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J. He



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    O01 - Prognostic and Predictive Biomarkers I (ID 94)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      O01.02 - MicroRNA Signature Predicts Survival in Resectable Small-Cell Lung Cancer (ID 1641)

      10:40 - 10:50  |  Author(s): J. He

      • Abstract
      • Slides

      Background
      Small-cell lung cancer (SCLC) is one of the most aggressive types of cancer, yet the molecular mechanisms underlying its devastating clinic outcome remain elusive. In this study, we investigated whether microRNA (miRNA) expression profiles can predict clinical outcomes of SCLC patients.

      Methods
      A total of 82 patients with very limited SCLC, who received surgical resection followed by adjuvant chemotherapy according to the standard of care, were enrolled in this study. All the tumor samples used for miRNA profiling were required to contain at least 60% tumor cells and RNA was isolated from formalin-fixed paraffin-embedded specimens. First, we surveyed 924 miRNAs for their expressions from 42 SCLC patients to discover survival relevant miRNAs and develop prognostic models, which were then validated in an independent cohort of 40 cases. A risk score of miRNA signature for survival prediction was calculated according to a combination of expression level of the miRNA weighted by the regression coefficient derived by univariate Cox regression analysis. Kaplan-Meier overall survival curves were compared using the log-rank test and multivariate Cox regression model was used to test if the miRNA signature was an independent prognostic factor.

      Results
      For all the patients, the median follow up time was 57.2 months. Forty-four patients (53.7%) are still alive. Forty-two patients (51.2%) had recurrent disease and the median time to diagnosis of relapse was 12.3 months. In the training set, we identified that two miRNAs, miR-150 and miR-886-3p, were significantly associated with poor OS. The results compared between NL and SCLC tissues also verified that the miR-150 and miR-886-3p expression levels in SCLC were much lower than in normal lung samples (884±126 vs 2954±1652 for miR-150 and 1873±256 vs 3154±448 for miR-150 ). We then derived a miRNA signature 0.545×miR-150 + 0.617 ×miR-886-3p. Compared with patients with low-risk miRNA signature, patients with high-risk signature had significantly shorter median OS (12.6 months versus not reached, P=0.02). This signature was also demonstrated to be a significant predictor of survival in the validation set. Patients with high risk miRNA signatures had poor overall survival (P=0.005) and progression-free survival (P=0.017) compared to those with low-risk scores. It retained statistical significance in a model adjusting for age, gender and smoking status (HR 0.27, 95% CI 0.10-0.72, P=0.008), which suggesting that the miRNA signature may be an independent predictor of survival.

      Conclusion
      In this study, we developed a prognostic miR-150/miR-886-3p signature and validated in an independent dataset for resectable SCLC. Our results indicated that microRNAs may serve as promising molecular prognostic markers as well as new therapeutic targets for SCLC. Larger sample size studies are needed to further validate our findings.

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    O18 - Cancer Control and Epidemiology II (ID 133)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      O18.07 - A Retrospective Cohort Mortality Study in Jingchuan of china - the Largest Nickel Population in World (ID 94)

      11:35 - 11:45  |  Author(s): J. He

      • Abstract

      Background
      Nickel is an essential trace metal used in the occupational setting and is naturally found in the general environment, resulting in both occupational and nonoccupational exposures to individuals at varying levels. Exposure to nickel has been associated with several toxicites and the International Agency for Research on Cancer has concluded that there is sufficient evidence in humans associating exposure to nickel or nickel compounds with risk of lung cancer. We evaluated overall and cause-specific mortality among Chinese workers involved in nickel production or utilization in order to examine the long-term health effects of occupational exposure to nickel compounds.

      Methods
      The study design was a retrospective cohort mortality study including 432,526 workers who were involved with nickel mining or smelt between 2001 and 2010. We calculated standardized mortality ratios (SMR) using the death rates of Gansu Province in China, and estimated by the exact probabilities of the Poisson distribution.

      Results
      Overall, the all-cause mortality was decreased in all workers compared to the general population of Gansu province (SMR= 0.53, 95%CI: 0.51-0.55). Analyses examining cause-specific mortality revealed an increase in the mortality from bronchogenic carcinoma and lung cancer (SMR = 2.05, 95% CI = 1.84-2.29), cor pulmonale (SMR =4.08, 95% CI = 3.25-5.01), and silicosis (SMR = 13.59, 95%CI =11.90-15.52) in the workers exposed to nickel.

      Conclusion
      This study confirmed a significant excess of mortality from diseases of the lung including silicosis , lung cancer, and cor pulmonale among workers involved in nickel mining or smelt in China.

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    P1.15 - Poster Session 1 - Thymoma (ID 189)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Thymoma & Other Thoracic Malignancies
    • Presentations: 1
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      P1.15-002 - Results and Prognostic Features of Recurrent Thymoma (ID 3020)

      09:30 - 09:30  |  Author(s): J. He

      • Abstract

      Background
      This study sought to analyse the results and prognosis of recurrent thymoma.

      Methods
      Between 1991 and 2012, 32 patients who developed recurrence after radical resection of thymoma were reviewed.

      Results
      The initial Masaoka staging was stage I, 3; stage II, 14; stage III, 10; stage IVa, 4;and stage IVb, 1. World Health Organization tumor type: A and AB, 5; B1, 7; B2, 6; B3, 12; and unknown, 2. Among the 32 patients, relapses were found in the following sites: pleura (20 cases), tumor bed (10),non-tumor bed in mediastinum (one), lung (seven), chest wall (six), lymph node metastasis (four) , abdominal node metastasis (one),liver (one), pleural effusion (four), and overlapped recurrence (14).The patterns of recurrence: local recurrence, 6; regional recurrence, 8; distant recurrence, 5; local and regional recurrence, 6; regional and distant recurrence, 4; local, regional and distant recurrence, 3. The median recurrence interval was 42 months (range, 5–193 months). The median follow-up time after recurrence was 49.5 months (range, 1-136months). Overall 5-year survival after recurrence was 65.5%. 7 patients with relapse in the thorax are still alive after re-resection, with a median survival time of 26 months (range, 6-95 months). The perioperative mortality was 0% and the morbidity was 14%. 4 patients with local relapse were given radiotherapy (RT) alone, with a median survival of 60 months (range, 51-107months) and one was dead of progressive disease, probably due to lower reirradiation dose (50Gy), compared to others with radical radiation dose (60Gy). In patients with regional and/or distant relapse, 6 patients received chemotherapy, and had 37.5% of overall 5-year survival. 5 patients without re-treatment had 50% of overall 1-year survival, with median survival 3 months (range,1-20months). After re-treatment, 9 patients had re-relapse, and the re-relapse free survival rate was 63% at 5 years, with a median re-relapse free survival of 53 months (range, 11-69months). 1 of 15 patients with RT had radiation pneumonitis and recovered after management. In univariate analysis, age (<55y, ≥55y; p=0.009), patterns of relapse (p=0.042), and recurrence-free interval (<20months, ≥20months; p=0.038) were prognostic factors.

      Conclusion
      Reoperation for resectable thymoma recurrences is associated with better outcome and relative safety, and it should be recommended. In patients with local recurrence of thymoma, RT may get comparable survival to re-operation. RT/CT probably is the treatment of choice when re-resection is not feasible. Younger age, local and regional recurrence, and longer relapse-free interval are associated with positive prognosis.

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    P2.15 - Poster Session 2 - Thymoma (ID 191)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Thymoma & Other Thoracic Malignancies
    • Presentations: 1
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      P2.15-002 - Patterns and Predictors of Recurrence after radical resection of Thymoma (ID 3022)

      09:30 - 09:30  |  Author(s): J. He

      • Abstract

      Background
      Even after complete resection, recurrence of thymoma is not uncommon, but the recurrent patterns remain controversial. This study sought to define the patterns and predictors of relapse after complete resection of thymoma.

      Methods
      A single-institution retrospective study was performed of 331 patients who underwent radical resection of thymoma from 1991 through 2012.

      Results
      After a median follow-up of 59 months (range, 3-256), the recurrence rates was 6.9% (23/331). Overall 5- and 10-year survival rates were 92.3% and 84.9%. Cancer specific survival rates were 95% and 89.4% at 5 and 10 years, respectively. Recurrence-free survival rates were 93.6% and 87.2% at 5 and 10 years, respectively. Among the 23 patients, relapses were found in the following sites: pleura (thirteen cases), tumor bed (six), lung (six), chest wall (four), lymph node metastasis (two) , abdominal node metastasis (one),liver (one), pleural effusion (three), and over-lapped recurrence (nine). According to the definition of the International Thymic Malignancy Interest Group, 10 (43.5%) patients had local recurrence, 15 (65.2%) had regional recurrence, 10 (43.5%) had distant recurrence (six lung, one liver, one abdominal node metastasis, and two lymph node metastasis), and 9 (39.1%) had over-lapped recurrence. The difference in survival after recurrence between lung and regional relapse was statistically significant (p=0.027), but it was insignificant between lung and distant relapse (p=0.808). Recurrence rates correlated with the initial Masaoka stage: I, 1.0% (2/196); II, 9.7% (9/93) ; III, 24.2% (8/33); IVa, 42.9% (3/7); and IVb, 100% (1/1). The difference in recurrence between Masaoka stage I and II was stastically significant (p=0.000). And they also correlated with World Health Organization tumor type: A and AB, 3.2% ( 5/154 ); B1, 6% ( 4/67 ); B2, 6% ( 3/50 ); and B3, 22.7% ( 10/44). Tumor size demonstrated a step-up of recurrence at 8 cm (<8 cm, 62.8%; ≥8 cm, 37.2%; P=0.007). In multivariate analysis, Masaoka stage (p=0.005), tumor size (p=0.033), and WHO histology (p=0.046) were predictive of recurrence.

      Conclusion
      Pleura are the most common recurrent sites. Recurrence in the lung had poorer survival than the regional relapse, it should be included in the distant recurrence. Regional recurrence is the most common pattern of relapse, but local and distant recurrences are not infrequently observed. Advanced Masaoka stage, larger tumor size, and Type B3 were risk factors of recurrence.