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J. Levine

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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): J. Levine

      • Abstract

      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.

      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.

      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

      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.