Baseline 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.

Role of CYFRA 21-1 and CEA as prognostic and predictive markers in locally advanced and metastatic gastric carcinoma.

Tumor-associated serum markers have demonstrated predictive and prognostic value in patients being treated for malignancies. However, the clinical importance of tumor markers in gastric cancers (GC) is poorly standardized. The objective is to assess the clinical utility of cytokeratin-19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA) as serum tumor markers in advanced GC. In this prospective study, CYFRA 21-1 and CEA levels were measured at baseline and after three cycles of chemotherapy in patients with advanced GC. The association of tumor marker levels with prognosis and decline of tumor markers with radiological overall response rates (ORR) and survival were analyzed. In the 105 patients, the proportion of patients with elevated baseline CYFRA 21-1 and CEA levels was 55% (N = 58) and 37% (N = 39) based on predefined cutoffs. Response assessment was done for 61 patients who received a minimum of three cycles of chemotherapy. A 15% and 13% reduction of serum levels from baseline for CYFRA 21-1 and CEA were selected for defining "CYFRA 21-1 response" and "CEA-response," respectively. Both responses were significant predictors of radiological ORR. The median overall survival (OS) was 9.6 months in the entire cohort and 13 months for patients who received at least three cycles of chemotherapy. In multivariate analysis, baseline CEA levels and ECOG status were significant predictors of OS. In a subset analysis of patients receiving palliative chemotherapy, any of the tumor marker responses predicted improved 1-year OS. In advanced GC, CYFRA 21-1 and CEA decline from baseline appeared to be reliable surrogate markers of chemotherapy efficacy and improved survival.

Metastatik kolorektal kanserde regorafenib tedavi sonuçlarını etkileyen prognostik faktörler

Aim: We aimed to determine the efficacy and prognostic factors of Regorafenib in advanced colorectal cancer patients. Materials and Methods: This study was designed as single-center and retrospective. The study included 72 patients with metastatic colorectal cancer treated with Regorafenib. Univariate and multivariate analyses of factors affecting survival were generated by Cox Regression Models. Results: Twenty-three (31.9%) of the patients were female, the median age was 65 years. The median progression-free survival (PFS) and overall survival (OS) were 4.13 and 8.7 months, respectively. The carcinoembryonic antigen (CEA) level (p=0.001), and Eastern Cooperative Oncology Group (ECOG) score (p<0.001) were found to be prognostic in the multivariate model for PFS. ECOG (p<0.001), CEA level (p<0.001), dose reduction (p=0.003), and side of the primary tumor (p=0.037) were prognostic for OS. Conclusion: Our study revealed that ECOG, requiring dose reduction during the treatment, and lower baseline CEA levels were found to be prognostic.

A Real-World Retrospective Study to Evaluate the Reliability of Cetuximab plus Capecitabine versus Capecitabine as Maintenance Therapy in Patients with RAS and BRAF Wild-Type Metastatic Colorectal Cancer

Background: The optimal maintenance therapy for rat sarcoma (RAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) metastatic colorectal cancers (mCRCs) remains unclear. It is critical to evaluate the reliability of cetuximab-capecitabine (the observation group) relative to capecitabine alone (control group). Patients and Methods: In this retrospective analysis, patients with RAS and BRAF mCRC admitted to Huizhou Municipal Central Hospital, between January 2016 and October 2020 were enrolled and treated with cetuximab plus 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as an initial therapy. Patients whose disease was controlled after at least six cycles of treatment were administered a maintenance therapy until disease progression. We also analyzed the prognosis of patients according to clinicopathological features. Altogether, 39 RAS and BRAF mCRC patients were recruited from January 2016 to October 2020, with 18 cases in the treatment group and 21 cases in the control group. The difference in baseline clinicopathological features between the two treatments is not obvious. Results: The median progression-free survival after maintenance treatment in observation group (9.5 months [95% confidence interval (CI) = 6.4–12.6]), was significantly better than the control group (7.3 months [95% CI = 5.8–8.8]). During maintenance treatment, there were no deaths caused by treatment-related adverse events, and the overall incidence of rash acne was different between the observation and control groups (p < 0.05). Most adverse events were mild and easily controlled. Primary tumor site, baseline carcinoembryonic antigen levels, and microsatellite instability status were independent prognostic factors. Conclusion: Maintenance therapy using cetuximab plus capecitabine improved survival in patients with mCRC and was well tolerated by patients.

Efficacy and safety analysis of bevacizumab combined with capecitabine in the maintenance treatment of RAS-mutant metastatic colorectal cancer.

What is known and objectivesThe optimal strategy for maintenance therapy in patients with metastatic colorectal cancer (mCRC) remains controversial. Considering that, beyond progression, co‐therapy with bevacizumab and cytotoxic chemotherapy showed less toxicity and a significant disease control rate. We aimed to investigate the differences in efficacy and safety between bevacizumab combined with capecitabine maintenance therapy and capecitabine monotherapy for RAS‐mutant mCRC （as defined by mutations in KRAS and NRAS exons 2–4）controlled by bevacizumab plus FOLFIRI chemotherapy for at least 12 weeks.MethodsWe retrospectively analysed patients with RAS‐mutant mCRC admitted to the Department of Oncology, Huizhou Municipal Central Hospital from December, 2015 to December, 2020. All patients were first treated with bevacizumab combined with FOLFIRI for at least 12 weeks of induction therapy. 154 patients whose disease was brought under control then continued maintenance therapy. 78 patients were in the observation group (bevacizumab plus capecitabine) and 76 patients were in the control group (capecitabine alone). The efficacy and adverse effects of maintenance treatment were compared between the two groups. The clinicopathological characteristics such as sex, age, performance status (PS) score, primary tumour site, degree of pathological differentiation, baseline carcinoembryonic antigen (CEA) level, microsatellite instability (MSI) status, number of metastatic tumour sites and efficacy of induction treatment were compared in terms of prognosis.Results and discussionThe median progression‐free survival (mPFS)of patients was 9.0 months (95% CI 8.0–10.0) in the observation group and 7.2 months (95% CI 6.0–8.4) in the control group, with a statistically significant difference (p < 0.05). The baseline CEA level was an independent prognostic factor. Both groups tolerated the toxic side effects.What is new and conclusionBevacizumab combined with capecitabine was well tolerated and contributed to a longer PFS time than capecitabine alone, and it is worthy of popularization in clinical practice.

Survival outcome and treatment response of patients with young-onset locally advanced rectal cancer (YO-LARC) receiving total neoadjuvant therapy (TNT).

44 Background: Despite an alarming rise in incidence, data on survival outcome and treatment response of young-onset (age &lt; 50 years) locally advanced rectal cancer (YO-LARC) patients receiving total neoadjuvant therapy (TNT) are sparse. We retrospectively compared the outcome between YO-LARC and later-onset (aged 50 years or older) LARC (LO-LARC) patients treated with TNT. Methods: After the institutional review board approval, electronic medical records of the LARC (T3/T4 or node-positive) patients treated with TNT at a tertiary care cancer center between January 1, 2015, and June 30, 2020, were reviewed for data collection. TNT consisted of systemic chemotherapy with oxaliplatin-based regimens for 16 weeks followed by long-course radiation with concurrent capecitabine or 5-fluorouracil (CRT). Patients receiving only preoperative CRT were excluded. Most patients underwent surgical resection following the TNT. Non-operative management was offered to patients if TNT resulted in clinical complete response (cCR). The following comparisons between the YO-LARC and the LO-LARC patients were performed: patient characteristics, pathological complete response (pCR) rate, combined pCR + cCR rate, disease-free survival (DFS), and overall survival (OS). Results: Of 72 patients included in the analysis, 44(61%) were male, 49 (68%) were Caucasian, and 62 (86%) had clinical stage III disease. The study included 26 (36%) patients with YO-LARC (median age, 43 years) and 46 (64%) patients with LO-LARC (median age, 64 years). The comparison of patient characteristics that included gender, clinical stage, baseline carcinoembryonic antigen level, the distance of the tumor from the anal verge, presence of high-risk features, and histologic grade did not differ significantly between the groups. There were no statistically significant differences in pCR and combined pCR+cCR rates (p = 0.16) between the groups: YO-LARC, 12 % (3/26) and 15 % (4/26), respectively; LO-LARC, 22% (10/46) and 30% (14/46), respectively. Either group did not reach median DFS and OS after a median follow-up of 38 months for survivors. The estimated 5-year OS rates in patients with YO-LARC and LO-LARC were 86 % (95% confidence interval [CI], 69% to 100%) and 84% (95% CI, 68% to 100%), respectively (p = 0.92). The estimated 3-year DFS rates in patients with YO-LARC and LO-LARC were 67 % (95% CI, 50% to 89%) and 83% (95% CI, 72% to 95%), respectively (p = 0.19). Conclusions: The current retrospective analysis did not demonstrate significant differences in the pCR rates, combined pCR +cCR rates, DFS, or OS between the YO-LARC and LO-LARC patients treated with TNT.

'FLARE' of tumor marker in advanced gastric cancer treated with first-line systemic therapy.

Background:Transient tumor marker elevations caused by chemotherapy were defined as ‘Flare’ and have been demonstrated in some solid tumors. In clinical practice, we observed that some patients were accompanied by elevated tumor markers during treatment, but subsequent imaging proved that the treatment they received was effective.Objectives:We aimed to study the Flare and the prognosis in advanced gastric cancer.Design:This is an observational retrospective study. A total of 167 patients were enrolled in this study. Carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9 and CA125 values were obtained before the first, second, third, fourth, fifth and sixth cycles of treatment, respectively.Methods:Imaging for the first efficacy assessment was reviewed according to the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) criteria. Kaplan–Meier analyses and log-rank tests were performed for overall survival (OS) analyses. Univariate and multivariate Cox analyses were used to determine the prognostic factor for OS and progression-free survival (PFS).Results:37.1% of patients were accompanied with at least one tumor marker Flare during the course of treatment. The median time to tumor marker peak was 24–30 days and the Flare duration lasted 49–53 days. Patients with tumor markers Flare had a worse OS. Flare may be associated with the use of 5-fluorouracil. Baseline CEA and CA125 levels were the independent prognostic factors for OS and baseline CA125 level was the independent prognostic factor for PFS.Conclusion:Initial elevation of tumor markers during treatment is not an indication of tumor progression. Patients with tumor markers ‘Flare’ may had a worse OS.

Serum Biomarker Status with a Distinctive Pattern in Prognosis of Gastroenteropancreatic Neuroendocrine Carcinoma

Objective: Gastroenteropancreatic neuroendocrine carcinoma (GEPNEC) is a major research focus, but the application of biomarkers to guide its prognostication and management is unsatisfying. Clinical values of conventional serum biomarkers, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA199) warrant scrutiny. Methods: Patients diagnosed with GEPNEC with baseline NSE, CEA, and CA199 levels provided in Peking University Cancer Hospital were retrospectively studied. Relationships between biomarkers and prognosis were investigated by the χ2 test, Kaplan-Meier analysis, and univariate and multivariate Cox regression analyses. Results: A total of 640 GEPNEC patients were enrolled. NSE, CEA, and CA199 were elevated in 59.5%, 28.5%, and 21.3% of the population, respectively. Higher NSE had worse median overall survival (OS) (17.0 months vs. not reached, hazard ratio = 2.77 [2.06, 3.73], p < 0.001), and so did patients with higher CEA and CA199. Multivariable analysis confirmed that NSE and CA199 correlated with OS independently. Baseline NSE level and NSE remission predicted OS and the response of patients with first-line etoposide plus cisplatin (EP) treatment. Furthermore, we combined NSE/CEA/CA199 to segregate GEPNEC into novel subgroups, namely, adenocarcinoma-like NEC (ALN), neuroendocrine-like NEC (NLN), and triple-normal NEC (TNN). The groups shared distinctive clinicopathologic features and prognosis (21.0 months vs. 17.1 months vs. not reached, p < 0.001). The EP regimen remained the priority treatment option in NLN/TNN, while ALN was predisposed to “adenocarcinoma-like chemotherapy.” Conclusions: Elevation of NSE, CEA, or CA199 was common and independently indicates poor prognosis in GEPNEC patients. Serum biomarker-based subtypes suggest meaningful clinical implications and appropriate therapeutic approaches, illuminating promising ways to characterize the prognosis of GEPNEC.

A CLINICO-PATHOLOGICAL STUDY OF CARCINOMA BREAST WITH SPECIAL REFERENCE TO SERUM CEA LEVELS & ITS RELATIONSHIP WITH TREATMENT

BACKGROUND: Carcinoembryonic antigen (CEA) is used as a tumor marker for breast cancer (BC) &amp; follow up of patients pre- or post- chemotherapy. In order to better dene clinical usefulness of CEA in breast cancer patients (BCP) we determined its baseline pre-treatment levels and correlated them with main parameters of primary tumor and metastases.PATIENTS AND METHODS: The main experimental group consisted of 53 females with histologically conrmed diagnosis of BC. The obtained results have been compared with those of three follow-up groups: pre-operative, immediate post-operative and 2nd follow up Post operative patients with other types and locations of cancer. In both cancer groups the parameters of primary tumor (size, grade) and metastases (time interval to metastases, location, size) have been determined. Circulating levels of CEA were measured by the means of sandwich ELISA assay. Results were processed by means of t-test, two way analysis of variance in p value. RESULTS: Baseline levels of CEA in BCP were signicantly higher than in healthy women (p &lt; 0.0001), and in patients with other types and locations of cancer (p &lt; 0.007). There also was signicant difference (p &lt; 0.001) between serum CEA in other cancer patients and healthy women. Baseline CEA levels were in signicant positive correlation with the size of primary tumor both in all BCP (p &lt; 0.03) and in hyperCEA BCP (p &lt; 0.002), while in other cancer patients such a correlation did not exist. There was no correlation between CEA and degree of differentiation of primary tumor either in BCP or in other cancer patients. The average circulating levels of CEA in metastatic BCP were signicantly higher (p &lt; 0.03) in comparison to non-metastatic patients, while in other cancer patients such a difference did not show up. There was signicant correlation (p &lt; 0.0001) between circulating CEA and the size of metastases in all BCP and in subgroup of hyperCEA BCP, while in other cancer patients it was not a case. There was no correlation between serum CEA and other two metastatic parameters either in BCP or in other cancer patients. CEA does not have high tumor specicity for BC CONCLUSIONS: 1 since its baseline levels may be elevated in other types of cancer . Circulating levels of CEA in BCP are directly dependable on the size of both primary and metastatic tumor. CEA is a tumor antigen of less differentiated cancer cells. Circulating CEA is a good prognostic marker for patients with metastatic BC.

Association of Carcinoembryonic Antigen Reduction With Progression-free and Overall Survival Improvement in Advanced Non-small-cell Lung Cancer

BackgroundNon-small cell lung cancer elevates serum carcinoembryonic antigen (CEA). CEA determinations are not recommended currently. This study aims to identify the correlation between reducing serum CEA levels with progression-free survival (PFS) and overall survival. MethodsThis study assessed at baseline and in every scheduled visit serum CEA levels throughout first-line therapy. A sensitivity and specificity analysis identified the best cut-off point and correlated it with progression-free survival and overall survival. Multivariate Cox proportional hazard models were conducted. ResultsWe assessed 748 patients with elevated serum CEA levels at diagnosis. A ≥20% decrease from baseline was associated with a 2-fold median survival compared with patients with lower decreases (20.5 months vs 9.1 months; hazard ratio, 0.53; 95% confidence interval, 0.44 to –0.64; P < .001). CEA sensitivity and specificity to predict survival was 79.8% and 59.8%, respectively. A ≥10% decrease in CEA concentrations was associated with longer progression-free survival (7.7 months vs 5.9 months; hazard ratio, 0.71; 95% confidence interval, 0.57 to –0.88; P = .001) in those treated with chemotherapy, and in patients under tyrosine kinase inhibitors (11.9 months vs 7.3 months; hazard ratio, 0.63; 95% confidence interval, 0.47 to –0.83; P = .0001) and a ≥20% decrease. ConclusionIn patients with metastatic non-small cell lung cancer with an elevated baseline CEA level, the percentage decrease of CEA concentrations above the threshold during the first-line therapy was associated with more prolonged survival and progression-free intervals. Serum CEA determinations are a feasible, noninvasive option for monitoring and prognosis.

Prognostic value of CEA and CA19-9 in patients with local advanced rectal cancer receiving neoadjuvant chemoradiotherapy, radical surgery and postoperative chemotherapy.

BackgroundWe aim to investigate the prognostic factors and evaluate the role of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in local advanced rectal cancer (LARC) patients who received neoadjuvant chemoradiotherapy (neo-CRT), radical surgery and postoperative chemotherapy.MethodsIn total, 197 cases of LARC patients who underwent neo-CRT, total mesorectal excision (TME), and adjuvant chemotherapy were recruited. Serum levels of CEA and CA19-9 were detected both at baseline and after neo-chemoradiotherapy. Multivariate analysis was used to assess correlations between levels of CEA and CA19-9 and patients’ prognosis (survival, recurrence, and metastasis). Rates of survival, distant metastasis (DM), and local recurrence (LR) were estimated using Kaplan-Meier survival analysis, the log-rank test, and Cox proportional hazards.ResultsThe median follow-up time was 45.3 months, and a cohort of 197 patients was analyzed; 84 (42.6%) patients had elevated baseline CEA levels, 21 (10.7%) patients had elevated baseline CA19-9 levels, and 14 (7.1%) patients had both; 77.4% (65/84) patients with high CEA levels and 76.2% (16/21) with high CA19-9 levels returned to normal after neo-chemoradiotherapy. The Cox regression model suggested that elevated CEA was associated with an increased risk of disease-free survival (DFS) (HR: 2.058, 95% CI: 1.034–4.096, P=0.040) and DM (HR: 2.144, 95% CI: 1.058–4.346, P=0.034). Elevated CA19-9 was identified as an independent prognostic factor, with poorer overall survival (OS) (HR: 2.894, 95% CI: 1.196–7.006, P=0.018) and DFS (HR: 4.533, 95% CI: 2.067–9.940, P<0.001) and increased incidences of LR (HR: 6.139, 95% CI: 1.813–20.783, P=0.004) and DM (HR: 4.052, 95% CI: 1.892–8.678, P<0.001). Besides, combined CEA with CA19-9 was a stronger prognostic predictor. Patients with both high levels of CEA and CA19-9 had the poorest DFS (HR: 8.157, 95% CI: 3.232–20.591, P<0.001) and the highest risk of DM (HR: 8.790, 95% CI: 3.324–23.248, P<0.001).ConclusionsLARC patients with high levels of CEA or/and CA19-9 at initial treatment have a worse prognosis, even after neo-CRT, subsequent radical resection, and adjuvant chemotherapy. These findings suggest that this subset of patients requires more intensive treatment or additional treatment strategies.

P-309 Correlation between baseline CEA levels and TNM stage at presentation in colorectal cancers in an Indian population

CEA is an oncofetal antigen that is increasingly expressed in colorectal cancers. We aimed to examine the relationship between carcinoembryonic antigen (CEA) levels in the preoperative period and TNM staging in patients with colorectal cancer in the north Indian region.

Routine baseline serum carcinoembryonic antigen as a negative predictor of peritoneal metastasis in colorectal malignancies: a cost-effective tool in South India

Background: Colorectal cancer, a formidable health problem worldwide has upto 8% synchronous peritoneal carcinomatosis. As only diagnostic laparoscopy can identify them, in countries with economic burden, selection of patients for laparoscopy is ideal. Our aim is to evaluate whether the baseline Carcinoembryonic antigen (CEA) is a good selection tool.Methods: A retrospective study of 125 patients, who were diagnosed to have colorectal malignancy (any stage) and underwent elective surgery at our institution from 2012 till 2019 were included. The baseline serum CEA was compared with the intraoperative findings. The threshold levels of serum CEA compared were 6.5 and 100 ng/dl. The sensitivity, specificity, positive predictive value and negative predictive value for both thresholds were compared in 3 categories of patients, namely peritoneal metastasis (9 cases), metastasis to other organs (36 cases) and cases with no metastasis either in peritoneum or other organs (85 cases). The results were analysed using SPSS software.Results: The mean age was 65, sex ratio (male:female) was 72:53. The sensitivity, specificity, positive predictive value, negative predictive value (NPV) for CEA threshold of 6.5 ng/dl was 44.44%, 60.34%, 8% and 93.33% for category 1. For CEA threshold of 100 ng/dl, it was 33.33%, 97.41%, 50% and 94.95% for category 1. NPV was 96.55% for category 3 (the highest value).Conclusions: If the baseline CEA levels are less than 100 ng/dl, 96.55% of cases will not require a diagnostic laparoscopy. This hopefully will cut down the cost of unnecessary diagnostic laparoscopies, and reduce the morbidity of unnecessary laparotomies.

THE Role of Preoperative carcinoembryonic antigen in recurrence of resectable colorectal carcinoma.

SUMMARYIn colorectal carcinoma, carcinoembryonic antigen (CEA) is a recommended marker for surveillance after curative resection. The aim of the present study was to determine the association of preoperative CEA with recurrence of colorectal carcinoma in our population. The study included 55 patients with all operable stages of colorectal adenocarcinoma treated during the 2012-2014 period, evaluated retrospectively and followed-up for recurrence for 2 years. Data on the baseline (preoperative) CEA levels were retrieved from patient files. On data analysis, SPSS 16.0 was used. In patients with normal preoperative CEA, the rate of recurrence was significantly low (p=0.008) and the likelihood of no recurrence 1.55-fold greater as compared to patients with raised initial CEA levels (p=0.028). In patients with raised preoperative CEA, the risk of recurrence was 5.26-fold greater as compared to those with normal CEA levels (p=0.028). A significant weak positive correlation (rs=0.297) was found between raised CEA and recurrence. A highly significant (p=0.002) moderate positive correlation was recorded in patients aged <50 and moderate positive correlation of borderline significance in males (rs=0.324, p=0.058). Sensitivity was 94.4% and specificity 32.4% in predicting recurrence. Accordingly, preoperative elevated CEA showed a significant weak positive correlation with recurrence while normal preoperative CEA moderately decreased the likelihood of recurrence.

Prognostic factors in patients treated with transarterial radioembolization for unresectable and chemorefractory colorectal cancer with liver metastases

ABSTRACTBackground: Transarterial radioembolization (TARE) is used to treat unresectable colorectal cancer with liver metastases (CRCLM). This study aimed to assess survival after TARE and to identify potential prognostic factors in this patient population.Methods: Patients with unresectable and chemorefractory CRCLM treated with TARE at our institution between February 2006 and September 2015 were included in the study. Survival rate, hepatic tumor response, and potential prognostic factors were analyzed.Results: In the 43 study patients, the mean follow-up was 15.0 ± 14.2 months, with a median survival of 13.0 months and 1-, 2-, 3-, 4-, and 5-year survival rates of 52.1%, 24.9%, 21.4%, 21.4%, and 7.1%, respectively. The mean activity of yttrium-90 administered was 1.55 ± 0.28 GBq for the disease-controlled group and 1.19 ± 0.27 GBq for the progressive disease group (p= 0.031). Survival was correlated with Child-Pugh class (p< 0.001), hepatic tumor response (p= 0.001), and baseline carcinoembryonic antigen (CEA) level (p= 0.013).Conclusion: Child-Pugh class B, low degree of hepatic tumor response, and normal baseline CEA levels are prognostic factors for poorer survival after TARE in patients with unresectable and chemorefractory CRCLM. Hepatic tumor response is related to radiation activity delivered to the liver.

Independent prognostic impact of preoperative serum carcinoembryonic antigen and cancer antigen 15-3 levels for early breast cancer subtypes

BackgroundAlthough the prognosis for operable breast cancers is reportedly worse if serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels are above normal, the usefulness of this prognosis is limited due to the low sensitivity and specificity; in addition, the optimal cutoff levels remain unknown.MethodsA total of 1076 patients who were operated for breast cancers (test set = 608, validation set = 468) without evidence of metastasis were recruited, and their baseline and postoperative serum CEA and CA15-3 levels were analyzed. The optimal cutoff values of CEA and CA15-3 for disease-free survival (DFS) were 3.2 ng/mL and 13.3 U/mL, respectively, based on receiver operating characteristic curve and area under the curve analyses.ResultsThe DFS of patients with high CEA levels (CEA-high: n = 191, 5-year DFS 70.6%) was significantly worse (p < 0.0001) than that of CEA-low patients (n = 885, 5-year DFS 87.2%). There was a significant difference in DFS (p < 0.0001) between CA15-3-high and CA15-3-low patients (n = 314 and n = 762, respectively; 5-year DFS 71.8 vs. 89.3%). Significant associations between DFS and CA15-3 levels were observed irrespective of the subtypes. Multivariable analysis indicated that tumor size, lymph node metastasis, tumor grade, and CEA (p = 0.0474) and CA15-3 (p < 0.0001) levels were independent prognostic factors (hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.005–2.245 for CEA; HR 2.088, 95% CI 1.457–2.901 for CA15-3).ConclusionsThese findings suggest that CEA and CA15-3 levels might be useful for predicting the prognosis of patients with operable early breast cancer irrespective of the subtype. Serum levels at baseline may reflect tumor characteristics for metastatic potential even when these levels are within the normal ranges.

Baseline carcinoembryonic antigen as a predictive factor of ramucirumab efficacy in RAISE, a second-line metastatic colorectal carcinoma phase III trial

BackgroundThe RAISE phase III clinical trial demonstrated that ramucirumab + (folinic acid plus 5-fluorouracil plus irinotecan) FOLFIRI significantly improved overall survival (OS) versus placebo + FOLFIRI for second-line metastatic colorectal carcinoma (mCRC) patients failing bevacizumab- and oxaliplatin-based chemotherapy (hazard ratio [HR] = 0.84, 95% CI = 0.73–0.98, P = 0.022). Post hoc analyses of RAISE patient data examined the association of carcinoembryonic antigen (CEA) subgroups with efficacy parameters. MethodsCEA subgroups (≤10 versus >10 ng/ml) were based on 2X upper limit of normal (ULN) (5 ng/ml). The Kaplan–Meier method estimated the median OS and the progression-free survival (PFS). Log-rank test compared the survival distributions within the subgroups. Hazard ratio (HR) (95% confidence interval [CI]) and treatment-by-subgroup interaction p-values were calculated by Cox proportional hazards model. ResultsRamucirumab treatment prolonged survival for the CEA ≤10 subgroup (HR = 0.68; 95% CI = 0.50–0.92; P = 0.013) and CEA >10 subgroup (HR = 0.90; 95% CI = 0.76–1.07; P = 0.233). However, the ramucirumab OS benefit over placebo was greater for the CEA ≤10 subgroup than for the CEA >10 subgroup (median OS: 3.6 versus 0.8 months greater, respectively). The interaction P-value between CEA level and treatment effect on OS was 0.088. This trend was observed across randomisation strata and to a lesser extent for PFS (P = 0.594). ConclusionsAlthough patients in both high- and low-CEA subgroups derive OS and PFS benefits from ramucirumab treatment, the low baseline CEA level may identify a subgroup of patients with mCRC who obtain greater benefit from ramucirumab.

Baseline and On-Treatment Markers Determining Prognosis of First-Line Chemotherapy in Combination with Bevacizumab in Patients with Metastatic Colorectal Cancer

Background: In metastatic colorectal cancer, no upfront or on-treatment markers are available to determine the prognosis or efficacy for chemotherapy in combination with bevacizumab. Patients and Methods: The current analysis was performed to evaluate the prognostic value of disease and patient characteristics (age, number of metastatic sites, stage of primary tumor, performance status, carcinoembryonic antigen (CEA)) and on-treatment changes of CEA (response after 8-12 weeks of treatment and specific patterns of CEA kinetics) in patients from an observational cohort study of chemotherapy with bevacizumab. Results: Baseline factors were available from 1,438 patients. Patients with baseline CEA levels > 20 ng/ml, more than 1 metastatic site, and age > 75 years showed significantly lower progression-free (PFS) and overall survival in multivariate analysis. A CEA response of > 30% during treatment was associated with increased PFS. In addition, the pattern of CEA kinetics predicts survival and response to treatment. Conclusion: In summary, baseline CEA, number of metastatic sites, and age are strong independent prognostic factors for survival. By monitoring CEA, clear patterns with distinct prognostic value can be determined. CEA kinetics and/or response after 8-12 weeks might be a useful and simple tool to stratify the post-induction treatment approach based on individual prognosis in the future.

P2.03b-094 Prognostic Value of Serum Carcinoembryonic Antigen during Conventional Chemotherapy in Advanced (Non-)Small Cell Lung Cancer: Topic: Biomarkers

Carcinoembryonic antigen (CEA) is used as a biomarker in colon carcinoma, however in patients with (non-)small cell lung cancer ((N)SCLC) increased serum CEA levels are commonly found. Since decline of high CEA levels in colon carcinoma is predictive for objective response, it is hypothesized that (N)SCLC is also associated with increased CEA concentrations and decreases in CEA levels have prognostic value for therapy response. In this retrospective observational study, changes in CEA levels during first-line conventional chemotherapy were studied in 194 patients with advanced (N)SCLC. CEA data prior to treatment (baseline), on week 3, 6 and 12 were correlated with radiologic objective response, defined as partial or complete response according to RECIST 1.1, overall survival (OS) and presence or occurrence of brain metastases. In total, 122 patients (62.9%) receiving standard chemotherapy between 2012-2016 had elevated baseline CEA levels (>5 ng/mL) with overall radiologic response on week 12 of 27.0% (objective response patients without elevated baseline CEA 15.3%). Within these patients, statistically significant correlations were observed between CEA response (20% decline over baseline level) on week 6 and radiologic objective response on week 12 (OR=4.3, CI=1.8-11.1, p<0.001), resulting in a positive and negative predictive value of CEA levels of 65.9% and 69.5% respectively. When adjusted for tumor histology, significant differences in objective response were found in week 12 (NSCLC 15.2% vs SCLC 41.0%, p=0.001) and in patients with elevated baseline CEA (NSCLC 21.7% vs SCLC 43.3%, p=0.032). Statistically significant associations were found between CEA responses on week 6 and objective response on week 6 (OR=4.3, CI=1.8-11.1, p<0.001, adjusted OR=3.9) and CEA responses on week 3 and objective response on week 6 (OR=3.3, CI=1.3-8.5, p=0.007, adjusted OR=2.6). Median survival was 567 days, without significant differences according to CEA levels at diagnosis. No statistically significant associations were found between CEA responses on week 3, 6 and 12 and OS. High CEA concentrations at baseline were not associated with brain metastases at diagnosis or diagnosed within 3 months, even when adjusted for tumor histology. This is one of the first studies in advanced lung cancer which describes that CEA levels appear to be closely associated with objective response. These results show that CEA could be a predictive marker for chemotherapy efficacy in patients with advanced (N)SCLC. Further research to reveal whether CEA decline also predicts response in (N)SCLC patients undergoing novel targeted therapies or immunotherapy is ongoing.

Relevance of CEA and LDH in relation to KRAS status in patients with unresectable colorectal liver metastases

While the significance of carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH), and Kirsten rat sarcoma (KRAS) status as individual prognostic factors for patients with metastatic colorectal cancer has been addressed, the relationship and interdependence between these prognostic factors on survival is limited. Patients with unresectable colorectal liver metastases with known KRAS status, and with baseline CEA and LDH levels who were treated with hepatic arterial infusion and systemic chemotherapy were identified. Patients were divided into two groups: hepatic-only disease and extra-hepatic disease. A total of 193 patients were included: 121 with hepatic-only and 72 with extra-hepatic disease. In the hepatic-only group, median overall survival (OS) was 55 months. On multivariate analysis, KRAS mutated tumors (HR 1.7, P < 0.05), LDH >200 U/L (HR 2.0, P < 0.05), and prior chemotherapy (HR 2.1, P < 0.05) had lower OS. In patients with extra-hepatic disease, median OS was 32 months. On multivariate analysis, baseline CEA >200 ng/mL (HR 2.1, P = 0.051), LDH >200 U/L (HR 3.8, P < 0.05), and right-sided tumors (HR 2.8, P < 0.05) had lower OS. This analysis verifies two distinct patterns in terms of biomarkers in patients with unresectable colorectal liver metastases. In patients with hepatic-only disease, KRAS mutation and elevated LDH negatively influenced survival. In patients with extra-hepatic disease, elevated LDH negatively impacted survival.