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R. Harrington



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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-018 - Cumalative Biomarker Model Predicts 3-Year Recurrence in Resected Stage I Adenocarcinoma of the Lung (ID 1699)

      09:30 - 16:30  |  Author(s): R. Harrington

      • Abstract

      Background
      Stage I adenocarcinoma is the most curable form of non-small cell lung cancer (NSCLC), yet recurrence following complete resection is >30%. To improve this, it is important to identify indicators of tumor biology, which can predict a more aggressive disease course so adjuvant therapies can be considered. Osteopontin (OPN) is a regulator of malignant function in NSCLC. In more advanced NSCLC patients, plasma OPN levels correlate with prognosis. We hypothesize that pre-operative plasma OPN in combination with clinical factors can predict recurrence following resection in stage I adenocarcinoma.

      Methods
      A cohort of completely resected stage I adenocarcinoma patients without adjuvant or neoadjuvant therapy was prospectively collected and followed through 3 years. Pretreatment demographics, operative variables, pathologic characteristics, and time to progression were recorded. Histology was classified as solid or mixed with noninvasive features. Pre-operative plasma OPN was measured blinded and in duplicate by ELISA (R&D, Minneapolis, MN) and is reported in ng/ml. Cut points to predict recurrence were determined by X-tile (Yale University, CT) plots.

      Results
      There were 141 patients (50M/91F), 103 were stage IA. Median follow-up was 43.9 months and was complete in all to 3 years. Thirty-nine patients (27.8%) recurred by 3 years. The median pre-operative OPN was 54.9 (range, 2.3 – 150.6). OPN levels correlated with tumor size (r=0.25, p=0.003), but not with age, pack years, t-stage, extent of resection, or invasive histologic component. Median OPN was higher in males than females (62.9 vs. 50.5, p=0.009), and in current smokers compared to former/never smokers (68.5 vs. 53.3, p=0.04). In Cox regression analysis, an increased risk for recurrence was associated with preoperative plasma OPN >49.6 (HR=3.8, CI:1.7-7.8, p=0.001), solid histology (HR=2.5, CI:1.3-4.9, p=0.008) and male gender (HR=2.5, CI:1.3-4.6, p=0.005), but not with size, stage, age, pack years, and extent of resection. A model incorporating preoperative OPN and invasive histologic component stratified recurrence risk for both genders, but was highly significant in females (p=0.006) (Fig). Receiver operator curve (ROC) incorporating sex, OPN and invasive histologic component had AUC=0.76 (CI: 0.6-0.8, p=0.03). Figure 1

      Conclusion
      Circulating OPN provides a view of the tumor micro-environment and can serve as an important indicator of the course of the disease in resected NSCLC. When combined with sex and measures of histologic invasive component, plasma OPN >49.6 form a highly predictive cumulative model to predict early recurrence in resected stage I adenocarcinomas and should be validated to assess its value in selecting patients for adjuvant and tumor prevention protocols.

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    P3.07 - Poster Session 3 - Surgery (ID 193)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P3.07-019 - Sex-Based Differernces in Morbidity and Mortality Associated with Non-Small Cell Lung Cancer Resections (ID 1708)

      09:30 - 16:30  |  Author(s): R. Harrington

      • Abstract

      Background
      Stage for stage, women have superior survival compared to men with non-small cell lung cancer (NSCLC). This includes women undergoing resection, but little is reported regarding sex-based differences in operative morbidity, mortality, and length of hospital stay (LOS) following NSCLC resection.

      Methods
      We retrospectively evaluated all patients undergoing primary NSCLC resections at our institution from 01/07-12/08 to evaluate the prognostic significance of female sex on morbidity, mortality and LOS.

      Results
      A total 259 patients were included, 155 females and 104 males. The majority of resections were lobectomy (162/259) and by VATS (161/259). Women were significantly younger (70.6 vs. 74.0 years, p=0.006), reported fewer pack years smoked (30 vs. 44 years, p=0.001), had more adenocarcinoma histology (86% vs. 63%, p<0.001) and had higher percent predicated forced expiratory volume in 1 second (FEV1%)(84 vs. 77, p=0.014) than men. No other significant differences in pre-treatment demographics, tumor characteristics or surgical procedures were noted. A significantly reduced rate of post operative atrial fibrillation (5% vs. 13%, p=0.031), prolonged air leak (8% vs 16%, p=0.044), any complication (28% vs. 44%, p=0.007), and LOS (5.0 vs. 5.98 days, p=0.031) was noted for women. In multivariate analysis, which included age, pack years and FEV1%, male sex remained a significant predictor for the occurrence of a post-operative complication (p= 0.007). Figure 1

      Conclusion
      Sex-based differences in the morbidity associated with resection for NSCLC were noted, with a significant improvement in several important short –term outcomes for women compared to men. As the percent of female NSCLC patients increase, these data carry significant implications in procedural risk stratification and in comparison of modern surgical trials to historic controls.