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Tom Hei



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    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-87 - β-Adrenergic Antagonists Sensitizes Chemoradiation Therapy in Locally Advanced Non-Small Cell Lung Cancer (ID 864)

      10:15 - 18:15  |  Author(s): Tom Hei

      • Abstract
      • Slides

      Background

      Locally advanced non-small cell lung cancer (NSCLC) is highly resistant to chemoradiotherapy, and many cancer patients experience chronic stress. Studies suggest stimulation of β-adrenergic receptor (β-AR) promotes tumor invasion and therapy resistance. We investigated whether β-AR inhibition with beta-blockers acts as a chemotherapy and radiation sensitizer in vitro and in patients treated with chemoradiation followed by surgery for locally advanced NSCLC.

      Method

      We investigated the effects of the non-selective beta-blocker propranolol on two human lung adenocarcinoma cell lines (PC9, A549) treated with radiation or cisplatin. We retrospectively evaluated 77 patients with Stage IIIA NSCLC who received induction chemoradiation followed by surgery. Pathological and imaging response, metastatic rate and survival were analyzed using SPSSv20 and PrismGraphpad6.

      Result

      Propranolol combined with radiation or cisplatin decreased clonogenic survival of PC9 and A549 cells in vitro (p<0.05). Furthermore, propranolol decreased expression of p-PKA, a β-adrenergic pathway downstream activation target, in both cell lines compared to irradiation or cisplatin alone (p<0.05). In patients treated for Stage IIIA NSCLC, 16 took beta-blockers, 61 did not. Beta-blockade is associated with a trend to improved overall survival (OS) at 1 year (81.3% vs 57.4%, p=0.08) and distant metastasis-free survival (DMFS) (2.6 years vs 1.3 years, p=0.16). Although beta-blocker use was associated with decreased distant metastases (risk ratio [RR] 0.19; p=0.03), it did not affect primary tumor pathological response (p=0.40) or imaging response (p=0.36).

      Conclusion

      β-AR blockade enhanced radiation and cisplatin sensitivity of human non-small cell lung cancer cells in vitro. Beta-blockers use is associated with decreased distant metastases and potentially improved OS and DMFS. Additional studies are warranted to evaluate the role of beta-blockers as a chemoradiation sensitizer in locally advanced NSCLC.

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