Prognostic value of site-specific metastases in pancreatic adenocarcinoma: A Surveillance Epidemiology and End Results database analysis

AIM To evaluate the prognostic value of site-specific metastases among patients with metastatic pancreaticc arcinoma registered within the Surveillance, Epidemiology and End Results(SEER) database.METHODS SEER database(2010-2013) has been queried through SEER*Stat program to determine the presentation, treatment outcomes and prognostic outcomes of metastatic pancreatic adenocarcinoma according to the site of metastasis. In this study, metastatic pancreatic adenocarcinoma patients were classified according to the site of metastases(liver, lung, bone, brain and distant lymph nodes). We utilized chi-square test to compare the clinicopathological characteristics among different sites of metastases. We used Kaplan-Meier analysis and log-rank testing for survival comparisons. We employed Cox proportional model to perform multivariate analyses of the patient population; and accordingly hazard ratios with corresponding 95%CI were generated. Statistical significance was considered if a two-tailed P value < 0.05 was achieved. RESULTS A total of 13233 patients with stage Ⅳ pancreatic cancer and known sites of distant metastases were identified in the period from 2010-2013 and they were included into the current analysis. Patients with isolated distant nodal involvement or lung metastases have better overall and pancreatic cancer-specific survival compared to patients with isolated liver metastases(for overall survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001)(for pancreatic cancer-specific survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001). Multivariate analysis revealed that age < 65 years, white race, being married, female gender; surgery to the primary tumor and surgery to the metastatic disease were associated with better overall survival and pancreatic cancer-specific survival.CONCLUSION Pancreatic adenocarcinoma patients with isolated liver metastases have worse outcomes compared to patients with isolated lung or distant nodal metastases. Further research is needed to identify the highly selected subset of patients who may benefit from local treatment of the primary tumor and/or metastatic disease.

Prognostic impact of tumor deposits on overall survival in colorectal cancer:Based on Surveillance, Epidemiology, and End Results database

BACKGROUND In colorectal cancer, tumor deposits(TDs) are considered to be a prognostic factor in the current staging system, and are only considered in the absence of lymph node metastases(LNMs). However, this definition and the subsequent prognostic value based on it is controversial, with various hypotheses. TDs may play an independent role when it comes to survival and addition of TDs to LNM count may predict the prognosis of patients more accurately.AIM To assess the prognostic impact of TDs and evaluate the effect of their addition to the LNM count.METHODS The patients are derived from the Surveillance, Epidemiology, and End Results database. A prognostic analysis regarding impact of TDs on overall survival(OS) was performed using Cox regression model, and other covariates associating with OS were adjusted. The effect of addition of TDs to LNM count on N restaging was also evaluated. The subgroup analysis was performed to explore the different profile of risk factors between patients with and without TDs.RESULTS Overall, 103755 patients were enrolled with 14131(13.6%) TD-positive and 89624(86.4%) TD-negative tumors. TD-positive patients had worse prognosis compared with TD-negative patients, with 3-year OS rates of 47.3%(95%CI, 46.5%-48.1%) and 77.5%(95%CI, 77.2%-77.8%, P < 0.0001), respectively. On multivariable analysis, TDs were associated poorer OS(hazard ratio, 1.35;95%CI, 1.31-1.38;P < 0.0001). Among TD-positive patients, the number of TDs had a linear negative effect on disease-free survival and OS. After reclassifying patients by adding TDs to the LNM count, 885 of 19 965(4.4%) N1 patients were restaged as p N2, with worse outcomes than patients restaged as p N1(3-year OS rate: 78.5%, 95%CI, 77.9%-79.1% vs 63.2%, 95%CI, 60.1%-66.5%, respectively;P < 0.0001).CONCLUSION TDs are an independent prognostic factor for OS in colorectal cancer. The addition of TDs to LNM count improved the prognostic accuracy of tumor, node and metastasis staging.

Epidemiology and outcome of individuals with intraductal papillary neoplasms of the bile duct

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a rare distinct subtype of precursor lesions of biliary carcinoma.IPNB is considered to originate from luminal biliary epithelial cells,typically displays mucin-hypersecretion or a papillary growth pattern,and results in cystic dilatation[1].IPNB develops anywhere in the intrahepatic and extrahepatic biliary tracts,and can occur in various pathological stages from low-grade dysplasia to invasive carcinoma.IPNBs have similar phenotypic changes in the occurrence and development of all subtypes,and the prognosis is significantly better than that of traditional(nonpapillary)cholangiocarcinoma.AIM To evaluate the clinicopathological features of IPNB to provide evidence-based guidance for treatment.METHODS Invasive IPNB,invasive intraductal papillary mucinous neoplasm of the pancreas(IPMN),and traditional cholangiocarcinoma data for affected individuals from 1975 to 2016 were obtained from the Surveillance,Epidemiology,and End Results(SEER)database.Annual percentage changes(APCs)in the incidence and incidence-based(IB)mortality were calculated.We identified the independent predictors of overall survival(OS)and cancer-specific survival(CSS)in indivi duals with invasive IPNB.RESULTS The incidence and IB mortality of invasive IPNB showed sustained decreases,with an APC of-4.5%(95%CI:-5.1%to-3.8%)and-3.3%(95%CI:-4.1%to-2.6%)(P<0.001),respectively.Similar decreases in incidence and IB mortality were seen for invasive IPMN but not for traditional cholangiocarcinoma.Both OS and CSS for invasive IPNB were better than for invasive IPMN and traditional cholangiocarcinoma.A total of 1635 individuals with invasive IPNB were included in our prognosis analysis.The most common tumor sites were the pancreaticobiliary ampulla(47.9%)and perihilar tract(36.7%),but the mucin-related subtype of invasive IPNB was the main type,intrahepatically(approximately 90%).In the univariate and multivariate Cox regression analysis,age,tumor site,grade and stage,subtype,surgery,and chemotherapy were associated with OS and CSS(P<0.05).CONCLUSION Incidence and IB mortality of invasive IPNB trended steadily downward.The heterogeneity of IPNB comprises site and the tumor’s mucin-producing status.

Survival benefits and disparities in radiation therapy for elderly patients with pancreatic ductal adenocarcinoma

BACKGROUND Older patients represent a unique subgroup of the cancer patient population,for which the role of cancer therapy requires special consideration.However,the outcomes of radiation therapy(RT)in elderly patients with pancreatic ductal adenocarcinoma(PDAC)are not well-defined in the literature.AIM To explore the use and effectiveness of RT in the treatment of elderly patients with PDAC in clinical practice.METHODS Data from patients with PDAC aged≥65 years between 2004 and 2018 were collected from the Surveillance,Epidemiology,and End Results database.Multivariate logistic regression analysis was performed to determine factors associated with RT administration.Overall survival(OS)and cancer-specific survival(CSS)were evaluated using the Kaplan–Meier method with the log-rank test.Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors for OS.Propensity score matching(PSM)was applied to balance the baseline characteristics between the RT and non-RT groups.Subgroup analyses were performed based on clinical characteristics.RESULTS A total of 12245 patients met the inclusion criteria,of whom 2551(20.8%)were treated with RT and 9694(79.2%)were not.The odds of receiving RT increased with younger age,diagnosis in an earlier period,primary site in the head,localized disease,greater tumor size,and receiving chemotherapy(all P<0.05).Before PSM,the RT group had better outcomes than did the non-RT group[median OS,14.0 vs 6.0 mo;hazard ratio(HR)for OS:0.862,95%confidence interval(CI):0.819–0.908,P<0.001;and HR for CSS:0.867,95%CI:0.823–0.914,P<0.001].After PSM,the survival benefit associated with RT remained comparable(median OS:14.0 vs 11.0 mo;HR for OS:0.818,95%CI:0.768–0.872,P<0.001;and HR for CSS:0.816,95%CI:0.765–0.871,P<0.001).Subgroup analysis revealed that the survival benefits(OS and CSS)of RT were more significant in patients aged 65 to 80 years,in regional and distant stages,with no surgery,and receiving chemotherapy.CONCLUSION RT improved the outcome of elderly patients with PDAC,particularly those aged 65 to 80 years,in regional and distant stages,with no surgery,and who received chemotherapy.Further prospective studies are warranted to validate our results.

Data mining in clinical big data:the frequently used databases,steps,and methodological models

Many high quality studies have emerged from public databases,such as Surveillance,Epidemiology,and End Results(SEER),National Health and Nutrition Examination Survey(NHANES),The Cancer Genome Atlas(TCGA),and Medical Information Mart for Intensive Care(MIMIC);however,these data are often characterized by a high degree of dimensional heterogeneity,timeliness,scarcity,irregularity,and other characteristics,resulting in the value of these data not being fully utilized.Data-mining technology has been a frontier field in medical research,as it demonstrates excellent performance in evaluating patient risks and assisting clinical decision-making in building disease-prediction models.Therefore,data mining has unique advantages in clinical big-data research,especially in large-scale medical public databases.This article introduced the main medical public database and described the steps,tasks,and models of data mining in simple language.Additionally,we described data-mining methods along with their practical applications.The goal of this work was to aid clinical researchers in gaining a clear and intuitive understanding of the application of data-mining technology on clinical big-data in order to promote the production of research results that are beneficial to doctors and patients.

Risk stratification in gastric cancer lung metastasis: Utilizing an overall survival nomogram and comparing it with previous staging

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.

Epidemiologic characteristics and risk factors associated with overall survival for patients with mucinous colorectal cancer:A population-based study

BACKGROUND Mucinous adenocarcinoma(MC)has attracted much attention as a distinct histologic subtype of colorectal cancer in recent years.However,data about its epidemiologic and prognostic characteristics are limited.Therefore,patient data extracted from the National Cancer Institute’s Surveillance,Epidemiology,and End Results Program were collected to analyze the epidemiologic and clinicopathological characteristics of MC.AIM To determine the epidemiologic and clinicopathological characteristics of MC.METHODS The incidence trend of MC was calculated through the Joinpoint Regression Program.Cox regression analyses were performed to identify prognostic factors associated with overall survival(OS).A nomogram was established to predict the survival probability of individual patients with MC.RESULTS We found that rates of MC decreased from 4.50/100000 in 2000 to 1.54/100000 in 2018.Rates of MCs in patients aged≤50 years decreased 2.27%/year during 2000-2018.The incidence of appendiceal MCs increased from 0.14/100000 in 2000 to 0.24/100000 in 2018,while the incidence in other anatomic subsites continued to decrease.On multivariable Cox analyses,age,race,tumor site,T stage,N stage,M stage,surgery,and chemotherapy were associated with OS.A nomogram was developed based on these factors,and the area under the curve for 1-year,3-year,and 5-year OS in the training cohort was 0.778,0.778,and 0.768,respectively.CONCLUSION Our results demonstrated that MC incidence decreased in almost all anatomic subgroups except for the appendix.A nomogram predicting the survival probability of patients with MCs showed good performance.

National trends in resection of the distal pancreas

AIM:To investigate national trends in distal pancreatectomy(DP) through query of three national patient care databases.METHODS:From the Nationwide Inpatient Sample(NIS,2003-2009),the National Surgical Quality Improvement Project(NSQIP,2005-2010),and the Surveillance Epidemiology and End Results(SEER,2003-2009) databases using appropriate diagnostic and procedural codes we identified all patients with a diagnosis of a benign or malignant lesion of the body and/or tail of the pancreas that had undergone a partial or distal pancreatectomy.Utilization of laparoscopy was defined in NIS by the International Classification of Diseases,Ninth Revision correspondent procedure code;and in NSQIP by the exploratory laparoscopy or unlisted procedure current procedural terminology codes.In SEER,patients were identified by the International Classification of Diseases for Oncology,Third Edition diagnosis codes and the SEER Program Code Manual,third edition procedure codes.We analyzed the databases with respect to trends of inpatient outcome metrics,oncologic outcomes,and hospital volumes in patients with lesions of the neck and body of the pancreas that underwent operative resection.RESULTS:NIS,NSQIP and SEER identified 4242,2681 and 11 082 DP resections,respectively.Overall,laparoscopy was utilized in 15%(NIS) and 27%(NSQIP).No significant increase was seen over the course of the study.Resection was performed for malignancy in 59%(NIS) and 66%(NSQIP).Neither patient Body mass index nor comorbidities were associated with operative approach(P = 0.95 and P = 0.96,respectively).Mortality(3% vs 2%,P = 0.05) and reoperation(4% vs 4%,P = 1.0) was not different between laparoscopy and open groups.Overall complications(10% vs 15%,P < 0.001),hospital costs [44 741 dollars,interquartile range(IQR) 28 347-74 114 dollars vs 49 792 dollars,IQR 13 299-73 463,P = 0.02] and hospital length of stay(7 d,IQR 4-11 d vs 7 d,IQR 6-10,P < 0.001) were less when laparoscopy was utilized.One and two year survival after resection for malignancy were unchanged over the course of the study(ductal adenocarinoma 1-year 63.6% and 2-year 35.1%,P = 0.53;intraductal papillary mucinous neoplasm and nueroendocrine 1-year 90% and 2-year 84%,P = 0.25).The majority of resections were performed in teaching hospitals(77% NIS and 85% NSQIP),but minimally invasive surgery(MIS) was not more likely to be used in teaching hospitals(15% vs 14%,P = 0.26).Hospitals in the top decile for volume were more likely to be teaching hospitals than lower volume deciles(88% vs 43%,P < 0.001),but were no more likely to utilize MIS at resection.Complication rate in teaching and the top decile hospitals was not significantly decreased when compared to non-teaching(15% vs 14%,P = 0.72) and lower volume hospitals(14% vs 15%,P = 0.99).No difference was seen in the median number of lymph nodes and lymph node ratio in N1 disease when compared by year(P = 0.17 and P = 0.96,respectively).CONCLUSION:There appears to be an overall underutilization of laparoscopy for DP.Centralization does not appear to be occurring.Survival and lymph node harvest have not changed.

Risk factors,prognostic predictors,and nomograms for pancreatic cancer patients with initially diagnosed synchronous liver metastasis

BACKGROUND Liver metastasis(LM)remains a major cause of cancer-related death in patients with pancreatic cancer(PC)and is associated with a poor prognosis.Therefore,identifying the risk and prognostic factors in PC patients with LM(PCLM)is essential as it may aid in providing timely medical interventions to improve the prognosis of these patients.However,there are limited data on risk and prognostic factors in PCLM patients.AIM To investigate the risk and prognostic factors of PCLM and develop corresponding diagnostic and prognostic nomograms.METHODS Patients with primary PC diagnosed between 2010 and 2015 were reviewed from the Surveillance,Epidemiology,and Results Database.Risk factors were identified using multivariate logistic regression analysis to develop the diagnostic mode.The least absolute shrinkage and selection operator Cox regression model was used to determine the prognostic factors needed to develop the prognostic model.The performance of the two nomogram models was evaluated using receiver operating characteristic(ROC)curves,calibration plots,decision curve analysis(DCA),and risk subgroup classification.The Kaplan-Meier method with a logrank test was used for survival analysis.RESULTS We enrolled 33459 patients with PC in this study.Of them,11458(34.2%)patients had LM at initial diagnosis.Age at diagnosis,primary site,lymph node metastasis,pathological type,tumor size,and pathological grade were identified as independent risk factors for LM in patients with PC.Age>70 years,adenocarcinoma,poor or anaplastic differentiation,lung metastases,no surgery,and no chemotherapy were the independently associated risk factors for poor prognosis in patients with PCLM.The C-index of diagnostic and prognostic nomograms were 0.731 and 0.753,respectively.The two nomograms could accurately predict the occurrence and prognosis of patients with PCLM based on the observed analysis results of ROC curves,calibration plots,and DCA curves.The prognostic nomogram could stratify patients into prognostic groups and perform well in internal validation.CONCLUSION Our study identified the risk and prognostic factors in patients with PCLM and developed corresponding diagnostic and prognostic nomograms to help clinicians in subsequent clinical evaluation and intervention.External validation is required to confirm these results.

Comparison of clinicopathological characteristics and survival outcomes between gallbladder mucinous adenocarcinoma and gallbladder adenocarcinoma:A propensity score-matched study

BACKGROUND Gallbladder mucinous adenocarcinoma(GBMAC)is a rare subtype of gallbladder adenocarcinoma(GBAC),with limited knowledge of its survival outcomes from small case series and single-center retrospective analysis.AIM To compare the clinicopathological characteristics of GBMAC with typical GBAC and its prognostic factors to gain insights into this field.METHODS This study was conducted using data from the Surveillance,Epidemiology,and End Results database,including cases of GBMAC and typical GBAC diagnosed from 2010 to 2017.The Pearson chi-square test or Fisher exact test was used to examine the differences in clinicopathological features between these two cohorts.In addition,propensity score matching(PSM)analysis was performed to balance the selection biases.Univariate and multivariate Cox hazards regression analyses were performed to determine independent prognostic factors for cancer-speci
c survival(CSS)and overall survival(OS).The Kaplan–Meier curves and log-rank tests were used to assess the OS and CSS of GBMAC and typical GBAC patients.RESULTS The clinicopathological and demographic characteristics of GBMAC were different from typical GBAC.They included a larger proportion of patients with unmarried status,advanced American Joint Committee on Cancer(AJCC)stage,higher T stage,higher N1 stage rate and lower N0 and N2 stage rates(P<0.05).Multivariate analyses demonstrated that surgery[OS:Hazard ratio(HR)=2.27,P=0.0037;CSS:HR=2.05,P=0.0151],chemotherapy(OS:HR=6.41,P<0.001;CSS:HR=5.24,P<0.001)and advanced AJCC stage(OS:Stage IV:HR=28.99,P=0.0046;CSS:Stage III:HR=12.31,P=0.015;stage IV:HR=32.69,P=0.0015)were independent prognostic indicators for OS and CSS of GBMAC patients.Furthermore,after PSM analysis,there was no significant difference between GBMAC and matched typical GBAC patients regarding OS(P=0.82)and CSS(P=0.69).CONCLUSION The biological behaviors of GBMAC are aggressive and significantly different from that of typical GBAC.However,they show similar survival prognoses.Surgery,chemotherapy,and lower AJCC stage were associated with better survival outcomes.Further research is needed in the future to verify these results.

乳腺癌共发甲状腺癌的危险因素及预后分析

目的分析乳腺癌(BC)共发甲状腺癌(TC)的危险因素,探讨预后影响因素。方法在2020年监测、流行病学和结果(SEER)数据库搜集BC共发TC患者(共发组)以及单纯BC患者(单纯组)的信息,比较2组临床资料和生存信息。回顾性分析某医院住院的BC共发TC患者(共发组A)以及单纯BC患者(单纯组A)的临床资料,比较2组临床资料以及生存信息。结果①SEER数据库分析,共发组482例、单纯组500例,单因素分析显示首次确诊年龄和孕激素受体(PR)是BC共发TC的危险因素(P均<0.05),多因素分析显示首次确诊年龄(OR=1.800,95%CI:1.387~2.337,P<0.001)、PR(OR=1.364,95%CI:1.023~1.818,P=0.034)是BC共发TC的独立危险因素。剔除随访资料不完整者后的单因素分析显示肿瘤直径和PR是BC共发TC的预后因素(P<0.05),多因素分析显示肿瘤直径是BC共发TC的独立预后因素(OR=4.328,95%CI:1.410~13.288,P=0.010);单因素分析显示首次确诊年龄和肿瘤直径是单纯BC的预后因素(P均<0.05),多因素分析显示首次确诊年龄(OR=2.443,95%CI:1.014~5.889,P=0.047)、肿瘤直径(OR=2.030,95%CI:1.039~3.969,P=0.038)是单纯BC的独立预后因素。②某医院住院患者分析,共发组A 40例(50%),单纯组A 40例(50%)。单因素分析显示月经情况、PR、增殖指数Ki-67、TT_(3)是BC共发TC的危险因素(P<0.05);多因素分析显示月经情况(OR=0.175,95%CI:0.052~0.591,P=0.005)、PR(OR=5.686,95%CI:1.677~19.282,P=0.005)、Ki-67(OR=3.966,95%CI:1.133~13.875,P=0.031)是BC共发TC的独立危险因素。对80例患者进行随访,共发组A死亡6例,生存27例,失访7例;单纯组A死亡2例,生存29例,失访9例。2组患者Cox回归分析结果均无统计学意义(P均>0.05)。结论首次确诊年龄、月经情况、PR、Ki-67是BC共发TC的危险因素。肿瘤直径是BC共发TC的独立预后因素。首次确诊年龄和肿瘤直径是单纯BC的独立预后因素。

基于SEER数据库的乳腺髓样癌预后分析及预测模型构建

目的 分析典型乳腺髓样癌(TMBC)与不典型乳腺髓样癌(AMCB)的临床病理特征和预后差异,构建乳腺髓样癌(MBC)预后预测模型。方法 收集美国国家癌症研究所监测、流行病学及结局项目(SEER)数据库中2004年1月至2017年12月经病理学诊断为TMBC(2 017例)和AMCB(157例)的患者。比较两组患者临床病理特征,采用Kaplan-Meier法比较两组的总生存期(OS)和乳腺癌特异生存期(BCSS),并进行亚组分析。采用Cox回归分析影响MBC患者OS的危险因素;构建基于危险因素的OS预测模型,绘制ROC曲线、校正曲线和决策曲线评估模型的预测效能。结果 两组患者临床病理特征比较,差异均无统计学意义(均P>0.05),Kaplan-Meier生存曲线表明两组患者OS和BCSS比较,差异均无统计学意义(均P>0.05)。亚组分析显示,肿瘤直径>5 cm的亚组中AMCB患者OS较差。Cox单因素分析表明年龄、婚姻状况、原发侧、美国癌症联合委员会(AJCC)分期、淋巴结状态、孕激素受体、放化疗、肿瘤大小是MBC预后的危险因素,Cox多因素分析表明年龄、婚姻状况、AJCC分期、淋巴结状态、化疗、肿瘤大小是独立危险因素。基于独立危险因素构建预测MBC 1、3、5年OS的预后模型。ROC曲线、校正曲线和决策曲线均显示该模型有良好的预测效能。结论 TMBC与AMCB的临床病理特征和预后相似,构建MBC预后预测模型可有效预测MBC患者预后。

多发恶性肿瘤次原发食管癌的生存预后分析:基于人群的分析

目的 探讨次原发食管癌(SPE)易发因素及影响其预后的相关因素。方法 选取监测/流行病学和最终结果(SEER)数据库中,2000~2019年病理诊断明确食管癌病人,并从中筛选出以其他恶性肿瘤为首发,食管癌为次原发(secondary primary esophageal cancer-SPE)的病人资料,采用Logistic回归分析SPE发生的独立危险因素,并利用Cox比例风险分析影响预后的独立危险因素。结果 多原发恶性肿瘤伴食管癌病人13 520例,经筛选后SPE病人8 308例。Logistic多因素分析显示,年龄、肿瘤部位、肿瘤分化程度、病理学结果、SEER肿瘤侵犯程度及区域淋巴结的采取情况是影响发生SPE的独立因素,Cox多因素分析提示,年龄、确诊年限、种族、肿瘤分化程度、SEER肿瘤侵犯程度、手术、化疗、放疗及三联疗法均为影响SPE的独立危险因素。结论 年龄、确诊年限、种族、肿瘤分化程度、SEER肿瘤侵犯程度、手术、化疗、放疗及三联疗法是SPE发生的危险因素,手术可能是治疗的有效方式。

基于SEER数据库构建直肠癌术后患者的生存预测列线图及其验证

目的 分析直肠癌术后患者总生存期(OS)的影响因素并构建其风险预测列线图模型。方法 从SEER数据库中筛选2010—2015年经病理诊断为直肠癌并行手术治疗的患者14201例,按照7∶3的比例随机分为训练集9941例和验证集4260例;另收集兰州大学第二医院2017年1月1日—2021年12月31日与SEER数据库提取标准一致的直肠癌术后患者376例作为外部验证集。通过单因素及多因素COX回归分析并确定影响直肠癌术后患者OS的独立危险因素,据此构建列线图预测模型。通过C指数、受试者操作特征曲线下面积(AUC)评价该模型的区分能力,校准曲线评价该模型的预测值与实际值之间的接近程度。结果 多因素COX回归分析显示,直肠癌术后患者预后相关独立危险因素有13个,包括一般人口学(性别、年龄、婚姻状态)、肿瘤特征学[肿瘤原发部位、肿瘤分期、T分期、N分期、神经侵犯、癌胚抗原(CEA)水平、远处转移(肝转移、肺转移、骨转移)]及化疗(P<0.05)。基于这些独立危险因素构建了直肠癌术后患者生存预测的列线图模型,通过训练集及验证集C指数、AUC及校准曲线显示该预测模型的预测值与实际值具有较好的一致性。结论 基于SEER数据库构建的直肠癌术后患者生存预测的列线图效果良好,且将直肠癌肿瘤原发部位划分后发现发生在直肠的肿瘤较直肠乙状结肠交界处的肿瘤预后更差。

以SEER为基础的列线图构建和胰腺癌病人生存预测

目的:基于监测、流行病学和最终结果(surveillance,epidemiology,and end results,SEER)数据库,分析影响胰腺癌预后的独立因素并构建预测模型。方法:本研究从SEER数据库获取2010-2015年美国7801例胰腺癌病人的临床资料,以7∶3的比例随机分为建模组、验证组。对建模组临床变量进行多因素COX回归分析获得影响生存的独立因素,构建列线图。通过受试者操作特性(receiver operating characteristic,ROC)曲线和校准曲线验证模型的准确性。结果:年龄、原发部位、病理分级、T分期、N分期、M分期、手术方式、放疗、化疗与胰腺癌的预后相关,总生存的3年、5年ROC曲线下面积(area under cure,AUC)分别为0.90、0.91,癌症特异性生存分别为0.91、0.91。校准曲线显示观察值与预测值之间具有良好的一致性。经筛选得到的临床变量确实对胰腺癌预后有影响。结论:所构建的模型具有较好的预测准确性,有助于胰腺癌病人的临床决策和个性化治疗。

Factors associated with 5-year survival of combined hepatocellular and cholangiocarcinoma

BACKGROUND Combined hepatocellular and cholangiocarcinoma(HCC/CC)is a rare primary hepatic malignancy which carries a poor prognosis due to its aggressive nature.Few centers have enough cases to draw definitive conclusions and there is limited understanding of prognosis.Given the rarity of HCC/CC,an analysis of large national cancer database was needed to obtain larger number of HCC/CC cases.AIM To identify associated factors for 5-year survival of HCC/CC.METHODS We conducted a retrospective study of The Surveillance,Epidemiology,and End Results(SEER)database obtained from SEER*Stat 8.3.6 software.Previously defined histology code 8180 for the International Classification of Disease for Oncology,3rd edition was used to identify HCC/CC cases from 2004 to 2015.We collected demographics,American Joint Committee on Cancer(AJCC)stage,treatment,tumor size,and survival data.These data were converted to categorical variables.The Shapiro-Wilk normality test was used to assess normal distribution.Mann-Whitney U test was used to compare continuous variables without normal distribution,and t-test was used to compare continuous variables with a normal distribution.The Kaplan-Meier survival curve analyzed 5-year survival.Univariate and multivariate logistic regression model was used to analyze factors associated with 5-year survival.Multivariate Cox proportional hazard regression was done on 5-year survival.We defined P<0.05 was statistically significant.RESULTS We identified 497 patients with the following characteristics:Mean age 62.4 years(SD:11.3),149(30.0%)were female,racial distribution was:276(55.5%)white,53(10.7%)black,84(16.9%)Asian and Pacific Islander(API),77(15.5%)Hispanic,and 7(1.4%)others or unknown.Stage I/II disease occurred in 41.5%and tumor size<50 mm was seen in 35.6%of patients.Twenty-four(4.8%)received locoregional therapy(LRT),119(23.9%)underwent resection,and 50(10.1%)underwent liver transplantation.The overall median survival was 6 mo[Interquartile range(IQR):1-22].After multivariate logistic regression,tumor size<50 mm[Odds ratios(OR):2.415,P=0.05],resection(OR:12.849,P<0.01),and transplant(OR:27.129,P<0.01)showed significance for 5-year survival.Age>60,sex,race,AJCC stages,metastasis,and LRT were not significant.However,API vs white showed significant OR of 2.793(CI:1.120-6.967).Cox proportional hazard regression showed AJCC stages,tumor size<50 mm,LRT,resection,and transplant showed significant hazard ratio.CONCLUSION HCC/CC patients with tumor size<50 mm,resection,and transplant were associated with an increase in 5-year survival.API showed advantageous OR and hazard ratios over white,black.

Adenosquamous carcinoma may have an inferior prognosis to signet ring cell carcinoma in patients with stages Ⅰ and Ⅱ gastric cancer

BACKGROUND Primary gastric adenosquamous carcinoma(ASC)is an exceedingly rare histological subtype.Gastric signet ring cell carcinoma(SRC)is a unique subtype with distinct tumor biology and clinical features.The prognosis of gastric ASC vs SRC has not been well established to date.We hypothesized that further knowledge about these distinct cancers would improve the clinical management of such patients.AIM To investigate the clinicopathological characteristics and prognosis of gastric ASC vs SRC.METHODS A cohort of gastric cancer patients was retrospectively collected from the Surveillance,epidemiology,and end results program database.The 1:4 propensity score matching was performed among this cohort.The clinicopathological features and prognosis of gastric ASC were compared with gastric SRC by descriptive statistics.Kaplan-Meier method was utilized to calculate the median survival of the two groups of patients.Cox proportional hazard regression models were used to identify prognostic factors.RESULTS Totally 6063 patients with gastric ASC or SRC were identified.A cohort of 465 patients was recruited to the matched population,including 370 patients with SRC and 95 patients with ASC.Gastric ASC showed an inferior prognosis to SRC after propensity score matching.In the post-matching cohort,the median cancer specific survival was 13.0(9.7-16.3)mo in the ASC group vs 20.0(15.7-24.3)mo in the SRC group,and the median overall survival had a similar trend(P<0.05).ASC and higher tumor-node-metastasis stage were independently associated with a poor survival,while radiotherapy and surgery were independent protective factors for improved prognosis.Subgroup survival analysis revealed that the prognosis of ASC was inferior to SRC only in stages I and II patients.CONCLUSION ASC may have an inferior prognosis to SRC in patients with stages I and II gastric cancer.Our study supports radiotherapy and surgery for the future management of this clinically rare entity.

Long-term survival of patients with stage Ⅱ and Ⅲgastric cancer who underwent gastrectomy with inadequate nodal assessment

BACKGROUND Gastric cancer is an aggressive disease with frequent lymph node(LN)involvement.The NCCN recommends a D2 lymphadenectomy and the harvesting of at least 16 LNs.This threshold has been the subject of great debate,not only for the extent of surgery but also for more appropriate staging.The reclassification of stage IIB through IIIC based on N3b nodal staging in the eighth edition of the American Joint Committee on Cancer(AJCC)staging system highlights the efforts to more accurately discriminate survival expectancy based on nodal number.Furthermore,studies have suggested that pathologic assessment of 30 or more LNs improve prognostic accuracy and is required for proper staging of gastriccancer.AIM To evaluate the long-term survival of advanced gastric cancer patients who deviated from expected survival curves because of inadequate nodal evaluation.METHODS Eligible patients were identified from the Surveillance,Epidemiology,and End Results database.Those with stage II-III gastric cancer were considered for inclusion.Three groups were compared based on the number of analyzed LNs.They were inadequate LN assessment(ILA,<16 LNs),adequate LN assessment(ALA,16-29 LNs),and optimal LN assessment(OLA,≥30 LNs).The main outcomes were overall survival(OS)and cancer-specific survival.Data were analyzed by the Kaplan-Meier product-limit method,log-rank test,hazard risk,and Cox proportional univariate and multivariate models.Propensity score matching(PSM)was used to compare the ALA and OLA groups.RESULTS The analysis included 11607 patients.Most had advanced T stages(T3=48%;T4=42%).The pathological AJCC stage distribution was IIA=22%,IIB=18%,IIIA=26%,IIIB=22%,and IIIC=12%.The overall sample divided by the study objective included ILA(50%),ALA(35%),and OLA(15%).Median OS was 24 mo for the ILA group,29 mo for the ALA group,and 34 mo for the OLA group(P<0.001).Univariate analysis showed that the ALA and OLA groups had better OS than the ILA group[ALA hazard ratio(HR)=0.84,95%confidence interval(CI):0.79-0.88,P<0.001 and OLA HR=0.73,95%CI:0.68-0.79,P<0.001].The OS outcome was confirmed by multivariate analysis(ALA HR=0.68,95%CI:0.64-0.71,P<0.001 and OLA:HR=0.48,95%CI:0.44-0.52,P<0.001).A 1:1 PSM analysis in 3428 patients found that the OLA group had better survival than the ALA group(OS:OLA median=34 mo vs ALA median=26 mo,P<0.001,which was confirmed by univariate analysis(HR=0.81,95%CI:0.75-0.89,P<0.001)and multivariate analysis:(HR=0.71,95%CI:0.65-0.78,P<0.001).CONCLUSION Proper nodal staging is a critical issue in gastric cancer.Assessment of an inadequate number of LNs places patients at high risk of adverse long-term survival outcomes.

Development and validation of a prognostic nomogram for colorectal cancer after surgery

BACKGROUND A nomogram is a diagram that aggregates various predictive factors through multivariate regression analysis,which can be used to predict patient outcomes intuitively.Lymph node(LN)metastasis and tumor deposit(TD)conditions are two critical factors that affect the prognosis of patients with colorectal cancer(CRC)after surgery.At present,few effective tools have been established to predict the overall survival(OS)of CRC patients after surgery.AIM To screen out suitable risk factors and to develop a nomogram that predicts the postoperative OS of CRC patients.METHODS Data from a total of 3139 patients diagnosed with CRC who underwent surgical removal of tumors and LN resection from 2010 to 2015 were collected from the Surveillance,Epidemiology,and End Results program.The data were divided into a training set(n=2092)and a validation set(n=1047)at random.The Harrell concordance index(C-index),Akaike information criterion(AIC),and area under the curve(AUC)were used to assess the predictive performance of the N stage from the American Joint Committee Cancer tumor-node-metastasis classification,LN ratio(LNR),and log odds of positive lymph nodes(LODDS).Univariate and multivariate analyses were utilized to screen out the risk factors significantly correlating with OS.The construction of the nomogram was based on Cox regression analysis.The C-index,receiver operating characteristic(ROC)curve,and calibration curve were employed to evaluate the discrimination and prediction abilities of the model.The likelihood ratio test was used to compare the sensitivity and specificity of the final model to the model with the N stage alone to evaluate LN metastasis.RESULTS The predictive efficacy of the LODDS was better than that of the LNR based on the C-index,AIC values,and AUC values of the ROC curve.Seven independent predictive factors,namely,race,age at diagnosis,T stage,M stage,LODDS,TD condition,and serum carcinoembryonic antigen level,were included in the nomogram.The C-index of the nomogram for OS prediction was 0.8002(95%CI:0.7839-0.8165)in the training set and 0.7864(95%CI:0.7604-0.8124)in the validation set.The AUC values of the ROC curve predicting the 1-,3-,and 5-year OS were 0.846,0.841,and 0.825,respectively,in the training set and 0.823,0.817,and 0.835,respectively,in the validation test.Great consistency between the predicted and actual observed OS for the 1-,3-,and 5-year OS in the training set and validation set was shown in the calibration curves.The final nomogram showed a better sensitivity and specificity than the nomogram with N stage alone for evaluating LN metastasis in both the training set(-4668.0 vs-4688.3,P<0.001)and the validation set(-1919.5 vs-1919.8,P<0.001)through the likelihood ratio test.CONCLUSION The nomogram incorporating LODDS,TD,and other risk factors showed great predictive accuracy and better sensitivity and specificity and represents a potential tool for therapeutic decision-making.

Critical prognostic value of the log odds of negative lymph nodes/tumor size in rectal cancer patients

BACKGROUND The number of negative lymph nodes(NLNs)and tumor size are associated with prognosis in rectal cancer patients undergoing surgical resection.However,little is known about the prognostic significance of the NLN count after adjusting for tumor size.AIM To assess the prognostic impact of the log odds of NLN/tumor size(LONS)in rectal cancer patients.METHODS Data of patients with stage I–III rectal cancer were extracted from the Surveillance,Epidemiology,and End Results Program database.These patients were randomly divided into a training cohort and a validation cohort.Univariate and multivariate Cox regression analyses were used to determine the prognostic value of the LONS.The optimal cutoff values of LONS were calculated using the"X-tile"program.Stratified analysis of the effect of LONS on cancer-specific survival(CSS)and overall survival(OS)were performed.The Kaplan-Meier method with the log-rank test was used to plot the survival curve and compare the survival data among the different groups.RESULTS In all,41080 patients who met the inclusion criteria were randomly divided into a training cohort(n=28775,70%)and a validation cohort(n=12325,30%).Univariate and multivariate analyses identified the continuous variable LONS as an independent prognostic factor for CSS[training cohort:Hazard ratio(HR)=0.47,95%confidence interval(CI):0.44–0.51,P<0.001;validation cohort:HR=0.46,95%CI:0.41-0.52,P<0.001]and OS(training cohort:HR=0.53,95%CI:0.49-0.56,P<0.001;validation cohort:HR=0.52,95%CI:0.42-0.52,P<0.001).The Xtile program indicated that the difference in CSS was the most significant for LONS of-0.8,and the cutoff value of-0.4 can further distinguish patients with a better prognosis in the high LONS group.Stratified analysis of the effect of the categorical variable LONS on CSS and OS revealed that LONS was also an independent predictor,independent of pN stage,pT stage,tumor-node-metastasis stage,site,age,sex,the number of examined lymph nodes,race,preoperative radiotherapy and carcinoembryonic antigen level.CONCLUSION LONS is associated with improved survival of rectal cancer patients independent of other clinicopathological factors.