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Sugawara T, Rodriguez Franco S, Sherman S, Kirsch MJ, Colborn K, Franklin O, Ishida J, Grandi S, Al-Musawi MH, Gleisner A, Schulick RD, Del Chiaro M. Characteristics and prognosis of patients with pancreatic adenocarcinoma not expressing CA19-9: Analysis of the National Cancer Database. Pancreatology 2024; 24:1340-1347. [PMID: 39609173 DOI: 10.1016/j.pan.2024.11.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 09/25/2024] [Accepted: 11/12/2024] [Indexed: 11/30/2024]
Abstract
BACKGROUND Around 5-10 % of pancreatic cancer patients are non-expressors of carbohydrate antigen 19-9 (CA 19-9), which has an unknown impact on the aggressiveness and prognosis of pancreatic adenocarcinoma (PDAC). This study aimed to evaluate the characteristics and the prognosis of PDAC patients who do not express CA 19-9. METHODS Patients with PDAC diagnosed between 2010 and 2018 were identified in the National Cancer Database. Clinical characteristics were compared according to CA 19-9 levels stratified in four different groups: non-expressors (≤1.0 U/mL), normal range (1.1-37.0 U/mL), mildly elevated (37.1-97.9 U/mL), and CA 19-9 ≥98.0 U/mL. The characteristics were analyzed in the whole cohort and overall survival (OS) was evaluated in a subgroup of upfront resected patients who had cT1-3 tumors without distant metastases. RESULTS In total, 88,749 patients were included, of which 4.5 % were CA 19-9 non-expressors. The non-expressors had a higher risk of having distant metastasis at diagnosis, compared to patients with normal-range or mildly elevated CA 19-9 levels. In resected patients (n = 4008), CA 19-9 non-expressors had shorted median OS compared to patients with normal-range CA 19-9 levels (29.3 vs 34.4 months, p = 0.024). This OS association remained in a multivariable Cox regression model (adjusted HR 1.22, 95 % CI 1.04-1.44). CONCLUSIONS CA 19-9 non-expression is associated with distant metastatic disease at diagnosis and with death in resected non-metastatic patients compared to normal-range CA 19-9 levels. This clinically relevant subgroup requires alternative biomarkers, and may need consideration of more extensive preoperative staging and intensive perioperative systemic therapy.
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Affiliation(s)
- Toshitaka Sugawara
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA; Department of Hepatobiliary and Pancreatic Surgery, Institute of Science Tokyo, Tokyo, Japan
| | - Salvador Rodriguez Franco
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA
| | - Samantha Sherman
- Department of Surgery, Parkview Hospital Randallia, Fort Wayne, Indiana, USA
| | - Michael J Kirsch
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA
| | - Kathryn Colborn
- Adult and Child Center for Outcomes Research and Delivery Science, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA; Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
| | - Oskar Franklin
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA; Department of Diagnostics and Intervention, Surgery, Umeå University, Sweden
| | - Jun Ishida
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA; Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Samuele Grandi
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA
| | - Mohammed H Al-Musawi
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA
| | - Ana Gleisner
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA; University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, CO, USA
| | - Richard D Schulick
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA; University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, CO, USA
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA; University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, CO, USA.
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Pinson J, Henriques J, Beaussire L, Sarafan-Vasseur N, Sa Cunha A, Bachet JB, Vernerey D, Di Fiore F, Schwarz L. New Biomarkers to Define a Biological Borderline Situation for Pancreatic Adenocarcinoma: Results of an Ancillary Study of the PANACHE01-PRODIGE48 Trial. Ann Surg 2024; 280:734-744. [PMID: 39101207 DOI: 10.1097/sla.0000000000006468] [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: 08/06/2024]
Abstract
OBJECTIVE To investigate in patients treated for a resectable pancreatic ductal adenocarcinoma [pancreatic adenocarcinoma (PA)], the prognostic value of baseline carbohydrate antigen 19.9 (CA19-9) and circulating tumor DNA (ctDNA) for overall survival (OS), to improve death risk stratification, based on a planned ancillary study from PANACHE01-PRODIGE 48 trial. BACKGROUND Biological borderline situation that was first used by the MD Anderson, became a standard practice following the international consensus conference in 2016 to manage PA. Regarding the risk of systemic disease, especially in the setting of "markedly elevated" CA19-9, neoadjuvant therapy is advised to avoid unnecessary surgery, with a risk of early recurrence. To best define biological borderline situations, new biomarkers are needed. METHODS Characteristics at diagnosis and OS were compared between patients with or without ctDNA status available. OS was estimated with the Kaplan-Meier method and compared with a log-rank test. The restricted cubic spline approach was used to identify the optimal threshold for biological parameters for death risk stratification. Univariate and multivariate Cox proportional hazard models were estimated to assess the association of ctDNA status and other parameters with OS. RESULTS Among the 132 patients from the primary population for analysis in the PANACHE01 -PRODIGE 48 trial, 92(71%) were available for ctDNA status at diagnosis. No selection bias was identified between patients with or without ctDNA status. Fourteen patients (15%) were ctDNA+ and exhibited a higher risk for death [ P = 0.0188; hazard ratio (95% CI): 2.28 (1.12-4.63)]. In the 92 patients with ctDNA status available among the other parameters analyzed, only CA19-9 was statically associated with OS in univariate analysis. Patients with a log of CA19-9 equal or superior to 4.4 that corresponds to a CA19-9 of 80 UI/mL were identified at higher risk for death [ P = 0.0143; hazard ratio (95% CI): 2.2 (1.15-4.19)]. In multivariate analysis, CA19-19 remained independently associated with OS ( P = 0.0323). When combining the 2 biomarkers, the median OS was 19.4 [IC 95%: 3.8-not reached (NR)] months, 30.2 (IC 95%: 17.1-NR) months and NR (IC 95%: 39.3-NR) for "CA19-9 high and ctDNA+ group," "CA19-9 high or ctDNA+ group," and "CA19-9 low and ctDNA- group," respectively (log-rank P = 0.0069). CONCLUSIONS Progress in the management of potentially operable PA remains limited, relying solely on strategies to optimize the sequence of complete treatment, based on modern multidrug chemotherapy (FOLFIRINOX, GemNabPaclitaxel) and surgical resection. The identification of risk criteria, such as the existence of systemic disease, is an important issue, currently referred to as "biological borderline disease." Few data, particularly from prospective studies, allow us to identify biomarkers other than CA19-9. Combining ctDNA with CA19-9 could be of interest to best define biological borderline situations in PA.
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Affiliation(s)
- Jean Pinson
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Normandie University, UNIROUEN, Rouen University Hospital, Rouen, France
| | - Julie Henriques
- Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France
| | - Ludivine Beaussire
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Normandie University, UNIROUEN, Rouen University Hospital, Rouen, France
| | - Nasrin Sarafan-Vasseur
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Normandie University, UNIROUEN, Rouen University Hospital, Rouen, France
| | - Antonio Sa Cunha
- Department of Hepato-Biliary and Pancreatic Surgery, and Liver Transplantation, Paul Brousse Hospital, AP-HP, Villejuif, France
| | - Jean-Baptiste Bachet
- Department of Hepato-Gastroenterology, Sorbonne University, Pitié-Salpêtrière Hospital, Paris, France
| | - Dewi Vernerey
- Methodology and Quality of Life in Oncology Unit, Besançon University Hospital, Besançon, France
| | - Frederic Di Fiore
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Normandie University, UNIROUEN, Rouen University Hospital, Rouen, France
- Department of Digestive Oncology, Rouen University Hospital, Rouen, France
| | - Lilian Schwarz
- Department of Digestive Surgery, Rouen University Hospital, Rouen, France
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Normandie University, UNIROUEN, Rouen University Hospital, Rouen, France
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Servin-Rojas M, Fong ZV, Fernandez-Del Castillo C, Ferrone CR, Lee H, Lopez-Verdugo F, Qiao G, Rocha-Castellanos DM, Lillemoe KD, Qadan M. Tumor Size Reduction and Serum Carbohydrate Antigen 19-9 Kinetics After Neoadjuvant FOLFIRINOX in Patients With Pancreatic Ductal Adenocarcinoma. Surgery 2024; 175:471-476. [PMID: 37949693 DOI: 10.1016/j.surg.2023.09.041] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 08/03/2023] [Accepted: 09/26/2023] [Indexed: 11/12/2023]
Abstract
BACKGROUND Changes in tumor size and serum carbohydrate antigen 19-9 are commonly reported markers used to assess response to neoadjuvant therapy in pancreatic ductal adenocarcinoma. We evaluated the impact of the percentual tumor size reduction and carbohydrate antigen 19-9 kinetics on resectability and response to neoadjuvant FOLFIRINOX. METHODS This was an institutional analysis of patients with non-metastatic (upfront resectable, borderline resectable, and locally advanced) pancreatic ductal adenocarcinoma who underwent neoadjuvant FOLFIRINOX. Resectability, pathologic response, disease recurrence, and overall survival were evaluated. RESULTS Among 193 patients who completed FOLFIRINOX, 60% underwent resection, and 91% were R0. Pathologically, complete, and near-complete responses were achieved in 4% and 40% of patients, respectively. Tumor size reduction (odds ratio 1.02 per 1%, P = .024) and normalization of carbohydrate antigen 19-9 (odds ratio 2.61, P = .035) were associated with increased odds of resectability. Concerning pathologic response, tumor size reduction (odds ratio 1.03 per 1%, P = .018) was associated with increased odds of a complete and near-complete response. Lastly, in resected patients, a postoperative increase in carbohydrate antigen 19-9 after prior normalization after neoadjuvant therapy were at an increased risk of recurrence (hazard ratio 9.58, P < .001) and worse survival (hazard ratio 10.4, P < .001) compared to patients who maintained normalization. CONCLUSION In patients with non-metastatic pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy, tumor size reduction was a significant predictor of resectability and pathologic response, including complete and near complete responses, whereas serum carbohydrate antigen 19-9 normalization predicted resectability, disease recurrence, and survival. Patients with a postoperative carbohydrate antigen 19-9 rise after prior normalization after administration of neoadjuvant therapy were at an increased risk of recurrence and worse overall survival.
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Affiliation(s)
- Maximiliano Servin-Rojas
- Department of Surgery, Massachusetts General Hospital, Boston, MA. http://www.twitter.com/servinrojasmd
| | - Zhi Ven Fong
- Department of Surgery, Massachusetts General Hospital, Boston, MA. http://www.twitter.com/zhivenfongmd
| | | | - Cristina R Ferrone
- Department of Surgery, Massachusetts General Hospital, Boston, MA. http://www.twitter.com/cferronemd
| | - Hang Lee
- Department of Biostatistics, Massachusetts General Hospital, Boston, MA
| | - Fidel Lopez-Verdugo
- Department of Surgery, Massachusetts General Hospital, Boston, MA. http://www.twitter.com/fidel_lv
| | - Guoliang Qiao
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Dario M Rocha-Castellanos
- Department of Surgery, Massachusetts General Hospital, Boston, MA. http://www.twitter.com/dariorochamd
| | - Keith D Lillemoe
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Motaz Qadan
- Department of Surgery, Massachusetts General Hospital, Boston, MA.
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Zhang XP, Xu S, Zhao ZM, Liu Q, Zhao GD, Hu MG, Tan XL, Liu R. Robotic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: Analysis of surgical outcomes and long-term prognosis in a high-volume center. Hepatobiliary Pancreat Dis Int 2023; 22:140-146. [PMID: 36171169 DOI: 10.1016/j.hbpd.2022.09.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 09/08/2022] [Indexed: 02/05/2023]
Abstract
BACKGROUND Robotic pancreaticoduodenectomy (RPD) has been reported to be safe and feasible for patients with pancreatic ductal adenocarcinoma (PDAC) of the pancreatic head. This study aimed to analyze the surgical outcomes and risk factors for poor long-term prognosis of these patients. METHODS Data from patients who underwent RPD for PDAC of pancreatic head were retrospectively analyzed. Multivariate Cox regression analysis was used to seek the independent prognostic factors for overall survival (OS), and an online nomogram calculator was developed based on the independent prognostic factors. RESULTS Of the 273 patients who met the inclusion criteria, the median operative time was 280.0 minutes, the estimated blood loss was 100.0 mL, the median OS was 23.6 months, and the median recurrence-free survival (RFS) was 14.4 months. Multivariate analysis showed that preoperative carbohydrate antigen 19-9 (CA19-9) [hazard ratio (HR) = 2.607, 95% confidence interval (CI): 1.560-4.354, P < 0.001], lymph node metastasis (HR = 1.429, 95% CI: 1.005-2.034, P = 0.047), tumor moderately (HR = 3.190, 95% CI: 1.813-5.614, P < 0.001) or poorly differentiated (HR = 5.114, 95% CI: 2.839-9.212, P < 0.001), and Clavien-Dindo grade ≥ III (HR = 1.657, 95% CI: 1.079-2.546, P = 0.021) were independent prognostic factors for OS. The concordance index (C-index) of the nomogram constructed based on the above four independent prognostic factors was 0.685 (95% CI: 0.640-0.729), which was significantly higher than that of the AJCC staging (8th edition): 0.541 (95% CI: 0.493-0.589) (P < 0.001). CONCLUSIONS This large-scale study indicated that RPD was feasible for PDAC of pancreatic head. Preoperative CA19-9, lymph node metastasis, tumor poorly differentiated, and Clavien-Dindo grade ≥ III were independent prognostic factors for OS. The online nomogram calculator could predict the OS of these patients in a simple and convenient manner.
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Affiliation(s)
- Xiu-Ping Zhang
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Shuai Xu
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China; Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
| | - Zhi-Ming Zhao
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Qu Liu
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Guo-Dong Zhao
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Ming-Gen Hu
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiang-Long Tan
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Rong Liu
- Faculty of Hepato-Biliary-Pancreatic Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.
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Chu LC, Wang ZJ, Kambadakone A, Hecht EM, He J, Narang AK, Laheru DA, Arif-Tiwari H, Bhosale P, Bolan CW, Brook OR, Bezuidenhout AF, Do RKG, Galgano SJ, Goenka AH, Guimaraes AR, Hough DM, Kulkarni N, Le O, Luk L, Mannelli L, Rosenthal M, Sangster G, Shah ZK, Soloff EV, Tolat PP, Zins M, Fishman EK, Tamm EP, Zaheer A. Postoperative surveillance of pancreatic ductal adenocarcinoma (PDAC) recurrence: practice pattern on standardized imaging and reporting from the society of abdominal radiology disease focus panel on PDAC. ABDOMINAL RADIOLOGY (NEW YORK) 2023; 48:318-339. [PMID: 36241752 DOI: 10.1007/s00261-022-03693-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 09/22/2022] [Accepted: 09/26/2022] [Indexed: 01/21/2023]
Abstract
PURPOSE Surgical resection is the only potential curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC), but unfortunately most patients recur within 5 years of surgery. This article aims to assess the practice patterns across major academic institutions and develop consensus recommendations for postoperative imaging and interpretation in patients with PDAC. METHODS The consensus recommendations for postoperative imaging surveillance following PDAC resection were developed using the Delphi method. Members of the Society of Abdominal Radiology (SAR) PDAC Disease Focused Panel (DFP) underwent three rounds of surveys followed by live webinar group discussions to develop consensus recommendations. RESULTS Significant variations currently exist in the postoperative surveillance of PDAC, even among academic institutions. Differentiating common postoperative inflammatory and fibrotic changes from tumor recurrence remains a diagnostic challenge, and there is no reliable size threshold or growth rate of imaging findings that can provide differentiation. A new liver lesion or peritoneal nodule should be considered suspicious for tumor recurrence, and the imaging features should be interpreted in the appropriate clinical context (e.g., CA 19-9, clinical presentation, pathologic staging). CONCLUSION Postoperative imaging following PDAC resection is challenging to interpret due to the presence of confounding postoperative inflammatory changes. A standardized reporting template for locoregional findings and report impression may improve communication of relaying risk of recurrence with referring providers, which merits validation in future studies.
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Affiliation(s)
- Linda C Chu
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| | - Zhen J Wang
- Department of Radiology, University of California San Francisco School of Medicine, San Francisco, CA, USA
| | - Avinash Kambadakone
- Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, USA
| | | | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Amol K Narang
- Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Daniel A Laheru
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Hina Arif-Tiwari
- Department of Medical Imaging, University of Arizona, Tuscon, AZ, USA
| | - Priya Bhosale
- Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Olga R Brook
- Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | | | - Richard K G Do
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Samuel J Galgano
- Department of Radiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA
| | - Ajit H Goenka
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Alexander R Guimaraes
- Department of Diagnostic Radiology, Oregon Health & Science University, Portland, OR, USA
| | - David M Hough
- Department of Radiology, Mayo Clinic, Rochester, MN, USA
| | - Naveen Kulkarni
- Department of Radiology, Medical College of Wisconsin & Froedtert Health, Milwaukee, WI, USA
| | - Ott Le
- Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lyndon Luk
- Department of Radiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Lorenzo Mannelli
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) SDN, Naples, Italy
| | - Michael Rosenthal
- Department of Imaging, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Guillermo Sangster
- Department of Radiology, Ochsner Louisiana State University Health Shreveport, Shreveport, LA, USA
| | - Zarine K Shah
- Department of Radiology, Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Erik V Soloff
- Department of Radiology, University of Washington, Seattle, WA, USA
| | - Parag P Tolat
- Department of Radiology, Medical College of Wisconsin & Froedtert Health, Milwaukee, WI, USA
| | - Marc Zins
- Department of Radiology, Hôpital Paris Saint Joseph, Paris, France
| | - Elliot K Fishman
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Eric P Tamm
- Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Atif Zaheer
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Watanabe F, Suzuki K, Noda H, Rikiyama T. Liquid biopsy leads to a paradigm shift in the treatment of pancreatic cancer. World J Gastroenterol 2022; 28:6478-6496. [PMID: 36569270 PMCID: PMC9782840 DOI: 10.3748/wjg.v28.i46.6478] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 10/25/2022] [Accepted: 11/21/2022] [Indexed: 12/08/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most cancers. Its 5-year survival rate is very low. The recent induction of neoadjuvant chemotherapy and improvements in chemotherapy for patients with pancreatic cancer have resulted in improved survival outcomes. However, the prognosis of pancreatic cancer is still poor. To dramatically improve the prognosis, we need to develop more tools for early diagnosis, treatment selection, disease monitoring, and response rate evaluation. Recently, liquid biopsy (circulating free DNA, circulating tumor DNA, circulating tumor cells, exosomes, and microRNAs) has caught the attention of many researchers as a new biomarker that is minimally invasive, confers low-risk, and displays an overall state of the tumor. Thus, liquid biopsy does not employ the traditional difficulties of obtaining tumor samples from patients with advanced PDAC to investigate their molecular biological status. In addition, it allows for long-term monitoring of the molecular profile of tumor progression. These could help in identifying tumor-specific alterations that use the target structure for tailor-made therapy. Through this review, we highlighted the latest discoveries and advances in liquid biopsy technology in pancreatic cancer research and showed how it can be applied in clinical practice.
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Affiliation(s)
- Fumiaki Watanabe
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Koichi Suzuki
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Hiroshi Noda
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
| | - Toshiki Rikiyama
- Department of Surgery, Saitama Medical Center, Jichi Medical University, Saitama 330-8503, Japan
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Yoon JK, Park MS, Kim SS, Han K, Lee HS, Bang S, Hwang HK, Hwang SH, Yun M, Kim MJ. Regional lymph node metastasis detected on preoperative CT and/or FDG-PET may predict early recurrence of pancreatic adenocarcinoma after curative resection. Sci Rep 2022; 12:17296. [PMID: 36241906 PMCID: PMC9568602 DOI: 10.1038/s41598-022-22126-y] [Citation(s) in RCA: 5] [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: 07/08/2022] [Accepted: 10/10/2022] [Indexed: 01/10/2023] Open
Abstract
The objective of this study was to evaluate the role of regional lymph node (LN) metastasis detected on preoperative CT and/or 18F-fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) scans in the prediction of early tumor recurrence after curative surgical resection of pancreatic ductal adenocarcinoma (PDAC). This retrospective study included 137 patients who underwent upfront surgery with R0 resection of PDAC between 2013 and 2016. Regional LN metastasis was identified using two criteria: positive findings for regional LN metastasis on either preoperative CT or FDG-PET scans (LNOR), or on both preoperative CT and FDG-PET scans (LNAND). A total of 55 patients had early tumor recurrence within 12 months after curative resection. Univariable and multivariable Cox proportional hazard regression analysis showed that preoperative carbohydrate antigen 19-9 (CA19-9) levels, preoperative locally advanced status, and regional LN metastasis (both LNOR and LNAND criteria) were significant risk factors for early recurrence. Positive LNOR and LNAND showed significantly poorer recurrence-free survival compared to negative regional LN metastasis groups (p = 0.048 and p = 0.020, respectively). Compared with the LNAND criteria, the LNOR criteria provided higher sensitivity (22.4% vs. 15.5%, p = 0.046) and a higher negative predictive value (61.9% vs. 59.8%, p = 0.046). The LNOR definition provided more sensitive and accurate performance in diagnosing preoperative regional LN metastasis.
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Affiliation(s)
- Ja Kyung Yoon
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Mi-Suk Park
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
| | - Seung-Seob Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyunghwa Han
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hee Seung Lee
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seungmin Bang
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ho Kyoung Hwang
- Division of Hepatobiliary and Pancreas, Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hyun Hwang
- Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Mijin Yun
- Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myeong-Jin Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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8
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de MEIRA-JÚNIOR JD, COSTA TN, MONTAGNINI AL, NAHAS SC, JUKEMURA J. ELEVATED CA 19-9 IN AN ASYMPTOMATIC PATIENT: WHAT DOES IT MEAN? ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2022; 35:e1687. [PMID: 36134819 PMCID: PMC9484821 DOI: 10.1590/0102-672020220002e1687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 01/21/2022] [Indexed: 11/22/2022]
Affiliation(s)
- José Donizeti de MEIRA-JÚNIOR
- Universidade de São Paulo, Medical School, University Hospital,
Department of Gastroenterology, Digestive Surgery Division - São Paulo (SP),
Brazil
| | - Thiago Nogueira COSTA
- Universidade de São Paulo, Medical School, University Hospital,
Department of Gastroenterology, Digestive Surgery Division - São Paulo (SP),
Brazil
| | - Andre Luis MONTAGNINI
- Universidade de São Paulo, Medical School, University Hospital,
Department of Gastroenterology, Digestive Surgery Division - São Paulo (SP),
Brazil
| | - Sergio Carlos NAHAS
- Universidade de São Paulo, Medical School, University Hospital,
Department of Gastroenterology, Digestive Surgery Division - São Paulo (SP),
Brazil
| | - Jose JUKEMURA
- Universidade de São Paulo, Medical School, University Hospital,
Department of Gastroenterology, Digestive Surgery Division - São Paulo (SP),
Brazil
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9
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Watanabe F, Suzuki K, Tamaki S, Abe I, Endo Y, Takayama Y, Ishikawa H, Kakizawa N, Saito M, Futsuhara K, Noda H, Konishi F, Rikiyama T. Optimal value of CA19-9 determined by KRAS-mutated circulating tumor DNA contributes to the prediction of prognosis in pancreatic cancer patients. Sci Rep 2021; 11:20797. [PMID: 34675229 PMCID: PMC8531317 DOI: 10.1038/s41598-021-00060-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 09/23/2021] [Indexed: 12/24/2022] Open
Abstract
Despite the acceptance of carbohydrate antigen 19-9 (CA19-9) as a valuable predictor for the prognosis of pancreatic ductal adenocarcinoma (PDAC), its cutoff value remains controversial. Our previous study showed a significant correlation between CA19-9 levels and the presence of KRAS-mutated ctDNA in the blood of patients with PDAC. Based on this correlation, we investigated the optimal cutoff value of CA19-9 before surgery. Continuous CA19-9 values and KRAS-mutated ctDNAs were monitored in 22 patients with unresectable PDAC who underwent chemotherapy between 2015 and 2017. Receiver operating characteristic curve analysis identified 949.7 U/mL of CA19-9 as the cutoff value corresponding to the presence of KRAS-mutated ctDNA. The median value of CA19-9 was 221.1 U/mL. Subsequently, these values were verified for their prognostic values of recurrence-free survival (RFS) and overall survival (OS) in 60 patients who underwent surgery between 2005 and 2013. Multivariate analysis revealed that 949.7 U/mL of CA19-9 was an independent risk factor for OS and RFS in these patients (P = 0.001 and P = 0.010, respectively), along with lymph node metastasis (P = 0.008 and P = 0.017), unlike the median CA19-9 level (P = 0.150 and P = 0.210). The optimal CA19-9 level contributes to the prediction of prognosis in patients with PDAC before surgery.
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Affiliation(s)
- Fumiaki Watanabe
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Koichi Suzuki
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan.
| | - Sawako Tamaki
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Iku Abe
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Yuhei Endo
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Yuji Takayama
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Hideki Ishikawa
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Nao Kakizawa
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Masaaki Saito
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Kazushige Futsuhara
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Hiroshi Noda
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
| | - Fumio Konishi
- Nerima Hikarigaoka Hospital, 2-11-1, Hikarigaoka, Nerima-ku, Tokyo, 179-0072, Japan
| | - Toshiki Rikiyama
- Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan
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10
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Lee B, Han HS, Lee JS, Yoon YS. Surgical Resection or Ablation for Recurrent Pancreatic Ductal Adenocarcinoma: An Analysis of Oncologic Outcomes According to the Recurrence Type. ANNALS OF SURGERY OPEN 2021; 2:e096. [PMID: 37635830 PMCID: PMC10455453 DOI: 10.1097/as9.0000000000000096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 08/08/2021] [Indexed: 11/27/2022] Open
Abstract
Objective To evaluate the survival benefits of curative-intent treatment (CIT, including surgery or ablation) for recurrent pancreatic ductal adenocarcinoma (PDAC) depending on the recurrence type and compared the survival outcomes with other treatment modalities. Background The treatment for recurrent PDAC is mostly chemotherapy or best supportive care (BSC). Still, the role of CIT for recurrent PDAC is not well established. Methods PDAC patients who underwent pancreatectomy between 2004 and 2019 were included. Recurrences were categorized as locoregional (LR), distant, or disseminated. Recurrent PDAC management was classified as CIT, chemotherapy ± radiation therapy (CTX ± RTX), or BSC. The survival after recurrence (SAR) rate was measured from the first day of recurrence to the date of death or last follow-up. Results Two hundred eighteen patients had recurrent PDAC and were analyzed (27 CIT, 128 CTX ± RTX, 63 BSC). The 1-, 3-, and 5-year SAR rates were 65.4%, 11.5%, and 11.5% for CIT, 42.1%, 4.0%, and 0% for CTX ± RTX, and 15.9%, 1.6%, and 0% for BSC, respectively. Subgroup analysis indicated the SAR rate was significantly better in the CIT group than in the CTX ± RTX and BSC groups in LR type (P = 0.027) and distant type (P < 0.001). In multivariate analysis, the albumin level at recurrence (hazard ratio, 2.14; 95% confidence interval, 1.15-18.3, P = 0.038) and operation time of the second operation (hazard ratio, 0.98; 95% confidence interval, 0.97-0.99, P = 0.021) were associated with a favorable prognosis of SAR in the CIT group. Conclusions CIT should be considered in recurrent PDAC for LR and distant metastases in selected patients.
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Affiliation(s)
- Boram Lee
- From the Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi-do, Korea
| | - Ho-Seong Han
- From the Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi-do, Korea
| | - Jun Suh Lee
- From the Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi-do, Korea
| | - Yoo-Seok Yoon
- From the Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi-do, Korea
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11
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Rasappan K, Shaw LKRMY, Chan LWM, Chuah KL, Cheng MHW. A case of raised CA 19-9 in a patient with desmoplastic fibroblastoma of the upper limb. Int Cancer Conf J 2021; 10:222-227. [PMID: 34221836 PMCID: PMC8206393 DOI: 10.1007/s13691-021-00485-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 04/16/2021] [Indexed: 02/06/2023] Open
Abstract
Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker widely accepted as the most useful blood test in diagnosing and monitoring pancreatic cancer. However, CA 19-9 may also be raised in other conditions such as colorectal, hepatic, lung, and ovarian carcinoma as well as benign conditions such as hepatobiliary and pulmonary diseases. CA 19-9 is rarely elevated above 200 U/ml in benign conditions with values exceeding 1000 U/ml being highly suggestive of malignancy. The mechanism of secretion in both malignant and benign conditions remains unclear. Desmoplastic fibroblastoma (DF) is a benign soft tissue tumor. CA 19-9 has not been reported in association with DF previously. We present a case of raised serum CA 19-9 in a 71-year-old male attributed solely to DF in his left cubital fossa. The patient's CA 19-9 level rose from 56 U/ml at the time of presentation to 3763.8 U/ml over a period of 9 months. Post-DF excision, the CA 19-9 level decreased to 1464 U/ml at 1 month, 162.3 U/ml at 2.5 months, and 24U/ml, within normal range, at 7 months post-surgery. CA 19-9 levels continued to remain at 24 U/ml 1.5 years post-tumor excision. The CA 19-9 level in this patient was highly elevated which is unusual in association with a benign tumor. The rate of decrease in CA 19-9 level post-excision was in keeping with that reported after pancreatic cancer resections. This is the first case of DF in association with raised CA 19-9.
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Affiliation(s)
- Kumaran Rasappan
- grid.240988.fDepartment of Orthopaedic Surgery, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, Singapore
| | | | - Lester Wai Mon Chan
- grid.240988.fDepartment of Orthopaedic Surgery, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, Singapore
| | - Khoon Leong Chuah
- grid.240988.fDepartment of Pathology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Mathew Hern Wang Cheng
- grid.240988.fDepartment of Orthopaedic Surgery, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, Singapore
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12
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Kowalchuk RO, Lester SC, Graham RP, Harmsen WS, Zhang L, Halfdanarson TR, Smoot RL, Gits HC, Ma WW, Owen D, Mahipal A, Miller RC, Wittich MAN, Cleary SP, McWilliams RR, Haddock MG, Hallemeier CL, Truty MJ, Merrell KW. Predicting Adverse Pathologic Features and Clinical Outcomes of Resectable Pancreas Cancer With Preoperative CA 19-9. Front Oncol 2021; 11:651119. [PMID: 34046346 PMCID: PMC8147692 DOI: 10.3389/fonc.2021.651119] [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: 01/08/2021] [Accepted: 04/20/2021] [Indexed: 12/15/2022] Open
Abstract
Background We evaluated preoperative CA 19-9 levels in patients with resected pancreatic cancer to analyze whether they were predictive of clinical outcomes and could help select patients for additional therapy. We hypothesized that elevated CA 19-9 would be associated with worse pathologic findings and oncologic outcomes. Methods This study assessed 509 patients with non-metastatic pancreatic adenocarcinoma who underwent resection at our institution from 1995-2011 and had preoperative CA 19-9 recorded. No patients received neoadjuvant therapy. CA 19-9 level was analyzed as a continuous and a dichotomized (> vs. ≤ 55 U/mL) variable using logistic and Cox models. Results Median follow-up was 7.8 years, and the median age was 66 years (33-90). 64% of patients had elevated preoperative CA 19-9 (median: 141 U/mL), that did not correlate with bilirubin level or tumor size. Most patients had ≥ T3 tumors (72%) and positive lymph nodes (62%). The rate of incomplete (R1 or R2) resection was 19%. Increasing preoperative CA 19-9 was associated with extra-pancreatic extension (p=0.0005), lymphovascular space invasion (p=0.0072), incomplete resection [HR (95% CI) 2.0 (1.2-3.5)], and lower OS [HR = 1.6 (1.3-2.0)]. Each doubling in preoperative CA 19-9 value was associated with an 8.3% increased risk of death [HR = 1.08 (1.02-1.15)] and a 10.0% increased risk of distant recurrence [HR = 1.10 (1.02-1.19)]. Patients classified as non-secretors had comparable outcomes to patients with normal CA 19-9. Conclusions Elevated preoperative CA 19-9 level was associated with adverse pathologic features, incomplete resection, and inferior clinical outcomes. Neither tumor size nor bilirubin confound an elevated CA 19-9 level. Preoperative CA 19-9 level may help select patients for additional therapy.
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Affiliation(s)
- Roman O Kowalchuk
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, United States
| | - Scott C Lester
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, United States
| | - Rondell P Graham
- Department of Pathology, Mayo Clinic, Rochester, MN, United States
| | | | - Lizhi Zhang
- Department of Pathology, Mayo Clinic, Rochester, MN, United States
| | | | - Rory L Smoot
- Department of Pancreas Surgery, Mayo Clinic, Rochester, MN, United States
| | - Hunter C Gits
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, United States
| | - Wen Wee Ma
- Department of Medical Oncology, Mayo Clinic, Rochester, MN, United States
| | - Dawn Owen
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, United States
| | - Amit Mahipal
- Department of Medical Oncology, Mayo Clinic, Rochester, MN, United States
| | - Robert C Miller
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, United States
| | | | - Sean P Cleary
- Department of Pancreas Surgery, Mayo Clinic, Rochester, MN, United States
| | | | - Michael G Haddock
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, United States
| | | | - Mark J Truty
- Department of Pancreas Surgery, Mayo Clinic, Rochester, MN, United States
| | - Kenneth W Merrell
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN, United States
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13
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Yu Y, Tong Y, Zhong A, Wang Y, Lu R, Guo L. Identification of Serum microRNA-25 as a novel biomarker for pancreatic cancer. Medicine (Baltimore) 2020; 99:e23863. [PMID: 33350781 PMCID: PMC7769376 DOI: 10.1097/md.0000000000023863] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 11/23/2020] [Indexed: 12/24/2022] Open
Abstract
To identify serum microRNA-25 (miR-25) as a diagnostic biomarker for pancreatic cancer (PCa) and to evaluate its supplementary role with serum carbohydrate antigen 19-9 (CA19-9) in early identification of cancers.Eighty patients with pancreatic cancer and 91 non-cancer controls were enrolled in this study. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression level of miR-25. Levels of CA19-9, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125) were measured by chemiluminescent immunoassay. The logistic model was established to evaluate the correlation of miR-25 with clinical characteristics. A risk model for PCa was conducted by R statistical software. Diagnostic utility for PCa and correlation with clinical characteristics were analyzed.The expression level of miR-25, in the PCa group was significantly higher (P < .05). Risk Model illustrated the relation between miR-25 and pancreatic cancer. With the combination of CA19-9, the performance of miR-25 in early stages (I+II) in the diagnosis of PCa was profoundly better than CA19-9 and miR-25 alone. This combination was more effective for discriminating PCa from non-cancer controls (AUC-ROC, 0.985; sensitivity, 97.50%; specificity, 90.11%) compared with CA19-9 alone or the combination of CA19-9 and CA125.The expression level of miR-25 among pancreatic cancer patients was significantly higher than that in the control group. miR-25 existed as one of the most relevant factors of PCa. miR-25 can serve as a novel noninvasive approach for PCa diagnosis, and with the supplementary of CA19-9, the combination was more effective, especially in early tumor screening.
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Affiliation(s)
- Yiwen Yu
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center
| | - Ying Tong
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center
| | - Ailing Zhong
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center
| | - Yanchun Wang
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center
| | - Renquan Lu
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Lin Guo
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
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14
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Liu H, Zenati MS, Rieser CJ, Al-Abbas A, Lee KK, Singhi AD, Bahary N, Hogg ME, Zeh HJ, Zureikat AH. CA19-9 Change During Neoadjuvant Therapy May Guide the Need for Additional Adjuvant Therapy Following Resected Pancreatic Cancer. Ann Surg Oncol 2020; 27:3950-3960. [PMID: 32318949 PMCID: PMC7931260 DOI: 10.1245/s10434-020-08468-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Neoadjuvant therapy (NAT) is increasingly utilized for pancreatic cancer, however the added benefit of adjuvant therapy (AT) in this setting is unknown. We hypothesized that the magnitude of CA19-9 response to NAT can guide the need for further AT in resected pancreatic cancer. METHODS CA19-9 secretors who received NAT for pancreatic cancer during 2008-2016 at a single institution were analyzed and CA19-9 response (difference between pre- and post-NAT values) was measured. Kaplan-Meier estimators and Cox proportional hazard ratio models were used to determine the optimal CA19-9 response at which AT ceases to confer any additional survival benefit after NAT. RESULTS A total of 241 patients (mean age 65.4 years, 50% female) with complete CA19-9 data who underwent NAT followed by resection were analyzed. In a cohort of patients (n = 78) in whom CA19-9 normalized with a decrease > 50% after NAT (optimal responders), AT was not associated with additional survival benefit (40.6 vs. 39.0 months, p = 0.815). Conversely, in the cohort of patients (n = 163) in whom NAT was not associated with normalization and a decrease of ≤ 50% in CA19-9 (suboptimal responders), receipt of AT was associated with a survival benefit (34.5 vs. 19.1 months, p < 0.001) following NAT. A Cox proportional hazards model confirmed CA19-9 normalization and decrease > 50% during NAT to predict no additional survival benefit from AT. CONCLUSIONS The magnitude of CA19-9 response to NAT may predict the need for further AT in resected pancreatic cancer. Prospective studies are needed to elucidate the optimal interplay of NAT and AT in pancreatic cancer.
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Affiliation(s)
- Hao Liu
- Division of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Mazen S Zenati
- Department of Surgery and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Caroline J Rieser
- Division of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Amr Al-Abbas
- Division of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Kenneth K Lee
- Division of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Aatur D Singhi
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Nathan Bahary
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Melissa E Hogg
- Department of Surgery, NorthShore University Health System, Chicago, IL, USA
| | - Herbert J Zeh
- Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Amer H Zureikat
- Division of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
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15
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Holm M, Saraswat M, Joenväärä S, Seppänen H, Renkonen R, Haglund C. Label-free proteomics reveals serum proteins whose levels differ between pancreatic ductal adenocarcinoma patients with short or long survival. Tumour Biol 2020; 42:1010428320936410. [PMID: 32586207 DOI: 10.1177/1010428320936410] [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] [Indexed: 11/15/2022] Open
Abstract
Pancreatic ductal adenocarcinoma is the most common and aggressive type of pancreatic cancer, with a 5-year survival rate that is less than 10%. New biomarkers to aid in predicting the prognosis of pancreatic ductal adenocarcinoma patients are needed. Previous proteomic studies have to a great extent focused on finding proteins of value for the diagnosis of pancreatic ductal adenocarcinoma. There is a lack of studies that have profiled the serum or plasma proteome in order to discover candidates for new prognostic biomarkers. In this study, we have used ultra-performance liquid chromatography-ultra-definition mass spectrometry to analyze the serum samples of 21 pancreatic ductal adenocarcinoma patients with short or long survival. Statistical analysis discovered 31 proteins whose expression differed significantly between pancreatic ductal adenocarcinoma patients with short or long survival. Pathway analysis discovered multiple canonical pathways enriched in this data set, with several pathways having roles in inflammation and lipid metabolism. The serum proteins identified here, which include complement components and several enzymes, could be of value as candidates for new noninvasive prognostic markers.
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Affiliation(s)
- Matilda Holm
- Department of Surgery, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Department of Pathology, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Applied Tumor Genomics Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Mayank Saraswat
- Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.,HUSLAB, Helsinki University Hospital, Helsinki, Finland.,Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Sakari Joenväärä
- Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.,HUSLAB, Helsinki University Hospital, Helsinki, Finland
| | - Hanna Seppänen
- Department of Surgery, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Risto Renkonen
- Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.,HUSLAB, Helsinki University Hospital, Helsinki, Finland
| | - Caj Haglund
- Department of Surgery, Faculty of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
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16
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Identifying Clinical Factors Which Predict for Early Failure Patterns Following Resection for Pancreatic Adenocarcinoma in Patients Who Received Adjuvant Chemotherapy Without Chemoradiation. Am J Clin Oncol 2019; 41:1185-1192. [PMID: 29727311 DOI: 10.1097/coc.0000000000000452] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES The role of radiation therapy (RT) in resected pancreatic cancer (PC) remains incompletely defined. We sought to determine clinical variables which predict for local-regional recurrence (LRR) to help select patients for adjuvant RT. MATERIALS AND METHODS We identified 73 patients with PC who underwent resection and adjuvant gemcitabine-based chemotherapy alone. We performed detailed radiologic analysis of first patterns of failure. LRR was defined as recurrence of PC within standard postoperative radiation volumes. Univariate analyses (UVA) were conducted using the Kaplan-Meier method and multivariate analyses (MVA) utilized the Cox proportional hazard ratio model. Factors significant on UVA were used for MVA. RESULTS At median follow-up of 20 months, rates of local-regional recurrence only (LRRO) were 24.7%, LRR as a component of any failure 68.5%, metastatic recurrence (MR) as a component of any failure 65.8%, and overall disease recurrence (OR) 90.5%. On UVA, elevated postoperative CA 19-9 (>90 U/mL), pathologic lymph node positive (pLN+) disease, and higher tumor grade were associated with increased LRR, MR, and OR. On MVA, elevated postoperative CA 19-9 and pLN+ were associated with increased MR and OR. In addition, positive resection margin was associated with increased LRRO on both UVA and MVA. CONCLUSIONS About 25% of patients with PC treated without adjuvant RT develop LRRO as initial failure. The only independent predictor of LRRO was positive margin, while elevated postoperative CA 19-9 and pLN+ were associated with predicting MR and overall survival. These data may help determine which patients benefit from intensification of local therapy with radiation.
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17
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Liu L, Xu HX, He M, Wang W, Wang WQ, Wu CT, Wei RQ, Liang Y, Gao HL, Liu C, Xu J, Long J, Ni QX, Shao CH, Wang J, Yu XJ. A novel scoring system predicts postsurgical survival and adjuvant chemotherapeutic benefits in patients with pancreatic adenocarcinoma: Implications for AJCC-TNM staging. Surgery 2018; 163:1280-1294. [PMID: 29548773 DOI: 10.1016/j.surg.2018.01.017] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2017] [Revised: 01/16/2018] [Accepted: 01/23/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND We evaluated the application of the latest 8th American Joint Committee on Cancer (AJCC) staging system in Chinese patients and determined whether the addition of biologic markers could improve the prediction of postsurgical survival in pancreatic adenocarcinoma (PC). METHODS This multicenter study involved 1,223 consecutive patients who underwent margin-negative pancreatectomy for PC. A scoring system was devised based on AJCC pathologic parameters and biologic markers and defined using a Cox proportional hazards model. Prognostic accuracies were evaluated by concordance index (C-index) and Akaike information criterion (AIC). RESULTS The 8th edition AJCC staging system had a better survival distribution of PC with different stages and a similar C-index (0.62 in the training cohort, 0.60 in the validation cohort) than the 7th edition (0.59 in the training cohort, 0.58 in the validation cohort). Nevertheless, survival of resected patients with stage IIA or IIB disease was indistinguishable. Incorporation of postoperative carbohydrate antigen 19-9 (CA19-9) levels and tumor grade into the 8th edition AJCC staging system generated a scoring system with better predictive accuracy for overall survival (OS) (C-index of 0.73 and AIC of 4301.05 in the training cohort, C-index of 0.71 and AIC of 3309.23 in the validation cohort). More importantly, patients with median or higher scores experienced OS benefits from adjuvant chemotherapy. CONCLUSION Postoperative CA19-9 levels and tumor grade are two well-known PC biologic markers that could be incorporated into a standard AJCC staging system to refine risk stratification and predict OS benefit from adjuvant chemotherapy in resected PC.
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Affiliation(s)
- Liang Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Pancreatic Cancer Institute, Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Hua-Xiang Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Pancreatic Cancer Institute, Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Min He
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Wei Wang
- Department of General Surgery, Huadong Hospital, Fudan University, Shanghai, China
| | - Wen-Quan Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Pancreatic Cancer Institute, Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Chun-Tao Wu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Pancreatic Cancer Institute, Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Rong-Qiang Wei
- Department of Pancreatic-Biliary Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Yun Liang
- Department of General Surgery, Huadong Hospital, Fudan University, Shanghai, China
| | - He-Li Gao
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Pancreatic Cancer Institute, Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Chen Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Pancreatic Cancer Institute, Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Pancreatic Cancer Institute, Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Jiang Long
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Pancreatic Cancer Institute, Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Quan-Xing Ni
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Pancreatic Cancer Institute, Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Cheng-Hao Shao
- Department of Pancreatic-Biliary Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Jian Wang
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xian-Jun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai Pancreatic Cancer Institute, Pancreatic Cancer Institute, Fudan University, Shanghai, China
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Systematic review on the role of serum tumor markers in the detection of recurrent pancreatic cancer. HPB (Oxford) 2018; 20:297-304. [PMID: 29366815 DOI: 10.1016/j.hpb.2017.11.009] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 11/22/2017] [Accepted: 11/26/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Biomarker testing can be helpful to monitor disease progression after resection of pancreatic cancer. This systematic review aims to give an overview of the literature on the diagnostic value of serum tumor markers for the detection of recurrent pancreatic cancer during follow-up. METHODS A systematic search was performed to 2 October 2017. All studies reporting on the diagnostic value of postoperatively measured serum biomarkers for the detection of pancreatic cancer recurrence were included. Data on diagnostic accuracy of tumor markers were extracted. Forest plots and pooled values of sensitivity and specificity were calculated. RESULTS Four articles described test results of CA 19-9. A pooled sensitivity and specificity of respectively 0.73 (95% CI 0.66-0.80) and 0.83 (95% CI 0.73-0.91) were calculated. One article reported on CEA, showing a sensitivity of 50% and specificity of 65%. No other serum tumor markers were discussed for surveillance purposes in the current literature. CONCLUSION Although testing of serum CA 19-9 has considerable limitations, CA 19-9 remains the most used serum tumor marker for surveillance after surgical resection of pancreatic cancer. Further studies are needed to assess the role of serum tumor marker testing in the detection of recurrent pancreatic cancer and to optimize surveillance strategies.
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19
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A Contemporary Review of the Treatment Landscape and the Role of Predictive and Prognostic Biomarkers in Pancreatic Adenocarcinoma. Can J Gastroenterol Hepatol 2018; 2018:1863535. [PMID: 29623263 PMCID: PMC5829312 DOI: 10.1155/2018/1863535] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Accepted: 01/17/2018] [Indexed: 02/07/2023] Open
Abstract
Pancreatic cancer continues to represent one of the leading causes of cancer-related morbidity and mortality in the developed world. Over the past decade, novel systemic therapy combination regimens have contributed to clinically meaningful and statistically significant improvements in overall survival as compared to conventional monotherapy. However, the prognosis for most patients remains guarded secondary to the advanced stages of disease at presentation. There is growing consensus that outcomes can be further optimized with the use of predictive and prognostic biomarkers whereby the former can be enriching for patients who would benefit from therapies and the latter can inform decision-making regarding the need and timing of advanced care planning. One of the challenges of current biomarkers is the lack of standardization across clinical practices such that comparability between jurisdictions can be difficult or even impossible. This inconsistency can impede widespread implementation of their use. In this review article, we provide a comprehensive overview of the contemporary treatment options for pancreatic cancer and we offer some insights into the existing landscape and future directions of biomarker development for this disease.
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20
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Regine WF, Winter K, Abrams RA, Safran H, Kessel IL, Chen Y, Fugazzi JA, Donnelly ED, DiPetrillo TA, Narayan S, Plastaras JP, Gaur R, Delouya G, Suh JH, Meyer JE, Haddock MG, Didolkar MS, Padula GDA, Johnson D, Hoffman JP, Crane CH. Postresection CA19-9 and margin status as predictors of recurrence after adjuvant treatment for pancreatic carcinoma: Analysis of NRG oncology RTOG trial 9704. Adv Radiat Oncol 2018; 3:154-162. [PMID: 29904740 PMCID: PMC6000159 DOI: 10.1016/j.adro.2018.01.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 01/16/2018] [Indexed: 12/30/2022] Open
Abstract
Purpose NRG Oncology RTOG 9704 was the first adjuvant trial to validate the prognostic value of postresection CA19-9 levels for survival in patients with pancreatic carcinoma. The data resulting from this study also provide information about predictors of recurrence that may be used to tailor individualized management in this disease setting. This secondary analysis assessed the prognostic value of postresection CA19-9 and surgical margin status (SMS) in predicting patterns of disease recurrence. Methods and materials This multicenter cooperative trial included participants who were enrolled as patients at oncology treatment sites in the United States and Canada. The study included 451 patients analyzable for SMS, of whom 385 were eligible for postresection CA19-9 analysis. Postresection CA19-9 was analyzed at cut points of 90, 180, and continuously. Patterns of disease recurrence included local/regional recurrence (LRR) and distant failure (DF). Multivariable analyses included treatment, tumor size, and nodal status. To adjust for multiple comparisons, a P value of ≤ .01 was considered statistically significant and > .01 to ≤ .05 to be a trend. Results For CA19-9, 132 (34%) patients were Lewis antigen-negative (no CA19-9 expression), 200 (52%) had levels <90, and 220 (57%) had levels <180. A total of 188 patients (42%) had negative margins, 152 (34%) positive, and 111 (25%) unknown. On univariate analysis, CA19-9 cut at 90 was associated with increases in LRR (trend) and DF. Results were similar at the 180 cut point. SMS was not associated with an increase in LRR on univariate or multivariate analyses. On multivariable analysis, CA19-9 ≥ 90 was associated with increased LRR and DF. Results were similar at the 180 cut point. Conclusions In this prospective evaluation, postresection CA19-9 was a significant predictor of both LRR and DF, whereas SMS was not. These findings support consideration of adjuvant radiation therapy dose intensification in patients with elevated postresection CA19-9.
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Affiliation(s)
| | - Kathryn Winter
- NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania
| | | | | | - Ivan L Kessel
- University of Texas Medical Branch, Galveston, Texas
| | - Yuhchyau Chen
- University of Rochester Medical Center, Rochester, New York
| | - James A Fugazzi
- Toledo Community Hospital Oncology Program CCOP, Toledo, Ohio
| | | | | | - Samir Narayan
- Michigan Cancer Research Consortium CCOP, Ann Arbor, Michigan
| | - John P Plastaras
- University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
| | | | - Guila Delouya
- Centre Hospitalier de l'Université de Montréal-Notre Dame, Montreal, Quebec
| | - John H Suh
- Cleveland Clinic Foundation, Cleveland, Ohio
| | | | | | | | | | | | | | - Christopher H Crane
- The University of Texas MD Anderson Cancer Center, Houston, Texas.,Memorial Sloan Kettering Cancer Center, New York, New York
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21
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Rayamajhi S, Balachandran A, Katz M, Reddy A, Rohren E, Bhosale P. Utility of (18) F-FDG PET/CT and CECT in conjunction with serum CA 19-9 for detecting recurrent pancreatic adenocarcinoma. Abdom Radiol (NY) 2018; 43:505-513. [PMID: 28900703 DOI: 10.1007/s00261-017-1316-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE The roles of different cross-sectional imaging in evaluating the recurrence of pancreatic adenocarcinoma are not well established. We evaluated the utility of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced computed tomography (CECT) in the diagnosis of recurrent pancreatic adenocarcinoma in conjunction with the tumor marker CA 19-9. METHODS We retrospectively reviewed the records of patients who underwent CECT and FDG PET/CT along with serum CA 19-9 measurement as a follow-up or on a clinical suspicion of recurrent disease after initial surgery for pancreatic adenocarcinoma. Two observers blinded to the other imaging modality results retrospectively reviewed and interpreted the images in consensus using a three-point scale (negative, equivocal, or positive). Pathologic analysis by biopsy or further clinical and radiologic follow-up determined the true status of the suspected recurrences. The imaging results were compared with CA 19-9 levels and true disease status. RESULTS Thirty-nine patients were included in the study. Thirty-three patients (85%) had proven recurrent cancer and six patients (15%) had no evidence of disease. Twenty-four patients had elevated CA 19-9 and 15 patients had normal CA 19-9. Sensitivity, specificity, and accuracy for recurrence were 90.9%, 100.0%, and 92.3% for PET/CT and 72.2%, 66.6%, and 71.7% for CECT, respectively. Sensitivity for locoregional recurrence was 94.4% for PET/CT but only 61.1% for CECT. PET/CT detected recurrence in 12 patients who had normal levels of CA 19-9. PET/CT showed lesions not visible on CECT in five (15%) patients. Although the sensitivity and specificity of PET/CT were higher than those of CECT, they were not statistically significant (p = 0.489 and p = 0.1489, respectively). CONCLUSION FDG PET/CT has a high sensitivity for pancreatic cancer recurrence. Normal CA 19-9 does not necessarily exclude these recurrences. FDG PET/CT is useful when CECT is equivocal and can detect recurrence in patients with normal CA 19-9.
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Affiliation(s)
| | - Aparna Balachandran
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 38, Houston, TX, 77030, USA
| | - Mathew Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Arun Reddy
- Department of Diagnostic Radiology, Baylor College of Medicine, Houston, TX, USA
| | - Eric Rohren
- Department of Nuclear Medicine, Medanta Hospital, Irba, Ranchi, India
| | - Priya Bhosale
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 38, Houston, TX, 77030, USA.
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Goh SK, Gold G, Christophi C, Muralidharan V. Serum carbohydrate antigen 19-9 in pancreatic adenocarcinoma: a mini review for surgeons. ANZ J Surg 2017; 87:987-992. [PMID: 28803454 DOI: 10.1111/ans.14131] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 05/24/2017] [Indexed: 12/12/2022]
Abstract
The optimal management of oncological conditions is reflected by the careful interpretation of investigations for screening, diagnosis, staging, prognostication and surveillance. Serum tumour markers are examples of commonly requested tests in conjunction with other imaging and endoscopic tests that are used to help clinicians to stratify therapeutic decisions. Serum carbohydrate antigen 19-9 (CA19-9) is a key biomarker for pancreatic cancers. Although this biomarker is considered clinically useful and informative, clinicians are often challenged by the accurate interpretation of elevated serum CA19-9 levels. Recognizing the pitfalls of normal and abnormal serum CA19-9 concentrations will facilitate its appropriate use. In this review, we appraised the biomarker, serum CA19-9, and highlighted the clinical utility and limitations of serum CA19-9 in the investigation and management of pancreatic cancers.
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Affiliation(s)
- Su Kah Goh
- Hepato-Pancreato-Biliary and Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
- Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
| | - Grace Gold
- Hepato-Pancreato-Biliary and Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
- Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
| | - Christopher Christophi
- Hepato-Pancreato-Biliary and Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
- Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
| | - Vijayaragavan Muralidharan
- Hepato-Pancreato-Biliary and Transplant Unit, Austin Hospital, Melbourne, Victoria, Australia
- Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
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23
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Zervos EE, Rosemurgy AS, Al-Saif O, Durkin AJ. Surgical Management of Early-Stage Pancreatic Cancer. Cancer Control 2017. [DOI: 10.1177/107327480401100204] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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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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25
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Kato Y, Takahashi S, Gotohda N, Konishi M. Prognostic Impact of the Initial Postoperative CA19-9 Level in Patients with Extrahepatic Bile Duct Cancer. J Gastrointest Surg 2016; 20:1435-43. [PMID: 27250990 DOI: 10.1007/s11605-016-3180-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Accepted: 05/26/2016] [Indexed: 01/31/2023]
Abstract
BACKGROUND The aim of this study was to investigate the prognostic impact of the initial serum postoperative CA19-9 levels in patients with extrahepatic bile duct cancer. METHODS Data of a total of 143 patients of extrahepatic bile duct cancer with elevated preoperative serum CA19-9 levels (>37 U/ml) who underwent surgery with curative intent were reviewed retrospectively. The patients were divided into the "Normalization group" and "Non-normalization group" (initial postoperative serum CA19-9 ≤37 and >37 U/ml, respectively), and the clinicopathological factors and survival outcomes in these groups were comparatively analyzed. RESULTS The cumulative 5-year overall survival (OS) rate and median survival time (MST) were 39.2 % and 42.9 months, respectively, in the Normalization group and 17.9 % and 24.0 months, respectively, in the Non-normalization group (P < 0.001). Presence of jaundice, a poorer histological differentiation grade (G3-4), lymph node metastasis, and initial postoperative serum CA19-9 level (>37 U/ml) were significant independent predictors of a poor prognosis on multivariate analysis. CONCLUSION Non-normalization of the serum CA19-9 level in the initial postoperative phase is a strong predictor of a poor prognosis and is a useful marker to identify patients who would need additional treatments and stricter follow-up.
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Affiliation(s)
- Yuichiro Kato
- Division of Hepatobiliary Pancreatic Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
| | - Shinichiro Takahashi
- Division of Hepatobiliary Pancreatic Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan
| | - Naoto Gotohda
- Division of Hepatobiliary Pancreatic Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan
| | - Masaru Konishi
- Division of Hepatobiliary Pancreatic Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan
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Post-adjuvant chemotherapy CA19-9 levels predict prognosis in patients with pancreatic ductal adenocarcinoma: A retrospective cohort study. Pancreatology 2016; 16:658-64. [PMID: 27178104 DOI: 10.1016/j.pan.2016.04.007] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Revised: 04/12/2016] [Accepted: 04/13/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Carbohydrate antigen 19-9 (CA19-9) is a widely used tumor marker for pancreatic ductal adenocarcinoma (PDAC). In addition, several studies have reported the utility of both pre- and postoperative CA19-9 levels as prognostic factors in resectable PDAC. However, little is known about the implications of post-adjuvant chemotherapy (AC) CA19-9 levels. The purpose of this study was to examine the utility of the post-AC CA19-9 level as a prognostic marker for relapse-free survival (RFS) in resectable PDAC. METHODS A total of 119 patients who completed AC were analyzed (normal post-AC CA19-9, n = 79; high post-AC CA19-9, n = 40). The upper limit of the normal (ULN) serum level of CA19-9 was 37 U/mL. RESULTS Median RFS was significantly shorter for patients with high post-AC CA19-9 levels than for those with normal post-AC CA19-9 (10.4 months vs. 29.6 months, respectively; p < 0.001). After adjustment, high post-AC CA19-9 level was an independent predictive factor for short RFS (hazard ratio for RFS, 2.72). Median overall survival was significantly shorter in patients with high post-AC CA19-9 levels than in those with normal postoperative CA19-9 levels (24.7 months vs. 92.1 months, respectively; p < 0.001). The optimal cutoff value of post-AC CA19-9 levels for prediction of early recurrence was >1.5 × UNL (55.5 U/mL), with a 74.2% positive predictive value. CONCLUSIONS The present results show that high post-AC CA19-9 level is an independent prognostic factor for short RFS in patients with resected PDAC. In addition, it may be useful for predicting early recurrence.
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27
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Abstract
CA19-9 (carbohydrate antigen 19-9, also called cancer antigen 19-9 or sialylated Lewis a antigen) is the most commonly used and best validated serum tumor marker for pancreatic cancer diagnosis in symptomatic patients and for monitoring therapy in patients with pancreatic adenocarcinoma. Normally synthesized by normal human pancreatic and biliary ductal cells and by gastric, colon, endometrial and salivary epithelia, CA 19-9 is present in small amounts in serum, and can be over expressed in several benign gastrointestinal disorders. Importantly, it exhibits a dramatic increase in its plasmatic levels during neoplastic disease. However, several critical aspects for its clinical use, such as false negative results in subjects with Lewis (a-b-) genotype and false positive elevation, occasional and transient, in patients with benign diseases, together with its poor positive predictive value (72.3 %), do not make it a good cancer-specific marker and renders it impotent as a screening tool. In the last years a large number of putative biomarkers for pancreatic cancer have been proposed, most of which is lacking of large scale validation. In addition, none of these has showed to possess the requisite sensitivity/specificity to be introduced in clinical use. Therefore, although with important limitations we well-know, CA 19-9 continues being the only pancreatic cancer marker actually in clinical use.
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Piagnerelli R, Marrelli D, Roviello G, Ferrara F, Di Mare G, Voglino C, Petrioli R, Marini M, Macchiarelli R, Roviello F. Clinical value and impact on prognosis of peri-operative CA 19-9 serum levels in stage I and II adenocarcinoma of the pancreas. Tumour Biol 2015; 37:1959-66. [PMID: 26334620 DOI: 10.1007/s13277-015-3986-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Accepted: 08/25/2015] [Indexed: 12/27/2022] Open
Abstract
CA 19-9 is a marker correlated to the clinical evolution of pancreatic adenocarcinoma. To analyze the clinical value of pre- and postoperative CA 19-9 serum levels in stage I and II pancreatic cancer. We analyzed 61 patients resected for pancreatic cancer. Patients were evaluated about the pre-operative CA 19-9 values and then divided into 3 groups: high, high-low and low, on the basis of pre- and postoperative CA 19-9 levels. The correlations between these groups and age, sex, pT, pN, tumor stage, jaundice, surgical radicality, tumor size, number of harvested and positive lymph nodes, grading, overall and major morbidities and post-operative mortality together with survival rates were analyzed. Higher values of pre-operative CA 19-9 were significantly correlated to the presence of jaundice, high pT, pN, stage and higher number of metastatic lymph nodes. In 49 patients (80.3 %) an R0 resection was performed. Five-year overall survival (OS) and disease free survival (DFS) were significantly better in patients with high levels of pre-operative CA 19-9, even in R0 cases. After stratification, 30 patients were included in the high group, 13 in the high-low group and 18 in the low group. A statistically significant correlation was found between the CA 19-9 groups and the lymph nodal positivity, not between CA 19-9 and pT. OS and DFS were significantly better in low group patients. We confirm the prognostic value of preoperative CA 19-9 serum levels. We do not support early postoperative modifications of CA19-9 as an adjunctive prognostic variable.
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Affiliation(s)
| | - Daniele Marrelli
- Surgical Oncology Unit, University of Siena, Siena, Italy. .,, Viale M. Bracci 16, Policlinico Santa Maria alle Scotte, 53100, Siena, Italy.
| | - Giandomenico Roviello
- Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
| | | | - Giulio Di Mare
- Surgical Oncology Unit, University of Siena, Siena, Italy
| | | | | | - Mario Marini
- Operative Endoscopy Unit, University of Siena, Siena, Italy
| | | | - Franco Roviello
- General and Minimally Invasive Surgery Unit, University of Siena, Siena, Italy
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Wang LS, Shaikh T, Handorf EA, Hoffman JP, Cohen SJ, Meyer JE. Dose escalation with a vessel boost in pancreatic adenocarcinoma treated with neoadjuvant chemoradiation. Pract Radiat Oncol 2015; 5:e457-e463. [PMID: 26077273 PMCID: PMC4814166 DOI: 10.1016/j.prro.2015.04.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2014] [Revised: 04/06/2015] [Accepted: 04/10/2015] [Indexed: 12/12/2022]
Abstract
PURPOSE Patients with pancreatic adenocarcinoma (PAC) are often treated with neoadjuvant chemoradiation (NACRT) in hopes of downstaging their disease for potential surgical resection. We hypothesized that increasing the radiation dose to the area of the tumor abutting the vessel(s) of concern would increase the rate of surgical resection in patients with borderline resectable PAC (BRPAC) and locally advanced PAC (LAPAC) treated with NACRT. METHODS AND MATERIALS We retrospectively reviewed consecutive cases of BRPAC and LAPAC treated with NACRT from January 2006 to December 2013, with or without a vessel boost (VB), at a single institution. The primary endpoints were rate of R0/R1 potentially curative surgical resection and acute toxicity. Univariate analysis with the Fisher exact test was performed to evaluate the effect of each variable. Multiple logistic regression was used to adjust for the following covariates: year of diagnosis, age, sex, carbohydrate antigen 19-9 (CA19-9) level at diagnosis, and BRPAC or LAPAC. RESULTS Of the 104 patients identified, 22% (n = 23) received a VB (median, 54 Gy; range, 54-64 Gy), and 78% (n = 81) received no boost (median, 50.4 Gy; range, 48.6-52.2 Gy). More patients in the VB group were treated from 2010 to 2013 (P < .001) and with intensity modulated radiation therapy (P = .002). Other baseline characteristics were balanced. After adjustment for covariates, there was a statistical trend toward increased surgical resection in patients who received a VB (odds ratio [OR], 2.77; 95% confidence interval [CI], 0.89-8.57; P = .077). Age (≥70 years; OR, 0.42; 95% CI, 0.16-1.05; P = .064) and LAPAC (OR, 0.32; 95% CI, 0.09-1.09; P = .068) also trended toward significance. CA19-9 ≥47.9 U/mL (OR, 0.24; 95% CI, 0.08-0.71; P = .010) was significant on multivariate analysis. There was no significant difference in acute or late toxicity between groups. CONCLUSIONS In our retrospective series, dose escalation was associated with an improved surgical resection rate in BRPAC and LAPAC patients treated with NACRT, although this improvement was not statistically significant.
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Affiliation(s)
- Lora S Wang
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Talha Shaikh
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Elizabeth A Handorf
- Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - John P Hoffman
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Steven J Cohen
- Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Joshua E Meyer
- Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
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Individualized radiotherapy (iRT) concepts for locally advanced pancreatic cancer (LAPC): indications and prognostic factors. Langenbecks Arch Surg 2015; 400:749-56. [DOI: 10.1007/s00423-015-1309-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2015] [Accepted: 05/26/2015] [Indexed: 12/25/2022]
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Kim J, Lee YS, Hwang IK, Kang BK, Cho JY, Yoon YS, Han HS, Hwang JH. Postoperative carcinoembryonic antigen as a complementary tumor marker of carbohydrate antigen 19-9 in pancreatic ductal adenocarcinoma. J Korean Med Sci 2015; 30:259-63. [PMID: 25729247 PMCID: PMC4330479 DOI: 10.3346/jkms.2015.30.3.259] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2014] [Accepted: 10/16/2014] [Indexed: 01/13/2023] Open
Abstract
The role of carcinoembryonic antigen (CEA) in pancreatic cancer remains poorly understood. Therefore, this study aimed to determine whether CEA is complementary to carbohydrate antigen 19-9 (CA19-9) in prognosis prediction after pancreatic cancer curative resection. We retrospectively reviewed records of 144 stage II curatively resected pancreatic cancer patients with preoperative and postoperative CEA and CA19-9 levels. Patients with normal preoperative CA19-9 were excluded. R0 resection margin, adjuvant treatment, and absence of angiolymphatic invasion were associated with better overall survival. There was no significant difference in median survival according to preoperative CEA levels. However, patients with normal postoperative CA19-9 (59.8 vs.16.2 months, P < 0.001) and CEA (29.4 vs. 9.3 months, P = 0.001) levels had longer overall survival than those with elevated levels. Among 76 patients with high postoperative CA19-9 levels, a better prognosis was observed in those with normal postoperative CEA levels than in those with elevated levels (19.1 vs. 9.3 months, P = 0.004). Postoperative CEA and CA19-9 levels are valuable prognostic markers in resected pancreatic cancer. Normal postoperative CEA levels indicate longer survival, even in patients with elevated postoperative CA19-9.
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Affiliation(s)
- Jaihwan Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yoon Suk Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - In Kyeom Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Bong Kyun Kang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Milman S, Arnold JL, Price M, Negassa A, Surks MI, Fleischer N, Whitney KD. MEDULLARY THYROID CANCER THAT STAINS NEGATIVE FOR CA 19-9 HAS DECREASED METASTATIC POTENTIAL. Endocr Pract 2015; 21:590-4. [PMID: 25716629 DOI: 10.4158/ep14357.or] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Presently, no clinical tools are available to diagnose the metastatic potential of medullary thyroid cancer (MTC) at disease presentation. Surveillance with calcitonin (Ct) and carcinoembryonic antigen (CEA) is currently recommended for the observation and diagnosis of metastatic disease after initial treatment of MTC. Recently, carbohydrate antigen (CA)19-9 staining has been associated with aggressive forms of MTC and metastatic spread. This pilot study explored whether positive CA19-9 staining of MTC tissue is associated with its metastatic potential. METHODS Sixteen cases of MTC were identified, and tissue specimens were immunostained for CA 19-9 and other MTC tumor markers. Clinical information about patients' MTC was collected through a retrospective chart review. RESULTS Overall, 63% of the specimens stained positive for CA19-9. The median size of positively staining specimens was 2.6 cm (interquartile range [IQR] 1.2-3.2) compared to 0.7 cm (0.5-1.2) in negatively staining MTC specimens (P = .04). All specimens from patients diagnosed with stage IV MTC stained positive for CA19-9, compared to only 40% of cases that were classified as stages I to III (P = .03). Furthermore, 100% of the primary specimens that were documented to have metastatic spread stained positive for CA19-9. The sensitivity for ruling out stage IV MTC based on negative staining for CA 19-9 was 100%. CONCLUSION Based on these results, we conclude that negative staining of MTC for CA19-9 may be associated with its decreased metastatic potential.
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Thomas RM, Truty MJ, Kim M, Kang Y, Zhang R, Chatterjee D, Katz MH, Fleming JB. The canary in the coal mine: the growth of patient-derived tumorgrafts in mice predicts clinical recurrence after surgical resection of pancreatic ductal adenocarcinoma. Ann Surg Oncol 2014; 22:1884-92. [PMID: 25404477 DOI: 10.1245/s10434-014-4241-1] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Indexed: 12/27/2022]
Abstract
BACKGROUND Recurrence after resection of pancreatic ductal adenocarcinoma (PDAC) is common, thus postoperative surveillance is critical for detection and treatment of recurrent disease. The development of biologically based techniques for early recurrence detection may enable more timely and effective treatment of such recurrences. METHODS Tumor fragments derived from patients who underwent potentially curative resection of PDAC were heterotopically implanted into NOD/SCID mice. Engraftment success rates and growth parameters were matched to clinicopathologic data, preoperative treatment status, and oncologic outcomes to correlate disease-free survival (DFS) and overall survival. RESULTS Seventy patients consented to participate with 56 (80 %) developing a mouse PDAC tumorgraft. Patients with successful engraftment had a shorter median DFS compared with patients whose tumorgrafts failed to engraft (9.8 vs. 40.9 mo, respectively; p < 0.01). Fifty patients received preoperative therapy with 36 (72 %) successful tumorgrafts from this cohort. On multivariate analysis, lymph node metastasis (hazard ratio [HR] 3, 95 % CI 1.4-6.7, p < 0.01) and successful engraftment (HR 5.8, 95 % CI 2-16.9, p < 0.01) were predictive of a shorter DFS in the preoperative therapy cohort. In patients who recurred, tumorgraft formation was identified at a median of 134.5 days before standard methods of radiographic recurrence detection (p < 0.01). CONCLUSIONS Patient-derived tumorgrafts from resected PDAC may potentially predict recurrence months before currently available surveillance modalities. This lead-time advantage may allow for earlier implementation or changes in therapy as successful engraftment, particularly in those having undergone preoperative therapy, may indicate a more biologically aggressive disease.
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Affiliation(s)
- Ryan M Thomas
- Department of Surgery, NF/SG VA Medical Center, Gainesville, FL, USA
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Sutton JM, Abbott DE. Neoadjuvant therapy for pancreas cancer: Past lessons and future therapies. World J Gastroenterol 2014; 20:15564-15579. [PMID: 25400440 PMCID: PMC4229521 DOI: 10.3748/wjg.v20.i42.15564] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2013] [Revised: 01/21/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgery-first strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.
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35
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Loc WS, Smith JP, Matters G, Kester M, Adair JH. Novel strategies for managing pancreatic cancer. World J Gastroenterol 2014; 20:14717-14725. [PMID: 25356034 PMCID: PMC4209537 DOI: 10.3748/wjg.v20.i40.14717] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2014] [Revised: 03/14/2014] [Accepted: 05/14/2014] [Indexed: 02/07/2023] Open
Abstract
With the incidence reports of pancreatic cancer increasing every year, research over the last several decades has been focused on the means to achieve early diagnosis in patients that are at a high risk of developing the malignancy. This review covers current strategies for managing pancreatic cancer and further discusses efforts in understanding the role of early onset symptoms leading to tumor progression. Recent investigations in this discussion include type 3c diabetes, selected biomarkers and pathways related to pancreatic intraepithelial neoplasia lesions, drug resistance, and advances in nanomedicine which may provide significant solutions for improving early detection and treatments in future medicine.
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Rossi ML, Rehman AA, Gondi CS. Therapeutic options for the management of pancreatic cancer. World J Gastroenterol 2014; 20:11142-11159. [PMID: 25170201 PMCID: PMC4145755 DOI: 10.3748/wjg.v20.i32.11142] [Citation(s) in RCA: 92] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Revised: 01/11/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Since its initial characterization, pancreatic ductal adenocarcinoma has remained one of the most devastating and difficult cancers to treat. Pancreatic cancer is the fourth leading cause of death in the United States, resulting in an estimated 38460 deaths annually. With few screening tools available to detect this disease at an early stage, 94% of patients will die within five years of diagnosis. Despite decades of research that have led to a better understanding of the molecular and cellular signaling pathways in pancreatic cancer cells, few effective therapies have been developed to target these pathways. Other treatment options have included more sophisticated pancreatic cancer surgeries and combination therapies. While outcomes have improved modestly for these patients, more effective treatments are desperately needed. One of the greatest challenges in the future of treating this malignancy will be to develop therapies that target the tumor microenvironment and surrounding pancreatic cancer stem cells in addition to pancreatic cancer cells. Recent advances in targeting pancreatic stellate cells and the stroma have encouraged researchers to shift their focus to the role of desmoplasia in pancreatic cancer pathobiology in the hopes of developing newer-generation therapies. By combining novel agents with current cytotoxic chemotherapies and radiation therapy and personalizing them to each patient based on specific biomarkers, the goal of prolonging a patient’s life could be achieved. Here we review the most effective therapies that have been used for the treatment of pancreatic cancer and discuss the future potential of therapeutic options.
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37
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Kwak YK, Lee JH, Lee MA, Chun HG, Kim DG, You YK, Hong TH, Jang HS. Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer. Radiat Oncol J 2014; 32:49-56. [PMID: 25061572 PMCID: PMC4104219 DOI: 10.3857/roj.2014.32.2.49] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Revised: 05/07/2014] [Accepted: 05/21/2014] [Indexed: 01/29/2023] Open
Abstract
Purpose Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Materials and Methods Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. Results With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Conclusion Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.
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Affiliation(s)
- Yoo-Kang Kwak
- Department of Radiation Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jong Hoon Lee
- Department of Radiation Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Myung-Ah Lee
- Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Hoo-Geun Chun
- Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Dong-Goo Kim
- Department of Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Young Kyoung You
- Department of Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Tae-Ho Hong
- Department of Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Hong Seok Jang
- Department of Radiation Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
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Osayi SN, Bloomston M, Schmidt CM, Ellison EC, Muscarella P. Biomarkers as predictors of recurrence following curative resection for pancreatic ductal adenocarcinoma: a review. BIOMED RESEARCH INTERNATIONAL 2014; 2014:468959. [PMID: 25050350 PMCID: PMC4094702 DOI: 10.1155/2014/468959] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2014] [Revised: 06/02/2014] [Accepted: 06/03/2014] [Indexed: 12/15/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDA) is the fourth most common cancer causing death in the United States. Early tumor recurrence is an important contributor to the dismal prognosis. The availability of an accurate prognostic biomarker for predicting disease recurrence following curative resection will be beneficial for patient care. Most of the currently studied biomarkers remain in the investigational phase, with CA 19-9 being the only biomarker currently approved by the FDA. Herein, we review the utility of CA 19-9 and other investigational cellular, gene, and molecular tumor markers for predicting PDA recurrence following curative surgical resection.
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Affiliation(s)
- Sylvester N. Osayi
- Department of Surgery and Center for Minimally Invasive Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Mark Bloomston
- Department of Surgery and Center for Minimally Invasive Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Carl M. Schmidt
- Department of Surgery and Center for Minimally Invasive Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - E. Christopher Ellison
- Department of Surgery and Center for Minimally Invasive Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Peter Muscarella
- Department of Surgery and Center for Minimally Invasive Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
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Combs SE, Habermehl D, Kessel KA, Bergmann F, Werner J, Naumann P, Jäger D, Büchler MW, Debus J. Prognostic impact of CA 19-9 on outcome after neoadjuvant chemoradiation in patients with locally advanced pancreatic cancer. Ann Surg Oncol 2014; 21:2801-7. [PMID: 24916745 DOI: 10.1245/s10434-014-3607-8] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND To asses the impact of CA 19-9 and weight loss/gain on outcome after neoadjuvant chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). METHODS We analyzed 289 patients with LAPC treated with CRT for LAPC. All patients received concomitant chemotherapy parallel to radiotherapy and adjuvant treatments. CA 19-9 and body weight were collected as prognostic and predictive markers. All patients were included into a regular follow-up with reassessment of resectability. RESULTS Median overall survival in all patients was 14 months. Actuarial overall survival was 37 % at 12 months, 12 % at 24 months, and 4 % at 36 months. Secondary resectability was achieved in 35 % of the patients. R0/R1 resection was significantly associated with increase in overall survival (p = 0.04). Intraoperative radiotherapy was applied in 50 patients, but it did not influence overall survival (p = 0.05). Pretreatment CA 19-9 significantly influenced overall survival using different cutoff values. With increase in CA 19-9 levels, the possibility of secondary surgical resection decreased from 46 % in patients with CA 19-9 levels below 90 U/ml to 31 % in the group with CA 19-9 levels higher than 269 U/ml. DISCUSSION This large group of patients with LAPC treated with neoadjuvant CRT confirms that CA 19-9 and body weight are strong predictive and prognostic factors of outcome. In the future, individual patient factors should be taken into account to tailor treatment.
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Affiliation(s)
- Stephanie E Combs
- Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany,
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40
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Castellanos JA, Merchant NB. Intensity of follow-up after pancreatic cancer resection. Ann Surg Oncol 2013; 21:747-51. [PMID: 24092447 DOI: 10.1245/s10434-013-3289-7] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2013] [Indexed: 01/05/2023]
Abstract
The prognosis of patients diagnosed with pancreatic adenocarcinoma remains dismal. Of the 15-20 % of patients who are candidates for potentially curative resection, 66-92 % will develop recurrent disease. Although guidelines for surveillance in the postoperative setting exist, they are not evidence based, and there is wide variability of strategies utilized. Current surveillance guidelines as suggested by the National Comprehensive Cancer Network (NCCN) include routine history and physical, measurement of serum cancer-associated antigen 19-9 (CA19-9) levels, and computed tomographic imaging at 3- to 6-month intervals for the first 2 years, and annually thereafter. However, the lack of prospective clinical data examining the efficacy of different surveillance strategies has led to a variability of the intensity of follow-up and a lack of consensus on its necessity and efficacy. Recent therapeutic advances may have the potential to significantly alter survival after recurrence, but a careful consideration of current surveillance strategies should be undertaken to optimize existing approaches in the face of high recurrence and low survival rates.
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Affiliation(s)
- Jason A Castellanos
- Division of Surgical Oncology and Endocrine Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
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41
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Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J Gastrointest Oncol 2012. [PMID: 22811878 DOI: 10.3978/j.ssn.2078-6891.2011.021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Serum carbohydrate antigen (CA 19-9) is the most common tumor marker assessed in pancreatic cancer patients; nevertheless few articles have comprehensively evaluated the evidence for its utility in pancreatic cancer management. METHODS Literature search was performed using Medline with keywords "pancreatic cancer", "tumor markers", "CA 19-9", "diagnosis", "screening", "prognosis", "resectability" and "recurrence". All English language articles pertaining to the role of CA 19-9 in pancreatic cancer were critically analyzed to determine its utility as a biomarker for pancreatic cancer. RESULTS Serum CA 19-9 is the most extensively validated pancreatic cancer biomarker with multiple clinical applications. CA 19-9 serum levels have a sensitivity and specificity of 79-81% and 82-90% respectively for the diagnosis of pancreatic cancer in symptomatic patients; but are not useful as a screening marker because of low positive predictive value (0.5-0.9%). Pre-operative CA 19-9 serum levels provide useful prognostic information as patients with normal levels (<37 U/mL) have a prolonged median survival (32-36 months) compared to patients with elevated levels (>37 U/mL) (12-15 months). A CA 19-9 serum level of <100 U/mL implies likely resectable disease whereas levels >100 U/mL suggest unresectablity or metastatic disease. Normalization or a decrease in post-operative CA 19-9 serum levels by ≥20-50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA 19-9 serum levels to normalize or an increase. Important limitations to CA 19-9 serum level evaluation in pancreatic cancer include poor sensitivity, false negative results in Lewis negative phenotype (5-10%) and increased false positivity in the presence of obstructive jaundice (10-60%). CONCLUSIONS CA 19-9 is the most extensively studied and validated serum biomarker for the diagnosis of pancreatic cancer in symptomatic patients. CA 19-9 serum levels can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. However, non-specific expression in several benign and malignant diseases, false negative results in Lewis negative genotype and an increased false positive results in the presence of obstructive jaundice severely limit the universal applicability of serum CA 19-9 levels in pancreatic cancer management.
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Haus-Cohen M, Assaraf YG, Binyamin L, Benhar I, Reiter Y. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J Gastrointest Oncol 2012; 109:750-8. [PMID: 14999785 DOI: 10.1002/ijc.20037] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Serum carbohydrate antigen (CA 19-9) is the most common tumor marker assessed in pancreatic cancer patients; nevertheless few articles have comprehensively evaluated the evidence for its utility in pancreatic cancer management. METHODS Literature search was performed using Medline with keywords "pancreatic cancer", "tumor markers", "CA 19-9", "diagnosis", "screening", "prognosis", "resectability" and "recurrence". All English language articles pertaining to the role of CA 19-9 in pancreatic cancer were critically analyzed to determine its utility as a biomarker for pancreatic cancer. RESULTS Serum CA 19-9 is the most extensively validated pancreatic cancer biomarker with multiple clinical applications. CA 19-9 serum levels have a sensitivity and specificity of 79-81% and 82-90% respectively for the diagnosis of pancreatic cancer in symptomatic patients; but are not useful as a screening marker because of low positive predictive value (0.5-0.9%). Pre-operative CA 19-9 serum levels provide useful prognostic information as patients with normal levels (<37 U/mL) have a prolonged median survival (32-36 months) compared to patients with elevated levels (>37 U/mL) (12-15 months). A CA 19-9 serum level of <100 U/mL implies likely resectable disease whereas levels >100 U/mL suggest unresectablity or metastatic disease. Normalization or a decrease in post-operative CA 19-9 serum levels by ≥20-50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA 19-9 serum levels to normalize or an increase. Important limitations to CA 19-9 serum level evaluation in pancreatic cancer include poor sensitivity, false negative results in Lewis negative phenotype (5-10%) and increased false positivity in the presence of obstructive jaundice (10-60%). CONCLUSIONS CA 19-9 is the most extensively studied and validated serum biomarker for the diagnosis of pancreatic cancer in symptomatic patients. CA 19-9 serum levels can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. However, non-specific expression in several benign and malignant diseases, false negative results in Lewis negative genotype and an increased false positive results in the presence of obstructive jaundice severely limit the universal applicability of serum CA 19-9 levels in pancreatic cancer management.
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Affiliation(s)
- Maya Haus-Cohen
- Department of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel
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43
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Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J Gastrointest Oncol 2012; 3:105-19. [PMID: 22811878 DOI: 10.3978/j.issn.2078-6891.2011.021] [Citation(s) in RCA: 341] [Impact Index Per Article: 26.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2011] [Accepted: 04/27/2011] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Serum carbohydrate antigen (CA 19-9) is the most common tumor marker assessed in pancreatic cancer patients; nevertheless few articles have comprehensively evaluated the evidence for its utility in pancreatic cancer management. METHODS Literature search was performed using Medline with keywords "pancreatic cancer", "tumor markers", "CA 19-9", "diagnosis", "screening", "prognosis", "resectability" and "recurrence". All English language articles pertaining to the role of CA 19-9 in pancreatic cancer were critically analyzed to determine its utility as a biomarker for pancreatic cancer. RESULTS Serum CA 19-9 is the most extensively validated pancreatic cancer biomarker with multiple clinical applications. CA 19-9 serum levels have a sensitivity and specificity of 79-81% and 82-90% respectively for the diagnosis of pancreatic cancer in symptomatic patients; but are not useful as a screening marker because of low positive predictive value (0.5-0.9%). Pre-operative CA 19-9 serum levels provide useful prognostic information as patients with normal levels (<37 U/mL) have a prolonged median survival (32-36 months) compared to patients with elevated levels (>37 U/mL) (12-15 months). A CA 19-9 serum level of <100 U/mL implies likely resectable disease whereas levels >100 U/mL suggest unresectablity or metastatic disease. Normalization or a decrease in post-operative CA 19-9 serum levels by ≥20-50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA 19-9 serum levels to normalize or an increase. Important limitations to CA 19-9 serum level evaluation in pancreatic cancer include poor sensitivity, false negative results in Lewis negative phenotype (5-10%) and increased false positivity in the presence of obstructive jaundice (10-60%). CONCLUSIONS CA 19-9 is the most extensively studied and validated serum biomarker for the diagnosis of pancreatic cancer in symptomatic patients. CA 19-9 serum levels can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. However, non-specific expression in several benign and malignant diseases, false negative results in Lewis negative genotype and an increased false positive results in the presence of obstructive jaundice severely limit the universal applicability of serum CA 19-9 levels in pancreatic cancer management.
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Martin LK, Wei L, Trolli E, Bekaii-Saab T. Elevated baseline CA19-9 levels correlate with adverse prognosis in patients with early- or advanced-stage pancreas cancer. Med Oncol 2012; 29:3101-7. [PMID: 22729400 DOI: 10.1007/s12032-012-0278-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2012] [Accepted: 06/06/2012] [Indexed: 12/16/2022]
Abstract
CA19-9 is the most specific biomarker for pancreas cancer. We investigated the prognostic significance of normal (≤ 37 U/mL) versus elevated (>37 U/mL) CA19-9 levels in patients with resected and advanced pancreas cancer. Relevant data were obtained from patients treated for early-stage or advanced pancreatic adenocarcinoma at our institution. Log-rank tests were used to evaluate relationship between CA19-9 and clinical outcomes of interest for both early- and advanced-stage patients. A total of 123 patients were included (Group A: N = 30 stage I/II; Group B: N = 93 stage III/IV). In group A, elevated preoperative CA19-9 was significantly associated with lymph node involvement (p = 0.031), tumor ≥ 3 cm (p = 0.011), and lack of tumor differentiation (p = 0.048). Failure of postoperative CA19-9 to normalize predicted significantly worse DFS (p = 0.021). For group B, elevated baseline CA19-9 was associated with shorter OS on chemotherapy (p = 0.0008) and decline in CA19-9 >25 % with treatment was a significant predictor of improved OS (p = 0.0099). Higher than normal CA19-9 level is an adverse prognostic factor in both early and advanced settings and may prove to be useful in the selection of patients for more aggressive therapy in future trials. CA19-9 level decrease of >25 % predicts improved survival in advanced disease on chemotherapy.
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Affiliation(s)
- Ludmila Katherine Martin
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, M365 Starling Loving Hall, 320 West 10th Avenue, Columbus, OH 43210, USA
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Winter JM, Yeo CJ, Brody JR. Diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. J Surg Oncol 2012; 107:15-22. [PMID: 22729569 DOI: 10.1002/jso.23192] [Citation(s) in RCA: 175] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2012] [Accepted: 05/18/2012] [Indexed: 12/13/2022]
Abstract
Serum CA 19-9 is the only FDA approved biomarker recommended for use in the routine management of pancreatic ductal adenocarcinoma (PDA). Over 2,000 biomarker studies related to pancreatic cancer appear in the literature, highlighting the need to discover and develop improved tests. Diagnostic biomarkers have implications for early detection of PDA, prognostic markers predict patient survival and recurrence patterns, and predictive markers can help personalize treatment regimens.
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Affiliation(s)
- Jordan M Winter
- Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
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Five year results of US intergroup/RTOG 9704 with postoperative CA 19-9 ≤90 U/mL and comparison to the CONKO-001 trial. Int J Radiat Oncol Biol Phys 2012; 84:e291-7. [PMID: 22682806 DOI: 10.1016/j.ijrobp.2012.04.035] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2012] [Revised: 04/19/2012] [Accepted: 04/21/2012] [Indexed: 11/20/2022]
Abstract
PURPOSE Radiation Therapy Oncology Group (RTOG) trial 9704 was the largest randomized trial to use adjuvant chemoradiation therapy for patients with pancreatic cancer. This report analyzes 5-year survival by serum level of tumor marker CA 19-9 of ≤90 vs >90 U/mL and compares results to the those of the CONKO-001 trial. METHODS AND MATERIALS CA 19-9 expression was analyzed as a dichotomized variable (≤90 vs >90 U/mL). Cox proportional hazard models were used to identify the impact of the CA 19-9 value on overall survival (OS). Actuarial estimates of OS were calculated using the Kaplan-Meier method. RESULTS Both univariate (hazard ratio [HR] = 3.2; 95% confidence interval [CI], 2.3-4.3, P<.0001) and multivariate (HR = 3.1; 95% CI, 2.2-4.2, P<.0001) analyses demonstrated a statistically significant decrease in OS for CA 19-9 serum level of ≥90 U/mL. For patients in the gemcitabine (Gem) treatment arm with CA 19-9 <90 U/mL, median survival was 21 months. For patients with CA 19-9 ≥90 U/mL, this number dropped to 10 months. In patients with pancreatic head tumors in the Gem treatment arm with RT quality assurance per protocol and CA 19-9 of <90 U/mL, median survival and 5-year rate were 24 months and 34%. In comparison, the median survival and 5-year OS rate for patients in the Gem arm of the CONKO trial were 22 months and 21%. CONCLUSIONS This analysis demonstrates that patients with postresection CA 19-9 values ≥90 U/mL had a significantly worse survival. Patients with pancreatic head tumors treated with Gem with CA 19-9 serum level of <90 U/mL and per protocol RT had favorable survival compared to that seen in the CONKO trial. CA 19-9 is a stratification factor for the current RTOG adjuvant pancreas trial (0848).
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Sugiura T, Uesaka K, Kanemoto H, Mizuno T, Sasaki K, Furukawa H, Matsunaga K, Maeda A. Serum CA19-9 is a significant predictor among preoperative parameters for early recurrence after resection of pancreatic adenocarcinoma. J Gastrointest Surg 2012; 16:977-85. [PMID: 22411488 DOI: 10.1007/s11605-012-1859-9] [Citation(s) in RCA: 110] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2011] [Accepted: 02/26/2012] [Indexed: 01/31/2023]
Abstract
OBJECTIVE To evaluate the preoperative factors predictive of postoperative early recurrence in patients with resected pancreatic cancer focusing on the serum CA19-9 value. METHODS One hundred fifty-four patients undergoing surgical resection for pancreatic cancer were enrolled in this study. Univariate and multivariate analyses were performed to determine the predictors of early recurrence which was defined as relapse within 6 months after surgery. RESULTS On ROC curve analysis, the cutoff value of CA19-9 was determined to be 100 U/ml. Of 73 patients with CA19-9 value ≥ 100 U/ml, 39 (53 %) had early recurrence. In contrast, only 9 of 81 patients (11 %) with CA19-9 value < 100 U/ml developed a recurrence at an early period (p < 0.001). Multivariate analysis revealed that CA19-9 value ≥ 100 U/ml (odds ratio, 11.2) were significant predictors of early recurrence. The overall 3- and 5-year survival rates and median survival times were 47.3 %, 40.1 %, and 31 months in patients with CA19-9 value < 100 U/ml and 21.2 %, 9.4 %, and 16 months in patients with CA19-9 value ≥ 100 U/ml (p < 0.001). CONCLUSIONS A preoperative CA19-9 value ≥ 100 U/ml was a significant predictor of early recurrence and a poor prognosis after resection for pancreatic adenocarcinoma.
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Affiliation(s)
- Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan.
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Smith JP, Harms JF, Matters GL, McGovern CO, Ruggiero FM, Liao J, Fino KK, Ortega EE, Gilius EL, Phillips JA. A single nucleotide polymorphism of the cholecystokinin-B receptor predicts risk for pancreatic cancer. Cancer Biol Ther 2012; 13:164-74. [PMID: 22277584 DOI: 10.4161/cbt.13.3.18698] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
There currently are no tests available for early diagnosis or for the identification of patients at risk for development of pancreatic cancer. We report the discovery of single nucleotide polymorphism (SNP) in the cholecystokinin B receptor (CCKBR) gene predicts survival and risk of pancreatic cancer. Growth of human pancreatic cancer is stimulated by gastrin through the CCKBR and an alternatively spliced isoform of the CCKBR gene called CCKCR. One hundred and ten surgically resected benign and malignant pancreatic tissues as well as normal pancreas were prospectively evaluated for CCKBR genotype and protein expression. Analysis demonstrated the expression of the spliced isoform, CCKCR, was associated with a (SNP) (C > A) at position 32 of the intron 4 (IVS 4) of the CCKBR gene. Since the SNP is within an intron, it has not previously been identified in the GWAS studies. Only patients with the A/A or A/C genotypes, exhibited immunoreactivity to a selective CCKCR antibody. Survival among pancreatic cancer patients with the A-SNP was significantly shorter (p = 0.0001, hazard ratio = 3.63) compared with individuals with C/C genotype. Other variables such as surgical margins, lymph node status, histologic grade or adjuvant chemotherapy were not associated with survival. Furthermore, having one or two of the A-alleles was found to increase the risk of pancreatic adenocarcinoma by 174% (p = 0.0192) compared with the C/C wild type. Cancer cells transfected to overexpress the CCKCR demonstrated increased proliferation over controls. Genetic screening for this SNP may aid in early detection of pancreatic cancer in high risk subjects.
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Affiliation(s)
- Jill P Smith
- Penn State Hershey Medical Center, Medicine, Gastroenterology, Hershey, PA USA
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Humphris JL, Chang DK, Johns AL, Scarlett CJ, Pajic M, Jones MD, Colvin EK, Nagrial A, Chin VT, Chantrill LA, Samra JS, Gill AJ, Kench JG, Merrett ND, Das A, Musgrove EA, Sutherland RL, Biankin AV. The prognostic and predictive value of serum CA19.9 in pancreatic cancer. Ann Oncol 2012; 23:1713-22. [PMID: 22241899 PMCID: PMC3387824 DOI: 10.1093/annonc/mdr561] [Citation(s) in RCA: 217] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Current staging methods for pancreatic cancer (PC) are inadequate, and biomarkers to
aid clinical decision making are lacking. Despite the availability of the serum marker
carbohydrate antigen 19.9 (CA19.9) for over two decades, its precise role in the
management of PC is yet to be defined, and as a consequence, it is not widely used. Methods We assessed the relationship between perioperative serum CA19.9 levels, survival and
adjuvant chemotherapeutic responsiveness in a cohort of 260 patients who underwent
operative resection for PC. Results By specifically assessing the subgroup of patients with detectable CA19.9, we
identified potential utility at key clinical decision points. Low postoperative CA19.9
at 3 months (median survival 25.6 vs 14.8 months,
P = 0.0052) and before adjuvant chemotherapy were
independent prognostic factors. Patients with postoperative CA 19.9 levels >90 U/ml
did not benefit from adjuvant chemotherapy
(P = 0.7194) compared with those with a CA19.9 of
≤90 U/ml (median 26.0 vs 16.7 months, P = 0.0108).
Normalization of CA19.9 within 6 months of resection was also an independent favorable
prognostic factor (median 29.9 vs 14.8 months,
P = 0.0004) and normal perioperative CA19.9 levels
identified a good prognostic group, which was associated with a 5-year survival of
42%. Conclusions Perioperative serum CA19.9 measurements are informative in patients with detectable
CA19.9 (defined by serum levels of >5 U/ml) and have potential clinical utility in
predicting outcome and response to adjuvant chemotherapy. Future clinical trials should
prioritize incorporation of CA19.9 measurement at key decision points to prospectively
validate these findings and facilitate implementation.
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Affiliation(s)
- J L Humphris
- Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Australia
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Preoperative CA 19-9 Level Is an Important Prognostic Factor in Patients With Pancreatic Adenocarcinoma Treated With Surgical Resection and Adjuvant Concurrent Chemoradiotherapy. Am J Clin Oncol 2011; 34:567-72. [DOI: 10.1097/coc.0b013e3181f946fc] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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