1.Influence of concurrent and sequential combination of postoperative radiation and endocrine therapy (aromatase inhibitor or tamoxifen) on radiation-induced lung injury
Chengbo HAN ; Fan LI ; Jietao MA ; Wei JING ; Jianzhu ZHAO ; Huawei ZOU
Cancer Research and Clinic 2009;21(11):728-730
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.
2.Effect of osimertinib combined bevacizumab on lung adenocarcinoma with EGFR T790M mutation and its mechanisms
Zhicheng XIONG ; Yang LIU ; Xin SUN ; Jietao MA ; Shuling ZHANG ; Li SUN ; Jing SUN ; Xiaonuo ZHANG ; Chengbo HAN
Chinese Journal of Clinical Oncology 2017;44(15):744-749
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 (P<0.05). VEGF, HIF-1αexpression, and MVD were significantly low in the high-dose osimertinib-alone group (P<0.05). Increasing doses of osimertinib induced dose-dependent weakening of the p-EGFR, p-AKT, and p-ERK expression levels (P<0.05). In the low-dose osimertinib-plus-bevacizumab group and low-dose osimertinib-alone group, no significant difference in tumor volume and the above factors was observed. In the low-dose osimertinib-plus-bevacizumab group and high-dose osimertinib-alone group, tumor volumes did not exhibit significant difference (P=0.178). Moreover, VEGF, HIF-1αexpression, and MVD exhibited no significant difference. No significant difference in the p-EGFR, p-AKT, and p-ERK expression levels was found between high-dose osimertinib-alone group and low-dose osimertinib-plus-bevacizumab group (P>0.05). 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.
3.Safety and Efficacy of Chemotherapy and Radiotherapy for the Treatment of Unresectable Locally Advanced Non-small Cell Lung Cancer
Meng YUAN ; Chengbo HAN ; Jietao MA ; Letian HUANG ; Shuling ZHANG ; Li SUN
Journal of China Medical University 2017;46(12):1124-1128
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.
4.Efficacy and safety of endostar intracavitary infusion in treatment of malignant serous cavity effusion: A case control study
ZHANG Shuling ; MA Jietao ; ZHAO Jianzhu ; SUN Li ; JING Wei ; ZHOU Yang ; HUANG Letian ; HAN Chengbo
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2018;25(2):138-142
Objective To analyze the clinical efficacy and safety of endostar or carboplatin combined with endostar intracavitary perfusion in the treatment of malignant serous cavity effusion. Methods We retrospectively reviewed the clinical data of 78 cancer patients with malignant serous cavity effusion who received paracentesis and intracavitary endostar, or carboplatin combined with endostar in Shengjing Hospital of China Medical University between November 2011 and November 2016. There were 42 males and 36 females at a median age of 62 years ranging from 17 to 78 years. According to treatment methods, 78 patients were divided into two groups, in which 33 patients received intracavitary endostar combined with carboplatin (a combination group, 15 males and 18 females at a median age of 56 years ranging from 17 to 66 years), and 45 patients received intracavitary endostar (an endostar group, 27 males and 18 females at a median age of 63 years ranging from 38 to 78 years). The efficacy and safety of two methods were analyzed and compared. Results The response rate in the combination group was 75.8%, which was higher than that in the endostar group (60.0%, P=0.035). In quality of life improvement, there was no statistical difference between the two groups (P=0.113). The incidence of fatigue, myelosuppression and gastrointestinal reactions in the endostar group was significantly lower than that of the combination group (P=0.006, 0.000 and 0.017, respectively). Analysis of long-term efficacy revealed that the median time to progress (TTP) in the combination group and endostar group was 171 days and 143 days, respectively (P=0.030). Conclusion Intracavitary infusion of endostar alone, or carboplatin combined with endostar is effective and tolerable for controlling malignant serous cavity effusion. But for the patients with poor physical state who can not tolerant platinum perfusion, intracavitary infusion of endostar alone can be adopted to control malignant serous cavity effusion.