Median Carcinoembryonic Antigen Research Articles

Abstract 6408: Early carcinoembryonic antigen (CEA) dynamics to predict the efficacy of fruquintinib (F) + best supportive care (BSC) in patients with metastatic colorectal cancer (mCRC) enrolled in FRESCO-2

Abstract Background: The phase 3 FRESCO-2 trial (NCT04322539) demonstrated a significant survival benefit with fruquintinib (F) + BSC vs placebo (P) + BSC as third or later line of therapy for patients (pts) with mCRC. Based on the results of FRESCO-2, F was FDA-approved for adults with previously treated mCRC, irrespective of biomarker status. In mCRC, CEA levels and imaging are routinely used to monitor response to systemic therapy. We investigated early CEA changes during treatment in FRESCO-2 and possible relationships with efficacy. Methods: Pts with abnormal baseline (BL) CEA were included based on local lab reference ranges. Serum CEA levels were measured at BL and Day 1 (D1) of each 28-day cycle (C) except C1. Changes in CEA levels were analyzed at C2D1 and C3D1. CEA response was defined as ≥50% decrease from BL, and CEA progression was defined as ≥100% increase from BL. Tumor evaluation was performed by CT or MRI scan every 2 cycles. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method; hazard ratio (HR) was estimated via Cox proportional hazards model; p-value was generated from log rank test. Results: Overall, 88.3% (407/461) vs 90.4% (208/230) of pts had abnormal BL CEA in F vs P arms; median BL CEA values were similar between treatment arms (Table). At C3D1, the proportion of pts who had a CEA response was significantly higher with F vs P (35.5% vs 3.8%, P <0.001) and the proportion who had CEA progression was significantly lower (5.7% vs 47.2%, P <0.001). Pts in the F arm with CEA response at C3D1 had improved OS and PFS vs pts without CEA response and pts with CEA progression (Table). These results were consistent for pts who had an early CEA response at C2D1 (Table). Conclusion: CEA response at C2D1 and C3D1 could be considered an early predictor for improved OS and PFS. Pts with CEA response seem to benefit from F + BSC compared with pts without response or with CEA progression. Table. CEA changes from baseline in pts in the F + BSC vs P + BSC arms, and OS and PFS based on CEA response in pts in the F + BSC arm CEA changes from baseline by treatment arm (ITT population) F + BSC (N=461) P + BSC (N=230) Baseline, n 407 208 Median CEA (range), µg/L 132.4 (3.0-213000.0) 169.6 (3.2-90010.0) C2D1, n 340 151 Median CEA (range), µg/L 93.3 (2.0-98660.0) 133.5 (2.7-255910.0) Median change from baseline (range), % -19.2 (-90.5-467.8) 44.2 (-61.7-606.8) C3D1, n 245 53 Median CEA (range), µg/L 78.3 (1.7-133390.0) 145.2 (3.9-17782.0) Median change from baseline (range), % -31.0 (-91.4-2195.8) 90.5 (-68.9-3776.6) OS and PFS for pts in the F + BSC arm with or without CEA response at C2D1 and C3D1 Pts with early CEA response at C2D1(n=66) Pts without early CEA response at C2D1 (n=274) Pts with CEA response at C3D1 (n=87) Pts without CEA response at C3D1 (n=158) Median OS, months 10.0 7.4 11.1 8.5 HR (95% CI), P value 0.62 (0.44-0.89), P = 0.009 0.65 (0.46-0.92), P = 0.015 Median PFS, months 5.6 3.7 5.8 4.2 HR (95% CI), P value 0.68 (0.51-0.92), P = 0.01 0.58 (0.44-0.78), P = 0.0003 OS and PFS for pts in the F + BSC arm with CEA response or CEA progression at C2D1 and C3D1 Pts with early CEA response at C2D1(n=66) Pts with early CEA progression at C2D1 (n=15) Pts with CEA response at C3D1 (n=87) Pts with CEA progression at C3D1 (n=14) Median OS, months 10.0 4.3 11.1 5.6 HR (95% CI), P value 0.27 (0.14-0.51), P <0.0001 0.23 (0.12-0.45), P <0.0001 Median PFS, months 5.6 1.9 5.8 3.4 HR (95% CI), P value 0.30 (0.16-0.56), P <0.0001 0.25 (0.13-0.48), P <0.0001 Citation Format: Sara Lonardi, Arvind Dasari, Rocio Garcia-Carbonero, Takayuki Yoshino, Pilar García-Alfonso, Judit Kocsis, Chiara Cremolini, François Ghiringhelli, Ardaman Shergill, Howard S Hochster, Michel Ducreux, Dirk Arnold, Varsha Sundaresan, Siddha Kasar, Adela Pina, Ziji Yu, William R Schelman, Lucy Chen, Josep Tabernero. Early carcinoembryonic antigen (CEA) dynamics to predict the efficacy of fruquintinib (F) + best supportive care (BSC) in patients with metastatic colorectal cancer (mCRC) enrolled in FRESCO-2 [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 6408.

Real-world (RW) study in patients (pts) with metastatic colorectal cancer (mCRC) with long-term responses to regorafenib in the USA.

48 Background: Anecdotal evidence suggests that some pts with mCRC experience significantly longer responses to REG in clinical care settings, including a case exceeding 9 years. However, comprehensive studies on long-term responders to REG are lacking. We evaluated demographic/clinical characteristics of pts with long-term response (LTR) to REG using duration of treatment (DOT) as a surrogate for treatment response. Methods: This was a retrospective cohort study using the US nationwide de-identified Flatiron Health Electronic Health Record-derived database. The study period was January 1, 2013 to May 31, 2023, and adult pts with mCRC who initiated REG monotherapy (index date) from July 1, 2013 to December 31, 2022 were included. DOT for pts with LTR of ≥5 months (LTR5 [primary objective]; mos) or ≥4 mos (LTR4 [secondary objective]) were determined. Results: A total of2,326 eligible pts (median age 64 yrs; 56% male) had initiated REG during the study period. Overall, 346 pts (15%; median age 65 yrs) had LTR5 and 503 pts (22%; median age 65 yrs) had LTR4. Among pts with LTR5, 46% had stage IV disease at initial diagnosis, 68% had ECOG performance status (ECOG PS) 0‒1 at index, 64% received prior bevacizumab (BEV), and of pts tested at index with results, the median carcinoembryonic antigen (CEA) level was 35 ng/mL, and 51% and 5% had a KRAS and BRAF mutation at index, respectively; pts with LTR4 had similar characteristics (Table). Median time from initial CRC diagnosis to index date was 39.2 mos for pts with LTR5 and 38.6 mos for pts with LTR4. Of pts who initiated REG before 2019 (n = 1,070), 14% had LTR5 and 21% had LTR4; of pts who initiated REG from 2019 onwards (n = 1,256), 16% had LTR5 and 22% had LTR4. Among pts with LTR5, 33% and 23% had received REG as third-line (3L) or fourth-line (4L) treatment, respectively; among pts with LTR4, 34% and 23% had received REG as 3L or 4L treatment, respectively. Median time to discontinuation of REG was 7.3 (95% CI 6.9, 7.8) mos in pts with LTR5 and 6.0 (95% CI 5.7, 6.2) mos in pts with LTR4. Median follow-up time (from index date) was 13.3 mos and 11.1 mos in pts with LTR5 and LTR4, respectively. Conclusions: This is the first large-scale RW evidence study to describe demographic/clinical characteristics of pts with LTR to REG. Pts demonstrating LTR typically had favorable ECOG PS at REG initiation, less advanced disease at initial diagnosis, and the majority had received prior BEV. [Table: see text]

Long-term stability of pleural fluid carcinoembryonic antigen and its effect on the diagnostic accuracy for malignant pleural effusion.

The in vitro stability assessment is essential for investigating the diagnostic accuracy of pleural biomarkers. This study aimed to investigate the long-term stability of pleural fluid carcinoembryonic antigen (CEA) at -80°C to -70°C. In addition, we analyzed the effects of frozen storage on the diagnostic accuracy of CEA for malignant pleural effusion (MPE). Pleural fluid CEA of participants in two prospective cohorts were stored at -80°C to -70°C for 1-3 years. The CEA level in the stored specimen was measured with an immunoassay, and its level in the fresh specimen was extracted from medical records. The Bland-Altman method, Passing-Bablok regression, and Deming regression were used to analyze the agreement of CEA between the fresh and frozen pleural fluid. In addition, we used receiver operating characteristic (ROC) curves to evaluate the diagnostic accuracy of CEA in the fresh and frozen specimens for MPE. A total of 210 participants were enrolled. The median CEA levels in frozen and fresh pleural fluid specimens were similar (frozen, 2.32 ng/mL; fresh, 2.59 ng/mL; p < 0.01). The slopes and intercepts in the Passing-Bablok regression (intercept 0.01, slope 1.04) and Deming regression (intercept 0.65; slope 1.00) were not statistically significant (p > 0.05 for all). No significant difference was observed between the area under the ROC curves of CEA in the fresh and frozen specimens (p > 0.05 for all). Pleural fluid CEA is seemingly stable when stored at -80°C to -70°C for 1-3 years. Frozen storage does not significantly affect the diagnostic accuracy of CEA for MPE.

The initial report of phase I trial of VG2025, a non-attenuated HSV-1 oncolytic virus expressing IL-12 and IL-15/RA payloads, in patients with advanced solid tumors.

2580 Background: VG2025 is a non-attenuated HSV-1 Oncolytic virus (OV). The wildtype neurovirulence is controlled by the Transcription and Translation Dual Regulation (TTDR) of ICP27 and ICP34.5 proteins. IL-12, IL-15, IL-15Ra payloads are controlled by tumor promoter CxCR4. The native promoter of ICP27 was replaced with a promoter for Carcinoembryonic Antigen (CEA). Here we report a first-in-human, open label, study to evaluate the safety, pharmacokinetics (PK), and biologic effects of VG2025 in patients (pts) with advanced solid tumors progressed after standard of care from China and United States. The study is actively recruiting. NCT05266612. Methods: Dose escalation follows a 3+3 design at 4 dose levels as intratumoral, and image guided injections into deep lesions on days 1 and 15 of each 28 days treatment cycle. PK and viral shedding (DNA), samples from biopsies, blood, urine, and swabs from injection site and other anatomical locations were analyzed by PCR. Changes of cytokines and lymphocyte subsets in blood were also observed as pharmacodynamic parameters. Results: As of 10 Jan 2023, 10 pts received doses of 1.0x10^8 and 2.0x10^8 PFU. 5 males and 5 females with the median age of 58 years were enrolled. 20% were PD(L)1 refractory, 20% had 2 Prior lines of therapy and 60% ≥3. The Median CEA level was 7.4. Tumor types were: 2 Duodenal Adeno Ca., 1 Pancreatic, 1 Ovarian, 1 Leiomyosarcoma, 1 Salivary Duct Ca., 1 Hepatocellular Ca (HCC), 1 Intrahepatic Cholangiocarcinoma (ICC), 1 Colorectal Ca (CRC) and 1 Colon Ca. No Dose Limiting Toxicities were observed. Any grade treatment-related AEs (TRAEs) was 70%, the most common TRAEs was fever 60%. Grade ≥3 TRAEs were 50% [3 pts had grade 4 Lymphocyte decreased (all recovered)], 1 had grade 3 COVID-19 and 1 had grade 3 nausea and vomiting. 4 pt had SAEs (2 cases of COVID-19, 1 Ascites and 1 Nausea and Vomiting). No TRAEs leading to dose reduction and treatment discontinuation. No pts had positive viral shedding. 4 pts were efficacy evaluable; ORR 25% (1 pt with ICC had confirmed PR with -45%) and DCR 100% based on RECIST v1.1. The PR pt had meaningful reductions in CEA levels. Tumor shrinkage was also observed in non-injected lesions demonstrating an abscopal effect. Nanostring analysis of paired biopsies from the PR pt demonstrate upregulation of genes for integrin signaling pathway, activation of CD8+ T cells and T cell-based immunity, upregulation of antigen-presenting MHC (HLA-DQA1 and HLA-DRB1) and chemokine receptor (CMKLR1) genes. Cellular immunity was activated by upregulation of Th1 cells, macrophage-associated genes and downregulation of Treg-associated genes. The results are consistent with the mechanism of action of VG2025. Analysis is ongoing with other subjects. Conclusions: Monotherapy activity was observed with an acceptable safety profile in heavily pretreated pts with advanced solid tumors. Clinical trial information: NCT05266612 .

Revisiting ab initio carcinoembryonic antigen and CA19-9 tumor markers in colorectal carcinoma in association with anatomotopographic location and staging of disease.

This study purposed to evaluate preoperative two tumor markers, namely, carcinoembryonic antigen and carbohydrate antigen (CA)19-9, in colorectal cancer for anatomotopographic location with disease stage and to assess their utility for diagnostic staging purposes. The study retrospectively incorporated patients who had undergone surgery for colorectal cancer at our department in 2015-2018 and in whom carcinoembryonic antigen and CA19-9 tumor markers had been preoperatively analyzed. The obtained data were then statistically processed using R-project. A total of 155 patients had been incorporated, of whom 96 (62%) were men and 59 (38%) were women. Rectum was the most common location (74 patients, 48%), and the least represented stage was IV (18, 12%). The marker carcinoembryonic antigen was obtained in all 155 cases, while CA19-9 was in 105. The median carcinoembryonic antigen was 3 (0.34-1104.25), and the median CA19-9 was 12 (0.18-840.00). A significance was recognized between median carcinoembryonic antigen and disease stage (p-value=0.016), with stages I, II, and III (medians 2, 3, and 2) different from stage IV (median 13), while no significance for CA19-9 was recognized (p-value=0.343). No significance between either marker and location (carcinoembryonic antigen: p=0.276; CA19-9: p=0.505) was detected. The testing was performed at a significance level of alpha=0.05. This study revealed a significance between the marker carcinoembryonic antigen, but not CA19-9, and the disease stage, while no relationship of either of these markers with tumor location was found. Herewith, the study confirmed that higher carcinoembryonic antigen values may suggest the finding of more advanced forms of colorectal cancer and thus a worse prognosis of this malignant phenomenon.

Potential diagnostic value of the hematological parameters lymphocyte-monocyte ratio and hemoglobin-platelet ratio for detecting colon cancer.

ObjectiveTo evaluate the efficacy of using the lymphocyte–monocyte ratio (LMR), hemoglobin–platelet ratio (HPR), and carcinoembryonic antigen (CEA) levels alone or in combination for diagnosing colon cancer.MethodsWe assessed 124 consecutive patients who were pathologically diagnosed with colon cancer and 131 patients who were diagnosed with benign colon tumors in this retrospective study. We then analyzed correlations between LMR, HPR, and clinicopathological findings. The diagnostic values of LMR, HPR, and CEA alone or in combination in colon cancer patients were evaluated by receiver operating characteristic curves.ResultsThe median LMR, HPR, and CEA values in colon cancer patients showed significant correlation with the depth of tumor invasion, lymph node metastasis, and TNM stage. Moreover, there was a significant difference in HPR between patients with tumor size ≥5 cm and those with tumor size <5 cm. Compared with LMR, HPR, or CEA alone, combinations of CEA with LMR, CEA with HPR, and HPR with LMR all had higher area under the curve values, among which the combination of all three (LMR, HPR, and CEA) had the highest area under the curve.ConclusionThe combination of LMR, HPR, and CEA may be a valuable indicator for monitoring colon cancer.

Pre- and Postoperative Levels of Carcinoembryonic Antigen in Microsatellite Stable Versus Instable Colon Cancer: a Retrospective Analysis.

The prognosis of microsatellite stable (MSS) versus instable (MSI) tumors is an ongoing matter of debate, with differences in expression of carcinoembryonic antigen (CEA) in these two tumor subsets being inconsistently reported to date. The aim of this study was to investigate CEA expression in the context of clinical parameters in MSS and MSI tumors. Clinical, pathological, and biochemical parameters of colon cancer patients who underwent curative surgery were documented in a database and compared between MSS and MSI cases. The pre- to postoperative trend of CEA was analyzed. Survival was assessed using the Kaplan-Meier (log rank) test. One hundred sixty-nine patients were included in the study. Compared to those with MSS tumors, there was a higher proportion of preoperatively elevated CEA among those with MSI tumors (p = 0.067). Median CEA values decreased over the pre- to postoperative course with MSS (p = 0.01) but not MSI (p = 0.093) tumors. The distribution of N classification differed between MSS and MSI tumors (p = 0.014). Patients with MSI tumors had superior survival. Despite the better prognosis, MSI tumors are associated with increases in CEA. Our findings shed light on discrepancies related to the prognostic evaluation of MSI tumors. Furthermore, in follow-up of colorectal cancers, CEA measurements should be interpreted differently for MSI and MSS tumors.

Carcinoembryonic antigen (CEA) and other surrogate inflammatory biomarkers in COVID-19

It has been two years since the global outbreak of the highly contagious and deadly corona virus disease (COVID-19) caused by SARS-CoV-2 first emerged in China. Since then, various diagnostic, prognostic and treatment strategies undertaken to address the pandemic have been dynamically evolving. Predictive and prognostic role of various biomarkers in COVID-19 has been a subject of intense exploration. We aimed to determine the association of Carcinoembryonic antigen (CEA) and various surrogate inflammatory biomarkers with the severity of COVID-19 disease. This retrospective cohort study was carried out on 98 patients admitted in Jaypee Hospital, Noida with COVID-19 disease. Information regarding demographics, laboratory parameters and clinical history was collected from Hospital Information System. Serum levels of CEA and other biomarkers such as Neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), Interleukin-6 (IL-6), Ferritin, and Procalcitonin (PCT) were assessed. Correlation analyses were performed between the parameters and acute respiratory distress syndrome (ARDS) stages. Logistic regression and ROC curve analysis were performed to assess the various parameters for distinguishing COVID-19 patients requiring ICU admission. Mean hospital stay, NLR, CEA, IL-6, CRP, Ferritin (P&lt; 0.0001) and PCT (P =0.01) were significantly higher in ICU patients when compared to general ward patients. NLR, median serum CEA, IL-6, and CRP levels were significantly higher in non-survivor compared to the survivors (P&lt; 0.0001, 0.0341 and 0.0092). CEA correlated well with disease severity based upon ARDS classification and was a better marker to differentiate patient according to ARDS stages (ARDS 0 vs 2 P= 0.0006; 0 vs 3 P&lt; 0.0001; ARDS 1 vs 2 P= 0.0183; 1 vs 3 P=0.0006). The area under the Receiver operating characteristic (ROC) curve for CEA was 0.7467 (95% CI- 0.64885- 0.84459) which revealed the potential of CEA as a biomarker to distinguish COVID-19 patients requiring ICU admission. CEA can be used to predict the severity of COVID-19 associated ARDS as well as patients requiring ICU admission. Along with routine inflammatory biomarkers (NLR, CRP, IL-6, PCT, and ferritin), CEA should be used for early identification of critical COVID-19 positive patients and for assessing prognosis.

Serum carcinoembryonic antigen and carbohydrate antigen 19-9 as preoperative diagnostic biomarkers of extrahepatic bile duct cancer.

BackgroundSerum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 have been proposed as useful preoperative biomarkers of extrahepatic bile duct cancer (EBDC). This study investigated the accuracy of CEA and CA19-9 for preoperative diagnosis of EBDC.MethodsPatients who underwent surgery for EBDC at a tertiary centre between 1995 and 2018 were studied, and those with concurrent hepatobiliary diseases (including gallbladder cancer, intraductal papillary mucinous neoplasms of pancreas), which could affect CEA or CA19-9 levels, were excluded. The control group included patients who underwent cholecystectomy for benign gallbladder diseases during the same period. Diagnostic accuracy was determined using sensitivity, specificity and area under the receiver operating characteristic curve (AUC).ResultsAfter excluding 23 patients, 687 patients (488 men and 199 women, mean age 65.8 years) were compared with the control group of 2310 patients. Median CEA and CA19-9 levels were 1.8 μg/l and 47.0 kU/l in patients with EBDC. CEA (cut-off 5.0 μg/l) showed AUC of 0.541, sensitivity 9.0 per cent and specificity 99.2 per cent, whereas CA19-9 (cut-off 37.0 kU/l) showed AUC of 0.753, sensitivity 56.2 per cent and specificity 94.5 per cent. Sensitivity of CA19-9 was lower in early (T stages 0–II) than advanced (T stages III and IV) cancer (47.0 versus 64.9 per cent), and also lower in N0 stage cancer than lymph node metastasis (50.1 versus 68.8 per cent).ConclusionSerum CEA and CA19-9 showed low sensitivity limiting their usefulness as diagnostic biomarkers of EBDC.

Optimal cutoff value of preoperative CEA and CA19-9 for prognostic significance in patients with stage II/III colon cancer.

This unicentric, retrospective cohort study aimed to identify the optimal cutoff values of preoperative serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) for the prognosis in patients with stage II/III colon cancer. After excluding 43 patients with CA19-9 levels < 0.2 U/mL, 588 were included. Receiver operating characteristic curves were constructed to determine the optimal cutoff values of CEA and CA 19-9 for disease relapse. The median CEA and CA19-9 values were 3.6 (interquartile range: 2.1-7.2ng/mL) and 14.3 (interquartile range: 8.1-30.0) U/mL, respectively. The optimal cutoff values of CEA and CA19-9 were 5.4ng/mL and 22.4 U/mL, respectively. A multivariate analysis of relapse-free survival (RFS) showed that cancer stage, CEA, and CA19-9 were significant independent factors. The RFS of patients with stages II and III colon cancer was significantly stratified by CEA (< 5.4/ ≥ 5.4ng/mL) and CA19-9 (< 22.4/ ≥ 22.4 U/mL). Prognostication based on the reference values (< 5.0ng/mL for CEA and < 37.0 U/mL for CA19-9) was less significant than that based on the optimal cutoff values. Both elevated CEA and CA19-9 had no value dependency on RFS: RFS curves were similar between extremely elevated CEA (≥ 54.0ng/ml) and intermediate CEA (5.4-54.0ng/ml) and between extremely elevated CA19-9 (≥ 224.0 U/ml) and intermediate CA19-9 (22.4-224.0 U/ml). The optimal cutoff values of preoperative CEA and CA19-9 for RFS were 5.4ng/ml and 22.4 U/mL, respectively, in patients with stages II and III colon cancer. Further relapse risk stratification is possible using these values.

Cyst Fluid Carcinoembryonic Antigen Level Difference between Mucinous Cystic Neoplasms and Intraductal Papillary Mucinous Neoplasms.

Background/AimsThe role of cyst fluid carcinoembryonic antigen (CEA) level in differentiating mucinous pancreatic cystic lesions (PCLs) is controversial. We investigated the role of cyst fluid CEA in differentiating low-risk (LR)-intraductal papillary mucinous neoplasms (IPMNs) from high-risk (HR)-IPMNs and LR-mucinous cystic neoplasms (MCNs). MethodsThis was a retrospective study of 466 patients with PCLs who underwent endoscopic ultrasound-guided fine-needleaspiration over a 7-year period. On histology, low-grade dysplasia and intermediate-grade dysplasia were considered LR, whereas high-grade dysplasia and invasive carcinoma were considered HR. ResultsData on cyst fluid CEA levels were available for 50/102 mucinous PCLs with definitive diagnoses. The median CEA (range) levels were significantly higher in HR cysts than in LR cysts (2,624 [0.5–266,510] ng/mL vs. 100 [16.8–53,445]ng/mL, p=0.0012). The area under the receiver operating characteristic curve (AUROC) was 0.930 (95% confidence interval [CI], 0.5–0.8; p<0.001) for differentiating LR-IPMNs from LR-MCNs. The AUROC was 0.921 (95% CI, 0.823–1.000; p<0.001) for differentiating LR-IPMNs from HR-IPMNs. Both had a CEA cutoff level of >100ng/mL, with a negative predictive value (NPV) of 100%. ConclusionsCyst fluid CEA levels significantly vary between LR-IPMNs, LR-MCNs, and HR-IPMNs. A CEA cutoff level of >100ng/mL had a 100% NPV in differentiating LR-IPMNs from LR-MCNs and HR-IPMNs.

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.

452P A phase Ib dose escalation study of binimetinib plus mFOLFIRI in patients with metastatic RAS mutated colorectal cancer

Preclinical and early clinical evidence suggest that MEK inhibition (MEKi) acts synergistically when combined with cytotoxics in RAS mutated (mt) metastatic colorectal tumours (mCRC). We investigated the safety and clinical activity of MEKi, binimetinib, and mFOLFIRI in patients (pts) with RAS mt mCRC (NCT02613650). Eligibility criteria: Pts >18 years with RAS mt mCRC, ECOG 0-1, acceptable organ function, radiographic measurable disease, and progression or ineligibility to oxaliplatin. Pts were treated with binimetinib plus mFOLFIRI, in a dose-escalated standard 3+3 design, to determine the maximum tolerated dose (MTD) and report the dose-limiting toxicities (DLTs). A 6-day lead-in period with binimetinib alone was required prior to combination therapy. Binimetinib was dosed at two levels – 30mg BID and 45mg BID - and was given on days 1-12/14-day cycle po with mFOLFIRI every 14 days iv. After determination of MTD, an additional 12 patients will be enrolled in the dose expansion phase to assess preliminary efficacy. 13 pts were enrolled in the dose escalation phase: 7 pts on the first binimetinib dose level and 6 on the second. Median age was 56 yrs (44-71), 9 were male and 9 had received prior treatment with irinotecan. The mean number of prior therapies was 2 (1-6) and the median carcinoembryonic antigen (CEA) level on screening was 84.9 ng/mL (7.2-476.3). The most common grade 1-2 adverse effects (AEs) (N) included rash (10), nausea (9), diarrhoea (8), vomiting (7), fatigue (5) and mucositis (4). Grade 3 AEs included anaemia (1), rash (1), heart failure (1), and fatigue (1). One pt had grade 4 neutropenia related to mFOLFIRI. One pt had a DLT (decreased cardiac ejection fraction) on dose level 1 and 3 additional patients were added to dose level 1. Two pts discontinued the study due to grade 2 AEs (stomatitis and pruritus) and 2 withdrew consent. The mean number of cycles received was 8 (2-29). Best response included 1 partial response and 5 stable disease (all had received prior irinotecan and 3/6 had progressive disease on it). Four pts remained on the study for >6 months (32-67 weeks). The study is currently on the dose expansion phase after 6 pts were treated at MTD (dose level 2). This cohort will enroll only irinotecan refractory pts. MEKi plus mFOLFIRI is tolerable and showed preliminary efficacy in the dose escalation cohort in pts with RAS mt mCRC and prior exposure to irinotecan.

Sa1443 CYST FLUID CARCINOEMBRYONIC ANTIGEN DIFFERENCE AMONG MUCINOUS CYSTIC NEOPLASMS AND INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS

Cyst fluid carcinoembryonic antigen (CEA) is a useful marker for differentiating between mucinous from nonmucinous pancreatic cystic lesions (PCLs). However, the role of cyst fluid CEA levels in differentiation between mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs) as well as between the low risk (LR) and high risk (HR) mucinous lesions are scanty. We aimed to analyse this subject. This was a retrospective study of 52 patients with mucinous PCls diagnosed by cyto/histo-pathology out of 466 patients who underwent endoscopic-ultrasonography-guided fine-needle aspiration for PCLs over a seven-year period. On histology, low- and intermediate-grade dysplasia were considered as LR, and high-grade dysplasia and invasive carcinoma were considered as HR. Cyst fluid CEA was available for 52/102 mucinous and 44/121 nonmucinous PCLs with definitive diagnoses. The median cyst fluid CEA [Range] values were significantly higher in mucinous compared with nonmucinous cysts (1079 ng/mL [0.5-266510 ] versus 6 ng/mL [0.2-309]), and LR-MCNs compared with LR-IPMNs (7954.7 ng/mL, [299.6-53445] versus 51.3 ng/mL [16.8-132.2]), and HR-IPMNs compared with LR-IPMNs (2624 ng/mL [0.5-266510] versus 100 ng/mL [16.8-53445]). The AUROC was 0.930 (95% confidence interval [CI]: 0.5-0.8) to differentiate between LR-IPMNs and LR-MCNs and 0.921 (95% CI: 0.823-1.000) to differentiate between LR-IPMNs and HR-IPMNs using cyst fluid CEA. Both showed cutoff values of >100 ng/mL and demonstrated a sensitivity of 100/100, specificity of 75/75, and positive and negative predictive values of 66.7/78.9 and 100/100, respectively. Cyst fluid CEA is useful in differentiation between LR-MCNs from LR-IPMNs and LR-IPMNs from HR-IPMNs. Diagnosis using a cyst fluid CEA cutoff value of 100 ng/mL showed a 100% negative predive value in differentiating LR-IPMNs from LR-MCNs and HR-IPMNs.

Synergistic Association of Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 on the Risk of Abnormal Glucose Regulation.

PurposeCarcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are tumor-associated antigens. An increased serum level of CEA and CA19-9 separately has been reported in diabetes. In this study, we examined the composite effect of elevated serum levels of both CEA and CA19-9 on subjects with type 2 diabetes and prediabetes.Patients and MethodsA total of 3568 adults who attended a health examination were enrolled into this cross-sectional study. Subjects were grouped into four groups according to the median serum CEA and CA19-9 levels.ResultsSubjects with high CEA and high CA19-9 levels had the highest proportions of diabetes (43.9%) and prediabetes (33.04%). There was a statistically significant trend in the proportion of diabetes across the four groups (P < 0.001). Multivariable logistic regression analysis revealed higher risks of type 2 diabetes in subjects with high CEA and low CA19-9 levels (odds ratio [OR] = 2.10, 95% confidence interval [CI]: 1.39–3.18, P < 0.001) and in those with high CA19-9 and low CEA levels (OR = 2.18, 95% CI: 1.42–3.34, P < 0.001) than in those with low CEA and low CA19-9 levels; among these four groups, the highest risk of type 2 diabetes was observed in subjects with high CEA and high CA19-9 levels (OR = 2.65, 95% CI: 1.81–3.88, P < 0.001). The risk of prediabetes was significantly higher only in subjects with high CEA and high CA19-9 levels compared to those with low CEA and low CA19-9 levels (OR = 1.32, 95% CI: 1.08–1.61, P = 0.006).ConclusionCEA and CA19-9 had a synergistic ability to increase the risk of type 2 diabetes and prediabetes.

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.

Prognostic significance of preoperative serum CEA in primary mucinous ovarian carcinoma: a retrospective cohort study.

PurposeThe purpose of this study was to evaluate the prognostic significance of preoperative serum carcinoembryonic antigen (CEA) in primary mucinous ovarian carcinoma (MOC).Patients and methodsWe reviewed 57 patients with primary MOC, in whom preoperative serum CEA had been measured. All patients were treated at Peking Union Medical College Hospital between June 1996 and September 2016.ResultsPreoperative serum CEA was elevated (>5.0 ng/mL) in 10 patients (17.5%), with a median serum CEA of 9.6 ng/mL (5.4–111.7 ng/mL). CEA was significantly associated with preoperative serum cancer antigen 125 (P=0.002), surgical debulking status (P=0.015), and tumor stage (P=0.001). Univariate analysis showed that patients with elevated CEA had significantly worse overall survival (OS) than patients with normal CEA (5-year OS: 50.8% vs 91.9%, respectively; P=0.013), but there was no significant difference in progression-free survival between the two groups (P=0.307). Multivariate analysis further demonstrated that advanced stage was an independent prognostic predictor for OS (P=0.002, HR: 15.925, 95% CI: 2.745–92.404).ConclusionElevated preoperative serum CEA was strongly correlated with advanced stage in primary MOC, which may indicate a poorer prognosis. Further investigation of the intrinsic relationship between CEA and primary MOC is now required.

Correction: Kinetic change of serum carcinoembryonic antigen can early predict progression in patients with metastatic non-small cell lung cancer during maintenance therapy with bevacizumab plus pemetrexed.

[This corrects the article DOI: 10.18632/oncotarget.20456.].

P3.16-051 Implications of Preoperative Serum Tumor Levels on Pathological Characteristics in Patients with Lung Adenocarcinoma

Although preoperative serum tumor marker levels, such as carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC) are often evaluated in non-small cell lung cancer patients, the implication of these levels are still unknown. This study examined the predictive effect of preoperative tumor marker levels on pathological characteristics of lung adenocarcinoma. We retrospectively reviewed patients with lung adenocarcinoma who underwent macroscopic complete resection. The pathological metastasis and/or involvement was defined that positive pleural effusion or lavage cytology, pleural involvement, pulmonary metastasis, lymph node metastasis, and/or lymphovascular involvement were identified on pathological examination. To identify predictors for the pathological metastasis and/or involvement, tumor markers (CEA, SCC, Sialyl Lewisx-1 [SLX], cytokeratin-19 fragments [CYFRA], neuron-specific enolase [NSE], and pro-gastrin-releasing peptide [ProGRP]), and demographic and clinical factors were analyzed by a univariate analysis and multivariate logistic regression analysis. For the significant tumor markers, optimal cutoff points were determined with a receiver operating characteristic analysis. Of the 263 eligible patients, 138 were male and 125 were female. The median age was 70 years. The median preoperative CEA, SCC, SLX, CYFRA, NSE, and ProGRP levels were 3.7 ng/ml, 0.8 ng/ml, 28 U/ml, 1.8 ng/ml, 8.4 ng/ml, and 46.9 pg/ml, respectively. According to the 7th edition of the TNM classification, 186 patients (71%) had c-stage IA disease, 48 (18%) had c-stage IB disease, 26 (10%) had c-stage II disease, and 3 (1%) had c-stage III disease. Positive pleural effusion, positive pleural lavage cytology, pleural involvement, pulmonary metastasis, lymph node metastasis, lymphatic permeation, and vascular invasion were identified in 3 (1%), 4 (2%), 48 (18%), 9 (3%), 28 (11%), 20 (8%), and 35 patients (13%), respectively, and in total, 83 patients (32%) developed the pathological metastasis and/or involvement. The univariate analysis identified CEA, smoking index, size, solid size, and c-stage as significant predictors. A multivariate analysis revealed CEA (OR: 1.113, p=0.005) and solid size (OR: 1.052, p<0.001) as significant predictors. The optimal cutoff point was determined as 6.0 ng/ml for the preoperative CEA, and 35 of the 63 patients (56%) with ≥6.0 ng/ml of CEA developed the pathological metastasis and/or involvement whereas 48 of the 200 patients (24%) with <6.0 ng/ml of CEA developed pathological metastasis and/or involvement. Our results suggested the predictive effect of the high preoperative CEA level on pathological metastasis and involvement in patients with lung adenocarcinoma, and thus, we may consider preoperative CEA to decide surgical procedure for these patients, such as the extent of pulmonary resection and lymphadenectomy.