1.Hua Xian Fang alleviates radiation-induced pulmonary fibrosis by upregulating the level of IFN-γ in blood and tissues
Junyang CHEN ; Pingjin ZOU ; Zengyi FANG ; Cuicui GONG ; Jie YIN ; Meihua CHEN ; Bing LIN ; Jinyi LANG
Chinese Journal of Radiation Oncology 2024;33(6):554-561
Objective:To investigate the therapeutic efficacy and underlying mechanisms of the traditional Chinese medicine formula "Hua Xian Fang" (HXF) in the treatment of radiation-induced pulmonary fibrosis (RIPF).Methods:In vivo experiment, 36 male specific pathogen free (SPF)-grade C57BL/6 mice aged 6-8 weeks were randomly divided into the control, irradiation (17 Gy thoracic irradiation), and irradiation+HXF groups (17 Gy thoracic irradiation+HXF). After 16 weeks, lung coefficient, HE staining and Masson staining were used to evaluate the degree of pulmonary inflammation and fibrosis. Immunohistochemistry was performed to measure the expression levels of α-smooth muscle actin (α-SMA) in lung tissues. Quantitative real-time PCR (qPCR) was performed to detect the mRNA expression levels of interferon-γ (IFN-γ). Enzyme linked immunosorbent assay (ELISA) was conducted to determine the levels of IFN-γ in serum and bronchoalveolar lavage fluid (BALF). During in vitro experiment, NIH/3T3 fibroblasts were stimulated with IFN-γ after 6 Gy irradiation, followed by 48 hours of culture. qPCR, immunofluorescence staining, and Western blot were used to assess the expression of α-SMA and collagen Ⅰ at the transcription and protein levels. One way ANOVA was used for multiple group comparisons, and Tukey test was used for inter group multiple comparisons. Results:Compared to the control group, mice in the irradiation group showed significant increases in lung coefficient, Szapiel score, Ashcroft score, and α-SMA expression in lung tissues (all P<0.001). Compared to the irradiation group, the irradiation+HXF group exhibited significant decreases in the above indicators (all P<0.001). qPCR demonstrated that the mRNA expression levels of IFN-γ were significantly higher in the irradiation+HXF group than that in the irradiation group ( P=0.001). ELISA results showed that the levels of IFN-γ in serum and BALF were significantly elevated in the irradiation+HXF group compared to those in the irradiation group ( P=0.032, 0.037). In vitro experiment revealed that after irradiation, the expression levels of α-SMA and collagen Ⅰ mRNA and protein in NIH/3T3 cells were significantly increased, while decreased after IFN-γ stimulation. Conclusion:HXF effectively alleviates RIPF, probably by the upregulation of IFN-γ in blood and tissues and inhibition of fibroblast activation.
2.Heterogeneity of cancer-associated fibroblasts and regulating roles in cancer radiotherapy
Meihua CHEN ; Shubin WANG ; Jinyi LANG
Chinese Journal of Radiation Oncology 2023;32(11):1020-1024
Cancer-associated fibroblasts (CAF) represent a crucial and abundant group of stromal cells in the tumor microenvironment (TME) and are effective targets for anti-tumor therapy. CAFs exhibit high heterogeneity and plasticity, which play a pivotal role in tumor initiation, progression, immune evasion, and therapy resistance. Radiotherapy (RT) is a fundamental treatment modality for malignant tumors that can reshape the TME through various mechanisms. Following RT, CAFs undergo a series of phenotypic changes and interact with multiple cells in the TME, promoting radioresistance and immune evasion through multiple pathways, such as enhancing tumor cell proliferation, modulating immune response, inducing angiogenesis, remodeling extracellular matrix, and reprogramming metabolism, etc., thereby affecting therapeutic effect. Targeting CAFs in combination with RT can improve anti-tumor efficacy and prognosis. In this article, research progress in CAFs in tumor RT was reviewed.
3.Meta-analysis of chrono-chemotherapy combined with radiotherapy for locally advanced nasopharyngeal carcinoma
Jianquan YANG ; Wen GUO ; Jinyi LANG ; Man LU
Chinese Journal of Radiation Oncology 2022;31(2):120-124
Objective:To systematically compare the efficacy and safety of chrono-chemotherapy combined with radiotherapy in patients with locally advanced nasopharyngeal carcinoma.Methods:Seven databases were searched, including the Cochrane Library (Issue 5, 2021), PubMed, Embase, CBM, CNKI, VIP and Wanfang Database. The method ological quality of the eligible studies was evaluated. The Meta-analysis was performed by the Revman 5.3 software.Results:Sixteen studies consisting of 1275 patients were finally included. Among them, 642 patients were treated with chrono-chemotherapy combined with radiotherapy and 633 patients received conventional chemotherapy combined with radiotherapy. Results showed that compared with conventional chemotherapy group, the effective rate was significantly elevated ( OR=1.66, 95% CI: 1.17-2.34, P=0.004), the incidence of leucopenia, thrombocytopenia, gastrointestinal reaction, grade 3-4 oral mucosal reaction and grade 3-4 radiothermitis was significantly reduced (all P<0.001), and the quantity of CD3, CD4 and CD4/CD8 was significantly increased in the chrono-chemotherapy group. Conclusion:Current evidence shows that compared with conventional chemotherapy, chrono-chemotherapy combined with radiotherapy could improve the effective rate, reduce adverse reactions and mitigate the destruction of immune function simultaneously.
4.Efficacy of concurrent chemoradiotherapy with S-1 vs. radiotherapy alone for elderly patients with esophageal cancer: a meta-analysis
Jianquan YANG ; Wen GUO ; Jinyi LANG ; Man LU
Chinese Journal of Radiation Oncology 2022;31(9):791-797
Objective:To evaluate the efficacy of concurrent radiotherapy combined with S-1 (CCRT) versus radiotherapy (RT) alone in elderly patients with esophageal cancer by Meta-analysis.Methods:The Cochrane Library, PubMed, Web of science, EMbase, CBM, CNKI, VIP and Wanfang database were searched. The eligible studies were subject to evaluation of methodological quality. The Meta-analysis was performed by the Revman 5.3 software.Results:A total of 1693 patients were enrolled in 23 studies. The results showed that CCRT increased the incidence of CR [ OR=2.08,95% CI (1.66-2.61), P<0.001] and PR [ OR=1.31,95% CI (1.08-1.60), P=0.007] and total response rate [ OR=2.99,95% CI (2.37-3.77), P<0.001]. Furthermore, CCRT improved the 1-year survival rate [ OR=2.56, 95% CI (1.94-3.38), P<0.001] and 2-year survival rate [ OR=2.33, 95% CI (1.77-3.08), P<0.001]. Meanwhile, CCRT reduced the incidence of leucopenia, thrombocytopenia, radioactive esophagitis, nausea and vomiting (all P<0.05), but there was no significant difference in the incidence of anemia and radiation pneumonia between two groups (both P>0.05). Conclusions:Available evidence suggests that CCRT combined with S-1 can improve therapeutic efficacy and prolong survival time in elderly patients with esophageal cancer, but CCRT may increase the incidence of treatment-related side effects. Due to the limitations of the number and quality of the included studies, the above conclusions need to be verified by more high-quality studies.
5.Research progress on dose-escalation at late-course of radiotherapy for locally advanced nasopharyngeal carcinoma patients with residual lesion
Yecai HUANG ; Yangkun LUO ; Peng ZHANG ; Weidong WANG ; Shichuan ZHANG ; Mei FENG ; Guohui XU ; Jinyi LANG
Chinese Journal of Radiation Oncology 2022;31(11):1055-1058
Nasopharyngeal carcinoma (NPC) is a common head and neck malignant tumor with high incidence in southern China. Local recurrence is one of the main failure modes of locally advanced NPC. The dose-escalation after radical radiotherapy for locally advanced NPC remains controversial. In the era of modern radiotherapy, the mainstream treatment mode of locally advanced NPC is neoadjuvant chemotherapy plus concurrent chemoradiotherapy. There is no consensus on whether to prescribe dose-escalation, how and when to conduct dose-escalation, how much dose to prescribe for patients with residual lesion proved by MRI or pathology. How to accurately determine the target volume and dose / fraction to maximize the local control of the tumor are the directions of clinical practice for locally advanced NPC, which remain to be further studied.
6.Correlation Between Immune Function Status and EBV DNA in Patients with Nasopharyngeal Carcinoma and Their Influence on Prognosis
Xueling WEI ; Mei LAN ; Xinhao PENG ; Hanyi ZHANG ; En LONG ; Hui LIU ; Jinyi LANG
Cancer Research on Prevention and Treatment 2021;48(6):600-606
Objective To explore the correlation between EBV DNA load and peripheral immune cells (including lymphocyte supsets and natural killer cells) before treatment in patients with NPC, and analyze the influence of circulating immune cell supsets related to EBV on the prognosis of NPC patients. Methods We retrospectively analyzed the general data of 203 NPC patients without distant metastasis at the first treatment, as well as the data of peripheral blood EBV DNA and circulating immune cell supset. The ROC curve analysis was used to determine the cutoff value of each circulating immune cell supset. Kaplan-Meier method was used for survival analysis, and Cox regression model was used for multi-factor prognostic correlation analysis. Results The 3-year OS, PFS, DMFS and LRFS of EBV DNA < 400 copies/ml group and EBV DNA≥400 copies/ml group were 99.2%
7.Analysis of long-term survival outcomes and late radiation toxicity of 132 nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy
Zengyi FANG ; Zifei WU ; Chuan WU ; Cheng LUO ; Mingquan GAO ; Xin LAI ; Liping LUO ; Weidong WANG ; Jinyi LANG
Chinese Journal of Radiation Oncology 2021;30(7):653-658
Objective:To retrospectively analyze the long-term survival (10-15 years) and late toxicity of nasopharyngeal carcinoma (NPC) patients after intensity-modulated radiotherapy (IMRT), aiming to provide reference for the optimal treatment of NPC.Methods:132 patients with NPC who were treated with IMRT in Sichuan Cancer Hospital from 2003 to 2009 were recruited. Among them, 3 patients were classified as stage Ⅰ, 22 cases of grade Ⅱ, 61 cases of grade Ⅲ, 43 cases of Ⅳ A and 3 cases of Ⅳ B, respectively. The median dose was 73.37Gy (66 to 85Gy), divided into 33 times. Twenty patients received radiotherapy alone, 112 cases of concurrent radiochemotherapy. The survival rate was calculated by Kaplan-Meier method and log- rank test. Univariate prognostic analysis was performed. Cox model was used to conduct multivariate prognostic analysis. The late radiation toxicity was evaluated by RTOG/EORTC criteria. Results:The median follow-up duration was 128 months (range, 3 to 191 months). The 10-and 15-year local control rates of NPC patients were 86.0% and 79.9%. The disease-free survival rates were 72.5% and 63.2%, and the overall survival (OS) rates were 65.2% and 57.1%. The local recurrence rate was 12.1%, and the distant metastasis rate was 16.7%. A total of 53 patients died, of whom 15 patients died of local recurrence, 20 patients died of distant metastasis and 18 patients died of other diseases (pneumonia, intracranial hemorrhage and accident, etc.). The 10-and 15-year non-tumor-related mortality rates were 11.3% and 13.6%. Univariate analysis showed that age, smoking habit, lactate dehydrogenase (LDH), T stage and clinical stage were the independent prognostic factors of OS in NPC patients. Multivariate analysis demonstrated that LDH, T stage and synchronous chemotherapy were the prognostic factors of OS in NPC patients. The incidence of gradeⅠ-Ⅱ late radiation injury (hearing impairment, dysphagia, dental caries and xerostomia) was 90.4%, and 8.5% for grade Ⅲ-Ⅳ late radiation injury (skin fibrosis, hearing impairment and radiation brain injury).Conclusions:The 10-and 15-year OS of NPC patients treated with IMRT is relatively high. With the prolongation of survival, the non-tumor-related mortality rate is increased. Distant metastasis is the main cause of treatment failure. The main late injuries include grade Ⅰ/Ⅱ hearing impairment, dysphagia, dental caries and xerostomia.
8.Radiotherapy for hepatocellular carcinoma downstaging: From palliative care to radical treatment
Zhaochong ZENG ; Jianguo SUN ; Jinyi LANG
Journal of Clinical Hepatology 2020;36(2):258-262
The purpose of tumor staging is to guide treatment, and the treatment for a certain stage should be adjusted based on the changes in disease condition, in order to facilitate better control of tumor. Therefore, the treatment of liver cancer requires follow-up and re-staging to develop better treatment regimens for patients, especially the opportunity for cure. Surgical resection is not suitable for large hepatocellular carcinoma confined to the liver, and after embolization chemotherapy combined with radiotherapy for tumor regression and downstaging, some patients may undergo surgical resection, and the incurable tumor can thus be cured. For liver cancer patients with portal vein tumor thrombus, surgical resection can be performed after tumor thrombus is reduced by neoadjuvant radiotherapy, and the patients undergoing neoadjuvant radiotherapy have a significant increase in survival time than those not undergoing neoadjuvant radiotherapy. Large hepatocellular carcinoma can be downstaged to small hepatocellular carcinoma after multimodality therapy, and then stereotactic radiotherapy or radiofrequency ablation can help to achieve radical treatment. There is an increasing number of clinical reports of radiotherapy for liver cancer downstaging, with a gradual increase in evidence-based level, and thus it holds promise for clinical application.
9. Radiation-induced changes in small world network in patients with nasopharyngeal carcinoma: a three-dimensional structure MRI imaging study
Xin XIN ; Chuandong CHENG ; Churong LI ; Jie LI ; Pei WANG ; Yin TIAN ; Gang YIN ; Jinyi LANG
Chinese Journal of Radiation Oncology 2019;28(11):811-816
Objective:
To investigate the radiotherapy (RT)-induced changes in the brain structural network in patients with nasopharyngeal carcinoma (NPC).
Methods:
Three-dimensional structural magnetic resonance data (3D-T1W) was adopted to investigate the structural network in 103 patients with NPC before and after receiving RT. The structural networks were then reconstructed using 3D-T1W. The radiation-induced changes in topology properties of small world network were analyzed by using graph theoretical analysis.
Results:
Patients showed small world properties before and after RT. Compared with the pre-RT group, the global and local efficiency were lower, the shortest path length was longer and the clustering coefficient was less in the post-RT group. In addition, the hub regions in the post-RT group were significantly different from those in the pre-RT group, mainly located in the left rolandic operculum, right inferior frontal gyrus, right parahippocampal gyrus, right lingual gyrus, bilateral supramarginal gyrus, left superior temporal gyrus and temporal pole of the right middle temporal gyrus.
Conclusion
It is speculated that RT leads to high efficiency of network topology and information transmission, which provides a novel perspective for exploring the RT-induced brain changes, diagnosis of RT-induced injury and evaluation of RT efficacy.
10.Artificial Intelligence: opportunities and challenges in radiotherapy
Yimin LI ; Mei LAN ; Jiayu ZHANG ; Pei WANG ; Jinyi LANG
Chinese Journal of Radiation Oncology 2019;28(6):476-480
Artificial Intelligence are emerging as poweful tools for many field including medicine.It has be applied to radiation therapy in different degree,such as automatic OAR or tumor volume segmentation,automatic radiotherapy planning,prediction of toxicity and prognostic,etc.In this article,the research progress on Artificial Intelligence in the radiotherapy for malignant tumor was reviewed.

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