Author of

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  P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall

  • 26738

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    P1.16-28 - The Impact of Spironolactone on the Lung Injury Induced by Concomitant Trastuzumab and Thoracic Radiotherapy (ID 12574)

    16:45 - 18:00  |  Author(s): Esin Celik
    • Abstract
    • Slides

    Background
    

    Radiation-induced lung injury (RILI) is a potentially life-threatening and dose-limiting side effect of thoracic irradiation. Trastuzumab (T), a monoclonal antibody directed against HER2, improves overall survival in patients with HER2 positive breast cancer. T concurrently with radiation thus increases the antitumor effect of radiation. There are same clinical evidences in the literature that T also radiosensibilizes human healthy tissues and in this way it could increase the toxicity of the treatment. The incidence of T-induced pneumonitis is 0.4–0.6%. Although infrequent; pulmonary toxicity due to T may be life-threatening. Aldosterone, which is a physiological activator of MR, is partially responsible for increases in the extracellular matrix turnover, as observed in fibrosis of the cardiac, kidney and lung tissues, and exerts its effects primarily on lung epithelium. Spironolactone (S), an aldosterone receptor antagonist, may have the ability to ameliorate pulmonary fibrosis.We hypothesized that S would be effective in the treatment of both RT and T-induced lung injury by correcting pulmonary fibrosis

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    This study included 80 female Wistar-Albino rats (250-300 g); use of which was approved by the Ethical Committee. Rats were divided into eight groups: group (G) 1 was control group; G2, G3 and G4 were RT, S and T groups; G5, G6, G7 and G8 were RT+T, T+S, RT+S and RT+T+S groups respectively. RT was applied under general anesthesia with intraperitoneally administered 90 mg/kg ketamine hydrochloride and 10 mg/kg xylazine. A single dose of 15 Gy was applied to the both lungs. T (6 mg/kg) was administered intraperitoneally and S (80 mg/kg) was administered by oral gavage. Rats were sacrificed via cervical dislocation at 6^th hour, 21^st day and 100^th day after RT and the lung samples were taken for microscopical examination.

    4c3880bb027f159e801041b1021e88e8 Result
    

    By 100^th days of RT inflammation score, lung fibrosis score and TGF- expression were significantly different within study groups (p values were 0.002, 0.001 and 0.043 respectively). Inflammation score of G8 was significantly lower than inflammation scores of G2 and G5 (p values: G2-G8= 0.004, and G5-G8=0.022). Inflammation score of G2 was significantly higher than G7 (p=0.028). There were significant differences regarding to fibrosis scores between G2-G8 (p=0.015), G2-G7 (p=0.017) and G5-G8 (p=0.011). TGF-β expression was higher in both G2 and G5 when compared to G8 (p = 0.038).

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Our results suggested that S is an effective treatment option for improving radiation-induced pulmonary fibrosis. These findings should be clarified with further preclinical and clinical studies.

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