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Venturino A, Colloca GA. Prognostic Effect of CEA Cut-Off in Patients with Resectable Colorectal Liver Metastases: A Meta-Analysis and Meta-Regression. J Gastrointest Cancer 2025; 56:117. [PMID: 40358861 DOI: 10.1007/s12029-025-01244-6] [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] [Accepted: 05/04/2025] [Indexed: 05/15/2025]
Abstract
BACKGROUND Although preoperative carcinoembryonic antigen (CEA) is a variable used in most prognostic scores assessing the outcome of patients with colorectal liver metastases (CRLM) undergoing resection, it is unclear what the optimal cut-off is or in which patient subgroups CEA is most relevant. The purpose of this study is to evaluate the prognostic effect of CEA in resected CRLM patients and to explore in which subgroups CEA is most closely associated with overall survival (OS). METHODS A systematic literature search was performed, selecting studies that evaluated a relationship between preoperative CEA and OS in patients undergoing CRLM radical surgery. A meta-analysis assessed the overall effect size of the relationship on the selected study cohorts, based on CEA cut-off. An evaluation of 21 baseline variables was performed to explore their possible effect on the relationship between CEA and OS. RESULTS The study confirms a significant negative prognostic effect of increased CEA on OS (HR 1.46, CI 1.30-1.65), but heterogeneity among studies is significant. The effect is consistent for all CEA cut-offs, although the relationship tends to weaken in more recent studies for cut-offs < 10 ng/mL. Meta-regressions also suggest that the prognostic effect may be more pronounced in the elderly. In addition, the effect of CEA ≥ 20 ng/mL on OS appears significantly reduced in the subgroup with mutated RAS carcinoma. CONCLUSIONS For patients with resectable CRLM, the CEA cut-off should be increased to 20 ng/mL, and evaluation in prospective studies of the more pronounced negative prognostic effect of preoperative CEA in the elderly and wild-type RAS CRLM patients is recommended.
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Affiliation(s)
| | - Giuseppe A Colloca
- Oncologia Medica & Innovation, Via Aicardi n. 37, I-18100, Imperia, Italy
- U. O. Oncologia Territoriale, AUSL Bologna, Bologna, Italy
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Chen Q, Chen J, Deng Y, Bi X, Zhao J, Zhou J, Huang Z, Cai J, Xing B, Li Y, Li K, Zhao H. Personalized prediction of postoperative complication and survival among Colorectal Liver Metastases Patients Receiving Simultaneous Resection using machine learning approaches: A multi-center study. Cancer Lett 2024; 593:216967. [PMID: 38768679 DOI: 10.1016/j.canlet.2024.216967] [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: 03/25/2024] [Revised: 05/14/2024] [Accepted: 05/15/2024] [Indexed: 05/22/2024]
Abstract
BACKGROUND To predict clinical important outcomes for colorectal liver metastases (CRLM) patients receiving colorectal resection with simultaneous liver resection by integrating demographic, clinical, laboratory, and genetic data. METHODS Random forest (RF) models were developed to predict postoperative complications and major complications (binary outcomes), as well as progression-free survival (PFS) and overall survival (OS) (time-to-event outcomes) of the CRLM patients based on data from two hospitals. The models were validated on an external dataset from an independent hospital. The clinical utility of the models was assessed via decision curve analyses (DCA). RESULTS There were 1067 patients included in survival prediction analyses and 1070 patients included in postoperative complication prediction analyses. The RF models provided an assessment of the model contributions of features for outcomes and suggested KRAS, BRAF, and MMR status were salient for the PFS or OS predictions. RF model of PFS showed that the Brier scores at 1-, 3-, and 5-year PFS were 0.213, 0.202 and 0.188; and the AUCs of 1-, 3- and 5-year PFS were 0.702, 0.720 and 0.743. RF model of OS revealed that Brier scores of 1-,3-, and 5-year OS were 0.040, 0.183 and 0.211; and the AUCs of 1-, 3- and 5-year OS were 0.737, 0.706 and 0.719. RF model for postoperative complication resulted in an AUC of 0.716 and a Brier score of 0.196. DCA curves clearly demonstrated that the RF models for these outcomes exhibited a superior net benefit across a wide range of threshold probabilities, signifying their favorable clinical utility. The RF models consistently exhibited robust performance in both internal cross-validation and external validation. The individualized risk profile predicted by the models closely aligned with the actual survival outcomes observed for the patients. A web-based tool (https://kanli.shinyapps.io/CRLMRF/) was provided to demonstrate the practical use of the prediction models for new patients in the clinical setting. CONCLUSION The predictive models and a web-based tool for personalized prediction demonstrated a moderate predictive performance and favorable clinical utilities on several key clinical outcomes of CRLM patients receiving simultaneous resection, which could facilitate the clinical decision-making and inform future interventions for CRLM patients.
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Affiliation(s)
- Qichen Chen
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
| | - Jinghua 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
| | - Yiqiao Deng
- 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
| | - 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
| | - 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
| | - 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
| | - 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
| | - Baocai Xing
- Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I, School of Oncology, Beijing Cancer Hospital and Institute, Peking University, Ministry of Education, Beijing, China.
| | - Yuan Li
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
| | - Kan Li
- Merck & Co., Inc., Rahway, NJ, USA.
| | - 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.
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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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Song HC, Zhou HC, Gu P, Bao B, Sun Q, Mei TM, Cui W, Yao K, Yao HZ, Zhang SY, Wang YS, Song RP, Wang JZ. Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases. World J Gastrointest Oncol 2024; 16:331-342. [PMID: 38425385 PMCID: PMC10900158 DOI: 10.4251/wjgo.v16.i2.331] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 12/05/2023] [Accepted: 12/25/2023] [Indexed: 02/02/2024] Open
Abstract
BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality, with the liver being the primary organ of metastasis. Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases (CRLMs). Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy. However, the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy. Body mass index (BMI) is one of the factors affecting the tumorigenesis and progression of colorectal cancer as well as prognosis after various antitumour therapies. Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight, particularly when receiving first-line chemotherapy regimens in combination with bevacizumab. AIM To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs. METHODS A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023. Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response. The Kaplan-Meier method with log rank test was used to compare progression-free survival (PFS) between patients with high and low BMI. BMI < 24.0 kg/m2 was defined as low BMI, and tumour regression grade 1-2 was defined as complete tumour response. RESULTS Low BMI was observed in 74 (58.7%) patients and complete tumour response was found in 27 (21.4%) patients. The rate of complete tumour response was significantly higher in patients with low BMI (29.7% vs 9.6%, P = 0.007). Multivariate analysis revealed that low BMI [odds ratio (OR) = 4.56, 95% confidence interval (CI): 1.42-14.63, P = 0.011], targeted therapy with bevacizumab (OR = 3.02, 95%CI: 1.10-8.33, P = 0.033), preoperative carcinoembryonic antigen level < 10 ng/mL (OR = 3.84, 95%CI: 1.19-12.44, P = 0.025) and severe sinusoidal dilatation (OR = 0.17, 95%CI: 0.03-0.90, P = 0.037) were independent predictive factors for complete tumour response. The low BMI group exhibited a significantly longer median PFS than the high BMI group (10.7 mo vs 4.7 mo, P = 0.011). CONCLUSION In CRLM patients receiving preoperative chemotherapy, a low BMI may be associated with better tumour response and longer PFS.
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Affiliation(s)
- Hua-Chuan Song
- Department of General Surgery, Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Hang-Cheng Zhou
- Department of Pathology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Ping Gu
- Department of Pathology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Bing Bao
- Department of Gastrointestinal Surgery, Tongcheng People’s Hospital, Tongcheng 231400, Anhui Province, China
| | - Quan Sun
- Department of Gastrointestinal Surgery, Suzhou Hospital Affiliated to Anhui Medical University, Suzhou 234000, Anhui Province, China
| | - Tian-Ming Mei
- Department of Gastrointestinal Surgery, Suzhou Hospital Affiliated to Anhui Medical University, Suzhou 234000, Anhui Province, China
| | - Wei Cui
- Department of General Surgery, Xuancheng People’s Hospital, Xuancheng 242000, Anhui Province, China
| | - Kang Yao
- Department of General Surgery, Xuancheng People’s Hospital, Xuancheng 242000, Anhui Province, China
| | - Huan-Zhang Yao
- Department of General Surgery, Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
| | - Shen-Yu Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Yong-Shuai Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Rui-Peng Song
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
| | - Ji-Zhou Wang
- Department of General Surgery, Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui Province, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, 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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Morbidity and Mortality of Neutropenic Patients in Visceral Surgery: A Narrative Review. Cells 2022; 11:cells11203314. [PMID: 36291181 PMCID: PMC9600855 DOI: 10.3390/cells11203314] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/16/2022] [Accepted: 10/18/2022] [Indexed: 11/29/2022] Open
Abstract
Leukocytes are essential for the function of the immune system and cell–cell interaction in the human body, but hematological diseases as well as chemotherapeutic treatments due to cancer lead to occasionally or even permanent leukocyte deficiency. Normally, more than 50% of leukocytes are neutrophilic granulocytes, and leukopenia is, therefore, mostly characterized by a decrease in neutrophilic granulocytes. The consequence of neutropenia is increased susceptibility to infection, but also healing disorders are suggestable due to the disturbed cell–cell interaction. While there is no surgical treatment for leucocyte disorders, patients suffering from neutropenia are sometimes in need of surgery for other reasons. Less is known about the morbidity and mortality of this patients, which is why this narrative review critically summarizes the results of recent research in this particular field. The results of this review suggest that neutropenic patients in need of emergency surgery have a higher mortality risk compared to non-neutropenic patients. In contrast, in elective surgery, there was not a clear tendency for a higher mortality risk of neutropenic patients. The role of neutrophilic granulocytes in inflammation and immunity in surgical patients is emphasized by the results, but most of the evaluated studies showed methodological flaws due to small sample sizes or risk of bias. Further research has to evaluate the risk for postoperative complications, particularly of infectious complications such as surgical site infections, in neutropenic patients undergoing elective surgery, and should address the role of neutrophilic function in postoperative morbidity and mortality.
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Neoadjuvant Chemotherapy Versus Upfront Surgery for Resectable Liver Metastases from Colorectal Cancer: a Multicenter, Propensity Score-Matched Cohort Study. J Gastrointest Surg 2022; 26:772-781. [PMID: 34664190 DOI: 10.1007/s11605-021-05175-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 09/25/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Adjuvant chemotherapy for resectable colorectal liver metastasis (CRLM) is widely used, but its efficacy lacks clear evidence. This retrospective cohort study investigated the effectiveness of neoadjuvant chemotherapy (NAC) compared to upfront surgery for CRLM. METHODS Data from patients with resectable CRLM were analyzed. Short-term outcomes and long-term prognosis were analyzed using propensity score matching. CRLM was stratified according to the H-classification (H1 and H2), and the effectiveness of adjuvant chemotherapy was analyzed in each group. RESULTS We analyzed 599 cases that were matched into an NAC group (n = 136) and an upfront surgery group (n = 136). The proportion of synchronous metastases, H2-classification, and postoperative chemotherapy rate did not differ between the groups. Overall survival (OS) after initial treatment was significantly worse in the NAC group than in the upfront surgery group (P = 0.029). The 5-, 7-, and 10-year OS rates for H1 patients were significantly better in the upfront surgery group than in the NAC group (64%, 51%, and 44% vs. 50%, 31%, and 18%, respectively) (P = 0.004). CONCLUSION Patients with resectable CRLM should undergo upfront surgery, because NAC did not improve OS after initial treatment in these patients.
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Hirokawa F, Ueno M, Nakai T, Kaibori M, Nomi T, Iida H, Tanaka S, Komeda K, Hayami S, Kosaka H, Hokuto D, Kubo S, Uchiyama K. Treatment strategy for resectable colorectal cancer liver metastases from the viewpoint of time to surgical failure. Langenbecks Arch Surg 2021; 407:699-706. [PMID: 34741671 DOI: 10.1007/s00423-021-02372-w] [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: 06/30/2021] [Accepted: 10/31/2021] [Indexed: 11/28/2022]
Abstract
PURPOSE The efficacy of pre or postoperative chemotherapy for resectable colorectal cancer liver metastases (CRLM) is disputed. This study aimed to examine the risk factors for time to surgical failure (TSF) and analyze the efficacy of pre or postoperative chemotherapy prior to liver resection for CRLM. METHODS The clinicopathological factors of 567 patients who underwent initial hepatectomy for CRLM at 7 university hospitals between April 2007 and March 2013 were retrospectively analyzed. The prognostic factors were identified and then stratified into two groups according to the number of preoperative prognostic factors: the high-score group (H-group, score 2-4) and the low-score group (L-group, score 0 or 1). RESULTS Patients who experienced unresectable recurrence within 12 months after initial treatment had a significantly shorter prognosis than other patients (p < 0.001). Multivariate analysis identified age ≥ 70 (p = 0.001), pT4 (p = 0.015), pN1 (p < 0.001), carbohydrate antigen 19-9 ≥ 37 U/ml (p = 0.002), Clavien-Dindo grade ≥ IIIa (p = 0.013), and postoperative chemotherapy (p = 0.006) as independent prognostic factors. In the H-group, patients who received chemotherapy had a better prognosis than those who did not (p = 0.001). CONCLUSION Postoperative chemotherapy is beneficial in colorectal cancer patients with more than two of the following factors: age ≥ 70, carbohydrate antigen 19-9-positivity, pT4, and lymph node metastasis.
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Affiliation(s)
- Fumitoshi Hirokawa
- Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan.
| | - Masaki Ueno
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Takuya Nakai
- Department of Surgery, Faculty of Medicine, Kinki University, Osaka-Sayama, Japan
| | - Masaki Kaibori
- Department of Surgery, Hirakata Hospital, Kansai Medical University, Hirakata, Osaka, Japan
| | - Takeo Nomi
- Department of Surgery, Nara Medical University, Kashihara, Japan
| | - Hiroya Iida
- Department of Surgery, Shiga University of Medical Science, Otsu, Japan
| | - Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Koji Komeda
- Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan
| | - Shinya Hayami
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Hisashi Kosaka
- Department of Surgery, Hirakata Hospital, Kansai Medical University, Hirakata, Osaka, Japan
| | - Daisuke Hokuto
- Department of Surgery, Nara Medical University, Kashihara, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kazuhisa Uchiyama
- Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan
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Chen Q, Mao R, Zhao J, Bi X, Li Z, Huang Z, Zhang Y, Zhou J, Zhao H, Cai J. Upgraded nomograms for the prediction of complications and survival in patients with colorectal liver metastases treated with neoadjuvant chemotherapy followed by hepatic resection. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:265. [PMID: 33708892 PMCID: PMC7940886 DOI: 10.21037/atm-20-3973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background To establish upgraded nomograms incorporating neoadjuvant chemotherapy (NAC)-related factors and preoperative testing markers to predict postoperative complications, progression-free survival (PFS) and overall survival (OS) in patients with colorectal liver metastases (CRLM). Methods Multivariate regression analyses were used to reveal independent predictors for postoperative complications, PFS and OS. Nomograms incorporating independent predictors were constructed, and discrimination and calibration were evaluated. Survival was estimated by the Kaplan-Meier method and compared using the log-rank test. Results A nomogram predicting postoperative complications was constructed based on preoperative serum gamma-glutamyl transpeptidase (GGT) ≥36 U/L, major liver resection, intraoperative blood loss ≥300 mL, primary site located in the right hemicolon and primary lymph node metastasis, with an area under the receiver operating characteristic curve (AUROC) of 0.750. The calibration curves and Hosmer-Lemeshow test revealed desirable model calibration (chi-square: 4.47, P=0.88). Moreover, a nomogram for the prediction of PFS was constructed based on tumour regression grade (TRG), primary lymph node metastasis, R0 resection and NAC cycles ≥5, with good discrimination (C-index: 0.663±0.024) and calibration, and one for predicting OS was constructed based on preoperative GGT ≥36 U/L, NAC toxicity, NAC cycles ≥5, primary lymph node metastasis and R0 resection, with favourable discrimination (C-index: 0.684±0.030) and calibration. Significant differences in PFS and OS were observed among patients stratified into three different risk groups (P<0.001) according to total scores based on the nomograms. Conclusions This study is the first to establish novel predictive nomograms specifically incorporating TRG, NAC toxicity and serum GGT level for the prediction of postoperative complications, PFS and OS in CRLM patients. The nomograms exhibit favourable discrimination and calibration to guide personalized CRLM management and therapy.
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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
| | - Rui Mao
- 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 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 Q, Mao R, Zhao J, Bi X, Li Z, Huang Z, Zhang Y, Zhou J, Zhao H, Cai J. From the completion of neoadjuvant chemotherapy to surgery for colorectal cancer liver metastasis: What is the optimal timing? Cancer Med 2020; 9:7849-7862. [PMID: 32886456 PMCID: PMC7643690 DOI: 10.1002/cam4.3283] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 05/21/2020] [Accepted: 06/11/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) has been widely performed in the treatment of colorectal cancer liver metastasis (CRLM) patients, but the optimal timing of surgery after NAC is unclear. The aim of this study was to investigate the optimal timing of surgery. METHODS From December 2010 to May 2018, 101 consecutive patients who received NAC followed by liver resection for CRLM were included in this study. The main outcome parameters were pathological response, progression-free survival (PFS), and overall survival (OS). The effect of time to surgery (TTS) on patient outcomes, defined as a high TTS and a low TTS according to an X-tile analysis, was investigated. To adjust for potential selection bias, propensity score matching at 1:2 was performed with two high TTS patients matched to one low TTS patient. Kaplan-Meier curves, logistic regression analyses, and Cox regression models were used for the data analysis. RESULTS The optimal cut-off value for the TTS was 5 weeks by X-tile analysis. The patients in this study were divided into low (≤5 weeks, n = 27) and high (>5 weeks, n = 74) TTS groups. Patients with a high TTS were more likely to have an unfavorable pathological response (75.7% vs 48.1%, P = .008). In multivariate analysis, a low TTS significantly predicted a better pathological response (OR = 3.397, 95% CI: 1.116-10.344, P = .031). Compared to patients with a high TTS, patients with a low TTS had significantly better PFS (P < .001, mPFS: 16 months vs 7 months) and better OS (P = .037, mOS: not reached vs 36 months). Multivariate analysis revealed that a TTS > 5 weeks was an independent predictor of decreased PFS (HR = 2.041, 95% CI: 1.152-3.616, P = .014) but not OS. After propensity matching, the patients with a low TTS had significantly better PFS (P < .001, mPFS: 18.2 months vs 10 months) and an equivalent OS (P = .115, mOS: not reached vs 41 months). Multivariate analysis revealed that a TTS > 5 weeks was an independent predictor of decreased PFS (HR = 3.031, 95% CI: 1.494-6.149, P = .002) but not OS. CONCLUSION The longer TTS after the completion of NAC may be disadvantageous for a favorable pathological response and long-term PFS. These results should be validated prospectively in a randomized trial.
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Affiliation(s)
- Qichen Chen
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Rui Mao
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jianjun Zhao
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Xinyu Bi
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Zhiyu Li
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Zhen Huang
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Yefan Zhang
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jianguo Zhou
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Hong Zhao
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jianqiang Cai
- Department of Hepatobiliary SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
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Cashin PH, Ghanipour L, Enblad M, Morris DL. Neutropenia in colorectal cancer treated with oxaliplatin-based hyperthermic intraperitoneal chemotherapy: An observational cohort study. World J Gastrointest Oncol 2020; 12:549-558. [PMID: 32461786 PMCID: PMC7235182 DOI: 10.4251/wjgo.v12.i5.549] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 04/14/2020] [Accepted: 04/24/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The implications of neutropenia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment have never been investigated. AIM To evaluate the occurrence of neutropenia and its effect on the risk of increased Clavien-Dindo morbidity as well as its effect on overall or disease-free survival. METHODS All patients with colorectal peritoneal metastases (1996-2015) completing cytoreductive surgery and oxaliplatin-based HIPEC treatment from a bi-institutional database (Uppsala and Sydney) were included in the study. Clavien-Dindo grade 3-4 morbidity differences between the neutropenia group vs non-neutropenia group were calculated and Kaplan-Meier curves with log rank test were rendered. Univariate and multivariable Cox regression models for disease-free survival were implemented. RESULTS Two hundred and forty-six patients were identified - 32 postoperative any-grade neutropenia patients and 214 non-neutropenia patients. The neutropenia group had more combination oxaliplatin + irinotecan treatment than the non-neutropenia group (66% vs 13%, P = 0.0001). The neutropenia group was not associated with increased Clavien-Dindo grade 3-4 morbidity. Median overall survival was 53 mo vs 37 mo for the neutropenia and non-neutropenia group, P = 0.07. Median disease-free survival was 16 mo vs 11 mo, respectively, P = 0.02. Neutropenia was an independent prognostic factor for disease-free survival with hazard ratio: 0.58, 95% confidence interval: 0.36-0.95, P = 0.03. CONCLUSION 13% of patients developed neutropenia which was not associated with increased Clavien-Dindo grade 3-4 morbidity. Neutropenia was an independent positive prognostic factor for disease-free survival and was associated with more intense HIPEC treatment. This is in direct contrast to the current paradigm of decreasing the treatment intensity.
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Affiliation(s)
- Peter H Cashin
- Department of Surgical Sciences, Section of Surgery, Uppsala University, Akademiska Sjukhuset, Uppsala 75185, Sweden
| | - Lana Ghanipour
- Department of Surgical Sciences, Section of Surgery, Uppsala University, Akademiska Sjukhuset, Uppsala 75185, Sweden
| | - Malin Enblad
- Department of Surgical Sciences, Section of Surgery, Uppsala University, Akademiska Sjukhuset, Uppsala 75185, Sweden
| | - David L Morris
- Department of Surgery, University of New South Wales, Sydney 2217, New South Wales, Australia
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Chen Q, Zheng Y, Zhao H, Cai J, Wang L, Zhao J, Bi X, Li Z, Huang Z, Zhang Y, Zhou J, Wu J. The combination of preoperative D-dimer and CA19-9 predicts lymph node metastasis and survival in intrahepatic cholangiocarcinoma patients after curative resection. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:192. [PMID: 32309339 PMCID: PMC7154446 DOI: 10.21037/atm.2020.01.72] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background To investigate the predictive role of D-dimer and its combination of preoperative CA19-9 for lymph node metastasis (LNM) and prognosis in intrahepatic cholangiocarcinoma (ICC) patients who underwent curative-intent resection. Methods One hundred and seventy-three patients admitted to our hospital between April 2012 and December 2018 were included. The combination of preoperative D-dimer and CA19-9 (CPDC) was scored as 0 (decreased D-dimer levels with decreased CA19-9 levels), 2 (elevated D-dimer levels with elevated CA19-9 levels), or 1 (all other combinations). Multivariate logistic regression analysis was performed to identify independent factors. Cox proportional hazard regression was adopted for the multivariate survival analysis. Results The CPDC score was an independent predictor of LNM and overall survival (OS) in the multivariate analyses. For the prediction of LNM, the area under the curve (AUC) for the CPDC score was 0.722 (95% CI: 0.613–0.831, P<0.001), and for the prediction of survival, the AUC for the CPDC score was 0.756 (95% CI: 0.658–0.854, P<0.001). The predictive capacity of the CPDC score was higher than that of D-dimer or CA19-9. Kaplan-Meier curve analysis revealed that a CPDC =2 was significantly associated with a worse OS (P<0.001, median OS: 8.00 versus 19.00 months versus not reached) and shorter progression-free survival (PFS) (P<0.001, median PFS: 4.00 versus 11.00 versus 15.00 months) than a CPDC =1 or CPDC =0 in ICC patients. There were significant differences in the OS comparisons between any two groups. Decreased preoperative CPDC was associated with worse OS and PFS in all subgroups except in the HBsAg (+) group. In the cirrhosis, HBsAg (−) and tumour size ≥5 cm subgroups, there were significant differences in the OS and PFS comparisons between any two groups. Conclusions The preoperative CPDC score is a convenient and powerful prognostic biomarker to predict LNM and OS for ICC patients after curative resection. Especially for radiologically-negative metastatic lymph node in ICC patients, CPDC could be helpful to assess the extent of lymph node dissection and make follow-up plans.
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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 100021, China
| | - Yiling Zheng
- 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 100021, 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 100021, 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 100021, China
| | - Liming Wang
- 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 100021, 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 100021, 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 100021, 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 100021, 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 100021, 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 100021, 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 100021, China
| | - Jianxiong Wu
- 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 100021, China
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