scholarly journals Serum carcinoembryonic antigen to predict recurrence in the follow-up of patients with colorectal cancer

2019 ◽  
Vol 34 (1) ◽  
pp. 60-68 ◽  
Author(s):  
Winesh Ramphal ◽  
Jeske R.E. Boeding ◽  
Maartje van Iwaarden ◽  
Jennifer M.J. Schreinemakers ◽  
Harm J.T. Rutten ◽  
...  

Introduction: Serum carcinoembryonic (CEA) antigen is used as a diagnostic screening tool during follow-up in colorectal cancer patients. However, it remains unclear whether preoperative serum CEA is a reliable marker in the follow-up to predict recurrence. The aim of the study is to determine the value of elevated pre- and postoperative serum carcinoembryonic antigen levels (CEA > 5 µg/L) as an independent prognostic factor for locoregional and distant recurrence in patients who underwent curative surgery for colorectal cancer. Methods: This single center retrospective observational cohort study includes patients who underwent curative surgery for colorectal cancer between 2005 and 2015 and had pre- and postoperative serum CEA measurements. Five-year disease-free survival and multivariate Cox regression analyses were performed to adjust for confounding factors. Results: Preoperative serum CEA level was measured in 2093 patients with colorectal cancer. No significant association was found between an elevated preoperative serum CEA and locoregional recurrence (adjusted hazard ratio (HR) 1.29 (95% confidence interval (CI) 0.91, 1.84; P=0.26)). However, a significant association was found between an elevated preoperative serum CEA and systemic recurrence (adjusted HR 1.58 (95% CI 1.25, 2.00; P<0.01)]. The five-year disease-free survival was lower in patients with elevated preoperative serum CEA levels ( P<0.01). Postoperative serum CEA level was the most sensitive for hepatic metastases during follow-up (73.3%). Conclusions: The preoperative serum CEA level is an independent prognostic factor for systemic metastasis after curative surgery for colorectal cancer in patients with stage I–III disease. The level is the most sensitive for hepatic metastasis compared to metastasis to other anatomic sites.

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22040-e22040
Author(s):  
H. J. Nielsen ◽  
N. Brünner ◽  
I. J. Christensen

e22040 Background: Introduction of independent prognostic markers may play a significant role in future treatment of early stage colorectal cancer (CRC). CEA is still the only recommended (ASCO and EGTM) serological marker in CRC. However, Tissue Inhibitor of Metallo Proteinases-1 (TIMP-1), which is a glycoprotein that acts as an inhibitor of most of the active matrix metalloproteinases, has previously been shown to carry independent prognostic information in patients with primary CRC. The purpose of the present study was to assess the combination of preoperative serum CEA and plasma TIMP-1as prognostic markers in patients undergoing resection for primary CRC. Methods: In the present prospective study serum and plasma samples were collected before surgery from 422 patients with primary CRC stage I-III. CEA was determined in serum by a commercial assay and TIMP-1 was determined in plasma using a thoroughly validated, in-house ELISA. Time to recurrence or death of CRC was registered and the association to serum CEA and plasma TIMP-1 levels were studied in a Cox multivariate model including age, gender, disease stage and tumor location. Hazard ratios and 95% confidence intervals (HR (95%CI)) for disease free survival (DFS) were calculated. Results: An event was recorded in 186 patients, 75 had local recurrence, 103 had a distant metastases (28 of these patients had both local recurrence and distant metastases) and 36 died from their cancer without a registered recurrence. Scoring CEA and TIMP-1 as continuous variables on a logarithmic scale (base 2), both serum CEA and plasma TIMP-1 were statistically significant in a multivariable analysis with HR=1.12 (1.03–1.21) and HR=1.51 (1.12–2.04), respectively. Additional calculations of low CEA plus low TIMP-1, high CEA plus low TIMP-1, low CEA plus high TIMP-1 and high CEA plus high TIMP-1 showed that high plasma TIMP-1 levels carried prominent information of poor prognosis independent of CEA. Conclusions: Preoperative serum CEA and plasma TIMP-1 levels were independent predictors of disease free survival for patients with primary CRC. Combination of the two proteins showed that TIMP-1 was a prominent predictor of poor DFS independent of CEA. [Table: see text]


2018 ◽  
Vol 103 (7-8) ◽  
pp. 322-330
Author(s):  
Harunobu Sato ◽  
Yoshikazu Koide ◽  
Miho Shiota ◽  
Hiroshi Takahashi ◽  
Zenichi Morise ◽  
...  

Objective: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the most common colorectal cancer markers. We aimed to identify the appropriate clinical conditions for measuring serum CEA and CA19-9 levels before surgery and during follow-up. Methods: This study included 1275 colorectal cancer patients who were divided into 3 groups according to preoperative CEA levels (group A, ≤5 ng/mL; group B, &gt;5–≤11 ng/mL; group C, &gt;11 ng/mL). Each group was subdivided into 2 groups according to preoperative CA19-9 levels (cutoff level: ≤37 U/mL). Recurrence and survival rates were analyzed. Results: Recurrence rate, disease-free survival after curative surgery, and prognosis were significantly worse in group A and B patients with high CA19-9 levels. At recurrence, CEA levels showed a greater increase in group B and C patients; CA19-9 levels increased in group A patients with high CA19-9 levels. At recurrence, high serum CA19-9 levels were observed in group A patients with high preoperative serum CA19-9 levels, even if the serum CEA level did not increase. Preoperative CA19-9 levels could predict recurrence and prognosis in groups A and B. Conclusion: Periodic CA19-9 determination is useful for monitoring recurrence among group A patients with high CA19-9 levels.


2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Sha Zhou ◽  
Jianhong Peng ◽  
Liuniu Xiao ◽  
Caixia Zhou ◽  
Yujing Fang ◽  
...  

AbstractResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.


2006 ◽  
Vol 72 (10) ◽  
pp. 875-879 ◽  
Author(s):  
Aziz Ahmad ◽  
Steven L. Chen ◽  
Maihgan A. Kavanagh ◽  
David P. Allegra ◽  
Anton J. Bilchik

Second-generation radiofrequency ablation (RFA) probes and their successors have more power, shorter ablation times, and an increased area of ablation compared with the first-generation probes used before 2000. We examined whether the use of the newer probes has improved the clinical outcome of RFA for hepatic metastases of colorectal cancer at our tertiary cancer center. Of 160 patients who underwent RFA between 1997 and 2003, 52 had metastases confined to the liver: 21 patients underwent 46 ablations with the first-generation probes and 31 patients underwent 58 ablations with the newer probes. The two groups had similar demographic characteristics. At a median follow-up of 26.2 months, patients treated with the newer probes had a longer median disease-free survival (16 months vs 8 months, P < 0.01) and a lower rate of margin recurrence (5.2% vs 17.4%); eight patients had no evidence of disease and one patient was alive with disease. By contrast, of the 46 patients treated with the first-generation probes, 2 patients had no evidence of disease and 1 patient was alive with disease. Newer-generation probes are associated with lower rates of margin recurrence and higher rates of disease-free survival after RFA of hepatic metastases from colorectal cancer.


2019 ◽  
Vol 47 (5) ◽  
pp. 1829-1842 ◽  
Author(s):  
Weimin Xu ◽  
Yilian Zhu ◽  
Wei Shen ◽  
Wenjun Ding ◽  
Tingyu Wu ◽  
...  

Objective Prognostic prediction of colorectal cancer (CRC) remains challenging because of its heterogeneity. Aberrant expression of caudal-type homeobox transcription factor 2 (CDX2) is strongly correlated with the prognosis of CRC. Methods Tissue samples of patients with CRC who underwent surgery in Xinhua Hospital (Shanghai, China) from January 2010 to January 2013 were collected. CDX2 expression was semiquantitatively evaluated via immunohistochemistry. Results In total, 138 patients were enrolled in this study from a prospectively maintained institutional cancer database. The median follow-up duration was 57.5 months (interquartile range, 17.0–71.0 months). In the Cox proportional hazards model, low CDX2 expression combined with stage T4 CRC was significantly the worst prognostic factor for disease-free survival (hazard ratio = 7.020, 95% confidence interval = 3.922–12.564) and overall survival (hazard ratio = 5.176, 95% CI = 3.237–10.091). In the Kaplan–Meier survival analysis, patients with low CDX2 expression and stage T4 CRC showed significantly worse disease-free survival and overall survival than those with low CDX2 expression alone. Conclusion CDX2 expression combined with the T stage was more accurate for predicting the prognosis of CRC. Determining the prognosis of CRC using more than one variable is valuable in developing appropriate treatment and follow-up strategies.


2016 ◽  
Vol 39 (6) ◽  
pp. 545-558 ◽  
Author(s):  
Elisabetta Bigagli ◽  
Carlotta De Filippo ◽  
Cinzia Castagnini ◽  
Simona Toti ◽  
Francesco Acquadro ◽  
...  

Author(s):  
Masatsune Shibutani ◽  
Kiyoshi Maeda ◽  
Hisashi Nagahara ◽  
Hiroshi Ohtani ◽  
Tetsuro Ikeya ◽  
...  

Abstract Objective: The aim of this retrospective study was to evaluate the prognostic significance of lymphopenia associated with chemotherapy in patients with colorectal cancer who received adjuvant chemotherapy after undergoing potentially curative surgery. Summary of background data: Lymphocyte plays an important role in anti-tumor immunity. Lymphopenia is sometimes induced during the period of adjuvant chemotherapy after potentially curative surgery for colorectal cancer. However, the prognostic significance of lymphopenia associated with chemotherapy is unknown. Methods: One hundred and fifteen patients who received adjuvant chemotherapy after potentially curative surgery for stage II/III colorectal cancer were enrolled in this study. All patients were classified into two groups, the lymphopenia group and the normal group, according to minimum lymphocyte count during the period of adjuvant chemotherapy. Lymphopenia was defined as a lymphocyte count of less than 1,000/Ã&#x8e;¼l. Lymphopenia associated with chemotherapy was found in 17 of the 115 patients (14.8%). Results: Lymphopenia was associated with a worse disease-free survival (p=0.018). Moreover, in a multivariate analysis, lymphopenia associated with chemotherapy was identified to be an independent prognostic factor.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15006-e15006
Author(s):  
E. Barrajon ◽  
A. Lopez ◽  
G. Esquerdo ◽  
J. M. Cervera

e15006 Background: The traditional end point for adjuvant clinical trials is overall survival (OS). Short-term disease-free survival (DFS) has been accepted as a surrogate of 5-year OS in colorectal cancer trials. Nevertheless, recent adjuvant trials have not shown a consistent improvement in OS despite a significant improvement in DFS. Two reasons may explain this effect: 1) a delay in relapse produced by treatment, not affecting the cure rate, or 2) more effective treatments in relapsing patients which delay death, hiding a real difference in cure rates. The aim of this project is to study the relationship between DFS and OS in trials of early colorectal cancer. Methods: Phase III comparative trials in colorectal cancer were searched in databases and cancer meetings. Trials were split to build and validate the model. United States 2000 population life table data were obtained from Berkeley Mortality Database. Survival curves were modelled according to a cured fraction following a Weibull distribution and a relapsing fraction following a binomial distribution. DFS was modelled as time to a single event and OS was modelled as time to two events. Cured fraction was estimated and odds ratio (OR) with 95% confidence interval was calculated for experimental arms. Time to achieve a plateau in DFS was estimated as the curve point with a risk of relapse below 1%. Regression analysis between DFS and OS was performed for different intervals of follow up. Results: Thirty six study arms reporting DFS were analyzed to build the model. The model is consistent with an annual event rate of 0.33. DFS curves with this event rate predict a mean cure rate of 0.58 (range: 0.11–0.73). Estimated time to achieve a plateau in DFS is 9.3 years (range: 8.3–11.2 years). Significance of OR is coherent with hazard ratio reported in the studies. Trials finished after 1999 show more OS related to DFS. Regression analysis between DFS and OS show changing parameters at different intervals of follow up and some non-linearities. Trial validation, and analysis with trials reporting relapse free survival will be presented. Conclusions: Follow up of up to 10 years in colon adjuvant trials appears to be appropriate to reliably detect benefit in OS instead of a delay effect on relapse. No significant financial relationships to disclose.


Tumor Biology ◽  
2019 ◽  
Vol 41 (6) ◽  
pp. 101042831984623 ◽  
Author(s):  
Elisabeth Odin ◽  
Arvid Sondén ◽  
Göran Carlsson ◽  
Bengt Gustavsson ◽  
Yvonne Wettergren

5-fluorouracil in combination with the folate leucovorin is the cornerstone in treatment of colorectal cancer. Transport of leucovorin into cells, and subsequent metabolic action, require expression of several genes. The aim was to analyze if tumoral expression of genes putatively involved in leucovorin transport, polyglutamation, or metabolism was associated with outcome of patients with stage III colorectal cancer treated with adjuvant chemotherapy. A total of 363 stage III colorectal cancer patients who received adjuvant bolus 5-fluorouracil + leucovorin alone, or in combination with oxaliplatin according to Nordic bolus regimes were included. Expression of 11 folate pathway genes was determined in tumors using quantitative real-time polymerase chain reaction and related to disease-free survival. The median follow-up time was 5 years. During follow-up, 114 (31%) patients suffered from recurrent disease. A high tumoral expression of the genes SLC46A1/PCFT, SLC19A1/RFC-1, ABCC3/MRP3, GGH, and MTHFD1L, which are involved in folate transport, polyglutamation, or metabolism, was associated with longer disease-free survival of the patients. Each of these genes either encodes mitochondrial enzymes or is being regulated by mitochondrial transcription factors. Expression of the SLC46A1/PCFT gene was most strongly associated with disease-free survival, regardless of treatment regimen. In conclusion, the results show that expression of folate pathway genes are associated with outcome of colorectal cancer patients treated with adjuvant 5-fluorouracil in combination with leucovorin. A prospective study needs to be conducted to determine if expression of these genes can be used to predict response to leucovorin and other folates that are now being tested in clinical studies. Moreover, there seems to be a link between folate metabolism and mitochondrial biogenesis and respiration that deserves further exploration.


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