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Fathi M, Taher HJ, Al-Rubiae SJ, Yaghoobpoor S, Bahrami A, Eshraghi R, Sadri H, Asadi Anar M, Gholamrezanezhad A. Role of molecular imaging in prognosis, diagnosis, and treatment of gastrointestinal cancers: An update on new therapeutic methods. World J Methodol 2024; 14:93461. [PMID: 39712556 PMCID: PMC11287540 DOI: 10.5662/wjm.v14.i4.93461] [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: 02/27/2024] [Revised: 05/31/2024] [Accepted: 07/15/2024] [Indexed: 07/26/2024] Open
Abstract
One of the leading causes of cancer-related death is gastrointestinal cancer, which has a significant morbidity and mortality rate. Although preoperative risk assessment is essential for directing patient care, its biological behavior cannot be accurately predicted by conventional imaging investigations. Potential pathophysiological information in anatomical imaging that cannot be visually identified can now be converted into high-dimensional quantitative image features thanks to the developing discipline of molecular imaging. In order to enable molecular tissue profile in vivo, molecular imaging has most recently been utilized to phenotype the expression of single receptors and targets of biological therapy. It is expected that molecular imaging will become increasingly important in the near future, driven by the expanding range of biological therapies for cancer. With this live molecular fingerprinting, molecular imaging can be utilized to drive expression-tailored customized therapy. The technical aspects of molecular imaging are first briefly discussed in this review, followed by an examination of the most recent research on the diagnosis, prognosis, and potential future clinical methods of molecular imaging for GI tract malignancies.
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Affiliation(s)
- Mobina Fathi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1983969411, Iran
| | | | | | - Shirin Yaghoobpoor
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1983969411, Iran
| | - Ashkan Bahrami
- Faculty of Medicine, Kashan University of Medical Sciences, Kashan 1617768911, Iran
| | - Reza Eshraghi
- Faculty of Medicine, Kashan University of Medical Sciences, Kashan 1617768911, Iran
| | - Hossein Sadri
- Faculty of Medicine, Kashan University of Medical Sciences, Kashan 1617768911, Iran
| | - Mahsa Asadi Anar
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1983969411, Iran
| | - Ali Gholamrezanezhad
- Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, United States
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Rong Z, Xu J, Yang J, Wang W, Tang R, Zhang Z, Tan Z, Meng Q, Hua J, Liu J, Zhang B, Liang C, Yu X, Shi S. CircRREB1 Mediates Metabolic Reprogramming and Stemness Maintenance to Facilitate Pancreatic Ductal Adenocarcinoma Progression. Cancer Res 2024; 84:4246-4263. [PMID: 39288082 DOI: 10.1158/0008-5472.can-23-3596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 05/24/2024] [Accepted: 09/09/2024] [Indexed: 09/19/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumor with limited treatment options and poor patient survival. Circular RNAs (circRNA) play crucial regulatory roles in the occurrence and development of various cancers, including PDAC. In this study, using circRNA sequencing of diverse PDAC samples, we identified circRREB1 as an oncogenic circRNA that is significantly upregulated in PDAC and is correlated with an unfavorable patient prognosis. Functionally, loss of circRREB1 markedly inhibited glycolysis and stemness, whereas elevated circRREB1 elicited the opposite effects. Mechanistically, circRREB1 interacted with PGK1, disrupting the association between PTEN and PGK1 and increasing PGK1 phosphorylation to activate glycolytic flux. Moreover, circRREB1 promoted WNT7B transcription by directly interacting with YBX1 and facilitating its nuclear translocation, consequently activating the Wnt/β-catenin signaling pathway to maintain PDAC stemness. Overall, these results highlight circRREB1 as a key regulator of metabolic and stemness properties of PDAC. Significance: CircRREB1 stimulates PGK1 to induce glycolysis and activates the Wnt/β-catenin signaling pathway to maintain stemness in pancreatic cancer, indicating the potential of circRREB1 as a biomarker and therapeutic target.
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MESH Headings
- Humans
- Carcinoma, Pancreatic Ductal/pathology
- Carcinoma, Pancreatic Ductal/metabolism
- Carcinoma, Pancreatic Ductal/genetics
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/metabolism
- Pancreatic Neoplasms/genetics
- Mice
- Animals
- RNA, Circular/genetics
- RNA, Circular/metabolism
- Glycolysis
- Neoplastic Stem Cells/metabolism
- Neoplastic Stem Cells/pathology
- Wnt Signaling Pathway
- Phosphoglycerate Kinase/metabolism
- Phosphoglycerate Kinase/genetics
- Disease Progression
- Prognosis
- Gene Expression Regulation, Neoplastic
- Cell Line, Tumor
- Mice, Nude
- Male
- Female
- Cell Proliferation
- Biomarkers, Tumor/metabolism
- Biomarkers, Tumor/genetics
- PTEN Phosphohydrolase/metabolism
- PTEN Phosphohydrolase/genetics
- Mice, Inbred BALB C
- Wnt Proteins/metabolism
- Wnt Proteins/genetics
- Metabolic Reprogramming
- Y-Box-Binding Protein 1
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Affiliation(s)
- Zeyin Rong
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Jianhui Yang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Wei Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Rong Tang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Zifeng Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Zhen Tan
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
- Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Qingcai Meng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Jie Hua
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Jiang Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Bo Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Chen Liang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
| | - Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, Shanghai, China
- Shanghai Pancreatic Cancer Institute, Shanghai, China
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Yoo J, Hyun SH, Lee J, Cheon M, Lee KH, Heo JS, Choi JY. Prognostic Significance of 18 F-FDG PET/CT Radiomics in Patients With Resectable Pancreatic Ductal Adenocarcinoma Undergoing Curative Surgery. Clin Nucl Med 2024; 49:909-916. [PMID: 38968550 DOI: 10.1097/rlu.0000000000005363] [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: 07/07/2024]
Abstract
PURPOSE This study aimed to investigate the prognostic significance of PET/CT radiomics to predict overall survival (OS) in patients with resectable pancreatic ductal adenocarcinoma (PDAC). METHODS We enrolled 627 patients with resectable PDAC who underwent preoperative 18 F-FDG PET/CT and subsequent curative surgery. Radiomics analysis of the PET/CT images for the primary tumor was performed using the Chang-Gung Image Texture Analysis toolbox. Radiomics features were subjected to least absolute shrinkage and selection operator (LASSO) regression to select the most valuable imaging features of OS. The prognostic significance was evaluated by Cox proportional hazards regression analysis. Conventional PET parameters and LASSO score were assessed as predictive factors for OS by time-dependent receiver operating characteristic curve analysis. RESULTS During a mean follow-up of 28.8 months, 378 patients (60.3%) died. In the multivariable Cox regression analysis, tumor differentiation, resection margin status, tumor stage, and LASSO score were independent prognostic factors for OS (HR, 1.753, 1.669, 2.655, and 2.946; all P < 0.001, respectively). The time-dependent receiver operating characteristic curve analysis showed that the LASSO score had better predictive performance for OS than conventional PET parameters. CONCLUSIONS The LASSO score using the 18 F-FDG PET/CT radiomics of the primary tumor was the independent prognostic factor for predicting OS in patients with resectable PDAC and may be helpful in determining therapeutic and follow-up plans for these patients.
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Affiliation(s)
- Jang Yoo
- From the Department of Nuclear Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju
| | - Seung Hyup Hyun
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
| | - Jaeho Lee
- Department of Preventive Medicine, Seoul National University College of Medicine
| | - Miju Cheon
- Department of Nuclear Medicine, Veterans Health Service Medical Center
| | | | - Jin Seok Heo
- Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joon Young Choi
- Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
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Lee W, Oh M, Kim JS, Sung M, Hong K, Kwak BJ, Park Y, Jun E, Song KB, Hwang DW, Lee JH, Yoo C, Kim KP, Park I, Jeong JH, Chang HM, Ryoo BY, Lee JB, Kim SC. Metabolic tumor burden as a prognostic indicator after neoadjuvant chemotherapy in pancreatic cancer. Int J Surg 2024; 110:4074-4082. [PMID: 38537071 PMCID: PMC11254192 DOI: 10.1097/js9.0000000000001389] [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: 12/20/2023] [Accepted: 03/11/2024] [Indexed: 07/19/2024]
Abstract
BACKGROUND There is no standardized assessment for evaluating response although neoadjuvant chemotherapy (NAT) is widely accepted for borderline resectable or locally advanced pancreatic cancer (BRPC or LAPC). This study was aimed to evaluate NAT response using positron emission tomography (PET) with 2-deoxy-2-[fluorine-18]fluoro-D-glucose ( 18 F-FDG-PET/CT) parameters alongside carbohydrate antigen (CA) 19-9 levels. METHODS Patients who underwent surgery after NAT for BRPC and LAPC between 2017 and 2021 were identified. The study assessed the prognostic value of PET-derived parameters after NAT, determining cutoff values using the K-adaptive partitioning method. It created four groups based on the elevation or normalization of PET parameters and CA19-9 levels, comparing survival between these groups. RESULTS Of 200 eligible patients, FOLFIRINOX and gemcitabine-based NAT was administered in 166 and 34 patients, respectively (mean NAT cycles, 8.3). In a multivariate analysis, metabolic tumor volume (MTV) demonstrated the most robust performance in assessing response [hazard ratio (HR) 3.11, 95% confidence interval (CI) 1.73-5.58, P <0.001] based on cutoff value of 2.4. Patients with decreased MTV had significantly better survival than those with elevated MTV among individuals with CA19-9 levels less than 37 IU/l (median survival; 35.5 vs. 20.9 months, P <0.001) and CA19-9 levels at least 37 IU/l (median survival; 34.3 vs. 17.8 months, P =0.03). In patients suspected to be Lewis antigen negative, the predictive performance of MTV was found to be limited ( P =0.84). CONCLUSION Elevated MTV is an influential prognostic factor for worse survival, regardless of post-NAT CA19-9 levels. These results could be helpful in identifying patients with a poor prognosis despite normalization of CA19-9 levels after NAT.
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Affiliation(s)
- Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine
| | - Minyoung Oh
- Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine
| | - Jae Seung Kim
- Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine
| | - Minkyu Sung
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine
| | - Kwangpyo Hong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine
| | - Bong Jun Kwak
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine
| | - Yejong Park
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine
| | - Eunsung Jun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine
| | - Changhoon Yoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine
| | - Kyu-pyo Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine
| | - Inkeun Park
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine
| | - Jae Ho Jeong
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine
| | - Heung-Moon Chang
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine
| | - Baek-Yeol Ryoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine
| | - Jung Bok Lee
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Gong R, Hu Y, Yu Q, Fang L, Ren H. Metabolic signatures in pancreatic ductal adenocarcinoma: diagnostic and therapeutic implications. JOURNAL OF PANCREATOLOGY 2023; 6:185-195. [DOI: 10.1097/jp9.0000000000000146] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2025] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the prototypical aggressive cancer that develops in nutrient-deficient and hypoxic microenvironment. PDAC overcomes these restrictions by employing unconventional tactics for the procurement and usage of fuel sources. The substantial reprogramming of PDAC cell metabolism is driven by oncogene-mediated cell-autonomous pathways. PDAC cells use glucose, glutamine, and lipids for energy and depend on autophagy and macropinocytosis for survival and growth. They also interact metabolically with non-cancerous cells, aiding tumor progression. Many clinical trials focusing on altered metabolism are ongoing. Understanding the metabolic regulation of PDAC cells will not only help to increase understanding of the mechanisms of disease progression but also provide insights for the development of new diagnostic and therapeutic approaches.
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Affiliation(s)
- Ruining Gong
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Center for GI Cancer Diagnosis and Treatment, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
| | - Yonglu Hu
- Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Qian Yu
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Center for GI Cancer Diagnosis and Treatment, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
| | - Lin Fang
- Phase I Clinical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - He Ren
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Center for GI Cancer Diagnosis and Treatment, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
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Ohira S, Ikawa T, Kanayama N, Minamitani M, Kihara S, Inui S, Ueda Y, Miyazaki M, Yamashita H, Nishio T, Koizumi M, Nakagawa K, Konishi K. Dual-energy computed tomography-based iodine concentration as a predictor of histopathological response to preoperative chemoradiotherapy for pancreatic cancer. JOURNAL OF RADIATION RESEARCH 2023; 64:940-947. [PMID: 37839063 PMCID: PMC10665298 DOI: 10.1093/jrr/rrad076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 09/08/2023] [Indexed: 10/17/2023]
Abstract
To explore predictors of the histopathological response to preoperative chemoradiotherapy (CRT) in patients with pancreatic cancer (PC) using dual-energy computed tomography-reconstructed images. This retrospective study divided 40 patients who had undergone preoperative CRT (50-60 Gy in 25 fractions) followed by surgical resection into two groups: the response group (Grades II, III and IV, evaluated from surgical specimens) and the nonresponse group (Grades Ia and Ib). The computed tomography number [in Hounsfield units (HUs)] and iodine concentration (IC) were measured at the locations of the aorta, PC and pancreatic parenchyma (PP) in the contrast-enhanced 4D dual-energy computed tomography images. Logistic regression analysis was performed to identify predictors of histopathological response. Univariate analysis did not reveal a significant relation between any parameter and patient characteristics or dosimetric parameters of the treatment plan. The HU and IC values in PP and the differences in HU and IC between the PP and PC (ΔHU and ΔIC, respectively) were significant predictors for distinguishing the response (n = 24) and nonresponse (n = 16) groups (P < 0.05). The IC in PP and ΔIC had a higher area under curve values [0.797 (95% confidence interval, 0.659-0.935) and 0.789 (0.650-0.928), respectively] than HU in PP and ΔHU [0.734 (0.580-0.889) and 0.721 (0.562-0.881), respectively]. The IC value could potentially be used for predicting the histopathological response in patients who have undergone preoperative CRT.
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Affiliation(s)
- Shingo Ohira
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
- Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka, 565-0871, Japan
- Department of Comprehensive Radiation Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Toshiki Ikawa
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
| | - Naoyuki Kanayama
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
| | - Masanari Minamitani
- Department of Comprehensive Radiation Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Sayaka Kihara
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
| | - Shoki Inui
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
| | - Yoshihiro Ueda
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
| | - Masayoshi Miyazaki
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
| | - Hideomi Yamashita
- Department of Radiology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Teiji Nishio
- Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Masahiko Koizumi
- Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Keiichi Nakagawa
- Department of Comprehensive Radiation Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Koji Konishi
- Department of Radiation Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 537-8567, Japan
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Zhu Z, Cheng K, Yun Z, Zhang X, Hu X, Liu J, Wang F, Fu Z, Yue J. [ 18F] AlF-NOTA-FAPI-04 PET/CT can predict treatment response and survival in patients receiving chemotherapy for inoperable pancreatic ductal adenocarcinoma. Eur J Nucl Med Mol Imaging 2023; 50:3425-3438. [PMID: 37328622 DOI: 10.1007/s00259-023-06271-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 05/18/2023] [Indexed: 06/18/2023]
Abstract
PURPOSE We investigated whether uptake of [18F] AlF-NOTA-FAPI-04 on positron emission tomography/computed tomography (PET/CT) could predict treatment response and survival in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS We prospectively evaluated 47 patients with histopathologically confirmed primary PDAC who provided pretreatment [18F] AlF-NOTA-FAPI-04 scans to detect fibroblast activation protein (FAP) on the tumor surface by uptake of [18F] AlF-NOTA-FAPI-04. PDAC specimens were immunohistochemically stained with cancer-associated fibroblast (CAF) markers. We obtained a second PET scan after one cycle of chemotherapy to study changes in FAPI uptake variables from before to during treatment. Correlations between baseline PET variables and CAF-related immunohistochemical markers were assessed with Spearman's rank test. Cox regression and Kaplan-Meier methods were used to assess relationships between disease progression and potential predictors. Receiver operating characteristic (ROC) curve analysis was used to define the optimal cut-off points for distinguishing patients according to good response vs. poor response per RECIST v.1.1. RESULTS The FAPI PET variables maximum and mean standardized uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), and total lesion FAP expression (TLF) were positively correlated with CAF markers (FAP, α-smooth muscle actin, vimentin, S100A4, and platelet-derived growth factor receptor α/β, all P < 0.05). MTV was associated with survival in patients with inoperable PDAC (all P < 0.05). Cox multivariate regression showed that MTV was associated with overall survival (MTV hazard ratio [HR] = 1.016, P = 0.016). Greater changes from before to during chemotherapy in SUVmax, MTV, and TLF were associated with good treatment response (all P < 0.05). ΔMTV, ΔTLF, and ΔSUVmax had larger areas under the curve than ΔCA19-9 for predicting treatment response. Kaplan-Meier analysis showed that the extent of change in MTV and TLF from before to after treatment predicted progression-free survival, with cut-off values (based on medians) of - 4.95 for ΔMTV (HR = 8.09, P = 0.013) and - 77.83 for ΔTLF (HR = 4.62, P = 0.012). CONCLUSIONS A higher baseline MTV on [18F] AlF-NOTA-FAPI-04 scans was associated with poorer survival in patients with inoperable PDAC. ΔMTV was more sensitive for predicting response than ΔCA19-9. These results are clinically meaningful for identifying patients with PDAC who are at high risk of disease progression.
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Affiliation(s)
- Ziyuan Zhu
- School of Clinical Medicine, Weifang Medical University, Weifang, China
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong, China
| | - Kai Cheng
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong, China
- PET/CT Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Zhang Yun
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong, China
| | - Xiang Zhang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong, China
| | - Xiaoyu Hu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong, China
| | - Jing Liu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong, China
| | - Fuhao Wang
- School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Zheng Fu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong, China.
- PET/CT Center, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, China.
| | - Jinbo Yue
- School of Clinical Medicine, Weifang Medical University, Weifang, China.
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong, China.
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Yoo J, Lee JM, Joo I, Lee DH, Yoon JH, Yu MH, Jang JY, Lee SH. Post-neoadjuvant treatment pancreatic cancer resectability and outcome prediction using CT, 18F-FDG PET/MRI and CA 19-9. Cancer Imaging 2023; 23:49. [PMID: 37217958 DOI: 10.1186/s40644-023-00565-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 05/01/2023] [Indexed: 05/24/2023] Open
Abstract
BACKGROUND CT prediction of resectability and prognosis following neoadjuvant treatment (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC) remains challenging. This study aims to determine whether addition of 18F-fluorodeoxyglucose (FDG) postiron emission tomography (PET)/MRI and carbohydrate antigen (CA) 19-9 to contrast-enhanced CT (CECT) can improve accuracy of predicting resectability compared to CECT alone and predict prognosis in PDAC patients after NAT. METHODS In this retrospective study, 120 PDAC patients (65 women; mean age, 66.7 years [standard deviation, 8.4]) underwent CECT, PET/MRI, and CA 19-9 examinations after NAT between January 2013 and June 2021. Three board-certified radiologists independently rated the overall resectability on a 5-point scale (score 5, definitely resectable) in three sessions (session 1, CECT; 2, CECT plus PET/MRI─no FDG avidity and no diffusion restriction at tumor-vessel contact indicated modification of CECT scores to ≥ 3; 3, CECT plus PET plus CA 19-9─no FDG avidity at tumor-vessel contact and normalized CA 19-9 indicated modification of CECT scores to ≥ 3). Jackknife free-response receiver operating characteristic method and generalized estimating equations were used to compare pooled area under the curve (AUC), sensitivity, and specificity of three sessions. Predictors for recurrence-free survival (RFS) were assessed using Cox regression analyses. RESULTS Each session showed different pooled AUC (session 1 vs. 2 vs. 3, 0.853 vs. 0.873 vs. 0.874, p = 0.026), sensitivity (66.2% [137/207] vs. 86.0% [178/207] vs. 84.5% [175/207], p < 0.001) and specificity (67.3% [103/153] vs. 58.8% [90/153] vs. 60.1% [92/153], p = 0.048). According to pairwise comparison, specificity of CECT plus PET/MRI was lower than that of CECT alone (adjusted p = 0.042), while there was no significant difference in specificity between CECT alone and CECT plus PET plus CA 19-9 (adjusted p = 0.081). Twenty-eight of 69 patients (40.6%) with R0 resection experienced tumor recurrence (mean follow-up, 18.0 months). FDG avidity at tumor-vessel contact on post-NAT PET (HR = 4.37, p = 0.033) and pathologically confirmed vascular invasion (HR = 5.36, p = 0.004) predicted RFS. CONCLUSION Combination of CECT, PET and CA 19-9 increased area under the curve and sensitivity for determining resectability, compared to CECT alone, without compromising the specificity. Furthermore, 18F-FDG avidity at tumor-vessel contact on post-NAT PET predicted RFS.
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Affiliation(s)
- Jeongin Yoo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.
- Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Korea.
- Department of Radiology, Konkuk University School of Medicine, Seoul, Korea.
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
- Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Radiology, Konkuk University School of Medicine, Seoul, Korea
| | - Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Mi Hye Yu
- Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Korea
- Department of Radiology, Konkuk University School of Medicine, Seoul, Korea
| | - Jin-Young Jang
- Department of General Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Sang Hyub Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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Meng Q, Fang Z, Mao X, Tang R, Liang C, Hua J, Wang W, Shi S, Yu X, Xu J. Metabolic reprogramming of cancer-associated fibroblasts in pancreatic cancer contributes to the intratumor heterogeneity of PET-CT. Comput Struct Biotechnol J 2023; 21:2631-2639. [PMID: 37153537 PMCID: PMC10160596 DOI: 10.1016/j.csbj.2023.04.003] [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: 12/02/2022] [Revised: 03/21/2023] [Accepted: 04/06/2023] [Indexed: 05/09/2023] Open
Abstract
Intratumor heterogeneity of positron emission tomography-computed tomography (PET-CT) is reflected by variable 18F-fluorodeoxyglucose (FDG) uptake. Increasing evidence has shown that neoplastic and non-neoplastic components can affect the total 18F-FDG uptake in tumors. Cancer-associated fibroblasts (CAFs) is considered as the main non-neoplastic components in tumor microenvironment (TME) of pancreatic cancer. Our study aims to explore the impact of metabolic changes in CAFs on heterogeneity of PET-CT. A total of 126 patients with pancreatic cancer underwent PET-CT and endoscopic ultrasound elastography (EUS-EG) before treatment. High maximum standardized uptake value (SUVmax) from the PET-CT was positively correlated with the EUS-derived strain ratio (SR) and indicated poor prognosis of patients. In addition, single-cell RNA analysis showed that CAV1 affected glycolytic activity and correlated with glycolytic enzyme expression in fibroblasts in pancreatic cancer. We also observed the negative correlation between CAV1 and glycolytic enzyme expression in the tumor stroma by using immunohistochemistry (IHC) assay in the SUVmax-high and SUVmax-low groups of pancreatic cancer patients. Additionally, CAFs with high glycolytic activity contributed to pancreatic cancer cell migration, and blocking CAF glycolysis reversed this process, suggesting that glycolytic CAFs promote malignant biological behavior in pancreatic cancer. In summary, our research demonstrated that the metabolic reprogramming of CAFs affects total 18F-FDG uptake in tumors. Thus, an increase in glycolytic CAFs with decreased CAV1 expression promotes tumor progression, and high SUVmax may be a marker for therapy targeting the neoplastic stroma. Further studies should clarify the underlying mechanisms.
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Affiliation(s)
- Qingcai Meng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Zengli Fang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Xiaoqi Mao
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Rong Tang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Chen Liang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Jie Hua
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Wei Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
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10
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Raja Arul GL, Toruner MD, Gatenby RA, Carr RM. Ecoevolutionary biology of pancreatic ductal adenocarcinoma. Pancreatology 2022; 22:730-740. [PMID: 35821188 DOI: 10.1016/j.pan.2022.06.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 06/01/2022] [Indexed: 12/11/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC), the most common histological subtype of pancreatic cancer, is an aggressive disease predicted to be the 2nd cause of cancer mortality in the US by 2040. While first-line therapy has improved, 5-year overall survival has only increased from 5 to ∼10%, and surgical resection is only available for ∼20% of patients as most present with advanced disease, which is invariably lethal. PDAC has well-established highly recurrent mutations in four driver genes including KRAS, TP53, CDKN2A, and SMAD4. Unfortunately, these genetic drivers are not currently therapeutically actionable. Despite extensive sequencing efforts, few additional significantly recurrent and druggable drivers have been identified. In the absence of targetable mutations, chemotherapy remains the mainstay of treatment for most patients. Further, the role of the above driver mutations on PDAC initiation and early development is well-established. However, these mutations alone cannot account for PDAC heterogeneity nor discern early from advanced disease. Taken together, management of PDAC is an example highlighting the shortcomings of the current precision medicine paradigm. PDAC, like other malignancies, represents an ecoevolutionary process. Better understanding the disease through this lens can facilitate the development of novel therapeutic strategies to better control and cure PDAC. This review aims to integrate the current understanding of PDAC pathobiology into an ecoevolutionary framework.
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Affiliation(s)
| | - Merih D Toruner
- Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, MN, USA
| | - Robert A Gatenby
- Department of Integrated Mathematical Oncology, Moffitt Cancer Center, Tampa, FL, USA
| | - Ryan M Carr
- Department of Oncology, Mayo Clinic, Rochester, MN, USA.
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11
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Mokhtar HM, Youssef A, Naguib TM, Magdy AA, Salama SA, Kabel AM, Sabry NM. The Significance of FDG PET/CT-Derived Parameters in Determining Prognosis of Cases with Pancreatic Adenocarcinoma: A Prospective Study. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:1027. [PMID: 36013494 PMCID: PMC9414036 DOI: 10.3390/medicina58081027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 07/26/2022] [Accepted: 07/27/2022] [Indexed: 12/24/2022]
Abstract
Background and objectives: Pancreatic adenocarcinoma represents one of the common malignancies with a relatively poor prognosis. However, early detection of this type of cancer may prove to be curable. Recent advancements in the radiological techniques might represent a hope for the early diagnosis and prediction of prognosis of pancreatic adenocarcinoma. This study aimed to assess the prognostic value of the primary tumor volumetric parameters obtained from FDG PET/CT first stage for the overall survival (OS) and progression-free survival (PFS) of patients with pancreatic adenocarcinoma and to explore the possible correlation between serum matrix metalloproteinase-2 (MMP-2) and the patients’ characteristics. Methods: Fifty patients with pancreatic adenocarcinoma were subjected to FDG PET/CT scan. The SUVpeak, SUVmax, and the metabolic tumor volume (MTV) were determined, as well as the SUVmean of the liver. Moreover, serum levels of MMP-2 were assessed. Follow-up of the patients was carried out for sixty months with determination of PFS and OS. Results: Peak SUV ≥ 3.9 was significantly correlated with the primary pancreatic lesions’ mean total glycolytic activity of >92 g, and MTV and was directly correlated with mortality. There was a positive correlation between peak SUV ≥ 3.9 and 50% SUVmax threshold > 82. Moreover, there was significant correlation between the total glycolytic activity and the studied clinicopathologic factors, except the age and sex of the patients and ECOG performance status. In addition, FDG uptake and the tumor glycolytic activity were substantially linked with a shorter PFS. Similarly, a strong correlation was found between MTV and PFS. Serum MMP-2 levels showed a significant relationship with the performance status, tumor stage, SUVmax threshold, and the glycolytic activity. Conclusions: Peak SUV, main lesion SUVmax, serum MMP-2, and the tumor glycolytic activity are good predictors of PFS of patients with pancreatic adenocarcinoma.
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Affiliation(s)
- Hwaida M. Mokhtar
- Radiodiagnosis Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt;
| | - Amira Youssef
- Clinical Pathology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt;
| | - Tamer M. Naguib
- Anesthesia and ICU Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt; (T.M.N.); (A.A.M.)
| | - Amr A. Magdy
- Anesthesia and ICU Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt; (T.M.N.); (A.A.M.)
| | - Samir A. Salama
- Division of Biochemistry, Department of Pharmacology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia;
| | - Ahmed M. Kabel
- Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
| | - Nesreen M. Sabry
- Clinical Oncology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt;
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12
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Pu Y, Wang C, Zhao S, Xie R, Zhao L, Li K, Yang C, Zhang R, Tian Y, Tan L, Li J, Li S, Chen L, Sun H. The clinical application of 18F-FDG PET/CT in pancreatic cancer: a narrative review. Transl Cancer Res 2021; 10:3560-3575. [PMID: 35116659 PMCID: PMC8799156 DOI: 10.21037/tcr-21-169] [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: 01/26/2021] [Accepted: 05/20/2021] [Indexed: 12/13/2022]
Abstract
Pancreatic cancer is one of the worst prognoses of all malignant tumors, with an annual incidence near its annual mortality rate. To improve the prognosis of patients with pancreatic cancer, it is essential to diagnose and evaluate pancreatic cancer early. Imaging examinations play an essential role in tumor detection, staging, and surgical resection assessment and can provide reliable evidence for the diagnosis and treatment of pancreatic cancer. Currently, imaging techniques commonly used for pancreatic cancer include endoscopic ultrasound (EUS), conventional ultrasound, magnetic resonance imaging (MRI), multidetector spiral computed tomography (MDCT), positron emission tomography/computed tomography (PET/CT), and others PET/CT is a new imaging device composed of PET and CT. 18F-Fluorodeoxyglucose (18F-FDG) is a commonly used tracer in the clinic. Cancer cells are more robust than other ordinary cells in that they can ingest glucose, and the structure of glucose is similar to the structure of 18F-FDG. Therefore, after the injection of 18F-FDG, 18F-FDG in tumor cells appears very thick during PET scanning. Therefore, PET/CT can determine the metabolic capacity and anatomical position of pancreatic tumor cells in the body accurately diagnose the patient's condition and tumor location. It plays a vital role in early diagnosis and accurate staging, predicts survival, and monitors therapeutic effectiveness and pancreatic cancer recurrence. Although 18F-FDG PET/CT has limitations in identifying inflammatory diseases and tumors, it still has good development potential. This article reviews the clinical application of 18F-FDG PET/CT in pancreatic cancer.
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Affiliation(s)
- Yongzhu Pu
- Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China
| | - Chun Wang
- Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China
| | - Sheng Zhao
- Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China
| | - Ran Xie
- Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China
| | - Lei Zhao
- Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China
| | - Kun Li
- Department of Radiology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China
| | - Conghui Yang
- Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China
| | - Rui Zhang
- Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China
| | - Yadong Tian
- Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China
| | - Lixian Tan
- Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China
| | - Jindan Li
- Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China
| | - Shujuan Li
- Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China
| | - Long Chen
- Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China
| | - Hua Sun
- Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, China
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13
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Tatewaki Y, Terao CM, Ariake K, Saito R, Mutoh T, Shimomura H, Motoi F, Mizuma M, Odagiri H, Unno M, Taki Y. Defining the Optimal Method for Measuring Metabolic Tumor Volume on Preoperative 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography as a Prognostic Predictor in Patients With Pancreatic Ductal Adenocarcinoma. Front Oncol 2021; 11:646141. [PMID: 33777807 PMCID: PMC7994512 DOI: 10.3389/fonc.2021.646141] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Accepted: 02/03/2021] [Indexed: 11/22/2022] Open
Abstract
Objectives Metabolic tumor volume (MTV) on 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is a promising prognostic predictor in pancreatic ductal adenocarcinoma (PDAC). However, the optimal segmentation method and threshold value to determine MTV for PDAC are still unclear. We explored the optimal method and threshold value for the prognostic value of MTV measured on pre-treatment 18F-FDG-PET/CT. Methods Seventy-three patients with resected PDAC who underwent 18F FDG-PET/CT before surgical resection were enrolled. MTV values of the tumor were measured on FDG-PET/CT by the two fixed-threshold methods using threshold values as 2.0, 2.5, 3.0, and 3.5 for the absolute method and 35%, 40%, 42%, 45%, and 50% for the relative method. Receiver operating characteristic curve analysis for prediction of 1-year survival rates was conducted for determining the optimal threshold values, and we selected the optimal method and threshold value considering area under the curve. The prognostic values of each FDG-PET/CT parameter for disease-specific survival and recurrence-free survival were assessed with Kaplan–Meier method and Cox proportional hazard models. Results In receiver operating characteristic curve analysis, MTV by the fixed-absolute threshold method based on a threshold value of 3.5 (MTV3.5) performed best in our study with area under the curve 0.724, sensitivity of 65%, and specificity of 75%. In univariate and multivariate analyses, MTV3.5 was significantly associated with disease-specific and recurrence-free survival. Conclusions MTV3.5 by absolute threshold on pre-treatment FDG-PET/CT was the best independent prognostic predictor in resectable PDAC compared with other absolute threshold values and relative threshold values.
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Affiliation(s)
- Yasuko Tatewaki
- Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.,Department of Geriatric Medicine and Neuroimaging, Tohoku University Hospital, Sendai, Japan
| | - Chiaki Maeda Terao
- Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
| | - Kyohei Ariake
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Ryoko Saito
- Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tatsushi Mutoh
- Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.,Department of Geriatric Medicine and Neuroimaging, Tohoku University Hospital, Sendai, Japan
| | - Hideo Shimomura
- Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.,Kousei Sendai Clinic, Sendai, Japan
| | - Fuyuhiko Motoi
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.,Department of Surgery I, Yamagata University Graduate School of Medical Science, Yamagata, Japan
| | - Masamichi Mizuma
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hayato Odagiri
- Division of Radiology, Tohoku University Hospital, Sendai, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yasuyuki Taki
- Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.,Smart-Aging International Research Center, Tohoku University, Sendai, Japan
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14
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Ge J, Li L, Ma Z, Jiang B, Yuan C, Wang H, Peng Y, Xiu D. A nomogram of preoperative predictors for occult metastasis in patients with PDAC during laparoscopic exploration. Gland Surg 2021; 10:279-289. [PMID: 33633984 DOI: 10.21037/gs-20-605] [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] [Indexed: 01/17/2023]
Abstract
Background Surgical resection is the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC). However, most of patients lose the chance of surgery due to the unresectable disease at the time of diagnosis. Despite the improvement of radiological imaging, a portion of patients intended for radical resection were proven to be unresectable at surgical exploration due to occult metastasis. Methods Patients who were aimed to undergo radical pancreatectomy for PDAC from 2010 to 2019 were reviewed retrospectively. All patients included underwent diagnostic laparoscopic exploration. Patients were divided into two groups depending on whether distant metastasis were encountered during exploration. Univariate and multivariate logistic regression analyses were used to identify risk factors for occult metastasis. A nomogram to predict occult metastasis of PDAC on exploration was developed and evaluated. Results A total of 273 patients who underwent diagnostic laparoscopic exploration were included in this study. Nineteen (7.0%) patients were found with distant metastasis during exploration. Multivariate logistic regression analysis showed that ALT>40U/L, CA19-9, CA125 and regional nodes enlargement were independent predictors for occult metastasis. Incorporating these four factors, the nomogram achieved concordance index of 0.799, with a well-fitted calibration curve. Conclusions Occult metastasis is not unusual during surgical exploration in patients with resectable or borderline resectable PDAC. The nomogram could achieve a personal prediction of unexpected distant metastasis on exploration. It may help to sift through patients with PDAC who would benefit from laparoscopic exploration.
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Affiliation(s)
- Jiachen Ge
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Lei Li
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Zhaolai Ma
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Bin Jiang
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Chunhui Yuan
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Hangyan Wang
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Ying Peng
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Dianrong Xiu
- Department of General Surgery, Peking University Third Hospital, Beijing, China
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15
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Arnone A, Laudicella R, Caobelli F, Guglielmo P, Spallino M, Abenavoli E, Martini AL, Filice R, Comis AD, Cuzzocrea M, Linguanti F, Evangelista L, Alongi P. Clinical Impact of 18F-FDG PET/CT in the Diagnostic Workup of Pancreatic Ductal Adenocarcinoma: A Systematic Review. Diagnostics (Basel) 2020; 10:diagnostics10121042. [PMID: 33287195 PMCID: PMC7761738 DOI: 10.3390/diagnostics10121042] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 11/29/2020] [Accepted: 11/30/2020] [Indexed: 12/13/2022] Open
Abstract
In this review, the performance of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the diagnostic workup of pancreatic ductal adenocarcinoma (PDAC) is evaluated. A comprehensive literature search up to September 2020 was performed, selecting studies with the presence of: sample size ≥10 patients and index test (i.e., “FDG” or “18F-FDG” AND “pancreatic adenocarcinoma” or “pancreas cancer” AND “PET” or “positron emission tomography”). The methodological quality was evaluated using the revised quality assessment of diagnostic accuracy studies (QUADAS-2) tool and presented according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Basic data (authors, year of publication, country and study design), patients’ characteristics (number of enrolled subjects and age), disease phase, type of treatment and grading were retrieved. Forty-six articles met the adopted research criteria. The articles were divided according to the considered clinical context. Namely, besides conventional anatomical imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI), molecular imaging with FDG PET/CT is an important tool in PDAC, for all disease stages. Further prospective studies will be necessary to confirm the cost-effectiveness of such imaging techniques by testing its real potential improvement in the clinical management of PDAC.
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Affiliation(s)
- Annachiara Arnone
- Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50134 Florence, Italy; (E.A.); (A.L.M.); (F.L.)
- Correspondence:
| | - Riccardo Laudicella
- Department of Biomedical and Dental Sciences and of Morpho-Functional Imaging, Nuclear Medicine Unit, University of Messina, 98125 Messina, Italy; (R.L.); (R.F.); (A.D.C.)
| | - Federico Caobelli
- Clinic of Radiology & Nuclear Medicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland;
| | - Priscilla Guglielmo
- Nuclear Medicine Division, University Hospital of Parma, 43126 Parma, Italy;
| | - Marianna Spallino
- Nuclear Medicine Unit, ASST “Papa Giovanni XXIII”, 24127 Bergamo, Italy;
| | - Elisabetta Abenavoli
- Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50134 Florence, Italy; (E.A.); (A.L.M.); (F.L.)
| | - Anna Lisa Martini
- Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50134 Florence, Italy; (E.A.); (A.L.M.); (F.L.)
| | - Rossella Filice
- Department of Biomedical and Dental Sciences and of Morpho-Functional Imaging, Nuclear Medicine Unit, University of Messina, 98125 Messina, Italy; (R.L.); (R.F.); (A.D.C.)
| | - Alessio Danilo Comis
- Department of Biomedical and Dental Sciences and of Morpho-Functional Imaging, Nuclear Medicine Unit, University of Messina, 98125 Messina, Italy; (R.L.); (R.F.); (A.D.C.)
| | - Marco Cuzzocrea
- Nuclear Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy;
| | - Flavia Linguanti
- Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50134 Florence, Italy; (E.A.); (A.L.M.); (F.L.)
| | - Laura Evangelista
- Nuclear Medicine Unit, Department of Medicine, Padova University Hospital, Via Giustiniani 2, 35128 Padova, Italy;
| | - Pierpaolo Alongi
- Unit of Nuclear Medicine, Fondazione Istituto G.Giglio, 90015 Cefalù, Italy;
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16
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Zou Q, Jiao J, Zou MH, Li MZ, Yang T, Xu L, Zhang Y. Semi-automatic evaluation of baseline whole-body tumor burden as an imaging biomarker of 68Ga-PSMA-11 PET/CT in newly diagnosed prostate cancer. Abdom Radiol (NY) 2020; 45:4202-4213. [PMID: 32948911 DOI: 10.1007/s00261-020-02745-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 08/31/2020] [Accepted: 09/03/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The prognostic value of baseline tumor burden of prostate cancer was rarely studied. We aimed to evaluate the whole-body tumor burden of 68Ga- prostate specific membrane antigen-HBED-CC (68Ga-PSMA-11) PET/CT in newly diagnosed prostate cancer semi-automatically, and explore its preliminary application in predicting prognosis. METHODS Similar to metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of 18F-FDG PET/CT, 68Ga-PSMA-11 PET/CT tumor burden parameters including whole-body PSMA tumor volume (wbPSMA-TV) and whole-body total lesions PSMA uptake (wbTL-PSMA) were acquired semi-automatically. The intra-observer and inter-observer reliability was analyzed. The relationship between tumor burden and prostate-specific antigen (PSA) value or Gleason score was investigated. The preliminary application of tumor burden in predicting progression-free survival (PFS) was explored. RESULTS Fifty-nine newly diagnosed prostate cancer patients were retrospectively analyzed. Semi-automatic quantification of whole-body tumor burden had excellent intra-observer and inter-observer consistency [all intra-class correlation coefficient (ICC) > 0.990]. wbPSMA-TV and wbTL-PSMA were 32.6 (range 1.0-3968.2) cm3 and 161.9 (range 6.0-24971.7), respectively. wbPSMA-TV and wbTL-PSMA correlated with PSA (r = 0.858, p < 0.001; r = 0.879, p < 0.001) and Gleason score (r = 0.793, p < 0.001; r = 0.805, p < 0.001) significantly. In univariate analysis, wbPSMA-TV, wbTL-PSMA, SUVmax, SUVpeak, SUVmean, PSMA-TV, TL-PSMA of primary tumor, fPSA and Gleason score were independent significant predictors of PFS (all p < 0.05). Moreover, in multivariate analysis, wbTL-PSMA [hazard ratio (HR): 1.001, p = 0.014] and Gleason score (HR: 5.124, p = 0.031) can significantly predict progression-free prognosis. CONCLUSIONS As imaging biomarkers, wbPSMA-TV and wbTL-PSMA correlated with clinical characteristics significantly. High wbTL-PSMA or Gleason score was associated with shorter PFS of newly diagnosed prostate cancer independently.
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17
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Torres JB, Mosley M, Koustoulidou S, Hopkins S, Knapp S, Chaikuad A, Kondoh M, Tachibana K, Kersemans V, Cornelissen B. Radiolabeled cCPE Peptides for SPECT Imaging of Claudin-4 Overexpression in Pancreatic Cancer. J Nucl Med 2020; 61:1756-1763. [PMID: 32414951 PMCID: PMC8679629 DOI: 10.2967/jnumed.120.243113] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 04/16/2020] [Indexed: 01/09/2023] Open
Abstract
Overexpression of tight-junction protein claudin-4 has been detected in primary and metastatic pancreatic cancer tissue and is associated with better prognosis in patients. Noninvasive measurement of claudin-4 expression by imaging methods could provide a means for accelerating detection and stratifying patients into risk groups. Clostridium perfringens enterotoxin (CPE) is a natural ligand for claudin-4 and holds potential as a targeting vector for molecular imaging of claudin-4 overexpression. A glutathione S-transferases (GST)-tagged version of the C terminus of CPE (cCPE) was previously used to delineate claudin-4 overexpression by SPECT but showed modest binding affinity and slow blood clearance in vivo. Methods: On the basis of the crystal structure of cCPE, a series of smaller cCPE194-319 mutants with putatively improved binding affinity for claudin-4 was generated by site-directed mutagenesis. All peptides were conjugated site-specifically on a C-terminal cysteine using maleimide-diethylenetriamine pentaacetate to enable radiolabeling with 111In. The binding affinity of all radioconjugates was evaluated in claudin-4-expressing PSN-1 cells and HT1080-negative controls. The specificity of all cCPE mutants to claudin-4 was assessed in HT1080 cells stably transfected with claudin-4. SPECT/CT imaging of BALB/c nude mice bearing PSN-1 or HT1080 tumor xenografts was performed to determine the claudin-4-targeting ability of these peptides in vivo. Results: Uptake of all cCPE-based radioconjugates was significantly higher in PSN-1 cells than in HT1080-negative controls. All peptides showed a marked improvement in affinity for claudin-4 in vitro when compared with previously reported values (dissociation constant: 2.2 ± 0.8, 3 ± 0.1, 4.2 ± 0.5, 10 ± 0.9, and 9.7 ± 0.7 nM). Blood clearance of [111In]In-cCPE194-319, as measured by SPECT, was considerably faster than that of [111In]In-cCPE.GST (half-life, <1 min). All radiopeptides showed significantly higher accumulation in PSN-1 xenografts than in HT1080 tumors at 90 min after injection of the tracer ([111In]In-cCPE194-319, 2.7 ± 0.8 vs. 0.4 ± 0.1 percentage injected dose per gram [%ID/g], P < 0.001; [111In]In-S313A, 2.3 ± 0.9 vs. 0.5 ± 0.1 %ID/g, P < 0.01; [111In]In-S307A + N309A + S313A, 2 ± 0.4 vs. 0.3 ± 0.1 %ID/g, P < 0.01; [111In]In-D284A, 2 ± 0.2 vs. 0.7 ± 0.1 %ID/g, P < 0.05; [111In]In-L254F + K257D, 6.3 ± 0.9 vs. 0.7 ± 0.2 %ID/g, P < 0.001). Conclusion: These optimized cCPE-based SPECT imaging agents show great promise as claudin-4-targeting vectors for in vivo imaging of claudin-4 overexpression in pancreatic cancer.
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Affiliation(s)
- Julia Baguña Torres
- Cancer Research United Kingdom and Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
| | - Michael Mosley
- Cancer Research United Kingdom and Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
| | - Sofia Koustoulidou
- Cancer Research United Kingdom and Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
| | - Samantha Hopkins
- Cancer Research United Kingdom and Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
| | - Stefan Knapp
- Institute of Pharmaceutical Chemistry and Structure Genomics Consortium, Goethe-University Frankfurt, Frankfurt am Main, Germany
- German Cancer Network, Mainz-Frankfurt, Germany; and
| | - Apirat Chaikuad
- Institute of Pharmaceutical Chemistry and Structure Genomics Consortium, Goethe-University Frankfurt, Frankfurt am Main, Germany
| | - Masuo Kondoh
- Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan
| | - Keisuke Tachibana
- Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan
| | - Veerle Kersemans
- Cancer Research United Kingdom and Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
| | - Bart Cornelissen
- Cancer Research United Kingdom and Medical Research Council Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom
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18
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Miyata T, Hayashi H, Yamashita YI, Matsumura K, Nakao Y, Itoyama R, Yamao T, Tsukamoto M, Okabe H, Imai K, Chikamoto A, Ishiko T, Baba H. Prognostic Value of the Preoperative Tumor Marker Index in Resected Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Institution Study. Ann Surg Oncol 2020; 28:1572-1580. [PMID: 32804325 DOI: 10.1245/s10434-020-09022-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 07/29/2020] [Indexed: 01/19/2023]
Abstract
BACKGROUND The prediction of prognostic outcomes can provide the most suitable strategy for patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to evaluate the clinical value of the preoperative tumor marker index (pre-TI) in predicting prognostic outcomes after resection for PDAC. METHODS For 183 patients who underwent pancreatic resection of PDAC, adjusted carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), pancreatic cancer-associated antigen-2 (DUpan-2), and s-pancreas-1 antigen (SPan-1) were retrospectively evaluated, and the positive number of these markers was scored as the pre-TI. RESULTS A high pre-TI (≥ 2) was significantly associated with a larger tumor and lymph node metastases, and the patients with a high pre-TI had worse prognostic outcomes in terms of both relapse-free survival (RFS) (P < 0.0001, log-rank) and overall survival (OS) (P < 0.0001, Λlog-rank) than the patients with a low pre-TI. The pre-TI was one of the independent factors of a poor prognosis for RFS (hazard ratio [HR], 2.36; P < 0.0001) and OS (HR, 2.27; P < 0.0001). In addition, even for the patients with normal adjusted CA19-9 values (n = 74, 40.4%), those with the high pre-TI had a significantly poorer prognosis than those with a low pre-TI (RFS: P = 0.002, log-rank; OS: P = 0.031, log-rank). CONCLUSIONS The pre-TI could be a potent predictive marker of prognostic outcomes for patients with resections for PDAC. Patients with a high pre-TI may need additional strategies to improve their prognosis.
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Affiliation(s)
- Tatsunori Miyata
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yo-Ichi Yamashita
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Kazuki Matsumura
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Yosuke Nakao
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Rumi Itoyama
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Takanobu Yamao
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Masayo Tsukamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Takatoshi Ishiko
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan.
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19
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Mohamed E, Needham A, Psarelli E, Carroll M, Vinjamuri S, Sanghera B, Wong WL, Halloran C, Ghaneh P. Prognostic value of 18FDG PET/CT volumetric parameters in the survival prediction of patients with pancreatic cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:1532-1538. [PMID: 32070641 DOI: 10.1016/j.ejso.2020.02.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 01/02/2020] [Accepted: 02/04/2020] [Indexed: 12/12/2022]
Abstract
PURPOSE To investigate the value of 18 FDG PET/CT volumetric parameters in the prediction of overall survival (OS) in patients with pancreatic cancer and also, assess their independence relative to well-established clinico-pathological variables. METHODS We conducted a retrospective analysis of patients with a confirmed diagnosis of pancreatic cancer who underwent 18 FDG PET/CT. The tumour maximum standardised uptake value (SUVmax) in addition to SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated. The prognostic value of 18 FDG PET/CT and clinico-pathological parameters for OS were assessed using univariate and multivariable analyses. RESULTS A sum of 89 patients were analysed in this study. Median survival for patients categorised as having high TLG (≥55) and low TLG (<55) was 18 vs 5 months (p < 0.001). Similarly, the respective high vs low SUVmean, MTV and SUVmax were 18 vs 6 months (p = 0.001), 16 vs 6 months (p = 0.002) and 18 vs 6 months (p = 0.001). Univariate analysis showed SUVmax, SUVmean, MTV, TLG, tumour size, tumour differentiation and presence of distant metastasis as prognostic factors for OS. On multivariable analysis, TLG (HR 2.0, 95% CI 1.26-3.18, p = 0.004) and the presence of distant metastasis (HR 3.37, 95% CI 1.97-5.77, p < 0.001) emerged as independent prognostic factors. Subgroup analysis identified TLG as the only significant PET metric after adjusting for the presence of distant metastasis. CONCLUSIONS 18 FDG PET/CT is a useful tool in the preoperative evaluation of patients with pancreatic cancer. Tumour TLG offer an independent prognostic value in both potentially operable and metastatic disease settings.
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Affiliation(s)
- Eyas Mohamed
- Department of Pancreaticobiliary Surgery, Royal Liverpool University Hospital, Liverpool, UK
| | - Alexander Needham
- Liverpool Cancer Research UK Cancer Trials Unit, Liverpool Cancer Research UK Centre, University of Liverpool, Liverpool, UK
| | - Eftychia Psarelli
- Liverpool Cancer Research UK Cancer Trials Unit, Liverpool Cancer Research UK Centre, University of Liverpool, Liverpool, UK
| | - Melvyn Carroll
- Department of Nuclear Medicine, Royal Liverpool University Hospital, Liverpool, UK
| | - Sobhan Vinjamuri
- Department of Nuclear Medicine, Royal Liverpool University Hospital, Liverpool, UK
| | - Bal Sanghera
- Paul Strickland Scanner Centre, Mount Vernon Hospital, Middlesex, UK
| | - Wai Lup Wong
- Paul Strickland Scanner Centre, Mount Vernon Hospital, Middlesex, UK
| | - Christopher Halloran
- Department of Pancreaticobiliary Surgery, Royal Liverpool University Hospital, Liverpool, UK; Liverpool Cancer Research UK Cancer Trials Unit, Liverpool Cancer Research UK Centre, University of Liverpool, Liverpool, UK
| | - Paula Ghaneh
- Department of Pancreaticobiliary Surgery, Royal Liverpool University Hospital, Liverpool, UK; Liverpool Cancer Research UK Cancer Trials Unit, Liverpool Cancer Research UK Centre, University of Liverpool, Liverpool, UK.
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20
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Fiore M, Taralli S, Trecca P, Scolozzi V, Marinelli L, Triumbari EKA, Caputo D, Angeletti S, Ciccozzi M, Coppola A, Greco C, Ippolito E, Calcagni ML, Coppola R, Ramella S. A Bio-Imaging Signature as a Predictor of Clinical Outcomes in Locally Advanced Pancreatic Cancer. Cancers (Basel) 2020; 12:2016. [PMID: 32717967 PMCID: PMC7464714 DOI: 10.3390/cancers12082016] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 07/20/2020] [Accepted: 07/22/2020] [Indexed: 12/25/2022] Open
Abstract
Purpose: To evaluate the predictive value of 18F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline 18F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured. The receiving operating characteristics (ROC) analysis was performed to define the cut-off point of SUVmax, MTV, TLG and CA 19-9 values to use in prediction of early progression (EP), local progression (LP) and overall survival (OS). Areas under the curve (AUCs) were assessed for all variables. Post-test probability was calculated to evaluate the advantage for parameters combination. Results: For EP, CA 19-9 level > 698 U/mL resulted the best marker to identify patient at higher risk with OR of 5.96 (95% CI, 1.66-19.47; p = 0.005) and a Positive Predictive Value (PPV) of 61%. For LP, the most significant parameter was TLG (OR 9.75, 95% CI, 1.64-57.87, p = 0.012), with PPV of 83%. For OS, the most significant parameter was MTV (OR 3.12, 95% CI, 0.9-10.83, p = 0.07) with PPV of 88%. Adding consecutively each of the other parameters, PPV to identify patients at risk resulted further increased (>90%). Conclusions: Pre-treatment CA 19-9 level, as well as MTV and TLG values of primary tumour at baseline 18F-FDG PET/CT and their combination, may represent significant predictors of EP, LP and OS in LAPC patients.
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Affiliation(s)
- Michele Fiore
- Radiation Oncology, Campus Bio-Medico University, 00128 Rome, Italy; (P.T.); (C.G.); (E.I.); (S.R.)
| | - Silvia Taralli
- UOC Medicina Nucleare, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.T.); (V.S.); (E.K.A.T.); (M.L.C.)
| | - Pasquale Trecca
- Radiation Oncology, Campus Bio-Medico University, 00128 Rome, Italy; (P.T.); (C.G.); (E.I.); (S.R.)
| | - Valentina Scolozzi
- UOC Medicina Nucleare, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.T.); (V.S.); (E.K.A.T.); (M.L.C.)
| | - Luca Marinelli
- Radiation Oncology, S. Andrea Hospital, Sapienza University of Rome, 00189 Rome, Italy;
| | - Elizabeth K. A. Triumbari
- UOC Medicina Nucleare, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.T.); (V.S.); (E.K.A.T.); (M.L.C.)
- Istituto di Medicina Nucleare, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Damiano Caputo
- Department of Surgery, Campus Bio-Medico University, 00128 Rome, Italy; (D.C.); (A.C.); (R.C.)
| | - Silvia Angeletti
- Unit of Clinical Laboratory Science, Campus Bio-Medico University, 00128 Rome, Italy;
| | - Massimo Ciccozzi
- Unit of Medical Statistic and Molecular Epidemiology, Campus Bio-Medico University, 00128 Rome, Italy;
| | - Alessandro Coppola
- Department of Surgery, Campus Bio-Medico University, 00128 Rome, Italy; (D.C.); (A.C.); (R.C.)
| | - Carlo Greco
- Radiation Oncology, Campus Bio-Medico University, 00128 Rome, Italy; (P.T.); (C.G.); (E.I.); (S.R.)
| | - Edy Ippolito
- Radiation Oncology, Campus Bio-Medico University, 00128 Rome, Italy; (P.T.); (C.G.); (E.I.); (S.R.)
| | - Maria Lucia Calcagni
- UOC Medicina Nucleare, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.T.); (V.S.); (E.K.A.T.); (M.L.C.)
- Istituto di Medicina Nucleare, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Roberto Coppola
- Department of Surgery, Campus Bio-Medico University, 00128 Rome, Italy; (D.C.); (A.C.); (R.C.)
| | - Sara Ramella
- Radiation Oncology, Campus Bio-Medico University, 00128 Rome, Italy; (P.T.); (C.G.); (E.I.); (S.R.)
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21
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Sperti C, Friziero A, Serafini S, Bissoli S, Ponzoni A, Grego A, Grego E, Moletta L. Prognostic Implications of 18-FDG Positron Emission Tomography/Computed Tomography in Resectable Pancreatic Cancer. J Clin Med 2020; 9:2169. [PMID: 32659933 PMCID: PMC7408707 DOI: 10.3390/jcm9072169] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 06/29/2020] [Accepted: 07/07/2020] [Indexed: 02/07/2023] Open
Abstract
There are currently no known preoperative factors for determining the prognosis in pancreatic cancer. The aim of this study was to examine the role of 18-fluorodeoxyglucose (18-FDG) positron emission tomography/computed tomography (18-FDG-PET/CT) as a prognostic factor for patients with resectable pancreatic cancer. Data were obtained from a retrospective analysis of patients who had a preoperative PET scan and then underwent pancreatic resection from January 2007 to December 2015. The maximum standardized uptake value (SUVmax) of 18-FDG-PET/CT was calculated. Patients were divided into high (>3.65) and low (≤3.65) SUVmax groups, and compared in terms of their TNM classification (Union for International Cancer Contro classification), pathological grade, surgical treatment, state of resection margins, lymph node involvement, age, sex, diabetes and serum Carbohydrate Antigen 19-9 (CA 19-9) levels. The study involved 144 patients, 82 with high SUVmax pancreatic cancer and 62 with low SUVmax disease. The two groups' disease-free and overall survival rates were significantly influenced by tumor stage, lymph node involvement, pathological grade, resection margins and SUVmax. Patients with an SUVmax ≤ 3.65 had a significantly better survival than those with SUVmax > 3.65 (p < 0.001). The same variables were independent predictors of survival on multivariate analysis. The SUVmax calculated with 18-FDG-PET/CT is an important prognostic factor for patients with pancreatic cancer, and may be useful in decisions concerning patients' therapeutic management.
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Affiliation(s)
- Cosimo Sperti
- Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, Via Giustiniani 2, 35128 Padua, Italy; (A.F.); (S.S.); (A.G.); (L.M.)
| | - Alberto Friziero
- Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, Via Giustiniani 2, 35128 Padua, Italy; (A.F.); (S.S.); (A.G.); (L.M.)
| | - Simone Serafini
- Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, Via Giustiniani 2, 35128 Padua, Italy; (A.F.); (S.S.); (A.G.); (L.M.)
| | - Sergio Bissoli
- Nuclear Medicine, Belluno General Hospital, Viale Europa 22, 32100 Belluno, Italy;
| | - Alberto Ponzoni
- Department of Radiology, Padua General Hospital, Via Giustiniani 2, 35128 Padua, Italy;
| | - Andrea Grego
- Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, Via Giustiniani 2, 35128 Padua, Italy; (A.F.); (S.S.); (A.G.); (L.M.)
| | - Emanuele Grego
- University of Padua, Via Giustiniani 2, 35128 Padua, Italy;
| | - Lucia Moletta
- Department of Surgery, Oncology and Gastroenterology, 3rd Surgical Clinic, University of Padua, Via Giustiniani 2, 35128 Padua, Italy; (A.F.); (S.S.); (A.G.); (L.M.)
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22
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Liang C, Shi S, Qin Y, Meng Q, Hua J, Hu Q, Ji S, Zhang B, Xu J, Yu XJ. Localisation of PGK1 determines metabolic phenotype to balance metastasis and proliferation in patients with SMAD4-negative pancreatic cancer. Gut 2020; 69:888-900. [PMID: 31611300 DOI: 10.1136/gutjnl-2018-317163] [Citation(s) in RCA: 110] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 08/23/2019] [Accepted: 09/02/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive type of GI tumour, and it possesses deregulated cellular energetics. Although recent advances in PDAC biology have led to the discovery of recurrent genetic mutations in Kras, TP53 and SMAD4, which are related to this disease, clinical application of the molecular phenotype of PDAC remains challenging. DESIGN We combined molecular imaging technology (positron emission tomography/CT) and immunohistochemistry to evaluate the correlation between the maximum standardised uptake value and SMAD4 expression and examined the effect of SMAD4 on glycolysis through in vitro and in vivo experiments. Furthermore, we identified the effect of SMAD4 on metabolic reprogramming by metabolomics and glucose metabolism gene expression analyses. Dual luciferase reporter assays and chromatin immunoprecipitation were performed to identify whether SMAD4 functioned as a transcription factor for phosphoglycerate kinase 1 (PGK1) in PDAC cells. Proliferative and metastatic assays were performed to examine the effect of PGK1 on the malignant behaviour of PDAC. RESULTS We provide compelling evidence that the glycolytic enzyme PGK1 is repressed by transforming growth factor-β/SMAD4. Loss of SMAD4 induces PGK1 upregulation in PDAC, which enhances glycolysis and aggressive tumour behaviour. Notably, in SMAD4-negative PDAC, nuclear PGK1 preferentially drives cell metastasis via mitochondrial oxidative phosphorylation induction, whereas cytoplasmic PGK1 preferentially supports proliferation by functioning as a glycolytic enzyme. The PDAC progression pattern and distinct PGK1 localisation combine to predict overall survival and disease-free survival. CONCLUSION PGK1 is a decisive oncogene in patients with SMAD4-negative PDAC and can be a target for the development of a therapeutic strategy for SMAD4-negative PDAC.
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Affiliation(s)
- Chen Liang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College Fudan University, Shanghai, China.,Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College Fudan University, Shanghai, China.,Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Yi Qin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College Fudan University, Shanghai, China.,Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Qingcai Meng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College Fudan University, Shanghai, China.,Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Jie Hua
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College Fudan University, Shanghai, China.,Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Qiangshen Hu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College Fudan University, Shanghai, China.,Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Shunrong Ji
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College Fudan University, Shanghai, China.,Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Bo Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College Fudan University, Shanghai, China.,Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College Fudan University, Shanghai, China.,Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xian-Jun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China .,Department of Oncology, Shanghai Medical College Fudan University, Shanghai, China.,Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
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Cui SJ, Tang TY, Zou XW, Su QM, Feng L, Gong XY. Role of imaging biomarkers for prognostic prediction in patients with pancreatic ductal adenocarcinoma. Clin Radiol 2020; 75:478.e1-478.e11. [PMID: 32037002 DOI: 10.1016/j.crad.2019.12.023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 12/30/2019] [Indexed: 12/13/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumours. PDAC has a poor prognosis; therefore, it is necessary to perform further risk stratification. Identifying prognostic factors before treatment might help to implement suitable and personalised treatment for individuals and avoid side effects. Conventional staging systems and tumour biomarkers are fundamental to establish prognosis; however, they have obvious limitations. Novel imaging biomarkers extracted from advanced imaging techniques offer opportunities to evaluate underlying tumour physiological characteristics, such as mutational status, cellular composition, local microenvironment, tumour metabolism, and biological behaviour. Thus, imaging biomarkers might help the decision making of oncologists and surgeons. The present review discusses the functions of imaging biomarkers for prognostic prediction in patients with PDAC and their potential value for further translation in clinical practice.
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Affiliation(s)
- S-J Cui
- The Second Clinical Medical College, Zhejiang Chinese Medical University, 310053, Hangzhou, China; Department of Radiology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, 310013, Hangzhou, China
| | - T-Y Tang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - X-W Zou
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China
| | - Q-M Su
- Department of General Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - L Feng
- Department of Nuclear Medicine, The Second Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - X-Y Gong
- Department of Radiology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, 310013, Hangzhou, China; Institute of Artificial Intelligence and Remote Imaging, Hangzhou Medical College, 310000, Hangzhou, China.
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24
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PET in Gastrointestinal, Pancreatic, and Liver Cancers. Clin Nucl Med 2020. [DOI: 10.1007/978-3-030-39457-8_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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25
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Incerti E, Vanoli EG, Broggi S, Gumina C, Passoni P, Slim N, Fiorino C, Reni M, Mapelli P, Cattaneo M, Zanon S, Calandrino R, Gianolli L, Di Muzio N, Picchio M. Early variation of 18-fluorine-labelled fluorodeoxyglucose PET-derived parameters after chemoradiotherapy as predictors of survival in locally advanced pancreatic carcinoma patients. Nucl Med Commun 2019; 40:1072-1080. [PMID: 31365502 DOI: 10.1097/mnm.0000000000001065] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
OBJECTIVE To investigate if early variation of PET-derived parameters after concomitant chemoradiotherapy (CRT) predicts overall survival (OS), local relapse free survival (LRFS), distant relapse free survival (DRFS) and progression free survival (PFS) in locally advanced pancreatic cancer (LAPC) patients. METHODS Fifty-two LAPC patients (median age: 61 years; range: 35-85) with available FDG PET/CT before and after RT (2-6 months, median: 2) were enrolled from May 2005 to June 2015. The predictive value of the percentage variation of mean/maximum standard uptake value (ΔSUVmean/max), metabolic tumour volume (ΔMTV) and total lesion glycolysis (ΔTLG), estimated considering different uptake thresholds (40-50-60%), was investigated between pre- and post-RT PET. The percentage difference between gastrointestinal cancer-associated antigen (ΔGICA) levels measured at the time of PET was also considered. Log-rank test and Cox regression analysis were performed to assess the prognostic value of considered PET-derived parameters on survival outcomes. RESULTS The median follow-up was 13 months (range: 4-130). At univariate analysis, ΔTLG50 showed borderline significance in predicting OS (P = 0.05) and was the most significant parameter correlated to LRFS and PFS (P = 0.001). Median LRFS was 4 and 33 months if ΔTLG50 was below or above 35% respectively (P = 0.0003); similarly, median PFS was 3 vs 6 months (P = 0.0009). No significant correlation was found between PET-derived parameters and DRFS, while the ΔGICA was the only borderline significant prognostic value for this endpoint (P = 0.05). CONCLUSION PET-derived parameters predict survival in LAPC patients; in particular, ΔTLG50 is the strongest predictor. The combination of these biochemical and imaging biomarkers is promising in identifying patients at higher risk of earlier relapse.
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Affiliation(s)
| | | | | | | | | | | | | | - Michele Reni
- Department of Oncology, IRCCS San Raffaele Scientific Institute
| | - Paola Mapelli
- Unit of Nuclear Medicine
- Vita-Salute San Raffaele University, Milan, Italy
| | | | - Silvia Zanon
- Department of Oncology, IRCCS San Raffaele Scientific Institute
| | | | | | | | - Maria Picchio
- Unit of Nuclear Medicine
- Vita-Salute San Raffaele University, Milan, Italy
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26
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Wang L, Dong P, Shen G, Hou S, Zhang Y, Liu X, Tian B. 18F-Fluorodeoxyglucose Positron Emission Tomography Predicts Treatment Efficacy and Clinical Outcome for Patients With Pancreatic Carcinoma: A Meta-analysis. Pancreas 2019; 48:996-1002. [PMID: 31404025 DOI: 10.1097/mpa.0000000000001375] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
OBJECTIVES F-Fluorodeoxyglucose positron emission tomography (FDG-PET) has been an important modality for detecting malignancies. Recently, an increasing number of studies reported the utility of FDG-PET parameters in predicting clinical outcomes and treatment assessment in variety of cancers. We aimed at clarifying both the prognostic role and assessment value of FDG-PET in pancreatic carcinoma. METHODS We systematically searched electronic databases of PubMed, Embase, Cochrane Library, and Web of Science to identify relevant studies to conduct this meta-analysis. Comparative analyses of the pooled hazard ratio (HR) for overall survival were performed to assess the utility of FDG-PET parameters in prognosis evaluation and treatment assessment by random-effect model. RESULTS Twenty-three studies with 1762 patients met the inclusion criteria of this meta-analysis. The pooled results revealed that greater maximum standardized uptake value of the primary tumor was significantly correlated with poorer overall survival (HR, 1.31; 95% confidence interval, 1.15-1.50; P < 0.001). Besides, greater reduction of maximum standardized uptake value after treatments indicated significant better overall survival (HR, 0.68; 95% confidence interval, 0.47-0.98; P = 0.037). CONCLUSIONS F-Fluorodeoxyglucose positron emission tomography parameters might be helpful not only for predicting survival outcome but also for selecting potentially efficacious treatments in patients with pancreatic carcinoma.
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Affiliation(s)
- Li Wang
- From the Departments of Pancreatic Surgery
| | - Ping Dong
- Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Guohua Shen
- Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, China
| | | | - Yi Zhang
- From the Departments of Pancreatic Surgery
| | - Xubao Liu
- From the Departments of Pancreatic Surgery
| | - Bole Tian
- From the Departments of Pancreatic Surgery
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27
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Zhou C, Zhao Y, Yin Y, Hu Z, Atyah M, Chen W, Meng Z, Mao H, Zhou Q, Tang W, Wang P, Li Z, Weng J, Bruns C, Popp M, Popp F, Dong Q, Ren N. A robust 6-mRNA signature for prognosis prediction of pancreatic ductal adenocarcinoma. Int J Biol Sci 2019; 15:2282-2295. [PMID: 31595147 PMCID: PMC6775308 DOI: 10.7150/ijbs.32899] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Accepted: 08/03/2019] [Indexed: 01/04/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. PDAC prognostic and diagnostic biomarkers are still being explored. The aim of this study is to establish a robust molecular signature that can improve the ability to predict PDAC prognosis. 155 overlapping differentially expressed genes between tumor and non-tumor tissues from three Gene Expression Omnibus (GEO) datasets were explored. A least absolute shrinkage and selection operator method (LASSO) Cox regression model was employed for selecting prognostic genes. We developed a 6-mRNA signature that can distinguish high PDAC risk patients from low risk patients with significant differences in overall survival (OS). We further validated this signature prognostic value in three independent cohorts (GEO batch, P < 0.0001; ICGC, P = 0.0036; Fudan, P = 0.029). Furthermore, we found that our signature remained significant in patients with different histologic grade, TNM stage, locations of tumor entity, age and gender. Multivariate cox regression analysis showed that 6-mRNA signature can be an independent prognostic marker in each of the cohorts. Receiver operating characteristic curve (ROC) analysis also showed that our signature possessed a better predictive role of PDAC prognosis. Moreover, the gene set enrichment analysis (GSEA) analysis showed that several tumorigenesis and metastasis related pathways were indeed associated with higher scores of risk. In conclusion, identifying the 6-mRNA signature could provide a valuable classification method to evaluate clinical prognosis and facilitate personalized treatment for PDAC patients. New therapeutic targets may be developed upon the functional analysis of the classifier genes and their related pathways.
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Affiliation(s)
- Chenhao Zhou
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Yue Zhao
- Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany
- Department of Surgery, Otto-von-Guericke University, Magdeburg, Germany
| | - Yirui Yin
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Zhiqiu Hu
- Institute of Fudan Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Manar Atyah
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Wanyong Chen
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
- Institute of Fudan Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Zhefeng Meng
- Institute of Fudan Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Huarong Mao
- Institute of Fudan Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Qiang Zhou
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Weiguo Tang
- Institute of Fudan Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Pengcheng Wang
- Institute of Fudan Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Zhanming Li
- Institute of Fudan Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Jialei Weng
- Institute of Fudan Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
| | - Christiane Bruns
- Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany
| | - Marie Popp
- Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany
| | - Felix Popp
- Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Cologne, Germany
| | - Qiongzhu Dong
- Institute of Fudan Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
- Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Ning Ren
- Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
- Institute of Fudan Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China
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Zhou W, Yang F, Peng J, Wang F, Lin Y, Jiang W, Yang X, Li L, Lu Z, Wan D, Pan Z, Fan W. High pretreatment serum CA19-9 level predicts a poor prognosis for patients with stage III colon cancer after curative resection and adjuvant chemotherapy. J Cancer 2019; 10:3810-3818. [PMID: 31333798 PMCID: PMC6636281 DOI: 10.7150/jca.31375] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Accepted: 05/10/2019] [Indexed: 01/01/2023] Open
Abstract
Carbohydrate antigen 19-9 (CA19-9) is one of the most widely used tumor markers in gastrointestinal cancer. However, serum CA19-9 is not a recommended routine measurement in colon cancer. In this study, we evaluated the value of the preoperative serum CA19-9 level for the prediction of postoperative prognosis in stage III colon cancer. The medical records of 367 consecutive patients with stage III colon cancer who underwent curative resection followed by adjuvant chemotherapy with oxaliplatin and capecitabine between December 2007 and April 2015 were retrospectively reviewed. We determined the optimal cutoff value of CA19-9 for 3-year recurrence using the receiver operating characteristic (ROC) method. Differences in disease-free survival (DFS) and overall survival (OS) rates stratified by CA19-9 level were compared by using Kaplan-Meier and log-rank tests. A Cox proportional hazards model was used to identify prognostic variables for DFS and OS. The statistically determined best cutoff value for CA19-9 was 24 U/ml. High CA19-9 levels (> 24 U/ml) were significantly associated with poorly differentiated tumors, abnormal carcinoembryonic antigen (CEA) levels, and a high cumulative incidence of lung metastasis. Additionally, compared with low CA19-9 levels, high preoperative CA19-9 levels were associated with inferior 3-year DFS and OS rates, especially for high-risk patients (T4Nany or TanyN2). Multivariate analyses revealed that CA19-9 was an independent factor associated with both DFS (hazard ratio [HR], 2.248; 95% confidence interval [CI], 1.393-3.628; P = 0.001) and OS (HR: 2.081; 95% CI: 1.137-3.808; P = 0.017). The results of this study showed that high levels of preoperative serum CA19-9 indicated a worse prognostic outcome for stage III colon cancer patients. An early follow-up protocol to assess lung metastasis and a full course of adjuvant chemotherapy should be used for these patients.
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Affiliation(s)
- Wenhao Zhou
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Fan Yang
- Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine Guangzhou, 510060, P.R. China
| | - Jianhong Peng
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Fulong Wang
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Yuzhu Lin
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Wu Jiang
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Xia Yang
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Liren Li
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Zhenhai Lu
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Desen Wan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Zhizhong Pan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
| | - Wenhua Fan
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, P.R. China
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Preoperative maximum standardized uptake value and carbohydrate antigen 19-9 were independent predictors of pathological stages and overall survival in Chinese patients with pancreatic duct adenocarcinoma. BMC Cancer 2019; 19:456. [PMID: 31092213 PMCID: PMC6521479 DOI: 10.1186/s12885-019-5691-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2018] [Accepted: 05/08/2019] [Indexed: 02/07/2023] Open
Abstract
Background Purpose of this study was to analyze whether preoperative maximum standardized uptake value (SUVmax) and carbohydrate antigen 19–9 (CA19–9) levels might provide prognostic information in Chinese patients with pancreatic duct adenocarcinoma (PDAC) after pancreaticoduodenectomy (PD). Methods Standard PD was performed on 109 patients with PDAC by the same operative team, and all patients received preoperative positron emission tomography/computed tomography examination and blood test. Results Patients had a mean age of 59 ± 9.35 years. Females accounted for 38.5%. Mean levels of SUVmax, carcino-embryonic antigen (CEA) and CA19–9 were 5.70 ± 2.76, 3.95 ± 4.16ng/mL and 321.62 ± 780.71kU/L. In univariate Logistic regression analysis, preoperative SUVmax, CEA and CA19–9 levels (p < 0.05 for all) rather than other preoperative variables (p > 0.05 for all) were significantly related to AJCC stages. Multivariate Logistic regression analysis showed that preoperative SUVmax and CA19–9 levels (p < 0.05 for all) rather than other preoperative variables (p > 0.05 for all) were significantly associated with AJCC stages. Mean overall survival (OS) was 21 ± 14.50 months. In univariate Cox regression analysis, age, SUVmax, CEA and CA19–9 levels before operation (p < 0.05 for all) rather than other preoperative variables (p > 0.05 for all) were significantly related to OS. Multivariate Cox regression analysis showed that age, SUVmax and CA19–9 levels before operation (p < 0.05 for all) rather than other preoperative variables (p > 0.05 for all) were significantly associated with OS. Conclusions This study demonstrated that preoperative SUVmax and CA19–9 levels independently predicted pathological stages and OS of patients with PDAC after PD. These preoperative variables might have significant prognostic implication in patients with PDAC after PD. Patients with abnormal SUVmax and CA19–9 levels should be paid special attention to in operative strategy and perioperative management.
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Zhang A, Ren S, Yuan Y, Li X, Zhu X, Jiang L, Li D, Zuo C. Prognostic values of 18F-FDG PET/CT metabolic parameters and clinical figures in locally advanced pancreatic cancer underwent chemotherapy combined with stereotactic body radiation therapy. Medicine (Baltimore) 2019; 98:e15064. [PMID: 30921238 PMCID: PMC6455984 DOI: 10.1097/md.0000000000015064] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 03/02/2019] [Indexed: 01/14/2023] Open
Abstract
Stereotactic body radiation therapy (SBRT) has emerged to be a preference treatment for locally advanced pancreatic cancer (LAPC) patients. In this study, we aimed to investigate the prognostic roles of F-FDG PET/CT metabolic parameters and clinical figures in LAPC patients underwent chemo-SBRT combined therapy.During January 2013 to January 2017, 23 LAPC patients who underwent F-FDG PET/CT within 2 weeks before treatment were recruited and retrospectively analyzed. Maximum standardized uptake values (SUVmax), SUVmean, metabolic tumor volume (MTV), total lesion glycolysis (TLG), chemoradiotherapy (CRT) sequence, and relevant clinical figures were grouped upon the median values, then analyzed by Kaplan-Meier method and Cox proportional hazard models for their prognostic evaluation.The median overall survival (OS) and progression-free survival (PFS) of all patients were 16.7 months and 11.3 months, respectively. According to the statistic results, the longest diameter of tumor (LDT), MTV, TLG, and CRT sequence were associated with OS (all P <.05). Among which, LDT and MTV were proved to be the independent prognostic factors for OS (hazard ratio [HR]: 3.437, 3.015, both P <.05). Additionally, LDT and CRT sequence were found associated with PFS (both P <.05), and CRT sequence was the independent prognostic factor for PFS in chemo-SBRT treated LAPC patients (HR: 0.130, P <.05).For LAPC patients received chemotherapy and SBRT combined therapy, MTV and LDT showed independent prognostic values for OS. Meanwhile, CRT sequence was an independent PFS prediction factor.
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Affiliation(s)
- Anyu Zhang
- Department of Nuclear Medicine, Changhai Hospital Affiliated to Second Military Medical University, Shanghai, Department of Nuclear Medicine, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu
| | | | | | - Xiao Li
- Department of Nuclear Medicine
| | - Xiaofei Zhu
- Department of Radiation Oncology, Changhai Hospital Affiliated to Second Military Medical University, Shanghai, China
| | - Lingong Jiang
- Department of Radiation Oncology, Changhai Hospital Affiliated to Second Military Medical University, Shanghai, China
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Rho SY, Yun M, Kang CM, Lee SH, Hwang HK, Lee WJ. Different biological behaviors in left-sided pancreatic cancer according to Yonsei criteria: Proposal of a modified Yonsei criteria score. Pancreatology 2018; 18:990-995. [PMID: 30201440 DOI: 10.1016/j.pan.2018.09.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 08/12/2018] [Accepted: 09/01/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Our institutional experience has demonstrated that bloodless and margin-negative resection is the most potent prognostic factor in treating left-sided pancreatic cancer and we developed selection guideline. The Yonsei criteria (YC) is selection criteria for oncologically safe and effective resection of left-sided pancreatic cancer by a minimally invasive approach. In this study, we investigated whether left-sided pancreatic cancer with YC can be more individualized to predict long-term survival by using clinically and pathologically detectable parameters. METHODS From January 2000 to December 2015, 105 patients underwent distal pancreatectomy for left-sided pancreatic cancer. The medical records of the patients were retrospectively reviewed. RESULTS Among clinically and pathologically detectable parameters to predict tumor conditions, radiologically determined tumor size (p = 0.080) and SUVmax (p = 0.086) were identified as predictors of early tumor recurrence with marginal significance. Among them, 20% of the patients with YC were identified as having the most favoring tumor condition, with an modified YC score of 3. The patient group with the lowest mYC score was found to have a very long disease-free survival time, with a mean of 108 months, which was statistically different from those with other mYC scores (mYC score = 4, mean 47.1 months [95% CI: 27.8-69.5] vs. mYC score = 5, mean 36.7 months [95% CI: 12.7-60.7], vs. mYC score = 6, mean 10.7 months [95% CI: 3.9-17.4]). CONCLUSIONS Modified Yonsei criteria score can predict long-term survival in resected left-sided pancreatic cancer. And patients within YC with a mYC score = 3 could have a favorable survival outcome.
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Affiliation(s)
- Seoung Yoon Rho
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine, South Korea; Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, South Korea
| | - Mijin Yun
- Department of Nuclear Medicine, Yonsei University College of Medicine, South Korea
| | - Chang Moo Kang
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine, South Korea; Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, South Korea.
| | - Sung Hwan Lee
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine, South Korea; Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, South Korea
| | - Ho Kyoung Hwang
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine, South Korea; Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, South Korea
| | - Woo Jung Lee
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine, South Korea; Pancreatobiliary Cancer Center, Yonsei Cancer Center, Severance Hospital, Seoul, South Korea
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Ma W, Wang M, Li X, Huang H, Zhu Y, Song X, Dai D, Xu W. Quantitative 18F-FDG PET analysis in survival rate prediction of patients with non-small cell lung cancer. Oncol Lett 2018; 16:4129-4136. [PMID: 30214552 PMCID: PMC6126162 DOI: 10.3892/ol.2018.9166] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Accepted: 10/13/2017] [Indexed: 12/19/2022] Open
Abstract
The aim of the present study was to investigate the prognostic value of quantitative [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) parameters for patients with non-small cell lung cancer (NSCLC). The present study conducted a retrospective review of the medical records of 203 patients with NSCLC, of which 193 patients underwent baseline 18F-FDG PET/CT prior to initial therapy. Multivariate analyses using Cox's proportional hazards regression were performed for the assessment of the association between initial PET/CT measurements and overall survival (OS). The multivariate models were adjusted for sex, age, smoking status, disease stage, standardized uptake value (SUV), standardized uptake value corrected for lean body mass (SUL), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and standard deviation of SUV (SD). Kaplan-Meier (K-M) estimator curves were constructed following the formation of three approximately equal-sized groups using tertiles for each PET/CT measurement (n=65, 64 and 64). OS curves were plotted using K-M estimator curves. Results demonstrated significant associations between OS and MTVPET volume computerized assisted reporting (PETVCAR), MTV2.5, MTV25%, MTV42% and TLGPETVCAR; however, no significant associations were identified between OS and MTV50%, MTV75%, TLG2.5, all SUV and SUL. Subgroup analyses according to pathology demonstrated that there were statistically significant associations between OS and stage (P<0.001), MTV50% (P=0.002) and MTV42% (P=0.004) in the adenocarcinoma group, and SULmean (P=0.010), MTV25% (P=0.005) and MTV42% (P=0.001) in the squamous cell carcinoma group; however, no significant differences were identified between any other group. Furthermore, there was a significant association between OS and MTV42% (P=0.02) and MTV50% (P=0.04) in the early-stage group; however, no significant differences were identified in the advanced-stage group. K-M estimator curve analyses demonstrated that the pathology (P=0.01), stage (P<0.001) and all PET metabolic parameters with the exception of SD were significantly associated with OS (P<0.05). No significant associations were demonstrated between SD and OS. In conclusion, 18F-FDG PET/CT MTVPETVCAR, MTV2.5, MTV25%, MTV42% and TLGPETVCAR exhibit prognostic values with regard to OS. Overall, selection of appropriate metabolic parameters may predict NSCLC prognosis.
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Affiliation(s)
- Wenchao Ma
- Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China
- Tianjin Clinical Research Center for Cancer, Hexi, Tianjin 300060, P.R. China
| | - Minshu Wang
- Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China
- Tianjin Clinical Research Center for Cancer, Hexi, Tianjin 300060, P.R. China
| | - Xiaofeng Li
- Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China
- Tianjin Clinical Research Center for Cancer, Hexi, Tianjin 300060, P.R. China
| | - Hui Huang
- Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China
- Tianjin Clinical Research Center for Cancer, Hexi, Tianjin 300060, P.R. China
| | - Yanjia Zhu
- Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China
- Tianjin Clinical Research Center for Cancer, Hexi, Tianjin 300060, P.R. China
| | - Xiuyu Song
- Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China
- Tianjin Clinical Research Center for Cancer, Hexi, Tianjin 300060, P.R. China
| | - Dong Dai
- Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China
- Tianjin Clinical Research Center for Cancer, Hexi, Tianjin 300060, P.R. China
| | - Wengui Xu
- Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China
- National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China
- Tianjin Clinical Research Center for Cancer, Hexi, Tianjin 300060, P.R. China
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Nie K, Zhang YX, Nie W, Zhu L, Chen YN, Xiao YX, Liu SY, Yu H. Prognostic value of metabolic tumour volume and total lesion glycolysis measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography in small cell lung cancer: A systematic review and meta-analysis. J Med Imaging Radiat Oncol 2018; 63:84-93. [PMID: 30230710 DOI: 10.1111/1754-9485.12805] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 08/17/2018] [Indexed: 01/26/2023]
Abstract
The aim of this study was to evaluate the prognostic value of metabolic tumour volume (MTV) and total lesion glycolysis (TLG) for small cell lung cancer (SCLC). MEDLINE, EMBASE and Cochrane Library databases were systematically searched. The pooled hazard ratio (HR) was used to measure the influence of MTV and TLG on survival. The subgroup analysis according to VALSG stage and the measured extent of MTV was performed. Patients with high MTV values experienced a significantly poorer prognosis with a HR of 2.42 (95% CI 1.46-4.03) for overall survival (OS) and a HR of 2.78 (95% CI 1.39-5.53) for progression-free survival (PFS) from the random effect model, and the pooled HR from the fixed effect model was 2.10 (95% CI 1.77-2.50) for OS and 2.27 (95% CI 1.83-2.81) for PFS. Patients with high TLG experienced a poorer prognosis with a HR of 1.61 (95% CI: 1.24-2.07) for OS from the random effect model, and the pooled HR from the fixed effect model was 1.64 (95% CI 1.37-1.96). Heterogeneity among studies was high for MTV in both OS and PFS meta-analyses (I2 = 87% and 88% respectively). After removing one outlier study the heterogeneity was substantially reduced (I2 = 0%) and the pooled HR for the effect of MTV on OS was 1.80 (1.51-2.16, P < 0.00001), and on PFS it was 1.86 (1.49-2.33, P < 0.00001), using either the fixed or random effects model. High MTV is associated with a significantly poorer prognosis OS and PFS, and high TLG is associated with a significantly poorer prognosis regarding OS for SCLC.
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Affiliation(s)
- Kai Nie
- Department of Imaging and Nuclear Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Yu-Xuan Zhang
- School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, UK
| | - Wei Nie
- Department of Respiration, Shanghai Chest Hospital affiliated to Shanghai Jiaotong University, Shanghai, China
| | - Lin Zhu
- Department of Imaging and Nuclear Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Yi-Nan Chen
- Department of Radiology, Shanghai Chest Hospital affiliated to Shanghai Jiaotong University, Shanghai, China
| | - Yong-Xin Xiao
- Department of Imaging and Nuclear Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Shi-Yuan Liu
- Department of Imaging and Nuclear Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Hong Yu
- Department of Imaging and Nuclear Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, China.,Department of Radiology, Oriental Hospital Affiliated Tongji University, Shanghai, China
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Xu HX, Li S, Wu CT, Qi ZH, Wang WQ, Jin W, Gao HL, Zhang SR, Xu JZ, Liu C, Long J, Xu J, Ni QX, Yu XJ, Liu L. Postoperative serum CA19-9, CEA and CA125 predicts the response to adjuvant chemoradiotherapy following radical resection in pancreatic adenocarcinoma. Pancreatology 2018; 18:671-677. [PMID: 30153903 DOI: 10.1016/j.pan.2018.05.479] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 05/13/2018] [Accepted: 05/15/2018] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the prediction of benefits from adjuvant chemoradiotherapy by postoperative serum CA19-9, CA125 and CEA. METHODS The relations between benefits from adjuvant chemoradiotherapy and levels of postoperative serum CA19-9, CA125 and CEA were investigated in 804 pancreatic adenocarcinoma patients who received radical resection. RESULTS Adjuvant chemoradiotherapy was an independent factor for late recurrence [12.2 vs. 8.5 months, P = 0.001 for recurrence free survival (RFS)] and long survival [23.7 vs. 17.0 months, P < 0.001 for overall survival (OS)] in resected pancreatic adenocarcinoma. Postoperative serum CA19-9, CA125 and CEA were independent risk predictors for poor surgical outcome in pancreatic adenocarcinoma (P < 0.001 for all). Adjuvant chemradiotherapy (hazard ratio: 0.359, 95% confidence interval: 0.253-0.510, P < 0.001 for OS; hazard ratio: 0.522, 95% confidence interval: 0.387-0.705, P < 0.001 for RFS) were confirmed to improve the surgical outcome in patients with abnormal levels of any one of the three postoperative markers, but not in patients with normal levels of the three postoperative markers. In the subgroup of patients with negative lymph node, its improvement of surgical outcome was also significant in patients with abnormal levels of any one of postoperative serum CA19-9, CA125 and CEA (hazard ratio: 0.412, 95% confidence interval: 0.244-0.698, P = 0.001 for OS; hazard ratio: 0.546, 95% confidence interval: 0.352-0.847, P = 0.007 for RFS). CONCLUSION Postoperative serum CA19-9, CA125 and CEA could serve as predictors of response for adjuvant chemoradiotherapy even if the status of lymph nodes is negative.
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Affiliation(s)
- Hua-Xiang Xu
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China
| | - Shuo Li
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China
| | - Chun-Tao Wu
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China
| | - Zi-Hao Qi
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China
| | - Wen-Quan Wang
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China
| | - Wei Jin
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China
| | - He-Li Gao
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China
| | - Shi-Rong Zhang
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China
| | - Jin-Zhi Xu
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China
| | - Chen Liu
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China
| | - Jiang Long
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China
| | - Quan-Xing Ni
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China
| | - Xian-Jun Yu
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China.
| | - Liang Liu
- Department of Pancreatic Surgery, Fudan University, Shanghai Cancer Center, Shanghai, 20032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China.
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Wang G, Li Y, Yang Z, Xu W, Yang Y, Tan X. ROS mediated EGFR/MEK/ERK/HIF-1α Loop Regulates Glucose metabolism in pancreatic cancer. Biochem Biophys Res Commun 2018; 500:873-878. [PMID: 29702094 DOI: 10.1016/j.bbrc.2018.04.177] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Accepted: 04/22/2018] [Indexed: 11/26/2022]
Abstract
To investigate the glycometabolism associated mechanism in invasion and metastasis of pancreatic cancer, We screened out genes involved in anaerobic glycolysis headed by HIF-1α,using pre-established a pair of pancreatic cancer cell lines. In this study, we further detected the glucose metabolism state not only in the cells but all also in two groups of patients with different SUVmax on 18F-FDG PET/CT. The data suggests that ROS mediated EGFR/MEK/ERK/HIF-1α loop is activated in high glucose metabolic samples both in vitro and in vivo: The increasing of HIF-1α expression is controlled by activation of EGFR/MEK/ERK pathway in hypoxia condition, HIF-1α inhibits excessive release of ROS, the reduction of ROS further activates EGFR to form a positive feedback loop. This difference is closely related to invasion and metastasis capacity of pancreatic cancer, and can be rescued by separate or combined inhibition of EGFR or HIF-1α in various degree. These results indicate a new clue to develop therapy of pancreatic cancer by regulating the glucose metabolism.
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Affiliation(s)
- Gang Wang
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, 110004, China; Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
| | - Yifeng Li
- 101K, The First Clinical Department of China Medical University, Shenyang, 110122, China.
| | - Zeyu Yang
- Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
| | - Weina Xu
- Department of Radiology and Nuclear Medicine, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
| | - Yifan Yang
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
| | - Xiaodong Tan
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
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36
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Chen Y, Shao Z, Chen W, Xie H, Wu Z, Qin G, Zhao N. A varying-coefficient cox model for the effect of CA19-9 kinetics on overall survival in patients with advanced pancreatic cancer. Oncotarget 2018; 8:29925-29934. [PMID: 28404893 PMCID: PMC5444714 DOI: 10.18632/oncotarget.15557] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Accepted: 01/23/2017] [Indexed: 12/12/2022] Open
Abstract
Purpose To evaluate the relationship between serum CA19-9 and overall survival in patients with advanced pancreatic cancer. Methods 109 advanced pancreatic cancer patients with gemcitabine based first-line chemotherapy were included. The effect of pretreatment CA19-9 level on overall survival was modeled by Cox proportional hazard regression. The effect of CA19-9 kinetics on overall survival was modeled by an extended Cox regression with a time varying coefficient and a time varying covariate. Results Univariate analysis indicated that baseline CA19-9 correlated with OS (HR = 1.66, p < 0.01) and this association remained significant within multivariate analysis (HR = 1.56, P < 0.01). For the analysis of CA19-9 kinetics, the extended Cox model showed that the effect of CA19-9 on overall survival changed with time: increased in the first two months and reached the top at a HR of about 2, then decreased for the next two months to a HR of about 1.56 and finally tended to be stable. The combination of pretreatment CA19-9 and CA19-9 at 2 month may better evaluate the patients’ prognosis compared to pretreatment CA19-9 alone. Conclusion Pretreatment CA19-9 and CA19-9 kinetics may serve as a useful serum biomarker in advanced pancreatic cancer.
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Affiliation(s)
- Yuntao Chen
- Department of Biostatistics, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai 200032, China.,Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China
| | - Zhenyi Shao
- Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China
| | - Wen Chen
- Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China
| | - Hua Xie
- Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China
| | - Zhenyu Wu
- Department of Biostatistics, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai 200032, China.,Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China
| | - Guoyou Qin
- Department of Biostatistics, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai 200032, China.,Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China
| | - Naiqing Zhao
- Department of Biostatistics, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai 200032, China.,Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China
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Ma KW, Cheung TT, She WH, Chok KSH, Chan ACY, Dai WC, Chiu WH, Lo CM. Diagnostic and Prognostic Role of 18-FDG PET/CT in the Management of Resectable Biliary Tract Cancer. World J Surg 2018; 42:823-834. [PMID: 28905105 DOI: 10.1007/s00268-017-4192-3] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES Role of 18-FDG PET/CT had been well established in other more prevalent malignancies such as colorectal and lung cancer; however, this is not as well defined in cholangiocarcinoma. Literature focusing on the prognostic values of preoperative PET/CT for resectable cholangiocarcinoma is scarce. METHOD This is a retrospective cohort of 66 consecutive patients who had received curative resection for cholangiocarcinoma from 2010 to 2015. All patients had preoperative 18-FDG PET/CT performed. Accuracy of metastatic lymph node detection of PET/CT and the prognostic value of maximum standard uptake value (SUV-max) was explored. RESULTS There were 38 male and 28 female recruited, and the median age was 66. Intrahepatic cholangiocarcinoma (ICC) constituted the majority (59.1%) of the cases, followed by hilar cholangiocarcinoma (22.8%), gallbladder cancer (13.6%) and common bile duct cancer (4.5%). The 3-year disease-free survival (DFS) and overall survival (OS) of the whole population were 27.1 and 39.2%, respectively. The median follow-up duration was 27 months. The accuracy of PET/CT in metastatic lymph node detection was 72.7% (P = 0.005, 95% CI 0.583-0.871) and 81.8% (P = 0.011, 95% CI 0.635-0.990) in whole population and ICC subgroup analysis, respectively. SUV-max was shown by multivariate analysis to be an independent factor for DFS (P = 0.007 OR 1.16, 95% CI 1.04-1.29) and OS (P = 0.012 OR 1.145, 95% CI 1.030-1.273) after resection. SUV-max of 8 was shown to be a discriminant cut-off for poor oncological outcomes in patients with early cholangiocarcinoma (TNM stage I or II) after curative resection (3-year DFS: 21.2 vs. 63.2%, P = 0.004, and 3-year OS: 29 vs. 74% P = 0.048, respectively). CONCLUSION PET/CT is a reliable imaging modality for metastatic lymph node detection in cholangiocarcinoma. Tumour SUV-max is an independent factor for oncological outcomes in patients with resectable disease. For patients who have TNM stage I or II cholangiocarcinoma, tumour SUV-max over 8 is associated with significantly inferior disease-free and overall survival even after curative resection.
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Affiliation(s)
- Ka Wing Ma
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
| | - Tan To Cheung
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China.
| | - Wong Hoi She
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
| | - Kenneth Siu Ho Chok
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
| | - Albert Chi Yan Chan
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
| | - Wing Chiu Dai
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
| | - Wan Hang Chiu
- Department of Radiology, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
| | - Chung Mau Lo
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
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Xiang J, Hu Q, Qin Y, Ji S, Xu W, Liu W, Shi S, Liang C, Liu J, Meng Q, Liang D, Ni Q, Xu J, Zhang B, Yu X. TCF7L2 positively regulates aerobic glycolysis via the EGLN2/HIF-1α axis and indicates prognosis in pancreatic cancer. Cell Death Dis 2018; 9:321. [PMID: 29476053 PMCID: PMC5833500 DOI: 10.1038/s41419-018-0367-6] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2017] [Revised: 01/14/2018] [Accepted: 01/25/2018] [Indexed: 12/30/2022]
Abstract
Patients with pancreatic ductal adenocarcinoma have much worse prognoses, and much effort has been directed toward understanding the molecular biological aspects of this disease. Accumulated evidence suggests that constitutive activation of the Wnt/β-catenin signalling contributes to the oncogenesis and progression of pancreatic cancer. Transcription factor 7-like2/transcription factor 4 (TCF7L2/TCF4), a β-catenin transcriptional partner, plays a vital role in the Wnt/β-catenin signalling pathway. In the present study, we investigated the clinicopathological significance of TCF7L2 in pancreatic cancer. Our results demonstrated that patients with higher TCF7L2 expression had worse prognosis. Our in vitro studies demonstrated that TCF7L2 positively regulated aerobic glycolysis by suppressing Egl-9 family hypoxia inducible factor 2 (EGLN2), leading to upregulation of hypoxia inducible factor 1 alpha subunit (HIF-1α). The impact of TCF7L2 on aerobic glycolysis was further confirmed in vivo by assessing 18FDG uptake in pancreatic cancer patients and in a subcutaneous xenograft mouse model. In summary, we identified novel predictive markers for prognosis and suggest a previously unrecognized role for TCF7L2 in control of aerobic glycolysis in pancreatic cancer.
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Affiliation(s)
- Jinfeng Xiang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China
| | - Qiangsheng Hu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China
| | - Yi Qin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China
| | - Shunrong Ji
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China
| | - Wenyan Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China
| | - Wensheng Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China
| | - Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China
| | - Chen Liang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China
| | - Jiang Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China
| | - Qingcai Meng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China
| | - Dingkong Liang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China
| | - Quanxing Ni
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China.
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China.
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China.
| | - Bo Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China.
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China.
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China.
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 200032, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China.
- Pancreatic Cancer Institute, Fudan University, 200032, Shanghai, China.
- Shanghai Pancreatic Cancer Institute, 200032, Shanghai, China.
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Zhang Y, Yang C, Cheng H, Fan Z, Huang Q, Lu Y, Fan K, Luo G, Jin K, Wang Z, Liu C, Yu X. Novel agents for pancreatic ductal adenocarcinoma: emerging therapeutics and future directions. J Hematol Oncol 2018; 11:14. [PMID: 29386069 PMCID: PMC5793409 DOI: 10.1186/s13045-017-0551-7] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2017] [Accepted: 12/28/2017] [Indexed: 02/08/2023] Open
Abstract
A poor prognosis of pancreatic ductal adenocarcinoma (PDAC) associated with chemoresistance has not changed for the past three decades. A multidisciplinary diagnosis followed by surgery and chemo(radiation)therapy is the main treatment approach. However, gemcitabine- and 5-fluorouracil-based therapies did not present satisfying outcomes. Novel regimens targeting pancreatic cancer cells, the tumor microenvironment, and immunosuppression are emerging. Biomarkers concerning the treatment outcome and patient selection are being discovered in preclinical or clinical studies. Combination therapies of classic chemotherapeutic drugs and novel agents or novel therapeutic combinations might bring hope to the dismal prognosis for PDAC patients.
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Affiliation(s)
- Yiyin Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Shanghai Pancreatic Cancer Institute, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
| | - Chao Yang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Shanghai Pancreatic Cancer Institute, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
| | - He Cheng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Shanghai Pancreatic Cancer Institute, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
| | - Zhiyao Fan
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Shanghai Pancreatic Cancer Institute, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
| | - Qiuyi Huang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Shanghai Pancreatic Cancer Institute, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
| | - Yu Lu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Shanghai Pancreatic Cancer Institute, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
| | - Kun Fan
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Shanghai Pancreatic Cancer Institute, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
| | - Guopei Luo
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Shanghai Pancreatic Cancer Institute, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
| | - Kaizhou Jin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Shanghai Pancreatic Cancer Institute, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
| | - Zhengshi Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Shanghai Pancreatic Cancer Institute, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
- Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China
| | - Chen Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
- Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
- Shanghai Pancreatic Cancer Institute, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
- Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
- Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
- Shanghai Pancreatic Cancer Institute, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
- Pancreatic Cancer Institute, Fudan University, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
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Pergolini I, Crippa S, Salgarello M, Belfiori G, Partelli S, Ruffo G, Pucci A, Zamboni G, Falconi M. SUVmax after (18)fluoro-deoxyglucose positron emission tomography/computed tomography: A tool to define treatment strategies in pancreatic cancer. Dig Liver Dis 2018; 50:84-90. [PMID: 29017830 DOI: 10.1016/j.dld.2017.09.122] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2017] [Revised: 09/13/2017] [Accepted: 09/14/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND (18)fluoro-deoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) might be a useful tool in the management of pancreatic ductal adenocarcinoma (PDAC). AIMS The aim of this study was to analyze maximum standard uptake value (SUVmax) after 18FDG-PET/CT as predictor of survival outcomes and method to determine treatment strategies. METHODS A consecutive series of patients who underwent preoperative 18FDG-PET/CT and subsequent resection for PDAC were retrospectively reviewed. Patients who underwent neoadjuvant chemotherapy were excluded. RESULTS 46 patients were included in the analysis. Median follow-up was 27 months (4-67). Patients who recurred within 12 months showed a significantly higher preoperative median SUVmax (8.1 vs 6.1, p=0.039). Receiver operating characteristics (ROC) curves for disease-free survival (DFS) and disease-specific survival (DSS) identified SUVmax of 6.0 as optimal cut-off. Multivariate analysis showed that SUVmax ≥ 6.0 was an independent predictor of poor DFS (HR 2.288, p=0.024) and DSS (HR 4.875, p<0.001). The combination of SUVmax ≥6.0 with CA19.9 ≥200U/ml was significantly associated with survival outcomes in comparison to patients without concordantly elevated values. CONCLUSION SUVmax ≥6.0 is an independent predictor of DFS and DSS in resected PDAC. 18FDG-PET/CT might be considered in the preoperative evaluation of patients with pancreatic cancer.
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Affiliation(s)
- Ilaria Pergolini
- Department of Surgery, Universita' Politecnica delle Marche, Ancona, Italy
| | - Stefano Crippa
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Matteo Salgarello
- Department of Nuclear Medicine, Ospedale Sacro Cuore-Don Calabria, Negrar, Italy
| | - Giulio Belfiori
- Department of Surgery, Universita' Politecnica delle Marche, Ancona, Italy
| | - Stefano Partelli
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giacomo Ruffo
- Department of Surgery, Ospedale Sacro Cuore-Don Calabria, Negrar, Italy
| | - Alessandro Pucci
- Department of Surgery, Universita' Politecnica delle Marche, Ancona, Italy
| | - Giuseppe Zamboni
- Department of Pathology, Ospedale Sacro Cuore-Don Calabria, Negrar, Italy
| | - Massimo Falconi
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.
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Shi G, Zhang J, Lu Z, Liu D, Wu Y, Wu P, Yin J, Yuan H, Zhu Q, Chen L, Fu Y, Peng Y, Wang Y, Jiang K, Miao Y. A novel messenger RNA signature as a prognostic biomarker for predicting relapse in pancreatic ductal adenocarcinoma. Oncotarget 2017; 8:110849-110860. [PMID: 29340021 PMCID: PMC5762289 DOI: 10.18632/oncotarget.22861] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 11/04/2017] [Indexed: 01/09/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) death rate and recurrence rate have remained obstinately high. Current methods can not satisfy the need of predicting cancer relapse accurately. Utilizing expression profiles of 10 GEO datasets (N = 774), we identified 154 differentially expressed genes (DEGs) between PDAC and normal pancreas tissue or paracancerous tissue. Next we built a 16-mRNA-based signature by means of the LASSO COX regression model. We also validated the prognostic value of the signature. Patients were classified into high-risk and low-risk group according to the signature risk score; 1 year RFS was 45% (95% CI: 31.6%–63.9%) for high-risk group in contrast to 92.5% (95% CI: 86.3%–99.1%) for low-risk group. Moreover, it could predict RFS well in cases with the receipt of different treatment modalities. The 16-mRNA-based signature was an independent and powerful prognostic biomarker for RFS for PDAC patients (HR = 7.74, 95% CI: 3.25–18.45, p < 0.0001).
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Affiliation(s)
- Guodong Shi
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.,Pancreas Institute of Nanjing Medical University, Nanjing 210029, China
| | - Jingjing Zhang
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.,Pancreas Institute of Nanjing Medical University, Nanjing 210029, China
| | - Zipeng Lu
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.,Pancreas Institute of Nanjing Medical University, Nanjing 210029, China
| | - Dongfang Liu
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.,Pancreas Institute of Nanjing Medical University, Nanjing 210029, China
| | - Yang Wu
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.,Pancreas Institute of Nanjing Medical University, Nanjing 210029, China
| | - Pengfei Wu
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.,Pancreas Institute of Nanjing Medical University, Nanjing 210029, China
| | - Jie Yin
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.,Pancreas Institute of Nanjing Medical University, Nanjing 210029, China
| | - Hao Yuan
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.,Pancreas Institute of Nanjing Medical University, Nanjing 210029, China
| | - Qicong Zhu
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.,Pancreas Institute of Nanjing Medical University, Nanjing 210029, China
| | - Lei Chen
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.,Pancreas Institute of Nanjing Medical University, Nanjing 210029, China
| | - Yue Fu
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.,Pancreas Institute of Nanjing Medical University, Nanjing 210029, China
| | - Yunpeng Peng
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.,Pancreas Institute of Nanjing Medical University, Nanjing 210029, China
| | - Yan Wang
- Endoscopy Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Kuirong Jiang
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.,Pancreas Institute of Nanjing Medical University, Nanjing 210029, China
| | - Yi Miao
- Pancreas Center, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.,Pancreas Institute of Nanjing Medical University, Nanjing 210029, China
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42
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Zhang Y, Qin L, Zhang C. Investigation of Association Between Borderline Pancreatic Head Cancer and Glucose Uptake by Using Positron-Emission Tomographic Studies. Med Sci Monit 2017; 23:4947-4953. [PMID: 29036034 PMCID: PMC5655162 DOI: 10.12659/msm.904746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND In the background of the well-known importance of positron-emission tomographic studies (PET) in the prediction of pancreatic oncologic problems, we designed and performed this investigation to study the link between borderline pancreatic head cancer and glucose uptake by using PET. MATERIAL AND METHODS We retrospectively investigated patients during the period of almost 4 years (May 2013 to December 2016). Patients underwent potentially curative resection for borderline exocrine pancreatic head adenocarcinoma without undergoing neoadjuvant therapy. We divided our PET protocol into 2 sets of methods as per renal calyces: 1) U-RC type in which renal calyx (RC) has relatively higher value than that of 18F-fluoro-2-deoxyglucose (18F-FDG) uptake and 2) S-RC type in which renal calyx has similar value than that of 18F-FDG uptake. RESULTS A total of 67 patients were enrolled after reclassification on the basis of majority-agreement. Among these patients, U-RC type was found in 22 patients (32.8%) while S-RC type was found in 45 patients (67.2%). Significant statistical differences were observed for each of the 2 types of pancreatic head cancer (U-RC type and S-RC type) in terms of adjusted cancer antigen 19-9 (CA 19-9), size of the tumor, tumor volume (TV2.8), maximum standard uptake value (SUV↑), and lesion glycolysis (LG). A significantly longer disease-free survival time was shown by U-RC type (n=18) pancreatic cancer in comparison to S-RC type (n=42) (25.3 vs. 11.2 months). Additionally, U-RC type (n=4) had higher disease-free survival than did aS-RC type (n=3) (29.4 vs. 12.5 months). CONCLUSIONS Our PET protocol appears to be an indicator for estimation of recurrence of pancreatic head cancer and is as an indispensable asset to oncologists.
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Affiliation(s)
- Ying Zhang
- Department of Nuclear Medicine, Liaocheng People's Hospital, Liaocheng, Shandong, China (mainland)
| | - Lei Qin
- Department of Nuclear Medicine, Liaocheng People's Hospital, Liaocheng, Shandong, China (mainland)
| | - Changming Zhang
- Department of Nuclear Medicine, Liaocheng People's Hospital, Liaocheng, Shandong, China (mainland)
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PET–Computed Tomography and Precision Medicine in Pancreatic Adenocarcinoma and Pancreatic Neuroendocrine Tumors. PET Clin 2017; 12:407-421. [DOI: 10.1016/j.cpet.2017.05.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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44
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Luo Y, Hu G, Ma Y, Guo N, Li F. Acinar cell carcinoma of the pancreas presenting as diffuse pancreatic enlargement: Two case reports and literature review. Medicine (Baltimore) 2017; 96:e7904. [PMID: 28930825 PMCID: PMC5617692 DOI: 10.1097/md.0000000000007904] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Revised: 07/17/2017] [Accepted: 07/19/2017] [Indexed: 12/11/2022] Open
Abstract
RATIONALE Pancreatic acinar cell carcinoma (ACC) is a rare malignant tumor of exocrine pancreas. It is typically a well-marginated large solid mass arising in a certain aspect of the pancreas. Diffuse involvement of ACC in the pancreas is very rare, and may simulate pancreatitis in radiological findings. We report 2 cases of ACC presenting as diffuse enlargement of the pancreas due to tumor involvement without formation of a distinct mass. PATIENT CONCERNS The patients consisted of a 41-year-old man with weight loss and a 77-year-old man who was asymptomatic. DIAGNOSES Computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed diffuse enlargement of the pancreas forming a sausage-like shape with homogenously increased FDG activity. INTERVENTIONS Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) biopsy of the pancreatic lesion was performed. OUTCOMES Histopathology results from the pancreas confirmed the diagnosis of pancreatic ACC. LESSONS Because diffuse enlargement of the pancreas is a common imaging feature of pancreatitis, recognition of this rare morphologic pattern of ACC is important for radiological diagnosis of this tumor.
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Affiliation(s)
- Yaping Luo
- Department of Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, P.R. China
| | - Guilan Hu
- Department of Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, P.R. China
| | - Yanru Ma
- Department of Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, P.R. China
| | - Ning Guo
- Department of Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, P.R. China
| | - Fang Li
- Department of Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital
- Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, P.R. China
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Zhu D, Wang L, Zhang H, Chen J, Wang Y, Byanju S, Liao M. Prognostic value of 18F-FDG-PET/CT parameters in patients with pancreatic carcinoma: A systematic review and meta-analysis. Medicine (Baltimore) 2017; 96:e7813. [PMID: 28816978 PMCID: PMC5571715 DOI: 10.1097/md.0000000000007813] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Revised: 07/13/2017] [Accepted: 07/31/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The identification of pancreatic carcinoma (PC) patients with poor prognosis is a priority in clinical oncology because of their high 5-year mortality. However, the prognostic value of pretreatment F-fluorodeoxyglucose (F-FDG)- positron emission tomography (PET)/computed tomography (CT) parameters in PC patients is controversial and no consensus exists as to its predictive capability. This meta-analysis was performed to comprehensively explore the prognostic significance of F-FDG-PET/CT parameters in patients with pancreatic carcinoma. METHODS Extensive literature searches of the PubMed, Embase, Web of Science, and Cochrane Library databases were conducted to identify literature published until March 5, 2017. Comparative analyses of the pooled hazard ratios (HRs) for event-free survival (EFS) and overall survival (OS) were performed to assess their correlations with pretreatment maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Either the fixed- or the random-effects model was adopted, depending on the heterogeneity observed across studies. Subgroup and sensitivity analyses were performed to assess the robustness of the results. RESULTS Sixteen studies including 1146 patients were identified. The pooled HRs for the probability of EFS were 1.90 (95% confidential interval (CI): 1.48-2.45) for SUVmax, 1.76 (95% CI: 1.20-2.58) for MTV, and 1.81 (95% CI: 1.27-2.58) for TLG. The pooled HRs for the probability of OS were 1.21 (95% CI: 1.12-1.31) for SUVmax, 1.56 (95% CI: 1.13-2.16) for MTV, and 1.70 (95% CI: 1.25-2.30) for TLG. A slight publication bias was detected using Begg test. After adjustment using the trim and fill procedure, the corrected HRs were not significantly different. The results of the subgroup analyses by SUVmax, MTV, and TLG showed that these factors may have similar prognostic significance. CONCLUSION F-FDG-PET/CT parameters, such as SUVmax, MTV, and TLG, may be significant prognostic factors in patients with pancreatic carcinoma. F-FDG-PET/CT imaging could be a promising tool to provide prognostic information for these patients.
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Affiliation(s)
| | - Lisha Wang
- Department of Neurology, ZhongNan Hospital of WuHan University, Wuhan City, People's Republic of China
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Heterogeneity index evaluated by slope of linear regression on 18F-FDG PET/CT as a prognostic marker for predicting tumor recurrence in pancreatic ductal adenocarcinoma. Eur J Nucl Med Mol Imaging 2017. [PMID: 28634684 DOI: 10.1007/s00259-017-3755-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been investigated as a method to predict pancreatic cancer recurrence after pancreatic surgery. We evaluated the recently introduced heterogeneity indices of 18F-FDG PET/CT used for predicting pancreatic cancer recurrence after surgery and compared them with current clinicopathologic and 18F-FDG PET/CT parameters. METHODS A total of 93 pancreatic ductal adenocarcinoma patients (M:F = 60:33, mean age = 64.2 ± 9.1 years) who underwent preoperative 18F-FDG PET/CT following pancreatic surgery were retrospectively enrolled. The standardized uptake values (SUVs) and tumor-to-background ratios (TBR) were measured on each 18F-FDG PET/CT, as metabolic parameters. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were examined as volumetric parameters. The coefficient of variance (heterogeneity index-1; SUVmean divided by the standard deviation) and linear regression slopes (heterogeneity index-2) of the MTV, according to SUV thresholds of 2.0, 2.5 and 3.0, were evaluated as heterogeneity indices. Predictive values of clinicopathologic and 18F-FDG PET/CT parameters and heterogeneity indices were compared in terms of pancreatic cancer recurrence. RESULTS Seventy patients (75.3%) showed recurrence after pancreatic cancer surgery (mean recurrence = 9.4 ± 8.4 months). Comparing the recurrence and no recurrence patients, all of the 18F-FDG PET/CT parameters and heterogeneity indices demonstrated significant differences. In univariate Cox-regression analyses, MTV (P = 0.013), TLG (P = 0.007), and heterogeneity index-2 (P = 0.027) were significant. Among the clinicopathologic parameters, CA19-9 (P = 0.025) and venous invasion (P = 0.002) were selected as significant parameters. In multivariate Cox-regression analyses, MTV (P = 0.005), TLG (P = 0.004), and heterogeneity index-2 (P = 0.016) with venous invasion (P < 0.001, 0.001, and 0.001, respectively) demonstrated significant results. CONCLUSIONS The heterogeneity index obtained using the linear regression slope, could be an effective predictor of pancreatic cancer recurrence after pancreatic cancer surgery, in addition to 18F-FDG PET/CT volumetric parameters and clinicopathologic parameters.
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Nakajo M, Kajiya Y, Tani A, Jinguji M, Nakajo M, Nihara T, Fukukura Y, Yoshiura T. A pilot study of the diagnostic and prognostic values of FLT-PET/CT for pancreatic cancer: comparison with FDG-PET/CT. Abdom Radiol (NY) 2017; 42:1210-1221. [PMID: 27891549 DOI: 10.1007/s00261-016-0987-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
PURPOSE The purpose of the study was to examine the diagnostic and prognostic values of 18F-fluorothymidine (FLT)-PET/CT for pancreatic cancer by comparing with 18F-fluorodeoxyglucose (FDG)-PET/CT. METHODS Fifteen patients with newly diagnosed pancreatic cancer underwent both FLT and FDG-PET/CT scans before treatment. The sensitivity, specificity, and accuracy in detecting nodal and distant metastases were compared between both scans using McNemar exact or χ 2 test. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic significance was assessed by Cox proportional hazards analysis. RESULTS Both scans visualized all primary cancers. The sensitivity, specificity, and accuracy per patient basis for detecting nodal metastasis were equal and 63.6% (7/11), 100% (4/4), and 73.3% (11/15) for both scans, and for detecting distant metastasis were 100% (6/6), 88.9% (8/9), and 93.3% (14/15) for FDG-PET/CT, and 50.0% (3/6), 100% (9/9), and 80.0% (12/15) for FLT-PET/CT, respectively, without significant difference in each of them between both scans (p > 0.05). However, of 4 patients with multiple liver metastases, FDG-PET/CT was positive in all, but FLT-PET/CT was negative in three patients. At univariate analysis, only FLT-SUVmax correlated with PFS (hazard ratio, 1.306, p = 0.048), and FDG total lesion glycolysis (TLG), FLT-SUVmax, and FLT-total lesion proliferation (TLP) correlated with OS (p = 0.021, p = 0.005, and p = 0.022, respectively). At bivariate analysis, FLT-SUVmax was superior to FDG-TLG or FLT-TLP for prediction of OS [HR (adjusted for FDG-TLG), 1.491, p = 0.034, HR (adjusted for FLT-TLP), 1.542, p = 0.023]. CONCLUSION FLT-PET/CT may have a potential equivalent to FDG-PET/CT for detecting primary and metastatic cancers except liver metastasis. FLT-SUVmax can provide the most significant prognostic information.
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Affiliation(s)
- Masatoyo Nakajo
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.
- Department of Radiology, Nanpuh Hospital, 14-3 Nagata, Kagoshima, 892-8512, Japan.
| | - Yoriko Kajiya
- Department of Radiology, Nanpuh Hospital, 14-3 Nagata, Kagoshima, 892-8512, Japan
| | - Atsushi Tani
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Megumi Jinguji
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Masayuki Nakajo
- Department of Radiology, Nanpuh Hospital, 14-3 Nagata, Kagoshima, 892-8512, Japan
| | - Tohru Nihara
- Department of Gastroenterology, Nanpuh Hospital, 14-3 Nagata, Kagoshima, 892-8512, Japan
| | - Yoshihiko Fukukura
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Takashi Yoshiura
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
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Chong JU, Hwang HK, Lee JH, Yun M, Kang CM, Lee WJ. Clinically determined type of 18F-fluoro-2-deoxyglucose uptake as an alternative prognostic marker in resectable pancreatic cancer. PLoS One 2017; 12:e0172606. [PMID: 28235029 PMCID: PMC5325284 DOI: 10.1371/journal.pone.0172606] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Accepted: 02/07/2017] [Indexed: 12/11/2022] Open
Abstract
PURPOSE To investigate the association between clinical PET (positron emission tomography) type and oncologic outcome in resectable pancreatic cancer. METHODS Between January 2008 and October 2012, patients who underwent potentially curative resection for resectable pancreatic ductal adenocarcinoma without neoadjuvant treatment were retrospectively investigated. Clinical PET type was defined as follows: pancreatic cancer with similar 18FDG uptake to renal calyx was determined as kidney-type (K-type), and relatively lower 18FDG uptake than that of renal calyx was regarded as Non-K type. RESULTS A total of 53 patients were enrolled. After agreement-based reclassification, agreement based K-type (aK-type) was noted in 34 patients (64.2%), and agreement based Non-K type (aNon K-type) was found in 19 patients (35.8%). There was a significant difference between aK-type and aNon K-type pancreatic cancer (tumor size (P = 0.030), adjusted CA 19-9 (P = 0.007), maximum standard uptake value (SUVmax,P<0.001), metabolic tumor volume (MTV2.5, P<0.001), total lesion glycolysis (TLG, P<0.001)). K-type pancreatic cancer (n = 31) showed a significantly shorter disease-free time compared with Non-K type (n = 16) (10.8 vs. 24.1 months, P = 0.013). It was also noted that aK-type showed inferior disease-free survival to that of aNon-K type pancreatic cancer (11.9 vs. 28.6 months, P = 0.012). CONCLUSIONS Clinical PET type is a reliable clinical marker to estimate aggressive tumor biology and can be utilized in predicting tumor recurrence and necessity for postoperative chemotherapy.
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Affiliation(s)
- Jae Uk Chong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Pancreaticobiliary Cancer Clinic, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
| | - Ho Kyoung Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Pancreaticobiliary Cancer Clinic, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
| | - Jin Ho Lee
- Department of Surgery, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea
| | - Mijin Yun
- Pancreaticobiliary Cancer Clinic, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Chang Moo Kang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Pancreaticobiliary Cancer Clinic, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
| | - Woo Jung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
- Pancreaticobiliary Cancer Clinic, Yonsei Cancer Center, Severance Hospital, Seoul, Korea
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Xu HX, Liu L, Xiang JF, Wang WQ, Qi ZH, Wu CT, Liu C, Long J, Xu J, Ni QX, Yu XJ. Postoperative serum CEA and CA125 levels are supplementary to perioperative CA19-9 levels in predicting operative outcomes of pancreatic ductal adenocarcinoma. Surgery 2017; 161:373-384. [PMID: 27838102 DOI: 10.1016/j.surg.2016.08.005] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2016] [Revised: 07/23/2016] [Accepted: 08/03/2016] [Indexed: 01/18/2023]
Abstract
BACKGROUND Carbohydrate antigen (CA19-9) is a well-established marker to monitor disease status after resection of pancreatic cancer. However, few serum markers have been reported to improve the prognostic ability of postoperative CA19-9, especially in patients with normal postoperative CA19-9. METHODS A total of 353 patients with pancreatic ductal adenocarcinoma treated by radical resection were reviewed retrospectively, and a prospective cohort including 142 patients with resectable pancreatic head carcinoma was analyzed as a validation cohort. Perioperative CA19-9 and postoperative serum markers (CEA, CA242, CA72-4, CA50, CA125, CA153, and AFP) were investigated. RESULTS Patients with postoperative normalization of CA19-9 had improved survival times (recurrence-free survival: 11.9 months; overall survival: 22.5 months) compared with those with decreased but still elevated postoperative CA19-9 (recurrence-free survival: 6.8 months, P < .001; overall survival: 13.5 months, P < .001) or those with increased postoperative CA19-9 (recurrence-free survival: 3.5 months, P < .001; overall survival: 7.9 months, P < .001), which was similar to those with consistently normal CA19-9 during perioperative periods (recurrence-free survival: 10.6 months, P = .799; overall survival: 24.1 months, P = .756). Normal postoperative CA19-9 levels were an independent indicator for a positive outcome after operation, regardless of preoperative CA19-9 levels. Elevated postoperative CEA and CA125 were identified further as independent risk factors for patients with normal postoperative CA19-9, while elevated postoperative CA125 and nondecreased postoperative CA19-9 were independent prognostic markers for patients with elevated postoperative CA19-9. CONCLUSION The postoperative monitoring of CEA and CA125 provided prognostic significance to the measurement of CA19-9 in pancreatic cancer after resection.
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Affiliation(s)
- Hua-Xiang Xu
- Department of Pancreatic Surgery, Pancreatic Cancer Institute, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Cancer Center, Shanghai, P.R. China
| | - Liang Liu
- Department of Pancreatic Surgery, Pancreatic Cancer Institute, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Cancer Center, Shanghai, P.R. China
| | - Jin-Feng Xiang
- Department of Pancreatic Surgery, Pancreatic Cancer Institute, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Cancer Center, Shanghai, P.R. China
| | - Wen-Quan Wang
- Department of Pancreatic Surgery, Pancreatic Cancer Institute, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Cancer Center, Shanghai, P.R. China
| | - Zi-Hao Qi
- Department of Pancreatic Surgery, Pancreatic Cancer Institute, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Cancer Center, Shanghai, P.R. China
| | - Chun-Tao Wu
- Department of Pancreatic Surgery, Pancreatic Cancer Institute, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Cancer Center, Shanghai, P.R. China
| | - Chen Liu
- Department of Pancreatic Surgery, Pancreatic Cancer Institute, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Cancer Center, Shanghai, P.R. China
| | - Jiang Long
- Department of Pancreatic Surgery, Pancreatic Cancer Institute, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Cancer Center, Shanghai, P.R. China
| | - Jin Xu
- Department of Pancreatic Surgery, Pancreatic Cancer Institute, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Cancer Center, Shanghai, P.R. China
| | - Quan-Xing Ni
- Department of Pancreatic Surgery, Pancreatic Cancer Institute, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Cancer Center, Shanghai, P.R. China
| | - Xian-Jun Yu
- Department of Pancreatic Surgery, Pancreatic Cancer Institute, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Cancer Center, Shanghai, P.R. China.
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Bai L, Guo C, Wang J, Liu X, Li Y, Li M, Guo Y, Duan X. 18F-fludrodeoxyglucose maximal standardized uptake value and metabolic tumor burden are associated with major chemotherapy-related tumor markers in NSCLC patients. Onco Targets Ther 2016; 9:6315-6324. [PMID: 27789962 PMCID: PMC5072511 DOI: 10.2147/ott.s113832] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Objective Metabolic activity and tumor burden are significant for prognosis and metastasis of non-small cell lung cancer (NSCLC), including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Chemotherapy resistance is a great challenge for treating NSCLC patients and is also closely related with several biomarkers such as epidermal growth factor receptor (EGFR), p53, and excision repair cross-complementing group 1 protein (ERCC1). Our purpose was to determine the correlation between positron emission tomography/computed tomography (PET/CT) parameters and tumor markers-related chemotherapy resistance in NSCLC. Methods Forty-six NSCLC chemotherapy-naïve patients were enrolled. The SUVmax, MTV, and TLG were calculated by PET/CT imaging, and expression of EGFR, p53, and ERCC1 were analyzed by immunohistochemistry on tissues. SUVmax, MTV, and TLG compared for their performance in predicting the expression of EGFR, p53, and ERCC1 were illustrated with statistical analysis. Results SUVmax was significantly correlated with p53 expression (P=0.001), and MTV and TLG were significantly associated with ERCC1 (P=0.000; P=0.000). Furthermore, multiple stepwise regression analysis revealed that SUVmax was the primary predictor for p53, MTV and TLG was the primary predictor for ERCC1. SUVmax had a sensitivity of 91% and specificity of 50% for the detection of p53 positive. The sensitivities of MTV and TLG were 83% and 80%, and specificities were 69% and 75% for the detection of ERCC1 positive, respectively. When we suggested p53 or ERCC1 positive, the cutoff value of SUVmax, MTV, and TLG were 7.68, 23.62, and 129.65 cm3, respectively. Conclusion SUVmax, MTV, and TLG were closely associated with p53 and ERCC1’ expressions. Therefore, 18F-fludrodeoxyglucose PET/CT could be a new way of predicting p53 or ERCC1-related chemotherapy effect in NSCLC patients with more convenience.
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Affiliation(s)
- Lu Bai
- Department of Medical Imaging
| | | | - Jiansheng Wang
- Department of Oncological Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | | | - Yang Li
- Department of Medical Imaging
| | - Miao Li
- Department of Medical Imaging
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