the receiver operating characteristics (ROC) curve and calibration curve.

      Results
      The area under the ROC curve (AUC) of PU model(0.800; 95% CI 0.708 to 0.891) was larger than that of MAYO model(0.753; 95% CI 0.650 to 0.857) and VA model(0.728; 95% CI 0.623 to 0.833), but this difference was not statistically significant. Calibration curves showed that all the three models overestimated malignancy.Figure 1 Figure 1 Receiver operating characteristic curves of Mayo model, VA model and PU model. AUC(Mayo)= 0.753(95% CI 0.650 to 0.857). AUC(VA)= 0.728; 95% CI 0.623 to 0.833. AUC(PU)= 0.800; 95% CI 0.708 to 0.891.

      Conclusion
      Three prediction models are sufficiently accurate in SPN malignancy prediction in Chinese patients.