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Y. Xu



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    O02 - NSCLC - Combined Modality Therapy I (ID 111)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Combined Modality
    • Presentations: 1
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      O02.07 - Is there a survival benefit in patients with stage IIIA(N2) non-small cell lung cancer under neoadjuvant chemotherapy and/or radiotherapy followed by surgery administration: a systematic review and meta-analysis (ID 2164)

      10:30 - 12:00  |  Author(s): Y. Xu

      • Abstract
      • Presentation
      • Slides

      Background
      Optimal management of clinical stage IIIA (N2) non-small cell lung cancer (NSCLC) is controversial despite the conduct of several randomized controlled trials (RCTs). This article contributes to this problem by conducting a systematic review and meta-analysis of published RCTs.

      Methods
      A comprehensive literature search was performed in the Pubmed, Embase, Medline database (last search updated in May 2013) for relevant studies comparing patients with stage IIIA (N2)NSCLC undergoing surgery alone, chemotherapy and/or radiotherapy alone, or resection after neoadjuvant treatment with chemotherapy and/or radiotherapy. A systematic review and meta-analysis of available data were conducted using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards.

      Results
      The comparison contained two components. In the comparison of neoadjuvant therapy followed by surgery and radical chemoradiotherapy/radiotherapy, a fine homogeneity (χ[2]=2.26, p=0.52, I[2]=0.0%) between four studies with a total of 803 selected cases was detected between the overall survival (OS), and the combined hazard ratio (HR) was 0.95 (95% confidence interval [CI]: 0.81-1.10; p=0.47). Progression-free survival (PFS) was investigated in two studies and there was also no significant difference for the combined HR was 0.90 (95% CI: 0.77-1.05; p=0.19). In the comparison of neoadjuvant chemoradiotherapy (Neo-ChRT) and neoadjuvant chemotherapy(Neo-ChT) alone, three studies with a total of 229 selected cases were detected, with the combined HR of OS and PFS 0.79 (95% CI: 0.57–1.09; p=0.15) and 0.67 (95% CI: 0.39-1.15; p=0.15) respectively, but it did not reach the statistical significance. Observing the short-term therapeutic effect, these studies revealed that Neo-ChRT had increased the rate of mediastinal pCR by 15.48% (OR: 3.61, 95%CI: 1.07–12.15; P = 0.04). Comparing the incidence of main complications and mortality, there was no significant difference between neoadjuvant therapy followed by surgery and radical chemoradiotherapy /radiotherapy alone. Neoadjuvant chemoradiotherapy followed by surgery achievered higher response rates and similar postoperative mortality as compared to neoadjuvant chemotherapy followed by operation, without adding significant adverse events.Figure 1

      Conclusion
      Neoadjuvant chemotherapy and/or radiotherapy followed by surgery is not superior to that followed by definitive radiotherapy. Neoadjuvant chemoradiotherapy dose not improve survival compared to neoadjuvant chemotherapy alone. But it can increase the rate of downstaging and mediastinal pCR which were correlated with the better PFS and OS. Neoadjuvant treatment has not increased the incidence of postoperative complication and motality. Further studies should be conducted to determine the patients who will benefit from various administrations.

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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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      P1.08-023 - How to Minimize the Uncertainties of Internal Target Volume in 4DCT Scans for Stereotactic Body Radiation Therapy of Early Stage Non-small Cell Lung Cancer (ID 2832)

      09:30 - 16:30  |  Author(s): Y. Xu

      • Abstract

      Background
      Precise definition of the target volume is one of crucial factors in the management of early stage non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT). Recent studies have shown that individualized planning margins are required to account for the variability and unpredictability of lung tumor motion. The spatial and temporal information on tumor motion can be derived with respiration-correlated 4DCT scans. In this study, we investigated how these uncertainties may be individually minimized for SBRT of NSCLC.

      Methods
      Twelve patients with early stage NSCLC who were undergoing SBRT were imaged with free-breathing 3-dimensional computed tomography (3DCT) and 10-phase 4-dimensional CT (4DCT) for delineating gross tumor volume (GTV)3D and ITV10Phase (ITV2). The maximum intensity projection (MIP) CT was also calculated from 10-phase 4DCT for contouring ITVMIP (ITV1). Then, ITVCOMB (ITV3), and ITV10Phase+GTV3D (ITV4), were generated by combining ITVMIP, ITV0% phase and ITV50% phase, ITV10phase and GTV3D, respectively. All 5 volumes (GTV3D and ITV1 to ITV4) were delineated in the same lung window by the same radiation oncologist.

      Results
      The mean (range) tumor motion (RSI, RAP, RML, and R3D ) were 6 mm (2-11 mm), 3 mm (1-4 mm), 4 mm (0-6 mm), and 7 mm (3-12 mm), respectively. The trend of volume variation was GTV3D < ITV1 < ITV2 < ITV3 ≈ ITV4 . The means ± SDs of these volumes were 10 ± 7 cc, 10 ±8 cc, 12 ± 7 cc, 11 ± 8 cc, and 12 ± 8 cc, respectively. All comparisons between the target volumes showed statistical significance ( P<0.05), except for ITV3 and ITV4 (P= 0.732). The volume of the combining ITVMIP, ITV0% phase and ITV50% phase was closed to ITV10phase plus GTV3D.

      Conclusion
      Uncertainties in individualized ITVs for SBRT of early stage NSCLC could effectively be minimized by combining information from free-breathing 3DCT and 10-phase 4DCT. If these images cannot be efficiently contoured, a combination of ITVMIP, ITV0% phase and ITV50% phase could be an effective alternative.

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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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      P2.06-039 - The Status of Epidermal Growth Factor Rceptor (EGFR) Mutation, Protein Overexpression and Gene Amplification in Esophageal Squamous Cell Carcinomas (ID 2848)

      09:30 - 16:30  |  Author(s): Y. Xu

      • Abstract

      Background
      Epidermal growth factor receptor (EGFR) is widely distributed in human epithelial cell membrane, including esophageal squamous cell carcinoma (ESCC). The purpose of this study was to evaluate the relationship between malignant biological behavior and EGFR status in ESCC.

      Methods
      We investigated tumor specimens from 56 patients with surgically resected ESCC from 2004 through 2008. Immunohistochemistry (IHC) was performed to analyze the expression of EGFR. Fluorescence in situ hybridization (FISH) was performed to assess the EGFR gene amplification. EGFR mutations in exons 19-21 were detected by pyrosequencing technology. A chi-square test or Fisher exact test for independence was used to examine the correlation among the status of EGFR protein, gene and the several clinicopathological factors. Overall survival and disease-free survival were constructed using the Kaplan-Meier method, and the log-rank test was used to evaluate the statistical significance of differences. Multivariate analysis was performed using the Cox proportional hazard method.

      Results
      EGFR was overexpressed in 30 of 56 ESCC (53.6%) and was correlated with tumor differentiation (p=0.047) (Figure 1.). EGFR gene amplification was found in 13(23.2%) cases and was correlated with the presence of lymph node metastasis (p=0.001) and higher pathological tumor-node-metastasis (pTNM) stage (p=0.042). There was no EGFR mutation in the clinical samples of 56 patients with ESCC. In univariate analysis, there was no correlation between the prognosis and EGFR protein expression, but EGFR gene amplification was a significant predictor of better prognosis (p=0.031). The multivariate analysis revealed that EGFR gene amplification was significantly correlated with better disease-free survival (p=0.037) and overall survival (OS) (p=0.026). However, patients with EGFR gene amplification did more likely receive aggressive treatment in clinical practice.Figure 1

      Conclusion
      EGFR protein overexpression and gene amplification in ESCC were correlated with the malignant biological behavior, including tumor differentiation and lymph node metastasis. Further studies should be conducted to analyze the prognostic value of EGFR protein overexpression and gene amplification in patients with ESCC.

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    P2.09 - Poster Session 2 - Combined Modality (ID 213)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P2.09-014 - Concomitant Chemoradiotherapy Using Docetaxel and Cisplatin for Unresectable Stage III Lung Squamous Cell Carcinoma (ID 2846)

      09:30 - 16:30  |  Author(s): Y. Xu

      • Abstract

      Background
      Concomitant chemoradiotherapy is the standard treatment of unresectable stage III non-small cell lung cancer (NSCLC). However, the optimal chemotherapy regimen is still controversial, particularly in lung squamous cell carcinoma. We have conducted a phase II clinical trial in a Chinese population to evaluate concomitant treatment using docetaxel/cisplatin chemotherapy and thoracic radiotherapy followed by docetaxel/cisplatin consolidation chemotherapy in unresectable stage III lung squamous cell carcinoma. The purpose of this study is to evaluate the feasibility and activity, and also assess its impact on progression-free survival (PFS).

      Methods
      A total of 32 patients were enrolled between January 2011 and January 2013. Patients received concomitant docetaxel 30mg/m[2] on day 1 and day 8, cisplatin 25mg/m[2] on day 1 to day 3 repeated every 3 weeks for 2 cycles and thoracic radiotherapy, followed by docetaxel/cisplatin for 2 cycles as consolidation therapy (docetaxel 60mg/m[2] on day 1, cisplatin 25mg/m[2] on day 1 to day 3 repeated every 3 weeks). Objective response rate according to the RECIST criteria was recorded and toxicity was evaluated using the NCI Common Toxicity Criteria. The Kaplan–Meier method was used to evaluate patient survival. Univariate analysis of patient characteristics and tumor responses was conducted using the Chi-square and Fisher’s exact test.

      Results
      Eight (25.0%) and 20 patients (62.5%) had a complete or partial response, respectively, while 3 patient’s disease remained stable and 1 patient had progression of the disease. The overall response rate (87.2%, 95% confidence interval (CI): 63–97%) exceeded the goal per study design. The median PFS was 11.0 months (95% CI: 5.6–16.4 months). This approach obtained likely better effects than history control group. Main toxicity (grade 3 or greater, %): neutropenia 10 (31.3%); thrombocytopenia 7 (21.9%); anaemia 8 (25.0%); nausea/vomiting 5 (15.6%); anorexia 7 (21.9%), dysphagia 4 (12.5%), radiation pneumonitis 3 (9.4%) and fatigue 4 (12.5%).

      Conclusion
      This data suggests that concomitant treatment with docetaxel/cisplatin and thoracic radiotherapy was well tolerated, with promising activity in a Chinese population with unresectable stage III lung squamous cell carcinoma. Although the data presented herewith appears promising, this study is relatively small, and more data from randomized trials are needed to further validate this regimen.

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    P3.18 - Poster Session 3 - Pathology (ID 177)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P3.18-001 - Prognostic value of the IASLC/ATS/ERS classification in stage I lung adenocarcinoma patients (ID 348)

      09:30 - 16:30  |  Author(s): Y. Xu

      • Abstract

      Background
      A new lung adenocarcinoma classification proposed by the International Association for the Study of Lung Cancer, American Thoracic Society and European Respiratory Society (IASLC/ATS/ERS) has recently been published in 2011.We investigated the relationship between predominant subtype, according to the (IASLC/ATS/ERS) lung adenocarcinoma classification and prognosis in stage I lung adenocarcinoma in our hospital.

      Methods
      Two hundred and sixty-one patients with stage I lung adenocarcinoma operated in Zhejiang Cancer Hospital were identified between 2000 and 2010. Survival curves were plotted using the Kaplan–Meier method. The Cox proportional hazard model was used for multivariate analysis.

      Results
      The median age of the 261 patients was 59.8 years in current cohort. Of the 261 patients, 175 patients (67.1%) were never smokers, 86 patients (32.9%) were former or current smokers. The surgical procedure employed 245 lobec­tomy, 12 bilobectomy and 4 pneumonectomy. The pathologic stage was IA in 92 patients (35.2%), IB in 169 patients (64.8%).No cases were adenocarcinoma in situ and six were minimally invasive adenocarcinoma. Two hundred and fifty-five cases were invasive adenocarcinoma, in which 80 were papillary predominant, 76 were acinar predominant, 42 were micropapillary predominant, 34 were solid predominant, 19 were lepidic predominant subtypes, and 4 were variants of invasive adenocarcinoma. The 5-year DFS and OS rates for the all patients were 66.0%, 78.2%, respectively. Micropapillary predominant subtype (p=0.037), solid predominant subtype (p=0.035) were predictive of DFS. Patients with micropapillary and solid predominant tumors had significantly worse disease-free survival compared with other subtypes predominant tumors ( p＜0.001).Multivariate analysis revealed that the new classification was an independent predictor of disease-free survival and overall survival (p=0.002 and 0.015).

      Conclusion
      The predominant subtype in the primary tumor was associated with prognosis in resected stage stage I lung adenocarcinoma.

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    P3.24 - Poster Session 3 - Supportive Care (ID 160)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P3.24-017 - The Impact of Local Radiotherapy to the Primary Site for Patients with stage IV Non-Small Cell Lung Cancer (ID 1192)

      09:30 - 16:30  |  Author(s): Y. Xu

      • Abstract

      Background
      The prognosis of patients with non-small cell lung cancer and distant metastasis is poor. The aim of this study was to evaluate the value of local treatment to the primary site for patients with stage IV non-small cell lung cancer and oligometastatic disease at diagnosis, particularly the influence of local treatment to the primary site on prognosis.

      Methods
      From January 2004 to December 2011, 69 consecutive patients with stage IV non-small cell lung cancer treated with local palliative radiotherapy to the primary site were enrolled in this retrospective study. The prognosis factors including the patients’ general condition, disease characteristics and treatment factors were analysed. Patients were divided into two groups based on the number of distant metastases (Oligometastasis, OMT, 1-4 metastases; Polymetastasis, PMT, > 5 metastases). The relationship between the prognosis and treatment factors was explored. Overall survival was estimated using the Kaplan-Meier method, and prognostic factors were identified by univariate and multivariate analyses.

      Results
      The median overall survival was 14.1 (95%CI:7.3-20.8) months and the 1, 3-year overall survival rates were 53.0% and 9.0% , respectively. Gender, smoking index and performance status of Zubrod-ECOG-WHO were significantly associated with prognosis under univariate analysis. There was marginally significant associated with prognosis for those patients who received chemotherapy(P = 0.054) and received a sufficient dose of local palliative radiation to the primary site (at least 60Gy) (P = 0.063). On multiplicity analysis, chemotherapy and performance status retained significance. In the hierarchical analysis, patients who received at least 60 Gy of local radiotherapy to the primary site(P=0.048)(Fig 1.) and received chemotherapy (P= 0.041) achieved better overall survival in the OMT group.Figure 1

      Conclusion
      For non-small cell lung cancer with OMT, local aggressive treatment to the primary site may improve overall survival. Our results suggest that the selected non-small cell lung cancer patients with distant metastasis may benefit from aggressive local therapy.