BACKGROUND Gastric cancer(GC)is prevalent and aggressive,especially when patients have distant lung metastases,which often places patients into advanced stages.By identifying prognostic variables for lung metastasis i...BACKGROUND Gastric cancer(GC)is prevalent and aggressive,especially when patients have distant lung metastases,which often places patients into advanced stages.By identifying prognostic variables for lung metastasis in GC patients,it may be po-ssible to construct a good prediction model for both overall survival(OS)and the cumulative incidence prediction(CIP)plot of the tumour.AIM To investigate the predictors of GC with lung metastasis(GCLM)to produce nomograms for OS and generate CIP by using cancer-specific survival(CSS)data.METHODS Data from January 2000 to December 2020 involving 1652 patients with GCLM were obtained from the Surveillance,epidemiology,and end results program database.The major observational endpoint was OS;hence,patients were se-parated into training and validation groups.Correlation analysis determined va-rious connections.Univariate and multivariate Cox analyses validated the independent predictive factors.Nomogram distinction and calibration were performed with the time-dependent area under the curve(AUC)and calibration curves.To evaluate the accuracy and clinical usefulness of the nomograms,decision curve analysis(DCA)was performed.The clinical utility of the novel prognostic model was compared to that of the 7th edition of the American Joint Committee on Cancer(AJCC)staging system by utilizing Net Reclassification Improvement(NRI)and Integrated Discrimination Improvement(IDI).Finally,the OS prognostic model and Cox-AJCC risk stratification model modified for the AJCC system were compared.RESULTS For the purpose of creating the OS nomogram,a CIP plot based on CSS was generated.Cox multivariate regression analysis identified eleven significant prognostic factors(P<0.05)related to liver metastasis,bone metastasis,primary site,surgery,regional surgery,treatment sequence,chemotherapy,radiotherapy,positive lymph node count,N staging,and time from diagnosis to treatment.It was clear from the DCA(net benefit>0),time-de-pendent ROC curve(training/validation set AUC>0.7),and calibration curve(reliability slope closer to 45 degrees)results that the OS nomogram demonstrated a high level of predictive efficiency.The OS prediction model(New Model AUC=0.83)also performed much better than the old Cox-AJCC model(AUC difference between the new model and the old model greater than 0)in terms of risk stratification(P<0.0001)and verification using the IDI and NRI.CONCLUSION The OS nomogram for GCLM successfully predicts 1-and 3-year OS.Moreover,this approach can help to ap-propriately classify patients into high-risk and low-risk groups,thereby guiding treatment.展开更多
Background:Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial.Whether the results regarding o...Background:Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial.Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain.Methods:In this phase 3,double-blind,placebo-controlled trial,we randomly assigned(in a 1:1 ratio)participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab(at a dose of 200 mg)or placebo every 3 weeks for up to 17 cycles(approximately 1 year)or until recurrence,the occurrence of unacceptable toxic effects,or withdrawal of consent.A significant improvement in disease-free survival according to investigator assessment(the primary end point)was shown previously.Overall survival was the key secondary end point.Safety was a secondary end point.展开更多
BACKGROUND Increasingly extranodal marginal B-cell lymphoma of mucosa-associated lymphoid tissue,known as mucosa-associated lymphoid tissue(MALT)lymphoma,is a type of non-Hodgkin’s lymphoma.The prognosis of primary g...BACKGROUND Increasingly extranodal marginal B-cell lymphoma of mucosa-associated lymphoid tissue,known as mucosa-associated lymphoid tissue(MALT)lymphoma,is a type of non-Hodgkin’s lymphoma.The prognosis of primary gastric MALT(GML)patients can be affected by many factors.Clinical risk factors,including age,type of therapy,sex,stage and family hematologic malignancy history,also have significant effects on the development of the disease.The available data are mainly focused on epidemiology;in contrast,few studies have investigated the prognostic variables for overall survival(OS)in patients with primary GML.Based on the realities above,we searched a large amount of data on patients diagnosed with primary GML in the Surveillance,Epidemiology and End Results(SEER)database.The aim was to develop and verify a survival nomogram model that can predict the overall survival prognosis of primary GML by com-bining prognostic and determinant variables.AIM To create an effective survival nomogram for patients with primary gastric GML.METHODS All data of patients with primary GML from 2004 to 2015 were collected from the SEER database.The primary endpoint was OS.Based on the LASSO and COX regression,we created and further verified the accuracy and effectiveness of the survival nomogram model by the concordance index(C-index),calibration curve and timedependent receiver operating characteristic(td-ROC)curves.RESULTS A total of 2604 patients diagnosed with primary GML were selected for this study.A total of 1823 and 781 people were randomly distributed into the training and testing sets at a ratio of 7:3.The median follow-up of all patients was 71 mo,and the 3-and 5-year OS rates were 87.2%and 79.8%,respectively.Age,sex,race,Ann Arbor stage and radiation were independent risk factors for OS of primary GML(all P<0.05).The C-index values of the nomogram were 0.751(95%CI:0.729-0.773)and 0.718(95%CI:0.680-0.757)in the training and testing cohorts,respectively,showing the good discrimination ability of the nomogram model.Td-ROC curves and calibration plots also indicated satisfactory predictive power and good agreement of the model.Overall,the nomogram shows favorable performance in discriminating and predicting the OS of patients with primary GML.CONCLUSION A nomogram was developed and validated to have good survival predictive performance based on five clinical independent risk factors for OS for patients with primary GML.Nomograms are a low-cost and convenient clinical tool in assessing individualized prognosis and treatment for patients with primary GML.展开更多
BACKGROUND Fibrinogen-to-albumin ratio(FAR)has been found to be of prognostic significance for several types of malignant tumors.However,less is known about the association between FAR and survival outcomes in hepatoc...BACKGROUND Fibrinogen-to-albumin ratio(FAR)has been found to be of prognostic significance for several types of malignant tumors.However,less is known about the association between FAR and survival outcomes in hepatocellular carcinoma(HCC)patients.AIM To explore the association between FAR and prognosis and survival in patients with HCC.METHODS A total of 366 histologically confirmed HCC patients diagnosed between 2013 and 2018 in a provincial cancer hospital in southwestern China were retrospectively selected.Relevant data were extracted from the hospital information system.The optimal cutoff for baseline serum FAR measured upon disease diagnosis was established using the receiver operating characteristic(ROC)curve.Univariate and multivariate Cox proportional hazards models were used to determine the crude and adjusted associations between FAR and the overall survival(OS)of the HCC patients while controlling for various covariates.The restricted cubic spline(RCS)was applied to estimate the dose-response trend in the FAR-OS association.RESULTS The optimal cutoff value for baseline FAR determined by the ROC was 0.081.Multivariate Cox proportional hazards model revealed that a lower baseline serum FAR level was associated with an adjusted hazard ratio of 2.43(95%confidence interval:1.87–3.15)in the OS of HCC patients,with identifiable dose-response trend in the RCS.Subgroup analysis showed that this FAR-OS association was more prominent in HCC patients with a lower baseline serum aspartate aminotransferase or carbohydrate antigen 125 level.CONCLUSION Serum FAR is a prominent prognostic indicator for HCC.Intervention measures aimed at reducing FAR might result in survival benefit for HCC patients.展开更多
BACKGROUND Preoperative anemia is associated with increased postoperative morbidity and mortality and increased perioperative transfusion risk.For surgical patients,this affects physical and cognitive ability and qual...BACKGROUND Preoperative anemia is associated with increased postoperative morbidity and mortality and increased perioperative transfusion risk.For surgical patients,this affects physical and cognitive ability and quality of life,but it is an important and modifiable risk factor.AIM To determine the effect of preoperative anemia on the prognosis of gastric cancer(GC)patients and generate a prognostic nomogram to predict the postoperative overall survival(OS)of GC patients with preoperative anemia.METHODS Clinicopathological and follow-up data of GC patients treated at Zhejiang Provincial People's Hospital(China)from 2010 to 2015 were collected.Independent prognostic factors were screened by univariate and multivariate Cox regression analyses.Then,these factors were used to construct a nomogram to predict 1-,3-,and 5-year postoperative OS in preoperative anemic GC patients.The nomogram was assessed by calibration curves,receiver operating characteristic(ROC)curves,and decision curve analysis(DCA).RESULTS Nine hundred and sixty GC patients were divided into two groups(preoper atively anemic and nonanemic),and postoperative survival analysis was performed on both groups,yielding a shorter postoperative survival for preoperatively anemic patients than for nonanemic patients.A total of 347 GC patients with preoperative anemia were included.Age,preoperative alpha-fetoprotein level,monocyte count,lymphocyte count,clinicopathological stage,liver metastasis,and GC type were identified as independent prognostic factors for OS.The area under the ROC curve(AUC)of the nomogram for predicting 1-,3-,and 5-year OS was 0.831,0.845,and 0.840,respectively,for the training cohort,and the corresponding AUC values in the validation cohort were 0.827,0.829,and 0.812,respectively.Calibration curves and DCA indicated good performance of the nomogram.CONCLUSION In all,we have successfully produced and verified a useful nomogram for predicting OS in GC patients with preoperative anemia.This nomogram based on a variety of clinicopathological indices can provide an effective prognostic assessment and help clinicians choose an appropriate treatment strategy for GC patients with preoperative anemia.展开更多
BACKGROUND Distant metastasis,particularly visceral metastasis(VM),represents an important negative prognostic factor for prostate cancer(PCa)patients.However,due to the lower rate of occurrence of VM,studies on these...BACKGROUND Distant metastasis,particularly visceral metastasis(VM),represents an important negative prognostic factor for prostate cancer(PCa)patients.However,due to the lower rate of occurrence of VM,studies on these patients are relatively rare.Consequently,studies focusing on prognostic factors associated with PCa patients with VM are highly desirable.AIM To investigate the prognostic factors for overall survival(OS)in PCa patients with lung,brain,and liver metastases,respectively,and evaluate the impact of site-specific and number-specific VM on OS.METHODS Data on PCa patients with VM were extracted from the Surveillance,Epidemiology,and End Results database between 2010 and 2015.Univariate and multivariate Cox regression analyses were used to analyze the association between clinicopathological characteristics and survival of patients with different site-specific VM.Kaplan-Meier analyses and Log-rank tests were performed to analyze the differences among the groups.RESULTS A total of 1358 PCa patients with site-specific VM were identified from 2010 to 2015.Older age(>70 years)(P<0.001),higher stage(T3/T4)(P=0.004),and higher Gleason score(>8)(P<0.001)were found to be significant independent prognostic factors associated with poor OS in PCa patients with lung metastases.Higher stage(T3/T4)(P=0.047)was noted to be the only independent risk factor affecting OS in PCa patients with brain metastases.Older age(>70 years)(P=0.010)and higher Gleason score(>8)(P=0.001)were associated with shorter OS in PCa patients with liver metastases.PCa patients with isolated lung metastases exhibited significantly better survival outcomes compared with PCa patients with other single sites of VM(P<0.001).PCa patients with a single site of VM exhibited a superior OS compared with PCa patients with multiple sites of VM(P<0.001).CONCLUSION This is the first Surveillance,Epidemiology,and End Results-based study to determine prognostic factors affecting OS in PCa patients with different sitespecific VM.Clinical assessments of these crucial prognostic factors become necessary before establishing a treatment strategy for these patients with metastatic PCa.展开更多
BACKGROUND Rectal cancer(RC)patient stratification by different factors may yield variable results.Therefore,more efficient prognostic biomarkers are needed for improved risk stratification,personalized treatment,and ...BACKGROUND Rectal cancer(RC)patient stratification by different factors may yield variable results.Therefore,more efficient prognostic biomarkers are needed for improved risk stratification,personalized treatment,and prognostication of RC patients.AIM To build a novel model for predicting the presence of distant metastases and 3-year overall survival(OS)in RC patients.METHODS This was a retrospective analysis of 148 patients(76 males and 72 females)with RC treated with curative resection,without neoadjuvant or postoperative chemoradiotherapy,between October 2012 and December 2015.These patients were allocated to a training or validation set,with a ratio of 7:3.Radiomic features were extracted from portal venous phase computed tomography(CT)images of RC.The least absolute shrinkage and selection operator regression analysis was used for feature selection.Multivariate logistic regression analysis was used to develop the radiomics signature(Rad-score)and the clinicoradiologic risk model(the combined model).Receiver operating characteristic curves were constructed to evaluate the diagnostic performance of the models for predicting distant metastasis of RC.The association of the combined model with 3-year OS was investigated by Kaplan-Meier survival analysis.RESULTS A total of 51(34.5%)patients had distant metastases,while 26(17.6%)patients died,and 122(82.4%)patients lived at least 3 years post-surgery.The values of both the Rad-score(consisted of three selected features)and the combined model were significantly different between the distant metastasis group and the nonmetastasis group(0.46±0.21 vs 0.32±0.24 for the Rad-score,and 0.60±0.23 vs 0.28±0.26 for the combined model;P<0.001 for both models).Predictors contained in the combined model included the Rad-score,pathological N-stage,and T-stage.The addition of histologic grade to the model failed to show incremental prognostic value.The combined model showed good discrimination,with areas under the curve of 0.842 and 0.802 for the training set and validation set,respectively.For the survival analysis,the combined model was associated with an improved OS in the whole cohort and the respective subgroups.CONCLUSION This study presents a clinicoradiologic risk model,visualized in a nomogram,that can be used to facilitate individualized prediction of distant metastasis and 3-year OS in patients with RC.展开更多
BACKGROUND Signet ring cell carcinoma(SRCC)is an uncommon subtype in colorectal cancer(CRC),with a short survival time.Therefore,it is imperative to establish a useful prognostic model.As a simple visual predictive to...BACKGROUND Signet ring cell carcinoma(SRCC)is an uncommon subtype in colorectal cancer(CRC),with a short survival time.Therefore,it is imperative to establish a useful prognostic model.As a simple visual predictive tool,nomograms combining a quantification of all proven prognostic factors have been widely used for predicting the outcomes of patients with different cancers in recent years.Until now,there has been no nomogram to predict the outcome of CRC patients with SRCC.AIM To build effective nomograms for predicting overall survival(OS)and causespecific survival(CSS)of CRC patients with SRCC.METHODS Data were extracted from the Surveillance,Epidemiology,and End Results database between 2004 and 2015.Multivariate Cox regression analyses were used to identify independent variables for both OS and CSS to construct the nomograms.Performance of the nomograms was assessed by concordance index,calibration curves,and receiver operating characteristic(ROC)curves.ROC curves were also utilized to compare benefits between the nomograms and the tumor-node-metastasis(TNM)staging system.Patients were classified as high-risk,moderate-risk,and low-risk groups using the novel nomograms.Kaplan-Meier curves were plotted to compare survival differences.RESULTS In total,1230 patients were included.The concordance index of the nomograms for OS and CSS were 0.737(95%confidence interval:0.728-0.747)and 0.758(95%confidence interval:0.738-0.778),respectively.The calibration curves and ROC curves demonstrated good predictive accuracy.The 1-,3-,and 5-year area under the curve values of the nomogram for predicting OS were 0.796,0.825 and 0.819,in comparison to 0.743,0.798,and 0.803 for the TNM staging system.In addition,the 1-,3-,and 5-year area under the curve values of the nomogram for predicting CSS were 0.805,0.847 and 0.863,in comparison to 0.740,0.794,and 0.800 for the TNM staging system.Based on the novel nomograms,stratified analysis showed that the 5-year probability of survival in the high-risk,moderate-risk,and low-risk groups was 6.8%,37.7%,and 67.0%for OS(P<0.001),as well as 9.6%,38.5%,and 67.6%for CSS(P<0.001),respectively.CONCLUSION Convenient and visual nomograms were built and validated to accurately predict the OS and CSS rates for CRC patients with SRCC,which are superior to the conventional TNM staging system.展开更多
BACKGROUND There are few nomograms for the prognosis of Chinese patients with triplenegative breast cancer(TNBC).AIM To construct and validate a nomogram for overall survival(OS)of Chinese TNBC patients after surgery....BACKGROUND There are few nomograms for the prognosis of Chinese patients with triplenegative breast cancer(TNBC).AIM To construct and validate a nomogram for overall survival(OS)of Chinese TNBC patients after surgery.METHODS This study used the data of SEER*stat 8.3.5 and selected Chinese patients with TNBC operated on between 2010 and 2015.Univariate and multivariate Cox proportional hazard regression models were used.The identified variables were integrated to form a predictive nomogram and risk stratification model;it was assessed with C-indexes and calibration curves.RESULTS The median and maximal OS of the 336 patients was 39 and 83 mo,respectively.The multivariate analysis showed that age(P=0.043),marital status(P=0.040),tumor localization(P=0.030),grade(P=0.035),T classification(P=0.012),and N classification(P=0.002)were independent prognostic factors.The six variables were combined to construct a 1-,3-and 5-year OS nomogram.The C-indexes of the nomogram to predict OS were 0.766 and compared to the seventh edition staging system,which was higher(0.766 vs 0.707,P<0.001).In order to categorize patients into different prognostic groups,a risk stratification model was created.There was a significant difference between the Kaplan–Meier curves of the entire cohort and each disease stage according to the nomogram.CONCLUSION The nomogram provided prognostic superiority over the traditional tumor,node and metastasis system.It could help clinicians make individual OS or risk predictions for Chinese TNBC patients after surgery.展开更多
BACKGROUND The prognostic value of preoperative fluorine-18-fluorodeoxyglucose positronemission tomography(18 F-FDG PET)scan for determining overall survival(OS)in breast cancer(BC)patients is controversial.AIM To eva...BACKGROUND The prognostic value of preoperative fluorine-18-fluorodeoxyglucose positronemission tomography(18 F-FDG PET)scan for determining overall survival(OS)in breast cancer(BC)patients is controversial.AIM To evaluate the OS predictive value of preoperative PET positivity after 15 years.METHODS We performed a retrospective search of the Universitair Ziekenhuis Brussel patient database for nonmetastatic patients who underwent preoperative PET between 2002-2008.PET positivity was determined by anatomical region of interest(AROI)findings for breast and axillary,sternal,and distant sites.The prognostic role of PET was examined as a qualitative binary factor(positive vs negative status)and as a continuous variable[maximum standard uptake value(SUVmax)]in multivariate survival analyses using Cox proportional hazards models.Among the 104 identified patients who received PET,36 were further analyzed for the SUVmax in the AROI.RESULTS Poor OS within the 15-year study period was predicted by PET-positive status for axillary(P=0.033),sternal(P=0.033),and combined PET-axillary/sternal(P=0.008)nodes.Poor disease-free survival was associated with PET-positive axillary status(P=0.040)and combined axillary/sternal status(P=0.023).Cox models confirmed the long-term prognostic value of combined PETaxillary/sternal status[hazard ratio(HR):3.08,95%confidence interval:1.42-6.69].SUVmax of ipsilateral breast and axilla as continuous covariates were significant predictors of long-term OS with HRs of 1.25(P=0.048)and 1.54(P=0.029),corresponding to relative increase in the risk of death of 25%and 54%per SUVmax unit,respectively.In addition,the ratio of the ipsilateral axillary SUVmax over the contralateral axillary SUVmax was the most significant OS predictor(P=0.027),with 1.94 HR,indicating a two-fold relative increase of mortality risk.CONCLUSION Preoperative PET is valuable for prediction of long-term survival.Ipsilateral axillary SUVmax ratio over the uninvolved side represents a new prognostic finding that warrants further investigation.展开更多
BACKGROUND Cellular senescence is a recognized barrier for progression of chronic liver diseases to hepatocellular carcinoma(HCC). The expression of a cluster of genes is altered in response to environmental factors d...BACKGROUND Cellular senescence is a recognized barrier for progression of chronic liver diseases to hepatocellular carcinoma(HCC). The expression of a cluster of genes is altered in response to environmental factors during senescence. However, it is questionable whether these genes could serve as biomarkers for HCC patients.AIM To develop a signature of senescence-associated genes(SAGs) that predicts patients' overall survival(OS) to improve prognosis prediction of HCC.METHODS SAGs were identified using two senescent cell models. Univariate COX regression analysis was performed to screen the candidate genes significantly associated with OS of HCC in a discovery cohort(GSE14520) for the least absolute shrinkage and selection operator modelling. Prognostic value of this seven-gene signature was evaluated using two independent cohorts retrieved from the GEO(GSE14520) and the Cancer Genome Atlas datasets, respectively.Time-dependent receiver operating characteristic(ROC) curve analysis was conducted to compare the predictive accuracy of the seven-SAG signature and serum α-fetoprotein(AFP).RESULTS A total of 42 SAGs were screened and seven of them, including KIF18 B, CEP55,CIT, MCM7, CDC45, EZH2, and MCM5, were used to construct a prognostic formula. All seven genes were significantly downregulated in senescent cells andupregulated in HCC tissues. Survival analysis indicated that our seven-SAG signature was strongly associated with OS, especially in Asian populations, both in discovery and validation cohorts. Moreover, time-dependent ROC curve analysis suggested the seven-gene signature had a better predictive accuracy than serum AFP in predicting HCC patients' 1-, 3-, and 5-year OS.CONCLUSION We developed a seven-SAG signature, which could predict OS of Asian HCC patients. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.展开更多
AIM To integrate clinically significant variables related to prognosis after curative resection for gallbladder carcinoma(GBC) into a predictive nomogram.METHODS One hundred and forty-two GBC patients who underwent cu...AIM To integrate clinically significant variables related to prognosis after curative resection for gallbladder carcinoma(GBC) into a predictive nomogram.METHODS One hundred and forty-two GBC patients who underwent curative intent surgical resection at Peking Union Medical College Hospital(PUMCH) were included. This retrospective case study was conducted at PUMCH of the Chinese Academy of Medical Sciences and Peking Union Medical College(CAMS & PUMC) in China from January 1, 2003 to January 1, 2018. The continuous variable carbohydrate antigen 19-9(CA19-9) was converted into a categorical variable(cCA19-9) based on the normal reference range. Stages 0 to IIIA were merged into one category, while the remaining stages were grouped into another category. Pathological grade X(GX) was treated as a missing value. A multivariate Cox proportional hazards model was used to select variables to construct a nomogram. Discrimination and calibration of the nomogram were performed via the concordance index(C-index) and calibration plots. The performance of the nomogram was estimated using the calibration curve. Receiver operating characteristic(ROC) curve analysis and decision curve analysis(DCA) were performed to evaluate the predictive accuracy and net benefit of the nomogram, respectively.RESULTS Of these 142 GBC patients, 55(38.7%) were male, and the median and mean age were 64 and 63.9 years, respectively. Forty-eight(33.8%) patients in this cohort were censored in the survival analysis. The median survival time was 20 months. A series of methods, including the likelihood ratio test and Akaike information criterion(AIC) as well as stepwise, forward, and backward analyses, were used to select the model, and all yielded identical results. Jaundice [hazard ratio(HR) = 2.9; 95% confidence interval(CI): 1.60-5.27], cCA19-9(HR = 3.2; 95%CI: 1.91-5.39), stage(HR = 1.89; 95%CI: 1.16-3.09), and resection(R)(HR = 2.82; 95%CI: 1.54-5.16) were selected as significant predictors and combined into a survival time predictive nomogram(C-index = 0.803; 95%CI: 0.766-0.839). High prediction accuracy(adjusted C-index = 0.797) was further verified via bootstrap validation. The calibration plot demonstrated good performance of the nomogram. ROC curve analysis revealed a high sensitivity and specificity. A high net benefit was proven by DCA.CONCLUSION A nomogram has been constructed to predict the overall survival of GBC patients who underwent radical surgery from a clinical database of GBC at PUMCH.展开更多
AIM To investigate the predictive value of PIK3 CA and TP53 mutation status in colorectal cancer(CRC) patients treated with 5-fluorouracil-based chemotherapy.METHODS In this study, a total of 315 patients with histolo...AIM To investigate the predictive value of PIK3 CA and TP53 mutation status in colorectal cancer(CRC) patients treated with 5-fluorouracil-based chemotherapy.METHODS In this study, a total of 315 patients with histologically proven CRC were enrolled from Yangpu Hospital affiliated to Shanghai Tongji University between 2007 and 2011. Of these patients, 241 with stage Ⅱ/Ⅲ CRC received 5-fluorouracil-based adjuvant chemotherapy. Formalin-fixed paraffin-embedded lesion samples of the patients with curatively resected CRC were collected.Next-generation sequencing was performed to identify somatic gene mutations. The correlation of PIK3 CA and TP53 mutation status with overall survival(OS) was analyzed using a Cox proportional hazard model and the Kaplan-Meier method.RESULTS Among the 241 patients with stage Ⅱ/Ⅲ in this cohort, the PIK3 CA and/or TP53 mutation was detected in 177 patients, among which 54 patients had PIK3 CA and TP53 double mutations. The PIK3 CA or TP53 mutation was not significantly correlated with OS in univariate and multivariate analyses. Compared with patients without PIK3 CA and TP53 mutations, those with double PIK3 CA-TP53 mutations showed a significantly worse survival(univariate HR = 2.21; 95%CI: 1.15-4.24; multivariate HR = 2.02; 95%CI: 1.04-3.91). The PIK3 CA mutation located in the kinase domain showed a trend toward a shorter OS compared with wild-type tumors(multivariate HR = 1.56; 95%CI: 1.00-2.44; P = 0.052). The Kaplan-Meier curve showed that patients harboring the PIK3 CA mutation located in the kinase domain had a worse clinical outcome than those with wild-type status(Log-rank P = 0.041)CONCLUSION Double mutation of PIK3 CA and TP53 is correlated with a shorter OS in stage Ⅱ/Ⅲ CRC patients treated with 5-fluorouracil-based therapy.展开更多
AIM:Clinicopathologic factors predicting overall survival (OS) would help identify a subset to benefit from adjuvant therapy. METHODS: One hundred and sixty-nine patients patients from 1984 to 2009 with curative resec...AIM:Clinicopathologic factors predicting overall survival (OS) would help identify a subset to benefit from adjuvant therapy. METHODS: One hundred and sixty-nine patients patients from 1984 to 2009 with curative resections for pancreatic adenocarcinoma were included. Tumors were staged by American Joint Committee on Cancer 7th edition criteria. Univariate and multivariable analyses were performed using Kaplan-Meier methodology or Cox proportional hazard models. Log-rank tests were performed. Statistical inferences were assessed by two-sided 5% significance level. RESULTS: Median age was 67.1 (57.2-73.0) years with equal gender distribution. Tumors were in the head (89.3%) or body/tail (10.7%). On univariate analysis, adjuvant therapy, lymph node (LN) ratio, histologic grade, negative margin status, absence of peripancreatic extension, and T stage were associated with improved OS. Adjuvant therapy, LN ratio, histologic grade, number of nodes examined, negative LN status, and absence of peripancreatic extension were associated with improved recurrence-free survival (RFS). On multivariable analysis, LN ratio and carbohydrate antigen (CA) 19-9 levels were associated with OS. LN ratio was associated with RFS. CONCLUSION: The LN ratio and CA 19-9 levels are independent prognostic factors following curative resections of pancreatic cancer.展开更多
AIM: To investigate the role of single nucleotide polymorphisms(SNPs) in CD24 gene in susceptibility and overall survival of gastric cancer(GC).METHODS: We genotyped 3 tagging SNPs of CD24-P-534 in the promoter region...AIM: To investigate the role of single nucleotide polymorphisms(SNPs) in CD24 gene in susceptibility and overall survival of gastric cancer(GC).METHODS: We genotyped 3 tagging SNPs of CD24-P-534 in the promoter region, P170 in the coding region of exon 2 and P1527 in the 3′ untranslated region- using polymerase chain reaction-restriction fragment length polymorphism in specimens from 679 histologically-confirmed GC cases, 111 gastric atrophy(GA) cases and 976 tumor-free controls. Serumimmunoglobulin G antibodies to Helicobacter pylori(H. pylori) of all subjects were detected by enzyme-linked immunosorbent assay. CD24 expression was evaluated by immunohistochemistry in 131 GC specimens. Correlations between SNPs and risk of GC or GA were shown by P values and odd ratios(ORs) with 95% confidence intervals(95%CI) compared with the most common genotype of each SNP using the unconditional logistic regression model after adjusting for age, sex and H. pylori infection. Survival within each SNP group was plotted by Kaplan-Meier method and compared by log-rank test(recessive model). Hazard ratios with 95%CIs were computed by Cox regression model after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy.RESULTS: All of the three loci were in Hardy-Weinberg equilibrium in the control group. Median followup time for the 600 GC patients included in the survival analysis was 36.2 mo(range, 2.1-66.7 mo; 95%CI: 34.3-36.5 mo). Patients with the P-534 A/A genotype had significantly shorter survival(HR = 1.38, 95%CI: 1.01-1.88, P = 0.042) than did the C/C or C/A genotype carriers after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy. This trend was more evident in patients who lived longer than 2.5 years(HR = 7.55, 95%CI: 2.16-26.32, P = 0.001). The P170 T/T genotype was associated with a shorter lifespan than the non-T/T genotypes, but not significantly so. None of the three genetic variants was found to be associated with risk of GC(including tumor stage, grade and distant metastasis) or with risk of gastric atrophy. Furthermore, no difference of CD24 expression was found among the genotypes.CONCLUSION: The P-534 site in CD24 gene affects the overall survival of gastric cancer and may serve as a prognostic marker for gastric cancer.展开更多
AIM To clarify the prognostic significance of preoperative albumin-to-alkaline phosphatase ratio(AAPR) in cholangiocarcinoma(CCA) subjects receiving surgery.METHODS In this retrospective study, we included 303 CCA pat...AIM To clarify the prognostic significance of preoperative albumin-to-alkaline phosphatase ratio(AAPR) in cholangiocarcinoma(CCA) subjects receiving surgery.METHODS In this retrospective study, we included 303 CCA patients receiving surgery without preoperative therapy between 2002 and 2014. Clinicopathological characteristics(including AAPR) were analyzed to determine predictors of postoperative overall survival and recurrence-free survival(RFS). In addition,univariate and multivariate Cox proportional hazards models were conducted,followed by application of time-dependent receiver operating curves to identify the optimal cut-off.RESULTS Univariate and multivariate analyses revealed both decreased overall survival[hazard ratio(HR): 2.88, 95%CI: 1.19-5.78] and recurrence-free survival(HR: 2.31,95%CI: 1.40–3.29) in patients with AAPR < 0.41 compared to those with AAPR ≥0.41. The optimal cut-off of AAPR was 0.41. Of the 303 subjects, 253(83.5%) had an AAPR over 0.41. The overall 1-, 3- and 5-year survival rates were 70.2%, 38.0% and 16.5%, respectively in the low(< 0.41) AAPR group, which were significantly lower than those in the high(≥ 0.41) AAPR group(81.7%, 53.9%, and 33.4%,respectively)(P < 0.0001). Large tumor size, multiple tumors, and advanced clinical stage were also identified as significant predictors of poor prognosis.CONCLUSION Our outcomes showed that AAPR was a potential valuable prognostic indicator in CCA patients undergoing surgery, which should be further confirmed by prospective studies. Moreover, it is necessary to investigate the mechanisms concerning the correlation of low AAPR with poor post-operative survival in CCA patients.展开更多
BACKGROUND Colon cancer is among the most commonly diagnosed cancers in the United States with an estimated 97220 new cases expected by the end of 2018.It affects 1.2 million people around the world and is responsible...BACKGROUND Colon cancer is among the most commonly diagnosed cancers in the United States with an estimated 97220 new cases expected by the end of 2018.It affects 1.2 million people around the world and is responsible for about 0.6 million deaths every year.Despite decline in overall incidence and mortality over the past 30 years,there continues to be an alarming rise in early-onset colon cancer cases(<50 years).Patients are often diagnosed at late stages of the disease and tend to have poor survival.We previously showed that the WNT“gatekeeper”gene,secreted frizzled-related protein 4(SFRP4),is over-expressed in early-onset colon cancer.SFRP4 is speculated to play an essential role in cancer by inhibiting the epithelial mesenchymal transition(EMT).AIM To investigate the correlation between SFRP4 expression and EMT-linked genes in colon cancer and how it affects patient survival.METHODS SFRP4 expression relative to that of EMT-linked genes and survival analysis were performed using the University of California Santa Cruz Cancer Browser interface.RESULTS SFRP4 was found to be co-expressed with the EMT-linked markers CDH2,FN1,VIM,TWIST1,TWIST2,SNAI1,SNAI2,ZEB1,ZEB2,POSTN,MMP2,MMP7,MMP9,and COL1A1.SFRP4 expression negatively correlated with the EMTlinked suppressors CLDN4,CLDN7,TJP3,MUC1,and CDH1.The expression of SFRP4 and the EMT-linked markers was higher in mesenchymal-like samples compared to epithelial-like samples which potentially implicates SFRP4-EMT mechanism in colon cancer.Additionally,patients overexpressing SFRP4 presented with poor overall survival(P=0.0293).CONCLUSION Considering the implication of SFRP4 in early-onset colon cancer,particularly in the context of EMT,tumor metastasis,and invasion,and the effect of increased expression on colon cancer patient survival,SFRP4 might be a potential biomarker for early-onset colon cancer that could be targeted for diagnosis and/or disease therapy.展开更多
Both platinum-based doublet chemotherapy(PBC) and epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer(NSCLC). In early studi...Both platinum-based doublet chemotherapy(PBC) and epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer(NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival(OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials—involving 11,456 adult patients in 32 arms—were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian(predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs(r = 0.797, P < 0.001). The correlation was obvious in the trials in Asian populations(r = 0.936, P < 0.001) but was not statistically significant in the trials in predominantly Caucasian populations(r = 0.116, P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy.展开更多
BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures.Non-surgical treatment options like ...BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures.Non-surgical treatment options like radiotherapy and definitive chemoradiation(CRT)have been implemented.The trends in(non-)surgical treatment and its impact on overall survival(OS)in patients with proximal esophageal cancer are unclear,related to its rare disease status.To optimize treatment strategies and counseling of patients with proximal esophageal cancer,it is therefore essential to gain more insight through real-life studies.AIM To establish trends in treatment and OS in patients with proximal esophageal cancer.METHODS In this population-based study,patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry.The proximal esophagus consists of the cervical esophagus and the upper thoracic section,extending to 24 cm from the incisors.Trends in radiotherapy,chemotherapy,and surgery,and OS were assessed.Analyses were stratified by presence of distant metastasis.Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS,adjusted for patient,tumor,and treatment characteristics.RESULTS In total,2783 patients were included.Over the study period,the use of radiotherapy,resection,and CRT in non-metastatic disease changed from 53%,23%,and 1%in 1989-1994 to 21%,9%,and 49%in 2010-2014,respectively.In metastatic disease,the use of chemotherapy and radiotherapy increased over time.Median OS of the total population increased from 7.3 mo[95%confidence interval(CI):6.4-8.1]in 1989-1994 to 9.5 mo(95%CI:8.1-10.8)in 2010-2014(logrank P<0.001).In non-metastatic disease,5-year OS rates improved from 5%(95%CI:3%-7%)in 1989-1994 to 13%(95%CI:9%-17%)in 2010-2014(logrank P<0.001).Multivariable regression analysis demonstrated a significant treatment effect over time on survival.In metastatic disease,median OS was 3.8 mo(95%CI:2.5-5.1)in 1989-1994,and 5.1 mo(95%CI:4.3-5.9)in 2010-2014(logrank P=0.26).CONCLUSION OS significantly improved in non-metastatic proximal esophageal cancer,likely to be associated with an increased use of CRT.Patterns in metastatic disease did not change significantly over time.展开更多
Objective: This study aimed to establish a method to predict the overall survival(OS) of patients with stage Ⅰ-Ⅲ colorectal cancer(CRC) through coupling radiomics analysis of CT images with the measurement of tumor ...Objective: This study aimed to establish a method to predict the overall survival(OS) of patients with stage Ⅰ-Ⅲ colorectal cancer(CRC) through coupling radiomics analysis of CT images with the measurement of tumor ecosystem diversification.Methods: We retrospectively identified 161 consecutive patients with stage Ⅰ-Ⅲ CRC who had underwent radical resection as a training cohort. A total of 248 patients were recruited for temporary independent validation as external validation cohort 1, with 103 patients from an external institute as the external validation cohort 2. CT image features to describe tumor spatial heterogeneity leveraging the measurement of diversification of tumor ecosystem, were extracted to build a marker, termed the EcoRad signature. Multivariate Cox regression was used to assess the EcoRad signature, with a prediction model constructed to demonstrate its incremental value to the traditional staging system for OS prediction.Results: The EcoRad signature was significantly associated with OS in the training cohort [hazard ratio(HR)=6.670;95% confidence interval(95% CI): 3.433-12.956;P<0.001), external validation cohort 1(HR=2.866;95% CI: 1.646-4.990;P<0.001) and external validation cohort 2(HR=3.342;95% CI: 1.289-8.663;P=0.002).Incorporating the EcoRad signature into the prediction model presented a higher prediction ability(P<0.001) with respect to the C-index(0.813, 95% CI: 0.804-0.822 in the training cohort;0.758, 95% CI: 0.751-0.765 in the external validation cohort 1;and 0.746, 95% CI: 0.722-0.770 in external validation cohort 2), compared with the reference model that only incorporated tumor, node, metastasis(TNM) system, as well as a better calibration,improved reclassification and superior clinical usefulness.Conclusions: This study establishes a method to measure the spatial heterogeneity of CRC through coupling radiomics analysis with measurement of diversification of the tumor ecosystem, and suggests that this approach could effectively predict OS and could be used as a supplement for risk stratification among stage Ⅰ-Ⅲ CRC patients.展开更多
基金Supported by Peng-Cheng Talent-Medical Young Reserve Talent Training Program,No.XWRCHT20220002Xuzhou City Health and Health Commission Technology Project Contract,No.XWKYHT20230081and Key Research and Development Plan Project of Xuzhou City,No.KC22179.
文摘BACKGROUND Gastric cancer(GC)is prevalent and aggressive,especially when patients have distant lung metastases,which often places patients into advanced stages.By identifying prognostic variables for lung metastasis in GC patients,it may be po-ssible to construct a good prediction model for both overall survival(OS)and the cumulative incidence prediction(CIP)plot of the tumour.AIM To investigate the predictors of GC with lung metastasis(GCLM)to produce nomograms for OS and generate CIP by using cancer-specific survival(CSS)data.METHODS Data from January 2000 to December 2020 involving 1652 patients with GCLM were obtained from the Surveillance,epidemiology,and end results program database.The major observational endpoint was OS;hence,patients were se-parated into training and validation groups.Correlation analysis determined va-rious connections.Univariate and multivariate Cox analyses validated the independent predictive factors.Nomogram distinction and calibration were performed with the time-dependent area under the curve(AUC)and calibration curves.To evaluate the accuracy and clinical usefulness of the nomograms,decision curve analysis(DCA)was performed.The clinical utility of the novel prognostic model was compared to that of the 7th edition of the American Joint Committee on Cancer(AJCC)staging system by utilizing Net Reclassification Improvement(NRI)and Integrated Discrimination Improvement(IDI).Finally,the OS prognostic model and Cox-AJCC risk stratification model modified for the AJCC system were compared.RESULTS For the purpose of creating the OS nomogram,a CIP plot based on CSS was generated.Cox multivariate regression analysis identified eleven significant prognostic factors(P<0.05)related to liver metastasis,bone metastasis,primary site,surgery,regional surgery,treatment sequence,chemotherapy,radiotherapy,positive lymph node count,N staging,and time from diagnosis to treatment.It was clear from the DCA(net benefit>0),time-de-pendent ROC curve(training/validation set AUC>0.7),and calibration curve(reliability slope closer to 45 degrees)results that the OS nomogram demonstrated a high level of predictive efficiency.The OS prediction model(New Model AUC=0.83)also performed much better than the old Cox-AJCC model(AUC difference between the new model and the old model greater than 0)in terms of risk stratification(P<0.0001)and verification using the IDI and NRI.CONCLUSION The OS nomogram for GCLM successfully predicts 1-and 3-year OS.Moreover,this approach can help to ap-propriately classify patients into high-risk and low-risk groups,thereby guiding treatment.
文摘Background:Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial.Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain.Methods:In this phase 3,double-blind,placebo-controlled trial,we randomly assigned(in a 1:1 ratio)participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab(at a dose of 200 mg)or placebo every 3 weeks for up to 17 cycles(approximately 1 year)or until recurrence,the occurrence of unacceptable toxic effects,or withdrawal of consent.A significant improvement in disease-free survival according to investigator assessment(the primary end point)was shown previously.Overall survival was the key secondary end point.Safety was a secondary end point.
文摘BACKGROUND Increasingly extranodal marginal B-cell lymphoma of mucosa-associated lymphoid tissue,known as mucosa-associated lymphoid tissue(MALT)lymphoma,is a type of non-Hodgkin’s lymphoma.The prognosis of primary gastric MALT(GML)patients can be affected by many factors.Clinical risk factors,including age,type of therapy,sex,stage and family hematologic malignancy history,also have significant effects on the development of the disease.The available data are mainly focused on epidemiology;in contrast,few studies have investigated the prognostic variables for overall survival(OS)in patients with primary GML.Based on the realities above,we searched a large amount of data on patients diagnosed with primary GML in the Surveillance,Epidemiology and End Results(SEER)database.The aim was to develop and verify a survival nomogram model that can predict the overall survival prognosis of primary GML by com-bining prognostic and determinant variables.AIM To create an effective survival nomogram for patients with primary gastric GML.METHODS All data of patients with primary GML from 2004 to 2015 were collected from the SEER database.The primary endpoint was OS.Based on the LASSO and COX regression,we created and further verified the accuracy and effectiveness of the survival nomogram model by the concordance index(C-index),calibration curve and timedependent receiver operating characteristic(td-ROC)curves.RESULTS A total of 2604 patients diagnosed with primary GML were selected for this study.A total of 1823 and 781 people were randomly distributed into the training and testing sets at a ratio of 7:3.The median follow-up of all patients was 71 mo,and the 3-and 5-year OS rates were 87.2%and 79.8%,respectively.Age,sex,race,Ann Arbor stage and radiation were independent risk factors for OS of primary GML(all P<0.05).The C-index values of the nomogram were 0.751(95%CI:0.729-0.773)and 0.718(95%CI:0.680-0.757)in the training and testing cohorts,respectively,showing the good discrimination ability of the nomogram model.Td-ROC curves and calibration plots also indicated satisfactory predictive power and good agreement of the model.Overall,the nomogram shows favorable performance in discriminating and predicting the OS of patients with primary GML.CONCLUSION A nomogram was developed and validated to have good survival predictive performance based on five clinical independent risk factors for OS for patients with primary GML.Nomograms are a low-cost and convenient clinical tool in assessing individualized prognosis and treatment for patients with primary GML.
文摘BACKGROUND Fibrinogen-to-albumin ratio(FAR)has been found to be of prognostic significance for several types of malignant tumors.However,less is known about the association between FAR and survival outcomes in hepatocellular carcinoma(HCC)patients.AIM To explore the association between FAR and prognosis and survival in patients with HCC.METHODS A total of 366 histologically confirmed HCC patients diagnosed between 2013 and 2018 in a provincial cancer hospital in southwestern China were retrospectively selected.Relevant data were extracted from the hospital information system.The optimal cutoff for baseline serum FAR measured upon disease diagnosis was established using the receiver operating characteristic(ROC)curve.Univariate and multivariate Cox proportional hazards models were used to determine the crude and adjusted associations between FAR and the overall survival(OS)of the HCC patients while controlling for various covariates.The restricted cubic spline(RCS)was applied to estimate the dose-response trend in the FAR-OS association.RESULTS The optimal cutoff value for baseline FAR determined by the ROC was 0.081.Multivariate Cox proportional hazards model revealed that a lower baseline serum FAR level was associated with an adjusted hazard ratio of 2.43(95%confidence interval:1.87–3.15)in the OS of HCC patients,with identifiable dose-response trend in the RCS.Subgroup analysis showed that this FAR-OS association was more prominent in HCC patients with a lower baseline serum aspartate aminotransferase or carbohydrate antigen 125 level.CONCLUSION Serum FAR is a prominent prognostic indicator for HCC.Intervention measures aimed at reducing FAR might result in survival benefit for HCC patients.
基金the Major Science and Technology Project of Zhejiang Provincial Department of Science and Technology,No.2020C03030the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission,No.2022503200。
文摘BACKGROUND Preoperative anemia is associated with increased postoperative morbidity and mortality and increased perioperative transfusion risk.For surgical patients,this affects physical and cognitive ability and quality of life,but it is an important and modifiable risk factor.AIM To determine the effect of preoperative anemia on the prognosis of gastric cancer(GC)patients and generate a prognostic nomogram to predict the postoperative overall survival(OS)of GC patients with preoperative anemia.METHODS Clinicopathological and follow-up data of GC patients treated at Zhejiang Provincial People's Hospital(China)from 2010 to 2015 were collected.Independent prognostic factors were screened by univariate and multivariate Cox regression analyses.Then,these factors were used to construct a nomogram to predict 1-,3-,and 5-year postoperative OS in preoperative anemic GC patients.The nomogram was assessed by calibration curves,receiver operating characteristic(ROC)curves,and decision curve analysis(DCA).RESULTS Nine hundred and sixty GC patients were divided into two groups(preoper atively anemic and nonanemic),and postoperative survival analysis was performed on both groups,yielding a shorter postoperative survival for preoperatively anemic patients than for nonanemic patients.A total of 347 GC patients with preoperative anemia were included.Age,preoperative alpha-fetoprotein level,monocyte count,lymphocyte count,clinicopathological stage,liver metastasis,and GC type were identified as independent prognostic factors for OS.The area under the ROC curve(AUC)of the nomogram for predicting 1-,3-,and 5-year OS was 0.831,0.845,and 0.840,respectively,for the training cohort,and the corresponding AUC values in the validation cohort were 0.827,0.829,and 0.812,respectively.Calibration curves and DCA indicated good performance of the nomogram.CONCLUSION In all,we have successfully produced and verified a useful nomogram for predicting OS in GC patients with preoperative anemia.This nomogram based on a variety of clinicopathological indices can provide an effective prognostic assessment and help clinicians choose an appropriate treatment strategy for GC patients with preoperative anemia.
基金Supported by Department of Science and Technology of Jilin Province,No.20170623009TCJilin Province Development and Reform Commission,No.3J117B963428
文摘BACKGROUND Distant metastasis,particularly visceral metastasis(VM),represents an important negative prognostic factor for prostate cancer(PCa)patients.However,due to the lower rate of occurrence of VM,studies on these patients are relatively rare.Consequently,studies focusing on prognostic factors associated with PCa patients with VM are highly desirable.AIM To investigate the prognostic factors for overall survival(OS)in PCa patients with lung,brain,and liver metastases,respectively,and evaluate the impact of site-specific and number-specific VM on OS.METHODS Data on PCa patients with VM were extracted from the Surveillance,Epidemiology,and End Results database between 2010 and 2015.Univariate and multivariate Cox regression analyses were used to analyze the association between clinicopathological characteristics and survival of patients with different site-specific VM.Kaplan-Meier analyses and Log-rank tests were performed to analyze the differences among the groups.RESULTS A total of 1358 PCa patients with site-specific VM were identified from 2010 to 2015.Older age(>70 years)(P<0.001),higher stage(T3/T4)(P=0.004),and higher Gleason score(>8)(P<0.001)were found to be significant independent prognostic factors associated with poor OS in PCa patients with lung metastases.Higher stage(T3/T4)(P=0.047)was noted to be the only independent risk factor affecting OS in PCa patients with brain metastases.Older age(>70 years)(P=0.010)and higher Gleason score(>8)(P=0.001)were associated with shorter OS in PCa patients with liver metastases.PCa patients with isolated lung metastases exhibited significantly better survival outcomes compared with PCa patients with other single sites of VM(P<0.001).PCa patients with a single site of VM exhibited a superior OS compared with PCa patients with multiple sites of VM(P<0.001).CONCLUSION This is the first Surveillance,Epidemiology,and End Results-based study to determine prognostic factors affecting OS in PCa patients with different sitespecific VM.Clinical assessments of these crucial prognostic factors become necessary before establishing a treatment strategy for these patients with metastatic PCa.
文摘BACKGROUND Rectal cancer(RC)patient stratification by different factors may yield variable results.Therefore,more efficient prognostic biomarkers are needed for improved risk stratification,personalized treatment,and prognostication of RC patients.AIM To build a novel model for predicting the presence of distant metastases and 3-year overall survival(OS)in RC patients.METHODS This was a retrospective analysis of 148 patients(76 males and 72 females)with RC treated with curative resection,without neoadjuvant or postoperative chemoradiotherapy,between October 2012 and December 2015.These patients were allocated to a training or validation set,with a ratio of 7:3.Radiomic features were extracted from portal venous phase computed tomography(CT)images of RC.The least absolute shrinkage and selection operator regression analysis was used for feature selection.Multivariate logistic regression analysis was used to develop the radiomics signature(Rad-score)and the clinicoradiologic risk model(the combined model).Receiver operating characteristic curves were constructed to evaluate the diagnostic performance of the models for predicting distant metastasis of RC.The association of the combined model with 3-year OS was investigated by Kaplan-Meier survival analysis.RESULTS A total of 51(34.5%)patients had distant metastases,while 26(17.6%)patients died,and 122(82.4%)patients lived at least 3 years post-surgery.The values of both the Rad-score(consisted of three selected features)and the combined model were significantly different between the distant metastasis group and the nonmetastasis group(0.46±0.21 vs 0.32±0.24 for the Rad-score,and 0.60±0.23 vs 0.28±0.26 for the combined model;P<0.001 for both models).Predictors contained in the combined model included the Rad-score,pathological N-stage,and T-stage.The addition of histologic grade to the model failed to show incremental prognostic value.The combined model showed good discrimination,with areas under the curve of 0.842 and 0.802 for the training set and validation set,respectively.For the survival analysis,the combined model was associated with an improved OS in the whole cohort and the respective subgroups.CONCLUSION This study presents a clinicoradiologic risk model,visualized in a nomogram,that can be used to facilitate individualized prediction of distant metastasis and 3-year OS in patients with RC.
文摘BACKGROUND Signet ring cell carcinoma(SRCC)is an uncommon subtype in colorectal cancer(CRC),with a short survival time.Therefore,it is imperative to establish a useful prognostic model.As a simple visual predictive tool,nomograms combining a quantification of all proven prognostic factors have been widely used for predicting the outcomes of patients with different cancers in recent years.Until now,there has been no nomogram to predict the outcome of CRC patients with SRCC.AIM To build effective nomograms for predicting overall survival(OS)and causespecific survival(CSS)of CRC patients with SRCC.METHODS Data were extracted from the Surveillance,Epidemiology,and End Results database between 2004 and 2015.Multivariate Cox regression analyses were used to identify independent variables for both OS and CSS to construct the nomograms.Performance of the nomograms was assessed by concordance index,calibration curves,and receiver operating characteristic(ROC)curves.ROC curves were also utilized to compare benefits between the nomograms and the tumor-node-metastasis(TNM)staging system.Patients were classified as high-risk,moderate-risk,and low-risk groups using the novel nomograms.Kaplan-Meier curves were plotted to compare survival differences.RESULTS In total,1230 patients were included.The concordance index of the nomograms for OS and CSS were 0.737(95%confidence interval:0.728-0.747)and 0.758(95%confidence interval:0.738-0.778),respectively.The calibration curves and ROC curves demonstrated good predictive accuracy.The 1-,3-,and 5-year area under the curve values of the nomogram for predicting OS were 0.796,0.825 and 0.819,in comparison to 0.743,0.798,and 0.803 for the TNM staging system.In addition,the 1-,3-,and 5-year area under the curve values of the nomogram for predicting CSS were 0.805,0.847 and 0.863,in comparison to 0.740,0.794,and 0.800 for the TNM staging system.Based on the novel nomograms,stratified analysis showed that the 5-year probability of survival in the high-risk,moderate-risk,and low-risk groups was 6.8%,37.7%,and 67.0%for OS(P<0.001),as well as 9.6%,38.5%,and 67.6%for CSS(P<0.001),respectively.CONCLUSION Convenient and visual nomograms were built and validated to accurately predict the OS and CSS rates for CRC patients with SRCC,which are superior to the conventional TNM staging system.
基金Supported by the Special Fund Project of Guangdong Science and Technology,No.210728156901524,and No.210728156901519Medical Scientific Research Foundation of Guangdong Province,China,No.A2021432,and No.B2021448Shantou Medical Science and Technology Planning Project,No.210521236491457,and No.210625106490696.
文摘BACKGROUND There are few nomograms for the prognosis of Chinese patients with triplenegative breast cancer(TNBC).AIM To construct and validate a nomogram for overall survival(OS)of Chinese TNBC patients after surgery.METHODS This study used the data of SEER*stat 8.3.5 and selected Chinese patients with TNBC operated on between 2010 and 2015.Univariate and multivariate Cox proportional hazard regression models were used.The identified variables were integrated to form a predictive nomogram and risk stratification model;it was assessed with C-indexes and calibration curves.RESULTS The median and maximal OS of the 336 patients was 39 and 83 mo,respectively.The multivariate analysis showed that age(P=0.043),marital status(P=0.040),tumor localization(P=0.030),grade(P=0.035),T classification(P=0.012),and N classification(P=0.002)were independent prognostic factors.The six variables were combined to construct a 1-,3-and 5-year OS nomogram.The C-indexes of the nomogram to predict OS were 0.766 and compared to the seventh edition staging system,which was higher(0.766 vs 0.707,P<0.001).In order to categorize patients into different prognostic groups,a risk stratification model was created.There was a significant difference between the Kaplan–Meier curves of the entire cohort and each disease stage according to the nomogram.CONCLUSION The nomogram provided prognostic superiority over the traditional tumor,node and metastasis system.It could help clinicians make individual OS or risk predictions for Chinese TNBC patients after surgery.
文摘BACKGROUND The prognostic value of preoperative fluorine-18-fluorodeoxyglucose positronemission tomography(18 F-FDG PET)scan for determining overall survival(OS)in breast cancer(BC)patients is controversial.AIM To evaluate the OS predictive value of preoperative PET positivity after 15 years.METHODS We performed a retrospective search of the Universitair Ziekenhuis Brussel patient database for nonmetastatic patients who underwent preoperative PET between 2002-2008.PET positivity was determined by anatomical region of interest(AROI)findings for breast and axillary,sternal,and distant sites.The prognostic role of PET was examined as a qualitative binary factor(positive vs negative status)and as a continuous variable[maximum standard uptake value(SUVmax)]in multivariate survival analyses using Cox proportional hazards models.Among the 104 identified patients who received PET,36 were further analyzed for the SUVmax in the AROI.RESULTS Poor OS within the 15-year study period was predicted by PET-positive status for axillary(P=0.033),sternal(P=0.033),and combined PET-axillary/sternal(P=0.008)nodes.Poor disease-free survival was associated with PET-positive axillary status(P=0.040)and combined axillary/sternal status(P=0.023).Cox models confirmed the long-term prognostic value of combined PETaxillary/sternal status[hazard ratio(HR):3.08,95%confidence interval:1.42-6.69].SUVmax of ipsilateral breast and axilla as continuous covariates were significant predictors of long-term OS with HRs of 1.25(P=0.048)and 1.54(P=0.029),corresponding to relative increase in the risk of death of 25%and 54%per SUVmax unit,respectively.In addition,the ratio of the ipsilateral axillary SUVmax over the contralateral axillary SUVmax was the most significant OS predictor(P=0.027),with 1.94 HR,indicating a two-fold relative increase of mortality risk.CONCLUSION Preoperative PET is valuable for prediction of long-term survival.Ipsilateral axillary SUVmax ratio over the uninvolved side represents a new prognostic finding that warrants further investigation.
基金Supported by the National Natural Science Foundation of China,No.81773128 and No.81871998the Natural Science Basic Research Plan in Shaanxi Province of China,No.2018JM7013 and No.2017JM8039+1 种基金the Research Fund for Young Star of Science and Technology in Shaanxi Province,No.2018KJXX-022China Postdoctoral Science Foundation,No.2018M641000
文摘BACKGROUND Cellular senescence is a recognized barrier for progression of chronic liver diseases to hepatocellular carcinoma(HCC). The expression of a cluster of genes is altered in response to environmental factors during senescence. However, it is questionable whether these genes could serve as biomarkers for HCC patients.AIM To develop a signature of senescence-associated genes(SAGs) that predicts patients' overall survival(OS) to improve prognosis prediction of HCC.METHODS SAGs were identified using two senescent cell models. Univariate COX regression analysis was performed to screen the candidate genes significantly associated with OS of HCC in a discovery cohort(GSE14520) for the least absolute shrinkage and selection operator modelling. Prognostic value of this seven-gene signature was evaluated using two independent cohorts retrieved from the GEO(GSE14520) and the Cancer Genome Atlas datasets, respectively.Time-dependent receiver operating characteristic(ROC) curve analysis was conducted to compare the predictive accuracy of the seven-SAG signature and serum α-fetoprotein(AFP).RESULTS A total of 42 SAGs were screened and seven of them, including KIF18 B, CEP55,CIT, MCM7, CDC45, EZH2, and MCM5, were used to construct a prognostic formula. All seven genes were significantly downregulated in senescent cells andupregulated in HCC tissues. Survival analysis indicated that our seven-SAG signature was strongly associated with OS, especially in Asian populations, both in discovery and validation cohorts. Moreover, time-dependent ROC curve analysis suggested the seven-gene signature had a better predictive accuracy than serum AFP in predicting HCC patients' 1-, 3-, and 5-year OS.CONCLUSION We developed a seven-SAG signature, which could predict OS of Asian HCC patients. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Science,No.2017-I2M-4-003International Science and Technology Cooperation Projects,No.2015DFA30650 and No.2016YFE0107100+3 种基金Capital Special Research Project for Health Development,No.2014-2-4012Beijing Natural Science Foundation,No.L172055National Ten-thousand Talent ProgramBeijing Science and Technology Cooperation Special Award Subsidy Project
文摘AIM To integrate clinically significant variables related to prognosis after curative resection for gallbladder carcinoma(GBC) into a predictive nomogram.METHODS One hundred and forty-two GBC patients who underwent curative intent surgical resection at Peking Union Medical College Hospital(PUMCH) were included. This retrospective case study was conducted at PUMCH of the Chinese Academy of Medical Sciences and Peking Union Medical College(CAMS & PUMC) in China from January 1, 2003 to January 1, 2018. The continuous variable carbohydrate antigen 19-9(CA19-9) was converted into a categorical variable(cCA19-9) based on the normal reference range. Stages 0 to IIIA were merged into one category, while the remaining stages were grouped into another category. Pathological grade X(GX) was treated as a missing value. A multivariate Cox proportional hazards model was used to select variables to construct a nomogram. Discrimination and calibration of the nomogram were performed via the concordance index(C-index) and calibration plots. The performance of the nomogram was estimated using the calibration curve. Receiver operating characteristic(ROC) curve analysis and decision curve analysis(DCA) were performed to evaluate the predictive accuracy and net benefit of the nomogram, respectively.RESULTS Of these 142 GBC patients, 55(38.7%) were male, and the median and mean age were 64 and 63.9 years, respectively. Forty-eight(33.8%) patients in this cohort were censored in the survival analysis. The median survival time was 20 months. A series of methods, including the likelihood ratio test and Akaike information criterion(AIC) as well as stepwise, forward, and backward analyses, were used to select the model, and all yielded identical results. Jaundice [hazard ratio(HR) = 2.9; 95% confidence interval(CI): 1.60-5.27], cCA19-9(HR = 3.2; 95%CI: 1.91-5.39), stage(HR = 1.89; 95%CI: 1.16-3.09), and resection(R)(HR = 2.82; 95%CI: 1.54-5.16) were selected as significant predictors and combined into a survival time predictive nomogram(C-index = 0.803; 95%CI: 0.766-0.839). High prediction accuracy(adjusted C-index = 0.797) was further verified via bootstrap validation. The calibration plot demonstrated good performance of the nomogram. ROC curve analysis revealed a high sensitivity and specificity. A high net benefit was proven by DCA.CONCLUSION A nomogram has been constructed to predict the overall survival of GBC patients who underwent radical surgery from a clinical database of GBC at PUMCH.
基金Supported by the National Natural Science Foundation of China,No.81272480Science and Technology Commi-ssion of Shanghai Municipality,No.15411969900 and No.16DZ2342200
文摘AIM To investigate the predictive value of PIK3 CA and TP53 mutation status in colorectal cancer(CRC) patients treated with 5-fluorouracil-based chemotherapy.METHODS In this study, a total of 315 patients with histologically proven CRC were enrolled from Yangpu Hospital affiliated to Shanghai Tongji University between 2007 and 2011. Of these patients, 241 with stage Ⅱ/Ⅲ CRC received 5-fluorouracil-based adjuvant chemotherapy. Formalin-fixed paraffin-embedded lesion samples of the patients with curatively resected CRC were collected.Next-generation sequencing was performed to identify somatic gene mutations. The correlation of PIK3 CA and TP53 mutation status with overall survival(OS) was analyzed using a Cox proportional hazard model and the Kaplan-Meier method.RESULTS Among the 241 patients with stage Ⅱ/Ⅲ in this cohort, the PIK3 CA and/or TP53 mutation was detected in 177 patients, among which 54 patients had PIK3 CA and TP53 double mutations. The PIK3 CA or TP53 mutation was not significantly correlated with OS in univariate and multivariate analyses. Compared with patients without PIK3 CA and TP53 mutations, those with double PIK3 CA-TP53 mutations showed a significantly worse survival(univariate HR = 2.21; 95%CI: 1.15-4.24; multivariate HR = 2.02; 95%CI: 1.04-3.91). The PIK3 CA mutation located in the kinase domain showed a trend toward a shorter OS compared with wild-type tumors(multivariate HR = 1.56; 95%CI: 1.00-2.44; P = 0.052). The Kaplan-Meier curve showed that patients harboring the PIK3 CA mutation located in the kinase domain had a worse clinical outcome than those with wild-type status(Log-rank P = 0.041)CONCLUSION Double mutation of PIK3 CA and TP53 is correlated with a shorter OS in stage Ⅱ/Ⅲ CRC patients treated with 5-fluorouracil-based therapy.
文摘AIM:Clinicopathologic factors predicting overall survival (OS) would help identify a subset to benefit from adjuvant therapy. METHODS: One hundred and sixty-nine patients patients from 1984 to 2009 with curative resections for pancreatic adenocarcinoma were included. Tumors were staged by American Joint Committee on Cancer 7th edition criteria. Univariate and multivariable analyses were performed using Kaplan-Meier methodology or Cox proportional hazard models. Log-rank tests were performed. Statistical inferences were assessed by two-sided 5% significance level. RESULTS: Median age was 67.1 (57.2-73.0) years with equal gender distribution. Tumors were in the head (89.3%) or body/tail (10.7%). On univariate analysis, adjuvant therapy, lymph node (LN) ratio, histologic grade, negative margin status, absence of peripancreatic extension, and T stage were associated with improved OS. Adjuvant therapy, LN ratio, histologic grade, number of nodes examined, negative LN status, and absence of peripancreatic extension were associated with improved recurrence-free survival (RFS). On multivariable analysis, LN ratio and carbohydrate antigen (CA) 19-9 levels were associated with OS. LN ratio was associated with RFS. CONCLUSION: The LN ratio and CA 19-9 levels are independent prognostic factors following curative resections of pancreatic cancer.
基金National Natural Science Foundation of China,No.81373084 and No.81273065the Norman Bethune Program of Jilin Universit,No.2013025the Youth Fund of the First Hospital of Jilin University,No.JDYY42013014
文摘AIM: To investigate the role of single nucleotide polymorphisms(SNPs) in CD24 gene in susceptibility and overall survival of gastric cancer(GC).METHODS: We genotyped 3 tagging SNPs of CD24-P-534 in the promoter region, P170 in the coding region of exon 2 and P1527 in the 3′ untranslated region- using polymerase chain reaction-restriction fragment length polymorphism in specimens from 679 histologically-confirmed GC cases, 111 gastric atrophy(GA) cases and 976 tumor-free controls. Serumimmunoglobulin G antibodies to Helicobacter pylori(H. pylori) of all subjects were detected by enzyme-linked immunosorbent assay. CD24 expression was evaluated by immunohistochemistry in 131 GC specimens. Correlations between SNPs and risk of GC or GA were shown by P values and odd ratios(ORs) with 95% confidence intervals(95%CI) compared with the most common genotype of each SNP using the unconditional logistic regression model after adjusting for age, sex and H. pylori infection. Survival within each SNP group was plotted by Kaplan-Meier method and compared by log-rank test(recessive model). Hazard ratios with 95%CIs were computed by Cox regression model after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy.RESULTS: All of the three loci were in Hardy-Weinberg equilibrium in the control group. Median followup time for the 600 GC patients included in the survival analysis was 36.2 mo(range, 2.1-66.7 mo; 95%CI: 34.3-36.5 mo). Patients with the P-534 A/A genotype had significantly shorter survival(HR = 1.38, 95%CI: 1.01-1.88, P = 0.042) than did the C/C or C/A genotype carriers after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy. This trend was more evident in patients who lived longer than 2.5 years(HR = 7.55, 95%CI: 2.16-26.32, P = 0.001). The P170 T/T genotype was associated with a shorter lifespan than the non-T/T genotypes, but not significantly so. None of the three genetic variants was found to be associated with risk of GC(including tumor stage, grade and distant metastasis) or with risk of gastric atrophy. Furthermore, no difference of CD24 expression was found among the genotypes.CONCLUSION: The P-534 site in CD24 gene affects the overall survival of gastric cancer and may serve as a prognostic marker for gastric cancer.
基金National Key Project Research and Development Projects,No.S2016G9012International Science and Technology Cooperation Projects,No.2015DFA30650the Capital Special Research Project for Clinical Application,No.Z151100004015170
文摘AIM To clarify the prognostic significance of preoperative albumin-to-alkaline phosphatase ratio(AAPR) in cholangiocarcinoma(CCA) subjects receiving surgery.METHODS In this retrospective study, we included 303 CCA patients receiving surgery without preoperative therapy between 2002 and 2014. Clinicopathological characteristics(including AAPR) were analyzed to determine predictors of postoperative overall survival and recurrence-free survival(RFS). In addition,univariate and multivariate Cox proportional hazards models were conducted,followed by application of time-dependent receiver operating curves to identify the optimal cut-off.RESULTS Univariate and multivariate analyses revealed both decreased overall survival[hazard ratio(HR): 2.88, 95%CI: 1.19-5.78] and recurrence-free survival(HR: 2.31,95%CI: 1.40–3.29) in patients with AAPR < 0.41 compared to those with AAPR ≥0.41. The optimal cut-off of AAPR was 0.41. Of the 303 subjects, 253(83.5%) had an AAPR over 0.41. The overall 1-, 3- and 5-year survival rates were 70.2%, 38.0% and 16.5%, respectively in the low(< 0.41) AAPR group, which were significantly lower than those in the high(≥ 0.41) AAPR group(81.7%, 53.9%, and 33.4%,respectively)(P < 0.0001). Large tumor size, multiple tumors, and advanced clinical stage were also identified as significant predictors of poor prognosis.CONCLUSION Our outcomes showed that AAPR was a potential valuable prognostic indicator in CCA patients undergoing surgery, which should be further confirmed by prospective studies. Moreover, it is necessary to investigate the mechanisms concerning the correlation of low AAPR with poor post-operative survival in CCA patients.
基金Supported by the SAGES research grant(to Nfonsam VN)
文摘BACKGROUND Colon cancer is among the most commonly diagnosed cancers in the United States with an estimated 97220 new cases expected by the end of 2018.It affects 1.2 million people around the world and is responsible for about 0.6 million deaths every year.Despite decline in overall incidence and mortality over the past 30 years,there continues to be an alarming rise in early-onset colon cancer cases(<50 years).Patients are often diagnosed at late stages of the disease and tend to have poor survival.We previously showed that the WNT“gatekeeper”gene,secreted frizzled-related protein 4(SFRP4),is over-expressed in early-onset colon cancer.SFRP4 is speculated to play an essential role in cancer by inhibiting the epithelial mesenchymal transition(EMT).AIM To investigate the correlation between SFRP4 expression and EMT-linked genes in colon cancer and how it affects patient survival.METHODS SFRP4 expression relative to that of EMT-linked genes and survival analysis were performed using the University of California Santa Cruz Cancer Browser interface.RESULTS SFRP4 was found to be co-expressed with the EMT-linked markers CDH2,FN1,VIM,TWIST1,TWIST2,SNAI1,SNAI2,ZEB1,ZEB2,POSTN,MMP2,MMP7,MMP9,and COL1A1.SFRP4 expression negatively correlated with the EMTlinked suppressors CLDN4,CLDN7,TJP3,MUC1,and CDH1.The expression of SFRP4 and the EMT-linked markers was higher in mesenchymal-like samples compared to epithelial-like samples which potentially implicates SFRP4-EMT mechanism in colon cancer.Additionally,patients overexpressing SFRP4 presented with poor overall survival(P=0.0293).CONCLUSION Considering the implication of SFRP4 in early-onset colon cancer,particularly in the context of EMT,tumor metastasis,and invasion,and the effect of increased expression on colon cancer patient survival,SFRP4 might be a potential biomarker for early-onset colon cancer that could be targeted for diagnosis and/or disease therapy.
文摘Both platinum-based doublet chemotherapy(PBC) and epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer(NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival(OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials—involving 11,456 adult patients in 32 arms—were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian(predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs(r = 0.797, P < 0.001). The correlation was obvious in the trials in Asian populations(r = 0.936, P < 0.001) but was not statistically significant in the trials in predominantly Caucasian populations(r = 0.116, P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy.
文摘BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures.Non-surgical treatment options like radiotherapy and definitive chemoradiation(CRT)have been implemented.The trends in(non-)surgical treatment and its impact on overall survival(OS)in patients with proximal esophageal cancer are unclear,related to its rare disease status.To optimize treatment strategies and counseling of patients with proximal esophageal cancer,it is therefore essential to gain more insight through real-life studies.AIM To establish trends in treatment and OS in patients with proximal esophageal cancer.METHODS In this population-based study,patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry.The proximal esophagus consists of the cervical esophagus and the upper thoracic section,extending to 24 cm from the incisors.Trends in radiotherapy,chemotherapy,and surgery,and OS were assessed.Analyses were stratified by presence of distant metastasis.Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS,adjusted for patient,tumor,and treatment characteristics.RESULTS In total,2783 patients were included.Over the study period,the use of radiotherapy,resection,and CRT in non-metastatic disease changed from 53%,23%,and 1%in 1989-1994 to 21%,9%,and 49%in 2010-2014,respectively.In metastatic disease,the use of chemotherapy and radiotherapy increased over time.Median OS of the total population increased from 7.3 mo[95%confidence interval(CI):6.4-8.1]in 1989-1994 to 9.5 mo(95%CI:8.1-10.8)in 2010-2014(logrank P<0.001).In non-metastatic disease,5-year OS rates improved from 5%(95%CI:3%-7%)in 1989-1994 to 13%(95%CI:9%-17%)in 2010-2014(logrank P<0.001).Multivariable regression analysis demonstrated a significant treatment effect over time on survival.In metastatic disease,median OS was 3.8 mo(95%CI:2.5-5.1)in 1989-1994,and 5.1 mo(95%CI:4.3-5.9)in 2010-2014(logrank P=0.26).CONCLUSION OS significantly improved in non-metastatic proximal esophageal cancer,likely to be associated with an increased use of CRT.Patterns in metastatic disease did not change significantly over time.
基金supported by the National Key R&D Program of China (No. 2021YFF1201003)the Key R&D Program of Guangdong Province, China (No. 2021B0101420006)+2 种基金the National Science Fund for Distinguished Young Scholars (No. 81925023 and 82071892)the National Natural Science Foundation of China (No. 81771912 and 82071892)the National Natural Science Foundation for Young Scientists of China (No. 81701782 and 81901910).
文摘Objective: This study aimed to establish a method to predict the overall survival(OS) of patients with stage Ⅰ-Ⅲ colorectal cancer(CRC) through coupling radiomics analysis of CT images with the measurement of tumor ecosystem diversification.Methods: We retrospectively identified 161 consecutive patients with stage Ⅰ-Ⅲ CRC who had underwent radical resection as a training cohort. A total of 248 patients were recruited for temporary independent validation as external validation cohort 1, with 103 patients from an external institute as the external validation cohort 2. CT image features to describe tumor spatial heterogeneity leveraging the measurement of diversification of tumor ecosystem, were extracted to build a marker, termed the EcoRad signature. Multivariate Cox regression was used to assess the EcoRad signature, with a prediction model constructed to demonstrate its incremental value to the traditional staging system for OS prediction.Results: The EcoRad signature was significantly associated with OS in the training cohort [hazard ratio(HR)=6.670;95% confidence interval(95% CI): 3.433-12.956;P<0.001), external validation cohort 1(HR=2.866;95% CI: 1.646-4.990;P<0.001) and external validation cohort 2(HR=3.342;95% CI: 1.289-8.663;P=0.002).Incorporating the EcoRad signature into the prediction model presented a higher prediction ability(P<0.001) with respect to the C-index(0.813, 95% CI: 0.804-0.822 in the training cohort;0.758, 95% CI: 0.751-0.765 in the external validation cohort 1;and 0.746, 95% CI: 0.722-0.770 in external validation cohort 2), compared with the reference model that only incorporated tumor, node, metastasis(TNM) system, as well as a better calibration,improved reclassification and superior clinical usefulness.Conclusions: This study establishes a method to measure the spatial heterogeneity of CRC through coupling radiomics analysis with measurement of diversification of the tumor ecosystem, and suggests that this approach could effectively predict OS and could be used as a supplement for risk stratification among stage Ⅰ-Ⅲ CRC patients.
