Network meta-analyses (NMA) of survival data often rely on the proportional hazards (PH) assumption, however, this assumption fails when survival curves intersect. With the emergence of innovative therapies such as immunotherapy, the importance of NMA based on non-proportional hazards (non-PH) in the current evidence-based medicine evaluation of oncology drugs has become increasingly prominent. Fractional polynomial (FP) models do not rely on the assumption of PH, which can flexibly capture the characteristics of survival curves, and the corresponding fitting effects are better than those of the PH models. This study introduced a complete workflow in R for NMA using FP models with non-PH.
ObjectiveTo study the clinical value of changes of serumα-fetoprotein(AFP) and soluble cell adhesion molecule-1(sICAM-1) levels before and after surgical treatment of primary hepatocellular carcinoma(PHC) as predictors of patient survival.
MethodsThe clinical data and followed-up results of 86 patients with hepatocellular carcinoma received hepatectomy or radiofrequency ablation(RFA) in Xijing Hospital and the 451st Hospital of PLA were retrospectivly analyzed. The changes of peripheral blood AFP and sICAM-1 levels in patients before and in 1 month after treatment were observed and all patients were divided into different groups according to the changes in both two markers. Then survival rates of each group were analyzed.
ResultsThe patients with AFP < 20μg/L or sICAM-1 < 1 000 U/L before treatment had lower tumor recurrence rate and higher survival rate than patients with elevated serum levels of the both markers(AFP:P=0.018, P < 0.001;sICAM-1:P=0.027, P < 0.001). The larger tumor, late TNM stage, and higher rate of recurrence were associated with elevated serum levels of the both markers(AFP:P=0.016, P=0.026 and P=0.025;sICAM-1:P < 0.001, P=0.024 and P=0.032). The better survival situation was closely related with these cases treated with hepatectomy and their levels of both markers were lower than the above cutoff values both before and after treatment, or leves of both markers above the cut-off values returned to within the normal range after treatment (AFP:P=0.006, P=0.001;sICAM-1:P=0.001, P=0.002). The patients who had simultaneous increase of AFP and sICAM-1 after operation showed the worst tumor-free and overall survivals(P=0.007, P < 0.001).
ConclusionTo test the changes of serum AFP and sICAM-1 levels in early stage after treatment for patients who received radical resection of hepatocellular carcinoma has good clinical value for monitoring of tumor recurrence and predict prognosis.
Objective To investigate the prognostic factors of severe chronic obstructive pulmonary disease ( COPD) in elderly patients, and to guide the clinical assessment and appropriate interventions. Methods A prospective cohort study was carried out from May 1993 to December 2010. A total of 178 elderly patients with severe COPD were recruited for baseline survey, and followed up for the living conditions, whether used non-invasive ventilation, and causes of death. A survival analysis was performed on all patients stratified by lung function. The significant factors on survival rate were analyzed. Results In this cohort the survival rates were 49% and 12% in five and ten years, respectively. The important factors for prognosis were age [ relative risk( RR) = 1. 043, 95% confidence intervals( 95% CI = 1. 010-1. 050] , forced expired volume in one second ( FEV1 , RR = 0. 019, 95% CI = 0. 007-0. 052) , FEV1% pred ( RR = 1. 045, 95% CI = 1. 012-1. 079) , lung function grade ( RR = 2. 542, 95% CI = 1. 310-4. 931) , body mass index ( BMI, RR= 0. 945, 95% CI = 0. 895-0. 952) , and pulmonary heart disease ( RR = 1. 872, 95% CI = 1. 188- 2. 959) . In severe COPD, non-invasive ventilation ( NIV, RR = 1. 167, 95% CI = 0. 041-1. 674) , pulmonary heart disease ( RR = 3. 805, 95% CI = 1. 336-10. 836) , FEV1 ( RR = 0. 081, 95% CI = 1. 001-1. 168) , and arterial partial of oxygen ( PaO2 , RR=0. 956, 95% CI =0. 920-0. 993) were the independent predictors.The patients using NIV had longer survival than those without NIV. The 5 and 10 years survival rate in the patients with NIV were 78% and 50% , much higher than those without ventilation which were 30% and 25% , respectively. In extremely severe COPD, FEV1 ( RR=1. 059, 95% CI =1. 015-1. 105) , arterial partial of carbon dioxide ( PaCO2 , RR=1. 037, 95% CI = 1. 001-1. 074) , age ( RR= 1. 054, 95% CI = 1. 013-1. 096) and pulmonary heart disease ( RR = 1. 892, 95% CI = 1. 125-3. 181) were the independent predictors. Conclusions Age, BMI, FEV1 , PaO2 , PaCO2 , pulmonary heart disease, and NIV were prognostic factors in elderly patients with severe COPD. The prognostic factors between severe and extremely severe COPD were not identical. Patients with severe COPD should be given early intervention, including progressive nutritional support, and long-term home oxygen therapy combining with NIV.
ObjectiveTo explore the expression of chloride intracellular channel protein 1 (CLIC1) protein in the matched colorectal normal mucosa tissue, colorectal adenoma tissue， and colorectal cancer tissue, and its relationship with tumorigenesis, tumor progression， and prognosis of patients with colorectal cancer . MethodsThe expression of CLIC1 protein was detected in 150 cases of colorectal normal mucosa tissues, 62 cases of colorectal adenoma tissues, and 187 cases of colorectal cancer tissues by using immunohistochemistry tissue microarray, and the relationships between the expression of CLIC1 protein and clinicopathologic features, and the survival rate of patients with colorectal cancer were analyzed. ResultsThe positive rate of CLIC1 protein expression in normal mucosa tissues (26.00%, 39/150), colorectal adenoma tissues (66.13%, 41/62), and colorectal cancer tissues (82.89%, 187/155) increased in turn and the difference was statistically significant (Plt;0.001). The expression of CLIC1 protein was related to TNM staging (P=0.007), but it was not related to gender (P=0.553), age (P=0.206), tumor diameter (P=0.185), tumor differentiation (P=0.062), and tumor location (P=0.598). The median survival time after surgery in patients with CLIC1 protein positive expression was 80 months, and it was 111 months in patients with CLIC1 protein negative expression. The survival rate of patients with CLIC1 protein positive expression was lower than that with CLIC1 protein negative expression by log-rank test (66.40% vs. 80.00%, P=0.031). ConclusionsThe expression of CLIC1 protein is related to the tumorigenesis and progression of colorectal cancer as well as the survival of patients with colorectal cancer. CLIC1 is a potential tumor biomarker.
Objective To compare the oncologic results between laparoscopic and open approach for the treatment of rectal cancer. Methods Five hundred and twenty patients with rectal cancer from Jan. 2003 to Dec. 2008 were non-randomly divided into laparoscopic (LS) and open surgery (OS) group. Local recurrence, distant metastasis and survival rate were compared between two groups. Results One hundred and eighty-six cases received laparoscopic resection and 334 cases received open operation. There were no statistically significant differences (SSD) of demographic data between two groups (Pgt;0.05). Mean follow-up was 30.3 months. No SSD was observed in 3-year cumulative survival rate (83% in LS and 80% in OS, P=0.549), distant metastasis rate (12.5% in LS and 15.6% in OS, P=0.368), incidence of incision seeding (0.6% in LS and 0 in OS, P=0.189), or cumulative survival (P=0.142). The differences of local recurrences rate (4.8% in LS and 10.7% in OS, P=0.028), 3-year cumulative disease-free survival rate (81% in LS and 68% in OS, P=0.009), and cumulative disease-free survival (P=0.010) between two groups were statistical significant. The differences of cumulative survival, cumulative disease-free survival, local recurrences， and distant metastasis according to the TNM stageⅠ or Ⅱ between two groups were not statistical significant. The differences of cumulative disease-free survival and local recurrences according to the TNM stage Ⅲ reached statistical significance (P=0.045 and P=0.047, respectively). Conclusion Oncologic results of laparoscopic resection are similar to those of open resection for rectal carcinoma．
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.
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 establish a predictive model for survival and study it’s clinical value by reviewing the information of patients with hilar cholangiocarcinoma. MethodsMedical record of 196 patients with hilar cholangiocarcinoma were analyzed retrospectively. Seventeen possible clinicopathologic factors were selected. Cox model was used for univariate and multivariate analysis. Prognostic index (PI) was calculated based on the results of multivariate analysis. Patients with different PI were divided into three different risk level groups in order to compare the survival rate. Individual expected survival rate was calculated based on the median PI. Log cumulative hazards function plot was used to test Cox model proportional hazards assumption (PH assumption). ResultsThe significant prognostic factors influencing the survival rate were surgical procedure, surgical margin, and preoperative total bilirubin level (Plt;0.05). The predictive formula was PI=0.815×preoperative total bilirubin level+0.580×surgical margin－0.713×surgical procedure. According to the value of PI, all patients were divided into 3 groups, low risk group (PI≤－0.642), middle risk group (－0.642lt;PIlt;1.364), high risk group (PI≥1.364), and survival rate declined between groups and in groups with statistically significant difference (Plt;0.05). ConclusionThis model for survival can predict the prognosis of patients with hilar cholangiocarcinoma individually and help to conduct individual clinical therapy.
Abstract： Objective To evaluate surgical outcomes of patients with Marfan syndrome （MFS） complicated by type A aortic dissection （AAD） during follow-up. Methods We retrospectively reviewed clinical data of 44 patients with MFS complicated by AAD who were admitted to Wuhan Asia Heart Hospital from January 2006 to January 2012. There were 31 male patients and 13 female patients with their age of 12-54 （33.0±9.8） years. Twenty-three patients underwent Bentall procedure at different time after the onset of AAD， while the other 21 patients received conservative treatment in stead of surgery because of economical or other reasons. COX regression with time-varying covariates was performed to analyze related factors， using primary end point， primary end point＋secondary end point as the outcome variables respectively， to compare postoperative outcomes and quality of life between the surgical treatment patients and conservative treatment patients. Results Postoperatively 1 patient died of multiple organ failure， and the other 22 patients survived the surgery. All the 43 patients were followed up from 1 to 75 months. The 3-year survival rate of the 22 surgical treatment patients was 95.7%， and they all had a good quality of life during follow-up. The survival condition and quality of life of the 21 conservative treatment patients was poor， and 13 patients （61.9%） died with the 3-year survival rate of only 31.7%. The main causes of their death included acute cardiac tamponade， aortic dissection rupture， acute myocardial infarction andcardiogenic shock. COX regression with time-varying covariates showed that the treatment outcomes of the surgical treatment patients were statistically different from those of the conservative treatment patients after modifying the influence caused by different operating time （OR of T_COV_ =0.088， P=0.028） . The risk of death of surgical treatment was only 8.8% of that of conservative treatment. Conclusion The prognosis of patients with MFS complicated by AAD is very poor. Therefore， all these patient， both in acute stage and chronic stage， should undergo surgical treatment as early as possible. The short-term and follow-up outcomes of surgical treatment are satisfactory.
ObjectiveTo investigate the application status of survival analysis in studies published in Chinese oncology journals, and assess their reporting quality and summarize the existing problems, so as to promote the application of survival analysis and reporting quality.
MethodsStudies that used survival analysis were collected from 1 492 studies published in Chinese Journal of Oncology, Chinese Journal of Clinical Oncology, Chinese Journal of Radiation Oncology and Chinese Journal of Cancer Prevention and Treatment in 2013. The application status of survival analysis of included studies was analysed and their reporting quality was evaluated.
ResultsA total of 242 survival analysis studies were included. Among them, the utilization rates of Kaplan-Meier method, life table method, log-rank test, Breslow test and Cox proportional hazards model were 91.74%, 3.72%, 78.51%, 0.41% and 46.28%, respectively. 112 studies did multivariate analysis through Cox proportional hazards model. A total of 396 end points and 10 different types of survival time were reported. Overall survival (OS) was reported in 233 studies (92.15%). Survival terms were defined to 158 end points (39.90%) of 103 studies (42.56%). The follow-up rates were mentioned in 155 studies (64.05%), of which 4 studies were under 80% and the lowest was 75.25%, 55 studies were 100%. The main problems of survival analysis studies published in Chinese journals were as follows:None of the studies which used Cox proportional hazards model reported the proportional hazards assumption. None of the studies used the method of parametric survival analysis. 130 studies (53.72%) did not use the method of multiple factor analysis. 139 studies (57.44%) did not define the survival terms. Only 11 of 100 studies which reported loss to follow-up had stated how to treat it in the analysis. None of the studies reported the methods of calculating sample size. None of the studies reported the censoring proportion.
ConclusionThe methods of survival analysis are used in a low rate in studies published in Chinese oncology journals, and the overall reporting quality of survival analyses is poor. So the reporting guideline of survival analysis should be developed and the authors should be encouraged to cooperate with professional statisticians, in order to improve the design, analysis and reporting quality of survival analysis studies.
