Browsing by Author "Chen, Xiaofeng"
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Item Benefits of combination therapy with immune checkpoint inhibitors and predictive role of tumour mutation burden in hepatocellular carcinoma: A systematic review and meta-analysis(Elsevier, 2022-11) Zheng, Jiaxi; Shao, Minghai; Yang , Weifang; Ren , Justin; Chen, Xiaofeng; Yang, Haihua; Radiation Oncology, School of MedicineObjectives To investigate the clinical benefits of combination therapy with immune checkpoint inhibitors (ICIs) and best combination regimen for people with advanced hepatocellular carcinoma (HCC) and to explore the predictive performance of tumour mutation burden (TMB). Methods We conducted a systematic literature search to identify clinical trials. Meta-analysis and subgroup analyses were performed to estimate the benefits of combination regimens with PD-1/PD-L1 inhibitors for patients with advanced HCC and compare the effectiveness of PD-1/PD-L1 inhibitors and sorafenib as first-line therapy. Individualized analysis and Kaplan-Meier were used to assess the prognostic value of TMB. Results A total of 29 studies with 5396 patients were included. ICIs’ combination therapy had higher ORR (26 % vs 15 %) and DCR (73 % vs 55 %), longer PFS (5.5 vs 3.1 months) and OS (15.9 vs 12.6 months) compared to monotherapy. Anti-PD-1/PD-L1 agents provided improved ORR, DCR, PFS and OS compared to sorafenib. The overall ORs of ORR and DCR in subgroup analysis were 3.49 (95 % CI 2.36–5.17, p < 0.01) and 1.60 (95 % CI 1.15–2.21, p < 0.01). The overall HRs of PFS and OS were 0.68 (95 % CI 0.48–0.96, p = 0.03) and 0.73 (95 % CI 0.62–0.85, p < 0.01). PD-1/PD-L1 inhibitors plus anti-VEGF agents had an advantage in DCR (0.80 vs 0.48, meta-regression = − 0.32, P < 0.001), but an equal ORR (0.29 vs 0.26) compared to dual immune checkpoint inhibitors. The total OS in Dua-ICIs were 16.5 months (95 % CI 14.2–18.7), yet not reached in the major studies of ICI plus anti-VEGF regimen. In individualized analysis, the 1-year OS was superior for patients who had high-TMB (>10, mutations/Mb) than moderate-TMB (1–10, mutations/Mb; 28 % vs 15 %, P = 0.025). Conclusion Immune checkpoint inhibitors’ combination therapy improved clinical outcomes in the management of advanced hepatocellular carcinoma. However, the overall objective response rate still did not exceed 30%. PD-1/PD-L1 inhibitors plus anti-angiogenic agents and dual immunotherapy provided significantly increased survival over sorafenib, which also pose new challenges for future research, and more appropriate and guided control regimens are required. Also, TMB may be a promising prognostic biomarker for immunotherapy in HCC. However, the validation of prospective and large sample studies is needed.Item Closing gaps in medication taking for secondary prevention of coronary heart disease patients among US adults(Elsevier, 2022-11-11) Liu, Xiaowei; Tang, Lijiang; Tang, Ying; Du, Changqing; Chen, Xiaofeng; Xu, Cheng; Yan, Jing; Radiation Oncology, School of MedicineBackground: The secondary preventive medical remedies used in the U.S. general population, particularly those with numerous co-morbidities, are poorly understood. We aimed to assess health outcomes and the extent of their adherence to guideline-based secondary prevention medications among U.S. coronary heart disease (CHD) patients. Methods: We analysed information from the U.S. National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 on people in the United States aged 18 to 85 who had a personal history of coronary heart disease (CHD). Logistic regression analyses were used to identify characteristics related to healthcare access that were linked with not taking any indicated drugs among CHD and other co-morbidity patients in the U.S. Results: We gathered 4256 CHD patients aged 18 and above. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), statins, and antiplatelet medications were taken by 50.94%, 48.26%, 53.41 %, and 19.78% of the population, respectively. Surprising, not received recommended drugs was reached up to 21.12%, and taking all four drugs was only 7.64%. In conclusion, the logistic regression analysis revealed that the chance of not taking prescribed drugs increased with age (18-39), race (Hispanic and Non-Hispanic Black), low income, lack of insurance, and the absence of co-morbidities (hypertension, heart failure, and diabetes mellitus). Conclusions: The gap between the proposed secondary preventative measures and their actual execution remains sizable. In order to achieve 'Healthy Aging', a systematic approach for prevention of CHD is urgently needed.Item Crucial Genes in Aortic Dissection Identified by Weighted Gene Coexpression Network Analysis(Hindawi, 2022-02-07) Zhang, Hongliang; Chen, Tingting; Zhang, Yunyan; Lin, Jiangbo; Zhao, Wenjun; Shi, Yangyang; Lau, Huichong; Zhang, Yang; Yang, Minjun; Xu, Cheng; Tang, Lijiang; Xu, Baohui; Jiang, Jianjun; Chen, Xiaofeng; Radiation Oncology, School of MedicineBackground: Aortic dissection (AD) is a lethal vascular disease with high mortality and morbidity. Though AD clinical pathology is well understood, its molecular mechanisms remain unclear. Specifically, gene expression profiling helps illustrate the potential mechanism of aortic dissection in terms of gene regulation and its modification by risk factors. This study was aimed at identifying the genes and molecular mechanisms in aortic dissection through bioinformatics analysis. Method: Nine patients with AD and 10 healthy controls were enrolled. The gene expression in peripheral mononuclear cells was profiled through next-generation RNA sequencing. Analyses including differential expressed gene (DEG) via DEGseq, weighted gene coexpression network (WGCNA), and VisANT were performed to identify crucial genes associated with AD. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was also utilized to analyze Gene Ontology (GO). Results: DEG analysis revealed that 1,113 genes were associated with AD. Of these, 812 genes were markedly reduced, whereas 301 genes were highly expressed, in AD patients. DEGs were rich in certain categories such as MHC class II receptor activity, MHC class II protein complex, and immune response genes. Gene coexpression networks via WGCNA identified 3 gene hub modules, with one positively and 2 negatively correlated with AD, respectively. Specifically, module 37 was the most strongly positively correlated with AD with a correlation coefficient of 0.72. Within module 37, five hub genes (AGFG1, MCEMP1, IRAK3, KCNE1, and CLEC4D) displayed high connectivity and may have clinical significance in the pathogenesis of AD. Conclusion: Our analysis provides the possible association of specific genes and gene modules for the involvement of the immune system in aortic dissection. AGFG1, MCEMP1, IRAK3, KCNE1, and CLEC4D in module M37 were highly connected and strongly linked with AD, suggesting that these genes may help understand the pathogenesis of aortic dissection.Item Efficacy and Failure Patterns of Early SBRT to the Primary Tumor in Advanced EGFR-Mutation-Positive Lung Cancer with EFGR-TKI Treatment: A Prospective, Single Arm, Phase II Study(MDPI, 2022-11-22) Shi, Yangyang; Xu, Hailing; Raynor, William Y.; Ding, Jiapei; Lin, Ling; Zhou, Chao; Wang, Wei; Meng, Yinnan; Wu, Xiaomai; Chen, Xiaofeng; Lv, Dongqing; Yang, Haihua; Radiation Oncology, School of MedicineEarly stereotactic body radiation therapy (SBRT) to the primary tumor combined with epidermal growth factor receptor tyrosine kinase inhibitor (EFGR-TKI) treatment may increase progression-free survival (PFS) by delaying resistance in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). In this prospective, single arm, phase II study, patients with advanced NSCLC were treated with EGFR-TKI (icotinib 125 mg tid or gefitinib 250 mg qd) for one month followed by SBRT (40-60 Gy/5-8 F/5-10 d) to the primary tumor with concurrent EGFR-TKI until disease progression. The primary endpoint was PFS and the patterns of failure. Overall survival (OS) and adverse effects (AEs) were secondary endpoints. Overall, 41 advanced NSCLC patients with EGFR mutations received treatment with 24.42 months of median follow-up time. On average, SBRT was initiated 1.49 months after EGFR-TKI administration. Tumors were found to have an average shrinkage rate of 42.50%. Median PFS was 15.23 months (95% CI 13.10-17.36), while median OS was 27.57 months (95% CI 23.05-32.09). Thirty-three patients were found to have disease progression, of which new site failure (NF) (22 patients, 66.66%) was the most common pattern, followed by original site failure (OF) (7 patients, 21.21%) and simultaneous OF/NF (ONF) (4 patients, 12.12%). There were no Aes equal to or greater than grade 3, with the most frequent AE being radiation pneumonitis. Therefore, administering therapy targeted at the primary tumor using early SBRT after EGFR-TKI initiation is a new potentially safe and effective approach to treat EGFR-mutant advanced NSCLC.Item Enhanced CT-Based Radiomics to Predict Micropapillary Pattern Within Lung Invasive Adenocarcinoma(Frontiers Media, 2021-08-27) Xu, Yunyu; Ji, Wenbin; Hou, Liqiao; Lin, Shuangxiang; Shi, Yangyang; Zhou, Chao; Meng, Yinnan; Wang, Wei; Chen, Xiaofeng; Wang, Meihao; Yang, Haihua; Radiation Oncology, School of MedicineObjective: We aimed to investigate whether enhanced CT-based radiomics can predict micropapillary pattern (MPP) of lung invasive adenocarcinoma (IAC) in the pre-op phase and to develop an individual diagnostic predictive model for MPP in IAC. Methods: 170 patients who underwent complete resection for pathologically confirmed lung IAC were included in our study. Of these 121 were used as a training cohort and the other 49 as a test cohort. Clinical features and enhanced CT images were collected and assessed. Quantitative CT analysis was performed based on feature types including first order, shape, gray-level co-occurrence matrix-based, gray-level size zone matrix-based, gray-level run length matrix-based, gray-level dependence matrix-based, neighboring gray tone difference matrix-based features and transform types including Log, wavelet and local binary pattern. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to value the ability to identify the lung IAC with MPP using these characteristics. Results: Using quantitative CT analysis, one thousand three hundred and seventeen radiomics features were deciphered from R (https://www.r-project.org/). Then these radiomic features were decreased to 14 features after dimension reduction using the least absolute shrinkage and selection operator (LASSO) method in R. After correlation analysis, 5 key features were obtained and used as signatures for predicting MPP within IAC. The individualized prediction model which included age, smoking, family tumor history and radiomics signature had better identification (AUC=0.739) in comparison with the model consisting only of radiomics features (AUC=0.722). DeLong test showed that the difference in AUC between the two models was statistically significant (P<0.01). Compared with the simple radiomics model, the more comprehensive individual prediction model has better prediction performance. Conclusion: The use of radiomics approach is of great value in the diagnosis of tumors by non-invasive means. The individualized prediction model in the study, when incorporated with age, smoking and radiomics signature, had effective predictive performance of lung IAC with MPP lesions. The combination of imaging features and clinical features can provide additional diagnostic value to identify the micropapillary pattern in IAC and can affect clinical diagnosis and treatment.Item Failure patterns of locoregional recurrence after reducing target volumes in patients with nasopharyngeal carcinoma receiving adaptive replanning during intensity-modulated radiotherapy: a single-center experience in China(Springer Nature, 2023-11-16) Zhou, Xiate; Zhu, Jian; Zhou, Chao; Wang, Wei; Ding, Weijun; Chen, Meng; Chen, Kuifei; Li, Shuling; Chen, Xiaofeng; Yang, Haihua; Radiation Oncology, School of MedicineBackground: Previous researches have demonstrated that adaptive replanning during intensity-modulated radiation therapy (IMRT) could enhance the prognosis of patients with nasopharyngeal carcinoma (NPC). However, the delineation of replanning target volumes remains unclear. This study aimed to evaluate the feasibility of reducing target volumes through adaptive replanning during IMRT by analyzing long-term survival outcomes and failure patterns of locoregional recurrence in NPC. Methods: This study enrolled consecutive NPC patients who received IMRT at our hospital between August 2011 and April 2018. Patients with initially diagnosed, histologically verified, non-metastatic nasopharyngeal cancer were eligible for participation in this study. The location and extent of locoregional recurrences were transferred to pretreatment planning computed tomography for dosimetry analysis. Results: Among 274 patients, 100 (36.5%) received IMRT without replanning and 174 (63.5%) received IMRT with replanning. Five-year rates of locoregional recurrence-free survival (LRFS) were 90.1% (95%CI, 84.8% to 95.4%) and 80.8% (95%CI, 72.0% to 89.6%) for patients with and without replanning, P = 0.045. There were 17 locoregional recurrences in 15 patients among patients with replanning, of which 1 (5.9%) was out-field and 16 (94.1%) were in-field. Among patients without replanning, 19 patients developed locoregional recurrences, of which 1 (5.3%) was out-field, 2 (10.5%) were marginal, and 16 (84.2%) were in-field. Conclusions: In-field failure inside the high dose area was the most common locoregional recurrent pattern for non-metastatic NPC. Adapting the target volumes and modifying the radiation dose prescribed to the area of tumor reduction during IMRT was feasible and would not cause additional recurrence in the shrunken area.Item Potential influencing factors of aortic diameter at specific segments in population with cardiovascular risk(BMC, 2022-02-05) Chen, Tingting; Yang, Xingan; Fang, Xiaoxin; Tang, Lijiang; Zhang, Yang; Weng, Yingzheng; Zhang, Hongliang; Wu, Juntao; Mao, Ping; Xu, Baohui; Jiang, Jianjun; Chen, Xiaofeng; Radiation Oncology, School of MedicineBackground: Aortic diameter is a critical parameter for the diagnosis of aortic dilated diseases. Aortic dilation has some common risk factors with cardiovascular diseases. This study aimed to investigate potential influence of traditional cardiovascular risk factors and the measures of subclinical atherosclerosis on aortic diameter of specific segments among adults. Methods: Four hundred and eight patients with cardiovascular risk factors were prospectively recruited in the observational study. Comprehensive transthoracic M-mode, 2-dimensional Doppler echocardiographic studies were performed using commercial and clinical diagnostic ultrasonography techniques. The aortic dimensions were assessed at different levels: (1) the annulus, (2) the mid-point of the sinuses of Valsalva, (3) the sinotubular junction, (4) the ascending aorta at the level of its largest diameter, (5) the transverse arch (including proximal arch, mid arch, distal arch), (6) the descending aorta posterior to the left atrium, and (7) the abdominal aorta just distal to the origin of the renal arteries. Multivariable linear regression analysis was used for evaluating aortic diameter-related risk factors, including common cardiovascular risk factors, co-morbidities, subclinical atherosclerosis, lipid profile, and hematological parameters. Results: Significant univariate relations were found between aortic diameter of different levels and most traditional cardiovascular risk factors. Carotid intima-media thickness was significantly correlated with diameter of descending and abdominal aorta. Multivariate linear regression showed potential effects of age, sex, body surface area and some other cardiovascular risk factors on aortic diameter enlargement. Among them, high-density lipoprotein cholesterol had a significantly positive effect on the diameter of ascending and abdominal aorta. Diastolic blood pressure was observed for the positive associations with diameters of five thoracic aortic segments, while systolic blood pressure was only independently related to mid arch diameter. Conclusion: Aortic segmental diameters were associated with diastolic blood pressure, high-density lipoprotein cholesterol, atherosclerosis diseases and other traditional cardiovascular risk factors, and some determinants still need to be clarified for a better understanding of aortic dilation diseases.Item The prognostic value of circulating lymphocyte counts and ABO blood group in lung cancer stereotactic body radiation therapy: a retrospective study(AME, 2022) Chen, Meng; Chen, Kuifei; Li, Shuling; Meng, Yinnan; Shi, Yangyang; Chen, Xiaofeng; Yang, Haihua; Radiation Oncology, School of MedicineBackground: Clinically, there is a lack of simple and feasible indicators to predict the efficacy of stereotactic body radiation therapy (SBRT). Circulating lymphocyte counts (CLCs) is considered to be related to curative effect in conventional radiotherapy of lung cancer, and blood groups are also associated with the survival. In this study, we investigate the prognostic value of CLCs and ABO blood groups in lung cancer patients treated with SBRT. Methods: We retrospectively analyzed 191 patients who were treated with lung cancer SBRT in Taizhou Hospital of Zhejiang Province from September 2014 to December 2018. The medical record system of Taizhou Hospital was used to collect relevant clinical data, such as stage, CLC, ABO blood groups and other important clinical co-variates. The effects of SBRT were evaluated by patient reexamination image data and telephone follow-up. The RECIST 1.1 standard was used to evaluate the short-term efficacy in the first, third, and sixth months after SBRT. Progression-free survival (PFS) was defined as the time from the day of SBRT to disease progression or death from any cause. Overall survival (OS) was measured from the day of SBRT until the last follow-up or death. Survival curves and univariate, multivariate logistic-regression analyses were used to expound the prognostic factors for local control (LC), PFS, and OS of lung cancer SBRT patients. Results: Univariate and multivariate analysis results showed that post-SBRT CLCs were independent factors for the short-term efficacy 3 and 6 months after lung cancer SBRT [hazard ratio (HR) =0.249, P=0.037; HR =0.347, P=0.012]. Survival analyses showed that the PFS and OS of lung cancer SBRT patients with A blood type was significantly shorter than that in the other three non-A blood groups (PFS: 6.5 vs. 10 months, HR =1.535, P=0.020; OS: 24 vs. 41 months, HR =1.578, P=0.048). Moreover, the patients with high post-SBRT CLCs in the non-A blood group had the longest PFS and OS after lung cancer SBRT (HR =0.551, P=0.043). Conclusions: Lung cancer SBRT patients with high-post-SBRT CLCs and non-A blood groups seem to exhibits best curative effect, which represent a potential opportunity to improve the clinical management of these patients. The mechanisms of this association deserve further verification and investigation.Item Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection(Frontiers Media, 2022-08-11) Xu, Cheng; Liu, Xiaowei; Fang, Xiaoxin; Yu, Lei; Lau, Hui Chong; Li, Danlei; Liu, Xiaoman; Li, Haili; Ren, Justin; Xu, Baohui; Jiang, Jianjun; Tang, Lijiang; Chen, Xiaofeng; Radiation Oncology, School of MedicinePurpose: This study aims to illustrate the cellular landscape in the aorta of experimental aortic dissection (AD) and elaborate on the smooth muscle cells (SMCs) heterogeneity and functions among various cell types. Methods: Male Apolipoprotein deficient (ApoE-/-) mice at 28 weeks of age were infused with Ang II (2,500 ng/kg/min) to induce AD. Aortas from euthanized mice were harvested after 7 days for 10×Genomics single-cell RNA sequencing (scRNA-seq), followed by the identification of cell types and differentially expressed genes (DEGs). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted. Results: AD was successfully induced in ApoE-/- mice. scRNA-seq identified 15 cell clusters and nine cell types, including non-immune cells (endothelials, fibroblasts, and SMCs) and immune cells (B cells, natural killer T cell, macrophages, dendritic cells, neutrophils, and mast cells). The relative numbers of SMCs were remarkably changed, and seven core DEGs (ACTA2,IL6,CTGF,BGN,ITGA8,THBS1, and CDH5) were identified in SMCs. Moreover, we found SMCs can differentiate into 8 different subtypes through single-cell trajectory analysis. Conclusion: scRNA-seq technology can successfully identify unique cell composition in experimental AD. To our knowledge, this is the first study that provided the complete cellular landscape in AD tissues from mice, seven core DEGs and eight subtypes of SMCs were identified, and the SMCs have evolution from matrix type to inflammatory type.Item Single-cell RNA Sequencing Technology Revealed the Pivotal Role of Fibroblast Heterogeneity in Ang II-Induced Abdominal Aortic Aneurysms(Research Square, 2021-11-02) Weng, Yingzheng; Lou, Jiangjie; Bao, Yizong; Cai, Changhong; Zhu, Kefu; Du, Changqing; Chen, Xiaofeng; Tang, Lijiang; Radiation Oncology, School of MedicineThe mechanism of abdominal aortic aneurysm (AAA) has not been fully elucidated. In this study, we aimed to map the cellular heterogeneity, molecular alteration, and functional transformation of angiotensin (Ang) II-induced AAA in mice based on single-cell RNA sequencing (sc-RNA seq) technology. sc-RNA seq was performed on suprarenal abdominal aorta tissue from male Apoe-/- C57BL/6 mice of Ang II-induced AAA and shame models to determine the heterogeneity and phenotypic transformation of all cells. Immunohistochemistry was used to determine the pathophysiological characteristics of AAA. The single-cell trajectory was performed to predict the differentiation of fibroblasts. Finally ligand-receptor analysis was used to evaluate intercellular communication between fibroblasts and smooth muscle cells (SMCs). More than 27,000 cells were isolated and 25 clusters representing 8 types of cells were identified, including fibroblasts, macrophages, endothelial cells, SMCs, T lymphocytes, B lymphocytes, granulocytes, and natural killer cells. During AAA progression, the function and phenotype of different type cells altered separately, including activation of inflammatory cells, alternations of macrophage polarization, phenotypic transformation of vascular smooth muscle cells, and endothelial to mesenchymal transformation. The alterations of fibroblasts were the most conspicuous. Single-cell trajectory revealed the critical reprogramming genes of fibroblasts mainly enriched in regulation of immune system. Finally, the ligand-receptor analysis confirmed that disorder of collagen metabolism led by fibroblasts was one of the most prominent characteristics of Ang II-induced AAA. Our study revealed the cellular heterogeneity of Ang II-induced AAA. Fibroblasts may play a critical role in Ang II-induced AAA progression according to multiple biological functions, including immune regulation and extracellular matrix metabolic balance. Our study may provide us with a different perspective on the etiology and pathogenesis of AAA.