Development and validation of a Surveillance,Epidemiology, and End Results (SEER)-based prognostic nomogram for predicting survival in elderly patients with gastric cancer after surgery

BackgroundElderly gastric cancer (ELGC) remains one of the intensively investigated topics during the last decades. To establish a comprehensive nomogram for effective clinical practice and assessment is of significance. This study is designed to develop a prognostic nomogram for ELGC both in overall survival (OS) and cancer-specific survival (CSS).MethodsThe recruited cases were from the Surveillance, Epidemiology, and End Results (SEER) database and input for the construction of nomogram.ResultsA total of 4,414 individuals were recruited for this study, of which 2,208 were randomly in training group and 2,206 were in validation group. In univariate analysis of OS, significant variables (P<0.05) included age, marital status, grade, American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) stage, bone/brain/liver/lung metastasis and tumor size. In univariate analysis of CSS, significant variables (P<0.05) included age, grade, AJCC TNM stage, bone/brain/liver/lung metastasis and tumor size. In multivariate analysis of OS, sex, age, race, grade, TNM stage, lung metastasis and tumor size were considered as the significant variables and subjected to the establishment of nomogram. In multivariable analysis of CSS, age, grade, TNM, tumor size were considered as the significant variables and input to the establishment of nomogram. Sex, age, race, grade, TNM stage, lung metastasis and tumor size were included for the establishment of nomogram in OS while age, grade, TNM, tumor size were included to the establishment of nomogram in CSS. C-index, decision curve analysis (DCA) and the area under the curve (AUC) showed distinct value of newly established nomogram models. Both OS and CSS nomograms showed higher statistic power over the AJCC stage.ConclusionsThis study established and validated novel nomogram models of OS and CSS for ELGC based on population dataset.     

Development and validation of prognostic nomogram based on log odds of positive lymph nodes for patients with gastric signet ring cell carcinoma

ObjectiveOur aims were to establish novel nomogram models, which directly targeted patients with signet ring cell carcinoma (SRC), for individualized prediction of overall survival (OS) rate and cancer-specific survival (CSS).MethodsWe selected 1,365 SRC patients diagnosed from 2010 to 2015 from Surveillance, Epidemiology and End Results (SEER) database, and then randomly partitioned them into a training cohort and a validation cohort. Independent predicted indicators, which were identified by using univariate testing and multivariate analyses, were used to construct our prognostic nomogram models. Three methods, Harrell concordance index (C-index), receiver operating characteristics (ROC) curve and calibration curve, were used to assess the ability of discrimination and predictive accuracy. Integrated discrimination improvement (IDI), net reclassification improvement (NRI) and decision curve analysis (DCA) were used to assess clinical utility of our nomogram models.ResultsSix independent predicted indicators, age, race, log odds of positive lymph nodes (LODDS), T stage, M stage and tumor size, were associated with OS rate. Nevertheless, only five independent predicted indicators were associated with CSS except race. The developed nomograms based on those independent predicted factors showed reliable discrimination. C-index of our nomogram for OS and CSS was 0.760 and 0.763, which were higher than American Joint Committee on Cancer (AJCC) 8th edition tumor-node-metastasis (TNM) staging system (0.734 and 0.741, respectively). C-index of validation cohort for OS was 0.757 and for CSS was 0.773. The calibration curves also performed good consistency. IDI, NRI and DCA showed the nomograms for both OS and CSS had a comparable clinical utility than the TNM staging system.ConclusionsThe novel nomogram models based on LODDS provided satisfying predictive ability of SRC both in OS and CSS than AJCC 8th edition TNM staging system alone.     

Comparison of 4 lymph node staging systems for the prognostic prediction of esophagogastric junction adenocarcinoma with ≤15 retrieved lymph nodes

BackgroundDirectly applying the 8th American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) staging system to evaluate the prognosis of patients with esophagogastric junction adenocarcinoma (AEG) might lead to under-staging, when insufficient lymph nodes were retrieved during surgery. The prognostic value of 4 lymph nodes staging systems, 8th AJCC TNM N stage, lymph node ratio (LNR), log odds of positive lymph nodes (LODDS), and negative lymph nodes (NLN), in AEG patients having ≤15 retrieved lymph nodes were compared.Methods869 AEG patients diagnosed between 2004 and 2012 with ≤15 retrieved lymph nodes were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analyses were conducted to assess the association of cancer-specific survival (CSS) and overall survival (OS) with 8th AJCC TNM N stage, LNR, LODDS, and NLN respectively. Predictive survival ability was assessed and compared using linear trend χ2 score, likelihood ratio (LR) test, Akaike information criterion (AIC), Harrell concordance index (C-index), and Receiver Operative Curve (ROC).ResultsThe N stage, LNR, LODDS, and NLN were all independent prognostic predictors for CSS and OS in multivariate Cox models. Comparatively, LODDS demonstrated higher linear trend χ2 score, LR test score, C-index and integrated area under the curve (iAUC) value, and lower AIC in CSS compared to the other three systems. Moreover, for patients without regional lymph node metastasis, NLN showed higher C-index and lower AIC.ConclusionsLODDS showed better predictive performance than N, LNR, and NLN among patients with node-positive patients while NLN performed better in node-negative patients. A combination of LODDS and NLN has the potential to provide more prognostic information than the current AJCC TNM classification.     

Decreased albumin-to-alkaline phosphatase ratio predicted poor survival of resectable gastric cancer patients

BackgroundThe albumin-to-alkaline phosphatase ratio (AAPR) is an innovative prognostic index for various cancer patients, the clinical significance of the AAPR in patients with GC is unknown.MethodsWe retrospectively reviewed 227 resectable GC patients in our center. The Kaplan–Meier method and the Cox proportional hazards model were used to analyze the disease-free survival (DFS) and overall survival (OS). The Likelihood Ratio Test (LRT) and Akaike information criterion (AIC) were used to compare the prognostic abilities of the TNM and AAPR-TNM staging systems in DFS and OS predictionResultsThe AAPR was significantly decreased in GC patients, and the optimal cut-off value for resectable and benign gastric disease was 0.437 as determined by the receiver operating characteristic (ROC) curve. The correlation analysis revealed that decreased AAPR in GC was associated with T stage (P=0.004) and TNM stage (P=0.013). Decreased preoperative AAPR correlated with both unfavorable disease-free survival (DFS) and overall survival (OS). Cox regression analysis showed that the TNM stage (DFS: P=0.001, OS: P=0.002) and differential levels of AAPR (DFS: P<0.001, OS: P<0.001) were independent risk factors of DFS and OS. ROC analysis showed that the AAPR-TNM system was more superior than the TNM staging system for DFS (z=1.91, P=0.028) and OS (z=1.937, P=0.026) prediction. The likelihood ratio test (LRT) analysis indicated that the AAPR-TNM system had a significantly larger χ² for both DFS (35.58 vs. 34.51, P<0.001) and OS (32.92 vs. 30.07, P<0.001), and a lower Akaike information criterion (AIC) value both for DFS (1,032 vs. 1,065, P<0.001) and OS (869 vs. 898, P<0.001) compared to the TNM system.ConclusionsThe AAPR level significantly decreased in patients with GC, and impacted the prognosis of patients.     

Pattern of distant metastases and predictive nomograms in colorectal mucinous adenocarcinoma: a SEER analysis

BackgroundWe evaluated the metastatic patterns and explored the prognostic value of distant metastasis pattern in patients with metastatic colorectal mucinous adenocarcinoma (MC) using the Surveillance, Epidemiology, and End Results (SEER) database.MethodsBetween 2010 and 2015, newly diagnosed colorectal MC patients were selected using the SEER database. Patient prognosis was compared based on the clinicopathological parameters, treatment method, and the site and number of metastatic organs. Cox analyses were used to identify factors associated with overall survival (OS). A nomogram was built to predict the patient’s survival. Harrell’s concordance index (c-index) and calibration curves were used to analyze the discriminative ability of the prognostic factors.ResultsOf 3,088 patients diagnosed with colorectal MC, the liver was the only metastatic organ in 78.4% (997/1,271) of all liver metastasis cases, the lung was the only metastatic organ in 41.0% (164/400) of all lung metastasis cases, bone was the only metastatic organ in 26.6% (29/109) of all bone metastasis cases, and the brain was the only metastatic organ in 23.5% (4/17) of all brain metastasis cases. Compared with the untreated cases, those treated with chemotherapy, surgery, and radiotherapy had better OS (P<0.001). There were marked OS differences (P<0.001) between patients with and without liver and bone metastases. Patients with bone metastasis had the best survival, while those with brain metastasis had the worst survival (P<0.001). Patients with one metastatic site had better prognosis compared to those with two or three (P<0.001). Patients with liver metastasis had the best survival, while those with bone and brain metastasis had the worst survival (P<0.001). Multivariate analysis showed that age <65 years, non-black race, grade I, N0 stage, chemotherapy, radiation, surgery, liver metastasis, and bone metastasis were independent prognostic factors. A nomogram was constructed to predict survival probability. The c-index value was up to 0.745. The calibration plot showed that the nomogram was clinically useful.ConclusionsMetastatic MC (mMC) patients had a characteristic distant metastasis pattern. This study constructed a new and sufficiently accurate prognostic model of mMC based on population-based data. These findings can be utilized to predict prognosis and guide mMC patient management.     

Prognostic impact of lymph node harvest for patients with node-negative esophageal squamous cell carcinoma: a large-scale multicenter study

BackgroundWe examined the association between the number of resected lymph nodes and survival to determine the optimal lymphadenectomy for thoracic esophageal squamous cell carcinoma (ESCC) patients with negative lymph node.MethodsWe included 1,836 patients from Chinese three high-volumed hospitals with corresponding clinicopathological characters such as gender, age, tumor location, tumor grade and TNM stage of patients. The median follow-up of included patients was 45.7 months (range, 1.03–117.3 months). X-Tile plot was used to identify the lowest number of lymphadenectomy. The multivariate model’s construction was in use of parameters with clinical significance for survival and a nomogram based on clinical variable with P<0.05 in Cox regression analysis. Both two models were validated using a cohort extracted from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database between 1975 and 2016 (n=951).ResultsMore lymphadenectomy numbers were significantly associated with better survival in patients both in training cohort [hazard ratio (HR) =0.980; 95% confidence interval (CI): 0.971–0.988; P<0.001] and validation cohort (HR =0.980; 95% CI: 0.968–0.991; P=0.001). Cut-off point analysis determined the lowest number of 9 for thoracic ESCC patients in N0 stage through training cohort (C-index: 0.623; sensitivity: 80.7%; 1 − specificity: 72.5%) when compared with 10 in validation cohort (C-index: 0.643; sensitivity: 78.2%; 1 − specificity: 63.0%). The cut-off points of 9 were examined in training cohort and validated in the divided cohort from validation cohort (all P<0.05). Meanwhile, nomograms for both cohorts were constructed and the calibration curves for both cohorts agreed well with the actual observations in terms of predicting 3- and 5-year survival, respectively.ConclusionsLarger number for lymphadenectomy was associated with better survival in thoracic ESCC patients in N0 stage. Nine was what we got as the lowest number for lymphadenectomy in pN0 ESCC patients through this study, and our result should be confirmed further.     

A novel prognostic nomogram based on microvascular invasion and hematological biomarkers to predict survival outcome for hepatocellular carcinoma patients

PurposeThis study aimed to develop and validate a nomogram for overall survival (OS) prediction in which combine clinical characteristics and hematological biomarkers in patients with hepatocellular carcinoma (HCC).MethodsWe performed a retrospective analysis of 807 HCC patients. All the clinical data of these patients were collected through electronic medical record (EMR). The independent predictive variables were identified by cox regression analysis. We tested the accuracy of the nomograms by discrimination and calibration, and then plotted decision curves to assess the benefits of nomogram-assisted decisions in a clinical context, and compared with the TNM staging systems and microvascular invasion (MVI) on HCC prognosis.ResultsThe primary cohort consisted of 545 patients with clinicopathologically diagnosed with HCC from 2008 to 2013, while 262 patients from 2014 to 2016 in external validation cohort. Variables included in the nomograms were TNM Stage, microvascular invasion (MVI), alpha fetoprotein (AFP), platelet to lymphocyte ratio (PLR) and prothrombin time (PT). The C-index of nomogram was 0.768, which was superior than the C-index of TNM Stage (0.660, P < 0.001) and MVI(0.664, P < 0.001) alone in the primary cohort. In the validation cohort, the models had a C-index of 0.845, and were also statistically higher when compared to C-index values for TNM Stage (0.687, P < 0.001) and MVI(0.684, P < 0.001). Calibration curves showed adequate calibration of predicted and reported OS prediction throughout the range of HCC outcomes. Decision curve analysis demonstrated that the nomogram was clinically useful than the TNM Stage and MVI alone. Moreover, patients were divided into three distinct risk groups for OS by the nomogram: low risk group, middle risk group and a high risk group, respectively.ConclusionThe nomogram presents more accurate and useful prognostic power, which could be used to predict OS for patients with HCC.     

Prognostic value and clinicopathological correlation of the tumor regression grade in neoadjuvant chemotherapy for gastric adenocarcinoma: a retrospective cohort study

BackgroundNeoadjuvant chemotherapy (NACT) and radical gastrectomy are the gold standard treatments for resectable advanced gastric cancer (GC). However, the prognostic value of the pathological tumor regression grade (TRG) of NACT remains controversial. This retrospective study aimed to investigate the correlation between the TRG after NACT and clinicopathological features as well as its prognostic value in advanced GC.MethodsIn total, 551 patients with GC who received NACT combined with surgical resection at the Zhejiang Cancer Hospital from April 2004 to December 2019 were included. The demographic characteristics, treatment response, tumor characteristics, treatment regimens, and survival data were reviewed from the medical records of all patients. The Chi-square test was used to analyze the correlation between TRG and clinicopathological factors. Kaplan-Meier univariate analysis and Cox regression multivariate analysis were used to determine the independent risk factors affecting the prognosis of GC patients.ResultsAmong the 551 patients with advanced GC who accepted NACT treatment, 14 were determined to be in TRG 0, 98 in TRG 1, 257 in TRG 2, and 182 in TRG 3. Also, TRG was significantly correlated with the cT stage (P=0.015), ypT stage (P<0.001), ypN stage (P<0.001), ypTNM stage (P<0.001), vascular tumor thrombus (P<0.001), Borrmann classification (P=0.042), and lymph node ratio (LNR) (P<0.001). Furthermore, patients who had a good pathological response to NACT had a better prognosis, with a 3-year overall survival (OS) of 70.9% versus 48.8% in patients who had a poor pathological response. We also found that TRG (P=0.042, HR =1.65) was an independent prognostic factor affecting the OS of GC patients.ConclusionsTRG plays a significant role in the prognostic value in neoadjuvant chemotherapy for gastric adenocarcinoma. Patients with higher cT stage, higher levels of pre-CA199 and pre-CA125 may have worse pathological response.     

Development and validation of survival nomograms in colorectal cancer patients with synchronous liver metastases underwent simultaneous surgical treatment of primary and metastatic lesions

Colorectal cancer patients with synchronous liver metastases (CRSLM) can be treated by simultaneous surgery, that is the primary tumor and liver metastasis are removed at the same time. However, criteria for simultaneous surgery are underwent continuously modified and expanded. An appropriate selection of adequate candidates for simultaneous surgery is vital to get best benefits. A retrospective study including CRSLM patients underwent simultaneous surgical treatment was conducted. CRSLM patients from SEER database were screened as development set, while CRSLM patients in Harbin (China) were enrolled as validation set. Overall survival (OS) and cancer-specific survival (CSS) were applied as end-point. Variables were screen by LASSO-Cox regression, then Cox regression was applied to construct 1-, 3- and 5-year OS, and CSS nomograms. Nomograms were compared to TMN stage for survival prediction and evaluated by concordance indexes (C-indexes), Time-dependent receiver operating characteristic (ROC) curves, Decision Curve Analysis (DCA). 1347 and 112 CRSLM patients were included in the development set and validation set respectively. Nine factors were found associated with OS and CSS, i.e., Age, Primary Site, Differentiation grade, Histology type, T stage, N stage, Tumor size, Chemotherapy, CEA. Compared to the TNM stage, OS nomogram in development set and validation set got C-indexes values of 0.701 vs 0.641, 0.670 vs 0.557 respectively. Meanwhile, compared to the TNM stage, CSS nomogram in development set and validation set got C-indexes values of 0.704 vs 0.649, 0.677 vs 0.569 respectively. AUC values of the OS and CSS nomograms were higher than the TNM stage, DCA showed the OS and CSS nomograms got more clinical net benefit than the TNM stage, in both the development set and validation set. Our nomograms for predicting survival might be helpful to identify the right CRSLM patients who can get most benefit from simultaneous surgery.     

Prognostic value and association of sarcopenic obesity and systemic inflammatory indexes in patients with hepatocellular carcinoma following hepatectomy and the establishment of novel predictive nomograms

BackgroundThe specific impacts of sarcopenic obesity (SO) on hepatocellular carcinoma (HCC) and the association between SO and systemic inflammation remain unclear. This study aimed to investigate the prognostic value and association of SO and systemic inflammation with outcomes after hepatectomy for HCC and develop novel nomograms based on SO and inflammatory indexes for survival prediction.MethodsWe retrospectively enrolled 452 patients with HCC who underwent radical hepatectomy between January 2012 and March 2015 in Fujian Provincial Hospital as the training cohort. In addition, 275 patients during the same period were enrolled as the external validation cohort. Patients were classified into different groups according to the presence of sarcopenia and obesity. Different inflammation indexes were evaluated to select the best predictor of overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate logistic regression were performed to investigate the associations between inflammatory indexes and SO. The inflammatory indexes with the highest predictive values and SO were selected for subgroup analyses to establish a novel classification system: the SOLMR grade. SOLMR grades identified in the multivariate Cox analysis were selected to construct novel nomograms for OS and RFS.ResultsSO (P<0.001) was an independent risk factor for OS and RFS. The lymphocyte‐monocyte ratio (LMR) had the highest areas under the receiver operating characteristic (ROC) curves (AUCs) for OS (P<0.001) and RFS (P<0.001) and was identified as an independent factor of SO (P=0.001). SO and the LMR were selected to establish the SOLMR grade. Multivariate Cox analysis revealed that SOLMR grade was a significant independent predictor of OS (P<0.001) and RFS (P<0.001). Nomograms based on SOLMR grades were generated and accurately predicted 1-, 3- and 5-year OS and RFS in HCC patients. The C-index of the novel nomograms was higher than those of the other conventional staging systems (P<0.001).ConclusionsBoth SO and the LMR were independent risk factors for OS and RFS in HCC patients after hepatectomy. The LMR was an independent factor of SO. The novel nomograms developed from the SOLMR grading system combining SO with the LMR provide good prognostic estimates of the outcomes of HCC patients.     

Development of a prognostic prediction model based on microRNA-1269a in esophageal cancer

BACKGROUNDEsophageal cancer (ESCA) is a heterogeneous cancer with variable outcomes that are challenging to predict. MicroRNA (miR)-1269a is a newly discovered non-coding RNA that shows promising prognostic prediction in other cancers, but its clinical value in ESCA remains unclear.AIMTo explore the relationship between miR-1269a and its clinical value and to develop a nomogram to succinctly display this relationship.METHODSWe analyzed the expression of miR-1269a in 125 ESCA tissue samples with complete clinical data and 52 normal tissue samples. We determined the prognostic value of miR-1269a for overall survival (OS) and cancer-specific survival (CSS) and evaluated the association between miR-1269a and clinical variables including tumor location, histologic grade, metastatic stage, and American Joint Committee on Cancer (AJCC) stage using multivariate Cox analysis. Additionally, we developed a nomogram for OS and CSS based on miR-1269a expression using age and AJCC stage and assessed its prognostic performance. Using Gene Ontology and Kyoto Encyclopedia of Gene and Genomes analyses, we predicted the target genes of miR-1269a and analyzed their potential function in caner development.RESULTSThe expression of miR-1269a was significantly higher in ESCA patients than healthy controls. Patients with high expression of miR-1269a showed poor prognosis in OS and CSS, suffered increased rates of low differentiation and metastasis, and exhibited tumor stage T3 + T4, positive lymph stage, and AJCC stage III + IV. The area under the receiver operating characteristic curve of miR-1269a was 0.716 for OS and 0.764 for CSS. Multivariate Cox analysis revealed that AJCC stage and miR-1269a were independent factors for OS and CSS. Combing with age, we constructed a nomogram for prognostic prediction. Additionally, our nomogram showed excellent predictive performance for OS and CSS after 3 years and 5 years and was easy to use. Ultimately, the functional analysis suggested that miR-1269a was mostly involved in the PI3K-AKT signaling pathway.CONCLUSIONmiR-1269a can be used as a potential indicator for the prognosis of ESCA patients. We developed an easy-to-use nomogram with excellent ESCA prognostic prediction for clinical use.     

Perineural invasion is a prognostic factor in stage II colorectal cancer but not a treatment indicator for traditional chemotherapy: a retrospective cohort study

BackgroundPerineural invasion (PNI) is considered a risk factor of survival but does not yet inform treatment decisions, and has not been studied separately in stage II colorectal cancer (CRC) patients whose postoperative traditional chemotherapy is controversial. This cohort study aimed to assess the association of PNI with basic clinicopathological features and patient outcomes after curative resection and the effects of PNI on responses to adjuvant chemotherapy in stage II CRC.MethodsThe clinical data of 371 stage II CRC patients who underwent curative-intent surgery at the National Cancer Center/Cancer Hospital in 2014 were retrospectively reviewed. The adjuvant chemotherapy data were acquired from follow-up information. PNI status was examined, and the overall survival (OS) and disease-free survival (DFS) rates were analyzed.ResultsPNI was detected in 82 of the 371 patients (22.1%) and was closely correlated with preoperative serum carcinoembryonic antigen (CEA) levels (P=0.030), gross tumor type (P=0.010), tumor differentiation (P=0.010), p stage (P<0.001), and extramural vascular invasion (EMVI) (P<0.001). The median follow-up time was 71 months. The 5-year OS was 84.1% and 96.5% (P<0.001), and the 5-year DFS was 75.6% and 91.3% (P<0.001) for PNI-positive (+) and PNI-negative (−) patients, respectively. The multivariate regression analyses identified PNI as an independent negative prognostic factor for DFS [hazard ratio (HR): 2.95; 95% confidence interval (CI), 1.546–5.626; P=0.001] and OS (HR: 3.966; 95% CI, 1.642–9.575; P=0.002). Among PNI (+) patients, DFS and OS were positively correlated with CEA levels (P=0.005 and P=0.004, respectively). Postoperative chemotherapy failed to improve DFS (P=0.480 and P=0.267, respectively) and OS (P=0.940 and P=0.077, respectively) regardless of whether the patients were PNI positive or not.ConclusionsIn stage II CRC patients, PNI was a poor independent predictor for DFS and OS. Among PNI (+) patients, CEA levels were positively correlated with DFS and OS. Traditional postoperative adjuvant chemotherapy does not improve outcomes of PNI (+) patients. Therefore, as to the active role of PNI and vacancy for treatment in allusion to PNI, follow-up of PNI (+) patients with elevated CEA level should be strengthened and further research on drug conducted on PNI deserve to be carried on.     

Prognostic value of the ratio of carcinoembryonic antigen concentration to maximum tumor diameter in patients with stage II colorectal cancer

BackgroundRecently, a study from our center indicated that the ratio of preoperative carcinoembryonic antigen (CEA) concentration to maximum tumor diameter (DMAX) may be a prognostic marker for patients with rectal cancer. Therefore, the study aimed to evaluate whether this ratio (CEA/DMAX) has prognostic value for patients with stage II colorectal cancer (CRC).MethodsA prospectively maintained database was searched for patients with pathologically confirmed stage II CRC who underwent surgery between January 2010 and March 2019. Patients were stratified according to the mean CEA/DMAX value into low and high CEA/DMAX groups. Kaplan-Meier, univariable, and multivariable Cox regression analyses were used to evaluate whether the CEA/DMAX could predict overall survival (OS) and disease-free survival (DFS). Nomograms were constructed in terms of the results of multivariable Cox regression analyses.ResultsThe study included 2,499 patients with stage II CRC. The mean CEA/DMAX value was 2.33 (ng/mL per cm). Kaplan-Meier analyses revealed that, relative to the low CEA/DMAX group, the high CEA/DMAX group had significantly poorer OS (67.31% vs. 85.02%, P<0.001) and DFS (61.41% vs. 77.10%, P<0.001). The multivariable Cox regression analysis revealed that CEA/DMAX independently predicted OS (hazard ratio: 2.58, 95% confidence interval: 1.51–4.38, P<0.001) and DFS (hazard ratio: 1.97, 95% confidence interval: 1.38–2.83, P<0.001). Two simple-to-use nomograms comprising CEA/DMAX, age, T stage, and lymphovascular invasion were developed to predict 1-, 3-, and 5-year rates of OS and DFS among patients with stage II CRC. The nomograms had good performance based on the concordance index, receiver operating characteristic (ROC) curve analysis, and calibration curves. Subgroup analyses further confirmed that a high CEA/DMAX was associated with poor OS and DFS among patients with stage II colon cancer and among patients with stage II rectal cancer (both P<0.05).ConclusionsAmong patients with stage II CRC, a high CEA/DMAX independently predicted poor OS and DFS, and the predictive abilities were also observed in subgroup analyses of patients with stage II colon cancer or rectal cancer. Furthermore, we developed two nomograms that had good accuracy for predicting the prognosis of stage II CRC.     

Coupling radiomics analysis of CT image with diversification of tumor ecosystem: A new insight to overall survival in stage I−III colorectal cancer

ObjectiveThis 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.MethodsWe 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.ResultsThe 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.ConclusionsThis 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.     

Prognosis prediction model for a special entity of gastric cancer,linitis plastica

BackgroundGastric linitis plastica (GLP) is characteristic by its poor prognosis and highly aggressive characteristics compared with other types of gastric cancer (GC). However, the guidelines have not yet been distinguished between GLP and non-GLP.MethodsA total of 342 eligible patients with GLP identified in the Surveillance, Epidemiology, and End Results (SEER) dataset were randomly divided into training set (n=298) and validation set (n=153). A nomogram would be developed with the constructed predicting model based on the training cohort’s data, and the validation cohort would be used to validate the model. Principal component analysis (PCA) was used to evaluate the differences between groups. Cox regression and LASSO (least absolute shrinkage and selection operator) were used to construct the models. Calibration curve, time-dependent receiver operating characteristic (ROC) curve, concordance index (C-index) and decision curve analysis (DCA) were used to evaluate the predicting performance. Restricted mean survival time (RMST) was used to analyze the curative effect of adjuvant therapy.ResultsFor patients in training cohort, univariable and multivariable Cox analyses showed that age, examined lymph nodes (LN.E), positive lymph nodes (LN.P), lesion size, combined resection, and radiotherapy are independent prognostic factors for overall survival (OS), while chemotherapy can not meet the proportional hazards (PHs) assumption; age, race, lesion size, LN.E, LN.P, combined resection and marital status are independent prognostic factors for cancer-specific survival (CSS). The C-index of the nomogram was 0.678 [95% confidence interval (CI), 0.660–0.696] and 0.673 (95% CI, 0.630–0.716) in the training and validation cohort, respectively. Meanwhile, the C-index of the CSS nomogram was 0.671 (95% CI, 0.653–0.699) and 0.650 (95% CI, 0.601–0.691) in the training and validation cohort for CSS, respectively. Furthermore, the nomogram was well calibrated with satisfactory consistency. RMST analysis further determined that chemotherapy and radiotherapy might be beneficial for improving 1- and 3-year OS and CSS, but not the 5-year CSS.ConclusionsWe developed nomograms to help predict individualized prognosis for GLP patients. The new model might help guide treatment strategies for patients with GLP.     

Separate lateral parametrial lymph node dissection improves detection rate of parametrial lymph node metastasis in early-stage cervical cancer: 10-year clinical evaluation in a single center in China

ObjectiveTo investigate the clinical significance of separate lateral parametrial lymph node dissection (LPLND) in improving parametrial lymph node (PLN) and its metastasis detection rate during radical hysterectomy for early-stage cervical cancer.MethodsFrom July 2007 to August 2017, 2,695 patients with cervical cancer in stage IB1−IIA2 underwent radical hysterectomy were included. Of these patients, 368 underwent separate dissection of PLNs using the LPLND method, and 2,327 patients underwent conventional radical hysterectomy (CRH). We compared the surgical parameters, PLN detection rate and PLN metastasis rate between the two groups.ResultsCompared with CRH group, the rate of laparoscopic surgery was higher (60.3% vs. 15.9%, P<0.001), and the blood transfusion rate was lower (19.0%vs. 29.0%, P<0.001) in the LPLND group. PLNs were detected in 356 cases (96.7%) in the LPLND group, and 270 cases (11.6%) in the CRH group (P<0.001), respectively. The number of PLNs detected in the LPLND group was higher than that in the CRH group (median 3vs. 1, P<0.001). The PLN metastases were detected in 25 cases (6.8%) in the LPLND group, and 18 cases (0.8%) in the CRH group (P<0.001), respectively. In multivariable analysis, LPLND is an independent factor not only for PLN detection [odds ratio (OR)=228.999, 95% confidence interval (95% CI): 124.661−420.664; P<0.001], but also for PLN metastasis identification (OR=10.867, 95% CI: 5.381−21.946; P<0.001). ConclusionsLPLND is feasible and safe. The surgical method significantly improves the detection rate of PLN and avoids omission of PLN metastasis during radical hysterectomy for early-stage cervical cancer.     

A novel robust nomogram based on preoperative hemoglobin and albumin levels and lymphocyte and platelet counts (HALP) for predicting lymph node metastasis of gastric cancer

BackgroundAccurate assessment of lymph node status in gastric cancer (GC) patients can help to select appropriate treatment strategies for GC, but the diagnostic accuracy of conventional methods needs to be improved. The aim of this study was to investigate the predictive value of preoperative hemoglobin and albumin levels and lymphocyte and platelet counts (HALP) on lymph node status in GC patients and to construct a risk prediction model.MethodsThis study retrospectively analyzed the clinicopathological characteristics of 349 patients with GC who underwent radical gastrectomy, among which 250 patients were recruited in the training cohort and 99 patients in the independent validation cohort. Significant risk factors in univariate analysis were further identified as independent variables in multivariate logistic regression analysis, which were then incorporated and presented in a nomogram. Receiver operating characteristic (ROC) curves, Calibration curve and decision curve analysis (DCA) curves were used to evaluate the discrimination, prediction accuracy and clinical effectiveness of the modelResultsMultifactorial logistic regression analysis showed that alcohol use (OR =2.203, P=0.036), Depth of invasion (OR =7.756, P<0.001), differentiation (OR =2.252, P=0.018), carcinoembryonic antigen (CEA) (OR =2.443, P=0.017), carbohydrate antigen 19-9 (CA199) (OR =2.715, P=0.008) and HALP (OR =2.276, P=0.032) were independent risk factors for lymph node metastasis (LNM) in GC. We used these factors to construct a nomogram for predicting LNM in GC patients, and the ROC curves showed good discrimination of the model with AUC values of 0.854 (training cohort) and 0.868 (validation cohort), respectively, and the calibration curves showed good predictive ability of the nomogram, in addition to the DCA curves results showed the clinical usefulness of the model.ConclusionsIn conclusion, we established a nomogram for predicting LNM in patients with GC.     

Combining the systemic inflammation response index and prognostic nutritional index to predict the prognosis of locally advanced elderly esophageal squamous cell carcinoma patients undergoing definitive radiotherapy

BackgroundThe systemic inflammation response index (SIRI) and prognostic nutritional index (PNI) have been shown to be correlated with the prognosis of various solid tumors. This study sought to investigate the prognostic value of the SIRI and the PNI individually and in combination in locally advanced elderly esophageal squamous cell carcinoma (ESCC) patients treated with radical radiotherapy.MethodsThe data of 192 ESCC patients aged ≥65 years, who had been treated with definitive radiotherapy between 2013 and 2016, were retrospectively analyzed. The optimal cutoff values of SIRI and PNI were determined by receiver operating characteristic curves. Kaplan-Meier curves and Cox proportional hazards models were used to analyze the effect of the SIRI and PNI on overall survival (OS) and progression-free survival (PFS). The areas under the curve were measured to evaluate the predictive ability of the SIRI, PNI, and SIRI combined with PNI for OS.ResultsThe optimal cutoff values of the pretreatment SIRI and PNI were 1.03 and 49.60, respectively. The univariate and multivariate analyses demonstrated that T stage (P=0.021), TNM stage (P=0.022), synchronous chemotherapy (P=0.032), the SIRI (P=0.001), and the PNI (P=0.045) were independent prognostic factors for OS and N stage (P=0.004), synchronous chemotherapy (P=0.016) and the SIRI (P=0.004) were independent prognostic factors for PFS. The AUC of the combined SIRI and PNI (0.706; 0.612–0.801) was higher than those of the SIRI (0.648; 0.540–0.756) and the PNI (0.621; 0.523–0.720). Patients in the low-SIRI and high-PNI groups, especially those in clinical stage II or who received synchronous chemotherapy (P<0.001, P=0.002), had better OS and PFS than those in the other groups (P<0.001).ConclusionsThe SIRI and PNI are simple and reliable biomarkers for predicting long-term survival in elderly patients with locally advanced ESCC after radical radiotherapy. A high SIRI and a low PNI indicated poor prognosis, and the combination of the SIRI and PNI improved the accuracy of prognosis prediction and could be used to guide individualized treatment of patients.     

Survival and prognostic factors for postoperative primary appendiceal cancer: a retrospective cohort study based on the Surveillance,Epidemiology, and End Results database

BackgroundThe factors affecting the postoperative survival of patients with primary appendiceal cancer (PAC) have yet to be fully explored. And there are no clear guidelines for adjuvant treatment after appendectomy. Whether chemotherapy can prolong patient survival after appendectomy, is critical in guiding postoperative medications. The majority of studies on appendiceal cancer are single case reports, and they focused on the incidence of appendiceal cancer. The present study aimed to investigate the survival characteristics of patients with primary appendiceal cancer after surgery using the Surveillance, Epidemiology, and End Results (SEER) database.MethodsThe data of 2,891 cases of primary appendiceal cancer between 2004 to 2015 were obtained from the SEER database and subjected to survival analysis using the Kaplan-Meier method and Cox proportional-hazards model. The annual percentage change (APC) was calculated using the weighted least squares method.ResultsThe overall age-adjusted incidence rate per 100,000 population steadily increased from 0.58 in 2004 to 1.63 in 2015. For patients who received chemotherapy, the median overall survival (OS) was 65 months and the 5-year OS rate was 51.9%, and for patients who did not receive chemotherapy or whose chemotherapy status was unknown, the median OS was not reached and the 5-year OS rate was 78.9%. Age [35< age <69: hazard radio (HR) =2.147; 95% confidence interval (CI): 1.442–3.197, P<0.001; age >69: HR =5.259; 95% CI: 3.485–7.937, P<0.001], race (White race: HR =0.728; 95% CI: 0.590–0.899, P=0.003), histologic type (mucinous neoplasm: HR =0.690; 95% CI: 0.580–0.821, P<0.001; malignant carcinoid: HR =0.657; 95% CI: 0.536–0.806, P<0.001), grade (II: HR =1.794; 95% CI: 1.471–2.187, P<0.001; III: HR =2.905; 95% CI: 2.318–3.640, P<0.001; IV: HR =3.128; 95% CI: 2.159–4.533, P<0.001), and stage (localized: HR =0.236; 95% CI: 0.194–0.287, P<0.001; regional: HR =0.425; 95% CI: 0.362–0.499, P<0.001) were identified as independent predictors of survival. And after adjusting for known factors (age, sex, race, tumor size, marital status, histologic type, grade, stage), chemotherapy (HR =1.220; 95% CI: 1.050–1.417, P=0.009) was revealed to be an independent indicator of poor prognosis.ConclusionsThere was an increasing trend in the incidence of appendiceal cancer in the United States between 2004 and 2015. Chemotherapy was revealed to be an independent indicator of poor prognosis, which provide valuable insight into the therapy of primary appendiceal cancer. Large clinical trials of chemotherapy and targeted therapy for appendiceal cancer are urgently needed.