Carcinoembryonic Antigen Ratio Research Articles

The diagnostic value of pleural effusion/serum ratio of carcinoembryonic antigen and pleural effusion/serum ratio of interferon-γ in classification of pleural effusion.

Distinguishing between different types of pleural effusions (PEs) is crucial for clinical diagnosis and treatment. This study evaluates the diagnostic value of carcinoembryonic antigen (CEA) and interferon-gamma (IFN-γ) levels in PE and serum, as well as the PE/serum ratios of these markers, in classifying PE. We retrospectively analyzed 99 patients with PE, categorizing them into malignant pleural effusion (MPE), tuberculous pleural effusion (TPE), and benign PE groups. Levels of CEA and IFN-γ in PE and serum were quantified and their ratios were calculated. Diagnostic performance was assessed using receiver operating characteristic analysis, focusing on the area under the curve (AUC) to determine the efficacy of these biomarkers. Significantly elevated levels of CEA in PE and serum were observed in the MPE group compared to the benign and TPE groups, with the PE/serum CEA ratio offering substantial diagnostic value (AUCs: PE = 0.843, serum = 0.744). Conversely, IFN-γ levels in PE and serum were markedly higher in the TPE group, demonstrating notable diagnostic accuracy (AUCs: PE = 0.970, serum = 0.917). Both CEA and IFN-γ demonstrate high clinical utility in differentiating between MPE and TPE. The PE/serum ratio of these biomarkers enhances diagnostic accuracy, potentially facilitating earlier and more accurate therapeutic interventions.

Prognostic significance of preoperative to postoperative serum carcinoembryonic antigen ratio after lobectomy for lung adenocarcinoma.

Lung adenocarcinoma with a preoperatively elevated serum carcinoembryonic antigen (CEA) value has a relatively poor postoperative prognosis. Although surgical resection generally results in a reduction in the CEA value, the significance of the change in the CEA value on the prognostic outcome remains unclear. Our study included 133 patients who underwent lobectomy with curative intent for lung adenocarcinoma representing a preoperative CEA value > 5.0. Statistical analysis was performed using a receiver operating characteristic analysis and a stepwise Cox proportional hazards analysis. Both the postoperative CEA value and postoperative-to-preoperative CEA ratio (CEA ratio) significantly affected the survival. Although the CEA ratio was not predictive of the survival in patients with postoperative CEA ≤ 6.2ng/ml (n = 105), it was predictive in the remaining patients with postoperative CEA > 6.2ng/ml (n = 28). Patients with postoperative CEA > 6.2ng/ml and a CEA ratio ≥ 0.39 (n = 7) showed the worst survival outcome. According to the multivariate analysis, the CEA ratio and postoperative nodal status were significant predictors of the survival in overall patients. The CEA ratio may be a useful prognostic marker in patients who undergo lobectomy for lung adenocarcinoma and show postoperative CEA > 6.2ng/ml. A high CEA ratio may indicate the presence of a subclinical residual tumor, which may lead to the development of subsequent recurrence.

Distinction of ALK fusion gene- and EGFR mutation-positive lung cancer with tumor markers.

It is difficult to predict gene mutations individually based on clinical background alone. Tumor markers may help to predict each gene mutation. Identifying tumor markers that can predict gene mutation will facilitate timely genetic testing and intervention. We selected 134 cases of advanced or recurrent ALK-positive and 172 cases of advanced or recurrent EGFR-positive lung cancer from our clinical database. The cutoff values for the tumor markers were defined as 5.0 ng/mL or higher for carcinoembryonic antigen (CEA) and 3.5 ng/mL or higher for soluble fragment of cytokeratin 19 (CYFRA21-1) in accordance with the institutional standards. A positive CYFRA21-1:CEA ratio was defined as 0.7 or higher. The CEA-positivity rate was 49% for ALK-positive lung cancers and 73% for EGFR-positive lung cancers, which was significantly different (p < 0.001). The CYFRA21-1 positivity rate was significantly higher in ALK-positive lung cancer (36%) compared with EGFR-positive lung cancer (23%) (p = 0.034). The median CYFRA21-1:CEA ratio was 0.395 for the ALK group, which was significantly higher compared with 0.098 for the EGFR group (p < 0.001). These trends were similar when excluding histology other than adenocarcinoma. The median time-to-treatment failure (TTF) for initial tyrosine kinase inhibitor (TKI) therapy was 308 days for the high CYFRA21-1:CEA ratio group and 617 days for the low CYFRA21-1:CEA ratio group for ALK-positive lung cancer (p = 0.100). A higher proportion of patients with ALK-positive lung cancer were CYFRA21-1 positive and had higher CYFRA21-1:CEA ratios compared with EGFR-positive lung cancer patients.

Diagnostic accuracy of pleural fluid to serum carcinoembryonic antigen ratio and delta value for malignant pleural effusion: findings from two cohorts.

Pleural fluid (PF) carcinoembryonic antigen (CEA) is a widely used diagnostic marker for malignant pleural effusion (MPE). Recent studies revealed that PF to serum CEA was also a promising diagnostic parameter for MPE. We aimed to investigate whether PF to serum CEA ratio and delta CEA (PF minus serum CEA) provided added value to PF CEA in diagnosing MPE. Patients with pleural effusion in a retrospective cohort (BUFF) and a prospective cohort (SIMPLE) were included. The clinical characteristics of the patients were extracted from their medical records. The diagnostic value of CEA ratio and delta CEA was estimated by a receiver operating characteristics (ROC) curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). A total of 148 patients in the BUFF cohort and 164 patients in the SIMPLE cohort were enrolled. The BUFF cohort had 46 MPE patients and 102 benign pleural effusion (BPE) patients, and the SIMPLE cohort had 85 MPE patients and 79 BPE patients. In both cohorts, MPE patients had significantly higher PF CEA, serum CEA, CEA ratio, and delta CEA. The area under ROC curves (AUCs) of PF CEA, CEA ratio, and delta CEA were 0.78 (95% CI: 0.67-0.88), 0.80 (95% CI: 0.72-0.89) and 0.83 (95% CI: 0.75-0.91) in the BUFF cohort, and 0.89 (95% CI: 0.83-0.94), 0.86 (95% CI: 0.80-0.92), and 0.84 (95% CI: 0.78-0.91) in the SIMPLE cohort. The differences between the AUCs of PF CEA, CEA ratio, and delta CEA did not reach statistical significance. The continuous NRI and IDI of CEA ratio and delta CEA were <0. CEA ratio and delta value cannot provide added diagnostic value to PF CEA. The simultaneous determination of serum and PF CEA should not be adopted in clinical practice.

Early Postoperative Serum Carcinoembryonic Antigen Is a Stronger Independent Prognostic Factor for Stage II Colorectal Cancer Patients Than T4 Stage and Preoperative CEA.

BackgroundSerum carcinoembryonic antigen (CEA) is an important biomarker for diagnosis, prognosis, recurrence, metastasis monitoring, and the evaluation of the effect of chemotherapy in colorectal cancer (CRC). However, few studies have focused on the role of early postoperative CEA in the prognosis of stage II CRC.MethodsPatients with stage II CRC diagnosed between January 2007 and December 2015 were included. Receiver operating characteristic (ROC) curves were used to obtain the cutoff value of early postoperative CEA, CEA ratio and CEA absolute value. The areas under curves (AUCs) were used to estimate the predictive abilities of the CEA and T stage. The stepwise regression method was used to screen the factors included in the Cox regression analysis. Before and after propensity score (PS) - adjusted Cox regression and sensitivity analysis were used to identify the relationship between early postoperative CEA and prognosis. Meta-analysis was performed to verify the results. Kaplan-Meier survival curves were used to estimate the effects of CEA on prognosis.ResultsWe included 1081 eligible patients. ROC curves suggested that the cutoff value of early postoperative CEA was 3.66 ng/ml (P <0.001) and the AUC showed early postoperative CEA was the most significant prognostic marker in stage II CRC (P = 0.0189). The Cox regression and sensitivity analysis before and after adjusting for PS both revealed elevated early postoperative CEA was the strongest independent prognostic factor of OS, DFS, and CSS (P < 0.001). Survival analysis revealed that patients with elevated early postoperative CEA had lower OS (53.62% VS 84.16%), DFS (50.03% VS 86.75%), and CSS (61.77% VS 90.30%) than patients with normal early postoperative CEA (P < 0.001). When the postoperative CEA was positive, the preoperative CEA level showed no significant effect on the patient’s prognosis (all P-values were > 0.05). Patients with a CEA ratio ≤0.55 or CEA absolute value ≤-0.98 had a worse prognosis (all P-values were < 0.001). Survival analysis suggested that adjuvant chemotherapy for stage II CRC patients with elevated early postoperative CEA may improve the CSS (P = 0.040).ConclusionsEarly postoperative CEA was a better biomarker for prognosis of stage II CRC patients than T stage and preoperative CEA, and has the potential to become a high-risk factor to guide the prognosis and treatment of stage II CRC patients.

Prognostic Implication of Preoperative Serum Albumin to Carcinoembryonic Antigen Ratio in Colorectal Cancer Patients.

Background: Preoperative serum albumin (ALB) and carcinoembryonic antigen (CEA) were useful prognostic factors in colorectal cancer (CRC); however, the ALB to CEA ratio (ACR) and their individual prognostic efficacies have been less studied. Methods: A retrospective study with 156 CRC patients staged I to IV was performed. The prognostic efficacy of ACR was estimated and subsequently compared with ALB, CEA, and other systemic inflammation markers, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR). Differences in progression-free survival (PFS) and overall survival (OS) were determined by Kaplan–Meier (K-M) analysis, and the risk factors for survival were calculated by the Cox proportional hazards model. Results: A total of 31.41% (49 of 156) of patients presented with ACR-low disease, and these patients had tumors with advanced T stages, larger tumor diameters and distant metastases, and a lower LMR. When 5.98 was used as the cut-off point, it had a sensitivity of 58.50% and 61.50% and a specificity of 83.50% and 80.50% for PFS and OS, respectively. ACR displayed a superior prognostic efficacy than individual ALB, CEA and NLR, LMR, and PLR for both PFS and OS (except LMR). Patients in the ACR-low group displayed significantly worse PFS and OS than those in the ACR-high group. Finally, ACR was an independent prognostic factor for both PFS (HR = 0.31, 95% CI: 0.17−0.56, P < .01) and OS (HR = 0.33, 95% CI: 0.16−0.66, P < .01). Conclusions: ACR was a robust prognostic factor in CRC, and patients with a relatively low preoperative ACR would have significantly worse survival.

Preoperative Absolute Lymphocyte Count to Carcinoembryonic Antigen Ratio Is a Superior Predictor of Survival in Stage I to III Colorectal Cancer.

Background:Preoperative absolute lymphocyte count (ALC) and carcinoembryonic antigen (CEA) are useful prognostic indicators in colorectal cancer (CRC); however, the role of the ALC-to-CEA ratio (LCR) has been less addressed.Methods:A total of 189 stage I to III CRC patients who underwent radical resection were enrolled retrospectively. The significance of the LCR in predicting disease-free survival (DFS) and overall survival (OS) was calculated and compared with other markers based on ALC. The DFS and OS differences among the low- and high-LCR subgroups and risk factors for the outcome were estimated by Kaplan–Meier analysis and the Cox proportional hazards model, respectively.Results:Taking 0.28 as the cutoff point, the LCR has a sensitivity and a specificity of 75.60% and 77.00%, respectively, in predicting OS. The prognostic efficacy of LCR was significantly superior to that of other markers based on ALC for predicting DFS and OS. A total of 34.92% (66/189) of patients displayed a low LCR (<0.28), and these patients were more likely to present poor cell differentiation (P = .03), tumor deposits (P < .01) and advanced T (P < .01) and liver metastasis (P = .02). Patients with a low LCR had significantly worse DFS (Log Rank = 34.98, P < .01) and OS (Log Rank = 43.17, P < .01) than those with a high LCR. The LCR was an independent prognostic factor for both DFS (hazard ratio (HR) = 0.35, 95% confidence interval (CI): 0.20-0.62, P < .01) and OS (HR = 0.18, 95% CI: 0.08-0.37, P < .01).Conclusions:The LCR is a superior predictor of survival in stage I to III CRC, and patients with a low LCR have an inferior outcome; however, additional studies are required to validate its prognostic role.

Development and Validation of a Scoring System for Early Diagnosis of Malignant Pleural Effusion Based on a Nomogram.

BackgroundThe diagnostic value of clinical and laboratory features to differentiate between malignant pleural effusion (MPE) and benign pleural effusion (BPE) has not yet been established.ObjectivesThe present study aimed to develop and validate the diagnostic accuracy of a scoring system based on a nomogram to distinguish MPE from BPE.MethodsA total of 1,239 eligible patients with PE were recruited in this study and randomly divided into a training set and an internal validation set at a ratio of 7:3. Logistic regression analysis was performed in the training set, and a nomogram was developed using selected predictors. The diagnostic accuracy of an innovative scoring system based on the nomogram was established and validated in the training, internal validation, and external validation sets (n = 217). The discriminatory power and the calibration and clinical values of the prediction model were evaluated.ResultsSeven variables [effusion carcinoembryonic antigen (CEA), effusion adenosine deaminase (ADA), erythrocyte sedimentation rate (ESR), PE/serum CEA ratio (CEA ratio), effusion carbohydrate antigen 19-9 (CA19-9), effusion cytokeratin 19 fragment (CYFRA 21-1), and serum lactate dehydrogenase (LDH)/effusion ADA ratio (cancer ratio, CR)] were validated and used to develop a nomogram. The prediction model showed both good discrimination and calibration capabilities for all sets. A scoring system was established based on the nomogram scores to distinguish MPE from BPE. The scoring system showed favorable diagnostic performance in the training set [area under the curve (AUC) = 0.955, 95% confidence interval (CI) = 0.942–0.968], the internal validation set (AUC = 0.952, 95% CI = 0.932–0.973), and the external validation set (AUC = 0.973, 95% CI = 0.956–0.990). In addition, the scoring system achieved satisfactory discriminative abilities at separating lung cancer-associated MPE from tuberculous pleurisy effusion (TPE) in the combined training and validation sets.ConclusionsThe present study developed and validated a scoring system based on seven parameters. The scoring system exhibited a reliable diagnostic performance in distinguishing MPE from BPE and might guide clinical decision-making.

Prognostic significance of the postoperative/preoperative serum CEA level ratio in patients with solitary adrenal metastasis from lung cancer.

The present study aimed to evaluate the prognostic significance of the postoperative to preoperative serum carcinoembryonic antigen (CEA) level ratio (CEA ratio) in patients with lung cancer with solitary metastasis of the adrenal gland after adrenalectomy. Furthermore, the optimal CEA ratio cutoff value for predicting disease-free survival (DFS) in patients with lung cancer after adrenalectomy was determined. The medical records of patients with lung cancer with isolated adrenal metastasis who underwent adrenalectomy at the National Cancer Center Hospital East (Kashiwa, Japan) between January 2013 and December 2020 were retrospectively reviewed. Receiver operating characteristic curve analysis was used to segregate patients into two groups (high and low CEA groups) and the clinical prognosis for the two groups was determined. In addition, the association between the CEA ratio and clinical factors was determined. A total of 14 patients with a median age of 68 years (range, 50-75 years) were analyzed, of which 9 (64%) were males. The optimal cutoff value for the CEA ratio to predict DFS was 0.60. The high CEA ratio group (≥0.60) displayed poorer DFS and cancer-specific survival (P=0.03 and 0.02, respectively). The CEA ratio was significantly associated with the preoperative CEA level (P=0.01) and the high CEA ratio (≥0.60) group had lower preoperative CEA levels. The study suggested that the perioperative CEA ratio may be an important emerging prognostic factor for patients with lung cancer with solitary adrenal gland metastasis. As the sample size was limited, a further study with a larger cohort is required to validate the present findings.

Pancreatic Cancer Insights: Optimization of the Diagnostic Capacity of Tumor Biomarkers.

Pancreatic cancer (PC) is one of the deadliest malignancies. The aim of this study was to determine the usefulness of the carbohydrate antigen 19.9 (CA19.9)/ carcinoembryonic antigen (CEA) ratio as a diagnostic tool. This was a retrospective observational study (2015-2019), including laboratory requests with increased CA19.9 and CEA but no previous neoplasia. Receiver operating characteristic (ROC) curve analyses were performed for the CA19.9/CEA ratio and for CA19.9 and CEA alone for the detection of PC, and cutoff values for all strategies were selected separately and in combination. A total of 373 individuals were included. The area under the curve (AUC) for CA19.9/CEA was 0.872, whereas the AUC for CA19.9 was 0.847 and for CEA was 0.554. Cutoff values with the greatest diagnostic power were CA19.9/CEA >40, CA19.9 >1130 U/mL, and CEA > 14.5 U/mL. The combination of CA19.9/CEA > 40 with CA19.9 > 550 U/mL maximized the diagnostic accuracy for PC. Our results highlight the relevance of the measurement of serum CA19.9 and CEA in the detection of PC.

The carcinoembryonic antigen ratio is a potential predictor of survival in recurrent colorectal cancer.

The carcinoembryonic antigen (CEA) "value" itself is often useless in patients with a normal CEA level at initial presentation and those with tumor-irrelevant elevated CEA. Although the unified marker using CEA has been desirable for recurrent tumor staging as well as for primary tumor staging, little is known concerning its relationship with the survival of patients with recurrent colorectal cancer in particular. This retrospective historical study included patients who experienced disease relapse after curative surgery for stage I-III colorectal cancer between 2006 and 2018. A total of 129 patients with recurrent disease after curative surgery for colorectal cancer were included. We focused on the CEA "ratio" (CEA-R: the ratio of the CEA level at the time of recurrence to that measured 3months before recurrence) and aimed to evaluate the correlation between CEA-R and survival in recurrent colorectal cancer. Patients with a high CEA-R (≥ 2) exhibited significantly worse 2year survival than those with a low CEA-R (< 2) (88.1% vs. 44.9%, P < 0.001), irrespective of the CEA value before primary resection. Multivariate analyses demonstrated that the CEA-R (HR; 3.270, 95% CI 1.646-6.497, P = 0.001) was a significant prognostic factor. The CEA-R is a potential marker stratifying the survival of patients with disease relapse who exhibit aggressive biology at recurrent disease foci. As a novel marker, the CEA-R would serve as a clinical guide for tailoring treatment strategies at the time of disease relapse in patients with colorectal cancer.

Association between Primary Perioperative CEA Ratio, Tumor Site, and Overall Survival in Patients with Colorectal Cancer.

There are differences in the incidence, clinical presentation, molecular pathogenesis, and outcome of colorectal cancer (CRC) based on tumor location. Emerging research suggests that the perioperative carcinoembryonic antigen (CEA) ratio (post-op/pre-op CEA) is a prognostic factor for CRC patients. We aimed to determine the association between CEA ratio, tumor location, and overall survival (OS) among patients with CRC. We analyzed 427 patients who underwent resection for CRC at the University of Kansas Medical Center. After excluding those without pre- or post-operative CEA data, 207 patients were classified as either high (≥0.5) or low (<0.5) ratio. Primary outcomes were as follows: (1) OS stratified by CEA ratio; (2) OS stratified by tumor location; (3) OS stratified by tumor location among those with CEA elevation > 5 ng/mL at the time of recurrence. The Kaplan–Meier method was used to estimate survival rates. The median age was 62 years (inter-quartile range 51–71), 55% were male, 41% were smokers, 71% had left-sided tumors, the median pre-operative CEA was 3.1 ng/mL (inter-quartile range (IQR) 1.5–9.7), and 57% had a CEA ratio ≥0.5. The OS rates were 65.1% and 86.3% in patients with high versus low CEA ratios, respectively (log-rank p-value = 0.045). The OS rates were 64.4% and 77.3% in patients with right-sided vs. left-sided tumors, respectively (log-rank p-value = 0.5). Among patients with CEA levels greater than 5 at the time of recurrence, the OS rates were 42.9% and 43.4% in patients with right-sided vs. left-sided tumors, respectively (log-rank p-value = 0.7). There was a significantly higher survival among patients with low CEA ratios than among those with high CEA ratios. There was no difference in OS between left- versus right-sided tumors. Among patients with CEA elevation > 5 ng/mL at the time of recurrence, there was no difference in OS between left versus right-sided tumors. These findings warrant validation in a larger cohort as our sample size was limited.

Abstract 3197: Serum CEA change predicts tumor regression and prognosis in locally advanced rectal cancer

Abstract Objective: To investigate the value of carcinoembryonic antigen (CEA) change in predicting pathological tumor regression and outcome for locally advanced rectal cancer (LARC) patients received neoadjuvant therapy. Material and methods: LARC patients who received neoadjuvant therapy and radical tumor resection were retrospectively collected. The predictive value of baseline CEA, post-treatment CEA and post/pre-treatment CEA ratio for tumor regression grade (TRG), overall survival and diseases free survival were estimated by logistic regression or cox proportional hazard regression. Results: 700 LARC patients were enrolled in the study with 475 (67.9%) cases of male patients and median age of 56 (20-87). Of the all patients enrolled, multivariate analysis showed post-treatment CEA (OR=1.142, 95% CI: 1.073-1.215, P&amp;lt;0.001) was an independent predictor for TRG. 284 patients with elevated baseline CEA were analyzed. Among them, 168 patients (59.2%) have normalized CEA. Multivariate analysis showed post-treatment CEA (OR=1.068, 95% CI: 1.007-1.133, P=0.027), CEA ratio (OR=3.463, 95% CI: 1.269-9.446, P=0.015) were independent predictors for TRG(Table 1). Of the all patients enrolled, multivariate analysis showed low preoperative albumin level (HR=0.919, 95% CI: 0.886-0.952, P&amp;lt;0.001), tumor deposit (HR=3.226, 95% CI: 1.470-7.077, P=0.003), nerve infiltration (HR=3.602, 95% CI: 1.736-7.476, P=0.001), high post-treatment CEA (HR=1.029, 95% CI: 1.010-1.049, P=0.003) were independent unfavored predictors for overall survival of LARC patients. 700 patients were divided into 3 groups: A group with normal baseline CEA (n=416,59.4%); B group with normalized CEA (n=168,24.0%); C group with elevated baseline and post-treatment CEA (n=116,16.6%). The overall survival and disease free survival of group B were comparable to that of group A (P=0.588,0.053) and significantly better than that of group C (B vs. C: P=0.010, 0.003; A vs. C: P=0.007, &amp;lt;0.001). Conclusion: 1. Post-treatment CEA is an independent predictor for TRG of LARC patients and higher post-treatment CEA precdicted poor overall survival. 2. Post/pre-treatment CEA ratio is an independent predictor for TRG of LARC patients with elevated baseline CEA. Citation Format: Zerong Cai, Lingyu Huang, Ping Lan, Xiaojian Wu. Serum CEA change predicts tumor regression and prognosis in locally advanced rectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3197.

BRAF-V600E and microsatellite instability prediction through CA-19-9/CEA ratio in patients with colorectal cancer.

Early identification of colorectal cancer (CRC) patients that are BRAF-V600E mutant and/or microsatellite instability-high (MSI-High), has both prognostic and predictive value. We wanted to highlight an observation of utilizing 2 simple, rapid and universally available lab tests, i.e., carbohydrate cancer antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) tumor markers, the ratio (CA-19-9/CEA) of which can distinctly identify these patients from other molecular subsets of CRC. All patients with metastatic CRC from December 2016 to February 2019 were identified, and included in the study if they had both CA19-9 and CEA tests available. Circulating tumor DNA (ctDNA) testing and tissue genetic testing results were used to categorize patients into BRAF V600E microsatellite stable (MSS), MSI-High, RAS mutant MSS and RAS/RAF wild type CRCs. Kruskal-Wallis test was used to compare the CA19-9/CEA ratio between mutation types and the pairwise p values were adjusted for multiple comparisons with Holm method. For sensitivity analysis, the same analysis was repeated for the mean and median ratio of each patient. All tests were two-sided with alpha level set at 0.05 for statistical significance. BRAF-V600E MSS CRC patients had a discordantly profound elevation in CA-19-9 levels as opposed to the CEA levels. Patients in the BRAF V600E MSS subset had the highest median CA19-9/CEA ratio versus the least median ratio in MSI-High patients. The median of maximum CA-19-9/CEA ratio was 28.92 (range, 2.76-707.27) in BRAF-V600E MSS patients and 4.06 (range, 0.46-166.74) in MSI-High subset of patients. To date, this is the first report utilizing the ratio of tumor markers CA19-9/CEA as a predictive rather than just prognostic tool to identify BRAF-V600E MSS and MSI-High CRC patients.

Value of tumor diameter to preoperative carcinoembryonic antigen ratio in evaluating prognosis of non-metastatic colorectal cancer patients

Objective To explore the value of tumor diameter to preoperative carcinoembryonic antigen (CEA) ratio (TCR) in predicting prognosis of patients with non-metastatic colorectal cancer. Methods The clinical data of 144 patients with colorectal cancer in Hainan Hospital of PLA General Hospital between July 2012 and December 2017 were retrospectively analyzed. Patients were divided into the low TCR group and the high TCR group according to the optimal value of TCR in predicting the disease-free survival (DFS) determined by the receiver operating characteristic curve (ROC). The clinicopathological features of both groups were analyzed, and the influencing factors of DFS were also analyzed by using Cox proportional hazard model. Results ROC analysis showed that TCR had a certain value in predicting DFS, and area under the curve (AUC) was 0.614 (95% CI 0.507-0.722); when the value of TCR was set at 0.690, the sensitivity and specificity of predicting the 3-year DFS rate was 46.3% and 70.9%, respectively. According to 0.690 of TCR, there were 50 cases in the low TCR ( 0.05). Univariate analysis showed that TCR, preoperative CEA level and TNM stage played a role in predicting DFS of patients (all P < 0.05), while Cox multivariate analysis indicated that TCR < 0.690 (HR = 2.369, 95% CI 1.279-4.388, P = 0.006) and Ⅲ stage in TNM stage (HR = 2.214, 95% CI 1.346-3.640, P = 0.002) were the independent risk factors of influencing DFS (all P < 0.01). The 3-year DFS rate of patients in the low TCR group was lower than that of those in the high TCR group (62.0% vs. 83.0%, P = 0.007). Conclusion TCR could have a certain value in judging the prognosis of non-metastatic colorectal cancer patients, and low TCR patients have a poorer prognosis. Key words: Colorectal neoplasms; Tumor diameter; Carcinoembryonic antigen; Disease-free survival; Prognosis

CEA Decline Predicts Tumor Regression and Prognosis in Locally Advanced Rectal Cancer Patients with Elevated Baseline CEA.

Purpose: To investigate the value of carcinoembryonic antigen (CEA) decline in predicting pathological tumor regression and outcome for locally advanced rectal cancer (LARC) patients who received neoadjuvant therapy with elevated baseline CEA.Methods: LARC patients with elevated pre-treatment CEA who received neoadjuvant therapy and radical tumor resection were retrospectively collected. Serum CEA level during treatment were recorded and the predictive value of pre-treatment CEA, post-treatment CEA and CEA ratio (CEApost-treatment /CEApre-treatment) for tumor regression grade (TRG), overall survival and diseases free survival were estimated by logistic regression or cox proportional hazard regression.Results: Two hundred and eighty-four LARC patients with elevated pre-treatment CEA were enrolled and the baseline, post-treatment CEA level and CEA ratio were 11.87 (5.02-731.31) ng/ml, 4.23 (0.50-173.80) ng/ml and 0.31(0.01-2.55) respectively. CEA level in 59.2% of the patients declined to normal after neoadjuvant therapy. Multivariate analysis showed that CEA ratio was an independent predictor for TRG (OR=3.463, 95% CI: 1.269-9.446, P=0.015) and tumor downstage (OR=0.393, 95% CI: 0.187-0.829, P=0.014). Patients with normalized post-treatment CEA level had better overall survival (P=0.010) and disease free survival (P=0.003) than those with elevated CEA level. Higher post-treatment CEA was an independent unfavored predictor for overall survival in LARC patients with elevated pre-treatment CEA (OR=1.042, 95% CI: 1.017-1.067, P=0.001).Conclusion: Post/pre-treatment CEA ratio predicted tumor regression in term of TRG and tumor downstage for LARC patients with elevated pre-treatment CEA and higher post-treatment CEA predicted poor overall survival.

The prognostic value of the postoperative serum CEA levels/preoperative serum CEA levels ratio in colorectal cancer patients with high preoperative serum CEA levels.

PurposeThis study aimed to assess the prognostic value of the postoperative serum carcinoembryonic antigen (CEA) levels/preoperative serum CEA levels ratio (CEA ratio) in colorectal cancer (CRC) patients with high preoperative serum CEA levels and to identify the optimal prognostic cutoff value.Patients and methodsThe medical records of 187 CRC patients in a single center who underwent surgery between September 2012 and September 2014 were retrospectively reviewed. CEA ratio was defined as the ratio between the postoperative serum CEA and preoperative serum CEA. The optimal cutoff values for the CEA ratio were determined by time-dependent receiver operating characteristic (ROC) curve analyses. The Chi-square test or Fisher’s exact probability test were used to test the correlation between CEA ratio and clinicopathological characteristics. Univariate, multivariate, and subgroup Cox proportional hazards analysis were used to identify independent prognostic factors. Kaplan–Meier method was used for establishing survival curves.ResultsThe median follow-up time was 62 months (range 3–88 months). The optimal CEA ratio cutoff value closely related to disease-free survival was 0.295. In the Chi-square test, the CEA ratio was associated with pN stage (p=0.003) and postoperative CEA (p<0.001). In the multivariate analysis, the CEA ratio was an independent prognostic factor for disease-free survival (p=0.003, HR 2.300 [95% CI: 1.326–3.988]) and cancer-special survival (p=0.003, HR 2.525 [95% CI: 1.381–4.614]). The CEA ratio reflected the prognosis of CRC patients more accurately than postoperative CEA levels alone, and the CEA ratio of 0.295 was more likely to reflect the prognosis than other cutoff values.ConclusionThe CEA ratio is a simple and useful tool for further forecasting the prognosis of CRC patients with high preoperative CEA levels and may help develop strategies for the postoperative treatment of CRC patients.

Association between primary tumor site, perioperative CEA ratio, smoking status, and overall survival in patients with colorectal cancer.

e15156 Background: There are differences in the incidence, clinical presentation, molecular pathogenesis and outcome of colorectal cancer (CRC) based on tumor location. Emerging research suggests that perioperative carcinoembryonic antigen (CEA) ratio (post-op/pre-op CEA) is a prognostic factor for CRC patients. We aimed to determine the association between tumor location, CEA ratio, smoking status and overall survival (OS) among patients with CRC. Methods: We analysed 323 patients who underwent resection for CRC at KUMC. After excluding those without pre- or post-operative CEA data, 162 patients were classified as either high ( &gt; = 0.5) or low ( &lt; 0.5) ratio. Primary outcomes were: 1) OS stratified by tumor location; 2) OS stratified by CEA ratio; and 3) whether the association between CEA ratio and OS differed by tumor location, after adjusting for stage and smoking status. Kaplan-Meier method was used to estimate survival rates, and Cox proportional hazards models for multivariate analysis. Results: The median age was 63 years (inter-quartile range 53-72), 61% male, 43% smokers, 73% left-sided tumors, median pre-operative CEA was 3.0 (IQR 1.5-7), and 64% had CEA ratio &gt; = 0.5. The OS rates were 85.7% and 91.9% in patients with left-sided vs right-sided tumors respectively (log-rank p-value = 0.9). The OS rates were 83.5% and 91.5% in patients with high vs low CEA ratios respectively (log-rank p-value = 0.3). The effect of CEA ratio on OS was significantly different when stratified by tumor location (p-value for interaction &lt; 0.001). However, in the stratified analysis, the n was too small to permit further inferential analysis. In multivariate analysis, both tumor location (HR 0.6; p = 0.5) and CEA ratio (HR 1.5; p = 0.5) were not significantly associated with OS after adjusting for smoking status and tumor stage. Smoking was significantly associated with higher rates of death (HR 3.9; p = 0.04) when adjusted for tumor location, CEA ratio, and tumor stage. Conclusions: There was no difference in OS between left versus right-sided tumors. The association between CEA ratio and OS was significantly modified by tumor location. However, to attribute this modification to left vs right warrants validation in a larger cohort as our sample size was limited. Smoking increases mortality irrespective of right vs left sided CRC.

Association between primary tumor site, perioperative CEA ratio, and overall survival in patients with colorectal cancer.

518 Background: There are differences in the incidence, clinical presentation, molecular pathogenesis and outcome of colorectal cancer (CRC) based on the tumor location. Emerging research suggests that the perioperative carcinoembryonic antigen (CEA) ratio is a prognostic factor for CRC patients. We aimed to determine the association between tumor location, perioperative CEA ratio, and 5-year survival among patients with CRC. Methods: We analyzed 111 patients who underwent resection for CRC at KUMC. After excluding patients without pre- or post-operative CEA data, 62 patients for whom we could calculate a CEA ratio (post-op/pre-op CEA) were classified as either high ( ≥ 0.5) or low ( &lt; 0.5) ratio. The primary outcomes were: 1) overall survival (OS) stratified by tumor location; 2) OS stratified by CEA ratio; and 3) whether there was effect modification by tumor location, of the association between perioperative CEA ratio and OS, after adjusting for tumor stage and smoking status. Kaplan-Meier method was used to estimate survival rates, and Cox proportional hazards models for multivariate analysis. Results: The median age was 61 years, 54% male, 31% smokers, 74% left-sided tumors, median pre-operative CEA was 3.3, and 60% had CEA ratio ≥ 0.5. The OS rates were 89.1% and 81.3% in patients with left-sided versus right-sided tumors respectively (p-value = 0.4). The OS rates were 83.8% and 92.0% in patients with high versus low CEA ratios respectively (p-value = 0.3). There was effect modification by tumor location on association between CEA ratio and OS, after adjusting for smoking status and tumor stage (p-value &lt; 0.001). However, in the stratified analysis, the n was too small to permit inferential analysis. In multivariate analysis, both tumor location (HR 0.4; p = 0.3) and perioperative CEA ratio (HR 2.7; p = 0.3) were not significantly associated with OS after adjusting for smoking status and tumor stage. Conclusions: There was no difference in OS between left versus right-sided tumors. The association between perioperative CEA ratio and OS was significantly modified by tumor location. However, to attribute this modification to left versus right warrants validation in a larger cohort as our sample size was limited.

Ratio of carcinoembryonic antigen in pleural fluid and serum for the diagnosis of malignant pleural effusion.

Background:Tumour markers in pleural fluid and their diagnostic value are subject to debate. Although there are several studies on this topic, standardized cut-off values do not exist. In this study we investigated the potential of a ratio of carcinoembryonic antigen (CEA) in pleural fluid and serum, serving as an individual marker for pleural cancer manifestation.Methods:A total of 201 consecutive patients with unclear pleural effusion were included in the study; 98 were diagnosed with malignant pleural effusion and 103 had an effusion due to other, benign reasons. CEA levels in pleural fluid and serum were measured.Results:By using receiver operating characteristics analysis, at the cut-off of 1.0, the CEA ratio showed a specificity of 92% and sensitivity of 85%, with a positive predictive value of 91% and a negative predictive value of 87%. These results are higher than in previous investigations on different pleural tumour markers and their combination.Conclusions:The CEA ratio is a useful tool in predicting pleural carcinosis. Elevated results in cytology-negative patients should lead to further investigations, such as repeated cytological examination or thoracoscopy.