|
1
|
Zanin L, Sachkova A, Panciani PP, Rohde V, Fontanella MM, Schatlo B. Liquid Biopsy in Low-Grade Glioma: A Systematic Review and a Proposal for a Clinical Utility Score. Cell Mol Neurobiol 2023; 43:3833-3845. [PMID: 37704931 PMCID: PMC10661806 DOI: 10.1007/s10571-023-01406-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 08/28/2023] [Indexed: 09/15/2023]
Abstract
Liquid biopsy research on Low-Grade gliomas (LGG) has remained less conspicuous than that on other malignant brain tumors. Reliable serum markers would be precious for diagnosis, follow- up and treatment. We propose a clinical utility score (CUS) for biomarkers in LGG that mirrors their clinical usefulness. We conducted a PRISMA review. We examined each biomarker classifying them by CUS and Level of Evidence (LOE). We identified four classes of biomarkers: (1). Circulating protein-(a) vitronectin discriminates LGG from HGG (Sn:98%, Sp:91%, CUS: 3, LOE: III), (b) CTLA-4 discriminates LGG from HGG, (cutoff: 220.43 pg/ml, Sn: 82%, Sp: 78%, CUS:3, LOE:III), (c) pre-operative TGF b1 predict astrocytoma (cutoff: 2.52 ng/ml, Sn: 94.9%, Sp: 100%, CUS:3, LOE:VI). (2). micro-RNA (miR)-(a) miR-16 discriminates between WHO IV and WHO II and III groups (AUC = 0.98, CUS:3, LOE: III), (b) miR-454-3p is higher in HGG than in LGG (p = 0.013, CUS:3, LOE: III), (c) miR-210 expression is related to WHO grades (Sn 83.2%, Sp 94.3%, CUS: 3, LOE: III). (3). Circulating DNA-(a) IDH1R132H mutation detected in plasma by combined COLD and digital PCR (Sn: 60%, Sp: 100%, CUS: 3, LOE: III). 4. Exosomes-(a) SDC1 serum levels could discriminate GBM from LGG (Sn: 71%, Sp: 91%, CUS: 2C, LOE: VI). Our investigation showed that miRs appear to have the highest clinical utility. The LOE of the studies assessed is generally low. A combined approach between different biomarkers and traditional diagnostics may be considered. We identified four main classes of biomarkers produced by LGG. We examined each biomarker, classifying them by clinical utility score (CUS) and level of evidence (LOE). Micro-RNA (miRs) appears to have the highest CUS and LOE.
Collapse
Affiliation(s)
- Luca Zanin
- Unit of Neurosurgery, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy
| | - Alexandra Sachkova
- Institute of Clinical Pharmacology, University Medical Center Göttingen, Georg-August University, 37075, Göttingen, Germany
| | - Pier Paolo Panciani
- Unit of Neurosurgery, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy.
| | - Veit Rohde
- Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany
| | - Marco Maria Fontanella
- Unit of Neurosurgery, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy
| | - Bawarjan Schatlo
- Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany
| |
Collapse
|
|
2
|
Ma X, Guan X, Ma C, Quan J, Zhao Z, Chen H, Huang H, Wei R, Liu Z, Jiang Z, Chen Y, Wang X. A novel risk stratification for predicting prognosis of colorectal cancer patients with bone metastasis. J Gastrointest Oncol 2021; 12:933-943. [PMID: 34295546 PMCID: PMC8261323 DOI: 10.21037/jgo-20-586] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 03/28/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Our understanding in prognosis of bone metastasis (BM) from colorectal cancer (CRC) is limited. We aimed to establish a clinical risk stratification for individually predicting the survival of CRC patients with BM. METHODS A total of 200 CRC patients with BM were included in this study. Survival time from BM diagnosis was estimated using the Kaplan-Meier method. The multivariable COX regression model identified the risk factors on cancer specific survival (CSS). Based on weighted scoring system, the stratification model was constructed to classify patients with BM according to prognostic risk. Discrimination power and calibration ability of risk stratification were measured. RESULTS The median CSS time was 11 months after BM diagnosis. Lymph node metastasis, Carbohydrate antigen 199 (CA199) levels, bone involvement, Karnofsky Performance Status (KPS) scores, primary tumor resection, bisphosphonates therapy and radiotherapy were identified as predictors of CSS. Four risk groups were stratified according to weighted scoring system, including low risk, medium risk, medium-high risk and high risk group, with 35, 16, 9 and 5 months of median CSS, respectively (P=0.000). The risk stratification displayed good accuracy in predicting CSS, with acceptable discrimination and calibration. CONCLUSIONS This novel risk stratification predicts CSS in CRC patient with BM using easily accessible clinicopathologic factors, which is recommended for use in individualized clinical decision making in patient with BM.
Collapse
Affiliation(s)
- Xiaolong Ma
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xu Guan
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chenxi Ma
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jichuan Quan
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhixun Zhao
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haipeng Chen
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haiyang Huang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ran Wei
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zheng Liu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zheng Jiang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yinggang Chen
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Xishan Wang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
3
|
Joo JI, Lim SW, Oh BY. Prognostic Impact of Carcinoembryonic Antigen Levels in Rectal Cancer Patients Who Had Received Neoadjuvant Chemoradiotherapy. Ann Coloproctol 2021; 37:179-185. [PMID: 33971705 PMCID: PMC8273711 DOI: 10.3393/ac.2020.11.27] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Accepted: 11/27/2020] [Indexed: 01/21/2023] Open
Abstract
PURPOSE Carcinoembryonic antigen (CEA) is a useful marker for rectal cancer. The aim of this study was to investigate the prognostic impact of CEA level according to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer patients who underwent radical surgery. METHODS A total of 245 patients with rectal cancer who underwent radical surgery were retrospectively evaluated. Serum CEA level was measured preoperatively and postoperatively. We compared survival outcomes based on CEA level before and after surgery according to nCRT. RESULTS Of the 245 patients, elevation of CEA level was observed preoperatively in 79 and postoperatively in 30, respectively. Eighty-seven (35.5%) patients received nCRT, and elevated CEA level was a significant prognostic factor both before and after surgery. In patients who had not received nCRT, an elevated CEA level was a significant prognostic factor before surgery but was not significant after surgery. In a multivariate analysis for prognostic factors, elevation of preoperative CEA level was an independent prognostic factor of disease-free survival (DFS) regardless of nCRT. Postoperative CEA level was an independent prognostic factor of DFS in patients who had received nCRT but was not a factor in patients who had not received nCRT. CONCLUSION Serum CEA level was an independent prognostic factor both preoperatively and postoperatively in rectal cancer patients who had received nCRT.
Collapse
Affiliation(s)
- Jung Il Joo
- Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Sang Woo Lim
- Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Bo Young Oh
- Department of Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| |
Collapse
|
|
4
|
Gao TM, Bai DS, Qian JJ, Zhang C, Jin SJ, Jiang GQ. Real-world clinical significance of nonbiological factors with staging, prognosis and clinical management in rectal cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 47:990-998. [PMID: 33046280 DOI: 10.1016/j.ejso.2020.10.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 08/03/2020] [Accepted: 10/05/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND The clinical guidance of the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging system is established only in biological factors and does not include nonbiological factors (NBFs). We assessed the clinical value of incorporating NBFs into the TNM staging system in point of the clinical management and prognostic prediction accuracy of rectal cancer. METHODS We used the Surveillance, Epidemiology and End Results (SEER) database and identified 12,515 patients with rectal cancer who were diagnosed between 1 January 2011 and 31 December 2015. Multivariate Cox proportional hazards regression analysis and Kaplan-Meier curves were used to determine the probabilities of cancer-specific survival (CSS) according to different TNM-NBF stages. RESULTS Multivariate Cox regression analysis showed that county percentage with a bachelor's degree, insurance status, unemployment status, and marital status were all significant prognostic NBFs (p < 0.05). The concordance index of TNM-NBF stages was 0.815 (95% confidence interval (CI) 0.8072-0.8228). Multivariate Cox analyses showed that, compared with NBF0-stage, NBF1-stage was contacted with a 54.5% increased risk of cancer-specific mortality in rectal cancer, which increased to 68.3% in non-metastatic rectal cancer (all p < 0.001). NBF0-stage showed a CSS benefit as compared with NBF1-stage (p < 0.001). CONCLUSIONS We found that NBF-stage was an independent prognostic factor for survival in rectal cancer. The influence of NBFs on survival in rectal cancer warrants greater clinical attention. Furthermore, the consolidation of NBF-stage into the TNM staging system is crucial to better prognostic prediction accuracy and individualized risk-adaptive therapies.
Collapse
Affiliation(s)
- Tian-Ming Gao
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, 225001, China; Department of Hepatobiliary Surgery, The Second Clinical College, Dalian Medical University, Dalian, 116044, China
| | - Dou-Sheng Bai
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, 225001, China
| | - Jian-Jun Qian
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, 225001, China
| | - Chi Zhang
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, 225001, China
| | - Sheng-Jie Jin
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, 225001, China
| | - Guo-Qing Jiang
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, 225001, China.
| |
Collapse
|
|
5
|
Baqar AR, Wilkins S, Staples M, Angus Lee CH, Oliva K, McMurrick P. The role of preoperative CEA in the management of colorectal cancer: A cohort study from two cancer centres. Int J Surg 2019; 64:10-15. [DOI: 10.1016/j.ijsu.2019.02.014] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Revised: 02/07/2019] [Accepted: 02/19/2019] [Indexed: 01/19/2023]
|
|
6
|
Hu H, Huang J, Lan P, Wang L, Huang M, Wang J, Deng Y. CEA clearance pattern as a predictor of tumor response to neoadjuvant treatment in rectal cancer: a post-hoc analysis of FOWARC trial. BMC Cancer 2018; 18:1145. [PMID: 30458734 PMCID: PMC6247708 DOI: 10.1186/s12885-018-4997-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Accepted: 10/25/2018] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND The clinical factors that accurately predict the response to preoperative treatment in rectal cancer were yet unknown. The carcinoembryonic antigen (CEA) clearance pattern during neoadjuvant treatment has been developed and the predictive value explored in rectal cancer patients with elevated CEA levels (> 5 ng/mL). METHODS The training cohort was derived from the FOWARC prospective phase III trial, and 71/483 eligible patients were included. The validation cohort consisted of 75/587 consecutive rectal cancer patients from Xiangya Hospital between 2014 and 2015. The kinetic changes in serum CEA were measured at different time points during the neoadjuvant treatment. An exponential trend line was drawn using the CEA values. The patients were categorized into two groups based on the R2 value of the trend line, which indicates the correlation coefficient between the exponential graph and measured CEA values: exponential decrease group (0.9 < R2 ≤ 1.0) and non-exponential decrease group (R2 ≤ 0.9). RESULTS In multivariate analysis, the patients in the CEA exponential decrease group had significantly high adequate rate of downstaging (ypT0-2N0M0), and pathologic complete response (pCR) rates after neoadjuvant treatment in the training cohort. The predictive values of the CEA clearance pattern for tumor downstaging and pCR were further confirmed in an independent validation cohort. CONCLUSIONS The CEA clearance pattern was an independent predictor of tumor response to neoadjuvant treatment in patients with rectal cancer. It might serve as an adjunct in the assessment of complete clinical response and guide individualized treatment strategies. TRIAL REGISTRATION NCT01211210.
Collapse
Affiliation(s)
- Huabin Hu
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Yuancunheng 2nd Road, Guangzhou, 510655, People's Republic of China
| | - Jin Huang
- Department of Oncology, Xiangya Hospital of Central South University, Changsha, China
| | - Ping Lan
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Yuancunheng 2nd Road, Guangzhou, 510655, People's Republic of China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, China
| | - Lei Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Yuancunheng 2nd Road, Guangzhou, 510655, People's Republic of China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, China
| | - Meijin Huang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Yuancunheng 2nd Road, Guangzhou, 510655, People's Republic of China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, China
| | - Jianping Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Yuancunheng 2nd Road, Guangzhou, 510655, People's Republic of China. .,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, China.
| | - Yanhong Deng
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Yuancunheng 2nd Road, Guangzhou, 510655, People's Republic of China.
| |
Collapse
|
|
7
|
Recurrence Risk After Up-to-Date Colon Cancer Staging, Surgery, and Pathology: Analysis of the Entire Swedish Population. Dis Colon Rectum 2018; 61:1016-1025. [PMID: 30086050 DOI: 10.1097/dcr.0000000000001158] [Citation(s) in RCA: 130] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Developments in the quality of care of patients with colon cancer have improved surgical outcome and thus the need for adjuvant chemotherapy. OBJECTIVE To investigate the recurrence rate in a large population-based cohort after modern staging, surgery, and pathology have been implemented. DESIGN This was a retrospective registry study. SETTINGS Data from patients included in the Swedish Colorectal Cancer Registry covering 99% of all cases and undergoing surgery for colon cancer stages I to III between 2007 and 2012 were obtained. PATIENTS In total, 14,325 patients who did not receive any neoadjuvant treatment, underwent radical surgery, and were alive 30 days after surgery were included. MAIN OUTCOME MEASURES Tumor and node classification and National Comprehensive Cancer Network-defined risk factors for recurrence were used to assess overall and stage-specific 5-year recurrence rates. RESULTS The median follow-up of nonrecurrent cases was 77 months (range, 47-118 mo). The 5-year recurrence rate was 5% in stage I, 12% in stage II, and 33% in stage III patients. In patients classified as having pT3N0 cancer with no or 1 risk factor, the 5-year recurrence rates were 9% and 11%. Risk factors for shorter time to recurrence were male sex, more advanced pT and pN classification, vascular and perineural invasion, emergency surgery, lack of central ligature, short longitudinal resection margin, postoperative complications, and, in stage III, no adjuvant chemotherapy. LIMITATIONS The registry does not contain some recently identified factors of relevance for recurrence rates, and some late recurrences may be missing. CONCLUSIONS The recurrence rate is less than that previously observed in historical materials, but current, commonly used risk factors are still useful in evaluating recurrence risks. Stratification by pT and pN classification and the number of risk factors enables the identification of large patient groups characterized by such a low recurrence rate that it is questionable whether adjuvant treatment is motivated. See Video Abstract at http://links.lww.com/DCR/A663.
Collapse
|
|
8
|
Liu Q, Luo D, Cai S, Li Q, Li X. Real-World Implications of Nonbiological Factors with Staging, Prognosis and Clinical Management in Colon Cancer. Cancers (Basel) 2018; 10:263. [PMID: 30096811 PMCID: PMC6115817 DOI: 10.3390/cancers10080263] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 08/05/2018] [Accepted: 08/06/2018] [Indexed: 01/17/2023] Open
Abstract
Background: The present study analyzed the nonbiological factors (NBFs) together with the American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) staging system to generate a refined, risk-adapted stage for the clinical treatment of colon cancer. Methods: Eligible patients (N = 28,818) with colon cancer between 1 January 2010 and 31 December 2014, were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier curves and Cox proportional hazards regression, analyzed the probabilities of cancer-specific survival (CSS) in patients with colon cancer, with different NBF-TNM stages. Results: Insurance status, marital status, and median household income were significant prognostic NBFs in the current study (p < 0.05). The concordance index of NBF-TNM stage was 0.857 (95% confidence interval (CI) = 0.8472⁻0.8668). Multivariate Cox analyses, indicated that NBF1-stage was independently associated with a 50.4% increased risk of cancer-specific mortality in colon cancer (p < 0.001), which increased to 77.1% in non-metastatic colon cancer. NBF0-stage improved in CSS as compared to the NBF1-stage in the respective stages (p < 0.05). Conclusions: The new proposed NBF-stage was an independent prognostic factor in colon cancer. Effect of NBFs on the survival of colon cancer necessitates further clinical attention. Moreover, the incorporation of NBF-stage into the AJCC TNM staging system is essential for prognostic prediction, and clinical guidance of adjuvant chemotherapy in stage II and III colon cancer.
Collapse
Affiliation(s)
- Qi Liu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
| | - Dakui Luo
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
| | - Sanjun Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
| | - Qingguo Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
| | - Xinxiang Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
| |
Collapse
|
|
9
|
Liu Q, Luo D, Cai S, Li Q, Li X. P-TNM staging system for colon cancer: combination of P-stage and AJCC TNM staging system for improving prognostic prediction and clinical management. Cancer Manag Res 2018; 10:2303-2314. [PMID: 30104899 PMCID: PMC6074826 DOI: 10.2147/cmar.s165188] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
AIM This study focused on improving the American Joint Committee on Cancer TNM staging system and demonstrated an improvement in prognostic accuracy and clinical management of colon cancer using the P-TNM staging system. PATIENTS AND METHODS Eligible patients (N=56,800) were identified from the Surveillance, Epidemiology, and End Results database between January 1, 2010, and December 31, 2014. The P-stage (P0 or P1) was assigned to each patient based on age at diagnosis, tumor grade, and tumor size. The outcome of interest was cancer-specific survival (CSS). The Cox proportional hazards regression analyses were used to identify independent prognostic factors and analyze the CSS probabilities of patients with colon cancer having different P-TNM stages, respectively. RESULTS A total of 29,627 patients were assigned to P0-stage and 27,173 patients were assigned to P1-stage. The P1-stage was associated with a 98.1% increased risk of cancer-specific mortality (hazard ratio =1.981, 95% confidence interval =1.891-2.076, P<0.001), which was higher in patients with nonmetastatic colon cancer. The P1-stage patients had improvement in CSS compared with those in P0-stage in respective stages (P<0.001). Moreover, CSS decreased in stage I-P1 compared with stage IIA-P0 or IIIA-P0 (P<0.001), stage IIIA-P1 compared with stage IIA-P0 (P<0.001), stage IIB-P1 compared with stage IIIB-P0 or IIC-P0 (P<0.001), stage IIIB-P1 compared with stage IIC-P0 (P<0.001), and stage IIC-P1 compared with stage IIIC-P0 (P<0.001). CONCLUSION P-stage was an independent prognostic factor for colon cancer. This study strongly supported the incorporation of P-stage into the American Joint Committee on Cancer TNM staging system for a better approach to prognostication and, thus, more individualized risk-adaptive therapies in colon cancer.
Collapse
Affiliation(s)
- Qi Liu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China,
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China,
| | - Dakui Luo
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China,
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China,
| | - Sanjun Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China,
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China,
| | - Qingguo Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China,
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China,
| | - Xinxiang Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China,
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China,
| |
Collapse
|
|
10
|
González A, Vizoso F, Allende MT, Sánchez MT, Balibrea JL, Ruibal A. Preoperative CEA and TAG-72 Serum Levels as Prognostic Indicators in Resectable Gastric Carcinoma. Int J Biol Markers 2018; 11:165-71. [PMID: 8915712 DOI: 10.1177/172460089601100305] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
We evaluated in 74 patients with resectable primary gastric carcinoma, the prognostic value of the preoperative circulating serum levels of CEA and TAG-72. Serum levels of CEA were above the cutoff level of 6 ng/ml in 18.9% of patients; TAG-72 levels were higher than 6 U/ml in 31% of patients. Pretreatment mean CEA levels were significantly lower (p<0.01) in patients with stage I tumors (2.9 ± 0.3 ng/ml) than in those with more advanced tumors (stage II: 14.5 ± 6.8 ng/ml; stage HI-TV: 6.8 ± 1.5 ng/ml). Similarly, significant differences in mean TAG-72 serum levels were found between stage I (3.5 ± 1.8 U/ml) and stage II and stage III-IV (30.4 ± 20.7 U/ml and 26.1 ± 9.7 U/ml, respectively) (p<0.05). In addition, TAG-72 levels were also higher in poorly differentiated and moderately differentiated tumors (38.5 ± 20.1 U/ml and 23.1 ± 9.4 U/ml, respectively) than in well differentiated tumors (4.4 ± 0.9 U/ml) (p<0.05). The results further indicated that high preoperative serum levels of CEA predicted shorter relapse-free survival duration (p<0.01), and that high TAG-72 levels were associated with shorter relapse-free and overall survival (p < 0.0001 and p < 0.0005, respectively). In addition, separate Cox multivariate analysis showed that preoperative TAG-72 was, after stage, the strongest factor to predict both relapse-free and overall survival (p < 0.0001 and p < 0.005, respectively) in patients with gastric cancer.
Collapse
Affiliation(s)
- A González
- Department of General Surgery, General Hospital of Segovia, Spain
| | | | | | | | | | | |
Collapse
|
|
11
|
Sagar PM, Taylor OM, Cooper EH, Benson EA, McMahon MJ, Finan PJ. The Tumour Marker CA 195 in Colorectal and Pancreatic Cancer. Int J Biol Markers 2018; 6:241-6. [PMID: 1795132 DOI: 10.1177/172460089100600405] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The aim of this study was to measure the serum level of the tumour markers CA 195 and CEA in patients with either colorectal or pancreatic cancer both before and at serial intervals after operation. CA 195 and CEA were measured in 199 patients with colorectal cancer and 52 patients with pancreatic cancer. The median concentrations of CA 195 were 3.0 u/ml (interquartile range 3.0-4.5 u/ml) in patients with a Dukes’ stage A lesion, 5.8 u/ml (3.0-18.2 u/ml) in patients with a Dukes’ stage B lesion, 6.1 u/ml (3.0-24.7 u/ml) in patients with a Dukes’ stage C and 23.8 u/ml (11.1-409.0 u/ml) in patients with metastatic disease (normal range 0-7 u/ml). The median levels of CEA were 2.6 ng/ml (1.7-3.3 ng/ml) for Dukes’ stage A, 3.3 ng/ml (1.7-7.2 ng/ml) for Dukes’ stage B, 3.7 ng/ml (2.2-7.9 ng/ml) for Dukes’ stage C and 34.5 ng/ml (13.3-289.4 ng/ml) for metastatic disease. A rising level of CA 195 or CEA after operation suggested recurrence of the tumour. In none of these patients was the recurrence operable. In patients with pancreatic adenocarcinoma, the level of CA 195 was significantly higher in patients with metastatic disease but it did not discriminate between resectable and unresectable disease. The duration of survival correlated with the initial level of CA 195 (Rs = –0.66, p < 0.001).
Collapse
Affiliation(s)
- P M Sagar
- Department of Chemical Pathology, University of Leeds, UK
| | | | | | | | | | | |
Collapse
|
|
12
|
Andicoechea A, Vizoso F, Alexandre E, Cuesta E, Díez MC, Riera L, García-Muñiz J, Martínez E, Ruibal A. Preoperative Carbohydrate Antigen 195 (CA195) and CEA Serum Levels as Prognostic Factors in Patients with Colorectal Cancer. Int J Biol Markers 2018. [DOI: 10.1177/172460089801300307] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
We evaluated in 214 patients with primary colorectal cancer the prognostic value of the preoperative serum levels of CEA and CA195. For CEA these levels were above the cutoff of 6 ng/ml in 31.3% of patients, whereas for CA195 they were higher than 12 U/ml in 35.9% of patients. The simultaneous use of both antigens increased the sensitivity to 49%, which was significantly higher than that of CEA (p<0.001) and CA195 (p<0.01) taken singly. The mean preoperative CEA levels were significantly (p<0.001) correlated with Dukes’ stage only, while there was a significant correlation between preoperative serum levels of CA195 and Dukes’ stage (p<0.001), grade of differentiation (p<0.01) and tumor location (p<0.05). The results indicated that high preoperative serum levels of CEA and CA195 were associated with a shorter overall survival (p<0.0001). In addition, separate Cox multivariate analysis showed that preoperative CA195 was, after Dukes’ stage, the strongest factor to predict overall survival (p<0.0001).
Collapse
Affiliation(s)
| | - F. Vizoso
- Servicio de Cirugía General, Hospital de Jove, Gijón
| | - E. Alexandre
- Servicio de Cirugía General, Hospital de Jove, Gijón
| | - E. Cuesta
- Servicio de Cirugía General, Hospital de Jove, Gijón
| | - M. Cruz Díez
- Servicio de Cirugía General, Hospital de Jove, Gijón
| | - L. Riera
- Servicio de Cirugía General, Centro Médico de Asturias, Oviedo
| | | | - E. Martínez
- Servicio de Cirugía General, Hospital Central de Asturias, Oviedo
| | - A. Ruibal
- Servicio de Medicina Nuclear, Hospital Central de Asturias, Oviedo - Spain
| |
Collapse
|
|
13
|
Qiu MZ, Lin JZ, Wang ZQ, Wang FH, Pan ZZ, Luo HY, Li YH, Zhou ZW, He YJ, Xu RH. Cutoff value of carcinoembryonic antigen and carbohydrate antigen 19-9 elevation levels for monitoring recurrence in patients with resectable gastric adenocarcinoma. Int J Biol Markers 2018; 24:258-64. [DOI: 10.1177/172460080902400407] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background The aim of this longitudinal study was to try and improve the specificity of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in monitoring tumor recurrence in patients with resectable gastric adenocarcinoma by setting suitable elevation levels. Methods One hundred eighty-one patients with resectable gastric adenocarcinoma were considered. Serum samples were obtained preoperatively and every 3 months postoperatively. Results Preoperative CEA and CA19-9 positivity rates were 19.9% and 18.2%. The specificity and sensitivity of CEA elevation to monitor recurrence were 92.9% and 23.4% versus 76.5% and 78.9% in CEA-negative versus CEA-positive patients, respectively. For CA19-9 the specificity and sensitivity were 95.0% and 18.8% versus 60.0% and 83.3% in CA19-9-negative versus CA19-9-positive patients, respectively. When we set the elevation level of CEA at 5 ng/mL, the specificity of CEA elevation to monitor recurrence increased to 94.1% for CEA-positive patients. The specificity increased to 93.3% for CA19-9-positive patients when the CA19-9 elevation level was set at 100 U/mL. Conclusions For CEA- or CA19-9-positive patients with resectable gastric adenocarcinoma we can increase the specificity of CEA and CA19-9 by setting the elevation level of CEA at 5 ng/mL and CA19-9 at 100 U/mL.
Collapse
Affiliation(s)
- Miao-Zhen Qiu
- State Key Laboratory of Oncology in South China, Guangzhou
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou
| | - Jun-Zhong Lin
- State Key Laboratory of Oncology in South China, Guangzhou
- Department of Abdominal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou - People's Republic of China
| | - Zhi-Qiang Wang
- State Key Laboratory of Oncology in South China, Guangzhou
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou
| | - Feng-Hua Wang
- State Key Laboratory of Oncology in South China, Guangzhou
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou
| | - Zhi-Zhong Pan
- State Key Laboratory of Oncology in South China, Guangzhou
- Department of Abdominal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou - People's Republic of China
| | - Hui-Yan Luo
- State Key Laboratory of Oncology in South China, Guangzhou
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou
| | - Yu-Hong Li
- State Key Laboratory of Oncology in South China, Guangzhou
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou
| | - Zhi-Wei Zhou
- State Key Laboratory of Oncology in South China, Guangzhou
- Department of Abdominal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou - People's Republic of China
| | - You-Jian He
- State Key Laboratory of Oncology in South China, Guangzhou
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou
| | - Rui-Hua Xu
- State Key Laboratory of Oncology in South China, Guangzhou
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou
| |
Collapse
|
|
14
|
Boysen AK, Wettergren Y, Sorensen BS, Taflin H, Gustavson B, Spindler KLG. Cell-free DNA levels and correlation to stage and outcome following treatment of locally advanced rectal cancer. Tumour Biol 2017; 39:1010428317730976. [DOI: 10.1177/1010428317730976] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Accurate staging of rectal cancer remains essential for optimal patient selection for combined modality treatment, including radiotherapy, chemotherapy and surgery. We aimed at examining the correlation of cell free DNA with the pathologic stage and subsequent risk of recurrence for patients with locally advanced rectal cancer undergoing preoperative chemoradiation. We examined 75 patients with locally advanced rectal cancer receiving preoperative chemoradiation. Blood samples for translational use were drawn prior to rectal surgery. The level of cell free DNA was quantified by digital droplet PCR and expressed as copy number of beta 2 microglobulin. We found a median level of cell free DNA in the AJCC stages I-III of 3100, 8300, and 10,700 copies/mL respectively. For patients with 12 sampled lymph nodes or above, the median level of cell free DNA were 2400 copies/mL and 4400 copies/mL (p = 0.04) for node negative and node positive disease respectively. The median follow-up was 39 months and 11 recurrences were detected (15%). The median level for patients with recurrent disease was 13,000 copies/mL compared to 5200 copies/mL for non-recurrent patients (p = 0.08). We have demonstrated a correlation between the level of total cell free DNA and the pathologic stage and nodal involvement. Furthermore, we have found a trend towards a correlation with the risk of recurrence following resection of localized rectal cancer.
Collapse
Affiliation(s)
| | - Yvonne Wettergren
- Surgical Oncology Laboratory, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Boe Sandahl Sorensen
- Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
| | - Helena Taflin
- Surgical Oncology Laboratory, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Bengt Gustavson
- Surgical Oncology Laboratory, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | | |
Collapse
|
|
15
|
Hontani K, Tsuchikawa T, Hiwasa T, Nakamura T, Ueno T, Kushibiki T, Takahashi M, Inoko K, Takano H, Takeuchi S, Dosaka-Akita H, Kuwatani M, Sakamoto N, Hatanaka Y, Mitsuhashi T, Shimada H, Shichinohe T, Hirano S. Identification of novel serum autoantibodies against EID3 in non-functional pancreatic neuroendocrine tumors. Oncotarget 2017; 8:106206-106221. [PMID: 29290942 PMCID: PMC5739727 DOI: 10.18632/oncotarget.22175] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Accepted: 10/14/2017] [Indexed: 12/16/2022] Open
Abstract
Pancreatic neuroendocrine tumors (pNETs) are relatively rare heterogenous tumors, comprising only 1–2% of all pancreatic neoplasms. The majority of pNETs are non-functional tumors (NF-pNETs) that do not produce hormones, and as such, do not cause any hormone-related symptoms. As a result, these tumors are often diagnosed at an advanced stage because patients do not present with specific symptoms. Although tumor markers are used to help diagnosis and predict some types of cancers, chromogranin A, a widely used tumor marker of pNETs, has significant limitations. To identify novel NF-pNET-associated antigens, we performed serological identification of antigens by recombinant cDNA expression cloning (SEREX) and identified five tumor antigens (phosphatase and tensin homolog, EP300-interacting inhibitor of differentiation 3 [EID3], EH domain-containing protein 1, galactoside-binding soluble 9, and BRCA1-associated protein). Further analysis using the AlphaLISA® immunoassay to compare serum antibody levels revealed that antibody levels against the EID3 antigen was significantly higher in the patient group than in the healthy donor group (n = 25, both groups). In addition, higher serum anti-EID3 antibody levels in NF-pNET patients correlated with shorter disease-free survival. The AUC calculated by ROC analysis was 0.784 with moderate diagnostic accuracy. In conclusion, serum anti-EID3 antibody levels may be useful as a tumor marker for prediction of tumor recurrence in NF-pNETs.
Collapse
Affiliation(s)
- Koji Hontani
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Takahiro Tsuchikawa
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Takaki Hiwasa
- Department of Biochemistry and Genetics, Chiba University, Chuo Ku, Chiba 260-8670, Japan
| | - Toru Nakamura
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Takashi Ueno
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Toshihiro Kushibiki
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Mizuna Takahashi
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Kazuho Inoko
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Hironobu Takano
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Satoshi Takeuchi
- Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Hirotoshi Dosaka-Akita
- Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Masaki Kuwatani
- Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Yutaka Hatanaka
- Department of Translational Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Tomoko Mitsuhashi
- Department of Translational Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Hideaki Shimada
- Department of Surgery, School of Medicine, Toho University, Ota-ku, Tokyo 143-8541, Japan
| | - Toshiaki Shichinohe
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
| |
Collapse
|
|
16
|
Incorporation of serum carcinoembryonic antigen levels into the prognostic grouping system of colon cancer. Int J Colorectal Dis 2017; 32:821-829. [PMID: 28185003 DOI: 10.1007/s00384-017-2772-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/01/2017] [Indexed: 02/07/2023]
Abstract
PURPOSE This study aimed to clarify the significance of preoperative serum carcinoembryonic antigen (CEA) on disease-free survival (DFS) in colon cancer and propose a new prognostic grouping system. METHODS A multiinstitutional retrospective cohort of 7296 colon cancer patients who underwent R0 surgery between 1997 and 2006 was analyzed. We stratified preoperative serum CEA values into three categories (C-stages): C0 (normal CEA), C1A (up to double the cutoff value), and C1B (more than double the cutoff value) and stratified each TNM stage by C-stage. Multivariate analyses using Cox regression models were used to analyze the significance of C-stage on 5-year DFS. RESULTS CEA level was an independent factor affecting DFS; the 5-year DFS of patients with C0 and C1, as well as those with C1A and C1B, differed significantly (C0 84.6%, C1 69.8%, C1A 72.7%, and C1B 66.4%, P < 0.0001). Additionally, the DFS of pStages IIC and C1B was significantly lower than of pStages IIIA and C0 (65.8 vs. 87.7%, respectively; hazard ratio 3.44, 95% confidence interval 1.97-5.88, P < 0.0001). Moreover, the 5-year DFS of pStages IIIA and C0 or C1A did not differ significantly from pStages I and C1A (87.7 vs. 87.7%, P = 0.90 and 86.4 vs. 87.7%, P = 0.78, respectively). CONCLUSIONS pStage IIC and C1B disease should be considered candidates for intensive adjuvant chemotherapy. Conversely, pStages IIIA and C0 or C1A could be exempted from adjuvant chemotherapy. Incorporating C-stage into the current TNM staging system may facilitate decision making regarding the use of adjuvant chemotherapy in colon cancer patients.
Collapse
|
|
17
|
Incorporation of CEA Improves Risk Stratification in Stage II Colon Cancer. J Gastrointest Surg 2017; 21:770-777. [PMID: 28290141 DOI: 10.1007/s11605-017-3391-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Accepted: 02/28/2017] [Indexed: 01/31/2023]
Abstract
High-risk features are used to direct adjuvant therapy for stage II colon cancer. Currently, high-risk features are identified postoperatively, limiting preoperative risk stratification. We hypothesized carcinoembryonic antigen (CEA) can improve preoperative risk stratification for stage II colon cancer. The National Cancer Database (NCDB 2004-2009) was reviewed for stage II colon adenocarcinoma patients undergoing curative intent resection. A novel risk stratification including both traditional high-risk features (T4 lesion, <12 lymph nodes sampled, and poor differentiation) and elevated CEA was developed. Unadjusted Kaplan-Meier and adjusted Cox proportional hazards analyzed overall survival. Concordance Probability Estimates (CPE) assessed discrimination. Seventy-four thousand nine hundred forty-five patients were identified; 40,844 (54.5%) had CEA levels reported and were included. Chemotherapy administration was similar between normal and elevated CEA groups (23.8 vs. 25.1%, p = 0.003). Compared to patients with CEA elevation, 5-year overall survival in patients with normal CEA was improved (74.5 vs. 63.4%, p < 0.001). Restratification incorporating CEA resulted in reclassification of 6912 patients (16.9%) from average to high risk. CPE increased for novel risk stratification (0.634 vs. 0.612, SE = 0.005). The routinely available CEA test improved risk stratification for stage II colon cancer. CEA not only may improve staging of colon cancer but may also help guide additional therapy.
Collapse
|
|
18
|
Kim CG, Ahn JB, Jung M, Beom SH, Heo SJ, Kim JH, Kim YJ, Kim NK, Min BS, Koom WS, Kim H, Roh YH, Ma BG, Shin SJ. Preoperative Serum Carcinoembryonic Antigen Level as a Prognostic Factor for Recurrence and Survival After Curative Resection Followed by Adjuvant Chemotherapy in Stage III Colon Cancer. Ann Surg Oncol 2016; 24:227-235. [PMID: 27699609 DOI: 10.1245/s10434-016-5613-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) is the most widely used tumor marker in colon cancer; however, there has been controversy regarding the significance of preoperative serum CEA level as a prognostic factor for recurrence. In this study, we evaluated the optimal cutoff value and prognostic significance of preoperative serum CEA level in stage III colon cancer. METHODS Based on a retrospective cohort of 965 patients with stage III colon cancer who underwent elective curative surgery and adjuvant chemotherapy with fluoropyrimidine and oxaliplatin (training set), we determined the optimal cutoff value of CEA for recurrence using the Contal and O'Quigley method. We assessed the prognostic value of this cutoff value in terms of disease-free survival (DFS) and overall survival (OS) in a prospective cohort of 268 patients with stage III colon cancer (validation set). A Cox proportional hazards model was used to explore the association of prognostic variables with DFS and OS. RESULTS The statistically determined best cutoff value for CEA was 3 ng/mL in the training set. A high CEA level (≥3 ng/mL) was associated with inferior DFS (hazard ratio [HR] 4.609, 95 % confidence interval [CI] 2.028-10.474) and OS (HR 3.956, 95 % CI 1.127-13.882) in the validation set, while multivariate analysis showed that a high CEA level was an independent risk factor for DFS and OS in both study subsets. CONCLUSION Preoperative serum CEA level is an independent prognostic factor for DFS and OS in patients with stage III colon cancer after curative resection and adjuvant chemotherapy.
Collapse
Affiliation(s)
- Chang Gon Kim
- Department of Medical Oncology, Yonsei Cancer Center, Seoul, Korea.,Graduate School of Medical Science and Engineering, KAIST, Daejeon, Korea
| | - Joong Bae Ahn
- Department of Medical Oncology, Yonsei Cancer Center, Seoul, Korea
| | - Minkyu Jung
- Department of Medical Oncology, Yonsei Cancer Center, Seoul, Korea
| | - Seung Hoon Beom
- Department of Medical Oncology, Yonsei Cancer Center, Seoul, Korea
| | - Su Jin Heo
- Department of Medical Oncology, Yonsei Cancer Center, Seoul, Korea
| | - Jee Hung Kim
- Department of Medical Oncology, Yonsei Cancer Center, Seoul, Korea
| | - Young Jin Kim
- Department of Medical Oncology, Yonsei Cancer Center, Seoul, Korea
| | - Nam Kyu Kim
- Department of Surgery, Yonsei Cancer Center, Seoul, Korea
| | - Byung Soh Min
- Department of Surgery, Yonsei Cancer Center, Seoul, Korea
| | - Woong Sub Koom
- Department of Radiation Oncology, Yonsei Cancer Center, Seoul, Korea
| | - Hoguen Kim
- Department of Pathology, Yonsei Cancer Center, Seoul, Korea
| | - Yun Ho Roh
- Biostatistics Collaboration Unit, Department of Research Affairs, Yonsei University College of Medicine, Seoul, Korea
| | - Bo Gyoung Ma
- Biostatistics Collaboration Unit, Department of Research Affairs, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Joon Shin
- Department of Medical Oncology, Yonsei Cancer Center, Seoul, Korea.
| |
Collapse
|
|
19
|
Park JS, Chon HJ, Jeung HC, Shin SJ, Rha SY, Ahn JB, Lee KY, Kim NK, Chung HC. High-risk clinicopathological features and their predictive significance in Korean patients with stage II colon cancer. J Cancer Res Clin Oncol 2016; 142:2051-9. [PMID: 27447697 DOI: 10.1007/s00432-016-2208-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Accepted: 07/11/2016] [Indexed: 01/18/2023]
Abstract
PURPOSE We investigated the prognostic factors for recurrence in Korean patients with stage II colon cancer and evaluated their predictive significance with 5-fluorouracil (FU)-based adjuvant chemotherapy. METHODS We analyzed the relationship between clinicopathological features and relapse-free survival (RFS) of 716 stage II colon cancer patients who underwent curative resection. Predictive values were assessed using 5-year RFS and 5-year cancer-specific survival (CSS). RESULTS The 5-year RFS, 5-year CSS, 5-year disease-free survival, and 5-year overall survival rates were 87.4, 94.9, 84.8, and 90.5 %, respectively. T4 stage (hazard ratio [HR], 2.342; 95 % confidence interval [CI], 1.348-4.068; p = 0.003), preoperative bowel obstruction or perforation (HR 2.428; 95 % CI 1.241-4.752; p = 0.010), and age older than 70 years (HR 1.740; 95 % CI 1.130-2.678; p = 0.012) were poor prognostic factors for recurrence in multiple Cox regression analyses. In 60 patients with T4 disease, 5-FU-based adjuvant chemotherapy was associated with improved 5-year CSS of the patients (90.3 vs. 46.7 %; HR 0.135; 95 % CI 0.035-0.517; p = 0.003). CONCLUSIONS We found discordance between the risk factors for recurrence and the predictive value for 5-FU-based adjuvant chemotherapy in Korean patients with stage II colon cancer. Future prospective clinical trials selectively targeting high-risk patients are needed.
Collapse
Affiliation(s)
- Ji Soo Park
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
- Song-Dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Medicine, Graduate School of Yonsei University, Seoul, Republic of Korea
| | - Hong Jae Chon
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
- Song-Dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Medicine, Graduate School of Yonsei University, Seoul, Republic of Korea
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Hei-Cheul Jeung
- Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
- Song-Dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Joon Shin
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
- Song-Dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sun Young Rha
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
- Song-Dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Joong Bae Ahn
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea
- Song-Dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kang Young Lee
- Department of Surgery, Colorectal Cancer Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Nam Kyu Kim
- Department of Surgery, Colorectal Cancer Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyun Cheol Chung
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
- Song-Dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
| |
Collapse
|
|
20
|
Can serum dynamics of carcinoembryonic antigen level during neoadjuvant chemoradiotherapy in rectal cancer predict tumor response and recurrence? A multi-institutional retrospective study. Int J Colorectal Dis 2016; 31:1595-601. [PMID: 27464635 DOI: 10.1007/s00384-016-2629-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/18/2016] [Indexed: 02/04/2023]
Abstract
PURPOSE We evaluate whether the change of carcinoembryonic antigen (CEA) level before and after preoperative chemoradiotherapy (CRT) in rectal cancer affects tumor response and recurrence or not. METHODS We retrospectively analyzed 1447 rectal cancer patients who underwent preoperative CRT followed by curative surgery. All patients received preoperative radiotherapy of 50.4 Gy in 28 fractions with 5-fluorouracil or capecitabine. Total mesorectal excision was performed 4 to 8 weeks after preoperative CRT. CEA levels were checked before and after CRT. Clinical and pathologic factors were analyzed for tumor response and recurrence. RESULTS Post-CRT CEA level (cutoff value, 2.5 ng/mL) was not a significant factor for tumor response on the multivariate analysis (p = 0.095). Patients were categorized according to the pre- and post-CRT CEA level (group A: pre-CRT CEA ≤5 ng/mL; group B: pre-CRT CEA >5 ng/mL and post-CRT CEA ≤2.5 ng/mL; group C: pre-CRT CEA >5 ng/mL and post-CRT CEA >2.5 ng/mL). The relapse-free survival (RFS) at 5 years was significantly higher in group A than in groups B and C (82.6 vs. 73.7 % vs. 72.2 %, p < 0.001). The overall survival (OS) at 5 years was significantly higher in group A than in groups B and C (90.1 vs. 84.4 % vs. 83.4 %, p < 0.001). However, there is no significant difference for RFS and OS between groups B and C (all, p > 0.05). CONCLUSIONS Decline of elevated CEA level (>5 ng/mL) during preoperative chemoradiotherapy has no significant effect on tumor response and recurrence in rectal cancer.
Collapse
|
|
21
|
Tarantino I, Warschkow R, Schmied BM, Güller U, Mieth M, Cerny T, Büchler MW, Ulrich A. Predictive Value of CEA for Survival in Stage I Rectal Cancer: a Population-Based Propensity Score-Matched Analysis. J Gastrointest Surg 2016; 20:1213-22. [PMID: 27067235 DOI: 10.1007/s11605-016-3137-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Accepted: 03/21/2016] [Indexed: 01/31/2023]
Abstract
BACKGROUND The aim of the study was to assess whether preoperative carcinoembryonic antigen (CEA) level is an independent predictor of overall- and cancer-specific survival in stage I rectal cancer. METHODS Stage I rectal cancer patients were identified in the Surveillance, Epidemiology, and End Results database between 2004 and 2011. The impact of an elevated preoperative CEA level (C1-stage) compared with a normal CEA level (C0-stage) on overall and cancer-specific survival was assessed using risk-adjusted Cox proportional hazard regression models and propensity score methods. RESULTS Overall, 1932 stage I rectal cancer patients were included, of which 328 (17 %) patients had C1-stage. The 5-year overall and cancer-specific survival for patients with C0-stage were 85.7 % (95 % CI 83.2-88.2 %) and 94.7 % (95 % CI 93.1-96.3 %), versus 76.8 % (95 % CI 70.9-83.1 %) and 88.1 % (95 % CI 83.3-93.2 %) for patients with C1-stage (P < 0.001 and P = 0.001). The negative impact of C1-stage on overall and cancer-specific survival was confirmed by risk-adjusted Cox proportional hazard regression analysis (hazard ratio [HR] = 1.57, 95 % CI = 1.15-2.16, P = 0.007 and 2.04, 95 % CI = 1.25-3.33, P = 0.006), and after propensity score matching (overall survival [OS]: HR = 1.46, 95 % CI = 1.02-2.08, P = 0.044 and cancer-specific survival [CSS]: HR = 3.28, 95 % CI = 1.78-6.03, P < 0.001). CONCLUSION This is the first population-based investigation of a large cohort of exclusively stage I rectal cancer patients providing compelling evidence that elevated preoperative CEA level is a strong predictor of worse overall and cancer-specific survival.
Collapse
Affiliation(s)
- Ignazio Tarantino
- Department of General, Abdominal and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Rene Warschkow
- Department of Surgery, Kantonsspital St. Gallen, 9007, St. Gallen, Switzerland.,Institute of Medical Biometry and Informatics, University of Heidelberg, 69120, Heidelberg, Germany
| | - Bruno M Schmied
- Department of Surgery, Kantonsspital St. Gallen, 9007, St. Gallen, Switzerland
| | - Ulrich Güller
- Department of Medical Oncology and Hematology, Kantonsspital St. Gallen, 9007, St. Gallen, Switzerland.,University Clinics for Visceral Surgery and Medicine, University Hospital Berne, 3010, Berne, Switzerland
| | - Markus Mieth
- Department of General, Abdominal and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Thomas Cerny
- Department of Medical Oncology and Hematology, Kantonsspital St. Gallen, 9007, St. Gallen, Switzerland
| | - Markus W Büchler
- Department of General, Abdominal and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Alexis Ulrich
- Department of General, Abdominal and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
| |
Collapse
|
|
22
|
Wang JY, Sun J, Huang MY, Wang YS, Hou MF, Sun Y, He H, Krishna N, Chiu SJ, Lin S, Yang S, Chang WC. STIM1 overexpression promotes colorectal cancer progression, cell motility and COX-2 expression. Oncogene 2015; 34:4358-4367. [PMID: 25381814 PMCID: PMC4426254 DOI: 10.1038/onc.2014.366] [Citation(s) in RCA: 115] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2012] [Revised: 09/11/2014] [Accepted: 09/19/2014] [Indexed: 12/16/2022]
Abstract
Tumor metastasis is the major cause of death among cancer patients, with >90% of cancer-related death attributable to the spreading of metastatic cells to secondary organs. Store-operated Ca(2+) entry (SOCE) is the predominant Ca(2+) entry mechanism in most cancer cells, and stromal interaction molecule 1 (STIM1) is the endoplasmic reticulum (ER) Ca(2+) sensor for store-operated channels. Here we reported that the STIM1 was overexpressed in colorectal cancer (CRC) patients. STIM1 overexpression in CRC was significantly associated with tumor size, depth of invasion, lymph node metastasis status and serum levels of carcinoembryonic antigen. Furthermore, ectopic expression of STIM1 promoted CRC cell motility, while depletion of STIM1 with short hairpin RNA inhibited CRC cell migration. Our data further suggested that STIM1 promoted CRC cell migration through increasing the expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). Importantly, ectopically expressed COX-2 or exogenous PGE2 were able to rescue migration defect in STIM1 knockdown CRC cells, and inhibition of COX-2 with ibuprofen and indomethacin abrogated STIM1-mediated CRC cell motility. In short, our data provided clinicopathological significance for STIM1 and SOCE in CRC progression, and implicated a role for COX-2 in STIM1-mediated CRC metastasis. Our studies also suggested a new approach to inhibit STIM1-mediated metastasis with COX-2 inhibitors.
Collapse
Affiliation(s)
- Jaw-Yuan Wang
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
- Division of Gastrointestinal and General Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
- Department of Radiation Oncology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Jianwei Sun
- Comprehensive Melanoma Research Center, Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
| | - Ming-Yii Huang
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
- Department of Radiation Oncology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Radiation Oncology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Yu-Shiuan Wang
- Department of Genomic Medicine, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Feng Hou
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
- Department of Surgery, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Yan Sun
- Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
| | - Huifang He
- Comprehensive Melanoma Research Center, Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
| | - Niveditha Krishna
- Comprehensive Melanoma Research Center, Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
| | - Siou-Jin Chiu
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
- Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan
| | - Shengchen Lin
- Comprehensive Melanoma Research Center, Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
| | - Shengyu Yang
- Comprehensive Melanoma Research Center, Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
| | - Wei-Chiao Chang
- Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
- Department of Clinical Pharmacy, Taipei Medical University, Taipei 110, Taiwan
- Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan
| |
Collapse
|
|
23
|
Kim CH, Lee SY, Kim HR, Kim YJ. Prognostic Effect of Pretreatment Serum Carcinoembryonic Antigen Level: A Useful Tool for Prediction of Distant Metastasis in Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy and Total Mesorectal Excision. Medicine (Baltimore) 2015; 94:e1291. [PMID: 26252304 PMCID: PMC4616603 DOI: 10.1097/md.0000000000001291] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Many studies have reported the prognostic value of pretreatment serum carcinoembryonic antigen (pre-CEA) levels on colorectal cancer outcomes. However, controversy remains concerning the significance of pre-CEA levels in patients with rectal cancer treated with neoadjuvant chemoradiotherapy (CRT). Our aim in this study was to investigate the prognostic role of the pre-CEA level in patients with locally advanced rectal cancer undergoing neoadjuvant CRT followed by total mesorectal excision (TME).A total of 419 patients with stages II and III rectal cancer treated with neoadjuvant CRT followed by TME with available pre-CEA data were included. The outcomes studied were 5-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS). Optimal pre-CEA cutoff values to predict DMFS were determined based on current smoking history.The median pre-CEA level of smokers was 3.8 ng/mL, and that of nonsmokers was 2.8 ng/mL (P < 0.01). Pre-CEA levels of 6.6 ng/mL for nonsmokers and 11.4 ng/mL for smokers were determined to best separate patients on the basis of time to distant metastasis by using log-rank statistics. The pre-CEA level was associated with DMFS (hazard ratio = 1.743, 95% confidence interval = 1.129-2.690, P = 0.01). The pre-CEA level was not associated with LRFS or DFS.The pre-CEA level appears to be a significant preoperative prognostic factor. Moreover, it is as valuable as any known pathologic factor. Future studies evaluating oncologic outcomes should take into consideration the pre-CEA level.
Collapse
Affiliation(s)
- Chang Hyun Kim
- Form the Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Gwangju, Korea
| | | | | | | |
Collapse
|
|
24
|
Thirunavukarasu P, Talati C, Munjal S, Attwood K, Edge SB, Francescutti V. Effect of Incorporation of Pretreatment Serum Carcinoembryonic Antigen Levels Into AJCC Staging for Colon Cancer on 5-Year Survival. JAMA Surg 2015; 150:747-755. [DOI: 10.1001/jamasurg.2015.0871] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
| | - Chetasi Talati
- Department of Internal Medicine, University of Buffalo, Buffalo, New York
| | - Sumeet Munjal
- Department of Internal Medicine, University of Buffalo, Buffalo, New York
| | - Kris Attwood
- Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, New York
| | - Stephen B. Edge
- Department of Surgery, Baptist Memorial Health Care, Memphis, Tennessee
| | - Valerie Francescutti
- Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York
| |
Collapse
|
|
25
|
Gaertner WB, Kwaan MR, Madoff RD, Melton GB. Rectal cancer: An evidence-based update for primary care providers. World J Gastroenterol 2015; 21:7659-7671. [PMID: 26167068 PMCID: PMC4491955 DOI: 10.3748/wjg.v21.i25.7659] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Revised: 04/04/2015] [Accepted: 05/21/2015] [Indexed: 02/07/2023] Open
Abstract
Rectal adenocarcinoma is an important cause of cancer-related deaths worldwide, and key anatomic differences between the rectum and the colon have significant implications for management of rectal cancer. Many advances have been made in the diagnosis and management of rectal cancer. These include clinical staging with imaging studies such as endorectal ultrasound and pelvic magnetic resonance imaging, operative approaches such as transanal endoscopic microsurgery and laparoscopic and robotic assisted proctectomy, as well as refined neoadjuvant and adjuvant therapies. For stage II and III rectal cancers, combined chemoradiotherapy offers the lowest rates of local and distant relapse, and is delivered neoadjuvantly to improve tolerability and optimize surgical outcomes, particularly when sphincter-sparing surgery is an endpoint. The goal in rectal cancer treatment is to optimize disease-free and overall survival while minimizing the risk of local recurrence and toxicity from both radiation and systemic therapy. Optimal patient outcomes depend on multidisciplinary involvement for tailored therapy. The successful management of rectal cancer requires a multidisciplinary approach, with the involvement of enterostomal nurses, gastroenterologists, medical and radiation oncologists, radiologists, pathologists and surgeons. The identification of patients who are candidates for combined modality treatment is particularly useful to optimize outcomes. This article provides an overview of the diagnosis, staging and multimodal therapy of patients with rectal cancer for primary care providers.
Collapse
|
|
26
|
Dawood S, Sirohi B, Shrikhande SV, Toh HC, Eng C. Potential Prognostic Impact of Baseline CEA Level and Surgery of Primary Tumor Among Patients with Synchronous Stage IV Colorectal Cancer: A Large Population Based Study. Indian J Surg Oncol 2015; 6:198-206. [PMID: 27217664 DOI: 10.1007/s13193-015-0419-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Accepted: 05/19/2015] [Indexed: 12/30/2022] Open
Abstract
Prognostic role of surgical resection of the primary tumor and baseline CEA among patients with synchronous stage IV colorectal cancer (CRC) remains an area of debate. The objective of this study was to determine the prognostic value of baseline CEA and surgical resection of the primary among patients with synchronous stage IV CRC in the era of modern chemotherapy and biologic therapy. The Surveillance, Epidemiology and End Results Registry was searched to identify patients with synchronous stage IV CRC diagnosed between 2004 and 2009. Colorectal-cancer-specific survival (CCS) was estimated using the Kaplan-Meier product limit method. Cox models were fitted to assess the multivariable relationship of various patient and tumor characteristics and CCS. Three hundred thirty-three thousand, three hundred ninety nine patients were identified in the SEER registry. Median CCS among patients with their primary tumor removed was 21 M vs. 7 M (primary intact) respectively (p < 0.001). Median CCS among patients who had an elevated vs. non-elevated baseline CEA level was 14 M vs. 24 M respectively (p < 0.0001). By multivariable analysis, patients with an elevated baseline CEA had a 56 % increased risk of death from CRC compared to those with a non-elevated CEA level (HR = 1.56, 95%CI 1.47-1.65, p < 0.0001). Similarly patients who underwent surgical resection of the primary tumor had a 33 % decreased risk of death from CRC compared to those who did not (HR = 0.61, 95%CI 0.54-0.69, p < 0.0001). In our review of this large population SEER based study, an elevated baseline CEA level and surgical resection of the primary tumor among patients with synchronous stage IV CRC appeared to impact survival outcomes. Prospective validation of these results in a surgically unresectable patient population will be required.
Collapse
Affiliation(s)
- Shaheenah Dawood
- Department of Medical Oncology, Dubai Hospital, Dubai Health Authority, Dubai, United Arab Emirates
| | - Bhawna Sirohi
- Department of Medical Oncology, Mazumdar Shaw Cancer Centre, Narayana Health, Bangalore, India
| | | | - Han-Chong Toh
- Department of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Cathy Eng
- Department of GI Medical Oncology, MD Anderson Cancer Center, Houston, TX USA
| |
Collapse
|
|
27
|
Rezende Junior HCD, Palma RT, Toloi GC, Martinez CAR, Waisberg J. Carcinoembryonic antigen levels in the peripheral and mesenteric venous blood of patients with rectal carcinoma. ARQUIVOS DE GASTROENTEROLOGIA 2014; 50:264-9. [PMID: 24474227 DOI: 10.1590/s0004-28032013000400005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/26/2013] [Accepted: 07/16/2013] [Indexed: 12/28/2022]
Abstract
CONTEXT The serum carcinoembryonic antigen (CEA) is an important prognostic factor in colorectal cancer, however the rectum presents different routes of venous drainage, stating that the level of CEA in peripheral and mesenteric rectal tumors may be different, depending on the location of the tumor in the rectal segment. OBJECTIVE The goal of this study was to evaluate the relationship between the peripheral and mesenteric venous levels of CEA and the association between these levels and the tumour location in the rectums of patients successfully operated on for rectal carcinoma. METHODS Thirty-two patients who were surgically treated for rectal carcinoma were divided into patients with tumours located in the upper rectum (n = 11) or lower rectum (n = 21). The CEA values were assessed by electrochemiluminescence immunoassay. Serum and mesenteric CEA levels were associated with the tumour anatomopathological characteristics: location, histological type, cellular differentiation grade, depth of invasion into the rectal wall, angiolymphatic invasion, tumour, node, and metastasis staging; and the CEA index (≤1.0 or ≥1.0 ng /mL). RESULTS Analysis of the serum CEA values using clinical and anatomopathological parameters revealed no significant association with tumour location, histological type, cellular differentiation grade, depth of invasion into the intestinal wall, and tumour, node, and metastasis staging. The mesenteric CEA levels were significantly associated with the tumour location (P = 0.01). The CEA values in the mesenteric venous blood and the presence of angiolymphatic invasion (P = 0.047) were significantly different. A significant relationship was found between the CEA index value and the rectal tumour location (P = 0.0001). CONCLUSIONS The CEA levels were higher in the mesenteric vein in tumours located in the upper rectum and in the presence of angiolymphatic invasion. CEA drainage from lower rectum adenocarcinomas preferentially occurs through the systemic pathway.
Collapse
Affiliation(s)
| | - Rogério Tadeu Palma
- Departamento de Cirurgia, Faculdade de Medicina do ABC, Santo AndréSP, Brasil
| | | | | | - Jaques Waisberg
- Departamento de Cirurgia, Faculdade de Medicina do ABC, Santo AndréSP, Brasil
| |
Collapse
|
|
28
|
Mayer RJ, Venook AP, Schilsky RL. Progress against GI cancer during the American Society of Clinical Oncology's first 50 years. J Clin Oncol 2014; 32:1521-30. [PMID: 24752046 DOI: 10.1200/jco.2014.55.4121] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Affiliation(s)
- Robert J Mayer
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA
| | - Alan P Venook
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA
| | | |
Collapse
|
|
29
|
Hu DL, Guo XD, Sun ZN, Zhao YM. Colon carcinoma treated with oxaliplatin and capecitabine in a 12-year-old child. World J Pediatr 2014; 10:86-8. [PMID: 24464671 DOI: 10.1007/s12519-014-0459-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Accepted: 10/16/2013] [Indexed: 11/26/2022]
Abstract
BACKGROUND XELOX (oxaliplatin 130 mg/m(2) iv, capecitabine 1000 mg/m(2) bid oral d1-14, q3w) chemotherapy has never been used in children. In this report, we present a case of a 12-year-old girl with colon adenocarcinoma, treated with surgery and XELOX chemotherapy. METHODS On admission, the girl complained of abdominal pain and intestinal obstruction. Physical examination revealed a distended abdomen with tenderness on the left upper quadrant. Barium enema revealed a stenotic lesion at the distal end of the transverse colon, and abdominal computed tomography showed acute obstruction and a colonic mass. Laparotomy was performed after the failure of conservative treatment. RESULTS The mass was originated from the transverse colon. Frozen sections of the specimens revealed an adenocarcinoma. Transverse colectomy was performed and regional lymph nodes were removed. Pathological examination confirmed that the mass was a poorly differentiated adenocarcinoma, and XELOX chemotherapy was used. No evidence of recurrent or metastatic tumor was found after 18 months. CONCLUSION Although complete resection is the most effective treatment, XELOX chemotherapy is beneficial to the improvement of clinical outcome of patients with colon adenocarcinoma.
Collapse
Affiliation(s)
- Dong-Lai Hu
- Department of Pediatric Surgery, Jinhua Hospital of Zhejiang University, Jinhua Municipal Central Hospital, Jinhua, 321000, China
| | | | | | | |
Collapse
|
|
30
|
Kin C, Kidess E, Poultsides GA, Visser BC, Jeffrey SS. Colorectal cancer diagnostics: biomarkers, cell-free DNA, circulating tumor cells and defining heterogeneous populations by single-cell analysis. Expert Rev Mol Diagn 2013; 13:581-99. [PMID: 23895128 DOI: 10.1586/14737159.2013.811896] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Reliable biomarkers are needed to guide treatment of colorectal cancer, as well as for surveillance to detect recurrence and monitor therapeutic response. In this review, the authors discuss the use of various biomarkers in addition to serum carcinoembryonic antigen, the current surveillance method for metastatic recurrence after resection. The clinical relevance of mutations including microsatellite instability, KRAS, BRAF and SMAD4 is addressed. The role of circulating tumor cells and cell-free DNA with regards to their implementation into clinical use is discussed, as well as how single-cell analysis may fit into a monitoring program. The detection and characterization of circulating tumor cells and cell-free DNA in colorectal cancer patients will not only improve the understanding of the development of metastasis, but may also supplant the use of other biomarkers.
Collapse
Affiliation(s)
- Cindy Kin
- Department of Surgery, Stanford University School of Medicine, CA, USA.
| | | | | | | | | |
Collapse
|
|
31
|
Huh JW, Kim CH, Lim SW, Kim HR, Kim YJ. Factors predicting long-term survival in colorectal cancer patients with a normal preoperative serum level of carcinoembryonic antigen. J Cancer Res Clin Oncol 2013; 139:1449-55. [PMID: 23765330 DOI: 10.1007/s00432-013-1459-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2013] [Accepted: 06/03/2013] [Indexed: 11/26/2022]
Abstract
PURPOSE The aim of this study was to determine which clinicopathological factors influenced the long-term survival after potentially curative resection of colorectal cancer patients with a normal preoperative serum level of carcinoembryonic antigen (CEA). METHODS A total of 1,732 patients who underwent curative surgery for primary nonmetastatic colorectal cancers from 1997 to 2009 were analyzed. Of these patients, 1,128 (65.1 %) had normal level of preoperative CEA (<5 ng/mL). The predicting factors for survival were analyzed. RESULTS When the serum CEA cutoff value was set at 2.4 ng/mL (median value), the high CEA groups displayed a higher percentage of older patients, males, large-diameter tumors, advanced T and N categories, and positive perineural invasion, compared to the low CEA groups. Multivariate analysis revealed that age, T category, N category, number of lymph nodes retrieved, operative method, lymphovascular invasion, perineural invasion, postoperative chemotherapy, and preoperative serum CEA level ≥ 2.4 ng/mL were independent predictors for 5-year overall survival, while tumor location, tumor size, T category, N category, lymphovascular invasion, and perineural invasion were independent predictors for 5-year disease-free survival. CONCLUSIONS Even if patients with colorectal cancer have a normal preoperative CEA before surgery, CEA may be useful for prognostic stratification using 2.4 ng/mL as the cutoff.
Collapse
Affiliation(s)
- Jung Wook Huh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | | | | | | | | |
Collapse
|
|
32
|
Yamaguchi K, Ogata Y, Akagi Y, Shirouzu K. Identification of high-risk factors as indicators for adjuvant therapy in stage II colon cancer patients treated at a single institution. Oncol Lett 2013; 6:659-666. [PMID: 24137386 PMCID: PMC3789105 DOI: 10.3892/ol.2013.1433] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2013] [Accepted: 06/19/2013] [Indexed: 02/07/2023] Open
Abstract
Although post-operative adjuvant chemotherapy (ACT) is only recommended for patients with stage II colon cancer who are at a high risk of recurrence, the definition of high risk remains unclear. The present study aimed to identify the risk factors for recurrence, which may also be indicators for adjuvant therapy, using a retrospective analysis of clinicopathological data obtained from stage II colon cancer patients who had undergone a curative resection. The present study also investigated the effects of ACT in patients who displayed the risk factors for recurrence. Univariate and multivariate analyses of the data collected from 377 stage II colon cancer patients, treated at Kurume University Hospital (Fukuoka, Japan) between 1982 and 2005, was conducted in order to determine and compare the risk factors for recurrence between the 163 patients who had undergone adjuvant therapy and the 214 patients who had not undergone adjuvant therapy. The risk factors for recurrence in patients who had not undergone adjuvant therapy were a serum carcinoembryonic antigen (CEA) level that was twice the cut-off value and pre-operative bowel obstruction. Adjuvant therapy provided no benefit to patients who presented with neither risk factor, but significantly decreased the recurrence rate in patients presenting with one or both risk factors. Based on these findings, serum CEA levels of twice the cut-off value and pre-operative bowel obstruction were proposed as indicators in the assessment for adjuvant chemotherapy following a curative resection for stage II colon cancer. These results warrant further clinical study of ACT in patients with one or both risk factors.
Collapse
Affiliation(s)
- Keizo Yamaguchi
- Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | | | | | | |
Collapse
|
|
33
|
Lee HC, Ling QD, Yu WC, Hung CM, Kao TC, Huang YW, Higuchi A. Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells. DRUG DESIGN DEVELOPMENT AND THERAPY 2013; 7:491-502. [PMID: 23818760 PMCID: PMC3693723 DOI: 10.2147/dddt.s45890] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Purpose We evaluated the higher levels of carcinoembryonic antigen (CEA) secreted by the LoVo human colon carcinoma cells in a medium containing anticancer drugs. Drug-resistant LoVo cells were analyzed by subcutaneously xenotransplanting them into mice. The aim of this study was to evaluate whether the drug-resistant cells isolated in this study were cancer-initiating cells, known also as cancer stem cells (CSCs). Methods The production of CEA was investigated in LoVo cells that were cultured with 0–10 mM of anticancer drugs, and we evaluated the increase in CEA production by the LoVo cells that were stimulated by anticancer drug treatment. The expression of several CSC markers in LoVo cells treated with anticancer drugs was also evaluated. Following anticancer drug treatment, LoVo cells were injected subcutaneously into the flanks of severe combined immunodeficiency mice in order to evaluate the CSC fraction. Results Production of CEA by LoVo cells was stimulated by the addition of anticancer drugs. Drug-resistant LoVo cells expressed lower levels of CSC markers, and LoVo cells treated with any of the anticancer drugs tested did not generate tumors within 8 weeks from when the cells were injected subcutaneously into severe combined immunodeficiency mice. These results suggest that the drug-resistant LoVo cells have a smaller population of CSCs than the untreated LoVo cells. Conclusion Production of CEA by LoVo cells can be stimulated by the addition of anticancer drugs. The drug-resistant subpopulation of LoVo colon cancer cells could stimulate the production of CEA, but these cells did not act as CSCs in in vivo tumor generation experiments.
Collapse
Affiliation(s)
- Hsin-chung Lee
- Graduate Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taoyuan
| | | | | | | | | | | | | |
Collapse
|
|
34
|
Ben-Ishay O, Peled Z, Othman A, Brauner E, Kluger Y. Clinical presentation predicts the outcome of patients with colon cancer. World J Gastrointest Surg 2013; 5:104-109. [PMID: 23671736 PMCID: PMC3646129 DOI: 10.4240/wjgs.v5.i4.104] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2012] [Revised: 12/03/2012] [Accepted: 03/09/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To elucidate the relationship between clinical presentation and outcome.
METHODS: A single institution retrospective chart review of patients admitted with the diagnosis of colon cancer. We used univariate and a multivariate analysis to identify symptoms association with mortality. An odds ratio based clinical score was created to evaluate the contribution of the quality of symptoms to outcome. Primary measure of outcome was survival.
RESULTS: During the study period, 236 patients met the inclusion criteria. Overall survival was 60.6%, mean follow-up 3.0 years. A bivariate analysis showed that increasing number of symptoms is not associated with mortality. However, a symptom-specific analysis performed using a logistic regression model controlling for age, stage and the duration of complaints revealed that the presence of melena was independently associated with mortality [P = 0.04, odds ratio (OR) 7.4], while rectal bleeding was associated with survival (P = 0.004, OR 3.9). Applying the proposed clinical score to an receiver operating characteristic curve showed that score > 1 had a strong association with mortality. The same logistic regression model was applied. The results showed that a score > 1 was an independent predictor of mortality (P < 0.001) and associated with node-positive disease (P = 0.008).
CONCLUSION: The quality of symptoms rather than quantity is correlated with outcome among patients with colon cancer. The proposed clinical scoring system may correctly predict the patient’s outcome.
Collapse
|
|
35
|
Biffi R, Botteri E, Bertani E, Zampino MG, Cenciarelli S, Luca F, Pozzi S, Cossu ML, Chiappa A, Rotmensz N, Bazolli B, Magni E, Sonzogni A, Andreoni B. Factors predicting worse prognosis in patients affected by pT3 N0 colon cancer: long-term results of a monocentric series of 137 radically resected patients in a 5-year period. Int J Colorectal Dis 2013; 28:207-15. [PMID: 22903336 DOI: 10.1007/s00384-012-1563-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/06/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND PURPOSE For patients with Stage II colon cancer, the use of adjuvant chemotherapy remains controversial. The purpose of this study was to identify clinical and/or pathological findings related to a worse prognosis in this category of patients. PATIENTS AND METHODS We retrospectively analyzed the data of consecutive patients, extracted by an institutional Tumour Registry, admitted to an affiliated University Hospital in Milan (European Institute of Oncology) for adenocarcinoma of the colon (all sites), between 2000 and 2005, and having a final pT3 N0 pathology staging after curative surgery. Adjuvant chemotherapy was decided as a result of a medical decision within a multidisciplinary Tumor Board. RESULTS Data of 137 patients were obtained, with a median follow-up of 77 months (range 6-131). Patients who received chemotherapy were younger than patients who did not. Nine patients out of 137 (6.5 %) died as a consequence of colon cancer recurrence; four of them had received adjuvant chemotherapy. Only histological grade III and mucinous histotype were found to impact on cumulative incidence of colon-related events (p 0.03 and 0.02, respectively); no impact was found on cumulative incidence of colonic neoplasm recurrence-related deaths (p 0.74 and 0.74, respectively). Number of analyzed LNs (lymph nodes) emerged as a factor possibly affecting the cumulative incidence of colon-related events (p 0.09) as well as the cumulative incidence of colonic neoplasm recurrence-related deaths (p 0.10). The risk of events was inversely proportional to the number of dissected LNs, even over 20 up to about 25 LNs. Never-smokers exhibited a lower incidence of colon-related events, although the difference was not statistically significant (p 0.09). All other analyzed variables did not show any impact on survival rate, including age, gender, ASA score, BMI, site of colonic neoplasm, multifocality, perivascular invasion, and use of adjuvant chemotherapy. CONCLUSIONS Histology grading G3 and mucinous histotype were predictors of worse outcome. Efforts to improve LN evaluation should result in clinically significant improvements in outcome, and also the quality of care for patients with radically resected stage II colon cancer.
Collapse
Affiliation(s)
- Roberto Biffi
- Division of Abdomino-Pelvic and Minimally Invasive Surgery, European Institute of Oncology, Via G. Ripamonti, 435, 20141, Milan, Italy.
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Aggarwal C, Meropol NJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, Picus J, Morse MA, Mitchell E, Miller MC, Cohen SJ. Relationship among circulating tumor cells, CEA and overall survival in patients with metastatic colorectal cancer. Ann Oncol 2013; 24:420-428. [PMID: 23028040 DOI: 10.1093/annonc/mds336] [Citation(s) in RCA: 128] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND We previously reported results of a prospective trial evaluating the significance of circulating tumor cells (CTCs) in patients with metastatic colorectal cancer (mCRC). This secondary analysis assessed the relationship of the CTC number with carcinoembryonic antigen (CEA) and overall survival. PATIENTS AND METHODS Patients with mCRC had CTCs measured at baseline and specific time points after the initiation of new therapy. Patients with a baseline CEA value ≥ 10 ng/ml and CEA measurements within ± 30 days of the CTC collection were included. RESULTS We included 217 patients with mCRC who had a CEA value of ≥ 10 ng/ml. Increased baseline CEA was associated with shorter survival (15.8 versus 20.7 months, P = 0.012). Among all patients with a baseline CEA value of ≥ 25 ng/ml, patients with low baseline CTCs (<3, n = 99) had longer survival than those with high CTCs (≥ 3, n = 58; 20.8 versus 11.7 months, P = 0.001). CTCs added prognostic information at the 3-5- and 6-12-week time points regardless of CEA. In a multivariate analysis, CTCs at baseline but not CEA independently predicted survival and both CTCs and CEA independently predicted survival at 6-12 weeks. CONCLUSIONS This study demonstrates that both CEA and CTCs contribute prognostic information for patients with mCRC.
Collapse
Affiliation(s)
- C Aggarwal
- Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania, Philadelphia.
| | - N J Meropol
- Department of Medicine, Division of Hematology-Oncology, Case Western Reserve University, Cleveland, USA
| | - C J Punt
- Department of Medical Oncology, Academic Medical Center, University of Amsterdam, The Netherlands
| | - N Iannotti
- Hematology Oncology Associates, Port Saint Lucie
| | | | - K D Sabbath
- Medical Oncology and Hematology, PC, New Haven
| | | | - J Picus
- Department of Medical Oncology, Washington University, St Louis
| | - M A Morse
- Department of Medical Oncology, Duke University Medical Center, Durham
| | - E Mitchell
- Department of Medicine, Division of Hematology-Oncology, Thomas Jefferson University, Philadelphia
| | | | - S J Cohen
- Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, USA
| |
Collapse
|
|
37
|
Tay CH, Lee HC, Yeung CY, Chan WT, Jiang CB, Liang DC. Different clinical manifestations between primary gastrointestinal malignancies and benign tumors in children. J Pediatr Gastroenterol Nutr 2012; 55:440-444. [PMID: 22343909 DOI: 10.1097/mpg.0b013e31824e88eb] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The purpose of the present study was to review the different clinical manifestations of primary gastrointestinal (GI) malignancies and benign tumors in pediatric patients. METHODS The demographic data, duration to diagnosis, clinical features, laboratory data, location and pathology of the tumors, and outcomes of pediatric patients from January 1984 to December 2009 were retrospectively reviewed. RESULTS A total of 24 GI malignancies and 62 benign tumors were diagnosed. Patients in the benign group were mostly diagnosed in the first decade of life (73%), whereas majority of patients with malignancies were older than 10 years (79%). The most common tumor location in the benign group was the colorectum, whereas in the malignant group, tumors were distributed equally in the small intestine and colorectum. The median duration from onset to diagnosis in the benign group was longer than that of the malignant group (P>00.05). There was statistically significant increase in the presence of hematochezia in patients with benign tumor compared with those with malignancy (P<00.05). Among the malignancies, 79% presented with abdominal pain, followed by weight loss (25%), anorexia (25%), palpable mass (25%), and fever (21%), with statistically significant differences compared with the benign group (P<00.05). Anemia was found in 47% to 63% of patients in both groups (P>00.05). Two patients with polyposis subsequently developed malignancy. CONCLUSIONS Different manifestations of GI malignancies and benign tumors may help pediatricians to detect these early. Patients with polyposis should be aware of the risk of malignant change.
Collapse
Affiliation(s)
- Chow-Hong Tay
- Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan
| | | | | | | | | | | |
Collapse
|
|
38
|
Ryu YJ, Kim CH, Kim HJ, Kang H, Lim SW, Huh JW, Ju JK, Kim YJ, Kim HR. Clinical significance of serial serum carcinoembryonic antigen values for treating rectal cancer with preoperative chemoradiotherapy. JOURNAL OF THE KOREAN SOCIETY OF COLOPROCTOLOGY 2012; 28:205-12. [PMID: 22993707 PMCID: PMC3440490 DOI: 10.3393/jksc.2012.28.4.205] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2012] [Accepted: 07/18/2012] [Indexed: 12/26/2022]
Abstract
Purpose Preoperative chemoradiotherapy is now widely accepted to treat rectal cancer; however, the prognosis for rectal cancer patients during and after chemoradiotherapy must be determined. The aim of this study was to evaluate the serial serum carcinoembryonic antigen (s-CEA) samples in patients with rectal cancer who underwent radical surgery after concurrent chemoradiotherapy (CRT). Methods This study evaluated 236 patients with rectal cancer who received preoperative CRT followed by curative surgery between June 2005 and June 2010. We measured the patient's s-CEA levels pre-CRT, post-CRT and post-surgery. Patients were classified into four groups according to their s-CEA concentrations (group 1, high, high, high; group 2, high, high, normal; group 3, high, normal, normal; group 4, normal, normal, normal). We analyzed the clinicopathologic factors and the outcomes among these groups. Results Of the 236 patients, 12 were in group 1, 31 were in group 2, 67 were in group 3, and 126 were in group 4. The 3-year disease-free survival rate in group 1 was poorer than those in group 3 (P = 0.007) and group 4 (P < 0.001). In a univariate analysis, type of surgery, clinical N stage, pathologic T or N stage, lymphovascular invasion, perineural invasion, and CEA group were prognostic factors. A multivariate analysis revealed that type of surgery, pathologic T stage, and lymphovascular invasion were independent prognostic factors; however, no statistical significance was associated with the CEA group. Conclusion High pre-CRT, post-CRT, and post-surgery s-CEA levels in patients with rectal cancer were associated with high rates of systemic recurrence and poor survival. Therefore, patients with sustained high s-CEA levels during CRT require careful monitoring after surgery.
Collapse
Affiliation(s)
- Young Jae Ryu
- Division of Colorectal Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea
| | | | | | | | | | | | | | | | | |
Collapse
|
|
39
|
Weber GF, Rosenberg R, Murphy JE, Meyer zum Büschenfelde C, Friess H. Multimodal treatment strategies for locally advanced rectal cancer. Expert Rev Anticancer Ther 2012; 12:481-94. [PMID: 22500685 DOI: 10.1586/era.12.3] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
This review outlines the important multimodal treatment issues associated with locally advanced rectal cancer. Changes to chemotherapy and radiation schema, as well as modern surgical approaches, have led to a revolution in the management of this disease but the morbidity and mortality remains high. Adequate treatment is dependent on precise preoperative staging modalities. Advances in staging via endorectal ultrasound, computed tomography, MRI and PET have improved pretreatment triage and management. Important prognostic factors and their impact for this disease are under investigation. Here we discuss the different treatment options including modern tumor-related surgical approaches, neoadjuvant as well as adjuvant therapies. Further clinical progress will largely depend on the broader implementation of multidisciplinary treatment strategies following the principles of evidence-based medicine.
Collapse
Affiliation(s)
- Georg F Weber
- Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA
| | | | | | | | | |
Collapse
|
|
40
|
Cabanillas F, Nieves-Plaza M, Quevedo G, Echenique IA. Rectal adenocarcinoma: proposal for a model based on pretreatment prognostic factors. PUERTO RICO HEALTH SCIENCES JOURNAL 2012; 31:52-58. [PMID: 22783696 PMCID: PMC3481993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
OBJECTIVE Currently the choice of chemotherapy regimen in rectal cancer is made prior to surgery in contrast to colon cancer where it is made postoperatively after the pathological stage has been determined. If we could identify which are the important pretreatment prognostic factors in rectal cancer, we could then target those patients with unfavorable features to investigate potentially more effective preoperative chemotherapy regimens aimed at those with unfavorable features. The present study aimed to determine pre-treatment prognostic factors that are associated with an unfavorable outcome. METHODS A retrospective review of 99 rectal cancer patients operated at the Auxilio Mutuo Hospital, San Juan, Puerto Rico, and the San Pablo Hospital, Bayamón, Puerto Rico was done. Socio-demographic, clinical and treatment data were collected. RESULTS Of the 99 cases, 54% were males. The mean age +/- standard deviation was 62.2 +/- 10.4. In age-adjusted Cox model, male gender (HR [95%CI]: 3.32 [1.09-10.13]), mucinous carcinoma (HR [95% CI]: 3.67 [1.25-10.77]), and clinical stages II & III (HR [95%CI]: 8.19 [1.08-62.08]) were predictors of poor prognosis. In the multivariate age-adjusted analysis, a tendency towards a poorer prognosis was observed for male patients (HR: 2.60), carcinoembryonic antigen level > or =5 ng/ml (HR: 2.55), mucinous carcinoma (HR: 2.96), and clinical stages II & III (HR: 4.96), although results were not statistically significant (p > 0.05). CONCLUSION Although current therapeutic results are relatively favorable with preoperative 5-fluorouracil and radiotherapy, future clinical trials should address the management of those cases with adverse pretreatment prognostic factors so that they can be treated with potentially more effective albeit more toxic chemotherapy regimens.
Collapse
|
|
41
|
Abstract
Huge advances have been made in the treatment of colon cancer over the last decade. Success has been most noticeable in stage IV disease - where careful selection of patients with small-volume disease for treatment with surgical resection ± perioperative chemotherapy has resulted in an improvement in survival of approximately 5-50%; and stage III - disease where the advent of 5-fluorouracil/oxaliplatin, as adjuvant treatment has also resulted in a significant prolongation in survival. Progression-free survival is now an established surrogate for overall survival, and has resulted in more timely reporting of adjuvant studies and therefore faster integration of promising agents into the clinic. Targeted agents, which have shown promise in the metastatic setting, are currently being examined in the adjuvant setting, although results so far are disappointing. Patients with high-risk stage II cancer remain a challenging group. They have a poorer prognosis than those with stage IIIA disease, and national and international guidance recommend offering chemotherapy after careful discussion of the pros and cons. Despite the fact that we have identified many of the biological features that make stage II disease higher risk, we still struggle to achieve the same improvement in survival for this subgroup compared with others. It may be that these patients required treatment with alternative regimens and predictive biomarkers would be particularly helpful.
Collapse
Affiliation(s)
- Janet S Graham
- Beatson West of Scotland Cancer Centre, Great Western Road, Glasgow, G12 0YN, Scotland, UK.
| | | |
Collapse
|
|
42
|
Mehta S, Shelling A, Muthukaruppan A, Lasham A, Blenkiron C, Laking G, Print C. Predictive and prognostic molecular markers for cancer medicine. Ther Adv Med Oncol 2011; 2:125-48. [PMID: 21789130 DOI: 10.1177/1758834009360519] [Citation(s) in RCA: 144] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Over the last 10 years there has been an explosion of information about the molecular biology of cancer. A challenge in oncology is to translate this information into advances in patient care. While there are well-formed routes for translating new molecular information into drug therapy, the routes for translating new information into sensitive and specific diagnostic, prognostic and predictive tests are still being developed. Similarly, the science of using tumor molecular profiles to select clinical trial participants or to optimize therapy for individual patients is still in its infancy. This review will summarize the current technologies for predicting treatment response and prognosis in cancer medicine, and outline what the future may hold. It will also highlight the potential importance of methods that can integrate molecular, histopathological and clinical information into a synergistic understanding of tumor progression. While these possibilities are without doubt exciting, significant challenges remain if we are to implement them with a strong evidence base in a widely available and cost-effective manner.
Collapse
Affiliation(s)
- Sunali Mehta
- School of Medical Sciences, University of Auckland, Auckland, New Zealand
| | | | | | | | | | | | | |
Collapse
|
|
43
|
Hung HY, Chen JS, Yeh CY, Changchien CR, Tang R, Hsieh PS, Tasi WS, You JF, You YT, Fan CW, Wang JY, Chiang JM. Effect of preoperative neutrophil-lymphocyte ratio on the surgical outcomes of stage II colon cancer patients who do not receive adjuvant chemotherapy. Int J Colorectal Dis 2011; 26:1059-65. [PMID: 21479566 DOI: 10.1007/s00384-011-1192-x] [Citation(s) in RCA: 110] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/04/2011] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Selection of appropriate stage II colon cancer patients for adjuvant chemotherapy is critical for improving survival outcome. With the aim of identifying more high risk factors for stage II colon cancer, this study aimed to determine whether the neutrophil-lymphocyte ratio (NLR) is a predictor of surgical outcomes in patients with stage II colon cancer who do not receive adjuvant chemotherapy. MATERIALS AND METHODS We enrolled 1,040 stage II colon cancer patients who had undergone colectomy at a single institution between January 1995 and December 2005 and did not receive adjuvant chemotherapy. RESULTS Of these 1,040 patients, 785 (75.5%) patients had a normal NLR and 255 (24.5%) had an elevated NLR. Those with an elevated NLR included patients ≥65 years, T4b cancer, carcinoembryonic antigen ≥5 ng/mL, and tumor obstruction or perforation. Patients with an elevated NLR had a significantly worse overall survival (OS) and worse disease-free survival (DFS) than did patients with a normal NLR. Cox regression analysis revealed that elevated NLR was an independent predictor of OS (P=0.012) but not DFS (P=0.255). CONCLUSION An elevated NLR is an independent predictor of OS but not DFS in stage II colon cancer patients who did not receive adjuvant chemotherapy. Preoperative NLR measurement in stage II colon cancer patients may be a simple method for identifying patients with a poor prognosis who can be enrolled in further trials of adjuvant chemotherapy.
Collapse
Affiliation(s)
- Hsin-Yuan Hung
- Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Chang Gung University, 5, Fu-Hsing St., Kuei-Shan, Linko, Tao-Yuan, Taiwan
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
44
|
Review of histopathological and molecular prognostic features in colorectal cancer. Cancers (Basel) 2011; 3:2767-810. [PMID: 24212832 PMCID: PMC3757442 DOI: 10.3390/cancers3022767] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2011] [Revised: 06/14/2011] [Accepted: 06/15/2011] [Indexed: 02/06/2023] Open
Abstract
Prediction of prognosis in colorectal cancer is vital for the choice of therapeutic options. Histopathological factors remain paramount in this respect. Factors such as tumor size, histological type and subtype, presence of signet ring morphology and the degree of differentiation as well as the presence of lymphovascular invasion and lymph node involvement are well known factors that influence outcome. Our understanding of these factors has improved in the past few years with factors such as tumor budding, lymphocytic infiltration being recognized as important. Likewise the prognostic significance of resection margins, particularly circumferential margins has been appreciated in the last two decades. A number of molecular and genetic markers such as KRAS, BRAF and microsatellite instability are also important and correlate with histological features in some patients. This review summarizes our current understanding of the main histopathological factors that affect prognosis of colorectal cancer.
Collapse
|
|
45
|
Abstract
BACKGROUND Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta superfamily and has been associated with activation of the p53 pathway in human cancer. The aim of this study was to assess the prognostic value of GDF15 in patients with colorectal cancer (CRC). METHODS Immunohistochemistry and tissue microarrays were used to analyse GDF15 protein expression in 320 patients with CRC. In a subgroup of 60 patients, the level of GDF15 protein in plasma was also measured using a solid-phase proximity ligation assay. RESULTS Patients with CRC with moderate to high intensity of GDF15 immunostaining had a higher recurrence rate compared with patients with no or low intensity in all stages (stages I-III) (HR, 3.9; 95% CI, 1.16-13.15) and in stage III (HR, 10.32; 95% CI, 1.15-92.51). Patients with high plasma levels of GDF15 had statistically shorter time to recurrence (P=0.041) and reduced overall survival (P=0.002). CONCLUSION Growth differentiation factor 15 serves as a negative prognostic marker in CRC. High expression of GDF15 in tumour tissue and high plasma levels correlate with an increased risk of recurrence and reduced overall survival.
Collapse
|
|
46
|
Thirunavukarasu P, Sukumar S, Sathaiah M, Mahan M, Pragatheeshwar KD, Pingpank JF, Zeh H, Bartels CJ, Lee KKW, Bartlett DL. C-stage in colon cancer: implications of carcinoembryonic antigen biomarker in staging, prognosis, and management. J Natl Cancer Inst 2011; 103:689-97. [PMID: 21421861 DOI: 10.1093/jnci/djr078] [Citation(s) in RCA: 123] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The American Joint Committee on Cancer (AJCC) has proposed the inclusion of pretreatment serum carcinoembryonic antigen (CEA) level (C-stage) into the conventional TNM staging system of colon cancer. We assessed the prognosis of various stages of colon cancer after such an inclusion. METHODS Data for all patients (N = 17 910) diagnosed with colonic adenocarcinoma (AJCC stages I, IIA, IIB, IIC, IIIA, IIIB, IIIC, and IV, based on TNM staging system) between January 1, 2004, and December 31, 2004, with a median follow-up of 27 months (range 0-35 months), were collected from the Surveillance, Epidemiology, and End Results database. C-stage (C0-stage = normal CEA level; C1-stage = elevated CEA level) was assigned to all patients with available CEA information (n = 9083). Multivariable analyses using Cox proportional hazards models were used to identify independent factors associated with prognosis. Prognosis of overall stages (AJCC stages I-IV and C0 or C1) was analyzed using Kaplan-Meier survival curves. All statistical tests were two-sided. RESULTS C1-stage was independently associated with a 60% increased risk of overall mortality (hazard ratio of death = 1.60, 95% confidence interval = 1.46 to 1.76, P < .001). Overall survival was decreased in patients with C1-stage cancer compared with C0-stage cancer of the respective overall stages (P < .05). Similarly, decreased overall survival was noted in patients with stage I C1 cancer compared with stage IIA C0 or stage IIIA C0 cancer (P < .001), in patients with stage IIA C1 cancer compared with stage IIIA C0 (P < .001), and in patients with stage IIB C1 or stage IIC C1 cancer compared with stage IIIB C0 cancer (P < .001). CONCLUSIONS C-stage was an independent prognostic factor for colon cancer. The results support routine preoperative CEA testing and C-staging upon diagnosis of colon cancer and the inclusion of C-stage in the conventional TNM staging of colon cancer.
Collapse
|
|
47
|
Jang NY, Kang SB, Kim DW, Kim JH, Lee KW, Kim IA, Kim JS. The role of carcinoembryonic antigen after neoadjuvant chemoradiotherapy in patients with rectal cancer. Dis Colon Rectum 2011; 54:245-52. [PMID: 21228676 DOI: 10.1007/dcr.0b013e3181fcee68] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE The purpose of this study was to evaluate the role of CEA after neoadjuvant chemoradiotherapy in patients with rectal cancer. METHODS This study involved 109 patients with rectal cancer who were treated with preoperative chemoradiotherapy and curative resection. Preoperative serum CEA levels were measured twice, before chemoradiotherapy administration and 4 weeks after chemoradiotherapy. Surgery was performed 6 to 9 weeks after neoadjuvant chemoradiotherapy. RESULTS The 3-year disease-free survival rate was 85.0%. On univariate analysis, prechemoradiotherapy CEA level, postchemoradiotherapy CEA level, tumor regression grade, ypT, ypN, circumferential resection margin, lymphatic invasion, venous invasion, and perineural invasion were associated with disease-free survival. Based on univariate analysis (group 1: prechemoradiotherapy CEA ≤ 3.5; group 2: prechemoradiotherapy CEA > 3.5, postchemoradiotherapy CEA ≤ 2.7; group 3: prechemoradiotherapy CEA >3.5, postchemoradiotherapy CEA > 2.7), we categorized patients into 3 groups according to their pre- and postchemoradiotherapy CEA levels (ng/mL). The 3-year disease-free survival rate was significantly better in groups 1 and 2 (94.7% and 88.0%) than in group 3 (52.6%, P < .001). On multivariate analysis, tumor regression grade (P = .036), ypN (P = .036), and CEA groups (P = .022) were identified as independent prognostic factors for disease-free survival. Furthermore, postchemoradiotherapy CEA ≤ 2.7 ng/mL was an independent predictor of good tumor regression (P = .001), ypT0 to 2 (P = .002), and ypN0 (P = .001). CONCLUSIONS Combined pre- and postchemoradiotherapy CEA levels could be useful as a prognostic factor for disease-free survival in patients with rectal cancer who undergo treatment with neoadjuvant chemoradiotherapy and curative resection. Postchemoradiotherapy CEA may be helpful in a selection of patients who want more conservative surgery after chemoradiotherapy.
Collapse
Affiliation(s)
- Na Young Jang
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, Republic of Korea
| | | | | | | | | | | | | |
Collapse
|
|
48
|
Huh JW, Oh BR, Kim HR, Kim YJ. Preoperative carcinoembryonic antigen level as an independent prognostic factor in potentially curative colon cancer. J Surg Oncol 2010; 101:396-400. [PMID: 20119979 DOI: 10.1002/jso.21495] [Citation(s) in RCA: 88] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE We evaluated the prognostic value of the preoperative serum carcinoembryonic antigen (CEA) level in patients with colon cancer. METHODS We reviewed 474 patients who underwent potentially curative resection for nonmetastatic colon cancer. Patients were categorized into two groups according to the preoperative serum CEA level: low CEA (<5 ng/ml) and high CEA (>or=5 ng/ml) groups. RESULTS During the median 45-month follow-up period, the 5-year overall and disease-free survival rates for patients with a low CEA level were 81.7% and 82.4%, respectively, which were significantly higher than the rates for those with a high CEA level (69.9%; P = 0.011 and 70.6%; P = 0.002, respectively). A multivariate analysis revealed that a preoperative serum CEA level was a significant independent prognostic factor for both overall survival (P = 0.021) and disease-free survival (P = 0.026). Both the overall and disease-free survival rates in patients with stage II tumors differed significantly between the low and high CEA groups, whereas the rates did not different between those with stage I and III tumors. CONCLUSIONS Preoperative serum CEA is a reliable predictor of recurrence and survival after curative surgery in patients with colon cancer, particularly in those classified as having stage II disease.
Collapse
Affiliation(s)
- Jung Wook Huh
- Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Gwangju, Korea
| | | | | | | |
Collapse
|
|
49
|
Chen J, Li Q, Wang C, Wu J, Zhao G. Prognostic significance of c-erbB-2 and vascular endothelial growth factor in colorectal liver metastases. Ann Surg Oncol 2010; 17:1555-63. [PMID: 20069460 DOI: 10.1245/s10434-009-0897-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2009] [Indexed: 12/22/2022]
Abstract
BACKGROUND The prognostic value of c-erbB-2 and vascular endothelial growth factor (VEGF) expression in colorectal liver metastases (CLM) is unclear. The purpose of this study was to clarify the relationship of c-erbB-2 and VEGF with the clinicopathological parameters and the survival results in CLM. METHODS For 44 patients who had undergone liver resection for CLM at Fudan University Cancer Hospital from 2000 to 2007, the expression of c-erbB-2 and VEGF in CLM and the corresponding primary cancer specimens were evaluated immunohistochemically. The correlations among c-erbB-2 and VEGF, clinicopathologic factors, and survival were then statistically analyzed. RESULTS Positive expression rates of c-erbB-2 and VEGF in CLM lesions were 38.64% and 52.72%, respectively. The expression of c-erbB-2 and VEGF in CLM were similar to that of corresponding primary tumor. c-erbB-2 expression correlated with number of metastatic lesions and the distribution of liver metastases. The expression of VEGF correlated with the size of liver metastatic lesion and distribution of liver metastases. A statistically significant association between the expression of c-erbB-2 and VEGF in both CLM and primary tumor was noted. Univariate analysis showed that VEGF was a prognostic factor. However, on multivariate analysis, expression of VEGF was not an independent prognostic marker. Patients with both negative expression of c-erbB-2 and VEGF expression had a better outcome than others. CONCLUSIONS VEGF might be a statistically significant prognostic factor. The combined analysis of c-erbB-2 and VEGF is of added prognostic value. An association exists between c-erbB-2 and VEGF. However, further studies are required to confirm this issue.
Collapse
Affiliation(s)
- Jinggui Chen
- Department of Abdominal Surgery, Cancer Hospital, Fudan University, Shanghai, People's Republic of China
| | | | | | | | | |
Collapse
|
|
50
|
Kim KH, Oh JH, Choi HS, Park JW, Park SC, Kim DY, Chang HJ, Baek JY, Kim SY. Pretreatment Serum CEA as a Prognostic Factor for Rectal Cancer Treated with Preoperative Chemoradiotherapy. JOURNAL OF THE KOREAN SOCIETY OF COLOPROCTOLOGY 2010. [DOI: 10.3393/jksc.2010.26.1.39] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Kyu Hyung Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Hwan Oh
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| | - Hyo Seong Choi
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| | - Ji Won Park
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| | - Seong Chan Park
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| | - Dae Yong Kim
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| | - Hee Jin Chang
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| | - Ji Yeon Baek
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| | - Sun Young Kim
- Center for Colorectal Cancer, National Cancer Center, Goyang, Korea
| |
Collapse
|