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Huang FJ, Fang YY, Wen JY, Li JJ, Lin Q, Su QY, Chen YY, Wang L, Zeng JJ, Chi BT, He RQ, Qin DY, Yang LH, Chen G. From PD-1/PD-L1 to tertiary lymphoid structures: Paving the way for precision immunotherapy in cholangiocarcinoma treatment. Hum Vaccin Immunother 2025; 21:2444697. [PMID: 39757910 DOI: 10.1080/21645515.2024.2444697] [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: 09/17/2024] [Revised: 12/07/2024] [Accepted: 12/16/2024] [Indexed: 01/07/2025] Open
Abstract
Cholangiocarcinoma (CCA) is a highly malignant hepatobiliary tumor characterized by limited treatment options and poor prognosis. The recent rise of immunotherapy has significantly influenced research in this field. This study presents a bibliometric analysis of 416 articles retrieved from the WOSCC, Wan fang Data, CNKI and VIP databases, spanning contributions from 32 countries, 589 institutions and 3,200 authors. The analysis identified "PD-L1," "PD-1" and "pembrolizumab" as central research foci, while "immune checkpoint inhibitors," "tumor immune microenvironment," "tertiary lymphoid structures" and "durvalumab" emerged as key areas of interest. These findings emphasize the pivotal role of immunotherapy in improving survival outcomes for CCA, and they highlight the significance of tertiary lymphoid structures within the tumor microenvironment as a promising target for future research. This study offers a strategic overview of the evolving landscape of CCA immunotherapy, providing valuable insights to guide future scientific endeavors in this domain.
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Affiliation(s)
- Fang-Ju Huang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Ye-Ying Fang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Jia-Ying Wen
- Department of Radiotherapy, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Jian-Jun Li
- Department of General Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Qian Lin
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Qin-Yan Su
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Yi-Yang Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Lei Wang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Jian-Jia Zeng
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Bang-Teng Chi
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Rong-Quan He
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Di-Yuan Qin
- Department of Computer Science and Technology, School of Computer and Electronic Information, Guangxi University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Li-Hua Yang
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
| | - Gang Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P. R. China
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Kato T, Okada K, Baba Y, Yasuda M, Ohshima Y, Takase K, Watanabe Y, Watanabe Y, Aikawa M, Okamoto K, Koyama I. Preoperative prognostic stratification and prediction of long-term outcomes after pancreatoduodenectomy for distal cholangiocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108691. [PMID: 39366161 DOI: 10.1016/j.ejso.2024.108691] [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: 08/26/2024] [Accepted: 09/13/2024] [Indexed: 10/06/2024]
Abstract
BACKGROUND Patients with distal cholangiocarcinoma (DCC) frequently receive adjuvant chemotherapy in preoperative and postoperative settings, but prediction of prognostic risk at the time of treatment selection remains challenging. METHODS This single-center retrospective study enrolled DCC patients who underwent initial pancreatoduodenectomy (PD) between 2009 and 2022. Preoperative clinical parameters were collected, and Cox regression analysis was used to identify risk factors for overall survival (OS). RESULTS Among 170 patients examined, the median tumor depth was 10 mm, and 37 % of the patients were diagnosed with pT3. Overall, 46 % of patients had lymph node metastasis. The median and 5-year OS was 58.2 months and 50 %, respectively. Multivariate analysis revealed tumor size on computed tomography (CT) ≥15 mm and main pancreatic duct (MPD) dilatation (≥3 mm) as independent risk factors for OS among various preoperative parameters; the prognosis was stratified based on these two parameters. Patients with one risk factor had similar outcomes (5-year OS: 39 %) to pStage IIB DCC (pT2N1 or pT3), while those with two risk factors had a prognosis akin to pStage IIIA (pN2), with a high early recurrence rate of 64 % (5-year OS: 8 %). Among non-risk group patients with low carbohydrate antigen (CA)19-9 levels (<37 U/mL), the prognosis was comparable (5-year OS: 72 %) to those with pStage I DCC. CONCLUSION A simple stratification approach was developed to predict long-term postoperative outcomes. To improve poor prognosis, intensive therapy, including neoadjuvant chemotherapy, should be considered for patients with two risk factors.
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Affiliation(s)
- Tomotaka Kato
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Katsuya Okada
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan.
| | - Yasutaka Baba
- Diagnostic Radiology, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Masanori Yasuda
- Pathology, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Yuhei Ohshima
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Kenichiro Takase
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Yuichiro Watanabe
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Yukihiro Watanabe
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Masayasu Aikawa
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Kojun Okamoto
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
| | - Isamu Koyama
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Yamane, Hidaka-City, Saitama-Pref, Japan
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Ying B, Tang T, Zhang LX, Xiong JW, Zhao KF, Li JW, Wu G. Precision therapy for intrahepatic cholangiocarcinoma: A case report on adjuvant treatment in a recurrent patient after surgery and literature review. Oncol Lett 2024; 27:56. [PMID: 38192668 PMCID: PMC10773204 DOI: 10.3892/ol.2023.14189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 10/23/2023] [Indexed: 01/10/2024] Open
Abstract
A 37-year-old female patient was diagnosed with intrahepatic cholangiocarcinoma (ICC), with the lesion located in the right lobe of the liver. Despite radical resection, postoperative adjuvant chemotherapy and a combination of adjuvant chemotherapy and immunotherapy, the patient continued to experience multiple instances of intrahepatic tumor metastases. Furthermore, the patient exhibited significant adverse reactions to systemic chemotherapy and had poor treatment tolerance. Guidance from paraffin section fluorescence in situ hybridization gene sequencing was used to select a combination of immunotherapy and targeted therapy treatments with programmed cell death 1 (PD-1)/PD-1 ligand 1 antibody durvalumab and the targeted drug pemigatinib. The patient tolerated the treatment and has continued to survive for 28 months. According to imaging evaluations, the lesions continued to decrease, with some disappearing completely. The tumor marker carbohydrate antigen 19-9 remained normal for >9 weeks during the treatment. This report described the patient's treatment process in detail and briefly reviewed relevant literature on the treatment progress of postoperative patients with ICC.
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Affiliation(s)
- Bao Ying
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Tao Tang
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Li-Xing Zhang
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Jian-Wei Xiong
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Kai-Feng Zhao
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Jia-Wei Li
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
| | - Guo Wu
- Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China
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Lee H, Min SK, Cho MS, Lee HK. Impact of Nrf2 overexpression on cholangiocarcinoma treatment and clinical prognosis. KOREAN JOURNAL OF CLINICAL ONCOLOGY 2023; 19:18-26. [PMID: 37449395 DOI: 10.14216/kjco.23004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Accepted: 06/19/2023] [Indexed: 07/18/2023]
Abstract
PURPOSE Nrf2 regulates antioxidant protein expression and protects against drug toxicity and oxidative stress, whereas Keap1 controls Nrf2 activity. The Keap1-Nrf2 pathway affects the prognosis of various cancers, however, its effect on cholangiocarcinoma chemoresistance and prognosis remains unclear. This study aimed to determine whether the Keap1-Nrf2 pathway affects chemoresistance and prognosis of distal cholangiocarcinoma. METHODS We investigated the correlation between Nrf2 and Keap1 expression and clinical characteristics and prognosis in 91 patients with distal cholangiocarcinoma who underwent curative surgery. Immunohistochemical staining was performed on paraffin blocks using primary antibodies against Nrf2 and Keap1. The relationship between Keap1 and Nrf2 protein expression levels, and clinical characteristics and prognosis was examined. RESULTS Nrf2 expression was not associated with overall survival in patients who did not receive adjuvant chemotherapy (P=0.994). Among patients receiving adjuvant chemotherapy, the Nrf2 low expression group had a significantly longer median overall survival than the Nrf2 high expression group in Kaplan-Meier survival analysis (P=0.019). In multivariate analysis, high expression of Nrf2 was confirmed as an independent poor prognostic factor in the group receiving adjuvant chemotherapy (P=0.041). CONCLUSION This study suggests that Nrf2 overexpression reduces the efficacy of adjuvant chemotherapy in distal cholangiocarcinoma.
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Affiliation(s)
- Huisong Lee
- Department of Surgery, Ewha Womans University College of Medicine, Seoul, Korea
| | - Seog Ki Min
- Department of Surgery, Ewha Womans University College of Medicine, Seoul, Korea
| | - Min-Sun Cho
- Department of Pathology, Ewha Womans University College of Medicine, Seoul, Korea
| | - Hyeon Kook Lee
- Department of Surgery, Ewha Womans University College of Medicine, Seoul, Korea
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Parente A, Kamarajah SK, Baia M, Tirotta F, Manzia TM, Hilal MA, Pawlik TM, White SA, Dahdaleh FS. Neoadjuvant Chemotherapy for Intrahepatic, Perihilar, and Distal Cholangiocarcinoma: a National Population-Based Comparative Cohort Study. J Gastrointest Surg 2023; 27:741-749. [PMID: 36749556 PMCID: PMC10073049 DOI: 10.1007/s11605-023-05606-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 01/09/2023] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Data supporting the utilization of neoadjuvant chemotherapy (NAC) in patients receiving resection for cholangiocarcinoma (CCA) remains uncertain. We aimed to determine whether NAC followed by resection improves long-term survival in intrahepatic (iCCA), perihilar (hCCA), and distal (dCCA) cholangiocarcinoma, analyzed separately. METHODS Patients undergoing surgery for iCCA, hCCA, and dCCA, receiving either none, NAC, or adjuvant chemotherapy (AC) from 2010 to 2016 were identified from the National Cancer Database (NCDB). Cox regression was performed to account for selection bias and to assess the impact of surgery alone (SA) versus either NAC or AC on overall survival (OS). RESULTS There were 9411 patients undergoing surgery for iCCA (n = 3772, 39.5%), hCCA (n = 1879, 20%), and dCCA (n = 3760, 40%). Of these, 10.6% (n = 399), 6.5% (n = 123), and 7.2% (n = 271) with iCCA, hCCA, and dCCA received NAC, respectively. On adjusted analyses, patients receiving NAC followed by surgery had significantly improved OS, compared to SA for iCCA (HR 0.75, CI95% 0.64-0.88, p < 0.001), hCCA (HR 0.72, CI95% 0.54-0.97, p = 0.033), and for dCCA (HR 0.65, CI95% 0.53-0.78, p < 0.001). However, sensitivity analyses demonstrated no differences in OS between NACs, followed by surgery or AC after surgery in iCCA (HR 1.19, CI95% 0.99-1.45, p = 0.068), hCCA (HR 0.83 CI95% 0.59-1.19, p = 0.311), and dCCA (HR 1.13 CI95% 0.91-1.41, p = 0.264). CONCLUSIONS This study associated NAC with increased OS for all CCA subtypes, even in patients with margin-negative and node-negative disease; however, no differences were found between NAC and AC. Our results highlight that a careful and interdisciplinary evaluation should be sought to consider NAC in CCA and warrant the need of larger studies to provide robust recommendation.
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Affiliation(s)
- Alessandro Parente
- HPB and Transplant Unit, Department of Surgical Science, University of Rome Tor Vergata, Rome, Italy
- Department of Surgery, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Trust, Birmingham, UK
| | - Sivesh K Kamarajah
- Department of Surgery, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Trust, Birmingham, UK.
- Academic Department of Surgery, Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
| | - Marco Baia
- Department of Surgery, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Trust, Birmingham, UK
| | - Fabio Tirotta
- Department of Surgery, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Trust, Birmingham, UK
| | - Tommaso M Manzia
- HPB and Transplant Unit, Department of Surgical Science, University of Rome Tor Vergata, Rome, Italy
| | - Mohammed Abu Hilal
- Department of Surgery, Fondazione Poliambulanza - Istituto Ospedaliero, Brescia, Italy
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Steven A White
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle University, Newcastle Upon Tyne, Newcastle, UK
| | - Fadi S Dahdaleh
- Edward-Elmhurst Health, Department of Surgical Oncology, Naperville, IL, USA
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Zhao LM, Shi AD, Yang Y, Liu ZL, Hu XQ, Shu LZ, Tang YC, Zhang ZL. Advances in molecular and cell therapy for immunotherapy of cholangiocarcinoma. Front Oncol 2023; 13:1140103. [PMID: 37064120 PMCID: PMC10090456 DOI: 10.3389/fonc.2023.1140103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 03/17/2023] [Indexed: 03/31/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a highly malignant tumor of the hepatobiliary system that has failed to respond to many traditional therapies to a certain extent, including surgery, chemotherapy and radiotherapy. In recent years, the new therapeutic schemes based on immunology have fundamentally changed the systemic treatment of various malignant tumors to a certain extent. In view of the immunogenicity of CCA, during the occurrence and development of CCA, some immunosuppressive substances are released from cells and immunosuppressive microenvironment is formed to promote the escape immune response of its own cells, thus enhancing the malignancy of the tumor and reducing the sensitivity of the tumor to drugs. Some immunotherapy regimens for cholangiocarcinoma have produced good clinical effects. Immunotherapy has more precise characteristics and less adverse reactions compared with traditional treatment approaches. However, due to the unique immune characteristics of CCA, some patients with CCA may not benefit in the long term or not benefit at all after current immunotherapy. At present, the immunotherapy of CCA that have been clinically studied mainly include molecular therapy and cell therapy. In this article, we generalized and summarized the current status of immunotherapy strategies including molecular therapy and cell therapy in CCA in clinical studies, and we outlined our understanding of how to enhance the clinical application of these immunotherapy strategies.
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Affiliation(s)
- Li-ming Zhao
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - An-da Shi
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Yan Yang
- Department of General Surgery, Shanxian Central Hospital, Heze, China
| | - Zeng-li Liu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
- Department of General Surgery, Qilu Hospital (Qingdao), Shandong University, Jinan, China
| | - Xiao-Qiang Hu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Li-Zhuang Shu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Yong-chang Tang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
- *Correspondence: Yong-chang Tang, ; Zong-li Zhang,
| | - Zong-li Zhang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
- *Correspondence: Yong-chang Tang, ; Zong-li Zhang,
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Jongkatkorn C, Luvira V, Suwanprinya C, Piampatipan K, Leeratanakachorn N, Tipwaratorn T, Titapun A, Srisuk T, Theeragul S, Jarearnrat A, Thanasukarn V, Pugkhem A, Khuntikeo N, Pairojkul C, Kamsa-Ard S, Bhudhisawasdi V. Compliance with enhanced recovery after surgery predicts long-term outcome after hepatectomy for cholangiocarcinoma. World J Gastrointest Surg 2023; 15:362-373. [PMID: 37032797 PMCID: PMC10080603 DOI: 10.4240/wjgs.v15.i3.362] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 12/09/2022] [Accepted: 02/28/2023] [Indexed: 03/27/2023] Open
Abstract
BACKGROUND Enhanced recovery after surgery (ERAS) program has been proved to improve postoperative outcome for many surgical procedures, including liver resection. There was limited evidence regarding the feasibility and benefit of ERAS in patients who underwent liver resection for cholangiocarcinoma.
AIM To evaluate the feasibility of ERAS in patients who underwent liver resection for cholangiocarcinoma and its association with patient outcomes.
METHODS We retrospectively analyzed 116 cholangiocarcinoma patients who underwent hepatectomy at Srinagarind Hospital, Khon Kaen University between January 2015 and December 2016. The primary outcome was the compliance with ERAS. To determine the association between ERAS compliance and patient outcomes. the patients were categorized into those adhering more than and equal to 50% (ERAS ≥ 50), and below 50% (ERAS < 50) of all components. Details on type of surgical procedure, preoperative and postoperative care, tumor location, postoperative laboratory results, and survival time were evaluated. The compliance with ERAS was measured by the percentage of ERAS items achieved. The Kaplan-Meier curve was used for survival analysis.
RESULTS The median percentage of ERAS goals achieved was 40% (± 12%). Fourteen patients (12.1%) were categorized into the ERAS ≥ 50 group, and 102 patients were in the ERAS < 50 group. Postoperative hospital stay was significantly shorter in the ERAS ≥ 50 group [8.9 d, 95% confidence interval (CI): 7.3-10.4 d] than in the ERAS < 50 group (13.7 d, 95%CI: 12.2-15.2 d) (P = 0.0217). No hepatobiliary-related complications or in-hospital mortality occurred in the ERAS ≥ 50 group. Overall survival was significantly higher in the ERAS ≥ 50 group. The median survival of the patients in the ERAS < 50 group was 1257 d (95%CI: 853.2-1660.8 d), whereas that of the patients in the ERAS ≥ 50 group was not reached.
CONCLUSION Overall ERAS compliance for patients who underwent liver resection for cholangiocarcinoma is poor. Greater ERAS compliance could predict in-hospital, short-term, and long-term outcomes of the patients.
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Affiliation(s)
| | - Vor Luvira
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Chalisa Suwanprinya
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | | | | | - Theerawee Tipwaratorn
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Attapol Titapun
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Tharatip Srisuk
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Suapa Theeragul
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Apiwat Jarearnrat
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Vasin Thanasukarn
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Ake Pugkhem
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Narong Khuntikeo
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Chawalit Pairojkul
- Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Supot Kamsa-Ard
- Department of Epidemiology and Biostatistics, Faculty of Public Health, Khon Kaen University, Khon Kaen 40002, Thailand
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Liu D, Wang J, Ma Z, Zhang N, Zhao Y, Yang X, Wen Z, Xie H. Treatment of unresectable intrahepatic cholangiocarcinoma using transarterial chemoembolisation with irinotecan-eluting beads: analysis of efficacy and safety. Cardiovasc Intervent Radiol 2022; 45:1092-1101. [PMID: 35588011 DOI: 10.1007/s00270-022-03108-z] [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: 11/14/2021] [Accepted: 02/22/2022] [Indexed: 12/24/2022]
Abstract
PURPOSE This retrospective study evaluated the efficacy, safety, and factors affecting the prognosis of transarterial chemoembolisation with irinotecan-eluting beads with CalliSpheres (DEB-TACE) for intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS We retrospectively collected data on 39 patients with unresectable ICC who received DEB-TACE therapy. We assessed the indicators of tumour response, progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. PFS and OS were analysed using Kaplan-Meier curves, while Cox analysis was used to identify factors affecting the prognosis. RESULTS The 3-month objective response rate (ORR) and disease control rate (DCR) of the 39 patients with unresectable ICC were 35.9% and 56.4%, respectively, while the 6-month ORR and DCR were 23.0% and 40.9%, respectively. The median OS and PFS were 11.0 months and 8.0 months, respectively. Cox analysis demonstrated that combined therapy (adjuvant sorafenib after DEB-TACE) and a low cancer antigen (CA) 125 level (≤ 35 U/ml) were independent favourable prognostic factors. Transient elevation of the aminotransferase level, nausea, vomiting, abdominal pain, fever, and hyper-bilirubinaemia were common adverse events in patients with unresectable ICC treated with DEB-TACE with CalliSphere beads (CBs). Hepatic abscess was the most serious complication, observed in one patient. CONCLUSIONS DEB-TACE with CBs is a safe and well-tolerated therapy in patients with unresectable ICC with a low incidence of adverse events and relatively prolonged survival. Combined therapy and low CA125 are prognostic factors associated with longer survival.
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Affiliation(s)
- Dong Liu
- Department of Radiology, The First Hospital of Tsinghua University, Beijing, 100016, China
| | - Junxiao Wang
- Department of Interventional Therapy, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China.,Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, Jilin, 130000, China
| | - Zhenhu Ma
- Department of Interventional Therapy, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China
| | - Ning Zhang
- Department of Liver Disease, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China
| | - Yun Zhao
- Department of Interventional Therapy, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China
| | - Xiang Yang
- Department of Interventional Therapy, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China
| | - Zhenyu Wen
- Department of Interventional Therapy, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China.,Department of Occupational and Environmental Health, School of Public Health, Jilin University, Changchun, Jilin, 130000, China
| | - Hui Xie
- Department of Interventional Therapy, Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China.
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9
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Wada Y, Shimada M, Morine Y, Ikemoto T, Saito Y, Baba H, Mori M, Goel A. A blood-based noninvasive miRNA signature for predicting survival outcomes in patients with intrahepatic cholangiocarcinoma. Br J Cancer 2022; 126:1196-1204. [PMID: 35079106 PMCID: PMC9023447 DOI: 10.1038/s41416-022-01710-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 11/17/2021] [Accepted: 01/14/2022] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND The prognosis in patients with intrahepatic cholangiocarcinoma (ICC) is generally poor. To improve treatment selection, we sought to identify microRNA (miRNA) signature associated with survival outcomes in ICC. METHODS We first analysed the miRNA expression profiles of primary ICC from two public datasets to identify a miRNA panel to detect patients for short-term survival. We then analysed 309 specimens, including 241 FFPE samples from two clinical cohorts (training: n = 177; validation: n = 64) and matched plasma samples (n = 68), and developed a risk-stratification model incorporating the panel and CA 19-9 levels to predict survival outcomes in ICC. RESULTS We identified a 7-miRNA panel that robustly classified patients with poor outcomes in the discovery cohorts (AUC = 0.80 and 0.88, respectively). We subsequently trained this miRNA panel in a clinical cohort (AUC = 0.83) and evaluated its performance in an independent validation cohort (AUC = 0.82) and plasma samples from the additional validation cohort (AUC = 0.78). Patients in both clinical cohorts who were classified as high-risk had significantly worse prognosis (p < 0.01). The risk-stratification model demonstrated superior performance compared to models (AUC = 0.85). CONCLUSIONS We established a novel miRNA signature that could robustly predict survival outcomes in resected tissues and liquid biopsies to improve the clinical management of patients with ICC.
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Affiliation(s)
- Yuma Wada
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
- Department of Surgery, Tokushima University, Tokushima, Japan
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Yuji Morine
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Tetsuya Ikemoto
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Yu Saito
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Masaki Mori
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA.
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Huang X, Niu X, You Z, Long Y, Luo F, Ye H. Comparison of Four Lymph Node Stage Methods for Predicting the Prognosis of Distal Cholangiocarcinoma Patients After Surgery. Front Oncol 2021; 11:779761. [PMID: 34926292 PMCID: PMC8678514 DOI: 10.3389/fonc.2021.779761] [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] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Accepted: 11/16/2021] [Indexed: 02/05/2023] Open
Abstract
Background The metastatic status of regional lymph nodes is an effective risk factor for the prognosis of distal cholangiocarcinoma (dCCA). But existing lymph node staging is not accurate enough and is susceptible to interference. This study aims to explore the predictive ability of the log odds of positive lymph nodes (LODDS) staging system of dCCA compared with existing lymph node staging systems. Methods A total of 928 dCCA patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database as the training cohort, and 207 dCCA patients from West China Hospital who underwent surgery were reviewed as the validation cohort. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were conducted to identify the most meaningful factors relevant to prognosis. The performance of four lymph node stage systems was compared by a model-based approach. Result Age at diagnosis, pathological grade, American Joint Committee on Cancer (AJCC) tumor 7th T stage, tumor size, radiotherapy, chemotherapy, and lymph node stage system were independent prognostic factors. The model with the LODDS system had a better model fit with the highest C-index (0.679) and 1-/3-/5- area under the receiver operating characteristic curve (AUC) (0.739/0.671/0.658) as well as the lowest Akaike information criterion (AIC) (5,020.52). External validation results from 207 dCCA patients showed a C-index of 0.647 and 1-/3-/5-AUC of 0.740/0.683/0.589. Compared with the lymph node ratio (LNR), AJCC 8th N system, and 7th N system, the 5-year net reclassification improvement (NRI) of the LODDS system was 0.030 (95% CI: -0.079 to 0.147), 0.042 (95% CI: -0.062 to 0.139), and 0.040 (95% CI: -0.057 to 0.146), respectively. The integrated discrimination improvement (IDI) of LODDS improved compared with the LNR model (0.016; 95% CI: -0.001 to 0.036), AJCC 8th N system (0.020; 95% CI: 0.003-0.037), and AJCC 7th N system (0.019; 95% CI: 0.002-0.036). Decision curve analysis (DCA) also shows a greater net benefit of LODDS. In lymph node-negative patients, LODDS reveals a positive linear relationship with the hazard ratio (HR). The stage capacity of LODDS in a subgroup analysis stratified by examined lymph node number (ELNN) was consistent. Conclusions The LODDS lymph node stage system has superior predictive performance as compared with the LNR, AJCC 7th, and 8th lymph node stage systems. Meanwhile, LODDS has a more detailed staging ability and good stability.
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Affiliation(s)
- Xiuyi Huang
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoya Niu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zhen You
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Youlin Long
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China
| | - Fan Luo
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Hui Ye
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
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11
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Luvira V, Satitkarnmanee E, Pugkhem A, Kietpeerakool C, Lumbiganon P, Pattanittum P. Postoperative adjuvant chemotherapy for resectable cholangiocarcinoma. Cochrane Database Syst Rev 2021; 9:CD012814. [PMID: 34515993 PMCID: PMC8437098 DOI: 10.1002/14651858.cd012814.pub2] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Cholangiocarcinoma (cancer in the bile duct) is an aggressive tumour for which surgical resection is a mainstay of treatment. Despite complete resection, recurrences of the cancer are common and lead to poor prognosis in patients. Postoperative adjuvant chemotherapy given after surgical resection may reduce the risk of cancer recurrence by eradicating residual cancer and micrometastatic lesions. The benefits and harms of postoperative adjuvant chemotherapy versus placebo, no intervention, or other adjuvant chemotherapies are unclear. OBJECTIVES To assess the benefits and harms of postoperative adjuvant chemotherapy versus placebo, no intervention, or other adjuvant chemotherapies for people with cholangiocarcinoma after curative-intent resection. SEARCH METHODS We performed electronic searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science for trials that met the inclusion criteria up to 28 April 2021. SELECTION CRITERIA Randomised clinical trials irrespective of blinding, publication status, or language comparing postoperative adjuvant chemotherapy versus placebo, no intervention, or a different postoperative adjuvant chemotherapy regimen for participants with curative-intent resection for cholangiocarcinoma. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods to develop and conduct the review. We conducted meta-analyses and presented results, where feasible, using a random-effects model and risk ratios (RR) with 95% confidence intervals (CI). We assessed risk of bias according to predefined domains suggested by Cochrane. We rated the certainty of evidence using the GRADE approach and presented outcome results in a summary of findings table. MAIN RESULTS We included five published randomised clinical trials. The trials included 931 adults (18 to 83 years old) who underwent curative-intent resection for cholangiocarcinoma. Four trials compared postoperative adjuvant chemotherapy (mitomycin-C and 5-fluorouracil (5-FU); gemcitabine; gemcitabine plus oxaliplatin; or capecitabine) versus no postoperative adjuvant chemotherapy (surgery alone) in 867 participants with cholangiocarcinoma only. A fifth trial compared postoperative adjuvant S-1 (a novel oral fluoropyrimidine derivative) chemotherapy versus gemcitabine in 70 participants with intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma (64 participants), and gallbladder carcinoma (6 participants). We assessed all of the included trials at overall high risk of bias. One trial was conducted in France, three in Japan, and one in the United Kingdom. We could not perform all planned comparison analyses due to lack of data. Three trials used intention-to-treat analyses. Another trial used per-protocol analysis. In the remaining trial one participant in the intervention group and one in the control group were lost to follow-up. However, the outcomes of these two participants were not described. Postoperative adjuvant chemotherapy versus no postoperative adjuvant chemotherapy We are very uncertain as to whether postoperative adjuvant chemotherapy has little to no effect on all-cause mortality versus no postoperative adjuvant chemotherapy (RR 0.92, 95% CI 0.84 to 1.01; 4 trials, 867 participants, very low-certainty evidence). We are very uncertain of the effect of postoperative adjuvant chemotherapy on serious adverse events (RR 17.82, 95% CI 2.43 to 130.82; 1 trial, 219 participants, very low-certainty evidence). The trial indicated that postoperative adjuvant chemotherapy could increase serious adverse events, as 19/113 (20.5%) of participants developed an adverse event, compared to 1/106 (1.1%) of participants in the no-postoperative adjuvant chemotherapy group. None of the included trials reported data on health-related quality of life, cancer-related mortality, time to recurrence of the tumour, and non-serious adverse events in participants with only cholangiocarcinoma. Adjuvant S-1 chemotherapy (fluoropyrimidine derivative) versus adjuvant gemcitabine-based chemotherapy The only available trial analysed all participants with intrahepatic, perihilar cholangiocarcinoma and gallbladder carcinoma together, with data on participants with cholangiocarcinoma not provided separately. The authors reported that one-year overall mortality after adjuvant S-1 therapy was lower than with adjuvant gemcitabine-based therapy following major hepatectomy for biliary tract cancer. There were no differences in two-year overall mortality. FUNDING two trials received support from drug companies; one trial received funding from the Japan Society of Clinical Oncology; one trial received support from "Programme Hospitalier de Recherche Clinique (PHRC2009) and Ligue Nationale Contre le Cancer"; and one trial did not provide information on support or sponsorship. We identified six ongoing randomised clinical trials. AUTHORS' CONCLUSIONS Based on the very low-certainty evidence found in four trials in people with curative-intent resection for cholangiocarcinoma, we are very uncertain of the effects of postoperative adjuvant chemotherapy (mitomycin-C and 5-FU; gemcitabine; gemcitabine plus oxaliplatin; or capecitabine) versus no postoperative adjuvant chemotherapy on mortality. The effects of postoperative adjuvant chemotherapy compared with no postoperative adjuvant chemotherapy on serious adverse events are also very uncertain, but the result of the single trial showed 20% higher occurrences of haematologic adverse events. We assessed the certainty of the evidence as very low due to overall high risk of bias, and imprecision. Due to insufficient power of the only identified trial, the best postoperative adjuvant chemotherapy regimen in people with only cholangiocarcinoma could not be established. We also lack randomised clinical trials with outcome data on adjuvant S-1 chemotherapy versus adjuvant gemcitabine-based chemotherapy in people with cholangiocarcinoma alone. There is a need for further randomised clinical trials designed to be at low risk of bias and with adequate sample size exploring the best adjuvant chemotherapy treatment after surgery in people with cholangiocarcinoma.
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Affiliation(s)
- Vor Luvira
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | | | - Ake Pugkhem
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Chumnan Kietpeerakool
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Pisake Lumbiganon
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Porjai Pattanittum
- Department of Epidemiology and Biostatistics, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand
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12
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Nguyen MLT, Toan NL, Bozko M, Bui KC, Bozko P. Cholangiocarcinoma Therapeutics: An Update. Curr Cancer Drug Targets 2021; 21:457-475. [PMID: 33563168 DOI: 10.2174/1568009621666210204152028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 11/12/2020] [Accepted: 11/20/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Cholangiocarcinoma (CCA) is the second most common hepatobiliary cancer and associated with a poor prognosis. Only one-third of CCA cases are diagnosed at operable stages. However, a high rate of relapse has been observed postoperatively. Besides screening for operable individuals, efficacious therapeutic for recurrent and advanced CCA is urgently needed. The treatment outcome of available therapeutics is important to clarify clinical indication and facilitate the development of treatment strategies. OBJECTIVE This review aims to compare the treatment outcome of different therapeutics based on both overall survival and progression-free survival. METHODS Over one hundred peer-reviewed articles were examined. We compared the treatment outcome between different treatment methods, including tumor resection with or without postoperative systematic therapy, chemotherapies including FOFLOX, and targeted therapies, such as IDH1, K-RAS, and FGFR inhibitors. Notably, the scientific basis and outcome of available treatment methods were compared with the standard first-line therapy. RESULTS CCAs at early stages should firstly undergo tumor resection surgery, followed by postoperative treatment with Capecitabine. Chemotherapy can be considered as a preoperative option for unresectable CCAs. Inoperable CCAs with genetic aberrances like FGFR alterations, IDH1, and KRAS mutations should be considered with targeted therapies. Fluoropyrimidine prodrug (S-1)/Gemcitabine/Cisplatin and nab-Paclitaxel/Gemcitabine/Cisplatin show favorable outcome which hints at the triplet regimen to be superior to Gemcitabine/Cisplatin on CCA. The triplet chemotherapeutic should be tested further compared to Gemcitabine/Cisplatin among CCAs without genetic alterations. Gemcitabine plus S-1 was recently suggested as the convenient and equivalent standard first-line for advanced/recurrent biliary tract cancer. CONCLUSION This review provides a comparative outcome between novel targeted therapies and currently available therapeutics.
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Affiliation(s)
- Mai Ly Thi Nguyen
- Department of Internal Medicine I, Universitätsklinikum Tübingen, Tübingen, Germany
| | - Nguyen Linh Toan
- Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam
| | - Maria Bozko
- Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Poland
| | - Khac Cuong Bui
- Department of Internal Medicine I, Universitätsklinikum Tübingen, Tübingen, Germany
| | - Przemyslaw Bozko
- Department of Internal Medicine I, Universitätsklinikum Tübingen, Tübingen, Germany
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13
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Wada Y, Shimada M, Yamamura K, Toshima T, Banwait JK, Morine Y, Ikemoto T, Saito Y, Baba H, Mori M, Goel A. A Transcriptomic Signature for Risk-Stratification and Recurrence Prediction in Intrahepatic Cholangiocarcinoma. Hepatology 2021; 74:1371-1383. [PMID: 33725402 PMCID: PMC8443691 DOI: 10.1002/hep.31803] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 01/06/2021] [Accepted: 02/23/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Tumor recurrence is frequent even in intrahepatic cholangiocarcinoma (ICC), and improved strategies are needed to identify patients at highest risk for such recurrence. We performed genome-wide expression profile analyses to discover and validate a gene signature associated with recurrence in patients with ICC. APPROACH AND RESULTS For biomarker discovery, we analyzed genome-wide transcriptomic profiling in ICC tumors from two public data sets: The Cancer Genome Atlas (n = 27) and GSE107943 (n = 28). We identified an eight-gene panel (BIRC5 [baculoviral IAP repeat containing 5], CDC20 [cell division cycle 20], CDH2 [cadherin 2], CENPW [centromere protein W], JPH1 [junctophilin 1], MAD2L1 [mitotic arrest deficient 2 like 1], NEIL3 [Nei like DNA glycosylase 3], and POC1A [POC1 centriolar protein A]) that robustly identified patients with recurrence in the discovery (AUC = 0.92) and in silico validation cohorts (AUC = 0.91). We next analyzed 241 specimens from patients with ICC (training cohort, n = 64; validation cohort, n = 177), followed by Cox proportional hazard regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model for recurrence in ICC. We subsequently trained this transcriptomic panel in a clinical cohort (AUC = 0.89; 95% confidence interval [CI] = 0.79-0.95), followed by evaluating its performance in an independent validation cohort (AUC = 0.86; 95% CI = 0.80-0.90). By combining our transcriptomic panel with various clinicopathologic features, we established a risk-stratification model that was significantly superior for the identification of recurrence (AUC = 0.89; univariate HR = 6.08, 95% CI = 3.55-10.41, P < 0.01; and multivariate HR = 3.49, 95% CI = 1.81-6.71, P < 0.01). The risk-stratification model identified potential recurrence in 85% of high-risk patients and nonrecurrence in 76% of low-risk patients, which is dramatically superior to currently used pathological features. CONCLUSIONS We report a transcriptomic signature for risk-stratification and recurrence prediction that is superior to currently used clinicopathological features in patients with ICC.
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Affiliation(s)
- Yuma Wada
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA,Department of Surgery, Tokushima University, Tokushima, Japan,Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Kensuke Yamamura
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA,Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Jasjit K Banwait
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
| | - Yuji Morine
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Tetsuya Ikemoto
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Yu Saito
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Masaki Mori
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Ajay Goel
- Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA,Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA
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14
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Adjuvant systemic treatment in resected biliary tract cancer: State of the art, controversies, and future directions. Cancer Treat Res Commun 2021; 27:100334. [PMID: 33592563 DOI: 10.1016/j.ctarc.2021.100334] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 02/07/2021] [Accepted: 02/09/2021] [Indexed: 01/04/2023]
Abstract
Biliary tract cancer (BTC) includes a heterogeneous group of aggressive malignancies comprising gallbladder cancer (GBC), ampulla of Vater cancer (AVC), intrahepatic cholangiocarcinoma (iCCA), and extrahepatic cholangiocarcinoma (eCCA). Unfortunately, potentially curative resection is possible in approximately the 25% of presenting patients, and relapse rates are high, with a notable proportion of BTCs experiencing disease recurrence. Recent years have seen the publication of several prospective clinical trials evaluating the role of adjuvant systemic treatments, and among these, the phase III BILCAP study provided evidence supporting the use of capecitabine after radical surgery in BTC patients; in fact, although the study failed to meet its primary endpoint, the capecitabine arm showed improved clinical outcomes in terms of overall survival (pre-planned sensitivity analysis in the intention-to-treat population and in the per-protocol analysis) and relapse-free survival. However, the BILCAP has been widely criticized, with several authors that have not accepted adjuvant capecitabine as novel standard of care. In this review, we summarize current state of the art regarding adjuvant systemic treatment in BTC, highlighting advantages and disadvantages of recent clinical trials, and suggesting new research directions in this setting.
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15
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Anti-tumour effect of the fourth-generation chimeric antigen receptor T cells targeting CD133 against cholangiocarcinoma cells. Int Immunopharmacol 2020; 89:107069. [PMID: 33242709 DOI: 10.1016/j.intimp.2020.107069] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 09/29/2020] [Accepted: 09/30/2020] [Indexed: 12/19/2022]
Abstract
Current treatment of cholangiocarcinoma (CCA) - a lethal bile duct cancer - is ineffective because the disease is usually diagnosed at late and advanced stage. Thus, a novel therapeutic modality is urgently required. Fourth-generation chimeric antigen receptor (CAR4) T cells was created to target CD133, a well-known cancer stem cell marker, that is highly expressed and associates with cancer progression. The anti-CD133-CAR4 T cells showed high efficacy against CD133-expressing CCA cells. Tumour cell lysis occurred in a dose- and CD133 antigen-dependent manner, and significantly higher, up to 57.59% ± 9.62 at effector to target ratio of 5:1 in a CCA cell line - KKU-213A cells, compared to mock control (p = 0.008). Similarly, significant IFN-γ (p = 0.011) and TNF-α (p = 0.002) upregulation was observed upon tumour treatment. The effectiveness of our anti-CD133-CAR4 T cells will be beneficial not only for CD133-expressing CCA, but also for other CD133-expressing tumours. This study may guide future in vivo study and clinical trials.
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16
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Shi XQ, Zhang JY, Tian H, Tang LN, Li AL. Role of adjuvant (chemo)radiotherapy for resected extrahepatic cholangiocarcinoma: a meta-analysis. J Zhejiang Univ Sci B 2020; 21:549-559. [PMID: 32633109 DOI: 10.1631/jzus.b1900691] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Adjuvant (chemo)radiotherapy (A(C)RT) may be an important supplement to surgery for extrahepatic cholangiocarcinoma (EHCC). However, whether all patients would achieve benefits from A(C)RT and which adjuvant regimen, adjuvant radiotherapy (ART) or adjuvant chemoradiotherapy (ACRT), would be preferred, are still undetermined. The low incidence of EHCC makes it difficult to carry out randomized controlled trials (RCTs); therefore, almost all clinical studies on radiotherapy are retrospective. We have conducted a meta-analysis of these retrospective studies. METHODS We conducted a meta-analysis of current retrospective studies using PubMed, Embase, and ClinicalTrials databases. All studies published in English that were related to A(C)RT and which analyzed overall survival (OS), disease-free survival (DFS), or locoregional recurrence-free survival (LRFS) were included. Estimated hazard ratios (HRs) were calculated for OS, DFS, and LRFS. RESULTS Data from eight studies including 685 patients were included. Our analysis showed that A(C)RT significantly improved OS (HR 0.69, 95% confidence interval (CI) 0.48-0.97, P=0.03), DFS (HR 0.60, 95% CI 0.47-0.76, P<0.0001), and LRFS (HR 0.27, 95% CI 0.17-0.41, P<0.00001) of EHCC overall. In subgroups, patients with microscopically positive resection margin (R1) could achieve a benefit from A(C)RT (HR 0.44, 95% CI 0.27-0.72, P=0.001). No statistically OS difference was observed in negative resection margin (R0) subgroup (HR 0.98, 95% CI 0.30-3.19, P=0.98).Significant OS benefit was found in patients who received concurrent ACRT (HR 0.40, 95% CI 0.26-0.62, P<0.0001), while the result of ART without chemotherapy showed no significant benefit (HR 1.14, 95% CI 0.29-4.50, P=0.85). In the distal cholangiocarcinoma subgroup, no significant difference was seen when ACRT and ART were included (HR 0.61, 95% CI 0.14-2.72, P=0.52), but a significant difference was seen when analyzing the concurrent ACRT only (HR 0.29, 95% CI 0.13-0.64, P=0.002). CONCLUSIONS A(C)RT may improve OS, DFS, and LRFS in EHCC patients, especially in those with R1 resection margins. ACRT may be superior to ART especially in distal patients.
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Affiliation(s)
- Xin-Qi Shi
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Jing-Yu Zhang
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Hua Tian
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Ling-Na Tang
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Ai-Lin Li
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
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17
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Zhou TY, Zhou GH, Zhang YL, Nie CH, Zhu TY, Wang HL, Chen SQ, Wang BQ, Yu ZN, Wu LM, Zheng SS, Sun JH. Drug-eluting beads transarterial chemoembolization with CalliSpheres microspheres for treatment of unresectable intrahepatic cholangiocarcinoma. J Cancer 2020; 11:4534-4541. [PMID: 32489470 PMCID: PMC7255354 DOI: 10.7150/jca.39410] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Accepted: 04/29/2020] [Indexed: 02/06/2023] Open
Abstract
Objective: This study aimed to evaluate the efficacy and safety of doxorubicin-loaded drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres microspheres (CSM) in treating unresectable intrahepatic cholangiocarcinoma (ICC). Methods: 88 unresectable ICC patients who received DEB-TACE treatment with CSM were retrospectively enrolled in this study. Information about treatment response, survival and adverse events were collected. The Kaplan-Meier curve was used to evaluate progression-free survival (PFS) and overall survival (OS), and factors affecting OS were determined by Cox's proportional hazards regression model. Results: Tumor response of the whole sample of 88 patients was partial response (PR) in 58 (65.9%) patients, stable disease (SD) in 19 (21.6%) and progressive disease (PD) in 11 (12.5%) at one month after therapy, with no complete responses (CR). The median PFS and OS were 3.0 months and 9.0 months respectively. Cox's proportional hazards regression analysis disclosed that subsequent treatment was an independent favorable prognostic factor, while cholangiectasis, extensive intrahepatic tumor burden and extrahepatic metastasis were the three prognostic factors associated with poor survival in ICC patients. Besides, common adverse events included nausea/vomiting, abdominal pain and transient elevation of liver transaminase in patients treated by DEB-TACE with CSM. Conclusion: DEB-TACE with CSM is safe and well-tolerated for unresectable ICC patients, with a low complication rate and a relative benefit in terms of survival. Subsequent treatments including systemic/loco-regional treatments is an independent favorable prognostic factor, but cholangiectasis, extensive intrahepatic tumor burden and extrahepatic metastases are the three prognostic factors associated with poor survival.
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Affiliation(s)
- Tan-Yang Zhou
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Guan-Hui Zhou
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Yue-Lin Zhang
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Chun-Hui Nie
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Tong-Yin Zhu
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Hong-Liang Wang
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Sheng-Qun Chen
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Bao-Quan Wang
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Zi-Niu Yu
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Li-Ming Wu
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Shu-Sen Zheng
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Jun-Hui Sun
- Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.,Zhejiang Provincial Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou 310003, Zhejiang Province, China.,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou 310003, Zhejiang Province, China
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18
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Zhang J, Wu L, Liu J, Lin M. A metastatic intrahepatic cholangiocarcinoma treated with programmed cell death 1 inhibitor: a case report and literature review. Immunotherapy 2020; 12:555-561. [PMID: 32372672 DOI: 10.2217/imt-2019-0100] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Intrahepatic cholangiocarcinoma is a disease with grave prognosis due to limited therapeutic regimens. Programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor have shown dramatic clinical effectiveness in multiple solid tumors. Here, we report the case that a patient with metastasis intrahepatic cholangiocarcinoma, being failure of first-line chemotherapy, was enrolled into the Phase I study of a PD-1 inhibitor, sintilimab. The patient achieved complete remission after three cycles of treatment with mild adverse reaction. In addition, the tumor mutational burden and the microsatellite instability status were low in the present case. Hence, PD-1 inhibitor might be a promising therapeutic approach for patients with advanced cholangiocarcinoma.
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Affiliation(s)
- Jingjing Zhang
- Research Center of Clinical Pharmacy, First Affiliated Hospital Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Zhejiang Provincial Key Laboratory for Drug Evaluation & Clinical Research, Hangzhou, China
| | - Lihua Wu
- Research Center of Clinical Pharmacy, First Affiliated Hospital Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Zhejiang Provincial Key Laboratory for Drug Evaluation & Clinical Research, Hangzhou, China
| | - Jian Liu
- Research Center of Clinical Pharmacy, First Affiliated Hospital Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Zhejiang Provincial Key Laboratory for Drug Evaluation & Clinical Research, Hangzhou, China
| | - Meihua Lin
- Research Center of Clinical Pharmacy, First Affiliated Hospital Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Zhejiang Provincial Key Laboratory for Drug Evaluation & Clinical Research, Hangzhou, China
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19
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Zhang Z, Zhou Y, Hu K, Wang D, Wang Z, Huang Y. Perineural invasion as a prognostic factor for intrahepatic cholangiocarcinoma after curative resection and a potential indication for postoperative chemotherapy: a retrospective cohort study. BMC Cancer 2020; 20:270. [PMID: 32228636 PMCID: PMC7106692 DOI: 10.1186/s12885-020-06781-w] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Accepted: 03/23/2020] [Indexed: 02/06/2023] Open
Abstract
Background In the past four decades, the incidence of cholangiocarcinoma, especially intrahepatic cholangiocarcinoma (ICC), has raised rapidly worldwide. Completeness of resection, max size of tumor and etc. are widely recognized as prognostic factors. However, the prognosis significance of perineural invasion (PNI) on recurrence-free survival (RFS) and overall survival (OS) in ICC patients is controversial. Methods ICC patients who underwent curative hepatectomy and diagnosed pathologically were retrospectively analyzed. Patients were grouped by existence of PNI and outcomes were compared between groups. The potential relationship between PNI and postoperative chemotherapy was also investigated. Results There was no significant difference in demographic, clinical staging or tumor index between two groups, except positive hepatitis B surface antigen and CA19–9. PNI negative group showed a better prognosis in RFS (P < 0.0001) and OS (P < 0.0001). COX regression analyses showed PNI as an independent risk factor in RFS and OS. ICC with postoperative chemotherapy showed better effects in the whole cohort on both RFS (P = 0.0023) and OS (P = 0.0011). In PNI negative group, postoperative chemotherapy also showed significant benefits on RFS and OS, however not in PNI positive group (P = 0.4920 in RFS and P = 0.8004 in OS). Conclusion PNI was an independent risk factor in R0-resected ICC, presenting worse recurrence and survival outcomes. Meanwhile, negative PNI may act as an indication of postoperative chemotherapy.
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Affiliation(s)
- Zeyu Zhang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yufan Zhou
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Kuan Hu
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Dong Wang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zhiming Wang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yun Huang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
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20
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Asaoka T, Kobayashi S, Hanaki T, Iwagami Y, Tomimaru Y, Akita H, Noda T, Gotoh K, Takeda Y, Tanemura M, Doki Y, Eguchi H. Clinical significance of preoperative CA19-9 and lymph node metastasis in intrahepatic cholangiocarcinoma. Surg Today 2020; 50:1176-1186. [PMID: 32221659 DOI: 10.1007/s00595-020-01992-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Accepted: 03/06/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE This study aimed to identify prognostic factors for patients with ICC after a curative resection and clarify the appropriate indications for surgical resection and postoperative adjuvant chemotherapy. METHODS This retrospective study included 81 patients who underwent curative resection for ICC between April 1995 and December 2014. Kaplan-Meier and Cox regression models were used to analyze the effects of clinicopathological features on overall and recurrence-free survival. RESULTS The cumulative 5-year overall survival of 81 patients was 57.2%, and the 5-year recurrence-free survival was 24.0%. The multivariate analysis identified the lymph node status and preoperative CA19-9 levels as independent prognostic factors for overall survival. The 5-year overall survival rates were 79.9% and 38.7% in patients with normal and elevated CA19-9, respectively (p < 0.0001). The 5-year overall survival rates of patients with and without nodal metastasis were 33.7% and 60.9%, respectively (p = 0.0007). After adjusting for prognostic factors identified in a Cox regression analysis, we found that nodal-positive disease was significantly associated with benefit from adjuvant chemotherapy (HR 0.32, p = 0.03). CONCLUSIONS Surgical resection with curative intent combined with regional lymph node dissection should be indicated for ICC patients with normal CA19-9 levels. Postoperative adjuvant chemotherapy should be administered to high-risk patients with a positive nodal status.
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Affiliation(s)
- Tadafumi Asaoka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan. .,Department of Surgery, Osaka Police Hospital, Osaka, Japan.
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Takehiko Hanaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yoshifumi Iwagami
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yoshito Tomimaru
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Takehiro Noda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kunihito Gotoh
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yutaka Takeda
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.,Department of Surgery, Kansai Rosai Hospital, Hyogo, Japan
| | - Masahiro Tanemura
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan.,Department of Surgery, Rinku General Medical Center, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan
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21
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Ke Q, Lin N, Deng M, Wang L, Zeng Y, Liu J. The effect of adjuvant therapy for patients with intrahepatic cholangiocarcinoma after surgical resection: A systematic review and meta-analysis. PLoS One 2020; 15:e0229292. [PMID: 32084210 PMCID: PMC7034847 DOI: 10.1371/journal.pone.0229292] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Accepted: 02/03/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUD Resection is still the only potentially curative treatment for patients with intrahepatic cholangiocarcinoma (ICC), but the prognosis remains far from satisfactory. However, the benefit of adjuvant therapy (AT) remains controversial, although it has been conducted prevalently. Hence, a meta-analysis was warranted to evaluate the effect of AT for patients with ICC after resection. PATIENTS AND METHODS PubMed, MedLine, Embase, the Cochrane Library, Web of Science were used to identify potentially eligible studies from Jan.1st 1990 to Aug. 31st 2019, investigating the effect of AT for patients with ICC after resection. Primary endpoint was overall survival (OS), and secondary endpoints was recurrence-free survival (RFS). Hazard ratio (HR) with 95% confidence interval (CI) was used to determine the effect size. RESULTS 22 studies with 10181 patients were enrolled in this meta-analysis, including 832 patients in the chemotherapy group, 309 patients in the transarterial chemoembolization (TACE) group, 1192 patients in the radiotherapy group, 235 patients in the chemoradiotherapy group, and 6424 patients in the non-AT group. The pooled HR for the OS rate and RFS rate in the AT group were 0.63 (95%CI 0.52~0.74), 0.74 (95%CI 0.58~0.90), compared with the non-AT group. Subgroup analysis showed that the pooled HR for the OS rate in the AT group compared with non-AT group were as follows: chemotherapy group was 0.57 (95%CI = 0.44~0.70), TACE group was 0.56 (95%CI = 0.31~0.82), radiotherapy group was 0.71 (95%CI = 0.39~1.03), chemoradiotherapy group was 0.73 (95%CI = 0.57~0.89), positive resection margin group was 0.60 (95%CI = 0.51~0.69), and lymph node metastasis (LNM) group was 0.67 (95%CI = 0.57~0.76). CONCLUSION With the current data, we concluded that AT such as chemotherapy, TACE and chemoradiotherapy could benefit patients with ICC after resection, especially those with positive resection margin and LNM, but the conclusion needed to be furtherly confirmed.
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Affiliation(s)
- Qiao Ke
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, PR, China
| | - Nanping Lin
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, PR, China
| | - Manjun Deng
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, PR, China
| | - Lei Wang
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, PR, China
- Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, PR, China
- * E-mail:
| | - Yongyi Zeng
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, PR, China
| | - Jingfeng Liu
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, PR, China
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, PR, China
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22
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Wang L, Deng M, Ke Q, Lou J, Zheng S, Bi X, Wang J, Guo W, Li F, Wang J, Zheng Y, Li J, Cheng S, Zhou W, Zeng Y. Postoperative adjuvant therapy following radical resection for intrahepatic cholangiocarcinoma: A multicenter retrospective study. Cancer Med 2020; 9:2674-2685. [PMID: 32072774 PMCID: PMC7163087 DOI: 10.1002/cam4.2925] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Revised: 01/13/2020] [Accepted: 01/27/2020] [Indexed: 02/05/2023] Open
Abstract
Background and Aims The prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection is far from satisfactory; however, the clinical value of adjuvant therapy (AT) remains controversial. This multicenter study aimed to evaluate the clinical value of AT and identify potential patients who would be benefited from AT. Methods Data from ICC patients who underwent radical resection were retrospectively collected from 12 hepatobiliary centers in China between December 2012 and December 2015. Patients were divided into AT and non‐AT groups based on whether AT was administered or not. Overall survival (OS) and disease‐free survival (DFS) were analyzed using the Kaplan‐Meier method before and after 1:2 propensity score matching (PSM). Subgroup analyses were conducted based on the established staging systems. Results A total of 412 patients were enrolled in this study, and 77 patients (18.9%) received AT, including 32 (7.8%) patients who received transarterial chemoembolization (TACE), 21 (5.1%) patients who received chemotherapy, 10 (2.4%) patients who received radiotherapy, and 14 (3.4%) patients who received adjuvant chemoradiotherapy. The median OS and DFS were both longer in the AT group than in the non‐AT group (43.0 months vs 21.0 months, P = .015; 16.0 months vs 11.0 months, P = .045, respectively), and the advantage of AT was confirmed for both the OS and DFS (P = .023; P = .046, respectively) after 1:2 PSM. Furthermore, based on the established nomogram, only “middle‐risk” patients receiving AT cherished a longer median OS (43.0 months vs 20.0 months, P = .033). In subgroup analyses that were stratified by different AT strategies, patients receiving postoperative chemotherapy had a longer median OS (37.0 months vs 21.0 months, P = .039), while patients receiving postoperative TACE had a longer median DFS (50.0 months vs 11.0 months, P = .007). Conclusion With the current data, we conclude that AT benefits ICC patients following radical resection, especially those “middle‐risk” patients, as evaluated by the established nomogram. However, exactly which patients are the most suitable for AT requires further study and validation.
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Affiliation(s)
- Lei Wang
- Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Manjun Deng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Qiao Ke
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Jianying Lou
- Department of Hepatobiliary Surgery, The Second Hospital Affiliated to Zhejiang University, Hangzhou, China
| | - Shuguo Zheng
- Department of Hepatobiliary Surgery, The Southwest Hospital Affiliated to the Army Medical University, Chongqing, China
| | - Xinyu Bi
- Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Jianming Wang
- Department of Hepatobiliary Surgery, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China
| | - Wei Guo
- Department of Hepatobiliary Surgery, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China
| | - Fuyu Li
- Department of Hepatobiliary Surgery, The West China Hospital of Sichuan University, Chengdu, China
| | - Jian Wang
- Department of Hepatobiliary Surgery, Renji Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China
| | - Yamin Zheng
- Department of Hepatobiliary Surgery, Xuanwu Hospital Affiliated to Capital Medical University, Beijing, China
| | - Jingdong Li
- Department of Hepatobiliary Surgery, The Affiliated Hospital of Chuanbei Medical University, Nanchong, China
| | - Shi Cheng
- Department of Hepatobiliary Surgery, Tiantan Hospital Affiliated to Capital Medical University, Beijing, China
| | - Weiping Zhou
- Department of Hepatobiliary Surgery Ⅲ, Eastern Hepatobiliary Surgery Hospital, Secondary Military Medical University, Shanghai, China
| | - Yongyi Zeng
- Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China.,Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
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