A novel prognosis marker based on combined preoperative carcinoembryonic antigen and systemic inflammatory response for resectable gastric cancer.
ABSTRACT: Background: Carcinoembryonic antigen (CEA) is one of the important indexes for the diagnosis and prognosis of gastrointestinal cancer. Systemic inflammatory response (SIR) is closely related to the occurrence and development of gastrointestinal cancer. Methods: A total of 803 patients who underwent radical gastrectomy in Qinghai University Affiliated Hospital from January 2012 to December 2016 were included as training set. Multivariable Cox proportional hazard regression was used to identify associations with outcome of gastric cancer (GC). CNLR was established by combining CEA and the neutrophils to lymphocytes ratio (NLR, a typical parameter in SIR) to generate a novel prognostic score system and its prognostic value was externally validated. Results: Multivariate analysis showed that CEA and NLR were independent prognostic factors for GC patients (both p < 0.05). A higher CNLR was significantly associated with older age, male sex, larger tumor size, vascular invasion and advanced stages (all p < 0.05). Patients with higher CNLR had poor prognosis than those with lower CNLR (p < 0.05). Multivariate analysis showed that CNLR was an independent prognostic factor (p < 0.05). Incorporation of the CNLR into a prognostic model including age and TNM stage generated a nomogram, which predicted accurately 3- and 5-year survival for GC patients. And similar results were obtained in the external validation set. Conclusions: The CNLR prognostic scoring system established by combining CEA and NLR is an independent prognostic factor for GC, which can be incorporated into the traditional TNM staging to improve the prediction of long-term survival outcomes.
Project description:<h4>Background</h4>Whether the change of the pre- and postoperative systemic inflammatory response (SIR) levels will affect the prognosis of gastric cancer (GC) is unclear. We aimed to investigate the dynamic changes in the pre- and postoperative SIR and their prognostic value for GC.<h4>Methods</h4>The clinicopathological data from 2257 patients who underwent radical gastrectomy between January 2009 and December 2014 at Fujian Medical University Union Hospital (FMUUH) were analyzed. Perioperative SIR changes were reported as changes in the lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII).<h4>Results</h4>The SIR levels showed different trends from postoperative months 1 to 12. Multivariate analysis showed that preoperative (pre)-LMR was an independent predictor for the prognosis (P?=?0.024). The postoperative 12-month (post-12-month) LMR predicted the 5-year overall survival (OS) rate with the highest accuracy (areas under the curve [AUC] 0.717). Patients were divided into four groups according to the optimal cutoff of the preoperative and post-12-month LMR: high pre-LMR to high postoperative (post)-LMR group, high pre-LMR to low post-LMR group, low pre-LMR to high post-LMR group, and low pre-LMR to low post-LMR group. The survival analysis showed 5-year OS rate was significantly higher in patients with high post-12-month LMR than in patients with low post-12-month LMR, regardless of pre-LMR levels (81.6% vs. 44.2%, P <?0.001). The prognostic accuracy was significantly improved by incorporating the post-12-month LMR in the tumor-node-metastasis (TNM) staging system (P =?0.003).<h4>Conclusions</h4>The remeasurement of LMR at post-12-month is helpful in predicting the long-term survival of GC.
Project description:Background The prognostic significance of peripheral blood-derived inflammation markers in patients with gastric cancer (GC) has not been elucidated. This study aimed to investigate the relationship between systemic inflammatory markers and GC prognosis. Methods A prospective observational cohort study involving 598 patients was conducted to analyze the prognosis of GC based on systemic inflammatory markers. The following peripheral blood-derived inflammation markers were evaluated: the neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), systemic immune-inflammation index (SII), C-reactive protein/albumin (CRP/Alb) ratio, Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), prognostic nutrition index (PNI), and prognostic index (PI). The receiver operating characteristics (ROC) curve and the Youden index were used to determine the optimal cutoff values. Univariate and multivariate analysis of prognostic factors was conducted accordingly. Results The optimal cutoff values of the PNI, fibrinogen, NLR, PLR, SII, and CRP/Alb were 49.5, 397?ng/dl, 2.5, 154, 556, and 0.05, respectively. Multivariate analysis showed that age, PLR, TNM stage, and chemotherapy were the independent prognostic factors for advanced gastric cancer (AGC). Adjuvant chemotherapy improved the long-term prognosis of patients with PLR ?154, but chemotherapy had no significant effect on the survival of patients with PLR <?154. Conclusions Our findings show that higher PLR (?154) is an independent risk factor for poor prognosis in GC patients. Besides, PLR can predict adjuvant chemotherapy (oxaliplatin/5-fluorouracil combination) response in patients with GC after surgery.
Project description:<b>Introduction:</b> Biomarkers are biological molecules entirely or partially participating in cancerous processes that function as measurable indicators of abnormal changes in the human body microenvironment. Aiming to provide an overview of associations between prognostic biomarkers and gastric cancer (GC), we performed this umbrella review analyzing currently available meta-analyses and grading the evidence depending on the credibility of their associations. <b>Methods:</b> A systematic literature search was conducted by two independent investigators of the PubMed, Embase, Web of Science, and Cochrane Databases to identify meta-analyses investigating associations between prognostic biomarkers and GC. The strength of evidence for prognostic biomarkers for GC were categorized into four grades: strong, highly suggestive, suggestive, and weak. <b>Results:</b> Among 120 associations between prognostic biomarkers and GC survival outcomes, only one association, namely the association between platelet count and GC OS, was supported by strong evidence. Associations between FITC, CEA, NLR, foxp3+ Treg lymphocytes (both 1- and 3-year OS), CA 19-9, or VEGF and GC OS were supported by highly suggestive evidence. Four associations were considered suggestive and the remaining 108 associations were supported by weak or not suggestive evidence. <b>Discussion:</b> The association between platelet count and GC OS was supported by strong evidence. Associations between FITC, CEA, NLR, foxp3+ Treg lymphocytes (both 1- and 3-year OS), CA 19-9, or VEGF and GC OS were supported by highly suggestive evidence, however, the results should be interpreted cautiously due to inadequate methodological quality as deemed by AMSTAR 2.0.
Project description:BACKGROUND:Chronic inflammation is considered as a hallmark of gastric cancer (GC) and plays a critical role in GC progression and metastasis. This study aimed to explore the prognostic values of preoperative fibrinogen-to-prealbumin ratio (FPR), fibrinogen-to-albumin ratio (FAR), and novel FPR-FAR-CEA (FFC) score in patients with GC undergoing gastrectomy. METHODS:A total of 273 patients with resectable GC were included in this retrospective study. We performed Kaplan-Meier and Cox regression analyses to assess the prognostic role of preoperative FPR, FAR, and FFC score in patients with GC and analyze their relationships with clinicopathological features. RESULTS:Receiver operating characteristic curve (ROC) analysis revealed that the optimal cutoff values for FPR and FAR were 0.0145 and 0.0784, respectively. The FFC score had a higher area under the ROC curve than FAR and CEA. Elevated FPR (? 0.0145) and FAR (? 0.0784) were significantly associated with old age, large tumor size, tumor invasion depth, lymph nodes metastasis, advanced TNM stage, large Borrmann type, and anemia status. Kaplan-Meier analysis showed that high FPR, FAR, and FFC score were related to poor survival. Multivariate analyses indicated that FPR, FFC score, TNM stage, and tumor size were significant independent factors for survival. CONCLUSIONS:Preoperative FPR and FFC score could be used as prospective noninvasive prognostic biomarkers for resectable GC.
Project description:<h4>Background</h4>The prognostic value of neutrophil-lymphocyte ratio (NLR) and Glasgow Prognostic Score (GPS) has been extensively validated in various cancers. We aimed to examine the usefulness of a combination of NLR and GPS (named CNG) for predicting survival outcomes in patients after curative resection for gastric cancer (GC).<h4>Methods</h4>We retrospectively analyzed the records of 1056 patients who underwent curative resection as initial treatment for GC from October 2000 to September 2012. The preoperative CNG was calculated as follows: patients with hypoalbuminemia (< 35 g/L), elevated C-reactive protein (> 10 mg/L), and elevated NLR (? 2) were allocated a score of 3; patients with two, one, or no abnormal values were allocated a score of 2, 1, or 0, respectively.<h4>Results</h4>The NLR and GPS were the only inflammatory variables independently associated with overall survival (OS) in multivariate analysis. When they were replaced by CNG in multivariate analysis, CNG was independently associated with OS (hazard ratio [HR] for CNG 1 [1.367, 95% CI: 1.065-1.755; P = 0.014], CNG 2 [1.887, 95% CI: 1.182-3.011; P = 0.008], and CNG 3 [2.224, 95% CI: 1.238-3.997; P = 0.008]; P = 0.020). In stage-matched analysis, the prognostic significance was still maintained in stage I-III (P = 0.002, P = 0.042, and P < 0.001, respectively). In addition, 5-year survival rates ranged from 92% (stage I) to 35% (stage III) and from 65%(CNG 0) to 18%(CNG 3) with tumor-nodes-metastasis (TNM) stage or CNG alone. However, the combination of TNM and CNG stratified 5-year survival rates from 98% (TNM I, CNG 0) to 12% (TNM III, CNG 3).<h4>Conclusion</h4>The preoperative CNG is a novel predictor of postoperative survival, and the combination of CNG and TNM effectively stratifies outcomes in patients after curative resection for GC.
Project description:INTRODUCTION:To assess the ability of the Age-Adjusted Charlson Comorbidity Index (ACCI) to predict survival after radical gastrectomy in patients with gastric cancer (GC). METHOD:Data from patients with GC who underwent radical gastrectomy from January 2008 to December 2012 in Fujian Medical University Union Hospital were retrospectively analyzed. Patients were categorized into either high ACCI group or low ACCI group based on the effect of ACCI on long-term GC prognosis. 1:1 propensity score matching (PSM) was used to reduce confounding bias. To further analyze the impact of ACCI on the long-term prognosis of patients after radical gastrectomy, a nomogram was built based on the Cox proportional hazards regression model. RESULTS:A total of 1476 patients were included in the analysis. After PSM, there was no statistically significant differences in tumor location, tumor size and tumor stage between low ACCI group (429 cases) and high ACCI group (429 cases) (all P?>?0.05). Before and after PSM, the incidence of postoperative complications in high ACCI group was significantly higher than that in low ACCI group (P?<?0.05). The 5-year overall survival rate (OS) in low ACCI group was significantly higher than that in high ACCI group. Multivariate analysis showed that ACCI was an independent risk factor for OS (P?<?0.05). The Harrell's C-statistics (C-index) of TNMA, a prognostic evaluation system combining ACCI and TNM staging system, was significantly higher than that of TNM staging system in both the modeling and validation groups (all P?<?0.05). CONCLUSIONS:ACCI was an independent risk factor for the long-term prognosis of GC patients after radical gastrectomy that could effectively improve the predictive efficacy of the TNM staging system for GC.
Project description:Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and platelet count (PC) were shown to be prognostic in several solid malignancies. We analysed 603 R0 resected patients to assess whether NLR, PLR and PC correlate with other well-known prognostic factors and survival of patients with colorectal cancer (CRC). Receiver operating characteristic (ROC) curve analysis was performed to define cut-off values for high and low ratios of these indices. Univariate and multivariate analysis were used to determine the prognostic value of NLR, PLR and PC for overall and cancer-related survival. The distribution of NLR, PLR and PC in CRC patients was compared with 5270 healthy blood donors. The distribution of NLR, PLR and PC was significantly different between CRC patients and controls (all p?<?0.05). A significant but heterogeneous association was found between the main CRC prognostic factors and high values of NLR, PLR and PC. Survival appeared to be worse in patients with high NLR with cancers in AJCC/UICC TNM Stages I-IV; nonetheless its prognostic value was not confirmed for cancer-related survival in multivariate analysis. After stratification of patients according to AJCC/UICC TNM stages, high PC value was significantly correlated with overall and cancer-related survival in TNM stage IV patients.
Project description:<h4>Background</h4>Serum tumor markers including AFU, AFP, CEA, CA199, CA125 and CA724, are of great importance in the diagnosis, prognostic prediction and recurrence monitoring of gastrointestinal malignancies. However, their significance in gastric cancer (GC) patients with neoadjuvant therapy (NCT) is still uncertain. The aim of this study was to evaluate the predictive value of these six tumor markers in locally advanced GC patients who underwent NCT and curative surgery.<h4>Methods</h4>In total, 290 locally advanced GC patients who underwent NCT and D2 radical gastrectomy were retrospectively analyzed. Data on their tumor markers before (pre-) and after (post-) NCT and pathological characteristics were extracted from the database of our hospital. The optimal cutoff values of the six tumor markers were calculated by the ROC curve and Youden index. Their predictive significance was analyzed and survival curves for overall survival (OS) were obtained by the Kaplan-Meier method. Associations between categorical variables were explored by the chi-square test or Fisher's exact test. Multivariate analyses were performed by the Cox regression model.<h4>Results</h4>Pre- and post-CA199, -CA125 and -CA724 could predict overall survival (all P?<?0.05), but only the change (diff-) of CA199 was related to prognosis (P?=?0.05). In the multivariable analysis, pre- (P?=?0.014) and post-CA724 (P?=?0.036) remained significant, though diff-CA724 was not an independent prognostic factor (P?=?0.581). In addition, pre- and post-CA199, -CA125 and -CA724 were associated with lymph node metastasis (N- vs N+) and pathological stage (I-II vs III) (all P?<?0.05). Moreover, post-CA724 was related to the vascular or lymphatic invasion (P?=?0.019), while pre-CA724 was not (P?=?0.082). However, AFU, AFP and CEA showed no association with survival (P?>?0.05).<h4>Conclusions</h4>CA724 is an independent factor for prognosis and could be used to predict ypN and ypTNM stage in locally advanced GC patients undergoing NCT and curative resection.
Project description:The prognostic role of systemic inflammatory response (SIR) markers is unclear in patients with non-muscle invasive bladder cancer (NMIBC). Here, we aimed to investigate the prognostic role of various SIR markers in the oncological outcomes in non-muscle invasive bladder cancer (NMIBC) patients at a single institution in Korea. Neutrophil-lymphocyte ratio (NLR), derived-NLR (dNLR), and platelet-lymphocyte ratio (PLR) were examined as SIR markers. We retrospectively collected data of 1,698 NMIBC patients who underwent transurethral resection of the bladder (TURB) between 1990 and 2013. After excluding 147 patients, the study population finally consisted of 1,551 individuals. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) were analyzed by using Kaplan-Meier estimates. Multivariate Cox regression model was adopted to identify the predictors of oncological outcomes. Notably, elevated NLR (?2.0), dNLR (?1.5) and PLR (?124) were associated with poor OS outcomes. Patients with increased NLR, but not dNLR and PLR, only had poor CSS estimates compared to those with lower NLR. However, no significant differences were found in RFS and PFS according to the SIR status. In the multivariate Cox regression analysis, elevated NLR was identified as a key predictor of OS [hazard ratio (HR)=1.52, 95% confidence interval (CI)=1.19-1.95], in addition to age (HR=1.07, 95% CI=1.05-1.08), hemoglobin (HR=0.83, 95% CI=0.78-0.88), and high grade tumor (HR=1.88, 95% CI=1.45-1.08). With respect to CSS, increased NLR was also identified as an independent predictor (HR=1.12, 95% CI=1.01-1.25). In summary, our results indicate that NLR can be a very reliable SIR marker for predicting the oncological outcomes, particularly mortality outcomes.
Project description:BACKGROUND:The introduction of the new TNM staging system for thymic epithelial malignancies produced a significant increase in the proportion of patients with stage I disease. The identification of new prognostic factors could help to select patients for adjuvant therapies based on their risk of recurrence. Neutrophil-to-lymphocyte ratio (NLR) has recently gained popularity as reliable prognostic biomarker in many different solid tumors. The aim of this study is to assess the utility of NLR evaluation as a prognostic marker in patients with surgically-treated thymoma. METHODS:A retrospective analysis was conducted among patients who underwent resection for thymoma in a single center. Patients were divided in two groups, under (low-NLR-Group?=?47 patients, 60%) and above (high-NLR-Group?=?32 patients, 40%) a ROC-derived NLR cut-off (2.27). Associations with clinical-pathological variables were analyzed; disease-free survival (DFS) was identified as the primary endpoint. RESULTS:Between 2007 and 2017, 79 patients had surgery for thymoma. Overall 5-year DFS was 80%. Univariate survival analysis demonstrated that NLR was significantly related to DFS when patients were stratified for TNM stage (p?=?0.043). Five-year DFS in the low-NLR-Group and in the high-NLR-Group were respectively 100 and 84% in stage I-II, and 66 and 0% in stage III. TNM stage resulted as the only independent prognostic factor at multivariate analysis, with hazard ratio of 3.986 (95% CI 1.644-9.665, p?=?0.002). CONCLUSIONS:High preoperative NLR seems to be associated to a shorter DFS in patients submitted to surgery for thymoma and stratified for TNM stage.