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Gramkow MH, Mosgaard CS, Schou JV, Nordvig EH, Dolin TG, Lykke J, Nielsen DL, Pfeiffer P, Qvortrup C, Yilmaz MK, Larsen O, Bojesen SE, Jensen BV, Johansen JS. The prognostic role of circulating CA19-9 and CEA in patients with colorectal cancer. Cancer Treat Res Commun 2025; 43:100907. [PMID: 40132352 DOI: 10.1016/j.ctarc.2025.100907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 02/17/2025] [Accepted: 03/20/2025] [Indexed: 03/27/2025]
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) is the only prognostic circulating biomarker used in clinical practice for recurrence free (RFS), progression free (PFS) and overall survival (OS) in patients with colorectal cancer (CRC). Not all CRC tumors express this protein and carbohydrate antigen (CA)19-9 has been proposed as an adjunctive in prognostication. We aimed to test if CA19-9 yielded additional information to CEA regarding prognosis. PATIENTS AND METHODS We included 886 patients with CRC across eight clinical cohorts. Preoperative serum samples were collected from 376 patients with stage I-III CRC and from 510 with metastatic (m)CRC before 1st (n = 233), 3rd (n = 178) and 3rd/4th (n = 99) line chemotherapy. CA19-9 and CEA were determined by routine assays, the values were log-2 transformed and entered as variables in Cox regression models with RFS (stage I-III), PFS and OS as the outcomes, adjusted for age, sex, and site of primary tumor and mutual adjustment between CA199 and CEA. Random effects meta-analyses were conducted for stage I-III,1st line, and 3rd/4th line mCRC cohorts separately. RESULTS Meta-analyses showed that higher pre-treatment CA19-9 and CEA were associated with shorter RFS (CA19-9: hazard ratio per doubling of concentration (HR)=1.20, 95 % confidence interval (CI) 1.05-1.38; CEA: HR=1.22, 95 % CI 1.05-1.41) in stage I-III CRC. Only higher CEA was associated with shorter OS in 1st line mCRC (HR=1.07, 95 % CI 1.00-1.07). CONCLUSION CA19-9 might aid in identifying patients with a high risk of recurrence after primary radical resection. Further studies are needed to validate these findings.
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Affiliation(s)
- Mathias H Gramkow
- Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark; Danish Dementia Research Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Camilla S Mosgaard
- Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
| | - Jakob V Schou
- Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
| | - Ellen Hein Nordvig
- Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
| | - Troels Gammeltoft Dolin
- Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
| | - Jakob Lykke
- Department of Gastrointestinal Surgery, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
| | - Dorte L Nielsen
- Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Per Pfeiffer
- Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Camilla Qvortrup
- Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Mette K Yilmaz
- Department of Oncology, Aalborg University Hospital, Aalborg, Denmark
| | - Ole Larsen
- Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
| | - Stig E Bojesen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
| | - Benny V Jensen
- Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
| | - Julia S Johansen
- Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark; Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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Yuan C, Zeng L, Duan H, Suksatit B. Meta-analysis of the prognostic value of serum carcinoembryonic antigen in patients with colorectal cancer liver metastases after hepatectomy. Eur J Cancer Prev 2024; 33:334-346. [PMID: 37997904 DOI: 10.1097/cej.0000000000000859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2023]
Abstract
OBJECTIVES Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies. This meta-analysis was aimed at evaluating whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR). METHODS PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cutoff date of 27 February 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0. RESULTS This meta-analysis included 36 studies involving a total of 11 143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS: HR = 1.61, 95% CI = 1.49-1.75, P < 0.001) and recurrence-free survival (RFS: HR = 1.27, 95% CI = 1.11-1.45, P < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor overall survival (OS: HR = 2.66, 95% CI = 2.10-3.38, P < 0.001). CONCLUSION High preoperative and postoperative serum CEA levels in patients with CRCLM were significantly associated with poor prognosis, independent of treatment modality, mode of analysis, case origin, and cutoff value classification.
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Affiliation(s)
- Chenzhao Yuan
- Faculty of Nursing, Chiang Mai University, Chiang Mai, Thailand
| | - Lumin Zeng
- School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Hongxiang Duan
- Faculty of Nursing, Chiang Mai University, Chiang Mai, Thailand
- School of Nursing, Chengdu University, Chengdu, China
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Hao YJ, Chang LW, Yang CY, Lo LC, Lin CP, Jian YW, Jiang JK, Tseng FG. The rare circulating tumor microemboli as a biomarker contributes to predicting early colorectal cancer recurrences after medical treatment. Transl Res 2024; 263:1-14. [PMID: 37558203 DOI: 10.1016/j.trsl.2023.07.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 07/03/2023] [Accepted: 07/28/2023] [Indexed: 08/11/2023]
Abstract
Early prognosis of cancer recurrence remains difficult partially due to insufficient and ineffective screening biomarkers or regimes. This study evaluated the rare circulating tumor microemboli (CTM) from liquid biopsy individually and together with circulating tumor cells (CTCs) and serum CEA/CA19-9 in a panel, on early prediction of colorectal cancer (CRC) recurrence. Stained CTCs/CTM were detected by a microfluidic chip-based automatic rare-cell imaging platform. ROC, AUC, Kaplan-Meier survival, and Cox proportional hazard models regarding 4 selected biomarkers were analyzed. The relative risk, odds ratio, predictive accuracy, and positive/negative predictive value of biomarkers individually and in combination, to predict CRC recurrence were assessed and preliminarily validated. The EpCAM+Hochest+CD45- CTCs/CTM could be found in all cancer stages, where more recurrences were observed in late-stage cases. Significant correlations between CTCs/CTM with metastatic stages and clinical treatment were illustrated. CA19-9 and CTM could be seen as independent risk factors in patient survivals, while stratified patients by grouped biomarkers on the Kaplan-Meier analyses presented more significant differences in predicting CRC recurrences. By monitoring the panel of selected biomarkers, disease progressions of 4 CRC patients during follow-up visits after first treatments within 3 years were predicted successfully. This study unveiled the value of rare CTM on clinical studies and a panel of selected biomarkers on predicting CRC recurrences in patients at the early time after medical treatment, in which the CTM and serum CA19-9 could be applied in clinical surveillance and CRC management to improve the accuracy.
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Affiliation(s)
- Yun-Jie Hao
- Department of Engineering and System Science, National Tsing Hua University, Hsinchu, Taiwan
| | - Lu-Wey Chang
- Department of Engineering and System Science, National Tsing Hua University, Hsinchu, Taiwan
| | - Chih-Yung Yang
- Department of Teaching and Research, Taipei City Hospital, Taipei, Taiwan; Commission for General Education, National United University, Miaoli, Taiwan; General Education Center, University of Taipei, Taipei, Taiwan
| | - Liang-Chuan Lo
- National Genomics Center for Clinical and Biotechnological Applications, Cancer and Immunology Research Center, National Yang-Ming Chiao-Tung University, Taipei, Taiwan
| | - Chien-Ping Lin
- Department of Surgery, Division of Colorectal Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yuan-Wei Jian
- Department of Surgery, Division of Colorectal Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jeng-Kai Jiang
- Department of Surgery, Division of Colorectal Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Fan-Gang Tseng
- Department of Engineering and System Science, National Tsing Hua University, Hsinchu, Taiwan; Department of Chemistry, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing-Hua University, Hsinchu, Taiwan; Research Center for Applied Sciences, Taipei, Taiwan.
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Zhang XL, Wang HT, Tang Y, Lu Q, Yuan HX, Wang X, Liu LH, Zhu DX, Wang WP. Colorectal liver metastases: Correlations of contrast-enhanced ultrasound features with tumor clinicopathological factors and clinical outcomes following conversion therapy. Clin Hemorheol Microcirc 2024; 86:339-356. [PMID: 37927253 DOI: 10.3233/ch-231963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2023]
Abstract
OBJECTIVE To explore the prognostic impact of contrast-enhanced ultrasound (CEUS) features for initially unresectable colorectal liver metastases (CLMs) in a clinical setting of conversion therapy. METHODS Between March 2015 and November 2020, consecutive patients with CLMs who received conversion treatment were prospectively enrolled. All participants underwent liver CEUS at baseline. The primary endpoint was conversion resection rate (R0 and overall resection). Secondary endpoints were objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). RESULTS 104 participants who completed conversion treatment were included. CEUS enhancement pattern was correlated with index lesion (size and echogenicity), primary (site, differentiation, perineural invasion, and RAS genotype) and serum (CA19-9 level) characteristics (P = <0.001-0.016). CEUS enhancement pattern was significantly associated with R0 resection rate, ORR, PFS, and OS (P = 0.001-0.049), whereas enhancement degree was associated with PFS and OS (P = 0.043 and 0.045). Multivariate analysis showed that heterogeneous enhancement independently predicted R0 and overall resection (P = 0.028 and 0.024) while rim-like enhancement independently predicted ORR and OS (P = 0.009 and 0.026). CONCLUSION CEUS enhancement pattern was significantly associated with tumor characteristics and clinical outcomes following conversion therapy, and thus might be of prognosis impact for initially unresectable CLMs.
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Affiliation(s)
- Xiao-Long Zhang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hang-Tao Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yang Tang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qing Lu
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hai-Xia Yuan
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xi Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Li-Heng Liu
- Department of Radiology and Multi-Disciplinary Team of Colorectal Cancer, Zhongshan Hospital, Fudan University, Shanghai, China
| | - De-Xiang Zhu
- Department of General Surgery and Multi-Disciplinary Team of Colorectal Cancer, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wen-Ping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
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Tang F, Huang CW, Tang ZH, Lu SL, Bai T, Huang Q, Li XZ, Zhang B, Wu FX. Prognostic role of serum carcinoembryonic antigen in patients receiving liver resection for colorectal cancer liver metastasis: A meta-analysis. World J Gastrointest Surg 2023; 15:2890-2906. [PMID: 38222018 PMCID: PMC10784827 DOI: 10.4240/wjgs.v15.i12.2890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 11/03/2023] [Accepted: 11/28/2023] [Indexed: 12/27/2023] Open
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies. AIM To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR). METHODS PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cut-off date of February 27, 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0. RESULTS This meta-analysis included 36 studies involving a total of 11143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS) [hazard ratio (HR) = 1.61, 95% confidence interval (CI): 1.49-1.75, P < 0.001] and recurrence-free survival (HR = 1.27, 95%CI: 1.11-1.45, P < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor OS (HR = 2.66, 95%CI: 2.10-3.38, P < 0.001). A comparison by treatment modality, analysis modality, patient source, and cutoff-value showed that overall, high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis. CONCLUSION This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.
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Affiliation(s)
- Fan Tang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Cheng-Wen Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Zhi-Hong Tang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Shao-Long Lu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Tao Bai
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Qing Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Xing-Zhi Li
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Bin Zhang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Fei-Xiang Wu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Key Laboratory of High-Incidence-Tumor Prevention & Treatment, Ministry of Education, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Wang R, Xu B, Sun M, Pang X, Wang X, Zhu J, Lian J, Lu H. Dynamic monitoring of serum CEA and CA19-9 predicts the prognosis of postoperative stage II colon cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:107138. [PMID: 37925830 DOI: 10.1016/j.ejso.2023.107138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 10/04/2023] [Accepted: 10/23/2023] [Indexed: 11/07/2023]
Abstract
BACKGROUND We sought to investigate the prognostic significance of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) dynamics for stage II colon cancer patients undergoing radical resection. METHODS This study retrospectively analyzed 1517 stage II colon cancer patients admitted to the Harbin Medical University Cancer Hospital from January 2011 to December 2016. To observe the relationship between tumor markers dynamic monitoring and survival, we calculated cut-off values for ΔCEA and ΔCA19-9. Group according to the cut-off values and compare the differences in survival between subgroups. RESULTS Preoperative CA199 (HR = 3.122), postoperative CEA (HR = 2.941) and histological type (HR = 2.855) were independent prognostic factors in multivariate Cox proportional hazards models. The 5-year overall survival (OS) in the patients with normal preoperative CEA and CA19-9 was significantly better than the patients with elevated preoperative CEA or CA19-9 and the patients with elevated preoperative CEA and CA19-9 (92.6 % vs. 87.6 % vs. 81.0 %, P < 0.05). 469 patients with normal pre- and post-operative CEA had the highest 5-year OS (93.5 %, P < 0.05). Among the 177 patients with elevated pre- and post-operative CEA, the 5-year OS rate was only 81.8 % (P < 0.05). The cut-off values for Δ CEA and Δ CA19-9 in stage II colon cancer patients with elevated preoperative tumor markers were 2.625 ng/ml and 7.835 U/ml, respectively. The Kaplan-Meier curves showed that Δ CEA≥2.625 ng/ml and Δ CA19-9≥7.835 U/mL were associated with better outcome (87.8 % vs. 79.6 %, P < 0.05; 85.8 % vs. 79.1 %, P > 0.05). At the same time, we found that adjuvant chemotherapy significantly improved 5-year OS in patients with elevated preoperative CEA or CA19-9 (91.0 % vs. 80.9 % and 89.6 % vs. 80.2 %, P < 0.05). CONCLUSIONS Persistent postoperative elevation of CEA/CA19-9 is associated with a poor prognosis. CEA and CA19-9 may be high-risk factors for postoperative adjuvant therapy in stage II colon cancer patients. For stage II colon cancer patients with elevated preoperative CEA, patients with Δ CEA<2.625 ng/ml have poor survival and can improve prognosis by receiving adjuvant therapy.
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Affiliation(s)
- Ren Wang
- Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China
| | - Benjie Xu
- Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China
| | - Mingming Sun
- Department of Clinical Pharmacy, The Third Affiliated Hospital of Qiqihar Medical University, China
| | - Xiangyi Pang
- Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xin Wang
- Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China
| | - Jiahao Zhu
- Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China
| | - Jie Lian
- Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China.
| | - Haibo Lu
- Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China.
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Dou X, Xi J, Zheng G, Ren G, Tian Y, Dan H, Xie Z, Niu L, Duan L, Li R, Wu H, Feng F, Zheng J. A nomogram was developed using clinicopathological features to predict postoperative liver metastasis in patients with colorectal cancer. J Cancer Res Clin Oncol 2023; 149:14045-14056. [PMID: 37548773 DOI: 10.1007/s00432-023-05168-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 07/09/2023] [Indexed: 08/08/2023]
Abstract
PURPOSE The objective of this study is to examine the risk factors that contribute to the development of liver metastasis (LM) in patients who have suffered radical resection for colorectal cancer (CRC), and to establish a nomogram model that can be used to predict the occurrence of the LM. METHODS The present study enrolled 1377 patients diagnosed with CRC between January 2010 and July 2021. The datasets were allocated to training (n = 965) and validation (n = 412) sets in a randomly stratified manner. The study utilized univariate and multivariate logistic regression analyses to establish a nomogram for predicting LM in patients with CRC. RESULTS Multivariate analysis revealed that T stage, N stage, number of harvested lymph nodes (LNH), mismatch repair (MMR) status, neutrophil count, monocyte count, postoperative carcinoembryonic antigen (CEA) levels, postoperative cancer antigen 125 (CA125) levels, and postoperative carbohydrate antigen 19-9 (CA19-9) levels were independent predictive factors for LM after radical resection. These factors were then utilized to construct a comprehensive nomogram for predicting LM. The nomogram demonstrated great discrimination, with an area under the curve (AUC) of 0.782 for the training set and 0.768 for the validation set. Additionally, the nomogram exhibited excellent calibration and significant clinical benefit as confirmed by the calibration curves and the decision curve analysis, respectively. CONCLUSION This nomogram has the potential to support clinicians in identifying high-risk patients who may develop LM post-surgery. Clinicians can devise personalized treatment and follow-up plans, ultimately leading to an improved prognosis for patients.
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Affiliation(s)
- Xinyu Dou
- Xi'an Medical University, Xi'an, China
- Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jiaona Xi
- Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Gaozan Zheng
- Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Guangming Ren
- Xi'an Medical University, Xi'an, China
- Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Ye Tian
- Xi'an Medical University, Xi'an, China
- Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Hanjun Dan
- Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zhenyu Xie
- Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Liaoran Niu
- Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Lili Duan
- Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Ruikai Li
- Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Hongze Wu
- Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Fan Feng
- Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
| | - Jianyong Zheng
- Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
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Kobayashi K, Ono Y, Kitano Y, Oba A, Sato T, Ito H, Mise Y, Shinozaki E, Inoue Y, Yamaguchi K, Saiura A, Takahashi Y. Prognostic Impact of Tumor Markers (CEA and CA19-9) on Patients with Resectable Colorectal Liver Metastases Stratified by Tumor Number and Size: Potentially Valuable Biologic Markers for Preoperative Treatment. Ann Surg Oncol 2023; 30:7338-7347. [PMID: 37365416 DOI: 10.1245/s10434-023-13781-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 06/04/2023] [Indexed: 06/28/2023]
Abstract
BACKGROUND Although patients with resectable colorectal liver metastasis (CLM), a population with good prognosis, have been treated with upfront surgery, some patients have had a poor prognosis. This study aimed to investigate biologic prognostic factors in patients with resectable CLMs. METHODS This single-center retrospective study enrolled consecutive patients who underwent liver resection for initial CLMs at the Cancer Institute Hospital between 2010 and 2020. The study defined CLMs as resectable (tumor size < 5 cm; < 4 tumors; no extrahepatic metastasis) or borderline resectable (BR). Preoperative chemotherapy was administered to patients with BR CLMs. RESULTS During the study period, 309 CLMs were classified as resectable without preoperative chemotherapy and 345 as BR with preoperative chemotherapy. For the 309 patients with resectable CLMs, the independent poor prognostic factors associated with overall survival in the multivariable analysis were high tumor marker levels (CEA ≥ 25 ng/mL and/or CA19-9 ≥ 50 U/mL; (hazard ratio [HR], 2.45; p = 0.0007), no adjuvant chemotherapy (HR, 1.69; p = 0.043), and age of 75 years or older (HR, 2.09; p = 0.012). The 5-year survival rates for the patients with high tumor marker (TM) levels (CEA ≥25 ng/mL and/or CA19-9 ≥50 U/mL) were significantly worse than for those with low TM levels (CEA < 25 ng/mL and CA19-9 < 50 U/mL) (55.3% vs. 81.1%; p <0.0001) and similar to the rate for those with BR CLMs (52.1%; p = 0.864). Postoperative adjuvant chemotherapy had an impact on prognosis only in the high-TM group (HR, 2.65; p = 0.007). CONCLUSIONS High TM levels have a prognostic impact on patients with resectable CLMs stratified by tumor number and size. Perioperative chemotherapy improves long-term outcomes for patients with CLM and high TM levels.
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Affiliation(s)
- Kosuke Kobayashi
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan
| | - Yoshihiro Ono
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
| | - Yuki Kitano
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan
| | - Atsushi Oba
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan
| | - Takafumi Sato
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan
| | - Hiromichi Ito
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan
| | - Yoshihiro Mise
- Department of Hepatobiliary and Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Eiji Shinozaki
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Inoue
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan
| | - Kensei Yamaguchi
- Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akio Saiura
- Department of Hepatobiliary and Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Yu Takahashi
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
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Yoshikawa Y, Fukunaga M, Takahashi J, Shimizu D, Masuda T, Mizushima T, Yamada K, Mori M, Eguchi H, Doki Y, Ochiya T, Mimori K. Identification of the Minimum Combination of Serum microRNAs to Predict the Recurrence of Colorectal Cancer Cases. Ann Surg Oncol 2023; 30:233-243. [PMID: 36175711 PMCID: PMC9726799 DOI: 10.1245/s10434-022-12355-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 07/08/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Serum microRNAs (miRNAs) have been recognized as potential stable biomarkers for various types of cancer. Considering the clinical applications, there are certain critical requirements, such as minimizing the number of miRNAs, reproducibility in a longitudinal clinical course, and superiority to conventional tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9. This study aimed to identify serum miRNAs that indicate the recurrence of colorectal cancer (CRC), surpassing inter-tumor heterogeneity. METHODS We conducted an analysis of 434 serum samples from 91 patients with CRC and 71 healthy subjects. miRNAs were obtained from Toray Co., Ltd, and miRNA profiles were analyzed using a three-step approach. miRNAs that were highly expressed in patients with CRC than in the healthy controls in the screening phase, and those that were highly expressed in the preoperative samples than in the 1-month postoperative samples in the discovery phase, were extracted. In the validation phase, the extracted miRNAs were evaluated in 323 perioperative samples, in chronological order. RESULTS A total of 12 miRNAs (miR-25-3p, miR-451a, miR-1246, miR-1268b, miR-2392, miR-4480, miR-4648, miR-4732-5p, miR-4736, miR-6131, miR-6776-5p, and miR-6851-5p) were significantly concordant with the clinical findings of tumor recurrence, however their ability to function as biomarkers was comparable with CEA. In contrast, the combination of miR-1246, miR-1268b, and miR-4648 demonstrated a higher area under the curve (AUC) than CEA. These three miRNAs were upregulated in primary CRC tissues. CONCLUSION We identified ideal combinatorial miRNAs to predict CRC recurrence.
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Affiliation(s)
- Yukihiro Yoshikawa
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita Japan ,Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka Japan
| | | | - Junichi Takahashi
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita Japan
| | - Dai Shimizu
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita Japan
| | - Takaaki Masuda
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita Japan
| | - Tsunekazu Mizushima
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka Japan
| | - Kazutaka Yamada
- Coloproctology Center Takano Hospital, Kumamoto, Kumamoto Japan
| | - Masaki Mori
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka Japan
| | - Takahiro Ochiya
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Koshi Mimori
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita Japan
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10
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Wang R, Yan Z. A "conversion-deterioration-double mutation" theory for the evolution and progression of colorectal cancer. Cancer Med 2022; 11:2601-2611. [PMID: 35285179 PMCID: PMC9249989 DOI: 10.1002/cam4.4637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 01/11/2022] [Accepted: 01/28/2022] [Indexed: 11/09/2022] Open
Abstract
In this study, based on some clinical phenomena and recently published knowledge, we proposed our "conversion-deterioration-double mutation" theory, which provides a possible unifying explanation for the evolutionary process of colorectal cancer cells in the human body. In this theory, we proposed that there is a partial interconversion and a jump conversion relationship among normal colorectal epithelial cells, colorectal cancer cells, stem cells, and cancer stem cells (conversion). This conversion leads to tumor heterogeneity. We also proposed that well-differentiated cancer cells converted from cancer stem cells have a more aggressive pattern than primary cancer cells (deterioration). The deterioration of primary cancer cells leads to differences in treatment responses and prognosis. Finally, we speculate a double mutation theory, indicating that for metastasis to occur, both mutations of cancer cells and mutations of target organs are needed and should match and meet. All these three points constitute the "conversion-deterioration-double mutation" theory.
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Affiliation(s)
- Rui Wang
- Department of Critical Care MedicineShengjing Hospital of China Medical UniversityShenyangChina
| | - Zhaopeng Yan
- Department of General SurgeryShengjing Hospital of China Medical UniversityShenyangChina
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11
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More Liver Metastases Detected Intraoperatively Indicates Worse Prognosis for Colorectal Liver Metastases Patients after Resection Combined with Microwave Ablation. JOURNAL OF ONCOLOGY 2022; 2022:3819564. [PMID: 35498543 PMCID: PMC9050310 DOI: 10.1155/2022/3819564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 03/26/2022] [Accepted: 03/28/2022] [Indexed: 11/26/2022]
Abstract
Background Whether more tumor numbers detected in surgery compared to preoperative image affecting survival of colorectal liver metastases (CRLM) patients after hepatectomy combined with microwave ablation (MWA) remains unclear. Methods From 2013 to 2018, 85 CRLM patients who underwent hepatectomy combined with MWA were retrospectively assessed. Compared to the tumor numbers in preoperative image, patients with equal intraoperative tumor numbers were defined as the equal number group (n = 45); patients detected more tumor numbers in surgery were defined as the more number group (n = 40). Clinicopathological factors and prognosis were compared between two groups. Results Compared to the equal number group, the more number group was characterized by more lymphatic metastasis, synchronous metastasis of liver lesion, and tumor numbers over 5 (all P < 0.05). Median survival time was 46.7 months and 26.8 months in the equal and more number group. Significantly worse overall survival (OS) was found in more number group to the equal number group (P = 0.027). In Cox analysis, more tumor number than image and high level of carbohydrate antigen 19-9 (CA19-9) were poor prognostic factors for OS. Conclusion In patients receiving hepatectomy combined with MWA, detecting more liver metastases in surgery than preoperative image indicates poor long-term survival. These patients were characterized by more lymphatic metastasis, synchronous metastasis of liver lesion, and tumor numbers over 5. Intensive follow-up to detect early recurrence and potent postoperative therapy to improve survival may be justified in patients detected more tumor numbers in surgery with a high CA19-9 level.
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12
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Peng JH, Tai Y, Zhao YX, Luo BJ, Ou QJ, Pan ZZ, Zhang L, Lu ZH. Programmed death-ligand 1 expression in the tumour stroma of colorectal liver oligometastases and its association with prognosis after liver resection. Gastroenterol Rep (Oxf) 2021; 9:443-450. [PMID: 34733530 PMCID: PMC8560040 DOI: 10.1093/gastro/goaa077] [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: 04/11/2020] [Revised: 09/11/2020] [Accepted: 09/16/2020] [Indexed: 12/09/2022] Open
Abstract
Background The clinical value of programmed death-ligand 1 (PD-L1) expression in colorectal liver oligometastases (CLOs) remains undefined. This study aimed to detect PD-L1 in the microenvironment of CLOs and determine its association with patient prognosis. Methods We collected 126 liver-resection specimens from CLO patients who underwent curative liver resection between June 1999 and December 2016. Immunohistochemistry (IHC) was performed to assess PD-L1 expression in paraffin-embedded specimens. Overall survival (OS) and recurrence-free survival (RFS) were analysed using the Kaplan–Meier method and log-rank test. Results PD-L1 was mainly expressed in the stroma of liver oligometastases. Patients with high PD-L1 expression had a higher proportion of clinical-risk scores (CRSs) of 2–4 (67.7% vs 40.4%; P = 0.004). With a median 58-month follow-up, patients with high PD-L1 expression had a significantly lower 3-year OS rate (65.5% vs 92.7%; P = 0.001) and 3-year RFS rate (34.7% vs 83.8%; P < 0.001) than patients with low PD-L1 expression. Multivariate Cox analysis demonstrated that high PD-L1 expression (hazard ratio [HR] = 3.581; 95% confidence interval [CI] 2.301–9.972; P = 0.015), CRS 2–4 (HR = 6.960; 95% CI 1.135–42.689; P = 0.036) and increased preoperative CA19-9 (HR = 2.843; 95% CI 1.229–6.576; P = 0.015) were independent risk factors for OS. High PD-L1 expression (HR = 4.815; 95% CI 2.139–10.837; P < 0.001) and lymph-node metastasis (HR = 2.115; 95% CI 1.041–4.297; P = 0.038) were independent risk factors for RFS. Conclusion This study found that PD-L1 was commonly expressed in the tumour stroma of CLOs and high PD-L1 expression was associated with poor prognosis.
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Affiliation(s)
- Jian-Hong Peng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
| | - Yi Tai
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
| | - Yi-Xin Zhao
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
| | - Bao-Jia Luo
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
| | - Qing-Jian Ou
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
| | - Zhi-Zhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
| | - Lin Zhang
- Department of Clinical Laboratory, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China
| | - Zhen-Hai Lu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
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13
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Inoue H, Kawaguchi T, Ikoma H, Morimura R, Yamamoto Y, Ochiai T, Shimizu H, Arita T, Konishi H, Shiozaki A, Kuriu Y, Kubota T, Fujiwara H, Okamoto K, Takahashi H, Takabe K, Tsung A, Otsuji E. Oligometastasis scoring system for predicting survival of patients with colorectal liver metastasis after hepatectomy. J Surg Oncol 2021; 124:791-800. [PMID: 34196000 DOI: 10.1002/jso.26575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 05/19/2021] [Accepted: 05/22/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Oligometastasis, the presence of a small number of resectable metastatic tumors, usually has favorable outcomes. Here we examined whether the novel oligometastatic score (OLGS), which divides the number of colorectal liver metastases (CRLMs) by the time from colorectal resection to liver recurrence, better predicts CRLM patient survival than the commonly used clinical risk score. METHODS A total of 143 patients who underwent curative hepatectomy for CRLMs between 2007 and 2018 were analyzed. We investigated their clinical characteristics and outcomes using OLGS. RESULTS Of the 143 CRLM patients, 70 had synchronous CRLMs and 73 had metachronous CRLMs. Patients with metachronous CRLMs were divided into OLGS-low (n = 59) and OLGS-high (n = 14) subgroups. The 5-year overall survival (OS) rates after hepatectomy differed significantly between the subgroups (p < .001). In the multivariate Cox model, a high OLGS was an independent predictor of 5-year OS (p < .001), and the hazard ratio (HR) of the OLGS-high group (HR = 7.171) was higher than that of the high clinical risk score group (HR = 4.337). CONCLUSION The OLGS, a simple and handy scoring system, better predicts the 5-year OS of patients with CRLMs after hepatectomy and warrants prospective validation.
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Affiliation(s)
- Hiroyuki Inoue
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan
| | - Tsutomu Kawaguchi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan
| | - Hisashi Ikoma
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan
| | - Ryo Morimura
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan
| | - Yusuke Yamamoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan
| | - Toshiya Ochiai
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan.,Department of Surgery, North Medical Center Kyoto Prefectural, University of Medicine, Kyoto, Japan
| | - Hiroki Shimizu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan
| | - Tomohiro Arita
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan
| | - Hirotaka Konishi
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan
| | - Atsushi Shiozaki
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan
| | - Yoshiaki Kuriu
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan
| | - Takeshi Kubota
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan
| | - Hitoshi Fujiwara
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan
| | - Kazuma Okamoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan
| | - Hideo Takahashi
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Kazuaki Takabe
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Allan Tsung
- Division of Surgical Oncology, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural, University of Medicine, Kyoto, Japan
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14
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Takeda Y, Mise Y, Matsumura M, Hasegawa K, Yoshimoto J, Imamura H, Noro T, Yamamoto J, Ishizuka N, Inoue Y, Ito H, Takahashi Y, Saiura A. Accuracy of Modern Clinical Risk Score Including RAS Status Changes Based on Whether Patients Received Perioperative Chemotherapy for Colorectal Liver Metastases. World J Surg 2021; 45:2176-2184. [PMID: 33880608 DOI: 10.1007/s00268-021-05976-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/10/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND A modified Fong clinical score (m-Fong CS) that includes the RAS mutation status has recently been proposed and offered an improved survival stratification of patients who undergo surgery and systemic chemotherapy for colorectal liver metastases (CLM). The aim of this study is to assess whether a CS that includes RAS status is influenced by whether patients receive perioperative chemotherapy. METHODS We created a new CS using multivariate analysis of data of patients who underwent hepatectomy for CLM for the first time between 2010 and 2016 at a single hospital (n = 341, 79% received perioperative chemotherapy). The resulting CS and m-Fong CS were then validated in the patient cohort at three other hospitals (n = 309). Furthermore, the applicability of the two CS in the total cohort (n = 650) was tested according to whether the patients received perioperative chemotherapy. RESULTS The new CS comprised mutant RAS status, ≥4 CLMs, and a CA19-9 level ≥100 U/mL (1 point per factor). Both the new CS and m-Fong CS failed to stratify the survival of the 309 patients in the validation cohort, including those who did not receive perioperative chemotherapy (29%). Both of the CS accurately stratified the survival of patients who underwent perioperative chemotherapy but not of those who underwent surgery alone. CONCLUSION A CS that includes the RAS mutation status can stratify the survival of patients who undergo hepatectomy combined with perioperative chemotherapy, but it has limited value for patients who undergo surgery alone.
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Affiliation(s)
- Yoshinori Takeda
- Department of Hepato-Biliary-Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Ariake, Tokyo, 113-8421, Japan
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Hongo, Tokyo, Japan
| | - Yoshihiro Mise
- Department of Hepato-Biliary-Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Ariake, Tokyo, 113-8421, Japan
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Hongo, Tokyo, Japan
| | - Masaru Matsumura
- Clinical Research and Medical Development Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Clinical Research and Medical Development Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan
| | - Jiro Yoshimoto
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Hongo, Tokyo, Japan
| | - Hiroshi Imamura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Hongo, Tokyo, Japan
| | - Takuji Noro
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Junji Yamamoto
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Naoki Ishizuka
- Clinical Research and Medical Development Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Inoue
- Department of Hepato-Biliary-Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Ariake, Tokyo, 113-8421, Japan
| | - Hiromichi Ito
- Department of Hepato-Biliary-Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Ariake, Tokyo, 113-8421, Japan
| | - Yu Takahashi
- Department of Hepato-Biliary-Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Ariake, Tokyo, 113-8421, Japan
| | - Akio Saiura
- Department of Hepato-Biliary-Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Ariake, Tokyo, 113-8421, Japan.
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Hongo, Tokyo, Japan.
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Preoperative CA19-9: a competitive predictor of recurrence in patients with colorectal cancer liver metastases after hepatectomy. Int J Colorectal Dis 2021; 36:767-778. [PMID: 33420522 DOI: 10.1007/s00384-020-03828-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/25/2020] [Indexed: 02/04/2023]
Abstract
PURPOSE The role of preoperative carbohydrate antigen 19-9 (CA19-9) in colorectal cancer liver metastases (CRLM) patients is still unclear. The present study aimed to explore the prognostic significance of preoperative CA19-9 in those patients. METHODS A total of 691 CRLM patients were included in this study. X-tile analyses were performed to determine the optimal cut-off values of CA19-9 and carcinoembryonic antigen (CEA). Prognostic predictors were identified by multivariate analyses. RESULTS The optimal cut-off values of CA19-9 and CEA for 5-year recurrence-free survival (RFS) were 35.24 U/ml and 20.4 ng/ml, respectively. Patients with high-level CA19-9 had significantly worse RFS and overall survival (OS) than those with low-level CA19-9 (P = 0.001 and P = 0.002, respectively). In addition, patients with high-level CA19-9 had poor RFS and OS (P = 0.028 and P = 0.011, respectively) at low-level CEA. Multivariate analyses confirmed that preoperative CA19-9 was an independent predictor for RFS (hazard ratio [HR] 1.295; 95% confidence interval [CI] 1.043-1.607; P = 0.019) but not for OS (HR 1.213; 95% CI 0.902-1.631; P = 0.201). CONCLUSION CA19-9 is a promising predictor of recurrence for CRLM patients undergoing hepatectomy, and an effective supplement for patients with low-level CEA.
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Diagnostic and Prognostic Value of CEA and CA19-9 in Colorectal Cancer. Diseases 2021; 9:diseases9010021. [PMID: 33802962 PMCID: PMC8006010 DOI: 10.3390/diseases9010021] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 03/07/2021] [Accepted: 03/10/2021] [Indexed: 12/20/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. A diagnosis at early stages with enhanced screening methods is vital as metastases and recurrences increase mortality. The aim of this study was to analyze the tumor markers CEA and CA19-9 combined in correlation with diagnostics and prognosis. Therefore, 1487 patients with CRC who were diagnosed and treated between 2000 and 2015 at the University Hospital Ulm, Germany, were retrospectively evaluated. Overall and recurrence-free survival was analyzed in association with preoperative CEA and CA19-9 separately and combined and a multivariate analysis was performed. The 5-year overall survival was significantly shorter in patients with a CEA or CA19-9 level ≥200 compared to patients with an increased, but <200, or normal level (CEA: 69%/44%/7%; CA19-9: 66%/38%/8%). Patients with both tumor markers increased also showed a remarkably shorter 5-year survival rate (CEA+/CA19-9+: 23%). The multivariate analysis emphasizes these results (p-value < 0.0001). Patients with both tumor markers elevated had the shortest 5-year recurrence-free survival rate, followed by patients with either CEA or CA19-9 elevated (CEA-/CA19-9-: 79%; CEA+/CA19-9; CEA-/CA19-9+: 65%; CEA+/CA19-9+: 44%). In conclusion, measuring CEA and CA19-9 preoperatively in CRC patients is reasonable and could be useful as a prognostic factor.
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Chen Q, Li X, Zhao J, Bi X, Li Z, Huang Z, Zhang Y, Zhou J, Zhao H, Cai J. What is the optimal number of neoadjuvant chemotherapy cycles for resectable colorectal liver oligometastases? ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:7. [PMID: 33553300 PMCID: PMC7859783 DOI: 10.21037/atm-20-4289] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 09/30/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND The optimal number of neoadjuvant chemotherapy (NAC) cycles for resectable colorectal liver oligometastases (CLOM) remains unclear. The aim of this study was to investigate the optimal number of NAC cycles. METHODS One hundred twenty-nine consecutive patients were included in this study. X-tile analysis was implemented to investigate the optimal cut-off point for NAC cycles. Propensity score matching was performed to reduce selection bias. Kaplan-Meier curves and Cox risk regression models were used to analyse progression-free survival (PFS) and overall survival (OS). RESULTS The optimal cut-off point for NAC cycles was 5. There were no significant differences in R0 resection, pathological response or postoperative complications between the groups with a low number of NAC cycles group (≤5 cycles, n=80) and high number of NAC cycles (>5 cycles, n=49). Patients with a high number of NAC cycles were more likely to have NAC toxicity than those with a low number of cycles (87.8% vs. 65.0%, P=0.004). Multivariate analysis revealed that >5 NAC cycles was an independent predictor of reduced PFS (HR =1.808, 95% CI: 1.205-2.712, P=0.004) and reduced OS (HR =1.723, 95% CI: 1.041-2.851, P=0.034). In the oxaliplatin-based regimen group, patients with a low number of NAC cycles had a better PFS (P<0.001, mPFS: 14.7 vs. 5.4 months) and better OS (P=0.018, mOS: 57.7 months vs. 41.0 months) than those with a high number of cycles. After 1:1 propensity matching (34 cases vs. 34 cases), multivariate analysis revealed that >5 NAC cycles was an independent predictor of reduced PFS (HR =2.265, 95% CI: 1.281-4.007, P=0.005) and reduced OS (HR =2.813, 95% CI: 1.359-5.822, P=0.005). In the oxaliplatin-based regimen group, patients with a low number of NAC cycles had better PFS (P<0.001, mPFS: 17.5 vs. 5.6 months) and better OS (P=0.008, mOS: 59.0 vs. 31.8 months) than those with a high number of cycles. CONCLUSIONS Fewer than 5 NAC cycles was optimal for biologically resectable CLOM patients. Giving more than 5 NAC cycles was unnecessary because a higher number of NAC cycles has more unfavourable survival and higher NAC toxicities, while leading to similar R0 resection rates and pathological responses.
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Affiliation(s)
- Qichen Chen
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xingchen Li
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianjun Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinyu Bi
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhiyu Li
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhen Huang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yefan Zhang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianguo Zhou
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Chen Y, Chang W, Ren L, Chen J, Tang W, Liu T, Jian M, Liu Y, Wei Y, Xu J. Comprehensive Evaluation of Relapse Risk (CERR) Score for Colorectal Liver Metastases: Development and Validation. Oncologist 2020; 25:e1031-e1041. [PMID: 32181531 DOI: 10.1634/theoncologist.2019-0797] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 02/04/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The calculation of the tumor burden score (TBS) is not perfect because the bilobar spread of colorectal liver metastasis (CRLM) is neglected. The identification of an ideal prognostic scoring system for CRLM remains controversial. MATERIALS AND METHODS Patients who underwent curative intent liver resection for CRLM from one medical center were enrolled in cohort 1 (787 patients) and cohort 2 (162 patients). Tumor relapse-free survival (RFS) was the main outcome. A Cox regression model was used to identify independent predictors of prognosis. The time-dependent area under the curve, calibration curve, and C-index were employed to validate the predictive ability of the survival model. RESULTS Modified TBS (mTBS) was established by a mathematical equation with parameters including CRLM size, CRLM number, and unilobar or bilobar metastasis. Five preoperative predictors of worse RFS were identified in cohort 1 and incorporated into the Comprehensive Evaluation of Relapse Risk (CERR) score: KRAS/NRAS/BRAF-mutated tumor (1 point); node-positive primary (1 point); extrahepatic disease (1 point); carcinoembryonic antigen level > 200 ng/mL or carbohydrate antigen 19-9 (CA19-9) >200 U/mL (1 point); and mTBS between 5 and 11 (1 point) or 12 and over (2 points). Patients in cohort 1 were stratified by their CERR score into risk groups: the high-risk group (CERR score 4 or more), the medium-risk group (CERR score 2-3), and the low-risk group (CERR score 0-1). Importantly, internal validation in cohort 1 and further validation in cohort 2 both showed the superior discriminatory capacity of the CERR score. CONCLUSION mTBS should be promoted. The CERR score is a powerful prognostic tool that can help determine optimal clinical management strategies. IMPLICATIONS FOR PRACTICE This work resulted in the successful modification of the tumor burden score and development of a comprehensive and practical prognostic scoring system-the Comprehensive Evaluation of Relapse Risk (CERR) score. The CERR score, with a better prognostic discriminatory ability, outperformed the Fong score. Perhaps more importantly, the CERR score is a powerful prognostic tool because it unified the most consistently reported prognostic factors. Therefore, the CERR score can assist doctors in determining optimal clinical management strategies.
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Affiliation(s)
- Yijiao Chen
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Wenju Chang
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, People's Republic of China
| | - Li Ren
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, People's Republic of China
| | - Jingwen Chen
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, People's Republic of China
| | - Wentao Tang
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, People's Republic of China
| | - Tianyu Liu
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Mi Jian
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Yu Liu
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Ye Wei
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, People's Republic of China
| | - Jianmin Xu
- Colorectal Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
- Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Shanghai, People's Republic of China
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Peng J, Ou Q, Pan Z, Zhang R, Zhao Y, Deng Y, Lu Z, Zhang L, Li C, Zhou Y, Guo J, Wan D, Fang Y. Serum CNPY2 isoform 2 represents a novel biomarker for early detection of colorectal cancer. Aging (Albany NY) 2019; 10:1921-1931. [PMID: 30070972 PMCID: PMC6128441 DOI: 10.18632/aging.101512] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 07/27/2018] [Indexed: 02/06/2023]
Abstract
Since early diagnosis is very important for treating CRC, we decided to detect peripheral serum canopy fibroblast growth factor signaling regulator 2 (CNPY2) isoform 2 to verify its diagnostic value for CRC patients. Serum samples were collected from 430 CRC patients and 201 healthy controls. Enzyme-linked immunosorbent assay (ELISA) detection kits for CNPY2 isoform 2 were generated and then applied to measure serum CNPY2 isoform 2 concentrations. Serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were also measured. The median serum CNPY2 isoform 2 concentrations in all CRC patients were significantly higher than those in the healthy control group (all P<0.001). Those with stage I CRC presented the highest area under the receiver operating characteristic curve (AUC) for CNPY2 isoform 2 [0.707, 95% confidence interval (CI): 0.649-0.765, P<0.001]. The diagnostic efficiency of the combination of CNPY2 isoform 2, CEA and CA19-9 was significantly higher than that of each biomarker detected separately (all P<0.0167). Serum CNPY2 isoform 2 may be a valuable biomarker for the early detection of CRC and presents an improvement in the diagnostic efficiency by combination of CEA and CA19-9.
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Affiliation(s)
- Jianhong Peng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China
| | - Qingjian Ou
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China.,Department of Experimental Research, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China
| | - Zhizhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China
| | - Rongxin Zhang
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China
| | - Yujie Zhao
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China
| | - Yuxiang Deng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China
| | - Zhenhai Lu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China
| | - Lin Zhang
- Department of Clinical Laboratory Medicine, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China
| | - Caixia Li
- School of Mathematics and Computational Science Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Yaxian Zhou
- Senboll Biotechnology Co., Ltd., Pingshan Bio-Pharmacy Business Accelerator, Pingshan District, Shenzhen, Guangdong 518000, P. R. China
| | - Jian Guo
- Senboll Biotechnology Co., Ltd., Pingshan Bio-Pharmacy Business Accelerator, Pingshan District, Shenzhen, Guangdong 518000, P. R. China
| | - Desen Wan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China
| | - Yujing Fang
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China.,Department of Experimental Research, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South ; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China
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20
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Zhou W, Yang F, Peng J, Wang F, Lin Y, Jiang W, Yang X, Li L, Lu Z, Wan D, Pan Z, Fan W. High pretreatment serum CA19-9 level predicts a poor prognosis for patients with stage III colon cancer after curative resection and adjuvant chemotherapy. J Cancer 2019; 10:3810-3818. [PMID: 31333798 PMCID: PMC6636281 DOI: 10.7150/jca.31375] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Accepted: 05/10/2019] [Indexed: 01/01/2023] Open
Abstract
Carbohydrate antigen 19-9 (CA19-9) is one of the most widely used tumor markers in gastrointestinal cancer. However, serum CA19-9 is not a recommended routine measurement in colon cancer. In this study, we evaluated the value of the preoperative serum CA19-9 level for the prediction of postoperative prognosis in stage III colon cancer. The medical records of 367 consecutive patients with stage III colon cancer who underwent curative resection followed by adjuvant chemotherapy with oxaliplatin and capecitabine between December 2007 and April 2015 were retrospectively reviewed. We determined the optimal cutoff value of CA19-9 for 3-year recurrence using the receiver operating characteristic (ROC) method. Differences in disease-free survival (DFS) and overall survival (OS) rates stratified by CA19-9 level were compared by using Kaplan-Meier and log-rank tests. A Cox proportional hazards model was used to identify prognostic variables for DFS and OS. The statistically determined best cutoff value for CA19-9 was 24 U/ml. High CA19-9 levels (> 24 U/ml) were significantly associated with poorly differentiated tumors, abnormal carcinoembryonic antigen (CEA) levels, and a high cumulative incidence of lung metastasis. Additionally, compared with low CA19-9 levels, high preoperative CA19-9 levels were associated with inferior 3-year DFS and OS rates, especially for high-risk patients (T4Nany or TanyN2). Multivariate analyses revealed that CA19-9 was an independent factor associated with both DFS (hazard ratio [HR], 2.248; 95% confidence interval [CI], 1.393-3.628; P = 0.001) and OS (HR: 2.081; 95% CI: 1.137-3.808; P = 0.017). The results of this study showed that high levels of preoperative serum CA19-9 indicated a worse prognostic outcome for stage III colon cancer patients. An early follow-up protocol to assess lung metastasis and a full course of adjuvant chemotherapy should be used for these patients.
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Affiliation(s)
- Wenhao Zhou
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Fan Yang
- Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine Guangzhou, 510060, P.R. China
| | - Jianhong Peng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Fulong Wang
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Yuzhu Lin
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Wu Jiang
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Xia Yang
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Liren Li
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Zhenhai Lu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Desen Wan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Zhizhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Wenhua Fan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
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21
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Hidaka E, Maeda C, Nakahara K, Wakamura K, Ishiyama Y, Shimada S, Seki J, Takano Y, Oae S, Enami Y, Sawada N, Ishida F, Kudo SE. High Serum CA19-9 Concentration Predicts Poor Prognosis in Elderly Patients with Stage IV Colorectal Cancer. Gastrointest Tumors 2019; 5:117-124. [PMID: 30976583 PMCID: PMC6422141 DOI: 10.1159/000493793] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 09/17/2018] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND/AIM The optimal treatment strategy for elderly patients with stage IV colorectal cancer (CRC) remains controversial due to limited research data. The purpose of this study was to evaluate treatment results and to clarify the prognostic factors, especially poor prognosis factors, in elderly patients with stage IV CRC. METHODS We retrospectively reviewed the data of 82 elderly patients (aged ≥75 years) with stage IV CRC who underwent surgical treatment at our hospital between April 2001 and March 2017. Factors that affected prognosis and the ability to undergo treatment were analyzed via multivariate analysis. RESULTS The median overall survival (OS) in the patients with high pretreatment serum carbohydrate antigen 19-9 (CA19-9) concentration (> 370 U/mL) was significantly worse than in those with lower serum CA19-9 concentration (0-370 U/mL) (8.5 vs. 19.2 months, p = 0.0059). In univariate analysis, age (≥80 years) (p = 0.014), performance status of 1-3 (p = 0.028), and high pretreatment serum CA19-9 concentration (p = 0.014) were significant prognostic factors for poor OS. By contrast, resection of the primary tumor (p = 0.024), chemotherapy (p < 0.0001), and resection of distant metastasis (p = 0.0005) were significant prognostic factors for favorable OS. Multivariate analysis showed that a high pretreatment serum CA19-9 concentration was an independent prognostic factor for poor OS (p = 0.01). Meanwhile, resection of the primary tumor (p = 0.033), chemotherapy (p < 0.0001), and resection of distant metastasis (p = 0.0008) were prognostic factors for favorable OS. CONCLUSIONS A high pretreatment serum CA19-9 concentration (> 370 U/mL) was a reliable predictive factor for poor prognosis, and aggressive treatments should be performed carefully in these patients. Moreover, various treatments, including surgery and chemotherapy, might improve OS in elderly patients with stage IV CRC.
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Affiliation(s)
- Eiji Hidaka
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan
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22
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Peng J, Ou Q, Deng Y, Xiao B, Zhang L, Li J, Li Y, Wan D, Lu Z, Fang Y. TROP2 overexpression in colorectal liver oligometastases is associated with poor prognosis after liver resection. Ther Adv Med Oncol 2019; 11:1758835919897543. [PMID: 35173815 PMCID: PMC8842308 DOI: 10.1177/1758835919897543] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Accepted: 12/05/2019] [Indexed: 12/24/2022] Open
Abstract
Background: The aim of this study was to assess trophoblast antigen protein 2 (TROP2)
expression in liver oligometastases and its prognostic value for colorectal
liver oligometastasis (CLO) patients undergoing liver resection. Methods: We retrospectively selected 129 consecutive CLO patients who underwent
curative liver resection between June 1999 and December 2016.
Immunohistochemistry (IHC) was performed to detect TROP2 expression in
paraffin-embedded specimens. Recurrence-free survival (RFS) and overall
survival (OS) were analyzed using the Kaplan–Meier method and log-rank test,
and independent prognostic factors were identified with Cox regression
modeling. Results: TROP2 was expressed in 72.9% (94/129) of liver oligometastatic tissues. TROP2
expression in primary tumors and liver oligometastases was significantly
positively correlated (r = 0.758,
p < 0.001). Survival analysis indicated that CLO
patients with high TROP2 expression had worse 3-year RFS (44.2%
versus 66.4%, p = 0.007) and 3-year OS
rates (70.3% versus 85.4%, p = 0.035) than
did those with low TROP2 expression. Multivariate analysis indicated that
high TROP2 expression was independently associated with poor RFS [hazard
ratio (HR) = 2.017; 95% confidence interval (CI) 1.198–3.396;
p = 0.023] and OS (HR = 2.090; 95% CI 1.037–4.214;
p = 0.039). Gene expression profile analysis indicated
that high TROP2 expression was associated with TNFα signaling
via NF-κB, the inflammatory response and
epithelial–mesenchymal transition (EMT). Conclusions: TROP2 overexpression was associated with an unfavorable oncologic prognosis
in patients with CLO undergoing liver resection. Detecting TROP2 expression
may be valuable for guiding postoperative treatment among CLO patients.
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Affiliation(s)
- Jianhong Peng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
| | - Qingjian Ou
- Department of Colorectal Surgery, Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
| | - Yuxiang Deng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
| | - Binyi Xiao
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
| | - Lin Zhang
- Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
| | - Jibin Li
- Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
| | - Yin Li
- Department Endoscopic and Laser Cancer Center, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
| | - Desen Wan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, P. R. China
| | - Zhenhai Lu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong 510060, P. R. China
| | - Yujing Fang
- Department of Colorectal Surgery, Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong 510060, P. R. China
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23
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Chang H, Yu X, Chen K, Wang QX, Zhang S, Zeng ZF, Ding PR, Pan ZZ, Xiao WW, Gao YH. Prognostic Value of the Cycle Number of Perioperative Chemotherapy in Locoregionally Advanced Rectal Cancer: a Propensity Score Matching Analysis. J Cancer 2018; 9:4346-4354. [PMID: 30519339 PMCID: PMC6277658 DOI: 10.7150/jca.27251] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Accepted: 09/05/2018] [Indexed: 02/07/2023] Open
Abstract
Background: Appropriate cycle number of perioperative chemotherapy for patients with locoregionally advanced rectal cancer (LARC) remains unknown. This study aimed to evaluate how cycle number of perioperative chemotherapy influenced the prognosis of LARC patients. Methodology / Principal Findings: In this study, a total of 388 consecutive patients were enrolled and retrospectively reviewed if they were diagnosed with untreated stage cII-III LARC and treated with neoadjuvant chemoradiotherapy plus radical surgery followed by adjuvant chemotherapy or not. After grouping by the postoperative pathologic stage (yp0-I vs. ypII-III), propensity score matching was performed in each group to balance baseline characteristics between the patients treated with chemotherapy cycle ≤ 7 and those treated with chemotherapy cycle ≥ 8. The chemotherapy cycle was analyzed for its association with the survivals of the matched patients in the 2 groups, respectively. And the incidence of treatment-related complications was also compared. Through analysis, chemotherapy cycle ≥ 8 appeared to predict better overall, disease-free and distant-metastasis-free survivals in the whole cohort of matched patients (P values were 0.003, 0.002 and 0.004, respectively) and the ypII-III group (P values were 0.006, 0.005 and 0.014, respectively). But in the yp0-I group, chemotherapy of 8 cycles or more brought no improvement of survivals but only more acute toxicities (83.5% vs. 57.0%, P < 0.001). Conclusions / Significance: Chemotherapy cycle ≥ 8 was proven associated with improved prognosis of LARC patients, especially those with ypII-III disease. But prolonged chemotherapy should be performed with caution in patients with yp0-I stage.
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Affiliation(s)
- Hui Chang
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center.,State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine
| | - Xin Yu
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center.,State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine
| | - Kai Chen
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center.,State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine
| | - Qiao-Xuan Wang
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center.,State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine
| | - Shu Zhang
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center.,State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine
| | - Zhi-Fan Zeng
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center.,State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine
| | - Pei-Rong Ding
- State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine.,Department of Colorectal Surgery, Sun Yat-sen University Cancer Center
| | - Zhi-Zhong Pan
- State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine.,Department of Colorectal Surgery, Sun Yat-sen University Cancer Center
| | - Wei-Wei Xiao
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center.,State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine
| | - Yuan-Hong Gao
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center.,State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine
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24
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Chang H, Jiang W, Ye WJ, Tao YL, Wang QX, Xiao WW, Gao YH. Is long interval from neoadjuvant chemoradiotherapy to surgery optimal for rectal cancer in the era of intensity-modulated radiotherapy?: a prospective observational study. Onco Targets Ther 2018; 11:6129-6138. [PMID: 30288048 PMCID: PMC6160274 DOI: 10.2147/ott.s169985] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
OBJECTIVES To evaluate the impact of interval between neoadjuvant chemoradiotherapy (NACRT) and surgery on therapeutic and adverse effects of surgery, and long-term outcome of patients with locally advanced rectal cancer (RC), in the era of intensity-modulated radiotherapy (IMRT). PATIENTS AND METHODS Patients diagnosed with stage II-III RC and treated with IMRT-based NACRT followed by radical surgery were enrolled consecutively from April 2011 to March 2014. The data of all the patients were collected prospectively and grouped according to their NACRT-to-surgery interval. The therapeutic and adverse effects of surgery, and survivals were compared between the patients with interval ≤7 weeks and those with interval ≥8 weeks. RESULTS A total of 231 patients were eligible for analysis, including 106 cases with interval ≤7 weeks and 125 cases with interval ≥8 weeks. The therapeutic and adverse effects of surgery were similar between these two groups of patients. However, interval ≥8 weeks appeared to lead to poorer overall, distant-metastasis-free and disease-free survivals, compared with interval ≤7 weeks. The HRs were 1.805, 1.714, and 1.796 (P-values were 0.045, 0.049, and 0.028), respectively. CONCLUSION For patients with locally advanced RC, a long NACRT-to-surgery interval might bring a potential risk of increased distant metastasis rather than a better tumor regression in the era of IMRT.
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Affiliation(s)
- Hui Chang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China, ;
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China, ;
| | - Wu Jiang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China, ;
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Wei-Jun Ye
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China, ;
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China, ;
| | - Ya-Lan Tao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China, ;
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China, ;
| | - Qiao-Xuan Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China, ;
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China, ;
| | - Wei-Wei Xiao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China, ;
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China, ;
| | - Yuan-Hong Gao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China, ;
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China, ;
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Pan Z, Peng J, Lin J, Chen G, Wu X, Lu Z, Deng Y, Zhao Y, Sui Q, Wan D. Is there a survival benefit from adjuvant chemotherapy for patients with liver oligometastases from colorectal cancer after curative resection? Cancer Commun (Lond) 2018; 38:29. [PMID: 29843800 PMCID: PMC5993126 DOI: 10.1186/s40880-018-0298-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Accepted: 03/08/2018] [Indexed: 12/20/2022] Open
Abstract
Background Although colorectal oligometastases to the liver can potentially be cured with aggressive local ablation, the efficacy of adjuvant chemotherapy (ACT) for such metastasis remains unclear. The present study explored the effects of ACT on patients with colorectal liver oligometastases (CLO) after curative resections and aimed to identify patients who could benefit from ACT. Methods We retrospectively analyzed 264 eligible patients with CLO who underwent curative resection between September 1999 and June 2015. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and log-rank test; prognostic factors were a by Cox regression modeling. Results Among 264 patients, 200 (75.8%) patients received ACT and 64 (24.2%) did not receive ACT. These two groups did not significantly differ in clinicopathologic characteristics, and had comparable 3-year OS and RFS rates (RFS: 42.1% vs. 45.7%, P = 0.588; OS: 69.7% vs. 62.7%, P = 0.446) over a median follow-up duration of 35.5 months, irrespective of preoperative chemotherapy. ACT markedly improved 3-year OS in high-risk patients with Memorial Sloan-Kettering Cancer Center clinical risk scores (MSKCC-CRS) of 3–5 (68.2% vs. 33.8%, P = 0.015), but presented no additional benefit in patients with MSKCC-CRS of 0–2 (72.2% vs. 78.6%, P = 0.834). In multivariate analysis, ACT was independently associated with improved OS in patients with MSKCC-CRS of 3–5. Conclusions ACT might offer a prognostic benefit in high-risk patients with CLOs after curative liver resection, but not in low-risk patients. Therefore, patients’ risk status should be determined before ACT administration to optimize postoperative therapeutic strategies.
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Affiliation(s)
- Zhizhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Jianhong Peng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Junzhong Lin
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Gong Chen
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Xiaojun Wu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Zhenhai Lu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Yuxiang Deng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Yujie Zhao
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Qiaoqi Sui
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Desen Wan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
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Lin J, Peng J, Zhao Y, Luo B, Zhao Y, Deng Y, Sui Q, Gao Y, Zeng Z, Lu Z, Pan Z. Early recurrence in patients undergoing curative resection of colorectal liver oligometastases: identification of its clinical characteristics, risk factors, and prognosis. J Cancer Res Clin Oncol 2017; 144:359-369. [PMID: 29128882 PMCID: PMC5794819 DOI: 10.1007/s00432-017-2538-8] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 10/24/2017] [Indexed: 12/18/2022]
Abstract
PURPOSE Oligometastatic disease can potentially be cured when an optimal approach is performed. Early recurrence after liver resection is an intractable problem, and the clinical implications remain unknown in colorectal liver oligometastases (CLOM) patients. This study aimed to investigate the clinical characteristics, risk factors, and prognosis related to early recurrence in these patients. METHODS A total of 307 consecutive patients with CLOM undergoing curative liver resection were retrospectively reviewed between September 1999 and June 2016. Early recurrence was defined as any recurrence or death from CLOM that occurred within 6 months of liver resection. RESULTS With a median follow-up time of 31.7 months, the 3-year overall survival (OS) and recurrence-free survival rates were 68.7 and 42.5%, respectively. Forty-nine (16.0%) patients developed early recurrence and showed a poorer 3-year OS than those with non-early recurrence (22.3 vs. 75.8%, P < 0.001) or later recurrence (22.3 vs. 52.8 vs. 63.2%, P < 0.001). Moreover, early recurrence was identified as an independent predictor of 3-year OS [hazard ratio (HR) 6.282; 95% confidence interval (CI) 3.980-9.915, P < 0.001]. In multivariate analysis, a node-positive primary tumor [odds ratio (OR) 2.316; 95% CI 1.097-4.892, P = 0.028) and metastatic diameter > 3 cm (OR 2.560; 95% CI 1.290-5.078; P = 0.007) were shown to be risk factors for early recurrence. The salvage liver resection rate for patients with early recurrence was significantly lower than that for patients with later recurrence (4.1 vs. 19.7%, P = 0.010). CONCLUSIONS Early recurrence should be investigated in routine clinical practice, even in patients with CLOM after curative liver resection. Detailed preoperative comprehensive measurements might help stratify high-risk patients, and a non-surgical treatment for early recurrence might represent an effective alternative.
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Affiliation(s)
- Junzhong Lin
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Jianhong Peng
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Yixin Zhao
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Baojia Luo
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Yujie Zhao
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Yuxiang Deng
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Qiaoqi Sui
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China
| | - Yuanhong Gao
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.,Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China
| | - Zhifan Zeng
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.,Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China
| | - Zhenhai Lu
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.
| | - Zhizhong Pan
- State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.
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Peng J, Li H, Ou Q, Lin J, Wu X, Lu Z, Yuan Y, Wan D, Fang Y, Pan Z. Preoperative lymphocyte-to-monocyte ratio represents a superior predictor compared with neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for colorectal liver-only metastases survival. Onco Targets Ther 2017; 10:3789-3799. [PMID: 28794643 PMCID: PMC5538703 DOI: 10.2147/ott.s140872] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Systemic inflammation was recognized as an essential factor contributing to the development of malignancies. This study aimed to investigate the prognostic value of pre-operative lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in patients with colorectal liver-only metastases (CLOM) undergoing hepatectomy. We retrospectively enrolled 150 consecutive patients with CLOM between 2000 and 2012. The optimal cutoff values of continuous LMR, NLR, and PLR were determined using the receiver operating characteristic curve analysis. Recurrence-free survival (RFS) and overall survival (OS) related to the LMR, NLR, and PLR were analyzed using both Kaplan–Meier and multivariate Cox regression methods. Elevated LMR (≥2.82) and lower NLR (<4.63) were significantly associated with better RFS and OS in patients with CLOM after hepatectomy, instead of lower PLR (<150.17). Multivariate Cox analysis identified elevated LMR as the only independent inflammatory factor for better RFS (hazard ratio, 0.591; 95% CI, 0.32–0.844; P=0.008) and OS (hazard ratio, 0.426; 95% CI, 0.254–0.716; P=0.001). In the subgroup analysis, elevated LMR was a significant favorable factor in both 5-year RFS and OS of patients with male gender, lymph node metastases, colon cancer, liver tumor with the largest diameter <5 cm, preoperative carcinoembryonic antigen level <200 ng/mL, negative hepatitis B virus infection, non-anatomic liver resection, postoperative chemotherapy, and non-preoperative chemotherapy. This study demonstrated that the preoperative LMR was an independent predictor of RFS and OS in patients with CLOM undergoing hepatic resection, and it appeared to be superior to the NLR and PLR.
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Affiliation(s)
- Jianhong Peng
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Hui Li
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Qingjian Ou
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Junzhong Lin
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Xiaojun Wu
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Zhenhai Lu
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Yunfei Yuan
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Desen Wan
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Yujing Fang
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Zhizhong Pan
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
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