Elevated Carcinoembryonic Antigen Levels Research Articles

Risk of advanced neoplasia after removal of colorectal adenomas with high-grade dysplasia.

Many studies reported the presence of adenomas with high-grade dysplasia (HGD) at index colonoscopy increased the incidence of advanced neoplasia (AN) and colorectal cancer (CRC) following. However, the conclusion remains obscure due to lack of studies on the specific population of adenomas with HGD. This study aimed to assess the long-term risk of AN and CRC after removal of adenomas with HGD. A total of 814 patients who underwent adenomas with HGD removal between 2010 and 2019 were retrospectively analyzed. The outcomes were the incidences of AN and CRC during surveillance colonoscopy. Cox proportional hazards models were utilized to identify risk factors associated with AN and CRC. During more than 2000 person-years of follow-up, we found that AN and CRC incidence densities were 44.3 and 4.4 per 1000 person-years, respectively. The 10-year cumulative incidence of AN and CRC were 39.1% and 5.5%, respectively. In the multivariate model, synchronous low-risk polyps (HR 1.80, 95% CI 1.10-2.93) and synchronous high-risk polyps (HR 3.99, 95% CI 2.37-6.72) were risk factors for AN, whereas participation in surveillance colonoscopy visits (HR 0.56, 95% CI 0.36-0.88 for 1 visit; HR 0.10, 95% CI 0.06-0.19 for ≥ 2 visits) were associated with decreased AN incidence. Additionally, elevated baseline carcinoembryonic antigen (CEA) level (HR 10.19, 95% CI 1.77-58.59) was a risk factor for CRC, while participation in ≥ 2 surveillance colonoscopy visits (HR 0.11, 95% CI 0.02-0.56) were associated with decreased CRC incidence. Interestingly, for 11 patients who developed CRC after removal of adenomas with HGD, immunohistochemistry revealed that 8 cases (73%) were deficient mismatch repair CRCs. Patients who have undergone adenoma with HGD removal are at higher risk of developing AN and CRC, while surveillance colonoscopy can reduce the risk. Patients with synchronous polyps, or with elevated baseline CEA level are considered high-risk populations and require more frequent surveillance.

The efficacy and safety of continuous intravenous infusion of rh-endostatin combined with platinum-based doublet chemotherapy for advanced non-small-cell lung cancer.

Platinum-based doublet chemotherapy is commonly used in the treatment of non-small cell lung cancer (NSCLC). A growing body of evidence indicates that incorporating antiangiogenic agents into platinum-based chemotherapy may enhance the survival outcomes for NSCLC patients. However, the optimal administration protocol for intravenous recombinant human endostatin (rh-endostatin), an antiangiogenic agent, remains uncertain at present. This study aims to investigate the efficacy and safety of 5-d continuous intravenous infusion of rh-endostatin in combination with chemotherapy for patients with advanced NSCLC. The predictive biomarkers for this treatment regimen were further probed. This prospective, single-arm multicenter study enrolled a total of 48 patients with advanced NSCLC who were histologically or cytologically confirmed but had not received any prior treatment from January 2021 to December 2022. Prior to the chemotherapy, these patients received a continuous intravenous infusion of rh-endostatin (210mg) over a period of 120h, using an infusion pump. The chemotherapy regimen included a combination of platinum with either pemetrexed or paclitaxel, given in 21-day cycles. The primary endpoint of the study was median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and assessment of adverse events (AEs). The mPFS was 6.5 months (95% confidence interval (CI): 3.8-9.1m) while the mOS was 12.3 months (95% CI: 7.6-18.5m). The ORR and DCR was 52.1% and 75.0%, respectively. Leukopenia (52.1%), anemia (33.3%), and thrombocytopenia (20.8%) were the most common adverse effects and these toxicities were deemed acceptable and manageable. In addition, a correlation was noted between elevated serum carcinoembryonic antigen (CEA) levels and decreased PFS and OS. The incorporation of a 5-day continuous intravenous infusion of rh-endostatin into platinum-based doublet chemotherapy has demonstrated both safety and efficacy in the treatment of advanced NSCLC. Furthermore, the baseline serum levels of CEA may potentially function as a predictor for the efficacy of rh-endostatin when combined with chemotherapy in NSCLC patients. GOV: NCT05574998.

The Impact of Type 2 Diabetes Mellitus on Treatment Outcomes in Patients Operated for Stage III Rectal Adenocarcinoma

Introduction: Colorectal cancer (CRC) ranks as the world's fourth most prevalent cancer and is the third leading cause of death globally. Stage III CRC indicates localized spread to nearby lymph nodes without metastasis to other body parts. While numerous studies have explored outcomes in CRC patients based on various predictive factors, a comprehensive literature review has identified a gap in research specifically investigating surgical outcomes for stage III rectal adenocarcinoma in individuals with type 2 diabetes mellitus (DM2).Aim: To explore the impact of DM2 on treatment outcomes in patients undergoing surgery for stage III rectal adenocarcinoma.Patients and methods: Our retrospective cohort study involved 95 patients who underwent elective radical anterior rectal resection with established mechanical colorectal anastomosis. Patients were categorized into two groups based on DM2 status.Results: Univariate regression analysis demonstrated that DM2 patients face a significantly higher risk of preoperatively elevated carcinoembryonic antigen levels and postoperative complications such as surgical site infection, urinary issues, and anastomotic leakage. Kaplan-Meier analysis indicated a shorter time to complication onset, particularly anastomotic leakage, and a diminished overall survival in DM2 patients.Conclusion: DM2 emerged as a significant prognostic factor influencing the treatment outcomes of patients undergoing surgery for stage III rectal adenocarcinoma.

Analysis of risk factors for postoperative recurrence of stage I colorectal cancer: a retrospective analysis of a large population.

Colorectal cancer (CRC) is the third most common cancer worldwide. Patients diagnosed with stage I CRC typically do not require postoperative adjuvant treatment. However, postoperative recurrence is present in at least 40% of patients with CRC and often occurs in those with stage I disease. This study aimed to elucidate the current status of recurrence and clinicopathological characteristics in patients with stage I CRC. Data of indicated patients were obtained from 18 registries in Surveillance, Epidemiology, and End Results (SEER). The multivariable Fine-Gray regression model was used to identify the mortality risk of patients. Disparities in survival were analyzed using Kaplan-Meier curves. Logistic regression was employed to identify factors associated with recurrent risk overestimation. Our study indicated a recurrence rate of 15.04% (1,874/12,452) in stage I CRC cases. Notably, we identified race, age, T stage, and carcinoembryonic antigen (CEA) levels as independent risk factors for tumor recurrence, substantially impacting prognosis. Furthermore, gender, race (Black), age (>65 years), elevated CEA levels, and refusal or unknown status regarding radiotherapy significantly correlated with an adverse prognosis in patients with stage I CRC. We identified certain key clinicopathological features of patients with stage I CRC and demonstrated the survival benefits of radiotherapy, offering a new perspective on stage I CRC follow-up and treatment recommendations.

Prognostic factors associated with early recurrence following liver resection for colorectal liver metastases: a systematic review and meta-analysis

BackgroundColorectal cancer (CRC) is the 3rd most common malignancy with the liver being the most common site of metastases. The recurrence rate of colorectal liver metastases (CRLM) after liver resection (LR) is notably high, with an estimated 40% of patients experiencing recurrence within 6 months. In this context, we conducted a meta-analysis to synthesize and evaluate the reliability of evidence pertaining to prognostic factors associated with early recurrence (ER) in CRLM following LR.MethodsSystematic searches were conducted from the inception of databases to July 14, 2023, to identify studies reporting prognostic factors associated with ER. The Quality in Prognostic Factor Studies (QUIPS) tool was employed to assess risk-of-bias for included studies. Meta-analysis was then performed on these prognostic factors, summarized by forest plots. The grading of evidence was based on sample size, heterogeneity, and Egger’s P value.ResultsThe study included 24 investigations, comprising 12705 individuals, during an accrual period that extended from 2007 to 2023. In the evaluation of risk-of-bias, 22 studies were rated as low/moderate risk, while two studies were excluded because of high risk. Most of the studies used a postoperative interval of 6 months to define ER, with 30.2% (95% confidence interval [CI], 24.1–36.4%) of the patients experiencing ER following LR. 21 studies were pooled for meta-analysis. High-quality evidence showed that poor differentiation of CRC, larger and bilobar-distributed liver metastases, major hepatectomy, positive surgical margins, and postoperative complications were associated with an elevated risk of ER. Additionally, moderate-quality evidence suggested that elevated levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA199), lymph node metastases (LNM) of CRC, and a higher number of liver metastases were risk factors for ER.ConclusionThis review has the potential to enhance the efficacy of surveillance strategies, refine prognostic assessments, and guide judicious treatment decisions for CRLM patients with high risk of ER. Additionally, it is essential to undertake well-designed prospective investigations to examine additional prognostic factors and develop salvage therapeutic approaches for ER of CRLM.

The depth of perineural invasion is an independent prognostic factor for stage II colorectal cancer.

Perineural invasion (PNI) is the invasion of nerves by cancer cells and is associated with poor survival in stage II colorectal cancer. However, PNI can be further subdivided according to the depth of invasion, and the depth of PNI has not been clearly linked to prognosis. This study aimed to assess the prognostic value of different depths of PNI in stage II colorectal cancer. We defined PNI in the submucosal plexus and myenteric plexus as superficial perineural invasion (sup-PNI) and PNI in the subserous plexus as deep perineural invasion (deep-PNI). Patients were divided into three groups based on the depth of PNI: sup-PNI, deep-PNI and non-PNI. Then, univariate and multivariate Cox regression analyses were conducted to evaluate the role of PNI in the prognosis of stage II colorectal cancer. This study enrolled 3508 patients with stage II colorectal cancer who underwent resection for primary colorectal lesions between January 2013 and September 2019. Clinicopathological features, including elevated carcinoembryonic antigen (CEA) levels, T4 stage, poor differentiation, deficient DNA mismatch repair (dMMR), and vascular invasion, were correlated with deep-PNI. Multivariate analyses revealed that deep-PNI was associated with worse overall survival (OS; hazard ratio [HR], 3.546; 95% confidence interval [CI], 2.307-5.449; P < 0.001) and disease-free survival (DFS; HR, 2.921; 95% CI, 2.032-4.198; P < 0.001), compared with non-PNI. Conversely, no significant difference in OS or DFS was observed between the sup-PNI and non-PNI groups in multivariate analyses. The study demonstrated that the depth of PNI was an independent prognostic factor for patients with stage II colorectal cancer, and patients with deep PNI had a worse prognosis. Thus, patients with PNI require further subdivision according to the depth of invasion.

Elevated postoperative carcinoembryonic antigen guides adjuvant chemotherapy for stage II colon cancer: a multicentre cohort retrospective study

Most clinical doctors rely on high-risk factors recommended by guidelines to decide whether to undergo adjuvant chemotherapy for stage II colon cancer. However, these high-risk factors do not include postoperative carcinoembryonic antigen (CEA). This study aims to explore the elevation of postoperative CEA as a risk factor, in addition to other high-risk factors, to guide adjuvant chemotherapy for patients with stage II colon cancer. A retrospective analysis was conducted on stage II colon cancer patients who underwent curative surgery at Yunnan Cancer Hospital and The Sixth Affiliated Hospital of Sun Yat-Sen University from April 2008 to January 2019. Patients were classified into three groups based on high-risk factors recommended by guidelines and postoperative CEA levels: low-risk with normal postoperative CEA, low-risk with elevated postoperative CEA and high-risk. COX regression analysis was used to identify independent prognostic factors affecting patients’ recurrence free survival (RFS). The Kaplan–Meier method was used to create the patients’ RFS curve. The restricted cubic spline (RCS) curve was used to assess the correlation between postoperative CEA and RFS on a continuous scale. Among 761 patients, there were 444 males (62.01%), with a median [IQR] age of 58.0 (18.0–88.0) years. A group of 425 high-risk patients had a 3-year RFS of 82.2% (95% CI 78.5–86.1%), while a group of 291 low-risk patients had a 3-year RFS of 89.7% (95% CI 86.1–93.5%). There was a statistically significant difference between the two groups (HR 1.83; 95% CI 1.22–2.74; P = 0.0067). Among them, the 3-year RFS of 261 low-risk patients with normal postoperative CEA was 93.6% (95% CI 90.5–96.8%), while the 3-year RFS of 30 low-risk patients with elevated postoperative CEA was 57.3% (95% CI 41.8–71.4%). There was a significant difference compared to the 3-year RFS of 425 high-risk patients (overall log-rank P < 0.0001). The multivariate analysis adjusted by the COX proportional hazards model showed that low-risk patients with elevated postoperative CEA patients (HR 14.95, 95% CI 4.51–49.63, P < 0.0001) was independently associated with a 3-year RFS. The restricted cubic spline model showed that in stage II colon cancer patients with tumor diameter > 1.955 ng/mL, the risk of postoperative recurrence increased with increasing postoperative CEA levels. Patients with elevated postoperative CEA levels have a significantly increased risk of recurrence. They should be included as high-risk factors to guide adjuvant chemotherapy for stage II colon cancer.

Multiparametric evaluation of mediastinal lymph node metastases in clinical T0-T1c stage non-small-cell lung cancers.

This study aimed to determine the predictive factors of lymph node metastases in clinical T0-T1c stage non-small-cell lung cancers, so as to help making surgical strategy. From January 2016 to December 2017, patients with clinical T0-T1c stage non-small-cell lung cancers were retrospectively reviewed. We elucidated the lymph node metastatic incidence and distribution according to the primary tumour radiographic findings and maximal standard uptake values, and extracted the associated clinicopathological factors. Univariable and multivariable logistic regressions were used to identify independent predictive parameters for lymph node metastases. The performance of predictive model was evaluated using receiver operating characteristic analysis. A total of 517 patients were included. Seventy-two patients had lymph node metastases. Among patients with pure ground-glass nodule and solid component size ≤10 mm, none had any lymph node metastasis. Multivariable logistic regression analysis demonstrated that age, carcinoembryonic antigen level, solid component size, consolidation-tumour ratio and tumour maximal standard uptake values were independent predictors of lymph nodal metastases. Receiver operating characteristic analyses indicated that the area under the curve of predictive model in evaluating lymph node metastases was 0.838 (95% CI 0.791-0.886). Younger age, elevated carcinoembryonic antigen level, larger solid component size, higher consolidation-tumour ratio and tumour maximal standard uptake values were associated with lymph node involvement. Employing such a predictive model in the future may affect the surgical option of lymph node excision for patients in cT1 stage non-small-cell lung cancer.

Normal CEA Levels After Neoadjuvant Chemotherapy and Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion Predict Improved Survival from Colorectal Peritoneal Metastases.

Normal carcinoembryonic antigen (CEA) levels (≤ 2.5 ng/ml) after resection of localized colorectal cancer or liver metastases are associated with improved survival, however, these trends are understudied for colorectal peritoneal metastases (CRPM). We conducted a retrospective single-institution study of patients with CRPM undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) with and without neoadjuvant chemotherapy (NACT). CEA was measured before and after NACT and within 3 months after CRS/HIPEC. A total of 253 patients (mean age 55.3 years) with CRPM undergoing CRS/HIPEC had complete CEA data and 191 also underwent NACT with complete data. The median peritoneal carcinomatosis index score (PCI) of the overall cohort was 12 and 82.7% of patients had complete cytoreduction (CC0). In total, 64 (33.5%) patients had normal CEA levels after NACT with a median overall survival (OS) of 45.2 months compared with those with an elevated CEA (26.4 months, p = 0.004). Patients with normal CEA after NACT had a lower PCI found at the time of surgery than those with elevated CEA (10 versus 14, p < 0.001), 68 (26.9%) patients with an elevated preoperative CEA level experienced normalization after CRS/HIPEC, and 118 (46.6%) patients had elevated CEA after CRS/HIPEC. Patients who experienced normalization demonstrated similar OS to patients that had normal CEA levels pre- and post-surgery and improved OS compared with those with elevated postop CEA (median 41.9 versus 47 months versus 17.1 months, respectively, p < 0.001). Normal CEA levels after NACT and/or CRS/HIPEC are associated with improved survival for patients with CRPM. Patients that normalize CEA levels after surgery have similar survival to those with normal preoperative levels.

Correlation Between C-Reactive Protein (CRP) Level and Chemotherapy Response in Colorectal Cancer Patients Based on Carcinoembryonic Antigen (CEA) Levels in Post Definitive Operative and Adjuvant Chemotherapy Three Series at Prof. Dr. I.G.N.G Ngoerah Denpasar Hospital

Background: Colorectal cancer is the third leading cause of cancer-related deaths worldwide. Surgical therapy is the primary modality for early-stage cancer with curative goals; chemotherapy is the direct option in advanced cancer with palliative goals; radiotherapy is one of the primary therapy modalities for rectal cancer. The markers for chemotherapy response include CRP and CEA. Elevated CRP and CEA levels in CRC patients are associated with poor chemotherapy response. Objective: to determine the relationship between C-reactive protein (CRP) levels and chemotherapy response measured by Carcinoembryonic Antigen (CEA) levels in colorectal cancer patients at Prof. Dr. IGNG Ngoerah Hospital. Method: analytic observational study with a retrospective cohort study design. The sample in this study used the total consecutive sampling method. The analysis was carried out with the help of SPSS, including descriptive statistical tests, chi-square tests, and correlation tests with Spearman-Rho. Results: 58 patients were divided into 2 groups of 29 each for the group with high CRP levels (≥5 mg/dl) and low CRP levels (&lt;5 mg/dl). The male subjects with the most age &lt;60 years and stage III. Most duration of illness &lt; 2 years. The relationship between CRP levels and chemotherapy response was based on CEA, RR 3.2 [95% CI 1.1-9.6; p 0.030], and the value of the positive correlation coefficient with strong strength is r = 0.722. Conclusion: high CRP levels are significantly associated with a strong correlation to worse chemotherapy response in colorectal cancer patients characterized by a high risk of increasing CEA levels 3.7 times after three series of FOLFIRI adjuvant chemotherapy.

Unexplained increases in serum carcinoembryonic antigen levels in colorectal cancer patients during the postoperative follow-up period: an analysis of its incidence and longitudinal pattern

Background Carcinoembryonic antigen (CEA) monitoring facilitates the detection of recurrence in patients with colorectal cancer (CRC) after resection. False-positive CEA has been reported in CRC patients with certain comorbidities or smokers. However, limited information is currently available on the frequency of and changes in falsely elevated CEA levels in patients without these conditions. Materials and methods We retrospectively examined CRC patients who underwent surgical resection at our hospital between 2001 and 2017, had no recurrence for at least five years, and were free of known factors that may increase CEA. Postoperative CEA levels were retrieved until 2 years before the last contact. For comparison, we similarly selected patients who developed recurrence after resection of CRC during the same period, and CEA levels at initial presentation, at nadir, and at the time of recurrence were reviewed. The patterns of elevated CEA (>5 ng/ml) were classified as transient, repeated, or persistent based on longitudinal changes. The relationships between CEA and carbohydrate antigen 19-9, transaminases, creatinine, and C-reactive protein were examined. Results CEA elevation occurred in 90 (20%) out of 446 eligible patients without recurrence at least once during the mean postoperative period of 50.5 months, whereas CEA was >5 ng/ml in 117 (53%) of 221 patients when they developed recurrence. Twenty-seven patients without recurrence showed a transient elevation in CEA, 45 repeated elevations, and 18 a persistent elevation; the frequency of a high preoperative CEA level increased in this order. The majority (98%) of false elevations ranged between 5 and 15 ng/ml. CEA was not associated with other laboratory data. Conclusions Unexplained CEA elevations were observed in 20% of recurrence-free CRC patients after surgery, and were classified into three patterns based on longitudinal changes. A more detailed understanding of patient-specific fluctuations in CEA will prevent unnecessary imaging studies and reduce medical costs.

Prognostic Potential of Nectin Expressions in Colorectal Cancer: An Exploratory Study

Colorectal cancer (CRC) is a pressing global health challenge, with an estimated 1.9 million new cases in 2020. Ranking as the third most diagnosed cancer globally, CRC accounts for nearly 930,000 cancer-related deaths annually. Nectins, immunoglobulin-like adhesion molecules, are pivotal in intercellular adhesion formation and cellular function regulation. Altered nectin expression patterns have been identified in various cancers. However, the intricacies of their role in cancer development and progression remain underexplored. This study aimed to evaluate the expression of specific nectins in CRC tumors, explore their association with clinicopathological factors, and ascertain their potential as prognostic indicators for CRC patients post-resection. We retrospectively analyzed the medical records of 92 CRC patients who underwent surgical treatment between 2013 and 2014. Tumor specimens were re-evaluated to determine nectin expression using immunohistochemistry. The study identified heterogeneous expressions of nectin-2, -3, and -4 in 58%, 62.6%, and 87.9% of specimens, respectively. Elevated nectin-4 expression correlated with worse 5-year and overall survival rates, presenting a negative prognostic value (HR = 4, 95% CI: 2.4–6.8, p &lt; 0.001). Conversely, reduced nectin-3 expression was linked to poorer CRC prognosis (HR = 0.54; 95% CI: 0.31–0.96; p = 0.036). Nectin-4 expression positively correlated with elevated carcinoembryonic antigen (CEA) levels and advanced disease stages. In contrast, nectin-3 expression negatively correlated with CEA levels, tumor size, presence of distant metastases, and disease stage. Notably, tumors in the right colon were statistically more likely to express nectin-2 compared to those in the left. This study underscores the potential prognostic significance of nectins in CRC. The high prevalence of nectin-4-expressing cells offers promising avenues for further evaluation in targeted therapeutic interventions with already available agents such as PADCEV.

Identifying tumor markers-stratified subtypes (CA-125/CA19-9/carcinoembryonic antigen) in cervical adenocarcinoma.

There is a lack of research evaluating the effect of tumor markers for prognosis in cervical adenocarcinoma. We aimed to develop and validate a preoperative tumor-marker-based model including clinicopathological factors to clarify the prognostic value of endocervical adenocarcinoma. A total of 572 patients with cervical adenocarcinoma who were staged at the International Federation of Gynecology and Obstetrics (FIGO) IA-IIA were reviewed retrospectively. Preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-125 and CA19-9 levels were measured. The survival and recurrence patterns were analyzed according to the tumor-marker-related stratification. The predictive values of biomarkers and clinical variables were assessed with Cox regression and competing risk models. Patients with elevated preoperative tumor markers had evidently poor overall survival and recurrence-free survival. The triple-elevated tumor marker (TETM) subgroup had the worst overall survival and progression-free survival than the triple-negative tumor marker (TNTM) subgroup and the single-elevated tumor marker (SETM) subgroup. The most important predictors for overall survival were elevated tumor markers, FIGO-stage, tumor differentiation, lymphovascular space invasion (LVSI) and lymph nodes metastasis. The most important predictors for recurrence-free survival were elevated tumor markers, FIGO-stage, tumor differentiation, LVSI and deep stromal invasion. Stratified analysis showed that elevated CA-125 and CA19-9 were significantly associated with postoperative distant metastasis. A decision curve analysis confirmed that a combination of tumor markers as predictors significantly outperformed the other common predictors used (FIGO-stage, intermediate and high-risk factors, tumor differentiation, lymph nodes). Elevated preoperative serum CEA, CA-125, and CA19-9 levels exhibited poor overall survival and recurrence-free survival in cervical adenocarcinoma patients. Combined preoperative serum CA-125 and CA19-9 independently predicted distant metastasis in patients with endocervical adenocarcinoma.

Development and validation of prognostic nomograms for early-onset colon cancer in different tumor locations: a population-based study

ObjectiveThe prevalence of early-onset colon cancer (EOCC) among individuals below the age of 50 has shown a marked upward trend in recent years. The embryology, clinical symptoms, incidence, molecular pathways, and oncologic outcomes differ between right-sided and left-sided colon cancers. However, the differences have not been fully researched in EOCC. Our study aims to develop and validate prognostic nomograms predicting overall survival (OS) and cancer-specific survival (CSS) for EOCC in different tumor locations based on the Surveillance, Epidemiology, and End Results (SEER) database.MethodsUsing the SEER database, a total of 5,588 patients with EOCC were extracted and divided into development and validation cohorts in a random allocation ratio of 7:3 across three groups. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors influencing OS and CSS outcomes. These factors were then utilized to construct nomogram models. The prognostic capabilities of the three models were assessed through various evaluation metrics, including the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and validation cohorts respectively. Additionally, survival curves of the low- and high-risk groups were calculated using the Kaplan–Meier method together with the log-rank test.ResultsSignificant differences in clinical features were observed between right-sided and left-sided EOCCs, particularly in terms of OS (52 months vs 54 months) as demonstrated by Kaplan–Meier curves. Transverse-sided EOCCs exhibited clinical characteristics similar to right-sided EOCCs, suggesting a potential shared tumor microenvironment and therapeutic considerations. Advanced stage, liver metastasis, poor grade, elevated pretreatment carcinoembryonic antigen (CEA) level, chemotherapy, and perineural invasion were identified as independent prognostic factors across all three tumor locations and were incorporated into the nomogram model. Nomograms were constructed to predict the probability of 3- and 5-year OS and CSS. The C-index and calibration plots showed that the established nomograms had good consistency between actual clinical observations and predicted outcomes. ROC curves with calculated area under the curve (AUC) values exceeded 0.8 for all three groups in both the development and validation cohorts, indicating robust predictive performance for OS and CSS. Furthermore, decision curve analysis (DCA) plots revealed a threshold probability range of 0.1 to 0.9, within which the nomogram model exhibited maximum benefit. Kaplan–Meier curves exhibited significant differences between the low- and high-risk groups in EOCC for all three tumor locations in OS and CSS, further validating the prognostic value of the nomogram models.ConclusionsWe successfully developed three precise nomogram models for EOCCs in different tumor locations, providing valuable support for clinicians in guiding clinical treatments and facilitating further prospective follow-up studies.

The value of carcinoembryonic antigen stage in staging, prognosis, and management of colorectal cancer: results from two cohort studies.

Combining the carcinoembryonic antigen (CEA) level (C stage) with TNM staging can provide a more comprehensive prognostic assessment of colorectal cancer (CRC). However, the clinical value of incorporating CEA status into the TNM staging system needs to be evaluated. We used the SEER database (N = 49,350) and a retrospective cohort from China (N = 1,440). A normal CEA level was staged as C0 and an elevated CEA level was staged as C1. Restricted cubic spline analysis was used to examine the dose-response relationship between the CEA level and survival. The Kaplan-Meier method with the log-rank test was used to plot survival curves. Multivariable Cox proportional hazards regression models with forward stepwise variable selection were used to estimate the hazard ratios and 95% confidence intervals. Patients with C1 were more likely to have advanced disease than those with C0. CEA on a continuous scale was positively associated with mortality risk. Compared with patients with C0 stage, those with C1 stage had significantly lower survival rates. In the SEER dataset, C1 was independently associated with poor prognosis in patients with CRC, with an approximately 70% increased risk of mortality. Patients with C1 stage had significantly lower survival than those with C0 stage at all clinical stages. Incorporating the C stage into the TNM staging refined the prediction of prognosis of patients with CRC, with a gradual decline in prognosis from stage I C0 to stage IV C1. A similar pattern was observed in the present retrospective cohort study. At each lymph node stage, patients with C1 had significantly lower 5-year survival rates than patients with C0. Compared with lymph node positivity, CEA positivity may have a stronger correlation with a worse prognosis. Our findings not only validated the independent prognostic significance of CEA in CRC but also demonstrated its enhanced prognostic value when combined with TNM staging. Our study provides evidence supporting the inclusion of C stage in the TNM staging system.

SAT560 A Case of Medullary Thyroid Carcinoma with Increasing Carcinoembryonic Antigen and Stable Calcitonin Levels

Abstract Disclosure: K.N. Youssef: None. L. Salej: None. A. Gavrila-Filip: None. Background: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor arising from the parafollicular or C cells of the thyroid gland that secretes different tumor markers, including calcitonin (CT) and carcinoembryonic antigen (CEA). CT is only produced by parafollicular cells, while CEA is a non-specific marker produced in various normal tissues, such as epithelial cells of the gastrointestinal tract, lung, breast, and prostate. Different benign and malignant conditions are associated with elevated serum CEA levels. Clinical case: A 69 years-old active smoker male with a history of nasal squamous cell carcinoma (SCC) status post resection in the remote past and bilateral pulmonary nodules underwent total thyroidectomy for a thyroid nodule with FNA positive for medullary carcinoma. Surgical pathology revealed a unifocal 1.5 cm medullary carcinoma with clean surgical margins and no lymphadenopathy. Pre-operative studies included an elevated serum CT of 388 pg/mL (normal ≤ 10 pg/mL), normal serum calcium and PTH levels and a normal 24-hour urinary test for pheochromocytoma. Family history was irrelevant, and the RET proto-oncogene test was negative. Initial post-operative serum CT levels were undetectable and CEA levels were normal (0-4 ng/mL). CT levels increased slowly over the next five years and then they remained stable in the range of 32 to 45 pg/mL. Serum CEA started to rise progressively 7 years after the thyroid surgery up to 6.5 pg/mL. Follow-up neck ultrasounds showed no local recurrence or lymphadenopathy. An extensive evaluation was performed to search for possible MTC metastases and other etiologies for the elevated CEA levels. Bone scan was negative. Chest CT scans revealed enlarging small bilateral pulmonary nodules; stable calcified mediastinal lymph nodes were noted, consistent with chronic granulomatous disease. PET-CT scan showed pulmonary nodules, too small to characterize. The patient underwent a left lower pulmonary lobe robotic-assisted wedge resection. Surgical pathology revealed keratinizing SCC, though to represent primary lung SCC versus metastases from his prior nasal SCC. Upper endoscopy and colonoscopy with biopsy were negative for malignancy. On further workup, the patient was diagnosed with prostate adenocarcinoma and underwent surgery followed by external beam radiation with hormonal therapy. Serum CEA levels normalized one year after the prostate cancer treatment. Serum CT levels remained stable. Conclusion: In patients with MTC who show increasing serum CEA and stable CT levels during follow-up after the initial treatment, it is important to exclude other etiologies before concluding that this change is related to a progression of the medullary cancer. Reference: Carcinoembryonic Antigen. Kankanala VL, Mukkamalla SKR.2022 Jan 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Presentation Date: Saturday, June 17, 2023

Peripheral blood nutrient indices as biomarkers for anti‑PD‑1 therapy efficacy and prognosis in patients with advanced gastric cancer.

Immunotherapy offers survival benefits for patients with advanced gastric cancer, but not all populations can benefit from immunotherapy. Good nutritional status is fundamental to a patient's immune function and may have an impact on the efficacy of immunotherapy. The present study aimed to investigate changes in prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI) and albumin-globulin ratio (AGR) values before and after immunotherapy in patients with advanced gastric cancer. The study also aimed to determine the potential association of the aforementioned values with patient outcomes and prognosis. Body mass index (BMI), serum albumin, total protein, peripheral blood lymphocyte, neutrophil, carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA19-9) and a-fetoprotein (AFP) data were collected from 195 patients with advanced gastric cancer who underwent immunotherapy from January 2020 to October 2021. In addition, PNI, ALI and AGR values were calculated based on variables in blood collected from the patients within 3 days prior to immunotherapy and 3 weeks after immunotherapy. The results demonstrated that low PNI was associated with elevated CEA levels. Moreover, low ALI levels were associated with reduced BMI levels, elevated AFP levels, PD-L1 negative and first-line treatment. Comparison of responding and non-responding groups revealed that patients who responded to immunotherapy had higher PNI and AGR values than patients who did not respond, both before and after treatment, but had lower CEA and CA19-9 levels after treatment. Furthermore, in the non-responding group, PNI and AGR values were decreased and CEA values were increased following treatment compared with those prior to treatment. The objective response and disease control rates were higher in the high PNI and AGR groups compared with the low PNI and AGR groups, respectively. Moreover, PNI and AGR were found to be independent predictors of the short-term efficacy of immunotherapy for advanced gastric cancer, with cut-off values of 47.18 and 1.29, respectively. Univariate analysis revealed that ALI was associated with the progression-free survival (PFS) of patients, while multivariate analysis demonstrated that baseline PNI and AGR were independent predictors of PFS. In conclusion, tumor progression leads to a decline in the nutritional level of patients, and the present study indicated that effective immunotherapy may alleviate this deterioration to a certain extent. Furthermore, PNI and AGR exhibit potential in predicting the efficacy of immunotherapy and the prognosis of patients with advanced gastric cancer, and may exhibit potential as biomarkers in clinical practice.

Nomograms for predicting overall survival in colorectal cancer patients with metastasis to the liver, lung, bone, and brain.

The aim of this study was to identify the heterogeneous and homogeneous prognostic factors associated with distant metastasis to the liver, lung, bone, and brain in colorectal cancer (CRC) patients and then construct nomograms to predict the prognosis. CRC patients registered in the surveillance, epidemiology, and end results database between 2010 and 2017 were included. A Cox regression model was used to analyse homogeneous and heterogeneous prognostic factors, and Kaplan‒Meier analysis was performed to estimate overall survival (OS). Predictive nomograms were constructed, and their performance was evaluated with C-indexes, calibration curves and the area under the receiver operating characteristic (ROC) curve (AUC). A total of 37,641patients with distant metastasis to the liver, lung, bone, and brain were included. The median survival times of patients with liver metastasis, lung metastasis, bone metastasis, and brain metastasis were 12.00months (95% CI 11.73-12.27months), 10.00months (95% CI 9.60-10.41months), 5.00months (95% CI 4.52-5.48months), and 3.00months (95% CI 2.28-3.72months), respectively. An older age, higher N stage, elevated carcinoembryonic antigen level, no surgery at the primary site and no/unknown treatment with chemotherapy were identified as homogeneous prognostic factors for the four types of metastases. The calibration curves, C-indexes and AUCs exhibited good performance for predicting the OS of patients with distant metastases to the liver, lung, bone, and brain. CRC patients with distant metastasis to the liver, lung, bone, and brain exhibited homogeneous and heterogeneous prognostic factors, all of which were associated with shorter survival. The nomograms showed good accuracy and may be used as tools for clinicians to predict the prognosis of CRC patients with distant metastasis.

Significance of programmed death-ligand 1 expression in resected lung cancer and its relationship with EGFR mutation.

Several studies have reported that the high expression of programmed death-ligand 1 (PD-L1) within tumor cells predicts a poor prognosis. However, the relationship between the PD-L1 expression and lymph node metastasis or driver mutations in lung cancer remains poorly understood. A total of 356 consecutive patients who underwent surgical resection for primary lung cancer were included in the study. There were 268 adenocarcinomas including 100 EGFR mutations, 67 squamous cell carcinomas (Sq), and 21 other histologies. The high expression of PD-L1 was defined as a tumor proportion score (TPS) of ≥50. The relationship between the PD-L1 expression and clinicopathological factors and recurrence-free survival (RFS) was analyzed. The PD-L1 expression was high in 75 patients. It was significantly related to smoking history, Sq histology, driver mutation negative, elevated serum carcinoembryonic antigen levels, and lymph node metastasis. Among patients with driver mutations, a high PD-L1 TPS was found in patients with EGFR G719X mutation. A significant difference in RFS was observed in adenocarcinoma patients. A multivariate analysis of adenocarcinoma cases revealed that tumor size and lymph node metastasis were independent prognostic factors for poor RFS, while the PD-L1 expression was not. A logistic regression analysis revealed that the absence of driver mutations, lymph node metastasis, and a history of smoking were significantly associated with the high expression of PD-L1. Lymph node metastasis was positively related with the high expression of PD-L1, resulting in poor RFS. A high PD-L1 TPS was observed in patients with the EGFR G719X mutation.

Diagnostic Accuracy of Carcinoembryonic Antigen (CEA) in Detecting Colorectal Cancer Recurrence Depending on Its Preoperative Level

BackgroundSerum carcinoembryonic antigen (CEA) increase in patients with colorectal cancer (CRC) recurrence was observed to vary depending on their initial values. This study aimed to evaluate the diagnostic accuracy of CEA for detecting CRC recurrence in patients with normal and elevated initial CEA levels. MethodsA total of 261 CRC recurrence patients who underwent curative resection were included and divided into two groups, normal and elevated initial CEA. Analysis was performed comparing patient, tumor, and recurrence characteristics retrospectively. ResultsThere were 192 patients with normal and 69 with high initial CEA levels. Patient and tumor characteristics were similar. Eighty-six patients had elevated CEA at the time of recurrence, and the overall sensitivity of CEA for recurrence was 33.0%. In the high initial CEA group, 59.4% exhibited increased CEA level at recurrence, whereas in patients with normal initial CEA levels, only 23.4% showed elevated levels (p < 0.001). Patients with both high CEA preoperatively and at recurrence had more local recurrence, but there was no statistical significance (p = 0.053), and the rate of lung metastasis was higher in patients whose CEA remained normal at recurrence (38.3% vs. 24.4%, p = 0.026). The overall survival of patients with elevated CEA at recurrence was worse than those with normal CEA levels (56.9% vs. 42.4%, p = 0.003). ConclusionThe diagnostic accuracy of CEA for detecting recurrence depends on initial CEA level. Regardless of the initial CEA level, elevation at recurrence was significantly associated with overall survival in patients with recurrent CRC.