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08 April 2020, Volume 47 Issue 4 Previous Issue    Next Issue

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Comparison of efficacy and safety of PD-1 inhibitor monotherapy and combined with chemotherapy/targeted therapy in advanced malignant tumors Hou Lina, Dina Suolitiken, Guo Zhi, Chen Xiao, Ren Hua 2020, 47 (4):  193-198.  doi: 10.3760/cma.j.cn371439-20190731-00001 Abstract ( 1160 )   HTML ( 62 )   PDF (879KB) ( 395 )   Save Objective To compare the efficacy and safety of programmed death-1 (PD-1) inhibitors monotherapy and combined with chemotherapy/targeted therapy in the treatment of advanced malignant tumors. Methods The clinical data of 52 patients with advanced malignant tumors treated with PD-1 inhibitors from January 2017 to August 2018 in Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were analyzed. All the patients were divided into monotherapy group (n=23) and combined therapy group (n=29) according to the therapeutic regimen. The monotherapy group received only PD-1 inhibitors and the combined therapy group received PD-1 inhibitors combined with chemotherapy/targeted therapy. The therapeutic effects and adverse reactions of the two groups were compared. Results Of the 52 patients, 38 were evaluated according to the imaging results, including 15 in the monotherapy group and 23 in the combined therapy group. The overall response rates of the monotherapy group and combined therapy group were 33.33% (5/15) and 34.78% (8/23) respectively, with no significant difference (P=0.604). The disease control rates of the monotherapy group and combined therapy group were 80.00% (12/15) and 73.91% (17/23), with no significant difference (P=0.490). The median overall survival (OS) of the monotherapy group was 6.0 months, and that of the combined therapy group was 5.0 months, with no significant difference (χ 2=0.790, P=0.374). The median progression-free survival (PFS) of the monotherapy group was 6.0 months, and that of the combined therapy group was 5.0 months, with no significant difference (χ 2=0.371, P=0.542). The incidence of abdominal pain and diarrhea was lower in the monotherapy group [grade 1-2: 8.7% (2/23), grade 3 and above: 0] than that in the combined therapy group [grade 1-2: 27.59% (8/29), grade 3 and above: 6.90% (2/29); Z=2.211, P=0.027]. There were no significant differences in the incidence of bone marrow suppression, nausea and vomiting, rash, liver and kidney function impairment or treatment-related pneumonia between the two groups (all P>0.05). Conclusion For patients with advanced malignant tumors, there is no significant difference in OS and PFS whether PD-1 inhibitors are taken separately or together, but the incidence of abdominal pain and diarrhea in patients treated with PD-1 inhibitors alone is lower than that in patients treated with combined therapy. Figures and Tables | References | Related Articles | Metrics

Level of peripheral blood circulating tumor cells in lung cancer patients detected by CI-101 and its clinical significance Tian Linghan, Zhu Ling, Liu Xin, Ye Jingwen, He Jiahui, Wang Xicai 2020, 47 (4):  199-204.  doi: 10.3760/cma.j.cn371439-20200116-00002 Abstract ( 777 )   HTML ( 29 )   PDF (856KB) ( 275 )   Save Objective To explore the correlations between circulating tumor cells (CTCs) level in peripheral venous blood and clinicopathological characteristics and biomarkers of lung cancer patients using CI-101 cell search immunomagnetic bead enrichment technology combined with fluorescent cytochemical staining. Methods Blood samples were collected from 100 patients with first-diagnosed lung cancer treated in Department of Thoracic Surgery and Department of Cardiothoracic Surgery of Yunnan Cancer Hospital from March 2014 to September 2014, 40 patients with lung benign tumor (all confirmed by pathological biopsy) and 30 healthy volunteers from the physical examination center. CTCs in peripheral blood were enriched by CI-101 cell search immunomagnetic bead, the morphology of CTCs was analyzed by immunocytofluorescence technique, and tumor cells were identified using HE cell staining method. The recovery rate, sensitivity and specificity of CI-101 cell search instrument for CTCs were detected. The difference of positive rate of CTCs in peripheral blood among lung cancer patients, lung benign tumor patients and healthy volunteers was compared. The relationship between the positive rate of CTCs and the clinicopathological characteristics of patients with lung cancer was analyzed. The correlations between CTCs and serum tumor markers were analyzed by coefficient of contingency in patients with lung cancer and lung benign tumor. Results The recovery rate of CTCs by CI-101 cell search instrument was 72.0%-89.0%, and there was a significant linear correlation between the number of recovered cells and the number of incorporated cells. The correlation coefficient r=0.998 (P<0.001), the linear regression equation was y=0.781x+11.307, the sensitivity was 85.0%, and the specificity was 71.4%. The positive rate of CTCs in lung cancer patients (85.0%, 85/100) was higher than that in lung benign tumor patients (15.0%, 6/40) and healthy volunteers (46.7%, 14/30) (χ 2=62.798, P<0.001). The positive rate of CTCs in lung cancer patients was correlated with TNM stage (χ 2=19.059, P<0.001), tumor size (χ 2=13.830, P<0.001) and distant metastasis (χ 2=6.005, P=0.014). Coefficient of contingency analysis showed that the positive of CTCs was positively correlated with serum tumor markers CEA (φ=0.217, P=0.011), CA125 (φ=0.198, P=0.020), CA199 (φ=0.169, P=0.049), CA742 (φ=0.186, P=0.037) and cytokeratin 19 fragment (φ=0.461, P<0.001) in patients with lung cancer and lung benign tumor. Conclusion The application of CI-101 cell search instrument combined with immunomagnetic bead method can successfully enrich CTCs in peripheral venous blood of lung cancer patients. The positive rate of CTCs in patients with lung cancer has obvious correlation with tumor size, TNM stage, distant metastasis, serum tumor markers. It can be used as an auxiliary indicator for monitoring the condition of lung cancer patients. Figures and Tables | References | Related Articles | Metrics

Prognostic value of TCBI in middle-aged and elderly patients with thoracic esophageal squamous cell carcinoma receiving radiotherapy Jiang Tingting, Xu Xiaoting, Qin Songbing, Ma Chenying, Zhou Juying 2020, 47 (4):  205-210.  doi: 10.3760/cma.j.cn371439-20191210-00003 Abstract ( 615 )   HTML ( 24 )   PDF (874KB) ( 255 )   Save Objective To investigate the prognostic value of TCBI in middle-aged and elderly patients with thoracic esophageal squamous cell carcinoma (ESCC) who received radiotherapy. Methods The clinical data of 191 patients with thoracic ESCC who underwent radiotherapy in the department of Radiation Oncology of the First Affiliated Hospital of Soochow University from January 2010 to December 2015 were retrospectively analyzed. According to the TCBI value on admission [TCBI=serum triglyceride (mg/dl) × total cholesterol (mg/dl) × body weight (kg)/1 000], patients were divided into TCBI low-value group (n=79) and TCBI high-value group (n=112). The relationships between TCBI and clinicopathological characteristics of patients were analyzed. The Kaplan-Meier method was used to calculate the overall survival (OS). The log-rank test was adopted to compare the differences in survival between different groups. The Cox proportional hazard model was used to analyze the factors affecting the prognosis of middle-aged and elderly patients with thoracic ESCC. The receiver operating characteristics (ROC) curve was applied to verify the accuracy of TCBI for survival prediction. Results The mean pre-radiotherapy TCBI was 1 082±945 in all patients. The cutoff value of the TCBI was 749. The patients with TCBI<749 served as the TCBI low-value group , and patients with TCBI≥749 served as the TCBI high-value group. TCBI was associated with treatment (χ 2=4.235, P=0.040) and geriatric nutritional risk index (GNRI, χ 2=8.795, P=0.003). Univariate analysis suggested that male (HR=2.220, 95%CI: 1.223-4.030, P=0.009), stage N1-3 (HR=1.453, 95%CI: 1.023-2.065, P=0.037), GNRI<98 (HR=1.949, 95%CI: 1.168-3.255, P=0.011) and TCBI<749 (HR=1.846, 95% CI: 1.298-2.627, P=0.001) were risk factors affecting OS in middle-aged and elderly patients with thoracic ESCC. Besides, postoperative adjuvant radiotherapy (HR=0.641, 95%CI: 0.449-0.915, P=0.014) was a protective factor. Furthermore, multivariate analysis showed that male (HR=2.147, 95%CI: 1.173-3.929, P=0.013) and TCBI<749 (HR=1.664, 95%CI: 1.166-2.376, P=0.005) were independent risk factors for OS. Besides, postoperative adjuvant radiotherapy (HR=0.630, 95%CI: 0.439-0.903, P=0.012) was an independent protective factor. The area under the curve calculated by the ROC curve was 0.619, the sensitivity was 0.742, and the specificity was 0.496 (P=0.007), confirming the role of TCBI in the prognostic evaluation. Survival analysis showed that the median OS of patients in the TCBI high-value group was 42 months, and the 1-year and 3-year survival rates were 86.6% and 52.7%, significantly higher than those in the TCBI low-value group (20 months, 68.4% and 29.1% respectively; χ 2=12.286, P<0.001). Subgroup analysis showed that among patients with radical radiotherapy, 3-year survival rate in patients with lower TCBI (n=37) was lower than that in patients with higher values (n=36) (21.6% vs. 44.4%, χ 2=8.505, P=0.004). Conclusion TCBI is a predictor of OS for middle-aged and elderly patients with thoracic ESCC who received radiotherapy. The lower the TCBI, the poorer the survival prognosis. Figures and Tables | References | Related Articles | Metrics

Screening differential genes and prognostic analysis of gastric cancer based on TCGA database Zou Wenjing, He Shuixiang, Liu Dan, Li Xu 2020, 47 (4):  211-216.  doi: 10.3760/cma.j.cn371439-20190923-00004 Abstract ( 785 )   HTML ( 30 )   PDF (3807KB) ( 488 )   Save Objective To extract the genes associated with prognosis from the differential expressed genes in gastric cancer tissues by using a large number of gastric cancer genome data in the cancer genome atlas (TCGA) database. Methods Gene expression data of gastric adenocarcinoma were downloaded from TCGA database. After R language data preprocessing, edgeR was used to analyze the gene differential expression, and R language was used to identify the significant gene ontology (GO) terms and KEGG pathways in gene differential expression. Multivariate Cox stepwise regression analysis was used to predict the genes that affected survival. Genes obtained above were used for survival analysis online in Kaplan-Meier Plotter website (http://Kaplan-Meier Plotter.com). Results A total of 305 gastric cancer and 30 normal gastric tissues were retrieved in TCGA database, and 3 231 differential genes were screened out, including 2 005 up-regulated genes and 1 226 down-regulated genes. These genes were enriched in GO terms including antigen binding, serine hydrolase activity, receptor ligands activity, serine peptidase activity, serine type endopeptidase activity, glycosaminoglycans binding, cytokine activity, hormone activity, peptidase inhibitor activity, metallopeptidase activity and so on. The genes in KEGG pathway analysis were enriched in chemical carcinogen, neuractive receptor-ligand interaction, cytokine-cytokine receptor interaction, metabolism of xenobiotics by cytochrome P450, protein digestion and absorption, staphylococcus aureus infection, retinol metabolism, drug metabolism P450, steroid hormone metabolism, pancreatic secretion and so on. Cox analysis showed that GPX3 and SERPINE1 had significant effect on the survival of gastric cancer patients. Receiver operating characteristic curve analysis showed that the expressions of GPX3 and SERPINE1 had a certain predictive value for the survival time of gastric cancer patients, when the critical values of GPX3 and SERPINE1 were 0.46 and 0.68 respectively, the sensitivity was 60.35%, the specificity was 82.06%, and the area under the curve was 0.763 (95%CI: 0.828-0.936). Kaplan-Meier analysis showed that the high expressions of GPX3 (P<0.001) and SERPINE1 (P=0.001) were significantly related to the poor prognosis of gastric adenocarcinoma. Conclusion The higher expression of SERPINE1 and GPX3 genes, the shorter survival time of gastric cancer patients. They may be the targets for predicting the prognosis of gastric cancer. Figures and Tables | References | Related Articles | Metrics

Expressions of SIRT6 and survivin in gastric cancer tissue and their clinical significances Wang Ying, Yang Wei, Xiao Juxiang 2020, 47 (4):  217-222.  doi: 10.3760/cma.j.cn371439-20191230-00005 Abstract ( 516 )   HTML ( 19 )   PDF (2072KB) ( 257 )   Save Objective To discuss the relationships between the expressions of silence information regulator 6 (SIRT6) and survivin and clinicopathological features of gastric cancer, and to investigate their effects in gastric cancer. Methods The tumor tissues of 110 gastric cancer patients admitted to the First Affiliated Hospital of Xi'an Jiaotong University from March 2013 to October 2014, as well as 40 adjacent tissues and 20 normal tissues, were selected to detect the expressions of SIRT6 and survivin by immunohistochemistry. The correlations between the expression levels of SIRT6 and survivin and the clinicopathological features and prognosis of gastric cancer patients were analyzed. Results The positive rates of SIRT6 were 41.8% (46/110), 77.5% (31/40) and 85.0% (17/20) in gastric cancer, adjacent tissues and normal gastric tissues, respectively, and the difference among the three groups was statistically significant (χ 2=23.200, P<0.001). The positive rate of SIRT6 in gastric cancer tissue was lower than that in adjacent and normal tissues (χ 2=14.949, P<0.001; χ 2=12.634, P<0.001). The expression of SIRT6 was correlated with tumor differentiation (χ 2=19.654, P<0.001). The positive rates of survivin were 58.2% (64/110), 15.0% (6/40) and 0 (0/20) in gastric cancer, adjacent tissues and normal gastric tissues, respectively, and the difference among the three groups was statistically significant (χ 2=38.449, P<0.001). The positive rate of survivin in gastric cancer tissue was higher than that in adjacent and normal tissues (χ 2=21.976, P<0.001; χ 2=22.920, P<0.001). The expression of survivin was correlated with the depth of infiltration (χ 2=20.853, P<0.001). The expression of SIRT6 was correlated with survivin in gastric cancer tissues (C=0.211, P=0.024). Survival analysis showed that 3-year survival rate was 53.1% in the SIRT6 negative patients, lower than 78.3% in the positive patients, and the difference was statistically significant (χ 2=4.004, P=0.045), while the 3-year survival rates of the survivin positive and negative patients were 53.1% and 78.3%, and the difference was not significant (χ 2=3.717, P=0.054). Cox multivariate regression analysis showed that lymph node metastasis (RR=6.618, 95%CI: 2.152-20.358, P=0.001) and SIRT6 negative expression (RR=0.228, 95%CI: 0.081-0.644, P=0.005) were the risk factors for poor prognosis of gastric cancer. Conclusion SIRT6 is poorly expressed in gastric cancer tissues and is related to the prognosis of gastric cancer, while survivin is highly expressed in gastric cancer tissues. The expression of SIRT6 and survivin is negatively correlated, suggesting that the expression imbalance of SIRT6 and survivin may play an important role in the occurrence and development of gastric cancer. Figures and Tables | References | Related Articles | Metrics

Reviews

Relationship between circular RNA and cancer drug resistance Yuan Shuang, Sun Xiao, Wang Lihua 2020, 47 (4):  223-226.  doi: 10.3760/cma.j.cn371439-20191031-00006 Abstract ( 645 )   HTML ( 20 )   PDF (628KB) ( 286 )   Save Circular RNA is a member of the non-coding RNA family and can participate in biological functions in many ways, such as cell proliferation, cell cycle, invasion and metastasis. Recent studies have shown that circular RNA can be involved in post transcriptional regulation by sponge miRNA and RNA binding proteins. Thus, it can affect DNA repair, apoptosis, proliferation, cell transport, and intracellular enzymes those mediate drug resistance, so as to play an important regulatory role in drug resistance. Moreover, it has been confirmed that interfering with the expression of circular RNA can improve the sensitivity of cancer to drugs, suggesting that circular RNA may provide a new target for the study of drug resistance of cancer. References | Related Articles | Metrics

Treatment of local recurrenct nasopharyngeal carcinoma after radiotherapy Shen Jianjun 2020, 47 (4):  227-230.  doi: 10.3760/cma.j.cn371439-20190926-00007 Abstract ( 696 )   HTML ( 15 )   PDF (631KB) ( 308 )   Save The local control rate of nasopharyngeal carcinoma in the period of accurate intensity modulated radiotherapy is very high. Only 10% to 20% of the patients will have local or lymph node recurrence after the first radiotherapy. Locally recurrent nasopharyngeal carcinoma is still potentially curable. However, the retreatment of locally recurrent nasopharyngeal carcinoma needs to be optimized. According to the latest clinical research evidence, we explore the recurrence pattern of nasopharyngeal carcinoma and the choice of treatment of locally recurrent nasopharyngeal carcinoma. References | Related Articles | Metrics

Progress of medical treatment for thyroid cancer Wang Jiale, Cao Jun 2020, 47 (4):  231-235.  doi: 10.3760/cma.j.cn371439-20200224-00008 Abstract ( 595 )   HTML ( 18 )   PDF (639KB) ( 290 )   Save Thyroid cancer is a common malignant tumor of the head and neck and endocrine system, characterized by high morbidity and low mortality. The main clinical challenge is the treatment of patients with advanced or high-risk thyroid cancer. At present, the study on the molecular pathogenesis of thyroid cancer provide new opportunities for thyroid cancer, including chemotherapy, molecular targeted therapy and immunotherapy. References | Related Articles | Metrics

Radiosensitivity markers of non-small cell lung cancer Li Guanglie, Yan Ying 2020, 47 (4):  236-239.  doi: 10.3760/cma.j.cn371439-20190923-00009 Abstract ( 555 )   HTML ( 13 )   PDF (631KB) ( 259 )   Save Radiotherapy is one of the important local treatments for patients with non-small cell lung cancer. However, radiotherapy is often the biggest obstacle to the curative effect and the main cause of treatment failure. Looking for radiosensitivity markers is of great significance to discover specific resistance mechanism, improve efficacy and prognosis, and provide ideas and basis for radiosensitization treatment of non-small cell lung cancer. References | Related Articles | Metrics

Postoperative adjuvant targeted therapy for non-small cell lung cancer Tang Wenjie, Xie Peng 2020, 47 (4):  240-243.  doi: 10.3760/cma.j.cn371439-20191105-00010 Abstract ( 916 )   HTML ( 17 )   PDF (630KB) ( 326 )   Save As one of the main methods of postoperative adjuvant therapy for non-small cell lung cancer (NSCLC) patients, the clinical effect of platinum-containing dual-drug chemotherapy has reached a ceiling effect and it is difficult to further improve the survival of patients with NSCLC. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have become the standard first-line treatment for advanced NSCLC with EGFR mutation, but its value as postoperative adjuvant therapy is far to be investigated. Some studies have been carried out in this field in recent years. References | Related Articles | Metrics

Application of neoadjuvant therapy in the treatment of esophageal cancer Bu Qian, Huang Junxing 2020, 47 (4):  244-248.  doi: 10.3760/cma.j.cn371439-20190929-00011 Abstract ( 535 )   HTML ( 15 )   PDF (643KB) ( 279 )   Save Neoadjuvant therapy combined with surgery is a very promising clinical treatment strategy for esophageal cancer. Combined with its effectiveness and safety, neoadjuvant radiotherapy can be used as a treatment method for severe esophageal cancer and unresectable esophageal cancer. Neoadjuvant chemotherapy has a higher value in the treatment of adenocarcinoma. Neoadjuvant cheoradiotherapy can be used as the recommended treatment scheme for patients with squamous cancer. References | Related Articles | Metrics

The role of inflammatory cytokines in chemoresistance of epithelial ovarian cancer Yang Yiting, Cheng Zhongping 2020, 47 (4):  249-251.  doi: 10.3760/cma.j.cn371439-20191010-00012 Abstract ( 470 )   HTML ( 11 )   PDF (624KB) ( 309 )   Save Ovarian cancer is a common fatal malignant tumor in women. The most common pathological type is epithelial ovarian cancer (EOC) originating from the ovary or fallopian tube epithelium, accounting for 85%-90%. The standard treatment for EOC is tumor cytoreductive surgery. Postoperative platinum/paclitaxel chemotherapy, cell chemoresistance has become an important cause of recurrence and death in EOC patients. At present, many scholars believe that the tumor environment of ovarian cancer is rich in a broad spectrum of tumor pro-inflammatory cytokines and chemokines. Inflammation can increase the division and differentiation of epithelial cells. The long-term exposure of normal epithelial tissues to the inflammatory environment will gradually turn to malignant transformation. The inflammatory tumor microenvironment promotes the invasion and metastasis of transformed malignant tumor cells, and eventually develops drug resistance. References | Related Articles | Metrics