Abstract 6549: Preventive effect of compound Kushen injection in radiation induced lung pneumonitis

Abstract

Abstract Standard treatment for patients with unresectable lung cancer is concurrent radiation and chemotherapy either with carboplatin and paclitaxel. One of the most common adverse effects during the combined chemoradiation is inflammation in the lung, i.e. pneumonitis. This effect continues into the adjuvant phase of treatment, prohibiting many patients from receiving full course of the therapy. Thus, the agent that can alleviate these inflammatory responses while not interfering with the therapeutic effect of standard treatment, would be ultimately beneficial for the continuation of lung cancer treatment and improvement of patients' quality of life. Here we report the effect of a Chinese herbal medicine, Compound Kushen injection (CKI), in radiation induced pneumonitis (RIP) and its potential mechanisms. CKI (2, 4 or 8ml/kg) was given to C3Hf/KamL mice once a day for 8 weeks from the day of local thoracic irradiation (LTI, 13.5 Gy) or 2 weeks before LTI. MicroCT was performed to monitor the imaging changes representing inflammation of lung tissues and morbidity of mice was observed. Inflammation was also assessed by determination of serum cytokines and cyclooxygenase metabolites. DNA damage maker γH2AX was measured by western blot. Antitumor efficacy of CKI in combination with radiation and carboplatin was tested in KrasLA1 adenocarcinoma mouse model. Log rank tests showed that mice treated with CKI (4 ml/kg) started 2 weeks before LTI group had a significant reduction in time to death compared to that of LTI only group (p=0.006). Similarly, mice that received 8ml/kg CKI concurrently started with LTI group had significantly better survival than that of LTI only group (p=0.024). The result of lung microCT imaging and H&E staining of the lung suggested that lung tissues derived from CKI (8 ml/kg) treated mice had a significantly lower degree of pneumonitis than that of LTI only group (p < 0.05), suggesting CKI significantly prolonged the survival of the irradiated C3H mice by reducing pneumonitis. The levels of serum TNF-α and TGF-β in 72 hr CKI treated mice were 30% and 38%, respectively, lower than that of control mice (p < 0.05). Additionally, the intra-lung COX-2 metabolites, including PGE2, PGF2α and PGI2 in CKI treated mice were also lower than that of control mice. Furthermore, the antitumor efficacy of the CKI in combination with radiation and carboplatin in Kras lung adenocarcinoma was similar to that of radiation and carboplatin. Together, these data suggest that CKI significantly reduced radiation induced pneumonitis by potentially reducing the radiation induced inflammation in lung tissues. Clinical trial using CKI to prevent RIP is warranted. Citation Format: Ting Xu, Patrea Rhea, Tara Conway, Mihai Gagea, Lirong Wu, Zhongxing Liao, Peiying Yang. Preventive effect of compound Kushen injection in radiation induced lung pneumonitis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6549.