Carcinoembryonic Antigen Test Research Articles

Circulating Tumor DNA Predicts Early Recurrence Following Locoregional Therapy for Oligometastatic Colorectal Cancer.

(1) Background: Local therapies offer a potentially curative approach for patients with oligometastatic colorectal cancer (CRC). An evidence-based consensus recommendation for systemic therapy following definitive locoregional therapy is lacking. Tumor-informed circulating tumor DNA (ctDNA) might provide information to help guide management in this setting. (2) Methods: A multi-institutional retrospective study was conducted, including patients with CRC that underwent curative-intent locoregional therapy to an isolated site of metastatic disease, followed by tumor-informed ctDNA assessment. The Kaplan-Meier method and log-rank tests were used to compare disease-free survival based on ctDNA results. ctDNA test performance was compared to carcinoembryonic antigen (CEA) test results using McNemar's test. (3) Results: Our study cohort consisted of 87 patients treated with locoregional interventions who underwent ctDNA testing. The initial ctDNA test post-intervention was positive in 28 patients and negative in 59 patients. The median follow-up time was 14.0 months. Detectable ctDNA post-intervention was significantly associated with early disease recurrence, with a median disease-free survival (DFS) of 6.63 months compared to 21.30 months in ctDNA-negative patients (p < 0.001). ctDNA detected a numerically higher proportion of recurrences than CEA (p < 0.097). Post-intervention systemic therapy was not associated with improved DFS (p = 0.745). (4) Conclusions: ctDNA results are prognostically important in oligometastatic CRC, and further prospective studies are urgently needed to define its role in guiding clinical decisions.

Evaluating Carcinoembryonic Antigen and Glucose Levels in Pancreatic Cyst Fluid for Mucinous Versus Non-mucinous Differentiation.

A more precise identification of mucinous cysts will lower the likelihood of needless pancreatic surgery. Pancreatic cyst fluid (PCF) contains glucose and carcinoembryonic antigen (CEA), which serve as biomarkers to differentiate mucinous from non-mucinous pancreatic cystic neoplasms (PCNs). To evaluate the diagnostic accuracy of combined CEA and glucose levels in PCF for distinguishing mucinous from non-mucinous PCNs preoperatively. After receiving approval from the Institutional Ethical Committee of Indira Gandhi Institute of Medical Sciences, Patna, a cross-sectional validation research was carried out. All patients ≥18 years of age who had undergone pancreatic surgery or endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for a pancreatic cystic lesion and for whom PCF was acquired were eligible for inclusion. Patients were excluded if there was no PCF available, if they had been diagnosed with an extrapancreatic illness (such as ampullary adenoma), or if they could not be excluded due to pancreatic cancer generated from PCN. Diagnoses were pathologically confirmed. We performed measurements for CEA and glucose in PCF. CEA and glucose were measured using an Architect i2000SR analyzer (Abbott, Lake County, IL) and AU 5800 Beckman Coulter (Brea, CA), respectively. Diagnostic accuracy was evaluated by receiver operator characteristic (ROC) curves. PCF was obtained from 100 patients, of whom 54 (54%) had mucinous PCN and 46 (46%) had non-mucinous PCN. When CEA (cut-off ≥ 151 ng/ml) and glucose levels (cut-off ≤ 50 mg/dL) were combined, the results showed 46% sensitivity and 92% specificity. However, when CEA (cut-off ≥ 17 ng/ml) or glucose testing (cut-off ≤ 50 mg/dL) was used separately, the results showed 82% sensitivity and 73% specificity. The combined CEA and glucose testing in PCF demonstrated high specificity and sensitivity for differentiating mucinous from non-mucinous PCNs, suggesting its potential utility in preoperative diagnosis.

Abstract 1038: Identification of diagnostic biomarkers for colon adenocarcinoma by analyzing proteins in human-derived extracellular vesicles and particles

Abstract There is an unmet medical need for circulating biomarkers to improve early cancer detection in colon adenocarcinoma (COAD). We investigated the proteomic profile of extracellular vesicles and particles (EVPs) from the colon tissue explants and plasmas in COAD. The research aims to overcome the limitations of traditional serum Carcinoembryonic Antigen (CEA) testing and invasive procedures like colonoscopy. We analyzed EVPs sourced from tumor and adjacent non-tumor tissues and preoperative and postoperative plasma in COAD patients to identify potential EVP-based tumor diagnostic markers. In the Discovery phase with 50 COAD patients, we conducted a proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS), identifying approximately 50 markers each from tissue explants and plasma. These markers were validated in an independent cohort of 104 participants, including 84 COAD patients and 20 healthy controls. We utilized ELISA to quantify 11 selected EVP proteins. Notably, seven of these proteins exhibited significant differential expression in preoperative and postoperative plasma, highlighting their diagnostic relevance. These seven proteins also showed marked elevation in preoperative plasma compared to healthy controls, reinforcing their potential as diagnostic markers. The study extended to evaluate the diagnostic accuracy of these seven proteins, referred to as "EV-7 levels", across various stages of COAD. Their performance was compared with serum CEA levels and plasma cfDNA mutation rates, as detected by an FDA-approved liquid biopsy assay. The EV-7 levels demonstrated superior detection rates in the early stages of COAD, particularly in Stages I and II, in contrast to the serum CEA method. Among the 84 patients, 73 (86.9%) exhibited EV-7 levels exceeding the established cut-off. In the validation cohort, EV-7 levels were more accurate across different COAD stages than serum CEA levels and cfDNA mutation rates. CEA levels above 5 ng/ml were 27%, 45%, 42%, and 64% for Stages I through IV. cfDNA somatic mutation rates were 60%, 80%, 75%, and 75%. EV-7 levels exceeding the cut-off were 73%, 100%, 88%, and 84%, respectively, with Stages I and II having the highest detection rate among the three methods. ROC curve analysis for EV-7 levels in Stages I to IV showed statistically significant, with AUC values of 0.913, 1.000, 0.985, and 0.984, respectively. Our findings indicate that the seven EVP proteins are significantly present in the plasma of early-stage COAD patients. Integrating these markers with current diagnostic approaches could improve early cancer detection, showing promise for practical application in clinical settings. Citation Format: Yura Seo, Yoon Dae Han, Linda Bojmar, Kyung-A Kim, Yurin Seo, David Lyden, Han Sang Kim. Identification of diagnostic biomarkers for colon adenocarcinoma by analyzing proteins in human-derived extracellular vesicles and particles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1038.

Implementation of home ‘finger-prick’ carcino-embryonic antigen testing for colorectal cancer follow-up – A pilot study of user acceptability

AimRoutine carcino-embryonic antigen blood testing is required after colorectal cancer resection, requiring face-to-face appointments. This has workforce implications, and impacts patients’ lives. We assessed feasibility and acceptability of self-taken blood tests. Methods50 colorectal cancer patients with experience of face-to-face phlebotomy surveillance agreed to self-testing finger-prick kits. Follow-up questionnaires assessed perspectives and preferences. Results68% (50/74) of patients agreed to participate. 76% (38/50) successfully completed samples. 62% (29/47) felt it was no worse than their previous experience. Regarding future testing, 47% (22/47) preferred finger-prick testing. 19% (9/47) expressed no preference. This was unaffected by patient age. Qualitative assessment showed difficulties with pain, discomfort, and sample collection, but was more convenient and saved time for patients. ConclusionsMany preferred finger-prick assessment, but some found it challenging, unnecessary or less preferable. This may reduce burden of follow-up blood tests but currently would only be acceptable to a limited patient cohort.

Ultrasensitive Point-of-Care Detection of Protein Markers Using an Aptamer-CRISPR/Cas12a-Regulated Liquid Crystal Sensor (ALICS).

Despite extensive efforts, point-of-care testing (POCT) of protein markers with high sensitivity and specificity and at a low cost remains challenging. In this work, we developed an aptamer-CRISPR/Cas12a-regulated liquid crystal sensor (ALICS), which achieved ultrasensitive protein detection using a smartphone-coupled portable device. Specifically, a DNA probe that contained an aptamer sequence for the protein target and an activation sequence for the Cas12a-crRNA complex was prefixed on a substrate and was released in the presence of target. The activation sequence of the DNA probe then bound to the Cas12a-crRNA complex to activate the collateral cleavage reaction, producing a bright-to-dark optical change in a DNA-functionalized liquid crystal interface. The optical image was captured by a smartphone for quantification of the target concentration. For the two model proteins, SARS-CoV-2 nucleocapsid protein (N protein) and carcino-embryonic antigen (CEA), ALICS achieved detection limits of 0.4 and 20 pg/mL, respectively, which are higher than the typical sensitivity of the SARS-CoV-2 test and the clinical CEA test. In the clinical sample tests, ALICS also exhibited superior performances compared to those of the commercial ELISA and lateral flow test kits. Overall, ALICS represents an ultrasensitive and cost-effective platform for POCT, showing a great potential for pathogen detection and disease monitoring under resource-limited conditions.

Abstract B106: Assessing racial disparities in the receipt of quality care in the most prevalent cancers in American Indians

Abstract INTRODUCTION Previous SEER-Medicare analyses reported lower receipt of guideline concordant care for American Indian (AI) compared with White (WH) patients across several cancers. While large scale assessments are informative, there is a need to assess cancer outcomes and develop interventions at a level closer to communities. To address this gap, we assessed measures of quality care in AI and WH breast, prostate, and colorectal cancer patients. METHODS We assembled novel cohorts of AI and WH patients from the North Carolina (NC) cancer registry, the state with the largest AI population east of the Mississippi River. Eligible patients were diagnosed with breast, prostate, and colorectal cancers who linked to public and private insurance claims with continuous enrollment (2003-2019). Measures were assessed within 1 year of diagnosis unless stated otherwise. Breast cancer measures included receipt of: (1) HER2 testing within 3 months of diagnosis [NQF #1878]; (2) Tamoxifen/Aromatase Inhibitors for Stage I-III ER/PR+ [NQF #220]; (3) radiation among stage I-III breast conserving surgery or mastectomy patients [NQF #0219]. Stage II-III colorectal cancer measures included receipt of: (1) carcinoembryonic antigen (CEA) testing; (2) surveillance colonoscopy; and (3) computed tomography (CT) among resected patients [NCCN 2.2023 COL-8]. We assessed receipt of prostate-specific antigen (PSA) testing in the first 15 months after prostate cancer diagnosis to monitor disease recurrence. Poisson regression adjusting for sex, urbanicity, insurance type, and age at diagnosis was used to estimate risk ratios (RR) and 95% confidence intervals (CI) comparing the receipt of care between AI and WH patients. RESULTS The sample sizes of AI patients differed across measures, ranging from 104 colorectal to 554 prostate cancer patients. Evidence of disparity was mixed for the breast cancer measures. AI breast cancer patients less frequently received HER2 testing within 3 months of diagnosis (AI=61% vs WH=71%), although adjustment attenuated this association (RR=0.90; CI: 0.81-1.01). Among stage I-III breast cancer patients, AIs more frequently received radiation within 1 year of surgery (AI=75% vs WH=71%) compared with WH patients (RR=1.11; CI: 1.01-1.21). Across colorectal cancer measures, AI patients performed as well or better than WH patients. Notably, AI patients more frequently received CEA testing (AI=71% vs WH=59%), a difference that persisted after adjustment (RR=1.17; CI: 1.03-1.32). AI prostate cancer patients received PSAs less often in the 15 months following diagnosis (AI=82% vs WH=88%) than WH patients (RR=0.96; CI: 0.93-1.00). CONCLUSIONS The magnitude and direction of AI/WH disparities in receipt of quality cancer care differed across measures. Racial misclassification is a challenge in AI health outcomes research, which may misrepresent the experience of AIs. Nevertheless, our findings provide insight into specific areas of breast, prostate, and colorectal cancer care where local tailored interventions can be focused to improve care equity. Citation Format: Bradford E. Jackson, Marc E. Emerson, Lisa P. Spees, Chris D. Baggett, Hayley N. Morris, Ana I. Salas, Angelo Moore, Yadurshini Raveendran, Clare Meernik, Tomi Akinyemiju, Rachel Denlinger-Apte, Ronny A. Bell, Stephanie B. Wheeler. Assessing racial disparities in the receipt of quality care in the most prevalent cancers in American Indians [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B106.

The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer.

This study aimed to explore the value of color Doppler ultrasonography combined with carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in differential diagnosis of gastric stromal tumor (GST) and gastric cancer (GC). An analysis of the clinical data of 180 patients with clinically suspected gastric space occupying lesions. According to the postoperative pathological results, 180 suspected gastric space-occupying lesion patients were divided into GST group (n = 83) and GC group (n = 97). Color Doppler ultrasonography, serum tumor markers CEA and CA19-9 were compared. The research results showed that serum CEA and CA19-9 levels were lower in patients with GST group than those with GC group (both P < 0.001). With postoperative pathology as the gold standard, detection rates of GST and GC by combination of color Doppler ultrasound (CDUS), serum CEA, and CA19-9 were higher than those of each index alone (both P < 0.001). There was no difference between detection rates of GST and GC by combination of CDUS, serum CEA, and CA19-9 (P = 0.058). Color Doppler ultrasonography combined with serum tumor markers CEA and CA19-9 tests has a certain differential diagnostic value for GST and GC, which may provide a reliable reference basis for clinical diagnosis and treatment.

Study on the application of percutaneous closed pleural brushing combined with cell block technique in the diagnosis of malignant pleural effusion.

This study was to investigate the diagnostic value of percutaneous closed pleural brushing (CPBR) followed by cell block technique for malignant pleural effusion (MPE) and the predictive efficacy of pleural fluid carcinoembryonic antigen (CEA) for epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma patients with MPE. All patients underwent closed pleural biopsy (CPB) and CPBR followed by cell block examination. MPE-positive diagnostic rates between the two methods were compared. Univariate and multivariate analyses were performed to determine factors influencing the EGFR mutations. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of pleural fluid CEA for EGFR mutations. The cumulative positive diagnostic rates for MPE after single and twice CPBR followed by cell block examination were 80.5% and 89.0%, higher than CPB (45.7%, 54.3%) (P < 0.001). Univariate analysis showed that EGFR mutation was associated with pleural fluid and serum CEA (P < 0.05). Multivariate analysis showed that pleural fluid CEA was an independent risk factor for predicting EGFR mutation (P < 0.001). The area under the curve (AUC) of pleural fluid CEA for EGFR mutation prediction was 0.774, higher than serum CEA (P = 0.043), but no difference with the combined test (P > 0.05). Compared with CPB, CPBR followed by the cell block technique can significantly increase the positive diagnostic rate of suspected MPE. CEA testing of pleural fluid after CPBR has a high predictive efficacy for EGFR mutation in lung adenocarcinoma patients with MPE, implying pleural fluid extracted for cell block after CPBR may be an ideal specimen for genetic testing.

Value of enhanced computed tomography in differentiating small mesenchymal tumours of the gastrointestinal from smooth muscle tumours.

Computed tomography (CT) technology has been gradually used in the differentiation of small mesenchymal tumors of the stomach and intestines from smooth muscle tumours. To explore the value of enhanced CT in the differentiation of small mesenchymal tumors of the stomach and intestines from smooth muscle tumours. Clinical data of patients with gastric mesenchymal or gastric smooth muscle tumours who were treated in our hospital from May 2018 to April 2023 were retrospectively analysed. Patients were divided into the gastric mesenchymal tumor group and the gastric smooth muscle tumor group respectively (n = 50 cases per group). Clinical data of 50 healthy volunteers who received physical examinations in our hospital during the same period were selected and included in the control group. Serum levels of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), CA-125 and cytokeratin 19 fragment antigen 21-1 were compared among the three groups. The value of CEA and CA19-9 in the identification of gastric mesenchymal tumours was analysed using the receiver operating characteristic (ROC) curve. The Kappa statistic was used to analyse the consistency of the combined CEA and CA19-9 test in identifying gastric mesenchymal tumours. CEA levels varied among the three groups in the following order: The gastric mesenchymal tumour group > the control group > the gastric smooth muscle tumour group. CA19-9 levels varied among the three groups in the following order: The gastric mesenchymal group > the gastric smooth muscle group > the control group, the difference was statistically significant (P < 0.05). ROC analysis showed that the area under the curve of CEA and CA19-9 was 0. 879 and 0. 782, respectively. Enhanced CT has shown value in differentiating small mesenchymal tumors of the stomach and intestines from smooth muscle tumors.

Development and validation of a web-based predictive model for preoperative diagnosis of localized colorectal cancer and colorectal adenoma.

Localized colorectal cancer (LCC) has obscure clinical signs, which are difficult to distinguish from colorectal adenoma (CA). This study aimed to develop and validate a web-based predictive model for preoperative diagnosis of LCC and CA. We conducted a retrospective study that included data from 500 patients with LCC and 980 patients with CA who were admitted to Dongyang People's Hospital between November 2012 and June 2022. Patients were randomly divided into the training (n=1036) and validation (n=444) cohorts. Univariate logistic regression, least absolute shrinkage and selection operator regression, and multivariate logistic regression were used to select the variables for predictive models. The area under the curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to evaluate the performance of the model. The web-based predictive model was developed, including nine independent risk factors: age, sex, drinking history, white blood cell count, lymphocyte count, red blood cell distribution width, albumin, carcinoembryonic antigen, and fecal occult blood test. The AUC of the prediction model in the training and validation cohorts was 0.910 (0.892-0.929) and 0.894 (0.862-0.925), respectively. The calibration curve showed good consistency between the outcome predicted by the model and the actual diagnosis. DCA and CIC showed that the predictive model had a good clinical application value. This study first developed a web-based preoperative prediction model, which can discriminate LCC from CA and can be used to quantitatively assess the risks and benefits in clinical practice.

Carcinoembryonic antigen, carbohydrate antigen 199 and carbohydrate antigen 724 in gastric cancer and their relationship with clinical prognosis.

Gastric cancer (GC) is a common malignant tumor of the digestive system with a high degree of malignancy. It usually develops insidiously without any specific symptoms in the early stages. As one of the diseases caused by abnormal gene changes, GC has abnormal expression of various oncogenes and products during its development. Tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and carbohydrate antigen 724 (CA724) are not expressed or lowly expressed in normal people, but significantly increased after carcinogenesis. Monitoring the changes in the levels of tumor markers such as CEA, CA199 and CA724 is conducive to early diagnosis and evaluation of the occurrence of some solid tumors. To investigate the expression of CEA, CA199 and CA724 in GC and their correlation with clinical features, hoping to provide more effective markers for the early preventive diagnosis of GC. Of 87 patients with GC admitted to our hospital from September 2020 to December 2021 were included in the GC group, and another 80 healthy people who came to our hospital for physical examination with normal results during the same period were selected as the control group. The serum CEA, CA199, and CA724 levels were compared between the two groups, and the serum CEA, CA199, and CA724 levels were compared in patients with GC at different TNM stages, and the differences in the positive rates of CEA, CA199, and CA724 alone and in combination in detecting TNM stages of GC and GC were compared. In addition, the relationship between the levels of tumor markers CEA, CA199 and CA724 and the clinicopathological characteristics of GC patients was also analyzed. The relationship between the serum levels of CEA, CA199 and CA724 and the survival period of GC patients was analyzed by Pearson. The serum levels of CEA, CA199 and CA724 in GC group were significantly higher than those in control group (P < 0.05). With the increase of TNM stage, the serum CEA, CA199 and CA724 expression levels in GC patients increased significantly, and the differences between groups were statistically significant (P < 0.05). The positive rate of the CA724 single test was higher than that of CEA and CA199 single test (P < 0.05). The positive rate of the three combined tests was 95.40% (83/87), which was higher than that of CEA, CA199 and CA724 single tests. The difference was statistically significant (P < 0.05). The combined detection positive rates of CEA, CA199, and CA724 in stages I, II, III, and IV of GC were 89.66%, 93.10%, 98.85%, and 100.00% respectively, all of which were higher than the individual detection rates of CEA, CA199, and CA724. The differences were statistically significant (P < 0.05). There was no significant difference in serum CEA, CA199 and CA724 levels between GC patients with different genders, smoking history and alcohol history (P > 0.05). However, the serum CEA, CA199 and CA724 levels were significantly higher in GC patients aged ≥ 45 years, TNM stage III-IV, with lymph node metastasis and tumor diameter ≥ 5 cm than in GC patients aged < 45 years, TNM stage I-II, without lymph node metastasis and tumor diameter < 5 cm (P < 0.05). The expression levels of serum tumor markers CEA, CA199 and CA724 in patients with GC are high and rise with the increase of TNM stage. The levels of CEA, CA199 and CA724 are related to age, TNM stage, lymph node metastasis and tumor diameter. The combined detection of CEA, CA199 and CA724 is helpful to improve the diagnostic accuracy of GC with high clinical guidance value.

MOF-Based Biosensors for the Detection of Carcinoembryonic Antigen: A Concise Review.

Cancer has been considered one of the most serious diseases in recent decades. Early diagnosis of cancer is a crucial step for expedited treatment. Ideally, detection of cancer biomarkers, which are usually elevated because of cancer, is the most straightforward approach to detecting cancer. Among these biomarkers, the carcinoembryonic antigen (CEA) is considered one of the most important tumor markers for colorectal cancer. The CEA has also been recognized as a biomarker for other types of cancers, including breast, gastric, ovarian, pancreatic, and lung cancers. Typically, conventional CEA testing depends on immunoassay approaches, which are known to be complex, highly expensive, and time consuming. Accordingly, various types of biosensors have been designed for the detection of cancer biomarkers. The main prerequisites of these biosensors are high sensitivity, fast response, and low cost. Many nanostructures have been involved in the design of biosensors, such as nanoparticles of certain metals and metal oxides that are further functionalized to contribute to the sensing of the biomarkers. Alternatively, metal organic frameworks (MOFs), which are extended crystalline structures comprising metal clusters surrounded by organic linkers, have been shown to be highly promising for the development of biosensors. The 3D structure of MOFs results in a combination of high surface area and high interconnected porosity, which are believed to facilitate their function in the design of a biosensor. This review briefly classifies and describes MOF-based biosensor trials that have been published recently for the aim of detecting CEA.

Clinical Value of Combined Detection of Serum sTim-3 and CEA or CA19-9 for Postoperative Recurrence of Colorectal Cancer Diagnosis.

The present study aimed to evaluate the clinical value of Combined Detection of serum soluble T-cell immunoglobulin 3 (sTim-3) with carcinoembryonic antigen (CEA) or glycotype antigen 19-9 (CA19-9) for Postoperative Recurrence of Colorectal Cancer (CRC) Diagnosis. The serum sTim-3 was measured by highly sensitivity TRFIA, and serum CEA and CA19-9 were obtained through the collection of clinical data. Quantitative detection of serum sTim-3, CEA, CA19-9 in 90 patients after the CRC surgery (52 postoperative recurrence and 38 no-postoperative recurrence), 21 patients with colorectal benign tumors, and 67 healthy controls. To analyze the clinical diagnostic value of combined detection of sTim-3 with CEA or CA19-9 to test whether patients have recurrence after CRC surgery. The sTim-3 (15.94±11.24ng/mL) in patients after CRC surgery was significantly higher than in healthy controls (8.95±3.34ng/mL) and colorectal benign tumors (8.39±2.28ng/mL) (P < 0.05), and sTim-3 (20.33±13.04ng/mL) in CRC postoperative recurrent group was significantly higher than in the group without recurrence after CRC surgery (9.94±2.36ng/mL) (P < 0.05). In terms of detecting postoperative recurrence after CRC surgery, combined detection of sTim-3 and CEA (AUC: 0.819, sensitivity: 80.77%, specificity: 65.79%), sTim-3 and CA19-9 test (AUC: 0.813, sensitivity: 69.23%, specificity: 97.30%) was significantly better than the CEA single test (AUC: 0.547, sensitivity: 63.16%, specificity: 48.08%) and CA19-9 single test (AUC: 0.675 sensitivity: 65.38%, specificity: 67.57%), Delong test P < 0.05. The efficacy of CEA and CA19-9 single test was not optimal, and the combination of sTim-3 in serum could significantly improve the sensitivity and specificity of detecting patient recurrence after CRC surgery.

Early Detection of Molecular Residual Disease and Risk Stratification for Stage I to III Colorectal Cancer via Circulating Tumor DNA Methylation

Detection of molecular residual disease and risk stratification as early as possible may improve the treatment of patients with cancer. Efficient pragmatic tests are therefore required. To measure circulating tumor DNA (ctDNA) with 6 DNA methylation markers in blood samples and to evaluate the association of the presence of ctDNA with colorectal cancer (CRC) recurrence throughout the disease course. In this multicenter prospective longitudinal cohort study performed from December 12, 2019, to February 28, 2022, 350 patients with stage I to III CRC were recruited from 2 hospitals for collection of blood samples before and after surgery, during and after adjuvant chemotherapy, and every 3 months for up to 2 years. A multiplex, ctDNA methylation, quantitative polymerase chain reaction assay was used to detect ctDNA in plasma samples. A total of 299 patients with stage I to III CRC were evaluated. Of 296 patients with preoperative samples, 232 (78.4%) tested positive for any of the 6 ctDNA methylation markers. A total of 186 patients (62.2%) were male, and the mean (SD) age was 60.1 (10.3) years. At postoperative month 1, ctDNA-positive patients were 17.5 times more likely to relapse than were ctDNA-negative patients (hazard ratio [HR], 17.5; 95% CI, 8.9-34.4; P < .001). The integration of ctDNA and carcinoembryonic antigen tests showed risk stratification for recurrence with an HR of 19.0 (95% CI, 8.9-40.7; P < .001). Furthermore, ctDNA status at postoperative month 1 was strongly associated with prognosis in patients treated with adjuvant chemotherapy of different durations and intensities. After adjuvant chemotherapy, ctDNA-positive patients had a significantly shorter recurrence-free survival than did the ctDNA-negative patients (HR, 13.8; 95% CI, 5.9-32.1; P < .001). Longitudinal ctDNA analysis after the postdefinitive treatment showed a discriminating effect in that ctDNA-positive patients had poorer recurrence-free survival than did the ctDNA-negative patients (HR, 20.6; 95% CI, 9.5-44.9; P < .001). The discriminating effect was enhanced (HR, 68.8; 95% CI, 18.4-257.7; P < .001) when ctDNA status was maintained longitudinally. Postdefinitive treatment analysis detected CRC recurrence earlier than radiologically confirmed recurrence, with a median lead time of 3.3 months (IQR, 0.5-6.5 months). The findings of this cohort study suggest that longitudinal assessment of ctDNA methylation may enable the early detection of recurrence, potentially optimizing risk stratification and postoperative treatment of patients with CRC.

Abstract P3-03-18: M1 registration: Signaling patients who develop metachronous metastases after primary breast cancer

Abstract Background At the moment, over 180,000 breast cancer survivors are living in the Netherlands and survival after a breast cancer diagnosis and treatment is still increasing. Therefore, the number of survivors is rising, and these patients are at risk of metachronous metastases. Data at a national level on the development of metachronous metastases are limited, as this is not registered in the Netherlands Cancer Registry on a regular basis. Due to the vast amount of survivors, it is not feasible to actively monitor all patients to signal and register metachronous metastases. Applying machine learning may be an option to overcome this issue. The aim of our study is to develop a M1 detection algorithm based on hospital data to signal patients who developed metachronous metastases after their primary breast cancer treatment. Methods The Netherlands Cancer Registry (NCR) collects data on all individuals newly diagnosed with cancer in one of the 76 hospitals in the Netherlands since 1989. Dutch Hospital Data (DHD) collects and processes data from hospitals, including data on diagnosis and treatment. DHD data from 2019-2020 were linked to the NCR using a probabilistic matching method. We matched on date of birth, gender, diagnosis, postal code, hospital and patient ID. Column values that matched were weighted inversely proportional to the respective column’s probability distribution, where a match on a rare column value (e.g. postal codes with a relatively small population) increased the probability that the match was correct. Scores for each column were combined and patients with high matching scores were included in the algorithm development, validation and deployment. Actively signaled and manually registered data on metastases were available for subgroups of breast cancer patients included in previous studies (‘the golden standard’). First, 80% of these data was used to train the model, 20% was used to validate the model. Second, a pilot study was performed in which patients files were checked for 928 patients, sampled with variance in prediction probability, to evaluate a diverse range of cases. Results We included 4,395 patients. Variables that were included to predict metastases were i.e. specific medication for metastatic disease (palbociblib), counselling for metastatic breast cancer, Carcinoembryonic Antigen test, a confirmed diagnosis of metastases, and number of patient visits. The first validation step (including 20% of known data) showed that the model had a precision of 0.91 to predict metachronous metastases, 0.93 to predict free of metastases. The pilot study confirmed that a higher prediction probability of &amp;gt;0.8 correlated with a higher chance that a patient has metachronous metastases. However, false positive predictions did occur. Conclusion We developed a M1 detection algorithm to signal patients with metachronous metastases after breast cancer treatment on a national level. With this algorithm we are one step closer to identify all patients with metachronous metastases and to reach a complete registration of all breast cancer metastases reusing existing data sources. After review of patients with a high prediction probability, the model will be re-trained using these data and updated data from DHD. Citation Format: Linda de Munck, Daan Knoors, Harm Buisman, Koen Scholman, Janneke Verloop, Sabine Siesling. M1 registration: Signaling patients who develop metachronous metastases after primary breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-18.

A retrospective study of circulating tumor DNA for minimal residual disease detection in the management of colorectal cancer.

227 Background: Circulating tumor DNA (ctDNA) consists of small fragments of DNA released into the plasma from cancer cells. Tumor informed ctDNA testing by whole exome sequencing of the primary tumor coupled with multiplex polymerase chain reaction (PCR)-based next generation sequencing of cell free DNA in serum, can detect and quantify ctDNA, allowing for detection of minimal residual disease (MRD). Methods: We conducted a retrospective analysis of 120 patients with colorectal cancer who had at least one tumor-informed ctDNA MRD assay completed between May 6, 2019, and July 1, 2022, at Mayo Clinic, Rochester. Disease recurrence was defined as radiographic evidence consistent with recurrence with or without biopsy confirmation. Data are presented descriptively, including number of ctDNA assays completed, ctDNA positivity prior to disease recurrence, and ctDNA concordance with carcinoembryonic antigen (CEA). The study protocol was exempt after review by the Mayo Clinic Institutional Review Board. Results: One-hundred twenty patients were included in the study with median age at initial disease diagnosis of 67.0 years. Sixty-four percent were male and 94% were white. At time of initial diagnosis, 10 had stage I, 23 stage II, 60 stage III, and 25 stage IV disease. In 120 patients, 476 ctDNA assays were performed, and 110 recurrences were observed among 62 patients. There were 39 instances in which ctDNA was obtained prior to clinical detection of recurrence and of these, at least one ctDNA assay was positive in 28 cases (72%). CEA was obtained prior to recurrence in 88 instances and was elevated in only 39 cases (44%). Among 37 instances where both ctDNA and CEA testing were obtained prior to recurrence, ctDNA was positive in 27 cases (73%) while CEA was positive in 14 cases (38%). ctDNA was positive in 83% of recurrences involving liver and 62.5% of recurrences involving only the lungs. ctDNA and CEA positivity are shown by location of recurrence. ctDNA and CEA were discordant in 44% of instances in which the assays were completed within 2-weeks of each other. Results of a ctDNA assay impacted management decisions in 16% of cases. Conclusions: ctDNA detected 72% of recurrences with higher rates of detection in liver versus lung metastasis. ctDNA performed superiorly to serum CEA in detection of recurrence, suggesting a role in disease surveillance. However, ctDNA impacted disease management in only 16% of patients, suggesting need for better patient selection and further study for ctDNA-based disease management strategy (more details will be reported). [Table: see text]

Validation of combined carcinoembryonic antigen and glucose testing in pancreatic cyst fluid to differentiate mucinous from non-mucinous cysts

BackgroundMore accurate diagnosis of mucinous cysts will reduce the risk of unnecessary pancreatic surgery. Carcinoembryonic antigen (CEA) and glucose in pancreatic cyst fluid (PCF) can differentiate mucinous from non-mucinous pancreatic cystic neoplasms (PCN). The current study assessed the value of combined CEA and glucose testing in PCF.MethodsCross-sectional validation study including prospectively collected PCF from patients undergoing endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) and pancreatic surgery. We performed laboratory measurements for CEA and glucose and measured glucose levels by a hand glucometer. Primary outcome was diagnostic accuracy evaluated by receiver operator curves (ROC), sensitivity, specificity, positive, and negative predictive value (PPV, NPV).ResultsOverall, PCF was collected from 63 patients, including 33 (52%) with mucinous and 30 (48%) with non-mucinous PCN. Histopathology (n = 36; 57%), cytopathology (n = 2; 3%), or clinical and/or radiological diagnosis (n = 25; 40%) was used as reference standard. Combined CEA (cut-off ≥ 192 ng/ml) and laboratory glucose testing (cut-off ≤ 50 mg/dL) reached 92% specificity and 48% sensitivity, whereas either positive CEA (cut-off ≥ 20 ng/ml) or glucose testing (cut-off ≤ 50 mg/dL) showed 97% sensitivity and 50% specificity. Sensitivity and specificity were 80% and 68% for CEA ≥ 20 ng/mL versus 50% and 93% for CEA ≥ 192 ng/mL (the conventional cut-off level). Laboratory and glucometer glucose both reached 100% sensitivity and 60% and 45% specificity, respectively. None of the biomarkers and cut-offs reached a PPV exceeding 90%, whereas both glucose measurements had a NPV of 100% (i.e., high glucose excludes a mucinous cyst).ConclusionCombined CEA and glucose testing in PCF reached high specificity and sensitivity for differentiating mucinous from non-mucinous PCN. Glucose testing, whether alone or combined with the new CEA cut-off (≥ 20 ng/mL), reached > 95% sensitivity for mucinous cysts, whereas only glucose reached a NPV > 95%.Graphical abstract

Performance of circulating methylated Septin9 gene DNA in diagnosis and recurrence monitoring of colorectal cancer in Western China

Background and aimsMethylated Septin9 (mSEPT9) has been suggested for CRC detection. To assess the performance of mSEPT9 in Western China, we compared its diagnostic and recurrence monitoring values with fecal occult blood test (FOBT), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9). Material and methodsOverall 300 subjects including 209 CRC patients and 91 healthy subjects, who have performed mSEPT9, FOBT, CEA and CA19-9 tests, were involved. Sensitivity, specificity, and area under the ROC curve (AUC) were used to evaluate the efficacy of each method. ResultsPlasma mSEPT9 demonstrated an AUC of 0.860, and a sensitivity of 76.4 % for CRC detection. The sensitivity of mSEPT9 was higher than FOBT, CEA and CA 19-9. Though mSEPT9 presented a larger or equal sensitivity for stage Ⅱ-IV CRCs, FOBT showed a better sensitivity for stage I CRCs. Logistical analysis showed the ones with positive mSEPT9, FOBT and CEA were more likely to have CRC (all P < 0.01). Then, the three biomarkers built the nomogram predicting the probability of having CRC. The sensitivity of mSEPT9 was also much higher than CEA for CRC recurrence monitoring. ConclusionThe mSEPT9 test performed better than traditional tests for CRC detection, and should be recommended for FOBT-positive ones or individuals who refuse FOBT.

EP-373 Appropriate requesting of tumor marker, CEA, at a district hospital in Ireland: An audit cycle to improve practice

Abstract Aims Tumor markers play an important role in oncology and the appropriate requesting of tumor marker tests are facilitated by national and international guidelines, inappropriate use increases both the laboratory workload and overall cost of management. Our aim was to assess our practice against the ACBI (Association of Clinical Biochemists in Ireland) guidelines for carcinoembryonic antigen (CEA) and conduct teaching sessions to improve practice. Methods 1st cycle: All carcinoembryonic antigen (CEA) tests ordered in the hospital between the 1st to 31st of October 2020 were obtained through the HSE Online Lab Web Inquiry System, files were then reviewed for indications. Results from the initial audit were presented to the department and two separate teaching sessions were conducted to educate on the guidelines. 2nd cycle: All CEA test ordered from 1st January to 28th February 2021 were obtained, re-audited and results were compared. Results 76% of the tests ordered by General Surgery in the second cycle were appropriately ordered and incorrectly ordered tests decreased from 35.7% to 23.8%. Conclusions Through the process of this audit an improvement was seen in practice of the department. More tests ordered adhered to indications in guidelines.

Clinical application and prospect of MRD evaluation in lung cancer based on ctDNA level: A review.

Lung cancer is one of the most malignant cancers in China with a rising incidence rate. Despite the fact that surgical treatment is the only possible cure for lung cancer, its long-term efficacy is compromised by the high level of postoperative local recurrence rate. Minimal residual disease is the leading cause of tumor recurrence, yet the suggested combination of clinical, radiological and serological (carcinoembryonic antigen) tests fails to reveal the underlying residual tissue in all stage I-III lung cancer cases, which makes tumor recurrence surveillance timely. Through monitoring circulating tumor DNA, the minimal residual disease level can be accessed and provide guidance for more precise postoperative personalized treatment, and its scientific feasibility can revolutionize lung cancer therapy. In the present review we summarized the progress of circulating tumor DNA in lung cancer minimal residual disease detection and discussed its application value in guiding precise treatment of lung cancer.