ABSTRACT
Objective:This study was performed using preclinical transplanted animal experiments to analyce the effects and mechanisms of third-generation EGFR-TKIs combined with anti-angiogenic therapy, thereby providing theoretical basis for further clinical trials. Methods:Researchers constructed the transplant BALB/C nude mice models with H1975 lung adenocarcinoma cell line (EGFR T790M) and divided the mice into four groups and treated them with osimertinib (2.5 or 5 mg/kg/day, gavage) alone or plus bevacizumab (5 mg/kg/twice weekly, i.p.) when the tumors reached approximately 0.4-0.6 cm3 in volume. The tumor growth curve of tumor volume was drawn according to the time in every group. After 2 weeks of treatment, the mice were killed and the tumors were processed for immunohistochemical staining and Western blot analysis. Immunostaining was performed to detect:HIF-1α, VEGF, and microvessel density (MVD) by using SP method on paraffin sections. Western blot analysis was used to analyze the protein expression levels of EGFR, AKT, and ERK signal transduction pathways. Results:After 2 weeks of treatment in high-and low-dose osimertinib alone, tumor volume in the high-dose group was significantly less than in low-dose osimertinib-alone group (P0.05). In the high-dose osimertinib-plus-bevacizumab group, tumor growth was not significantly greater than that in the high-dose osimertinib-alone group (P=0.642). No significant difference was observed in the above factors.In the high-and low-dose osimertinib-plus-bevacizumab groups, tumor volume and the above factors did not exhibit significant differences (P>0.05). Conclusion:Osimertinib has obvious antitumor effects in EGFR-mutant lung adenocarcinoma with T790M mutation cell xenografts. Bevacizumab has a synergetic inhibitory effect with osimertinib against EGFR-mutant lung adenocarcinoma with T790M mutation cell xenografts. Bevacizumab enhanced the antitumor effects of osimertinib by reducing VEGF expression and the microvascular density of the tumor, thereby improving the tumor microenvironment. Bevacizumab can enhance the effect of osimertinib by suppressing EGFR, ERK, and AKT phosphorylation, thereby synergistically inhibiting EGFR activation and downstream signaling.
ABSTRACT
Objective The aim of this study was to retrospectively review the efficacy and safety of treatment for unresectable locally advanced non-small cell lung cancer (LA-NSCLC).Methods A total of 98 patients treated in our hospital between January 2010 and December 2015 were enrolled in this study.Patients were divided into three groups:the thoracic radiotherapy (TRT) alone,concurrent chemoradiotherapy,and sequential chemoradiotherapy groups.The progression-free survival (PFS) and overall survival (OS) were analyzed via the Kaplan-Meier method,and compared with the log-rank/Breslow test.The prognostic factors were analyzed using the Kaplan-Meier and Cox multivariate proportional hazards models.Results The median PFS in the concurrent therapy group was longer than that in the TRT alone group (P ＜ 0.05).The median OS was improved in patients treated with concurrent or sequential therapy than in the TRT alone group (P ＜ 0.05).N stage,chemotherapy regimens,and radiotherapy modalities were independent prognostic factors of PFS in all patients (P ＜0.05).Similarly,N stage was an independent prognostic factor of OS in all patients (P ＜ 0.05).Overall,the treatment was deemed safe.The occurrence of hematotoxicity related to Karnofsky performance score (KPS) and chemotherapy regimens (P ＜ 0.05).Conclusion Patients with a lower N stage who received cisplatin-based double chemoradiotherapy demonstrated improved survival rates.Survival was significantly improved in LA-NSCLC patients treated with concurrent or sequential therapies compared with TRT alone.Overall,the treatment is safe.KPS and chemotherapy combination regimens may increase the occurrence of hematotoxicity.
ABSTRACT
Objective To compare radiation-induced lung injury (RILI) between concurrent and sequential combination of postoperative radiotherapy and endocrine therapy. Methods A total of 118 patients subjected by radical or modified radical operation of breast cancer were enrolled in this study and received radiotherapy and endocrine therapy between Jan 2003 and December 2007. All the patients were categorized into four groups: radiotherapy (RT) plus concurrent aromatase inhibitor(AI): RT+AI; RT plus sequential AI:RT-AI; RT plus tamoxifen (TAM): RT+TAM; RT plus sequential TAM: RT-TAM. Radiotherapy was delivered by using various energy of electron (6, 9, 12 Mev β-ray) or 6 M.V X-ray for different target with a dose of 50 Gy (2 Gy/Fx, 5 fractions per week). RILI grades were classified according to RTOG/EORTC and Aoki evaluation criteria from one month to at least one year after radiotherapy. Results 30/118(25.4 %) patients was observed with RILI, RT+AI 22.7 % vs. RT-AI 20.0 %(P =0.806), RT+TAM 35.7 % vs. RT-TAM 24.2 %(P =0.328). The incident rate of RILI was higher in elder patients(>60 yr) than in other patients (33.9 % vs.16.9 %, P =0.05). Patients with positive chemotherapy history had a higher risk of RILI than those with chemotherapy-negtive history (P =0.039). Conclusion These findings suggest that RILI are associated with age and chemotherapy history, but not correlated with the sequence of radiotherapy and endocrine therapy.