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.

Nomogram model predicting the overall survival for patients with primary gastric mucosa-associated lymphoid tissue lymphoma

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.

Prognostic nutritional index in predicting survival of patients with gastric or gastroesophageal junction adenocarcinoma: A systematic review

BACKGROUND Gastric cancer is the third most common cause of cancer related death worldwide.Surgery with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortality rates remain high.Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy.The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed.The aim of this systematic review was to assess the role of the prognostic nutritional index(PNI)in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent.AIM To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma.METHODS A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival(OS)of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value.The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review.The review protocol was registered in the International Prospective Register of Systematic Reviews(PRO) RESULTS Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review.The patients were divided into high-and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study.The 5-year OS of patients in the low-PNI groups ranged between 39%and 70.6%,while in the high-PNI groups,it ranged between 54.9%and 95.8%.In most of the included studies,patients with high preoperative PNI showed statistically significant better OS than the low PNI groups.In multivariate analyses,low PNI was repeatedly recognised as an independent prognostic factor for poor survival.CONCLUSION According to the present study,low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.

Survival Rate and Factors Influencing It in Triptorelin-Castrated Metastatic Prostate Cancer Patients

Background: Most newly diagnosed prostate cancers in Benin are metastatic diseases and patients are reluctant to undergo orchiectomy. Still, chemical androgen deprivation therapy is not always available and not every patient can afford it. Thus, it will be interesting to evaluate the results of that therapy in the country. Objective: To analyze the survival rate and factors influencing it in metastatic prostate cancer patients who underwent triptorelin-based androgen deprivation therapy at the former Military Teaching Hospital of Cotonou from January 1, 2012, to December 31, 2022. Patients and Method: Metastatic prostate cancer patients received intragluteal injections of triptorelin 11.25 mg every 3 months. We retrospectively collected follow-up data from the patients’ medical records. By means of the software StataTM version 15, we performed a descriptive analysis of qualitative data. We used Kaplan-Meir method to estimate the overall survival rate in the whole cohort and in specific subgroups of patients. We compared survival rates by using the log-rank test. Results: 68 metastatic prostate cancer patients aged 47-86 years (mean = 69.9) with initial PSA ranging from 24.25 to 6334 ng/mL (mean = 666.1) started triptorelin-based castration. The tumor grade in 21 (33.3%), 14 (22.2%), 15 (23.8), 8 (12.7%), and 5 (7.9%) patients was respectively ISUP grade groups 5, 4, 3, 2, and 1. 15 (22.1%), 4 (5.9%), 2 (2.9%), 1 (1.5%), 11 (16.2%), and 7 (10.3%) patients respectively had hypertension, diabetes mellitus, peptic ulcer, asthma, unilateral or bilateral hydronephrosis, and paralysis. The mean nadir PSA level was 22.5 ng/mL (range: 0.01-220.25). The mean time to nadir PSA level was 8.9 months (range: 3-57). The overall survival rate was 42.6%. There was no significant survival difference between age groups (p = 0.475), relating to the presence of diabetes or hypertension (p = 0.757) or to the presence of paralysis or hydronephrosis (p = 0.090). The initial PSA level exerted no significant impact on patients’ survival (p = 0.461). Neither did the time to PSA nadir (p = 0.263). The PSA nadir less than 4 ng/mL (p = 0.005) and the PSA nadir less than 4 ng/mL achieved in 12 months or less (p = 0.002) were predictive of longer survival rate. The difference in survival rate through the ISUP grade groups was not significant (p = 0.061). Conclusion: The overall survival rate was 42.6% at 5 years. Achieving PSA nadir of less than 4 ng/mL in less than 12 months of castration was predictive of longer survival rate in triptorelin-castrated metastatic prostate cancer patients.

Nomogram based on clinical characteristics for predicting overall survival in gastric cancer patients with preoperative anemia

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.

Fibrinogen-to-albumin ratio predicts overall survival of hepatocellular carcinoma

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.

Prognostic factors for overall survival in prostate cancer patients with different site-specific visceral metastases: A study of 1358patients

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.

Prognostic nomograms for predicting overall survival and causespecific survival of signet ring cell carcinoma in colorectal cancer patients

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.

Overall Survival and Health Care Costs of Medicare Patients with Previously Treated Chronic Lymphocytic Leukemia

Background: Bendamustine-based regimens are often used in the management of patients with chronic lymphocytic leukemia (CLL) but few studies have analyzed the comorbidity- and/or adverse event (CAE)-related healthcare costs in patients receiving these regimens in a real-world setting. Aims: To describe all-cause and CAE-related healthcare costs in relapse/refractory (R/R) elderly patients with CLL treated with bendamustine-based regimens in a real-world setting. Methods: Adult patients with R/R CLL who received bendamustine-based regimens on/after January 2010 were selected from the Medicare Limited Data Set (LDS) 5% Standard Analytic Files. Selected patients were classified into cohorts based on the two most prevalent bendamustine-based regimens observed (index treatment): 1) bendamustine + rituximab (BR cohort) and 2) bendamustine monotherapy (B-mono cohort). For each cohort, all-cause and CAE-related healthcare costs, while on treatment, were reported per-patient-per-month (PPPM). Overall survival (OS) rates following initiation of the index treatment were described using age- and gender-adjusted Kaplan-Meier curves. Results: A total of 275 patients were included in the BR cohort and 100 patients in the B-mono cohort. Most patients were male and the mean age was approximately 75 years old. During treatment, total all-cause healthcare costs were $14,520 PPPM for the BR cohort and $13,125 PPPM for the B-mono cohort—outpatient costs (mainly driven by CLL-drug costs) represented 86.1% of the total all-cause healthcare costs for the BR cohort and 69.8% for the B-mono cohort. CAE costs accounted for 58.3% of the total all-cause healthcare costs for the BR cohort and 66.9% for the B-mono cohort. Median OS was 35 months in the BR cohort and 21 months in the B-mono cohort. Conclusion: In this population of elderly patients with R/R CLL treated with bendamustine-based regimens, CAEs were common and translated into important medical costs. Median OS was also relatively short suggesting an unmet medical need.

Is there utility for fluorine-18-fluorodeoxyglucose positron-emission tomography scan before surgery in breast cancer? A 15-year overall survival analysis

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.

Age is an independent adverse prognostic factor for overall survival in acute myeloid leukemia in Japan

AIM: To elucidate risk factors for survival of elderly acute myeloid leukemia(AML) patients in a real-world practice by observational study. METHODS: We conducted a population-based study in 213 adult and elderly AML patients(127 males and 86 females) in Kagawa Prefecture, Japan. To construct this cohort, we gathered all data for patients diagnosed with AML at 7 hospitals in Kagawa between 2006 and 2010. The primary end point was overall survival(OS) after AML diagnosis. Unadjusted Kaplan-Meier survival plots were used to determine OS in the overall cohort. Multivariate analysis was used to determine the independent adverse prognostic factors for OS, with the covariates of interest including age, gender, race/ethnicity, CCI, education, median income, metropolitan statistical area size and history of myelodysplastic syndrome.RESULTS: The average population of Kagawa during the study period was 992489, and the incidence of AML was 4.26 per 100000 person-years. A total of 197 patients with non-acute promyelocytic leukemia(non-APL)(119 males and 78 females) were also included. The median age of non-APL patients was 70 years(average 67, range 24-95). The 5-year OS rate was 21.1%. Subsequent analysis by age group showed that the survival rate declined with age; the 5-year OS rates of non-APL patients younger than 64 years, 65-74 years, and older than 75 years were 41.5%, 14.1%, and 8.9%, respectively. Multivariate analysis revealed that unfavorable risk karyotype, older age, poor performance status(PS)(3-4), lack of induction chemotherapy, and antecedent haematological disease were independent prognostic predictors. In the subgroup analysis, we also found that older patients with non-APL had lower complete remission rates and higher early death rates than younger patients, irrespective of PS. However, intensive chemotherapy was a significant predictor for longer survival not only in the patients < 75 years of age, but also in those over 75 with PS 0-2. CONCLUSION: Age would contribute considerable life expectancy to indicate induction chemotherapy with eligible dose of cytotoxic drugs for a favorable case even in advanced elderly.

Treatment patterns and survival outcomes in patients with nonmetastatic early-onset pancreatic cancer

BACKGROUND The incidence of patients with early-onset pancreatic cancer(EOPC;age≤50 years at diagnosis)is on the rise,placing a heavy burden on individuals,families,and society.The role of combination therapy including surgery,radiotherapy,and chemotherapy in non-metastatic EOPC is not well-defined.AIM To investigate the treatment patterns and survival outcomes in patients with non-metastatic EOPC.METHODS A total of 277 patients with non-metastatic EOPC who were treated at our institution between 2017 and 2021 were investigated retrospectively.Overall survival(OS),disease-free survival,and progression-free survival were estimated using the Kaplan-Meier method.Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors.RESULTS With a median follow-up time of 34.6 months,the 1-year,2-year,and 3-year OS rates for the entire cohort were 84.3%,51.5%,and 27.6%,respectively.The median OS of patients with localized disease who received surgery alone and adjuvant therapy(AT)were 21.2 months and 28.8 months,respectively(P=0.007).The median OS of patients with locally advanced disease who received radiotherapy-based combination therapy(RCT),surgery after neoadjuvant therapy(NAT),and chemotherapy were 28.5 months,25.6 months,and 14.0 months,respectively(P=0.002).The median OS after regional recurrence were 16.0 months,13.4 months,and 8.9 months in the RCT,chemotherapy,and supportive therapy groups,respectively(P=0.035).Multivariate analysis demonstrated that carbohydrate antigen 19-9 level,pathological grade,T-stage,N-stage,and resection were independent prognostic factors for non-metastatic EOPC.CONCLUSION AT improves postoperative survival in localized patients.Surgery after NAT and RCT are the preferred therapeutic options for patients with locally advanced EOPC.

Unveiling the secrets of gastrointestinal mucous adenocarcinoma survival after surgery with artificial intelligence:A population-based study

BACKGROUND Research on gastrointestinal mucosal adenocarcinoma(GMA)is limited and controversial,and there is no reference tool for predicting postoperative survival.AIM To investigate the prognosis of GMA and develop predictive model.METHODS From the Surveillance,Epidemiology,and End Results database,we collected clinical information on patients with GMA.After random sampling,the patients were divided into the discovery(70%of the total,for model training),validation(20%,for model evaluation),and completely blind test cohorts(10%,for further model evaluation).The main assessment metric was the area under the receiver operating characteristic curve(AUC).All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA’s prognosis.RESULTS This model had an AUC of 0.7433[95% confidence intervals(95%CI):0.7424-0.7442]in the discovery cohort,0.7244(GMA:0.7234-0.7254)in the validation cohort,and 0.7388(95%CI:0.7378-0.7398)in the test cohort.We packaged it into Windows software for doctors’use and uploaded it.Mucinous gastric adenocarcinoma had the worst prognosis,and these were protective factors of GMA:Regional nodes examined[hazard ratio(HR):0.98,95%CI:0.97-0.98,P<0.001]and chemotherapy(HR:0.62,95%CI:0.58-0.66,P<0.001).CONCLUSION The deep learning-based tool developed can accurately predict the overall survival of patients with GMA postoperatively.Combining surgery,chemotherapy,and adequate lymph node dissection during surgery can improve patient outcomes.

Development of preoperative prognostic models including radiological features for survival of singular nodular HCC patients

Background:Early singular nodular hepatocellular carcinoma(HCC)is an ideal surgical indication in clinical practice.However,almost half of the patients have tumor recurrence,and there is no reliable prognostic prediction tool.Besides,it is unclear whether preoperative neoadjuvant therapy is necessary for patients with early singular nodular HCC and which patient needs it.It is critical to identify the patients with high risk of recurrence and to treat these patients preoperatively with neoadjuvant therapy and thus,to improve the outcomes of these patients.The present study aimed to develop two prognostic models to preoperatively predict the recurrence-free survival(RFS)and overall survival(OS)in patients with singular nodular HCC by integrating the clinical data and radiological features.Methods:We retrospective recruited 211 patients with singular nodular HCC from December 2009 to January 2019 at Eastern Hepatobiliary Surgery Hospital(EHBH).They all met the surgical indications and underwent radical resection.We randomly divided the patients into the training cohort(n=132)and the validation cohort(n=79).We established and validated multivariate Cox proportional hazard models by the preoperative clinicopathologic factors and radiological features for association with RFS and OS.By analyzing the receiver operating characteristic(ROC)curve,the discrimination accuracy of the models was compared with that of the traditional predictive models.Results:Our RFS model was based on HBV-DNA score,cirrhosis,tumor diameter and tumor capsule in imaging.RFS nomogram had fine calibration and discrimination capabilities,with a C-index of 0.74(95%CI:0.68-0.80).The OS nomogram,based on cirrhosis,tumor diameter and tumor capsule in imaging,had fine calibration and discrimination capabilities,with a C-index of 0.81(95%CI:0.74-0.87).The area under the receiver operating characteristic curve(AUC)of our model was larger than that of traditional liver cancer staging system,Korea model and Nomograms in Hepatectomy Patients with Hepatitis B VirusRelated Hepatocellular Carcinoma,indicating better discrimination capability.According to the models,we fitted the linear prediction equations.These results were validated in the validation cohort.Conclusions:Compared with previous radiography model,the new-developed predictive model was concise and applicable to predict the postoperative survival of patients with singular nodular HCC.Our models may preoperatively identify patients with high risk of recurrence.These patients may benefit from neoadjuvant therapy which may improve the patients’outcomes.

Seven-senescence-associated gene signature predicts overall survival for Asian patients with hepatocellular carcinoma

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.

PIK3CA and TP53 mutations predict overall survival of stage Ⅱ/Ⅲ colorectal cancer patients

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.

Lymph node ratio and preoperative CA 19-9 levels predict overall survival and recurrence-free survival in patients with resected pancreatic adenocarcinoma

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.

CD24 genetic variants contribute to overall survival inpatients with gastric cancer

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.

Radiomics of rectal cancer for predicting distant metastasis and overall survival

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.

The impact of both platinum-based chemotherapy and EGFR-TKIs on overall survival of patients with advanced non-small cell lung cancer

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.