Survival data were widely used in oncology clinical trials. The methods used, such as the log-rank test and Cox regression model, should meet the assumption of proportional hazards. However, the survival data with non-proportional hazard (NPH) are also quite usual, which will decrease the power of these methods and conceal the true treatment effect. Therefore, during the trial design, we need to test the proportional hazard assumption and plan different analysis methods for different testing results. This paper introduces some methods that are widely used for proportional hazard testing, and summarizes the application condition, advantages and disadvantages of analysis methods for non-proportional hazard survival data. When the non-proportional hazard occurs, we need to choose the suitable method case by case and to be cautious in the interpretation of the results.
ObjectiveTo investigate the expression and clinical significance of cytochromes b561 (CYB561) in hepatocellular carcinoma (HCC). MethodsThe expression of CYB561 mRNA in HCC tissues and its relationship with prognosis were analyzed by database data. Immunohistochemistry (IHC) was used to detect the expression of CYB561 protein in 61 matched HCC tissues and their adjacent tissues, and the relationship between CYB561 protein expression and clinicopathological features and prognosis of HCC was analyzed. Kaplan-Meier method was used to draw the survival curve and Cox proportional hazard regression model was used to analyze the correlation between the expression of CYB561 protein and the prognosis of HCC. ResultsThe analysis of database data showed that the relative expression of CYB561 mRNA in HCC tissues was higher than that in adjacent tissues (P<0.001). Compared with HCC patients with negative expression of CYB561 mRNA, HCC patients with positive expression of CYB561 mRNA had worse overall survival (OS), relapse-free survival, progression-free survival and disease-free survival (all P<0.05). The results of IHC showed that the positive rates of CYB561 protein in HCC tissues and adjacent tissues were 57.38% (35/61) and 21.31%(13/61), respectively. The former was higher than the latter, with statistical significance (χ2=16.624, P<0.001). Survival analysis showed that the OS of patients with positive expression of CYB561 protein was worse than that of patients with negative expression (P<0.05). Multivariate Cox proportional hazard regression analysis showed that the positive expression of CYB561 protein was a risk factor for postoperative OS in HCC patients [HR=3.308, 95%CI (1.344, 8.144), P=0.009]. ConclusionCYB561 is positively expressed in HCC and suggests a worse survival, and may serve as a potential prognostic biomarker for HCC.
ObjectiveTo investigate the clinical characteristics and prognosis of resectable esophageal small cell carcinoma after surgical resection.MethodsA retrospective study of patients with resectable esophageal small cell carcinoma undergoing surgical resection from January 2009 to June 2015 in the Department of Thoracic Surgery, Sichuan Provincial Fourth People's Hospital and Department of Thoracic Surgery, West China Hospital of Sichuan University was performed. Survival analysis was conducted by Kaplan-Meier analysis and log-rank test. Cox regression model was used for identifying independent prognostic factors.ResultsA total of 53 patients with resectable esophageal small cell carcinoma were included for analysis. The mean age was 58.4 ± 8.3 years and there were 42 male patients and 11 female patients. Forty-two patients were diagnosed as pure esophageal small cell carcinoma while 11 patients were diagnosed with mixed esophageal small cell carcinoma, who were all mixed with squamous cell carcinoma. Most of the esophageal small cell carcinomas were located in the middle (58.5%) and lower (32.1%) segments of the esophagus. Thirty patients (56.6%) were found to have lymph node metastasis, and 7 patients (13.2%) were found to have lymphovascular invasion. According to the 2009 TNM staging criteria for esophageal squamous cell carcinoma, there were 12 patients with stage Ⅰ disease, 19 patients with stage Ⅱ disease, and 22 patients with stage Ⅲ disease. Most of the patients underwent left thoracotomy with two-field lymphadenectomy. Postoperatively, only twenty-two patients (41.5%) received adjuvant chemoradiotherapy. The median survival time of these patients was 20.1 months, and the 1- and 3-year survival rate was 75.5% and 33.1%, respectively. For prognosis, age, gender, pathological type, tumor location, and lymphovascular invasion had no significant impact on long-term survival of these patients. However, TNM stage (1 year survival rate: stage Ⅰ: 91.7%; stage Ⅱ: 78.9%; stage Ⅲ: 63.6%; P=0.004) and postoperative adjuvant therapy (1 year survival rate: 81.8% vs. 71.0%; P=0.005) had significant impact on the survival of patients with esophageal small cell carcinoma. In multivariate analysis, TNM stage and postoperative adjuvant therapy were independent prognostic factors for long-term prognosis of patients with esophageal small cell carcinoma.ConclusionEsophageal small cell carcinoma is very rare, with high malignancy and poor prognosis. For patients with resectable esophageal small cell carcinoma, the TNM staging system of esophageal squamous cell carcinoma can be used to direct the choice of treatment options. For early stage esophageal small cell carcinoma (stage Ⅰ/Ⅱ), surgery plus postoperative adjuvant chemoradiotherapy can be the prior therapeutic choice, while for locally advanced esophageal small cell carcinoma (stage Ⅲ), chemoradiotherapy should be the preferred treatment.
ObjectiveTo investigate the expression and clinical significance of HOXB7 mRNA and protein in colorectal cancer (CRC) tissues.MethodsThe expressions of HOXB7 mRNA were evaluated in 6 cases of adjacent colorectal mucosal (ACRM) tissues and 6 cases of CRC tissues by using RT-PCR. The HOXB7 protein expressions were evaluated in 30 cases of ACRM tissues and 98 cases of CRC tissues by using immunohistochemistry. The correlations between the expression of HOXB7 protein, and the clinicopathologic factors or the patient’ survival were analyzed.ResultsRT-PCR results showed that expression level of HOXB7 mRNA in CRC tissues was significantly higher than that of ACRM tissues (P=0.003). Immunohistochemistry results showed that significantly higher positive-expression rate of HOXB7 protein in CRC tissues compared with ACRM tissues (P<0.05). Positive expression of HOXB7 protein was associated with depth of tumor invasion, lymph node metastasis, and the TNM stage (P<0.05). Kaplan-Meier survival curves showed that positive expression of HOXB7 protein was not inversely correlated with survival of CRC patients (P=0.865).ConclusionPositive expression of HOXB7 protein is a novel biomarker for estimating the progression of CRC, but remains of textual research may be to confirm the significance of HOXB7 protein for prognosis evaluation.
ObjectiveTo investigate the prognostic value of preoperative serum albumin-to-globulin ratio (AGR) and neutrophil-lymphocyte ratio (NLR) in the overall survival (OS) of patients with esophageal squamous cell carcinoma (ESCC), and to establish an individualized nomogram model and evaluate its efficacy, in order to provide a possible evaluation basis for the clinical treatment and postoperative follow-up of ESCC patients. MethodsAGR, NLR, clinicopathological and follow-up data of ESCC patients diagnosed via pathology in the Department of Thoracic Surgery, The First Affiliated Hospital of Xinjiang Medical University from 2010 to 2017 were collected. The correlation between NLR/AGR and clinicopathological data were analyzed. Kaplan-Meier analysis and log-rank test were used for survival analysis. The optimal cut-off values of AGR and NLR were determined by X-tile software, and the patients were accordingly divided into a high-level group and a low-level group. At the same time, univariate and multivariate Cox regression analyses were used to identify independent risk factors affecting OS in the ESCC patients, and a nomogram prediction model was constructed and internally verified. The diagnostic efficacy of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve, and the clinical application value was evaluated by decision curve analysis. ResultsA total of 150 patients were included in this study, including 105 males and 45 females with a mean age of 62.3±9.3 years, and the follow-up time was 1-5 years. The 5-year OS rate of patients in the high-level AGR group was significantly higher than that in the low-level group (χ2=6.339, P=0.012), and the median OS of the two groups was 25 months and 12.5 months, respectively. The 5-year OS rate of patients in the high-level NLR group was significantly lower than that in the low-level NLR group (χ2=5.603, P=0.018), and the median OS of the two groups was 18 months and 39 months, respectively. Multivariate Cox analysis showed that AGR, NLR, T stage, lymph node metastasis, N stage, and differentiation were independent risk factors for the OS of ESCC patients. The C-index of the nomogram model was 0.689 [95%CI (0.640, 0.740)] after internal validation. The area under the ROC curve of predicting 1-, 3-, and 5-year OS rate was 0.773, 0.724 and 0.725, respectively. At the same time, the calibration curve and the decision curve suggest that the model had certain efficacy in predicting survival and prognosis. ConclusionPreoperative AGR and NLR are independent risk factors for ESCC patients. High level of AGR and low level of NLR may be associated with longer OS in the patients; the nomogram model based on AGR, NLR and clinicopathological features may be used as a method to predict the survival and prognosis of ESCC patients, which is expected to provide a reference for the development of personalized treatment for patients.
ObjectiveTo provide clinical reference for the perioperative management of esophageal cancer patients with different stages of chronic obstructive pulmonary disease (COPD) through investigating the impact of COPD on postoperative complications and survival in esophageal cancer patients undergoing oesophagectomy.MethodsThe clinical data of 163 patients who underwent radical resection of esophageal cancer in our department from January 2015 to January 2018 were retrospectively analyzed, including 124 males and 39 females, with a median age of 64 years (IQR: 23.8 years). They were divided into a COPD group (n=87) and a non-COPD group (n=76) according to the presence of COPD before operation. The clinical data were collected and the postoperative complications and 2-year survival between the two groups were compared and analyzed.ResultsThe incidence of major postoperative complications (pulmonary infection, respiratory failure, arrhythmia and anastomotic leakage) in the COPD group were higher than those in the non-COPD group (all P<0.05). Spearman correlation analysis showed that the severity of preoperative COPD was positively correlated with the incidence of postoperative complications in patients with esophageal cancer (r=0.437, P<0.001). The incidence of postoperative respiratory failure and mortality in patients with severe COPD were significantly higher than those in patients without COPD and those with mild or moderate COPD. The 2-year survival rate of patients with esophageal cancer in the COPD group was lower than that in the non-COPD group (56.1% vs. 78.5.%, P=0.001), and the severity of COPD was negatively correlated to the survival rate.ConclusionCOPD significantly increases the incidence of postoperative complications in patients with esophageal cancer, which is not conducive to the prognosis of patients, and the severity of COPD is correlated with postoperative complications and 2-year survival rate.
ObjectiveTo analyze the relevant risk factors affecting postoperative relapse-free survival (RFS) in the primary gastrointestinal stromal tumors (GIST) and develop a Nomogram predictive model of postoperative RFS for the GIST patients. MethodsThe patients diagnosed with GIST by postoperative pathology from January 2011 to December 2020 at the First Hospital of Lanzhou University and Gansu Provincial People’s Hospital were collected, and then were randomly divided into a training set and a validation set at a ratio of 7∶3 using R software function. The univariate and multivariate Cox regression analysis were used to identify the risk factors affecting the RFS for the GIST patients after surgery, and then based on this, the Nomogram predictive model was constructed to predict the probability of RFS at 3- and 5-year after surgery for the patients with GIST. The effectiveness of the Nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), consistency index (C-index), and calibration curve, and the clinical utility of the Nomogram and the modified National Institutes of Health (M-NIH) classification standard was evaluated using the decision curve analysis (DCA). ResultsA total of 454 patients were included, including 317 in the training set and 137 in the validation set. The results of multivariate Cox regression analysis showed that the tumor location, tumor size, differentiation degree, American Joint Committee onCancer TNM stage, mitotic rate, CD34 expression, treatment method, number of lymph node detection, and targeted drug treatment time were the influencing factors of postoperative RFS for the GIST patients (P<0.05). The Nomogram predictive model was constructed based on the influencing factors. The C-index of the Nomogram in the training set and validation set were 0.731 [95%CI (0.679, 0.783)] and 0.685 [95%CI (0.647, 0.722)], respectively. The AUC (95%CI) of distinguishing the RFS at 3- and 5-year after surgery were 0.764 (0.681, 0.846) and 0.724 (0.661, 0.787) in the training set and 0.749 (0.625, 0.872) and 0.739 (0.647, 0.832) in the validation set, respectively. The calibration curve results showed that a good consistency of the 3-year and 5-year recurrence free survival rates between the predicted results and the actual results in the training set, while which was slightly poor in the validation set. There was a higher net benefit for the 3-year recurrence free survival rate after GIST surgery when the threshold probability range was 0.19 to 0.57. When the threshold probability range was 0.44 to 0.83, there was a higher net benefit for the 5-year recurrence free survival rate after GIST surgery. And within the threshold probability ranges, the net benefit of the Nomogram was better than the M-NIH classification system at the corresponding threshold probability. ConclusionsThe results of this study suggest that the patients with GIST located in the other sites (mainly including the esophagus, duodenum, and retroperitoneum), with tumor size greater than 5 cm, poor or undifferentiated differentiation, mitotic rate lower than 5/50 HPF, negative CD34 expression, ablation treatment, number of lymph nodes detected more than 4, and targeted drug treatment time less than 3 months need to closely pay attentions to the postoperative recurrence. The discrimination and clinical applicability of the Nomogram predictive model are good.
Objective To investigate the prognostic differences and decision-making role in postoperative radiotherapy of four molecular subtypes in pT1-2N1M0 stage breast cancer. Methods The clinicopathological data of 1526 patients with pT1-2N1M0 breast cancer treated at West China Hospital of Sichuan University between 2008 and 2018 were retrospectively analyzed. χ2 test was used to compare the clinicopathological features among patients with different molecular subtypes. Kaplan-Meier survival analysis and log-rank test were used to draw the survival curves and compare the overall survival (OS) and breast cancer-specific survival (BCSS) among patients with different molecular subtypes. Cox regression model was used to determine the influencing factors of OS of patients after radical mastectomy. Results Among the 1526 patients with pT1-2N1M0 breast cancer, there were 674 cases (44.2%) of Luminal A subtype, 530 cases (34.7%) of Luminal B subtype, 174 cases (11.4%) of human epidermal growth factor receptor 2 (Her-2) overexpression subtype, and 148 cases (9.7%) of triple-negative subtype. The 5-year OS rates of Luminal A, Luminal B, Her-2 overexpression and triple negative patients were 98.6%, 94.3%, 95.5% and 91.2%, respectively (χ2=11.712, P=0.001), and the 5-year BCSS rates were 99.3%, 94.6%, 95.5% and 92.5%, respectively (χ2=18.547, P<0.001). Multiple Cox regression analysis showed that menstrual status [hazard ratio (HR)=0.483, 95% confidence interval (CI) (0.253, 0.923), P=0.028] and whether endocrine therapy [HR=2.021, 95%CI (1.012, 4.034), P=0.046] were prognostic factors for the 5-year OS rate of breast cancer patients after radical mastectomy (P<0.05). However, it failed to reveal that Luminal subtypes and postoperative radiotherapy were prognostic factors for the 5-year OS rate (P>0.05). Conclusions In pT1-2N1M0 breast cancer patients, the 5-year OS rate and 5-year BCSS rate in triple-negative patients are the lowest. The relationship between Luminal classification, postoperative radiotherapy and survival in patients after radical mastectomy needs further study in the future.
Objective To analyze the clinical efficacy and survival outcome of totally thoracoscopic redo mitral valve replacement and evaluate its efficiency and safety. Methods The clinical data of patients with totally thoracoscopic redo mitral valve replacement in Guangdong Provincial People’s Hospital between 2013 and 2019 were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to determine the risk factors for postoperative death. Results There were 48 patients including 29 females and 19 males with a median age of 53 (44, 66) years. All the procedures were performed successfully with no conversion to median sternotomy. A total of 15, 10 and 23 patients received surgeries under non-beating heart, beating heart and ventricular fibrillation, respectively. The in-hospital mortality rate was 6.25% (3/48), and the incidence of early postoperative complications was 18.75% (9/48). Thirty-five (72.92%) patients had their tracheal intubation removed within 24 hours after the operation. The 1- and 6-year survival rates were 89.50% (95%CI 81.30%-98.70%) and 82.90% (95%CI 71.50%-96.20%), respectively. Age>65 years was an independent risk factor for postoperative death (P=0.04). Conclusion Totally thoracoscopic redo mitral valve replacement is safe and reliable, with advantages of rapid recovery, reducing blood transfusion rate, reducing postoperative complications and acceptable long-term survival rate. It is worthy of being widely popularized in the clinic.
ObjectiveTo investigate the prognostic relevance of serum triglyceride (TG) levels in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis-associated interstitial lung disease (ILD). Methods A retrospective data collection was conducted on patients diagnosed with anti-MDA5 antibody-positive dermatomyositis-associated ILD at West China Hospital of Sichuan University between February 2017 and July 2021. The clinical data, laboratory tests, and imaging examinations were collected, and the patients were followed up. According to the survival and death status of patients, they were divided into survival group and death group. According to TG levels, the patients were divided into a TG high level group and a TG low level group. We employed Cox proportional hazard models to investigate the variables linked to the mortality of individuals afflicted with anti-MDA5 antibody-positive dermatomyositis-associated ILD. Results A total of 204 patients with anti-MDA5 antibody-positive dermatomyositis-associated ILD were included. Among them, whose age ranged from 30 to 81 years old, with an average of (49.5±11.8) years old, there were 69 males and 135 females, 53 deaths and 151 survivors, 57 cases of rapidly progressive pulmonary interstitial fibrosis (RPILD) and 47 cases of non-RPILD. The results of multivariate Cox regression analysis showed that TG≥1.65 mmol/L, combined with RPILD, combined with dyspnea, age, lactate dehydrogenase≥321 U/L, and albumin<30 g/L were independent factors affecting the long-term prognosis of patients (P<0.05). The Kaplan-Meier method analysis results showed that the survival rate of the TG high level group was lower than that of the TG low level group (P=0.032). Conclusions Elevated TG levels can serve as a clinical indicator of adverse prognosis in patients with dermatomyositis-associated ILD who exhibit positive anti-MDA5 antibody status. Additionally, age, comorbidity with RPILD, combined with dyspnea, lactate dehydrogenase≥321 U/L, and albumin<30 g/L are independent factors contributing to the increased mortality risk among individuals with dermatomyositis-associated ILD who test positive for anti-MDA5 antibody.