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Tsukamoto R, Sugimoto K, Ii Y, Irie T, Kawaguchi M, Kobari A, Tsuchiya Y, Honjo K, Kawai M, Ishiyama S, Takahashi M, Sakamoto K. Prognostic Impact of the Postoperative Carcinoembryonic Antigen Level after Curative Resection of Locally Advanced Rectal Cancer. J Anus Rectum Colon 2025; 9:69-78. [PMID: 39882227 PMCID: PMC11772802 DOI: 10.23922/jarc.2024-035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 10/03/2024] [Indexed: 01/31/2025] Open
Abstract
Objectives This study was conducted to investigate whether preoperative or postoperative carcinoembryonic antigen (CEA) with a new cut-off value is more optimal for predicting long-term outcomes in patients with Stage II/III rectal cancer, and to investigate the effectiveness of postoperative adjuvant chemotherapy (POAC) based on the CEA values. Methods Serum CEA levels were measured preoperatively (pre-CEA) and postoperatively (post-CEA). The area under the receiver operating curve (AUROC) was used to determine a cut-off for CEA. The cut-off for CEA relative to recurrence-free survival (RFS) was established as that giving the highest AUROC. In comparison of superiority between pre- and post- CEA levels, Akaike's information criterion (AIC) was used in the Cox proportional-hazard regression model. Results The subjects were 323 patients who underwent curative surgical treatment for Stage II/III rectal cancer. AIC values indicated that RFS was better stratified by a post-CEA level with a cut-off of 2.3 ng/ml compared with other classifications of pre- or post- CEA. In Stage III or high-risk Stage II cases, there was no effect of POAC on RFS in those with post-CEA <2.3 ng/ml (p=0.39), but in those with post-CEA ≥2.3 ng/ml there was a trend for better RFS in patients who received POAC compared to those without POAC (p=0.06). Conclusions Patients with post-CEA ≥2.3 ng/ml had worse long-term outcomes compared with those with post-CEA <2.3 ng/ml. Post-CEA with a cut-off of 2.3 ng/ml may be useful in determining the indication for POAC for in Stage III or high-risk Stage II cases.
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Affiliation(s)
- Ryoichi Tsukamoto
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Kiichi Sugimoto
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Yuki Ii
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Takahiro Irie
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Megumi Kawaguchi
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Aya Kobari
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Yuki Tsuchiya
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Kumpei Honjo
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Masaya Kawai
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Shun Ishiyama
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Makoto Takahashi
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Kazuhiro Sakamoto
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
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Momose H, Sugimoto K, Irie T, Nomura S, Ro H, Ishiyama S, Takahashi M, Pisanic T, Sakamoto K. Prognostic utility of circulating tumor DNA methylation analysis in stage IV colorectal cancer. J Surg Oncol 2024. [PMID: 39155651 DOI: 10.1002/jso.27824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 06/14/2024] [Indexed: 08/20/2024]
Abstract
BACKGROUND AND OBJECTIVES Our aim in this study was to investigate the usefulness of circulating tumor (ct) DNA methylation analysis for predicting long-term outcomes after resection in Stage IV colorectal cancer (CRC). METHODS Methylation analyses were performed on 95 plasma samples from patients with CRC who underwent surgery. The methylation status (relative methylation value: RMV) of CpG within the promoter region of three genes (CHFR, SOX11, and CDO1) was assessed to quantitative methylation-specific PCR (qMSP) analysis. RESULTS In the patients who had undergone resection of the primary tumor and metastatic organs with curative intent, the CHFR-RMV high group had significantly worse recurrence-free survival (RFS) compared with the CHFR-RMV low group (p = 0.001). Multivariate analysis revealed that CHFR-RMV was a significant independent prognostic factor (hazard ratio = 2.63 (1.29-5.36); p = 0.008). In the patients who had undergone resection of the primary tumor with metastatic organs with curative intent after neoadjuvant systemic chemotherapy, the SOX11-RMV high group had significantly worse RFS compared with the SOX11-RMV low group (p = 0.004). CONCLUSIONS The current study showed the usefulness of ctDNA methylation analysis for predicting the possibility of curative resection and long-term outcomes after resection in Stage IV CRC. A future prospective study is needed to obtain more conclusive results.
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Affiliation(s)
- Hirotaka Momose
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Kiichi Sugimoto
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Takahiro Irie
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Sachio Nomura
- Department of Pathology and Oncology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Hisashi Ro
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Shun Ishiyama
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Makoto Takahashi
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Thomas Pisanic
- Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Kazuhiro Sakamoto
- Department of Coloproctological Surgery, Juntendo University Faculty of Medicine, Tokyo, Japan
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Kang S, Kim SY, Hong YS, Kim TW, Choi KE, Kim MJ, Kim JE. CEA dynamics for predicting response after anti-EGFR monoclonal antibody treatment in metastatic colorectal cancer. Sci Rep 2023; 13:6735. [PMID: 37185297 PMCID: PMC10130020 DOI: 10.1038/s41598-023-33811-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 04/19/2023] [Indexed: 05/17/2023] Open
Abstract
Carcinoembryonic antigen (CEA) is the most widely used tumor marker in metastatic colorectal cancer (mCRC). However, its potential as a predictive marker of progression in mCRC during systemic chemotherapy, particularly in patients receiving monoclonal antibodies as a combination therapy, has remained of interest. Herein, we investigated whether CEA changes could predict disease progression and clinical outcomes in patients with mCRC cotreated with systemic chemotherapy and/or biologic agents. A total of 1261 patients with mCRC undergoing a first-line systemic treatment were included in this retrospective study. We analyzed the optimal cut-off value for CEA changes to predict progression at the first response evaluation by the treatment arm (chemotherapy alone, chemotherapy plus anti-vascular endothelial growth factor (VEGF) monoclonal antibody [mAb], and chemotherapy plus anti-epidermal growth factor receptor [EGFR] mAb). These cut-off values were then used to predict overall survival (OS) and progression-free survival (PFS). When stratified by their treatment arm, 891 (70.6%), 266 (21.0%), and 104 (8.2%) of the study patients were included in the chemotherapy alone-, anti-VEGF mAb, and anti-EGFR mAb groups, respectively. The optimal CEA cut-off values were 16.5% and 38.9% increase in the whole cohort and anti-EGFR mAb group, respectively, and these values showed high sensitivity and specificity for predicting disease progression. The patients in the entire population and anti-EGFR mAb group with CEA changes below these cut-off values showed significantly better OS and PFS outcomes compared those whose changes were above cut-off values. Among the patients with mCRC treated with anti-VEGF mAb, no associations were found between OS or PFS outcomes and CEA changes. CEA is potentially a good surrogate marker for predicting disease progression and survival outcomes in patients with mCRC receiving first-line systemic chemotherapy alone or chemotherapy with anti-EGFR mAb, whereas it is less effective in those treated with anti-VEGF mAb.
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Affiliation(s)
- Sora Kang
- Department of Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
- Division of Hemato-Oncology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, South Korea
| | - Sun Young Kim
- Department of Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Yong Sang Hong
- Department of Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Tae Won Kim
- Department of Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Ki Eun Choi
- Department of Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Min Jung Kim
- Department of Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Jeong Eun Kim
- Department of Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.
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Guo M, Jin N, Pawlik T, Cloyd JM. Neoadjuvant chemotherapy for colorectal liver metastases: A contemporary review of the literature. World J Gastrointest Oncol 2021; 13:1043-1061. [PMID: 34616511 PMCID: PMC8465453 DOI: 10.4251/wjgo.v13.i9.1043] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/17/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023] Open
Abstract
Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide, and up to 50% of patients with CRC develop colorectal liver metastases (CRLM). For these patients, surgical resection remains the only opportunity for cure and long-term survival. Over the past few decades, outcomes of patients with metastatic CRC have improved significantly due to advances in systemic therapy, as well as improvements in operative technique and perioperative care. Chemotherapy in the modern era of oxaliplatin- and irinotecan-containing regimens has been augmented by the introduction of targeted biologics and immunotherapeutic agents. The increasing efficacy of contemporary systemic therapies has led to an expansion in the proportion of patients eligible for curative-intent surgery. Consequently, the use of neoadjuvant strategies is becoming progressively more established. For patients with CRLM, the primary advantage of neoadjuvant chemotherapy (NCT) is the potential to down-stage metastatic disease in order to facilitate hepatic resection. On the other hand, the routine use of NCT for patients with resectable metastases remains controversial, especially given the potential risk of inducing chemotherapy-associated liver injury prior to hepatectomy. Current guidelines recommend upfront surgery in patients with initially resectable disease and low operative risk, reserving NCT for patients with borderline resectable or unresectable disease and high operative risk. Patients undergoing NCT require close monitoring for tumor response and conversion of CRLM to resectability. In light of the growing number of treatment options available to patients with metastatic CRC, it is generally agreed that these patients are best served at tertiary centers with an expert multidisciplinary team.
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Affiliation(s)
- Marissa Guo
- Department of Surgery, The Ohio State University Medical Center, Columbus, OH 43210, United States
| | - Ning Jin
- Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, United States
| | - Timothy Pawlik
- Department of Surgery, The Ohio State University, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Medical Center, Columbus, OH 43210, United States
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Gulhati P, Yin J, Pederson L, Schmoll HJ, Hoff P, Douillard JY, Hecht JR, Tournigand C, Tebbut N, Chibaudel B, Gramont AD, Shi Q, Overman MJ. Threshold Change in CEA as a Predictor of Non-Progression to First-Line Systemic Therapy in Metastatic Colorectal Cancer Patients With Elevated CEA. J Natl Cancer Inst 2021; 112:1127-1136. [PMID: 32191317 DOI: 10.1093/jnci/djaa020] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Revised: 12/17/2019] [Accepted: 01/28/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) levels are used in conjunction with imaging to monitor response to systemic therapy in metastatic colorectal cancer (mCRC). We sought to identify a threshold for CEA change from baseline to predict progressive disease (PD) in mCRC patients receiving first-line therapy. METHODS Patients from trials collected in the ARCAD database were included if baseline CEA was at least 10 ng/mL and repeat CEA was available within 14 days of first restaging scan. Optimal cutoffs for CEA change were identified by receiver operating characteristic analysis. Prediction performance of cutoffs was evaluated by sensitivity, specificity, and negative predictive value. Analyses were conducted by treatment class: chemotherapy alone, chemotherapy with anti-VEGF antibody, and chemotherapy with anti-EGFR antibody. RESULTS A total of 2643 mCRC patients treated with systemic therapy were included. Median percent change of CEA from baseline to first restaging for patients with complete response, partial response, or stable disease (non-PD) and PD was -53.1% and +23.6% for chemotherapy alone (n = 957) and -71.7% and -45.3% for chemotherapy with anti-VEGF antibody (n = 1355). The optimal area under the curve cutoff for differentiating PD from non-PD on first restaging was -7.5% for chemotherapy alone and -62.0% for chemotherapy with anti-VEGF antibody; chemotherapy alone, adjusted odds ratio = 6.51 (95% CI = 3.31 to 12.83, P < .001), chemotherapy with anti-VEGF antibody, adjusted odds ratio = 3.45 (95% CI = 1.93 to 6.18, P < .001). A 99% negative predictive value clinical cutoff for prediction of non-PD would avoid CT scan at first restaging in 21.0% of chemotherapy alone and 16.2% of chemotherapy with anti-VEGF antibody-treated patients. Among patients with stable disease on first restaging, those with decreased CEA from baseline had statistically significantly improved progression-free and overall survival. CONCLUSIONS Change in CEA from baseline to first restaging can accurately predict non-progression and correlates with long-term outcomes in patients receiving systemic chemotherapy.
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Affiliation(s)
- Pat Gulhati
- Department of Medical Oncology, Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA
| | - Jun Yin
- Department of Health Science Research, Mayo Clinic, Rochester, MN, USA
| | - Levi Pederson
- Department of Health Science Research, Mayo Clinic, Rochester, MN, USA
| | | | - Paulo Hoff
- Centro de Oncologia de Brasilia do Sirio Libanes-Unidade Lago Sul, Sao Paulo, Brazil
| | - Jean-Yves Douillard
- Integrated Centres for Oncology, Department of Medical Oncology, St-Herblain, France
| | - J Randolph Hecht
- David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | | | - Niall Tebbut
- Department of Oncology, Olivia Newton John Cancer Research Institute, Heidelberg, VIC, Australia
| | | | | | - Qian Shi
- Department of Health Science Research, Mayo Clinic, Rochester, MN, USA
| | - Michael James Overman
- Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Colloca GA, Venturino A, Guarneri D. Carcinoembryonic antigen reduction after medical treatment in patients with metastatic colorectal cancer: a systematic review and meta-analysis. Int J Colorectal Dis 2019; 34:657-666. [PMID: 30671635 DOI: 10.1007/s00384-018-03230-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/27/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE The introduction of new drugs and multimodal treatments for the management of patients with metastatic colorectal cancer (mCRC) has reduced the importance of time-to-event endpoints and reported the attention on the response-related endpoints. Furthermore, the prognostic role of the surgical scores before the resection of metastases has not been confirmed for multimodal treatments. The purpose of this research is to perform a meta-analysis of the studies that evaluated the relationship between carcinoembryonic antigen (CEA) response and outcome in patients with mCRC receiving systemic chemotherapy. METHODS A systematic review of the literature on two databases and a selection of studies that evaluated the relationship between CEA response and outcome were performed according to predefined criteria. After, three meta-analyses were carried out on the selected studies, each for each outcome variable. RESULTS Nineteen studies have been selected. Fourteen studies (1475 patients) have documented a close association between radiological response and CEA response (odds ratio (OR), 9.03; confidence intervals (CIs), 5.14-15.87; I2 statistic (I2), 72%). Four studies have reported a longer progression-free survival for patients with a CEA response (hazard ratio (HR), 0.73; CIs, 0.64-0.83; I2, 23%). Finally, 10 studies (13 study cohorts) have shown a strong relationship between CEA response and overall survival (OS) (HR, 0. 62; CIs, 0.55-0.70; I2, 35%). CONCLUSIONS CEA response merits further investigation as a surrogate endpoint of clinical trials of first-line medical therapy of patients with mCRC, and should be studied as a prognostic factor for those patients who are candidates for multimodal treatment strategies.
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Affiliation(s)
- Giuseppe Antonio Colloca
- Department of Oncology, Ospedale Civile di Sanremo, Via G. Borea n. 56, I-18038, Sanremo (Imperia), Italy.
| | - Antonella Venturino
- Department of Oncology, Ospedale Civile di Sanremo, Via G. Borea n. 56, I-18038, Sanremo (Imperia), Italy
| | - Domenico Guarneri
- Department of Oncology, Ospedale Civile di Sanremo, Via G. Borea n. 56, I-18038, Sanremo (Imperia), Italy
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The dynamic monitoring of CEA in response to chemotherapy and prognosis of mCRC patients. BMC Cancer 2018; 18:1076. [PMID: 30404612 PMCID: PMC6223053 DOI: 10.1186/s12885-018-4987-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 10/23/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The role of carcinoembryonic antigen (CEA) change patterns in tumor response and long-term outcome is unclear. This study aimed to investigate the correlation between changes in CEA levels and tumor response as a potential prognostic model. METHODS CEA levels were determined from baseline to progression. A χ2 test was used to assess the correlation between CEA changes and tumor response. Univariate and multivariate COX models were used to explore the correlation of CEA changes to progression-free survival (PFS) and overall survival (OS). RESULTS All 114 patients were divided into five groups according to CEA change pattern (A: patients had an initial fast CEA decrease that then turned into a slow increase; B: patients had an initial slow CEA decrease that then turned to a slow increase; C: patients had a continually slow CEA increase; D: patients had a continually fast CEA increase; E: patients had an initial fast CEA decrease that then turned into a fast increase). Patients in Group A had the longest OS and PFS while Group E patients had the shortest OS. Baseline to week 12 and week 12 to week 18 change rates were consistent with tumor response and progression, respectively. An increase in CEA level by ≥2.7% from week 12 to 18 was an independent negative prognostic factor of OS. CONCLUSIONS CEA changes mirror the tumor response to first-line chemotherapy and are associated with prognosis. CEA monitoring may be a substitute for computed tomography during the CEA stable period of treatment.
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Tong G, Xu W, Zhang G, Liu J, Zheng Z, Chen Y, Niu P, Xu X. The role of tissue and serum carcinoembryonic antigen in stages I to III of colorectal cancer-A retrospective cohort study. Cancer Med 2018; 7:5327-5338. [PMID: 30302946 PMCID: PMC6246925 DOI: 10.1002/cam4.1814] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Revised: 07/30/2018] [Accepted: 09/10/2018] [Indexed: 12/21/2022] Open
Abstract
PURPOSE Tissue carcinoembryonic antigen (t-CEA) and serum carcinoembryonic antigen (s-CEA) expression profiles are the most useful tumor markers for the diagnosis and evaluation of colorectal cancer (CRC) worldwide; however, their roles in CRC progression remain controversial. This study aimed to compare the prognostic values of both s-CEA and t-CEA in CRC. METHODS A total of 517 patients from January 2006 to December 2010 with stages I-III CRC were retrospectively examined, with 5-year postoperative follow-up and death as end-points. T-CEA expression, s-CEA expression, and clinical pathological parameters were inputted into the SPSS 21.0 software. The Kaplan-Meier method was used to analyze the 5-year disease-free survival (DFS) rate of patients in different tumor node metastasis (TNM) stages based on t-CEA and s-CEA expression. RESULTS Tumor differentiation and the number of positive lymph node harvests were significantly different among the t-CEA groups (P < 0.001, P = 0.002); however, clinicopathological features showed no significant difference. The groups with high s-CEA and t-CEA expression had a significantly poorer prognosis than those with low s-CEA (P = 0.021) and t-CEA (P < 0.01) expression, respectively. The multivariate analysis demonstrated that t-CEA was an independent prognostic factor in CRC (P < 0.001), but s-CEA was not (P = 0.339). The 5-year disease-free survival rates among the t-CEA groups were significantly different in stages I, II, and III of CRC (P = 0.001, P < 0.001, P < 0.001), whereas in the s-CEA groups, this difference was observed only in stage III (P = 0.014). CONCLUSION This study shows that postoperative t-CEA expression is an independent factor associated with poorer CRC prognosis and has a higher prognostic value than that of preoperative s-CEA expression.
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Affiliation(s)
- Guojun Tong
- Department of Colorectal SurgeryHuzhou Central HospitalZhejiangChina
- Central LaboratoryHuzhou Central HospitalZhejiangChina
| | - Wei Xu
- Pathological DepartmentHuzhou Central HospitalZhejiangChina
| | - Guiyang Zhang
- Department of Colorectal SurgeryHuzhou Central HospitalZhejiangChina
| | - Jian Liu
- Department of Colorectal SurgeryHuzhou Central HospitalZhejiangChina
| | - Zhaozheng Zheng
- Department of Colorectal SurgeryHuzhou Central HospitalZhejiangChina
| | - Yan Chen
- Department of Colorectal SurgeryHuzhou Central HospitalZhejiangChina
| | - Pingping Niu
- Central LaboratoryHuzhou Central HospitalZhejiangChina
| | - Xuting Xu
- Central LaboratoryHuzhou Central HospitalZhejiangChina
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Circulating Free Methylated Tumor DNA Markers for Sensitive Assessment of Tumor Burden and Early Response Monitoring in Patients Receiving Systemic Chemotherapy for Colorectal Cancer Liver Metastasis. Ann Surg 2018; 268:894-902. [PMID: 30080722 DOI: 10.1097/sla.0000000000002901] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Hermunen K, Lantto E, Poussa T, Haglund C, Österlund P. Can carcinoembryonic antigen replace computed tomography in response evaluation of metastatic colorectal cancer? Acta Oncol 2018; 57:750-758. [PMID: 29388498 DOI: 10.1080/0284186x.2018.1431400] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Response Evaluation Criteria in Solid Tumours (RECISTs 1.1) define computed tomography (CT) as the gold standard in response evaluation of patients with metastatic colorectal cancer (mCRC) who are undergoing chemotherapy. The aim of this study was to evaluate whether carcinoembryonic antigen (CEA), which is cheaper and easier to perform, can replace repeated CT. MATERIAL AND METHODS The study included 66 patients with non-resectable mCRC participating in a phase I-II study. CEA values were determined, and CT images were taken every 2 months. CT images were externally and retrospectively reviewed according to the RECIST 1.1 criteria. Different cut-off values for CEA change in percent (DeltaCEA%) compared with baseline or nadir value underwent testing to find patients with disease control (that is stable disease, partial or complete response) at 2, 4, 6 and 8 months, in order to identify those who could have continued with chemotherapy based on CEA values alone. CT verification is needed in progressive disease (PD), and therefore identifying PD patients was our secondary endpoint. RESULTS The results showed that by using a cut-off value of 0 for DeltaCEA%, disease control was seen in all patients at all measuring points (negative predictive value (NPV) = 1.0). Secondarily, increasing CEA was able to identify all PD patients (sensitivity (Se) = 1.0) and in 50-74% of the patients increasing CEA provided a lead time to PD on upcoming CT. It was possible to replace CT with CEA in all patients with decreasing CEA, meaning that 23-47% of CT scans could have been avoided at any given time point. CONCLUSION When the CEA level at a certain measuring point is the same or lower than CEA at baseline or at nadir (the measuring point with the lowest CEA value) during treatment, CEA can replace CT.
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Affiliation(s)
- Kethe Hermunen
- Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Eila Lantto
- Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | | | - Caj Haglund
- Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Programs Unit, Translational Cancer Biology Program, University of Helsinki, Helsinki, Finland
| | - Pia Österlund
- Faculty of Medicine and Life Sciences Tampere University and Department of Oncology, Tampere University Hospital, Tampere, Finland
- Department of Oncology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Ibrahim S, Raoul W, Lecomte T, Paintaud G, Ternant D. Pharmacokinetics partly explains the relationship between carcinoembryonic antigen level and survival of colorectal cancer patients treated with ramucirumab. Eur J Cancer 2018; 92:119-120. [PMID: 29329696 DOI: 10.1016/j.ejca.2017.12.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Accepted: 12/13/2017] [Indexed: 11/25/2022]
Affiliation(s)
- Sajida Ibrahim
- Université François-Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France
| | - William Raoul
- Université François-Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.
| | - Thierry Lecomte
- Université François-Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France; CHRU de Tours, Department of Hepato-Gastroenterology and Digestive Oncology, Tours, France
| | - Gilles Paintaud
- Université François-Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France; CHRU de Tours, Laboratory of Pharmacology-Toxicology, Tours, France
| | - David Ternant
- Université François-Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France; CHRU de Tours, Laboratory of Pharmacology-Toxicology, Tours, France
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Tsai H, Chang Y, Chu K, Chen C, Yeh Y, Ma C, Wu D, Kuo C, Chan H, Sheen M, Wang J. Carcinoembryonic Antigen in Monitoring of Response to Cetuximab plus FOLFIRI or FOLFOX-4 in Patients with Metastatic Colorectal Cancer. Int J Biol Markers 2018; 23:244-8. [DOI: 10.1177/172460080802300408] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
First-line treatment of metastatic colorectal cancer with combinations of cetuximab and irinotecan-based or oxaliplatin-based chemotherapy has shown promising efficacy. The clinical response to such treatment is generally assessed by tumor measurement through imaging. This study was performed to evaluate the correlation between serial changes in imaging results and carcinoembryonic antigen (CEA) levels. In 64 patients with metastatic colorectal cancer receiving cetuximab plus FOLFIRI or FOLFOX-4 chemotherapy we retrospectively analyzed the relationship between changes in serum CEA and changes in imaging results throughout the treatment course. Response in terms of serum CEA change was defined as a ≥50% drop in CEA level for more than 4 weeks. The sensitivity and specificity of serum CEA changes after targeted chemotherapy in relation to imaging results were 80.5% (33/41) and 73.9% (17/23), respectively, with a diagnostic accuracy of 78.1% (50/64). The progression-free survival time of responders assessed by serum CEA change was significantly longer than that of nonresponders (p=0.0091). Our results highlight the importance of serum CEA monitoring in assessing the response to targeted chemotherapy and in predicting the prognosis of patients with metastatic colorectal cancer.
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Affiliation(s)
- H.L. Tsai
- Department of Emergency Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung
- Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung
| | - Y.T. Chang
- Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung
| | - K.S. Chu
- Department of Anesthesia, Kaohsiung Medical University Hospital, Kaohsiung
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - C.F. Chen
- Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung
- Department of Surgery, Pingtung Hospital, Department of Health, Pingtung, Taiwan
| | - Y.S. Yeh
- Department of Emergency Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung
- Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung
| | - C.J. Ma
- Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung
| | - D.C. Wu
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
| | - C.H. Kuo
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
| | - H.M. Chan
- Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - M.C. Sheen
- Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - J.Y. Wang
- Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung - Taiwan
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Bevacizumab Pharmacokinetics Influence Overall and Progression-Free Survival in Metastatic Colorectal Cancer Patients. Clin Pharmacokinet 2017; 55:1381-1394. [PMID: 27312193 DOI: 10.1007/s40262-016-0406-3] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
OBJECTIVE Clinical response to bevacizumab varies between patients treated for metastatic colorectal cancer (mCRC). The aim of this study was to quantify individual factors affecting bevacizumab pharmacokinetic variability and assess the relationship between bevacizumab concentrations and clinical outcomes. METHODS Bevacizumab pharmacokinetics were assessed in 130 mCRC patients using a two-compartment pharmacokinetic population model. Overall and progression-free survival (PFS) were analyzed using Cox models. RESULTS The bevacizumab volume of distribution increased with height (p = 10-10) and was higher in patients with a 3/3 variable number tandem repeat of the FCGRT (Fc fragment of IgG receptor and transporter) gene (p = 0.039). The elimination rate constant increased with baseline carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF) concentrations, and was higher in patients with extra-hepatic metastases (p = 0.00029, 0.011, and 0.014). A bevacizumab trough concentration ≤15.5 mg/L was associated with both shorter overall survival and PFS (hazard ratio [95 % CI] 1.90 [1.20-2.99] and 1.76 [1.20-2.58], respectively). CONCLUSION High tumour burden is associated with low bevacizumab concentrations, and high bevacizumab concentration are associated with both decreased overall and progression-free survivals.
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Maffione AM, Rampin L, Blickman JG, Rubello D. Invited Editorial: Response to therapy assessment of colorectal liver metastasis. Eur J Radiol 2013; 82:903-4. [DOI: 10.1016/j.ejrad.2013.02.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2013] [Accepted: 02/25/2013] [Indexed: 11/29/2022]
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Kim G, Jung EJ, Ryu CG, Hwang DY. Usefulness of carcinoembryonic antigen for monitoring tumor progression during palliative chemotherapy in metastatic colorectal cancer. Yonsei Med J 2013; 54:116-22. [PMID: 23225807 PMCID: PMC3521272 DOI: 10.3349/ymj.2013.54.1.116] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
PURPOSE To evaluate the efficacy of carcinoembryonic antigen (CEA) measurement for monitoring tumor progression during palliative chemotherapy in metastatic colorectal cancer. MATERIALS AND METHODS Forty-eight patients with initially unresectable metastatic colorectal cancer (n=26, 54.2%) or recurrent unresectable metastatic colorectal cancer (n=22, 45.8%) received FOLFOX-4 chemotherapy for palliation. Serum CEA levels and carbohydrate antigen 19-9 levels were measured and computed tomography (CT) studies were performed prior to chemotherapy and after 3 cycles of chemotherapy. From the CT images, tumor responses were evaluated according to the Response Evaluation Criteria in Solid Tumors criteria and categorized as complete response, partial response, stable disease, and progressive disease. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of tumor marker assessments for determining tumor response were calculated. RESULTS The sensitivity, specificity and diagnostic accuracy of CEA assessment for prediction of disease progression were 50%, 77% and 69%, respectively. When the patients were dichotomized according to baseline CEA level, the initially elevated CEA group showed higher sensitivity and higher diagnostic accuracy compared to the initially normal CEA group (sensitivity=67% vs. 20%; diagnostic accuracy=71% vs. 62%). CONCLUSION CEA assessment could be useful for monitoring tumor progression during palliative chemotherapy in only patients with initially elevated CEA level.
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Affiliation(s)
- Gangmi Kim
- Department of Surgery, Konkuk University Medical Center, Seoul, Korea
| | - Eun-Joo Jung
- Department of Surgery, Konkuk University Medical Center, Seoul, Korea
| | - Chun-Geun Ryu
- Department of Surgery, Konkuk University Medical Center, Seoul, Korea
| | - Dae-Yong Hwang
- Department of Surgery, Konkuk University Medical Center, Seoul, Korea
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Song S, Hong JC, McDonnell SE, Koong AC, Minsky BD, Chang DT, Liauw SL. Combined modality therapy for rectal cancer: the relative value of posttreatment versus pretreatment CEA as a prognostic marker for disease recurrence. Ann Surg Oncol 2012; 19:2471-6. [PMID: 22327251 DOI: 10.1245/s10434-012-2266-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2011] [Indexed: 11/18/2022]
Abstract
PURPOSE To evaluate the prognostic significance of the first postsurgery carcinoembryonic antigen (CEA) level in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation (nCRT) and total mesorectal excision. METHODS A total of 100 patients underwent nCRT and had baseline and posttreatment CEA levels recorded within 6 months of surgery. The median radiotherapy dose was 50.4 Gy. Eighty-six patients received adjuvant 5-fluorouracil-based chemotherapy. Prognostic factors were analyzed for possible associations with freedom from failure (FFF) by univariate and multivariate analyses. Median follow-up was 30 months. RESULTS The median CEA (ng/ml) levels at baseline before nCRT, after nCRT, and after total mesorectal excision were 3.6, 1.7, and 1.3, respectively. Pathologic complete response was observed in 22%. FFF at 36 months was 78%. Local failure and distant failure occurred in 4 and 20% of the patients, respectively. On univariate analysis, pathologic complete response, margin status, and both pretreatment and postsurgery CEA levels were associated with recurrence (all P < 0.05). On multivariate analysis, pathologic complete response (P < 0.007), margin status (P < 0.001), and postsurgery CEA level (P = 0.003), but not baseline CEA level (P = 0.2), were found to be associated with recurrence. CONCLUSIONS After nCRT for rectal cancer, postsurgery CEA level may have more prognostic value than pretreatment level. Patients with a postsurgery CEA level of >2.5 ng/ml have higher rates of recurrence and may warrant closer surveillance.
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Affiliation(s)
- Suisui Song
- Department of Radiation and Cellular Oncology, The University of Chicago Hospitals, Chicago, IL, USA
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17
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Van Cutsem E, Dicato M, Arber N, Berlin J, Cervantes A, Ciardiello F, De Gramont A, Diaz-Rubio E, Ducreux M, Geva R, Glimelius B, Jones RG, Grothey A, Gruenberger T, Haller D, Haustermans K, Labianca R, Lenz H, Minsky B, Nordlinger B, Ohtsu A, Pavlidis N, Rougier P, Schmiegel W, Van de Velde C, Schmoll H, Sobrero A, Tabernero J. Molecular markers and biological targeted therapies in metastatic colorectal cancer: expert opinion and recommendations derived from the 11th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2009. Ann Oncol 2010; 21 Suppl 6:vi1-10. [DOI: 10.1093/annonc/mdq273] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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18
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de Haas RJ, Wicherts DA, Flores E, Ducreux M, Lévi F, Paule B, Azoulay D, Castaing D, Lemoine A, Adam R. Tumor marker evolution: comparison with imaging for assessment of response to chemotherapy in patients with colorectal liver metastases. Ann Surg Oncol 2010; 17:1010-23. [PMID: 20052553 PMCID: PMC2840671 DOI: 10.1245/s10434-009-0887-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2009] [Indexed: 01/01/2023]
Abstract
Background As the real clinical significance of carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA19.9) evolution during preoperative chemotherapy for colorectal liver metastases (CLM) is still unknown, we explored the correlation between biological and radiological response to chemotherapy, and their comparative impact on outcome after hepatectomy. Methods All patients resected for CLM at our hospital between 1990 and 2004 with the following eligibility criteria were included in the study: (1) preoperative chemotherapy, (2) complete resection of CLM, (3) no extrahepatic disease, and (4) elevated baseline tumor marker values. A 20% change of tumor marker levels while on chemotherapy was used to define biological response (decrease) or progression (increase). Correlation between biological and radiological response at computed tomography (CT) scan, and their impact on overall survival (OS) and progression-free survival (PFS) after hepatectomy were determined. Results Among 119 of 695 consecutive patients resected for CLM who fulfilled the inclusion criteria, serial CEA and CA19.9 were available in 113 and 68 patients, respectively. Of patients with radiological response or stabilization, 94% had similar biological evolution for CEA and 91% for CA19.9. In patients with radiological progression, similar biological evolution was observed in 95% of cases for CEA and in 64% for CA19.9. On multivariate analysis, radiological response (but not biological evolution) independently predicted OS. However, progression of CA19.9, but not radiological response, was an independent predictor of PFS. Conclusions In patients with CLM and elevated tumor markers, biological response is as accurate as CT imaging to assess “clinical” response to chemotherapy. With regards to PFS, CA19.9 evolution has even better prognostic value than does radiological response. Assessment of tumor markers could be sufficient to evaluate chemotherapy response in a nonsurgical setting, limiting the need of repeat imaging.
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Affiliation(s)
- Robbert J de Haas
- Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, Villejuif, France
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19
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Goldstein MJ, Mitchell EP. Carcinoembryonic Antigen in the Staging and Follow-up of Patients with Colorectal Cancer. Cancer Invest 2009; 23:338-51. [PMID: 16100946 DOI: 10.1081/cnv-58878] [Citation(s) in RCA: 288] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
CEA is a complex glycoprotein produced by 90% of colorectal cancers and contributes to the malignant characteristics of a tumor. It can be measured in serum quantitatively, and its level in plasma can be useful as a marker of disease. Because of its lack of sensitivity in the early stages of colorectal cancer, CEA measurement is an unsuitable modality for population screening. An elevated preoperative CEA is a poor prognostic sign and correlates with reduced overall survival after surgical resection of colorectal carcinoma. A failure of the CEA to return to normal levels after surgical resection is indicative of inadequate resection of occult systemic disease. Frequent monitoring of CEA postoperatively may allow identification of patients with metastatic disease for whom surgical resection or other localized therapy might be potentially beneficial. To identify this group, serial CEA measurement appears to be more effective than clinical evaluation or any other diagnostic modality, although its sensitivity for detecting recurrent disease is not as high for locoregional or pulmonary metastases as it is for liver metastases. Several studies have shown that a small percentage of patients followed postoperatively with CEA monitoring and who undergo CEA-directed salvage surgery for metastatic disease will be alive and disease-free 5 years after surgery. Furthermore, CEA levels after salvage surgery do appear to predict survival in patients undergoing resection of liver or pulmonary metastases. However, several authors argue that CEA surveillance is not cost-effective in terms of lives saved. In support of this argument, there is no clear difference in survival after resection of metastatic disease with curative intent between patients in whom the second-look surgery was performed on the basis of elevated CEA levels and those with other laboratory or imaging abnormalities. There is also no clear consensus on the frequency or duration of CEA monitoring, although the ASCO guidelines currently recommend every 2-3 months for at least 2 years after diagnosis. In the follow-up of patients undergoing palliative therapy, the CEA level correlates well with response, and CEA is indicative of not only response but may also identify patients with stable disease for whom there is also a demonstrated benefit in survival and symptom relief with combination chemotherapy. More recently, scintigraphic imaging after administration of radiolabeled antibodies afforded an important radionuclide technique that adds clinically significant information in assessing the extent and location of disease in patients with colorectal cancer above and beyond or complementary to conventional imaging modalities. Immunotherapy based on CEA is a rapidly advancing area of clinical research demonstrating antibody and T-cell responses.
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Affiliation(s)
- Mitchell J Goldstein
- Division of Neoplastic Diseases, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
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Hara M, Kanemitsu Y, Hirai T, Komori K, Kato T. Negative serum carcinoembryonic antigen has insufficient accuracy for excluding recurrence from patients with Dukes C colorectal cancer: analysis with likelihood ratio and posttest probability in a follow-up study. Dis Colon Rectum 2008; 51:1675-80. [PMID: 18633674 DOI: 10.1007/s10350-008-9406-1] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE This study was designed to determine the efficacy of carcinoembryonic antigen (CEA) monitoring for screening patients with colorectal cancer by using posttest probability of recurrence. METHODS For this study, 348 (preoperative serum CEA level elevated: CEA+, n = 119; or normal: CEA-, n = 229) patients who had undergone potentially curative surgery for colorectal cancer were enrolled. After five-year follow-up with measurements of serum CEA levels and imaging workup, posttest probabilities of recurrence were calculated. RESULTS Recurrence was observed in 39 percent of CEA+ patients and 30 percent in CEA- patients, and CEA levels were elevated in 33.3 percent of CEA+ patients and 17.5 percent of CEA- patients. With obtained sensitivity (68.4 percent, CEA+; 41 percent, CEA-), specificity (83 percent, CEA+; 91 percent, CEA-) and likelihood ratio (test positive: 4.0, CEA+; 4.4, CEA-; and test negative: 0.38, CEA+; 0.66, CEA-), posttest probability given the presence of CEA elevation in the CEA+ and CEA- was 72.2 and 65.5 percent, respectively, and that given the absence of CEA elevation was 20 and 22.2 percent, respectively. CONCLUSIONS Whereas postoperative CEA elevation indicates recurrence with high probability, a normal postoperative CEA is not useful for excluding the probability of recurrence.
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Affiliation(s)
- Masayasu Hara
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Japan
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21
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Liu L, Liao GQ, He P, Zhu H, Liu PH, Qu YM, Song XM, Xu QW, Gao Q, Zhang Y, Chen WF, Yin YH. Detection of circulating cancer cells in lung cancer patients with a panel of marker genes. Biochem Biophys Res Commun 2008; 372:756-60. [DOI: 10.1016/j.bbrc.2008.05.101] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2008] [Accepted: 05/20/2008] [Indexed: 11/29/2022]
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Nam JS, Shin JY, Kim KH, Park JI, Kim WW, Choi CS, Choi YG, Hong KH. Clinical Significance of Serum Carcinoembryonic Antigen (CEA) Level at Diagnosis of Liver Metastases in Patients with Colorectal Cancer. JOURNAL OF THE KOREAN SOCIETY OF COLOPROCTOLOGY 2008. [DOI: 10.3393/jksc.2008.24.6.439] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Affiliation(s)
- Jung-Su Nam
- Department of Surgery, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea
| | - Jin-Yong Shin
- Department of Surgery, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea
| | - Kyoung-Ha Kim
- Department of Surgery, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea
| | - Jeong-Ik Park
- Department of Surgery, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea
| | - Woon-Won Kim
- Department of Surgery, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea
| | - Chang-Soo Choi
- Department of Surgery, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea
| | - Young-Gil Choi
- Department of Surgery, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea
| | - Kwan-Hee Hong
- Department of Surgery, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea
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Chiu CH, Shih YN, Tsai CM, Liou JL, Chen YM, Perng RP. Serum tumor markers as predictors for survival in advanced non-small cell lung cancer patients treated with gefitinib. Lung Cancer 2007; 57:213-21. [PMID: 17449138 DOI: 10.1016/j.lungcan.2007.02.016] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2006] [Revised: 12/21/2006] [Accepted: 02/21/2007] [Indexed: 11/29/2022]
Abstract
BACKGROUND Though the imaging-based response (IBR) is the most frequently used index of the therapeutic effect in cancer patients, an index based on serum tumor markers might prove to be useful, especially in patients without measurable tumors. METHODS Paired pre- and post-treatment serum tumor markers (CEA, CA-125, and CA-199) were measured in 89 of 100 registered non-small cell lung cancer (NSCLC) patients who received gefitinib. Correlation and agreement analyses between the IBR at the 8th week and the tumor marker response (TMR) at the 4th or the 8th week were performed in patients with measurable lesions (n=68). Analysis of survival in relation to TMR was performed in all patients and in patients with no measurable lesions (n=21). RESULTS IBR was closely correlated with individual tumor marker responses and the response of all 3 markers combined at 4 weeks (P values ranged from <0.001 to 0.002). The agreements were also significant (P values ranged from 0.001 to 0.004). In the whole group, 4-week TMR was predictive for progression-free survival (P values ranged from <0.0001 to 0.0086). In patients without measurable lesions, differences in progression-free survival and overall survival were closely correlated with the 4-week CA-125 response, CA-199 response, and TMR(overall) (P values ranged from 0.0002 to 0.0399). However, the correlation between the 8-week TMR and either IBR or survival was not significant. CONCLUSIONS In gefitinib-treated NSCLC patients, correlation was good between 4-week TMR and IBR. Four-week TMR was predictive for survival. TMR may serve as a tool for assessing the gefitinib response in patients without measurable lesions.
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Affiliation(s)
- Chao-Hua Chiu
- Section of Thoracic Oncology, Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
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Wang WS, Lin JK, Lin TC, Chiou TJ, Liu JH, Yen CC, Chen PM. Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma. World J Gastroenterol 2005; 11:2166-70. [PMID: 15810086 PMCID: PMC4305789 DOI: 10.3748/wjg.v11.i14.2166] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer.
METHODS: A total of 86 patients with histologically confirmed metastatic colorectal cancers receiving treatment at Taipei Veterans General Hospital were enrolled. All patients had measurable metastatic lesions and life expectancies of more than 3 mo. Plasma vWF levels were measured by immuno-turbidimetric assay and compared with results from 40 non-metastatic colorectal cancer patients and 22 healthy controls. Patients with metastatic colorectal cancer were divided into two groups according to serum vWF levels and the differences between these two groups were analyzed using χ2 test. Data on age, gender, performance status, location of primary tumor, extent of metastasis, site of metastases, histological differentiation, serum CEA and plasma vWF levels were analyzed to determine association with survival. Survival curves were constructed by Kaplan-Meier product limit method and the data was analyzed using log-rank test on a microcomputer. Multivariate analysis using the Cox’s proportional hazards regression model was then performed to determine the independent prognostic indicators among all of the possible variables.
RESULTS: Colorectal cancer patients were identified as having significantly higher plasma vWF concentrations than healthy controls (P<0.05). Moreover, higher vWF plasma levels were associated with advanced tumor stage (P<0.05) and the presence of multiple metastases (P = 0.014). Patients with lower vWF plasma levels (≤160%) survived significantly longer than those with a higher plasma vWF level (log-rank test, P = 0.0043). By multivariate analysis, plasma vWF levels (P<0.001), the extent of metastasis (P = 0.012), and the performance status (P = 0.014) were identified as independent prognostic factors.
CONCLUSION: Our data indicates that high plasma vWF concentrations correlate with advanced diseases and significantly poor prognosis of patients with metastatic colorectal carcinoma. It may serve as a potential biological marker of disease progression in these patients.
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Affiliation(s)
- Wei-Shu Wang
- Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan, China
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Sørbye H, Dahl O. Transient CEA increase at start of oxaliplatin combination therapy for metastatic colorectal cancer. Acta Oncol 2004; 43:495-8. [PMID: 15360055 DOI: 10.1080/02841860410032380] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
In general a rising carcinoembryonic antigen (CEA) level means tumor progression. We observed a transient increase in CEA level despite objective response among patients receiving chemotherapy for metastatic colorectal cancer. This surge phenomenon has not previously been described for patients with metastatic colorectal disease. CEA was measured every second week in 27 patients receiving oxaliplatin, 5-fluororuracil, and folinic acid as first-line therapy against metastatic colorectal cancer. Four patients (15%, 95% CI 5-31%) met the criteria for therapy-induced CEA surge. The time of reaching maximum CEA level varied from 13 to 56 days. Median rise in CEA from baseline was 263% (range 24-632%). An initial rise of CEA during chemotherapy in colorectal cancer patients may therefore not always indicate progression of disease but may be a transient CEA surge in patients responding to chemotherapy.
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Affiliation(s)
- Halfdan Sørbye
- Department of Oncology and Section of Oncology, Institute of Medicine, Haukeland University Hospital, Norway.
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26
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Chen LT, Whang-Peng J. Current Status of Clinical Studies for Colorectal Cancer in Taiwan. Clin Colorectal Cancer 2004; 4:196-203. [PMID: 15377403 DOI: 10.3816/ccc.2004.n.020] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The incidence and age-adjusted mortality of colorectal cancer (CRC) has drastically increased in the past 2 decades in Taiwan. Fortunately, chemotherapy for metastatic CRC also showed improvement in terms of tumor response rate and survival in the corresponding time period. For its low toxicity profile and high objective response rate (17.5%-31.9% in patients who received low-dose 5-fluorouracil [5-FU] that failed and 53.3%-61.5% in patients who were chemotherapy-naive), weekly 24-hour infusion of high-dose 5-FU and leucovorin (LV) has been a favorable regimen for advanced CRC for medical oncologists in Taiwan. Investigators also put their effort in exploring the mechanisms of high efficacy and low toxicity profile of this regimen, as well as the prognostic factors in predicting tumor response to this regimen. With the emergence of new, active compounds for metastatic CRC, a simple 2-hour infusion of oxaliplatin plus 46-hour infusion of 5-FU/LV every 2 weeks has become a favorable regimen, with an overall response rate (ORR) of 40%-50% and overall survival of 18.2 months in chemotherapy-naive patients. Conversely, there were also studies to suggest that biweekly oxaliplatin plus weekly or biweekly bolus 5-FU/LV was shown to achieve a comparable tumor response and survival in 5-FU-refractory metastatic CRC. In patients who had been treated with oxaliplatin plus infusional 5-FU/LV that failed, salvage biweekly irinotecan plus bolus and infusional 5-FU/LV could achieve an ORR of 22.2% with a median duration of response of 8 months. As for oral fluoropyrimidine analogues, oral tegafur/uracil and capecitabine are available in Taiwan. In addition, a clinical trial of dendritic cell-based immunotherapy for chemotherapy-refractory metastatic CRC has also been initiated and is in progress.
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Affiliation(s)
- Li-Tzong Chen
- Division of Cancer Research, National Health Research Institutes, Taipei, Taiwan
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