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Shimane G, Kitago M, Yagi H, Abe Y, Hasegawa Y, Hori S, Tanaka M, Tsuzaki J, Yokoyama Y, Masugi Y, Takemura R, Kitagawa Y. Clinical Impact of Neoadjuvant Therapy for Resectable Pancreatic Ductal Adenocarcinoma: A Single-Center Retrospective Study. Ann Surg Oncol 2025; 32:2830-2840. [PMID: 39847284 PMCID: PMC11882687 DOI: 10.1245/s10434-024-16851-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 12/26/2024] [Indexed: 01/24/2025]
Abstract
BACKGROUND Neoadjuvant therapy is recommended for treating resectable pancreatic ductal adenocarcinoma (PDAC); however, its appropriate use in patients with resectable PDAC remains debatable. OBJECTIVE This study aimed to identify independent poor prognostic factors and evaluate the clinical significance of neoadjuvant therapy in patients with resectable PDAC. METHODS We retrospectively reviewed consecutive patients diagnosed with resectable PDAC at our institute between January 2003 and December 2022. We analyzed poor prognostic factors at the time of diagnosis in patients who underwent upfront surgery using the Cox proportional hazards model for overall survival (OS). The prognostic score was calculated by adding the individual prognostic factor scores. RESULTS Overall, 359 patients were included in this study, with 308 patients undergoing upfront surgery and the remaining 51 patients receiving neoadjuvant therapy. The R0 resection rate was significantly higher in the neoadjuvant therapy group (70.6%) than in the upfront surgery group (64.0%). Multivariate analysis in the upfront surgery group revealed the following independent poor prognostic factors: tumor size ≥ 35 mm, serum albumin level ≤ .5 g/dL, neutrophil-to-lymphocyte ratio ≥ 3.5, carbohydrate antigen 19-9 level ≥ 250 U/mL, and Duke pancreatic monoclonal antigen type 2 level ≥ 750 U/mL. Among patients with prognostic scores of 0-1 (n = 263), the intention-to-treat OS did not significantly differ between the neoadjuvant therapy and upfront surgery groups. Among those patients with a prognostic score of ≥ 2 (n = 96), the neoadjuvant therapy group had significantly longer intention-to-treat OS than the upfront surgery group. CONCLUSIONS Prognostic score-based stratification can help identify patients who could benefit from neoadjuvant therapy.
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Affiliation(s)
- Gaku Shimane
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
| | - Hiroshi Yagi
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Yuta Abe
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Yasushi Hasegawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Shutaro Hori
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Masayuki Tanaka
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Junya Tsuzaki
- Department of Radiology, Keio University School of Medicine, Tokyo, Japan
| | - Yoichi Yokoyama
- Department of Radiology, Keio University School of Medicine, Tokyo, Japan
| | - Yohei Masugi
- Division of Diagnostic Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Ryo Takemura
- Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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Heller M, Mann DA, Katona BW. Current Approaches of Pancreatic Cancer Surveillance in High-Risk Individuals. J Gastrointest Cancer 2025; 56:61. [PMID: 39932614 DOI: 10.1007/s12029-025-01184-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/25/2025] [Indexed: 02/14/2025]
Abstract
Currently, those recommended to undergo pancreatic cancer (PC) surveillance include appropriately aged individuals at high risk of PC due to an identifiable genetic susceptibility or those without identifiable genetic susceptibility who nonetheless have a strong family history of PC. With increases in identification of individuals at high risk for PC and increased use of PC surveillance in clinical practice, there has been increasing debate about who should undergo surveillance as well as how surveillance should be performed including use of imaging and blood-based testing. Furthermore, there is increasing interest in the outcomes of PC surveillance in high-risk individuals with some studies demonstrating that surveillance leads to downstaging of PC and improvements in survival. In this review, we summarize the current state of PC surveillance in high-risk individuals, providing an overview of the risk factors associated with PC, selection of high-risk individuals for PC surveillance, and the current, but non-uniform, recommendations for performing PC surveillance. Additionally, we review approaches to apply various imaging and blood-based tests to surveillance and the outcomes of PC surveillance.
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Affiliation(s)
- Melissa Heller
- Division of Hematology and Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Derek A Mann
- Division of Hematology and Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Bryson W Katona
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Blvd., 751 South Pavilion, Philadelphia, PA, 19104, USA.
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Corradi C, Gentiluomo M, Adsay V, Sainz J, Camisa PR, Wlodarczyk B, Crippa S, Tavano F, Capurso G, Campa D. Multi-omic markers of intraductal papillary mucinous neoplasms progression into pancreatic cancer. Semin Cancer Biol 2025; 109:25-43. [PMID: 39733817 DOI: 10.1016/j.semcancer.2024.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/19/2024] [Accepted: 12/23/2024] [Indexed: 12/31/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal and common form of pancreatic cancer, it has no specific symptoms, and most of the patients are diagnosed when the disease is already at an advanced stage. Chemotherapy typically has only a modest effect, making surgery the most effective treatment option. However, only a small percentage of patients are amenable to surgery. One viable strategy to reduce PDAC death burden associated with the disease is to focus on precursor lesions and identify markers able to predict who will evolve into PDAC. While most PDACs are believed to be preceded by pancreatic intraepithelial neoplasms (PanINs), 5-10 % arise from Intraductal papillary mucinous neoplasms (IPMNs), which are mass-forming cystic lesions that are very common in the general population. IPMNs offer an invaluable model of pancreatic carcinogenesis for researchers to analyse, as well as a target population for PDAC early detection by clinicians. The evolution of IPMN into cancer is a complex and multistep process, therefore the identification of individual markers will not be the solution. In recent years, multiple omics technologies have been instrumental to identify possible biomarkers of IPMN progression and carcinogenesis. The only foreseeable strategy will be to integrate multi-omics data, alongside clinical and morphological features, into a progression score or signature using either standard epidemiologic tools or artificial intelligence. The aim of this manuscript is to review the current knowledge on genetic biomarkers and to briefly mention also additional omics, such as metabolomics, the exposome, the miRNome and epigenomics of IPMNs.
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Affiliation(s)
| | | | - Volkan Adsay
- Department of Pathology, Koç University School of Medicine and Koç University Research Center for Translational Medicine, Istanbul, Turkey
| | - Juan Sainz
- Department of Biochemistry and Molecular Biology, University of Granada, Granada, Spain
| | - Paolo Riccardo Camisa
- Division of Pancreatic Surgery and Transplantation, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Barbara Wlodarczyk
- Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
| | - Stefano Crippa
- Division of Pancreatic Surgery and Transplantation, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Francesca Tavano
- Division of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy
| | - Gabriele Capurso
- Vita-Salute San Raffaele University, Milan, Italy; Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Daniele Campa
- Department of Biology, University of Pisa, Pisa, Italy.
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Vitale F, Zileri Dal Verme L, Paratore M, Negri M, Nista EC, Ainora ME, Esposto G, Mignini I, Borriello R, Galasso L, Alfieri S, Gasbarrini A, Zocco MA, Nicoletti A. The Past, Present, and Future of Biomarkers for the Early Diagnosis of Pancreatic Cancer. Biomedicines 2024; 12:2840. [PMID: 39767746 PMCID: PMC11673965 DOI: 10.3390/biomedicines12122840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 11/30/2024] [Accepted: 12/11/2024] [Indexed: 01/04/2025] Open
Abstract
Pancreatic cancer is one of the most aggressive cancers with a very poor 5-year survival rate and reduced therapeutic options when diagnosed in an advanced stage. The dismal prognosis of pancreatic cancer has guided significant efforts to discover novel biomarkers in order to anticipate diagnosis, increasing the population of patients who can benefit from curative surgical treatment. CA 19-9 is the reference biomarker that supports the diagnosis and guides the response to treatments. However, it has significant limitations, a low specificity, and is inefficient as a screening tool. Several potential biomarkers have been discovered in the serum, urine, feces, and pancreatic juice of patients. However, most of this evidence needs further validation in larger cohorts. The advent of advanced omics sciences and liquid biopsy techniques has further enhanced this field of research. The aim of this review is to analyze the historical evolution of the research on novel biomarkers for the early diagnosis of pancreatic cancer, focusing on the current evidence for the most promising biomarkers from different body fluids and the novel trends in research, such as omics sciences and liquid biopsy, in order to favor the application of modern personalized medicine.
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Affiliation(s)
- Federica Vitale
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Lorenzo Zileri Dal Verme
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Mattia Paratore
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Marcantonio Negri
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Enrico Celestino Nista
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Maria Elena Ainora
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Giorgio Esposto
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Irene Mignini
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Raffaele Borriello
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Linda Galasso
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Sergio Alfieri
- Centro Pancreas, Chirurgia Digestiva, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy;
| | - Antonio Gasbarrini
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Maria Assunta Zocco
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Alberto Nicoletti
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
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Ji Jang H, Soo Lee S, Baek S, Jeong B, Wook Kim D, Hee Kim J, Jung Kim H, Ho Byun J, Lee W, Cheol Kim S. Prognostic implication of extra-pancreatic organ invasion in resectable pancreas ductal adenocarcinoma in the pancreas tail. Eur J Radiol 2024; 181:111715. [PMID: 39241306 DOI: 10.1016/j.ejrad.2024.111715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 07/26/2024] [Accepted: 08/31/2024] [Indexed: 09/09/2024]
Abstract
OBJECTIVES To assess the prognostic significance of extra-pancreatic organ invasion in patients with resectable pancreatic ductal adenocarcinoma (PDAC) in the pancreas tail. MATERIALS & METHODS This retrospective study included patients with resectable PDAC in the pancreas tail who received upfront surgery between 2014 and 2020 at a tertiary institution. Preoperative pancreas protocol computed tomography (CT) scans evaluated tumor size, peripancreatic tumor infiltration, suspicious metastatic lymph nodes, and extra-pancreatic organ invasion. The influence of extra-pancreatic organ invasion, detected by CT or postoperative pathology, on pathologic resection margin status was evaluated using logistic regression. The impact on recurrence-free survival (RFS) was analyzed using multivariable Cox proportional hazard models (clinical-CT and clinical-pathologic). RESULTS The study included 158 patients (mean age, 65 years ± 8.8 standard deviation; 93 men). Extra-pancreatic organ invasion identified by either CT (p = 0.92) or pathology (p = 0.99) was not associated with a positive resection margin. Neither CT (p = 0.42) nor pathological (p = 0.64) extra-pancreatic organ invasion independently correlated with RFS. Independent predictors for RFS included suspicious metastatic lymph node (hazard ratio [HR], 2.05; 95 % confidence interval [CI], 1.08-3.9; p = 0.03) on CT in the clinical-CT model, pathological T stage (HR, 2.97; 95 % confidence interval [CI], 1.39-6.35; p = 0.005 for T2 and HR, 3.78; 95 % CI, 1.64-8.76; p = 0.002 for T3) and adjuvant therapy (HR, 0.62; 95 % confidence interval [CI], 0.42-0.92; p = 0.02) in the clinical-pathologic model. CONCLUSION Extra-pancreatic organ invasion does not independently influence pathologic resection margin status and RFS in patients with resectable PDAC in the pancreas tail after curative-intent resection; therefore, it should not be considered a high-risk factor.
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Affiliation(s)
- Hyeon Ji Jang
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
| | - Seunghee Baek
- Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Boryeong Jeong
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Dong Wook Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jin Hee Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
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Topkan E, Kucuk A, Ozturk D, Ozkan EE, Kılıç Durankuş N, Şenyürek Ş, Selek U, Pehlivan B. High Systemic Immune-Inflammation Index Values Before Treatment Predict Poor Pancreatic Cancer Outcomes After Definitive Chemoradiotherapy. Clin Med Insights Oncol 2024; 18:11795549241298552. [PMID: 39525980 PMCID: PMC11544671 DOI: 10.1177/11795549241298552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 10/22/2024] [Indexed: 11/16/2024] Open
Abstract
Background The systemic immune-inflammation index (SII) is an effective tool for predicting the prognosis of patients with cancer. However, its value in patients with locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) undergoing definitive chemoradiotherapy has yet to be addressed. Therefore, we aimed to retrospectively investigate the prognostic significance of the pretreatment SII on the survival outcomes of patients with unresectable LA-PDAC treated with concurrent chemoradiotherapy (C-CRT). Methods The study included 163 patients with LA-PDAC who had received C-CRT. Using receiver operating characteristic (ROC) curve analysis, the utility of a pre-C-CRT cutoff that could stratify survival results was investigated. The primary and secondary endpoints were the correlations between SII levels and overall survival (OS) and progression-free survival (PFS). Results At a median follow-up period of 15 months (range: 3.2-94.5), the median OS and PFS rates for the entire group were 15.7 months (95% confidence interval [CI]: 13.4-17.9), and 7.8 months (95% CI: 6.1-9.4), respectively. We divided the patients into 2 SII cohorts based on the ROC curve analysis (area under the curve [AUC]: 71.9%; sensitivity: 68.9%; specificity: 66.7%): SII < 538 (N = 70) and SII ⩾ 538 (N = 93). Comparative survival analysis showed significantly inferior median OS (13.0 vs 25.4 months; P < .001) and PFS (7.0 vs 15.2 months; P = .003) in patients with SII ⩾ 538 compared with those with SII < 538 before treatment. In multivariate analyses, the Eastern Cooperative Oncology Group (ECOG) performance of 2, N1-2 lymph node, CA 19-9 > 90 U/mL, and SII ⩾ 538 status emerged as independent prognosticators of inferior OS and PFS. Conclusions Present results indicate that patients with unresectable LA-PDAC who underwent C-CRT and had a pretreatment SII ⩾ 538 had significantly worse OS and PFS outcomes compared with those with lower SII values.
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Affiliation(s)
- Erkan Topkan
- Department of Radiation Oncology, Faculty of Medicine, Baskent University, Adana, Turkey
| | - Ahmet Kucuk
- Clinic of Radiation Oncology, Mersin Education and Research Hospital, Mersin, Turkey
| | - Duriye Ozturk
- Department of Radiation Oncology, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey
| | - Emine Elif Ozkan
- Department of Radiation Oncology, Suleyman Demirel University, Isparta, Turkey
| | | | - Şükran Şenyürek
- Department of Radiation Oncology, Koc University School of Medicine, Istanbul, Turkey
| | - Ugur Selek
- Department of Radiation Oncology, Koc University School of Medicine, Istanbul, Turkey
| | - Berrin Pehlivan
- Department of Radiation Oncology, Bahcesehir University, Istanbul, Turkey
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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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8
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Kawahara S, Aoyama T, Murakawa M, Kanemoto R, Matsushita N, Hashimoto I, Kamiya M, Maezawa Y, Kobayashi S, Ueno M, Yamamoto N, Oshima T, Yukawa N, Saito A, Morinaga S. Clinical usefulness of C-reactive protein-albumin-lymphocyte (CALLY) index as a prognostic biomarker in patients undergoing surgical resection of pancreatic cancer. Langenbecks Arch Surg 2024; 409:317. [PMID: 39432010 DOI: 10.1007/s00423-024-03512-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 10/14/2024] [Indexed: 10/22/2024]
Abstract
PURPOSE The C-reactive protein-albumin-lymphocyte (CALLY) index, which simultaneously evaluates the nutritional, immunological, and inflammatory statuses, is a new prognostic biomarker in patients with various cancers; however, no study has reported the clinical significance of the CALLY index in patients with pancreatic cancer. This study aimed to investigate whether the preoperative CALLY index is a prognostic biomarker in patients undergoing surgical resection of pancreatic cancer. METHODS We retrospectively enrolled 461 patients with pancreatic cancer who underwent surgical resection between January 2013 and December 2022. The overall survival (OS) and relapse-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional hazards regression models. RESULTS The optimal cut-off value for the preoperative CALLY index was 1.9. In the low CALLY group, patients were older (p = 0.012), more patients underwent pancreaticoduodenectomy (p = 0.002), the median tumor size was larger (p < 0.001), more patients had pathologically confirmed metastatic lymph nodes (p = 0.015) and worse pathological stage (p = 0.015), and fewer patients received adjuvant chemotherapy (p = 0.003). A low CALLY index was associated with decreased OS (22.1 vs. 37.9 months) and RFS (12.4 vs. 16.4 months). Univariate and multivariate analyses showed that the preoperative CALLY index was an independent prognostic factor for OS (p < 0.001) and RFS (p = 0.045). CONCLUSION The preoperative CALLY index is a prognostic biomarker for both OS and RFS in patients undergoing surgery for pancreatic cancer.
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Affiliation(s)
- Shinnosuke Kawahara
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-Ku, Yokohama, 241-8515, Japan.
| | - Toru Aoyama
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan
| | - Masaaki Murakawa
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-Ku, Yokohama, 241-8515, Japan
| | - Rei Kanemoto
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-Ku, Yokohama, 241-8515, Japan
| | - Naohiko Matsushita
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-Ku, Yokohama, 241-8515, Japan
| | - Itaru Hashimoto
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan
| | - Mariko Kamiya
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-Ku, Yokohama, 241-8515, Japan
| | - Yukio Maezawa
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan
| | - Satoshi Kobayashi
- Department of Gastroenterology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-Ku, Yokohama, 241-8515, Japan
| | - Makoto Ueno
- Department of Gastroenterology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-Ku, Yokohama, 241-8515, Japan
| | - Naoto Yamamoto
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-Ku, Yokohama, 241-8515, Japan
| | - Takashi Oshima
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-Ku, Yokohama, 241-8515, Japan
| | - Norio Yukawa
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan
| | - Aya Saito
- Department of Surgery, Yokohama City University, 3-9 Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan
| | - Soichiro Morinaga
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-Ku, Yokohama, 241-8515, Japan
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9
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Fields BC, Tzeng CWD. Locally Advanced Pancreas Cancer, Is There a Role for Surgery? Surg Clin North Am 2024; 104:1017-1030. [PMID: 39237161 PMCID: PMC11748233 DOI: 10.1016/j.suc.2024.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/07/2024]
Abstract
Locally advanced pancreatic cancer (LAPC) represents a unique clinical scenario in which the tumor is considered localized but unresectable due to anatomic factors. Despite a consensus against upfront surgery, no standard approach to induction therapy exists for patients with LAPC. Extended systemic therapy has shown promise in establishing tumor response and remains the standard of care. While associated with improved local control, the timing and role of radiation therapy remain in question. Following adequate response to induction chemotherapy, a safe attempt at margin-negative resection can be considered. Special attention should be given to required vascular skeletonization and/or resection with reconstruction.
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Affiliation(s)
- Brittany C Fields
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1484, Houston, TX 77030, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Unit 1484, Houston, TX 77030, USA.
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10
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Crippa S, Malleo G, Mazzaferro V, Langella S, Ricci C, Casciani F, Belfiori G, Galati S, D’Ambra V, Lionetto G, Ferrero A, Casadei R, Ercolani G, Salvia R, Falconi M, Cucchetti A. Futility of Up-Front Resection for Anatomically Resectable Pancreatic Cancer. JAMA Surg 2024; 159:1139-1147. [PMID: 39046713 PMCID: PMC11270270 DOI: 10.1001/jamasurg.2024.2485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 05/07/2024] [Indexed: 07/25/2024]
Abstract
Importance There are currently no clinically relevant criteria to predict a futile up-front pancreatectomy in patients with anatomically resectable pancreatic ductal adenocarcinoma. Objectives To develop a futility risk model using a multi-institutional database and provide unified criteria associated with a futility likelihood below a safety threshold of 20%. Design, Setting, and Participants This retrospective study took place from January 2010 through December 2021 at 5 high- or very high-volume centers in Italy. Data were analyzed during April 2024. Participants included consecutive patients undergoing up-front pancreatectomy at the participating institutions. Exposure Standard management, per existing guidelines. Main Outcomes and Measures The main outcome measure was the rate of futile pancreatectomy, defined as an operation resulting in patient death or disease recurrence within 6 months. Dichotomous criteria were constructed to maintain the futility likelihood below 20%, corresponding to the chance of not receiving postneoadjuvant resection from existing pooled data. Results This study included 1426 patients. The median age was 69 (interquartile range, 62-75) years, 759 patients were male (53.2%), and 1076 had head cancer (75.4%). The rate of adjuvant treatment receipt was 73.7%. For the model construction, the study sample was split into a derivation (n = 885) and a validation cohort (n = 541). The rate of futile pancreatectomy was 18.9% (19.2% in the development and 18.6% in the validation cohort). Preoperative variables associated with futile resection were American Society of Anesthesiologists class (95% CI for coefficients, 0.68-0.87), cancer antigen (CA) 19.9 serum levels (95% CI, for coefficients 0.05-0.75), and tumor size (95% CI for coefficients, 0.28-0.46). Three risk groups associated with an escalating likelihood of futile resection, worse pathological features, and worse outcomes were identified. Four discrete conditions (defined as CA 19.9 levels-adjusted-to-size criteria: tumor size less than 2 cm with CA 19.9 levels less than 1000 U/mL; tumor size less than 3 cm with CA 19.9 levels less than 500 U/mL; tumor size less than 4 cm with CA 19.9 levels less than 150 U/mL; and tumor size less than 5 cm with CA 19.9 levels less than 50 U/mL) were associated with a futility likelihood below 20%. Both disease-free survival and overall survival were significantly longer in patients fulfilling the criteria. Conclusions and relevance In this study, a preoperative model (MetroPancreas) and dichotomous criteria to determine the risk of futile pancreatectomy were developed. This might help in selecting patients for up-front resection or neoadjuvant therapy.
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Affiliation(s)
- Stefano Crippa
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Giuseppe Malleo
- Unit of Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, GB Rossi Hospital, Verona, Italy
| | - Vincenzo Mazzaferro
- Department of Oncology and Hemato-Oncology, University of Milano, Italy and HPB Surgery and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Serena Langella
- Department of General and Oncological Surgery, Mauriziano Hospital, Turin, Italy
| | - Claudio Ricci
- Division of Pancreatic Surgery, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Fabio Casciani
- Unit of Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, GB Rossi Hospital, Verona, Italy
| | - Giulio Belfiori
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Sara Galati
- Department of General and Oncological Surgery, Mauriziano Hospital, Turin, Italy
| | - Vincenzo D’Ambra
- Division of Pancreatic Surgery, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Gabriella Lionetto
- Unit of Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, GB Rossi Hospital, Verona, Italy
| | - Alessandro Ferrero
- Department of General and Oncological Surgery, Mauriziano Hospital, Turin, Italy
| | - Riccardo Casadei
- Division of Pancreatic Surgery, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy
| | - Giorgio Ercolani
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy
- Department of Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Roberto Salvia
- Unit of Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, GB Rossi Hospital, Verona, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy
- Department of Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
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11
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Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1724-1785. [PMID: 39389105 DOI: 10.1055/a-2338-3716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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12
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Seufferlein T, Mayerle J, Boeck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie Exokrines Pankreaskarzinom – Version 3.1. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e874-e995. [PMID: 39389103 DOI: 10.1055/a-2338-3533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/12/2024]
Affiliation(s)
| | | | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Gastroenterologie und Endokrinologie Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Medizinische Klinik und Poliklinik II Onkologie und Hämatologie, Universitätsklinikum Hamburg-Eppendorf, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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13
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Akita H, Mukai Y, Kubo M, Takahashi H, Hasegawa S, Kitakaze M, Matsuura N, Masuike Y, Sugase T, Shinno N, Kanemura T, Hara H, Sueda T, Nishimura J, Yasui M, Omori T, Miyata H, Ohue M, Wada H. A striking elevation of CA19-9 after preoperative therapy negates prognostic benefit from radical surgery in resectable and borderline resectable pancreatic cancer. Surgery 2024; 176:1215-1221. [PMID: 39079828 DOI: 10.1016/j.surg.2024.06.049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 05/28/2024] [Accepted: 06/23/2024] [Indexed: 09/10/2024]
Abstract
BACKGROUND Identifying patients who can be spared nonbeneficial surgery is crucial, as pancreatic cancer surgery is highly invasive, with substantial negative effects on quality of life. The study objective was to investigate a useful indicator of patients who do not gain prognostic benefit from radical surgery after neoadjuvant therapy for resectable and borderline resectable pancreatic cancer. METHOD We compared factors among 609 patients with resectable or borderline resectable pancreatic cancer receiving neoadjuvant therapy during 2005-2019. Patients were divided into a poor-prognosis group (no surgery or postresection recurrence within a year) and a good-prognosis group (no recurrence or recurrence >1 year after resection). RESULTS Patients who experience a recurrence within a year of resection (poor-prognosis group) did no better than patients who received neoadjuvant therapy and progressed but never made it to surgery. The value of carbohydrate antigen 19-9 after neoadjuvant therapy was the most significant indicator to predict the poor prognosis group and the elevation of carbohydrate antigen 19-9 (>200 U/mL) identified only poor prognosis group with high specificity of 96.6%. The overall survival of patients with more than 200 of carbohydrate antigen 19-9 after neoadjuvant therapy was significantly very poor and their 2-year survival rate was only 41.4%. CONCLUSION A striking elevation of carbohydrate antigen 19-9 after neoadjuvant therapy for resectable or borderline resectable pancreatic cancer is a good indicator of poor prognosis. Patients with carbohydrate antigen 19-9 >200 U/mL after neoadjuvant therapy should not undergo radical surgery.
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Affiliation(s)
- Hirofumi Akita
- Department of Surgery, Osaka International Cancer Institute, Japan.
| | - Yosuke Mukai
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Masahiko Kubo
- Department of Surgery, Osaka International Cancer Institute, Japan
| | | | | | | | | | - Yasunori Masuike
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Takahito Sugase
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Naoki Shinno
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Takashi Kanemura
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hisashi Hara
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Toshinori Sueda
- Department of Surgery, Osaka International Cancer Institute, Japan
| | | | - Masayoshi Yasui
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Takeshi Omori
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hiroshi Miyata
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Masayuki Ohue
- Department of Surgery, Osaka International Cancer Institute, Japan
| | - Hiroshi Wada
- Department of Surgery, Osaka International Cancer Institute, Japan
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14
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Bhandare MS, Gupta V, Chaudhari V, Nandy K, Ostwal V, Ramaswamy A, Nashikkar C, Engineer R, Krishnatry R, Shrikhande SV. Differential impact of incrementally elevated CA 19-9 levels on prognosis of resected pancreatic ductal adenocarcinoma. HPB (Oxford) 2024; 26:1237-1247. [PMID: 38944571 DOI: 10.1016/j.hpb.2024.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 06/11/2024] [Accepted: 06/12/2024] [Indexed: 07/01/2024]
Abstract
BACKGROUND CA 19-9 is an extremely useful biomarker for pancreatic ductal adenocarcinomas (PDACs). However, the optimal cut-off and prognostic significance at higher cut-offs are yet to be determined. METHODS Retrospective analysis included patients with PDAC who underwent curative resection from January 2010 to May 2020 at Tata Memorial Centre, Mumbai. The pretherapy CA 19-9 was dichotomized using various cut-off levels and analysed. RESULTS In 244 included patients, the median overall survival (OS) for those with CA19-9 level (IU/ml) < or >78, 200, 500, 1000, and 2000 was 27, 24, 23, 22, 21 months versus 18, 16, 15, 14, 13 months; respectively, and was statistically significant (p-value- 0.002, 0.001, 0.002, 0.002 and 0.004, respectively). The number of recurrences and mortality had significant correlation with CA 19-9 cut-offs. On multivariate analysis, adjuvant treatment completion (p-0.004) and decreasing or stable CA19-9 after Neoadjuvant therapy (NAT) (p- 0.031) were associated with improved OS. CONCLUSION The prognostic significance of CA 19-9 was observed at all the cut-off levels examined, beyond mere elevated value as per the standard cut-off level. In patients with high CA19-9 level, surgery should be offered if technically and conditionally feasible, only when a response in CA19-9 level to NAT is achieved.
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Affiliation(s)
- Manish S Bhandare
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India.
| | - Vikas Gupta
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India
| | - Vikram Chaudhari
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India
| | - Kunal Nandy
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | | | - Reena Engineer
- Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra, India
| | - Rahul Krishnatry
- Department of Radiation Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, Maharashtra, India
| | - Shailesh V Shrikhande
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai 400012, Maharashtra, India
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15
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Munnings R, Gibbs P, Lee B. Evolution of Liquid Biopsies for Detecting Pancreatic Cancer. Cancers (Basel) 2024; 16:3335. [PMID: 39409954 PMCID: PMC11475855 DOI: 10.3390/cancers16193335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 09/26/2024] [Accepted: 09/26/2024] [Indexed: 10/20/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterised by late diagnosis and poor prognosis. Despite advancements, current diagnostic and prognostic strategies remain limited. Liquid biopsy techniques, including circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), circulating tumour exosomes, and proteomics, offer potential solutions to improve PDAC diagnosis, prognostication, and management. A systematic search of Ovid MEDLINE identified studies published between 2019 and 2024, focusing on liquid biopsy biomarkers for PDAC. A total of 49 articles were included. ctDNA research shows some promise in diagnosing and prognosticating PDAC, especially through detecting mutant KRAS in minimal residual disease assays. CTC analyses had low sensitivity for early-stage PDAC and inconsistent prognostic results across subpopulations. Exosomal studies revealed diverse biomarkers with some diagnostic and prognostic potential. Proteomics, although relatively novel, has demonstrated superior accuracy in PDAC diagnosis, including early detection, and notable prognostic capacity. Proteomics combined with CA19-9 analysis has shown the most promising results to date. An update on multi-cancer early detection testing, given its significance for population screening, is also briefly discussed. Liquid biopsy techniques offer promising avenues for improving PDAC diagnosis, prognostication, and management. In particular, proteomics shows considerable potential, yet further research is needed to validate existing findings and comprehensively explore the proteome using an unbiased approach.
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Affiliation(s)
- Ryan Munnings
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia
- Department of Medical Education, Melbourne Medical School, Parkville, VIC 3052, Australia
| | - Peter Gibbs
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia
- Western Health, Footscray, VIC 3011, Australia
| | - Belinda Lee
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia
- Peter MacCallum Cancer Centre, Parkville, VIC 3052, Australia
- Northern Health, Epping, VIC 3076, Australia
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16
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Fujimoto T, Teraishi F, Kanehira N, Tajima T, Sakurai Y, Kondo N, Yamagami M, Kuwada A, Morihara A, Kitamatsu M, Fujimura A, Suzuki M, Takaguchi Y, Shigeyasu K, Fujiwara T, Michiue H. BNCT pancreatic cancer treatment strategy with glucose-conjugated boron drug. Biomaterials 2024; 309:122605. [PMID: 38754291 DOI: 10.1016/j.biomaterials.2024.122605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 05/01/2024] [Accepted: 05/05/2024] [Indexed: 05/18/2024]
Abstract
Multidisciplinary therapy centered on radical surgery for resectable pancreatic cancer is expected to prolong prognosis, but relies on CA19-9 biomarker levels to determine treatment strategy. Boron neutron capture therapy (BNCT) is a chemoradiotherapy using tumor hyperaccumulator boron drugs and neutron irradiation. The purpose of this study is to investigate novel boron drug agents for BNCT for pancreatic cancer. Bioinformatics was used to evaluate the uptake of current boron amino acid (BPA) drugs for BNCT into pancreatic cancer. The expression of the amino acid transporter LAT1, a BPA uptake transporter, was low in pancreatic cancer and even lower in high CA19-9 pancreatic cancer. In contrast, the glucose transporter was high in high CA19-9 pancreatic cancers and inversely correlated with LAT1 expression. Considering the low EPR effect in pancreatic cancer, we synthesized a small molecule Glucose-BSH, which is boron BSH bound to glucose, and confirmed its specific uptake in pancreatic cancer. uptake of Glucose-BSH was confirmed in an environment compatible with the tumor microenvironment. The therapeutic efficacy and safety of Glucose-BSH by therapeutic neutron irradiation were confirmed with BNCT. We report Glucose-BSH boron drug discovery study of a Precision Medicine BNCT with application to high CA19-9 pancreatic cancer.
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Affiliation(s)
- Takuya Fujimoto
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan; Neutron Therapy Research Center, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan
| | - Fuminori Teraishi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan
| | - Noriyuki Kanehira
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan; Neutron Therapy Research Center, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan
| | - Tomoyuki Tajima
- Graduate School of Environmental, Life, Natural Science, Okayama University, 3-1-1 Tsushima-Naka, Kita-ku, Okayama, 700-8530, Japan
| | - Yoshinori Sakurai
- Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan
| | - Natsuko Kondo
- Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan
| | - Masahiro Yamagami
- Graduate School of Environmental, Life, Natural Science, Okayama University, 3-1-1 Tsushima-Naka, Kita-ku, Okayama, 700-8530, Japan
| | - Atsushi Kuwada
- Graduate School of Environmental, Life, Natural Science, Okayama University, 3-1-1 Tsushima-Naka, Kita-ku, Okayama, 700-8530, Japan
| | - Akira Morihara
- Graduate School of Environmental, Life, Natural Science, Okayama University, 3-1-1 Tsushima-Naka, Kita-ku, Okayama, 700-8530, Japan
| | - Mizuki Kitamatsu
- Department of Applied Chemistry, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka, 577-8502, Japan
| | - Atsushi Fujimura
- Neutron Therapy Research Center, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan; Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Okayama, 700-8558, Japan
| | - Minoru Suzuki
- Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2, Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan
| | - Yutaka Takaguchi
- Graduate School of Environmental, Life, Natural Science, Okayama University, 3-1-1 Tsushima-Naka, Kita-ku, Okayama, 700-8530, Japan; Department of Material Design and Engineering, Faculty of Sustainable Design, University of Toyama, Toyama, 930-8555, Japan
| | - Kunitoshi Shigeyasu
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan
| | - Toshiyoshi Fujiwara
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan
| | - Hiroyuki Michiue
- Neutron Therapy Research Center, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama City, Okayama, 700-8558, Japan.
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17
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Schouten TJ, van Goor IWJM, Dorland GA, Besselink MG, Bonsing BA, Bosscha K, Brosens LAA, Busch OR, Cirkel GA, van Dam RM, Festen S, Groot Koerkamp B, van der Harst E, de Hingh IHJT, Intven MPW, Kazemier G, Liem MSL, van Lienden KP, Los M, de Meijer VE, Patijn GA, Schreinemakers JMJ, Stommel MWJ, van Tienhoven GJ, Verdonk RC, Verkooijen HM, van Santvoort HC, Molenaar IQ, Daamen LA. The Value of Biological and Conditional Factors for Staging of Patients with Resectable Pancreatic Cancer Undergoing Upfront Resection: A Nationwide Analysis. Ann Surg Oncol 2024; 31:4956-4965. [PMID: 38386198 PMCID: PMC11236903 DOI: 10.1245/s10434-024-15070-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 01/31/2024] [Indexed: 02/23/2024]
Abstract
BACKGROUND Novel definitions suggest that resectability status for pancreatic ductal adenocarcinoma (PDAC) should be assessed beyond anatomical criteria, considering both biological and conditional factors. This has, however, yet to be validated on a nationwide scale. This study evaluated the prognostic value of biological and conditional factors for staging of patients with resectable PDAC. PATIENTS AND METHODS A nationwide observational cohort study was performed, including all consecutive patients who underwent upfront resection of National Comprehensive Cancer Network resectable PDAC in the Netherlands (2014-2019) with complete information on preoperative carbohydrate antigen (CA) 19-9 and Eastern Cooperative Oncology Group (ECOG) performance status. PDAC was considered biologically unfavorable (RB+) if CA19-9 ≥ 500 U/mL and favorable (RB-) otherwise. ECOG ≥ 2 was considered conditionally unfavorable (RC+) and favorable otherwise (RC-). Overall survival (OS) was assessed using Kaplan-Meier and Cox-proportional hazard analysis, presented as hazard ratios (HRs) with 95% confidence interval (CI). RESULTS Overall, 688 patients were analyzed with a median overall survival (OS) of 20 months (95% CI 19-23). OS was 14 months (95% CI 10 months-median not reached) in 20 RB+C+ patients (3%; HR 1.61, 95% CI 0.86-2.70), 13 months (95% CI 11-15) in 156 RB+C- patients (23%; HR 1.86, 95% CI 1.50-2.31), and 21 months (95% CI 12-41) in 47 RB-C+ patients (7%; HR 1.14, 95% CI 0.80-1.62) compared with 24 months (95% CI 22-27) in 465 patients with RB-C- PDAC (68%; reference). CONCLUSIONS Survival after upfront resection of anatomically resectable PDAC is worse in patients with CA19-9 ≥ 500 U/mL, while performance status had no impact. This supports consideration of CA19-9 in preoperative staging of resectable PDAC.
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Affiliation(s)
- Thijs J Schouten
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
| | - Iris W J M van Goor
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
- Department of Radiation Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Galina A Dorland
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
| | - Marc G Besselink
- Amsterdam UMC, Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Bert A Bonsing
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Koop Bosscha
- Department of Surgery, Jeroen Bosch Hospital, Den Bosch, The Netherlands
| | - Lodewijk A A Brosens
- Department of Pathology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Olivier R Busch
- Amsterdam UMC, Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Geert A Cirkel
- Department of Medical Oncology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
- Department of Medical Oncology, Meander Medical Center, Amersfoort, The Netherlands
| | - Ronald M van Dam
- Department of Surgery, Maastricht UMC+,, Maastricht, The Netherlands
- GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
- Department of General and Visceral Surgery, University Hospital Aachen, Aachen, Germany
| | | | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | | | - Ignace H J T de Hingh
- GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Martijn P W Intven
- Department of Radiation Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Geert Kazemier
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Mike S L Liem
- Department of Surgery, Medical Spectrum Twente, Enschede, The Netherlands
| | - Krijn P van Lienden
- Department of Interventional Radiology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - Maartje Los
- Department of Medical Oncology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - Vincent E de Meijer
- Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Gijs A Patijn
- Department of Surgery, Isala Clinics, Zwolle, The Netherlands
| | | | - Martijn W J Stommel
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Geert Jan van Tienhoven
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Amsterdam UMC, Department of Radiation Oncology, location University of Amsterdam, Amsterdam, The Netherlands
| | - Robert C Verdonk
- Department of Gastroenterology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - Helena M Verkooijen
- Imaging Division, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Hjalmar C van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
| | - I Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
| | - Lois A Daamen
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands.
- Imaging Division, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
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18
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Gao X, In H. CA19-9 Benefits Prognostication of Pancreatic Cancer: Is It Time to Add CA19-9 to Its Staging Criteria? Ann Surg Oncol 2024; 31:4839-4840. [PMID: 38709364 DOI: 10.1245/s10434-024-15321-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 04/04/2024] [Indexed: 05/07/2024]
Affiliation(s)
- Xiang Gao
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - Haejin In
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
- Department of Health, Behavior and Policy, Rutgers University, Piscataway, NJ, USA.
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19
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Jeong B, Oh M, Lee SS, Kim N, Kim JS, Lee W, Kim SC, Kim HJ, Kim JH, Byun JH. Predicting Recurrence-Free Survival After Upfront Surgery in Resectable Pancreatic Ductal Adenocarcinoma: A Preoperative Risk Score Based on CA 19-9, CT, and 18F-FDG PET/CT. Korean J Radiol 2024; 25:644-655. [PMID: 38942458 PMCID: PMC11214925 DOI: 10.3348/kjr.2023.1235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 04/11/2024] [Accepted: 04/12/2024] [Indexed: 06/30/2024] Open
Abstract
OBJECTIVE To develop and validate a preoperative risk score incorporating carbohydrate antigen (CA) 19-9, CT, and fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT variables to predict recurrence-free survival (RFS) after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS Patients with resectable PDAC who underwent upfront surgery between 2014 and 2017 (development set) or between 2018 and 2019 (test set) were retrospectively evaluated. In the development set, a risk-scoring system was developed using the multivariable Cox proportional hazards model, including variables associated with RFS. In the test set, the performance of the risk score was evaluated using the Harrell C-index and compared with that of the postoperative pathological tumor stage. RESULTS A total of 529 patients, including 335 (198 male; mean age ± standard deviation, 64 ± 9 years) and 194 (103 male; mean age, 66 ± 9 years) patients in the development and test sets, respectively, were evaluated. The risk score included five variables predicting RFS: tumor size (hazard ratio [HR], 1.29 per 1 cm increment; P < 0.001), maximal standardized uptake values of tumor ≥ 5.2 (HR, 1.29; P = 0.06), suspicious regional lymph nodes (HR, 1.43; P = 0.02), possible distant metastasis on 18F-FDG PET/CT (HR, 2.32; P = 0.03), and CA 19-9 (HR, 1.02 per 100 U/mL increment; P = 0.002). In the test set, the risk score showed good performance in predicting RFS (C-index, 0.61), similar to that of the pathologic tumor stage (C-index, 0.64; P = 0.17). CONCLUSION The proposed risk score based on preoperative CA 19-9, CT, and 18F-FDG PET/CT variables may have clinical utility in selecting high-risk patients with resectable PDAC.
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Affiliation(s)
- Boryeong Jeong
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Minyoung Oh
- Department of Nuclear Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
| | - Nayoung Kim
- Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jae Seung Kim
- Department of Nuclear Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jin Hee Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
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20
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Sumiyoshi T, Uemura K, Shintakuya R, Okada K, Baba K, Harada T, Serikawa M, Ishii Y, Nakamura S, Arihiro K, Murakami Y, Takahashi S. Clinical Utility of the Combined Use of CA19-9 and DUPAN-2 in Pancreatic Adenocarcinoma. Ann Surg Oncol 2024; 31:4665-4672. [PMID: 38652196 PMCID: PMC11164736 DOI: 10.1245/s10434-024-15221-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 03/10/2024] [Indexed: 04/25/2024]
Abstract
PURPOSE Pancreatic ductal adenocarcinoma (PDAC) patients with normal carbohydrate antigen (CA) 19-9 levels can have early-stage cancer or advanced cancer without elevation of CA19-9 level; estimating their malignant potential is difficult. This study investigated the clinical utility of the combined use of preoperative CA 19-9 and Duke pancreatic monoclonal antigen type 2 (DUPAN-2) levels in patients with PDAC. METHODS Patients who underwent curative-intent surgery for PDAC between November 2005 and December 2021 were investigated. Eligible patients were classified into four groups based on these two markers. Among patients with normal CA19-9 levels, those with normal and high DUPAN-2 levels were classified into normal/normal (N/N) and normal/high (N/H) groups, respectively. Among patients with high CA19-9 levels, those with normal and high DUPAN-2 levels were classified into high/normal (H/N) and high/high (H/H) groups, respectively. Survival rates were compared between the groups. RESULTS Among 521 patients, the N/N, N/H, H/N, and H/H groups accounted for 25.0%, 10.6%, 35.1%, and 29.4% of patients, respectively. The proportions of resectable PDAC in the N/N and H/N groups (71.5% and 66.7%) were significantly higher than those in the N/H and H/H groups (49.1% and 54.9%) (P < 0.01). The 5-year survival rates in the N/N, N/H, H/N, and H/H groups were 66.0%, 31.1%, 34.9%, and 29.7%, respectively; the rate in the N/N group was significantly better than those in the other three groups (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). CONCLUSIONS Only patients with normal CA19-9 and DUPNA-2 values should be diagnosed with early-stage PDAC.
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Affiliation(s)
- Tatsuaki Sumiyoshi
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Kenichiro Uemura
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
| | - Ryuta Shintakuya
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Kenjiro Okada
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Kenta Baba
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Takumi Harada
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Masahiro Serikawa
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Yasutaka Ishii
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Shinya Nakamura
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
| | - Koji Arihiro
- Department of Anatomical Pathology, Hiroshima University, Hiroshima, Japan
| | - Yoshiaki Murakami
- Digestive Disease Center, Hiroshima Memorial Hospital, Hiroshima, Japan
| | - Shinya Takahashi
- Department of Surgery, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
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21
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Kobayashi K, Einama T, Tsunenari T, Yonamine N, Takao M, Takihata Y, Tsujimoto H, Ueno H, Tamura K, Ishida J, Kishi Y. Preoperative CA19‑9 level and dual time point FDG‑PET/CT as strong biological indicators of borderline resectability in pancreatic cancer: A retrospective study. Oncol Lett 2024; 27:279. [PMID: 38699663 PMCID: PMC11063755 DOI: 10.3892/ol.2024.14412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Accepted: 03/08/2024] [Indexed: 05/05/2024] Open
Abstract
Tumor resectability, which is increasingly determined based on preoperative chemotherapy, is critical in determining the best treatment for pancreatic cancers. The present study evaluated the usefulness of serum carbohydrate antigen 19-9 (CA19-9) and the preoperative 8F-fluorodeoxyglucose positron emission tomography/computed tomography standardized uptake value (SUV) percentage change (SUVmax%=[(SUVmax2-SUVmax1)/SUVmax1] ×100, where SUVmax1 and SUVmax2 represent the initial and delayed phases, respectively) as biological factors indicative of tumor resectability. The present study included patients with resectable pancreatic cancer who underwent complete surgical resection, for whom both CA19-9 and SUVmax% were documented using cut-off values of 500 U/ml and 24.25%, respectively. Patients were classified as follows: i) High CA19-9 and SUVmax%: both CA19-9 and SUVmax% were elevated; ii) high CA19-9 or SUVmax%: either CA19-9 or SUVmax% were elevated; or iii) low CA19-9 and SUVmax%: neither value met the cut-off. Relapse-free survival (RFS) and overall survival (OS) were calculated, for which univariate and multivariate analyses were performed. Of the 86 patients included, 39 were classified as high CA19-9 or SUVmax% and 12 as high CA19-9 and SUVmax%, with the former group having a significantly worse RFS (vs. low CA19-9 and SUVmax%; P<0.001; vs. high CA19-9 or SUVmax%; P=0.011) and OS (vs. low CA19-9 and SUVmax%, P=0.002; vs. high CA19-9 or SUVmax%, P<0.001). Therefore, high CA19-9 and SUVmax% was an independent predictor of worse RFS (P<0.001) and OS (P=0.003). In conclusion, CA19-9 and SUVmax% can be utilized as biological indicators of resectability.
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Affiliation(s)
- Kazuki Kobayashi
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan
| | - Takahiro Einama
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan
| | - Takazumi Tsunenari
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan
| | - Naoto Yonamine
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan
| | - Mikiya Takao
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan
| | - Yasuhiro Takihata
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan
| | - Hironori Tsujimoto
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan
| | - Hideki Ueno
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan
| | - Katsumi Tamura
- Department of Radiology, Tokorozawa PET Diagnostic Imaging Clinic, Tokorozawa, Saitama 359-1124, Japan
| | - Jiro Ishida
- Department of Radiology, Tokorozawa PET Diagnostic Imaging Clinic, Tokorozawa, Saitama 359-1124, Japan
| | - Yoji Kishi
- Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan
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22
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Waugh E, Glinka J, Breadner D, Liu R, Tang E, Allen L, Welch S, Leslie K, Skaro A. Survival benefit of neoadjuvant FOLFIRINOX for patients with borderline resectable pancreatic cancer. Ann Hepatobiliary Pancreat Surg 2024; 28:229-237. [PMID: 38296221 PMCID: PMC11128787 DOI: 10.14701/ahbps.23-107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 12/05/2023] [Accepted: 12/09/2023] [Indexed: 05/25/2024] Open
Abstract
Backgrounds/Aims While patients with borderline resectable pancreatic cancer (BRPC) are a target population for neoadjuvant chemotherapy (NAC), formal guidelines for neoadjuvant therapy are lacking. We assessed the perioperative and oncological outcomes in patients with BRPC undergoing NAC with FOLFIRINOX for patients undergoing upfront surgery (US). Methods The AHPBA criteria for borderline resectability and/or a CA19-9 level > 100 μ/mL defined borderline resectable tumors retrieved from a prospectively populated institutional registry from 2007 to 2020. The primary outcome was overall survival (OS) at 1 and 3 years. A Cox Proportional Hazard model based on intention to treat was used. A receiver-operator characteristics (ROC) curve was constructed to assess the discriminatory capability of the use of CA19-9 > 100 μ/mL to predict resectability and mortality. Results Forty BRPC patients underwent NAC, while 46 underwent US. The median OS with NAC was 19.8 months (interquartile range [IQR], 10.3-44.24) vs. 10.6 months (IQR, 6.37-17.6) with US. At 1 year, 70% of the NAC group and 41.3% of the US group survived (p = 0.008). At 3 years, 42.5 % of the NAC group and 10.9% of the US group survived (p = 0.001). NAC significantly reduced the hazard of death (adjusted hazard ratio, 0.20; 95% confidence interval, 0.07-0.54; p = 0.001). CA19-9 > 100 μ/mL showed poor discrimination in predicting mortality, but was a moderate predictor of resectability. Conclusions We found a survival benefit of NAC with FOLFIRINOX for BRPC. Greater pre-treatment of CA19-9 and multivessel involvement on initial imaging were associated with progression of the disease following NAC.
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Affiliation(s)
- Evelyn Waugh
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Juan Glinka
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Daniel Breadner
- Division of Medical Oncology, Department of Oncology, Western University, London, ON, Canada
| | - Rachel Liu
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Ephraim Tang
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Laura Allen
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Stephen Welch
- Division of Medical Oncology, Department of Oncology, Western University, London, ON, Canada
| | - Ken Leslie
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
| | - Anton Skaro
- Division of General Surgery, Department of Surgery, Western University, London, ON, Canada
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23
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Muaddi H, Kearse L, Warner S. Multimodal Approaches to Patient Selection for Pancreas Cancer Surgery. Curr Oncol 2024; 31:2260-2273. [PMID: 38668070 PMCID: PMC11049254 DOI: 10.3390/curroncol31040167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 04/05/2024] [Accepted: 04/08/2024] [Indexed: 04/28/2024] Open
Abstract
With an overall 5-year survival rate of 12%, pancreas ductal adenocarcinoma (PDAC) is an aggressive cancer that claims more than 50,000 patient lives each year in the United States alone. Even those few patients who undergo curative-intent resection with favorable pathology reports are likely to experience recurrence within the first two years after surgery and ultimately die from their cancer. We hypothesize that risk factors for these early recurrences can be identified with thorough preoperative staging, thus enabling proper patient selection for surgical resection and avoiding unnecessary harm. Herein, we review evidence supporting multidisciplinary and multimodality staging, comprehensive neoadjuvant treatment strategies, and optimal patient selection for curative-intent surgical resections. We further review data generated from our standardized approach at the Mayo Clinic and extrapolate to inform potential future investigations.
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Affiliation(s)
| | | | - Susanne Warner
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN 55902, USA; (H.M.)
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Dias E Silva D, Chung V. Neoadjuvant treatment for pancreatic cancer: Controversies and advances. Cancer Treat Res Commun 2024; 39:100804. [PMID: 38508132 DOI: 10.1016/j.ctarc.2024.100804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 02/28/2024] [Accepted: 03/02/2024] [Indexed: 03/22/2024]
Abstract
Despite the advancements in the treatment of localized pancreatic cancer, several unresolved issues persist in clinical practice, especially in the neoadjuvant setting. These include determining the criteria for selecting patients for treatment, identifying the most effective chemotherapy regimens, understanding the role of radiotherapy, and accurately assessing how patients respond to treatment. Current strategies for assessing patients before surgery involve thoroughly evaluating their overall health status, analyzing tumor markers, and using advanced imaging techniques. However, existing methods for staging the disease still have limitations when it comes to accurately detecting metastatic cancer. The ongoing debate between performing surgery upfront or administering neoadjuvant therapy highlights the need for robust clinical evidence to guide treatment decisions effectively. This review analyzes the evidence regarding controversial topics in neoadjuvant pancreatic cancer treatment and discusses further research efforts to enhance patient outcomes. To improve the outcomes found with surgery alone, multimodal treatment with chemotherapy.
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Affiliation(s)
| | - Vincent Chung
- City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, United States.
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25
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Li D, Peng Q, Wang L, Cai W, Liang M, Liu S, Ma X, Zhao X. Preoperative prediction of disease-free survival in pancreatic ductal adenocarcinoma patients after R0 resection using contrast-enhanced CT and CA19-9. Eur Radiol 2024; 34:509-524. [PMID: 37507611 DOI: 10.1007/s00330-023-09980-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 05/18/2023] [Accepted: 05/28/2023] [Indexed: 07/30/2023]
Abstract
OBJECTIVES To investigate the efficiency of a combination of preoperative contrast-enhanced computed tomography (CECT) and carbohydrate antigen 19-9 (CA19-9) in predicting disease-free survival (DFS) after R0 resection of pancreatic ductal adenocarcinoma (PDAC). METHODS A total of 138 PDAC patients who underwent curative R0 resection were retrospectively enrolled and allocated chronologically to training (n = 91, January 2014-July 2019) and validation cohorts (n = 47, August 2019-December 2020). Using univariable and multivariable Cox regression analyses, we constructed a preoperative clinicoradiographic model based on the combination of CECT features and serum CA19-9 concentrations, and validated it in the validation cohort. The prognostic performance was evaluated and compared with that of postoperative clinicopathological and tumor-node-metastasis (TNM) models. Kaplan-Meier analysis was conducted to verify the preoperative prognostic stratification performance of the proposed model. RESULTS The preoperative clinicoradiographic model included five independent prognostic factors (tumor diameter on CECT > 4 cm, extrapancreatic organ infiltration, CECT-reported lymph node metastasis, peripheral enhancement, and preoperative CA19-9 levels > 180 U/mL). It better predicted DFS than did the postoperative clinicopathological (C-index, 0.802 vs. 0.787; p < 0.05) and TNM (C-index, 0.802 vs. 0.711; p < 0.001) models in the validation cohort. Low-risk patients had significantly better DFS than patients at the high-risk, defined by the model preoperatively (p < 0.001, training cohort; p < 0.01, validation cohort). CONCLUSIONS The clinicoradiographic model, integrating preoperative CECT features and serum CA19-9 levels, helped preoperatively predict postsurgical DFS for PDAC and could facilitate clinical decision-making. CLINICAL RELEVANCE STATEMENT We constructed a simple model integrating clinical and radiological features for the prediction of disease-free survival after curative R0 resection in patients with pancreatic ductal adenocarcinoma; this novel model may facilitate preoperative identification of patients at high risk of recurrence and metastasis that may benefit from neoadjuvant treatments. KEY POINTS • Existing clinicopathological predictors for prognosis in pancreatic ductal adenocarcinoma (PDAC) patients who underwent R0 resection can only be ascertained postoperatively and do not allow preoperative prediction. • We constructed a clinicoradiographic model, using preoperative contrast-enhanced computed tomography (CECT) features and preoperative carbohydrate antigen 19-9 (CA19-9) levels, and presented it as a nomogram. • The presented model can predict disease-free survival (DFS) in patients with PDAC better than can postoperative clinicopathological or tumor-node-metastasis (TNM) models.
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Affiliation(s)
- Dengfeng Li
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Street South, Chaoyang District, Beijing, 100021, China
| | - Qing Peng
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Leyao Wang
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Street South, Chaoyang District, Beijing, 100021, China
| | - Wei Cai
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Street South, Chaoyang District, Beijing, 100021, China
| | - Meng Liang
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Street South, Chaoyang District, Beijing, 100021, China
| | - Siyun Liu
- GE Healthcare (China), Beijing, 100176, China
| | - Xiaohong Ma
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Street South, Chaoyang District, Beijing, 100021, China.
| | - Xinming Zhao
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.17, Panjiayuan Street South, Chaoyang District, Beijing, 100021, China.
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Boyev A, Prakash LR, Chiang YJ, Newhook TE, Bruno ML, Arvide EM, Dewhurst WL, Kim MP, Ikoma N, Lee JE, Snyder RA, Tzeng CWD, Katz MHG, Maxwell JE. Elevated CA 19-9 is associated with worse survival in patients with resected ampullary adenocarcinoma. Surg Oncol 2023; 51:101994. [PMID: 37742542 DOI: 10.1016/j.suronc.2023.101994] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 08/31/2023] [Accepted: 09/17/2023] [Indexed: 09/26/2023]
Abstract
BACKGROUND The prognostic utility of Carbohydrate Antigen 19-9 (CA 19-9) and Carcinoembryonic Antigen (CEA) in ampullary adenocarcinoma is unclear. We sought to evaluate the association between initial tumor marker levels and survival in patients with resected ampullary adenocarcinoma. METHODS This was a single-institution, retrospective cohort study of consecutive patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma from 1999 to 2021. CA 19-9 was assessed after biliary decompression. Contal and O'Quigley method determined optimal biomarker cutoff levels which were correlated with overall survival (OS) using the Kaplan-Meier method and Cox Proportional Hazards Regression. RESULTS A total of 180 patients underwent pancreatoduodenectomy. Patients with CA 19-9 >100 U/mL had a shorter median OS (28 vs. 132 months, p < 0.001) compared to patients with CA 19-9 ≤ 100 U/mL at diagnosis. Survival was similar between pancreaticobiliary and intestinal tumor subtypes when CA 19-9 was >100 U/mL (OS:25 vs. 33 months, p = 0.415). By Cox regression analysis, CA 19-9 >100 U/mL was independently associated with worse OS (HR 2.8, p = 0.001). CONCLUSIONS Preoperative CA 19-9 >100 U/mL was associated with shorter OS in patients with resected ampullary adenocarcinoma. CA 19-9 may be useful when counseling patients about prognosis or when considering the role of perioperative systemic therapy.
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Affiliation(s)
- Artem Boyev
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Laura R Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yi-Ju Chiang
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Timothy E Newhook
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Morgan L Bruno
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Elsa M Arvide
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Whitney L Dewhurst
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael P Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rebecca A Snyder
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jessica E Maxwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Zhang ZH, Bao YW, Zhao YJ, Wang JQ, Guo JT, Sun SY. Circulating tumor cells as potential prognostic biomarkers for early-stage pancreatic cancer: A systematic review and meta-analysis. World J Clin Oncol 2023; 14:504-517. [PMID: 38059182 PMCID: PMC10696218 DOI: 10.5306/wjco.v14.i11.504] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 09/14/2023] [Accepted: 10/26/2023] [Indexed: 11/22/2023] Open
Abstract
BACKGROUND Pancreatic cancer is difficult to be diagnosed early clinically, while often leads to poor prognosis. If optimal personalized treatment plan can be provided to pancreatic cancer patient at an earlier stage, this can greatly improve overall survival (OS). Circulating tumor cells (CTCs) are a collective term for various types of tumor cells present in the peripheral blood (PB), which are formed by detachment during the development of solid tumor lesions. Most CTCs undergo apoptosis or are phagocytosed after entering the PB, whereas a few can escape and anchor at distal sites to develop metastasis, increasing the risk of death for patients with malignant tumors. AIM To investigate the significance of CTCs in predicting the prognosis of early pancreatic cancer patients. METHODS The PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine, and ChinaInfo databases were searched for articles published through December 2022. Studies were considered qualified if they included patients with early pancreatic cancer, analyzed the prognostic value of CTCs, and were full papers reported in English or Chinese. Researches were selected and assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and the Newcastle-Ottawa Scale criteria. We used a funnel plot to assess publication bias. RESULTS From 1595 publications, we identified eight eligible studies that collectively enrolled 355 patients with pancreatic cancer. Among these original studies, two were carried out in China; three in the United States; and one each in Italy, Spain, and Norway. All eight studies analyzed the relevance between CTCs and the prognosis of patients with early-stage pancreatic cancer after surgery. A meta-analysis showed that the patients that were positive pre-treatment or post-treatment for CTCs were associated with decreased OS [hazard ratio (HR) = 1.93, 95% confidence interval (CI): 1.197-3.126, P = 0.007] and decreased relapse-free/disease-free/progression-free survival (HR = 1.27, 95%CI: 1.137-1.419, P < 0.001) in early-stage pancreatic cancer. Additionally, the results suggest no statistically noticeable publication bias for overall, disease-free, progression-free, and recurrence-free survival. CONCLUSION This pooled meta-analysis shows that CTCs, as biomarkers, can afford reliable prognostic information for patients with early-stage pancreatic cancer and help develop individualized treatment plans.
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Affiliation(s)
- Zi-Han Zhang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Yi-Wen Bao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Ya-Jun Zhao
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Jian-Quan Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Jin-Tao Guo
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Si-Yu Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
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Hu X, Hu D, Fu B, Li H, Ren G, Liu H, Song J, Kang X, Wang X, Pang H, Liu C, Zhang J, Wang Y. Survival benefit of local consolidative therapy for patients with single-organ metastatic pancreatic cancer: a propensity score-matched cross-sectional study based on 17 registries. Front Endocrinol (Lausanne) 2023; 14:1225979. [PMID: 38027134 PMCID: PMC10652880 DOI: 10.3389/fendo.2023.1225979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Accepted: 10/19/2023] [Indexed: 12/01/2023] Open
Abstract
Background The continuous exploration of oligometastatic disease has led to the remarkable achievements of local consolidative therapy (LCT) and favorable outcomes for this disease. Thus, this study investigated the potential benefits of LCT in patients with single-organ metastatic pancreatic ductal adenocarcinoma (PDAC). Methods Patients with single-organ metastatic PDAC diagnosed between 2010 - 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to minimize selection bias. Factors affecting survival were assessed by Cox regression analysis and Kaplan-Meier estimates. Results A total of 12900 patients were identified from the database, including 635 patients who received chemotherapy combined with LCT with a 1:1 PSM with patients who received only chemotherapy. Patients with single-organ metastatic PDAC who received chemotherapy in combination with LCT demonstrated extended median overall survival (OS) by approximately 57%, more than those who underwent chemotherapy alone (11 vs. 7 months, p < 0.001). Furthermore, the multivariate Cox regression analysis revealed that patients that received LCT, younger age (< 65 years), smaller tumor size (< 50 mm), and lung metastasis (reference: liver) were favorable prognostic factors for patients with single-organ metastatic PDAC. Conclusion The OS of patients with single-organ metastatic pancreatic cancer who received LCT may be prolonged compared to those who received only chemotherapy. Nevertheless, additional prospective randomized clinical trials are required to support these findings.
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Affiliation(s)
- Xiaolong Hu
- Department of Radiation Oncology, Beijing Geriatric Hospital, Beijing, China
| | - Dan Hu
- Outpatient Department of Feng Tai District No.4 Retired Cadres Retreat Center, Army PLA, Beijing, China
| | - Bowen Fu
- Department of Radiation Oncology, Air Force Medical Center PLA, Beijing, China
| | - Hongqi Li
- Department of Radiation Oncology, Air Force Medical Center PLA, Beijing, China
| | - Gang Ren
- Department of Radiation Oncology, Peking University Shou Gang Hospital, Beijing, China
| | - Hefei Liu
- Center for Ion Medicine, The First Affiliated Hospital, University of Science and Technology of China, Hefei, China
| | - Jiazhao Song
- Department of Radiation Oncology, Air Force Medical Center PLA, Beijing, China
| | - Xiaoli Kang
- Department of Radiation Oncology, Air Force Medical Center PLA, Beijing, China
| | - Xuan Wang
- Department of Radiation Oncology, Air Force Medical Center PLA, Beijing, China
| | - Haifeng Pang
- Department of Radiation Oncology, Air Force Medical Center PLA, Beijing, China
| | - Chen Liu
- Department of Radiation Oncology, Air Force Medical Center PLA, Beijing, China
| | - Jianchun Zhang
- Department of Radiation Oncology, Beijing Geriatric Hospital, Beijing, China
| | - Yingjie Wang
- Department of Radiation Oncology, Air Force Medical Center PLA, Beijing, China
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Garajová I, Peroni M, Gelsomino F, Leonardi F. A Simple Overview of Pancreatic Cancer Treatment for Clinical Oncologists. Curr Oncol 2023; 30:9587-9601. [PMID: 37999114 PMCID: PMC10669959 DOI: 10.3390/curroncol30110694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/13/2023] [Accepted: 10/24/2023] [Indexed: 11/25/2023] Open
Abstract
Pancreatic cancer (PDAC) is one of the most aggressive solid tumors and is showing increasing incidence. The aim of our review is to provide practical help for all clinical oncologists and to summarize the current management of PDAC using a simple "ABC method" (A-anatomical resectability, B-biological resectability and C-clinical conditions). For anatomically resectable PDAC without any high-risk factors (biological or conditional), the actual standard of care is represented by surgery followed by adjuvant chemotherapy. The remaining PDAC patients should all be treated with initial systemic therapy, though the intent for each is different: for borderline resectable patients, the intent is neoadjuvant; for locally advanced patients, the intent is conversion; and for metastatic PDAC patients, the intent remains just palliative. The actual standard of care in first-line therapy is represented by two regimens: FOLFIRINOX and gemcitabine/nab-paclitaxel. Recently, NALIRIFOX showed positive results over gemcitabine/nab-paclitaxel. There are limited data for maintenance therapy after first-line treatment, though 5-FU or FOLFIRI after initial FOLFIRINOX, and gemcitabine, after initial gemcitabine/nab-paclitaxel, might be considered. We also dedicate space to special rare conditions, such as PDAC with germline BRCA mutations, pancreatic acinar cell carcinoma and adenosquamous carcinoma of the pancreas, with few clinically relevant remarks.
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Affiliation(s)
- Ingrid Garajová
- Medical Oncology Unit, University Hospital of Parma, 43125 Parma, Italy; (M.P.)
| | - Marianna Peroni
- Medical Oncology Unit, University Hospital of Parma, 43125 Parma, Italy; (M.P.)
| | - Fabio Gelsomino
- Department of Oncology and Hematology, University Hospital of Modena, 41124 Modena, Italy
| | - Francesco Leonardi
- Medical Oncology Unit, University Hospital of Parma, 43125 Parma, Italy; (M.P.)
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Miyazawa M, Hirono S, Kawai M, Okada KI, Kitahata Y, Motobayashi H, Sato M, Yoshimura T, Ueno M, Hayami S, Miyamoto A, Shimizu A, Yamaue H. Radiographic duodenal invasion is associated with poor prognosis and early recurrence in patients with pancreatic ductal adenocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:106960. [PMID: 37353425 DOI: 10.1016/j.ejso.2023.06.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 06/05/2023] [Accepted: 06/14/2023] [Indexed: 06/25/2023]
Abstract
BACKGROUND The prognostic impact of radiographic duodenal invasion (rDI) of pancreatic ductal adenocarcinoma (PDAC) has yet to be fully elucidated. This retrospective study aimed to investigate the prognostic and clinicopathological significance of rDI in patients with PDAC after pancreatoduodenectomy (PD). MATERIALS AND METHODS We retrospectively analyzed 223 consecutive patients with resectable (R) and borderline resectable (BR)-PDAC that underwent up-front PD between 2002 and 2018. rDI was assessed by preoperative multi-detector row computed tomography. RESULTS Ninety-three (42%) patients with PDAC had rDI, and all of them had pathological DI (pDI). The rDI(+) group had larger tumor size, BR-PDAC was more common, there was higher serum CA19-9 level, and microscopic lymphovascular invasion was more common than in the rDI(-) group. rDI was associated with significant reduction in overall survival (OS) (P < 0.001) and recurrence-free survival (RFS) (P < 0.001). In multivariate analysis, rDI was an independent prognostic factor in OS [hazard ratio (HR) = 0.52; 95% confidence interval (CI) 0.38-0.73, P < 0.001] and RFS [HR = 0.56; 95% CI 0.40-0.78, P = 0.001]. rDI was also an independent risk factor for early recurrence within 12 months [odds ratio (OR) = 0.36; 95% CI 0.18-0.73, P = 0.005]. rDI had positive correlation with liver recurrence (P = 0.024). CONCLUSION Biological aggressiveness of PDAC with rDI implies short OS and early recurrence with frequent liver metastasis. Aggressive perioperative chemotherapy is recommended to improve prognosis, especially for R-PDAC patients with rDI.
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Affiliation(s)
- Motoki Miyazawa
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Seiko Hirono
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan; Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan.
| | - Manabu Kawai
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Ken-Ichi Okada
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Yuji Kitahata
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Hideki Motobayashi
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Masatoshi Sato
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Tomohiro Yoshimura
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Masaki Ueno
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Shinya Hayami
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Atsushi Miyamoto
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
| | - Atsushi Shimizu
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan; Division of Hepato-Biliary-Pancreatic Surgery, Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan
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Kwaśniewska D, Fudalej M, Nurzyński P, Badowska-Kozakiewicz A, Czerw A, Cipora E, Sygit K, Bandurska E, Deptała A. How A Patient with Resectable or Borderline Resectable Pancreatic Cancer should Be Treated-A Comprehensive Review. Cancers (Basel) 2023; 15:4275. [PMID: 37686551 PMCID: PMC10487031 DOI: 10.3390/cancers15174275] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/22/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high morbidity and mortality in which long-term survival rates remain disastrous. Surgical resection is the only potentially curable treatment for early pancreatic cancer; however, the right patient qualification is crucial for optimizing treatment outcomes. With the rapid development of radiographic and surgical techniques, resectability decisions are made by a multidisciplinary team. Upfront surgery (Up-S) can improve the survival of patients with potentially resectable disease with the support of adjuvant therapy (AT). However, early recurrences are quite common due to the often-undetectable micrometastases occurring before surgery. Adopted by international consensus in 2017, the standardization of the definitions of resectable PDAC (R-PDAC) and borderline resectable PDAC (BR-PDAC) disease was necessary to enable accurate interpretation of study results and define which patients could benefit from neoadjuvant therapy (NAT). NAT is expected to improve the resection rate with a negative margin to provide significant local control and eliminate micrometastases to prolong survival. Providing information about optimal sequential multimodal NAT seems to be key for future studies. This article presents a multidisciplinary concept for the therapeutic management of patients with R-PDAC and BR-PDAC based on current knowledge and our own experience.
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Affiliation(s)
- Daria Kwaśniewska
- Department of Oncology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (D.K.); (M.F.)
| | - Marta Fudalej
- Department of Oncology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (D.K.); (M.F.)
- Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
| | - Paweł Nurzyński
- Department of Oncology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (D.K.); (M.F.)
| | | | - Aleksandra Czerw
- Department of Health Economics and Medical Law, Medical University of Warsaw, 01-445 Warsaw, Poland
- Department of Economic and System Analyses, National Institute of Public Health NIH-National Research Institute, 00-791 Warsaw, Poland
| | - Elżbieta Cipora
- Medical Institute, Jan Grodek State University in Sanok, 38-500 Sanok, Poland
| | - Katarzyna Sygit
- Faculty of Health Sciences, Calisia University, 62-800 Kalisz, Poland
| | - Ewa Bandurska
- Centre for Competence Development, Integrated Care and e-Health, Medical University of Gdansk, 80-204 Gdansk, Poland
| | - Andrzej Deptała
- Department of Oncology, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (D.K.); (M.F.)
- Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
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32
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Jain AJ, Maxwell JE, Katz MHG, Snyder RA. Surgical Considerations for Neoadjuvant Therapy for Pancreatic Adenocarcinoma. Cancers (Basel) 2023; 15:4174. [PMID: 37627202 PMCID: PMC10453019 DOI: 10.3390/cancers15164174] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 08/04/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease process with a 5-year survival rate of only 11%. Neoadjuvant therapy in patients with localized pancreatic cancer has multiple theoretical benefits, including improved patient selection for surgery, early delivery of systemic therapy, and assessment of response to therapy. Herein, we review key surgical considerations when selecting patients for neoadjuvant therapy and curative-intent resection. Accurate determination of resectability at diagnosis is critical and should be based on not only anatomic criteria but also biologic and clinical criteria to determine optimal treatment sequencing. Borderline resectable or locally advanced pancreatic cancer is best treated with neoadjuvant therapy and resection, including vascular resection and reconstruction when appropriate. Lastly, providing nutritional, prehabilitation, and supportive care interventions to improve patient fitness prior to surgical intervention and adequately address the adverse effects of therapy is critical.
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Affiliation(s)
| | | | | | - Rebecca A. Snyder
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (A.J.J.)
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33
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Partyka O, Pajewska M, Kwaśniewska D, Czerw A, Deptała A, Budzik M, Cipora E, Gąska I, Gazdowicz L, Mielnik A, Sygit K, Sygit M, Krzych-Fałta E, Schneider-Matyka D, Grochans S, Cybulska AM, Drobnik J, Bandurska E, Ciećko W, Ratajczak P, Kamecka K, Marczak M, Kozłowski R. Overview of Pancreatic Cancer Epidemiology in Europe and Recommendations for Screening in High-Risk Populations. Cancers (Basel) 2023; 15:3634. [PMID: 37509296 PMCID: PMC10377815 DOI: 10.3390/cancers15143634] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/11/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023] Open
Abstract
Pancreatic cancer is the seventh most common cause of death in the group of oncological diseases. Due to the asymptomatic course, early diagnosis is difficult. Currently, early detection methods are only used in high-risk groups. A literature review based on the available results of observational studies on patients with pancreatic cancer and people from high-risk groups was used to summarize the knowledge on risk factors. The GLOBOCAN 2020 data were used to assess the epidemiological situation in Europe. A summary of screening recommendations was prepared based on the available documents from medical organizations and associations. Pancreatic cancer risk factors are divided into two main groups: non-modifiable factors, e.g., hereditary factors and age, which increase the risk of developing this disease, and modifiable factors-BMI, smoking, and alcohol consumption. Hereditary factors account for 10% of pancreatic cancer cases. The highly specialized methods of early detection, (MRI, CT, or EUS) are used for screening high-risk populations. Of all the imaging methods, EUS is considered the most sensitive for pancreatic cancer and allows an accurate assessment of the size of even small lesions (<30 mm) and the extent of tumour infiltration into blood vessels. The available studies vary on the level of sensitivity and specificity of these methods for the diagnosis of pancreatic cancer. EUS, MRI, and CT are also expensive procedures and in some patients can be invasive, which is one of the arguments against the introduction of population screening programs based on imaging methods. Therefore, it is important to look for viable solutions that would improve early detection. This is important from the point of view of healthcare systems in Europe, where almost 29% of all global pancreatic cancer cases are reported.
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Affiliation(s)
- Olga Partyka
- Department of Health Economics and Medical Law, Medical University of Warsaw, 01-445 Warsaw, Poland
| | - Monika Pajewska
- Department of Health Economics and Medical Law, Medical University of Warsaw, 01-445 Warsaw, Poland
- Department of Economic and System Analyses, National Institute of Public Health NIH-National Research Institute, 00-791 Warsaw, Poland
| | - Daria Kwaśniewska
- Department of Oncology, The National Institute of Medicine of the Ministry of Interior and Administration, 02-507 Warsaw, Poland
| | - Aleksandra Czerw
- Department of Health Economics and Medical Law, Medical University of Warsaw, 01-445 Warsaw, Poland
- Department of Economic and System Analyses, National Institute of Public Health NIH-National Research Institute, 00-791 Warsaw, Poland
| | - Andrzej Deptała
- Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
| | - Michał Budzik
- Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
| | - Elżbieta Cipora
- Medical Institute, Jan Grodek State University in Sanok, 38-500 Sanok, Poland
| | - Izabela Gąska
- Medical Institute, Jan Grodek State University in Sanok, 38-500 Sanok, Poland
| | - Lucyna Gazdowicz
- Medical Institute, Jan Grodek State University in Sanok, 38-500 Sanok, Poland
| | - Aneta Mielnik
- Medical Institute, Jan Grodek State University in Sanok, 38-500 Sanok, Poland
| | - Katarzyna Sygit
- Faculty of Health Sciences, Calisia University, 62-800 Kalisz, Poland
| | - Marian Sygit
- Faculty of Health Sciences, Calisia University, 62-800 Kalisz, Poland
| | - Edyta Krzych-Fałta
- Department of Basic of Nursing, Faculty of Health Sciences, Medical University of Warsaw, 01-445 Warsaw, Poland
| | - Daria Schneider-Matyka
- Department of Nursing, Faculty of Health Sciences, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland
| | - Szymon Grochans
- Department of Specialised Nursing, Faculty of Health Sciences, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland
| | - Anna M Cybulska
- Department of Nursing, Faculty of Health Sciences, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland
| | - Jarosław Drobnik
- Department of Family Medicine, Faculty of Medicine, Wrocław Medical University, 51-141 Wrocław, Poland
| | - Ewa Bandurska
- Center for Competence Development, Integrated Care and e-Health, Medical University of Gdansk, 80-204 Gdansk, Poland
| | - Weronika Ciećko
- Center for Competence Development, Integrated Care and e-Health, Medical University of Gdansk, 80-204 Gdansk, Poland
| | - Piotr Ratajczak
- Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, 60-806 Poznań, Poland
| | - Karolina Kamecka
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-131 Lodz, Poland
| | - Michał Marczak
- Collegium Management, WSB Merito University in Warsaw, 03-204 Warszawa, Poland
| | - Remigiusz Kozłowski
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-131 Lodz, Poland
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Omiya K, Oba A, Inoue Y, Kobayashi K, Wu YHA, Ono Y, Sato T, Sasaki T, Ozaka M, Sasahira N, Ito H, Saiura A, Takahashi Y. Serum DUPAN-2 could be an Alternative Biological Marker for CA19-9 Nonsecretors with Pancreatic Cancer. Ann Surg 2023; 277:e1278-e1283. [PMID: 35081567 DOI: 10.1097/sla.0000000000005395] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE This study investigates the use of serum DUPAN-2 in predicting the PC progression in CA19-9 nonsecretors. BACKGROUND Although we previously reported that serum CA19-9 >500U/ mL is a poor prognostic factor and an indication for enhanced neoadjuvant treatment, there is not a biomarker surrogate that equivalently predicts prognosis for CA19-9 nonsecretors. METHODS We evaluated consecutive PC patients who underwent pancreatectomy from 2005 to 2019. All patients were categorized as either nonsecretor or secretor (CA19-9 ≤ or >2.0U/mL). RESULTS Of the 984 resected PC patients, 94 (9.6%) were nonsecretors and 890 (90.4%) were secretors. The baseline characteristics were not statistically different between the 2 groups except for the level of DUPAN-2 (720 vs. 100U/mL, P < 0.001). Survival curves after resection were similar between the 2 groups (29.4 months vs. 31.3 months, P = 0.900). Survival curves of patients with DUPAN-2 >2000U/mL in the nonsecretors and patients with CA19-9 >500U/mL in the secretors were nearly equivalent as well (hazard ratio 2.08 vs. 1.89). In the multivariate analysis, DUPAN-2 >2000U/mL (hazard ratio 2.53, P = 0.010) was identified as independent prognostic factor after resection. CONCLUSION DUPAN-2 >2000U/mL in CA19-9 nonsecretors can be an unfavorable factor that corresponds to CA19-9 >500U/mL in CA19-9 secretors which is an indicator for enhanced neoadjuvant treatment. The current results shed light on the subset of nonsecretors with poor prognosis that were traditionally categorized in a group with a more favorable prognosis group.
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Affiliation(s)
- Kojiro Omiya
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Atsushi Oba
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Inoue
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kosuke Kobayashi
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Y H Andrew Wu
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Yoshihiro Ono
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takafumi Sato
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takashi Sasaki
- Department of Gastroenterological medicine, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; and
| | - Masato Ozaka
- Department of Gastroenterological medicine, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; and
| | - Naoki Sasahira
- Department of Gastroenterological medicine, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; and
| | - Hiromichi Ito
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akio Saiura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Yu Takahashi
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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Springfeld C, Ferrone CR, Katz MHG, Philip PA, Hong TS, Hackert T, Büchler MW, Neoptolemos J. Neoadjuvant therapy for pancreatic cancer. Nat Rev Clin Oncol 2023; 20:318-337. [PMID: 36932224 DOI: 10.1038/s41571-023-00746-1] [Citation(s) in RCA: 155] [Impact Index Per Article: 77.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/21/2023] [Indexed: 03/19/2023]
Abstract
Patients with localized pancreatic ductal adenocarcinoma (PDAC) are best treated with surgical resection of the primary tumour and systemic chemotherapy, which provides considerably longer overall survival (OS) durations than either modality alone. Regardless, most patients will have disease relapse owing to micrometastatic disease. Although currently a matter of some debate, considerable research interest has been focused on the role of neoadjuvant therapy for all forms of resectable PDAC. Whilst adjuvant combination chemotherapy remains the standard of care for patients with resectable PDAC, neoadjuvant chemotherapy seems to improve OS without necessarily increasing the resection rate in those with borderline-resectable disease. Furthermore, around 20% of patients with unresectable non-metastatic PDAC might undergo resection following 4-6 months of induction combination chemotherapy with or without radiotherapy, even in the absence of a clear radiological response, leading to improved OS outcomes in this group. Distinct molecular and biological responses to different types of therapies need to be better understood in order to enable the optimal sequencing of specific treatment modalities to further improve OS. In this Review, we describe current treatment strategies for the various clinical stages of PDAC and discuss developments that are likely to determine the optimal sequence of multimodality therapies by integrating the fundamental clinical and molecular features of the cancer.
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Affiliation(s)
- Christoph Springfeld
- Department of Medical Oncology, National Center for Tumour Diseases, Heidelberg University Hospital, Heidelberg, Germany
| | | | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Philip A Philip
- Wayne State University School of Medicine, Department of Oncology, Henry Ford Cancer Institute, Detroit, MI, USA
| | - Theodore S Hong
- Research and Scientific Affairs, Gastrointestinal Service Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Thilo Hackert
- Department of General, Visceral and Thoracic Surgery, University hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - John Neoptolemos
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
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Marin AM, Sanchuki HBS, Namur GN, Uno M, Zanette DL, Aoki MN. Circulating Cell-Free Nucleic Acids as Biomarkers for Diagnosis and Prognosis of Pancreatic Cancer. Biomedicines 2023; 11:biomedicines11041069. [PMID: 37189687 DOI: 10.3390/biomedicines11041069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/15/2023] [Accepted: 03/24/2023] [Indexed: 04/05/2023] Open
Abstract
A lack of reliable early diagnostic tools represents a major challenge in the management of pancreatic cancer (PCa), as the disease is often only identified after it reaches an advanced stage. This highlights the urgent need to identify biomarkers that can be used for the early detection, staging, treatment monitoring, and prognosis of PCa. A novel approach called liquid biopsy has emerged in recent years, which is a less- or non-invasive procedure since it focuses on plasmatic biomarkers such as DNA and RNA. In the blood of patients with cancer, circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) have been identified such as DNA, mRNA, and non-coding RNA (miRNA and lncRNA). The presence of these molecules encouraged researchers to investigate their potential as biomarkers. In this article, we focused on circulating cfNAs as plasmatic biomarkers of PCa and analyzed their advantages compared to traditional biopsy methods.
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Affiliation(s)
- Anelis Maria Marin
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Prof Algacyr Munhoz Mader 3775 Street, Curitiba 81350-010, Brazil
| | - Heloisa Bruna Soligo Sanchuki
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Prof Algacyr Munhoz Mader 3775 Street, Curitiba 81350-010, Brazil
| | - Guilherme Naccache Namur
- Center for Translational Research in Oncology (LIM24), Departamento de Radiologia e Oncologia, Instituto do Câncer do Estado de São Paulo (ICESP), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo 01246-000, Brazil
| | - Miyuki Uno
- Center for Translational Research in Oncology (LIM24), Departamento de Radiologia e Oncologia, Instituto do Câncer do Estado de São Paulo (ICESP), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo 01246-000, Brazil
| | - Dalila Luciola Zanette
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Prof Algacyr Munhoz Mader 3775 Street, Curitiba 81350-010, Brazil
| | - Mateus Nóbrega Aoki
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Prof Algacyr Munhoz Mader 3775 Street, Curitiba 81350-010, Brazil
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Botta GP, Huynh TR, Spierling‐Bagsic SR, Agelidis A, Schaffer R, Lin R, Sigal D. Neoadjuvant chemotherapy and radiotherapy outcomes in borderline-resectable and locally-advanced pancreatic cancer patients. Cancer Med 2023; 12:7713-7723. [PMID: 36478411 PMCID: PMC10134275 DOI: 10.1002/cam4.5523] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 11/07/2022] [Accepted: 11/25/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND There is no agreed upon standard of care for borderline-resectable pancreatic cancer (BRPC) or locally-advanced pancreatic cancer (LAPC) patients regarding the benefit of chemotherapy or radiation alone or in combination. PATIENTS AND METHODS We completed a retrospective cohort analysis of BRPC and LAPC patients at a cancer center with expertise in multi-disciplinary pancreatic ductal adenocarcinoma (PDAC) treatment over a 5-year period from 03/01/2014 to 03/01/2019 (cut-off date). The total evaluable newly diagnosed, treatment naïve, BRPC, and LAPC patients with adequate organ function and ability to obtain treatment after multidisciplinary review was 52 patients. After analysis, patients were evaluated for rates of resection, extent of resection (R0 or R1), median progression-free survival (mPFS), and median overall survival (mOS). RESULTS Patients were treated with chemotherapy alone (gemcitabine and nab-paclitaxel = 77% (20/26); FOLFIRINOX = 19% (5/26); single agent gemcitabine 3.8% (1/26)), or chemotherapy followed by chemoradiation (gemcitabine +5 Gy × 5 weeks), or chemoradiation alone prior to re-staging and potential resection. Of the 29% (15/52) of patients who went on to surgical resection, 73% (11/15) achieved R0 resection. An R0 resection was achieved in 35% (9/26) of patients treated with chemotherapy alone, 7.6% (1/13) in a patient treated with chemotherapy followed by radiation, and 7.6% (1/13) with concurrent chemoradiotherapy alone. Chemotherapy alone achieved a mPFS of 16.4 months (p < 0.0025) and mOS of 26.2 months (p < 0.0001), chemotherapy followed by chemoradiation was 13.0 months and 14.9 months respectively, while concurrent chemoradiotherapy was 6.9 months and 7.3 months. CONCLUSIONS AND RELEVANCE BRPC and LAPC patients capable of surgery after only receiving neoadjuvant treatment with chemotherapy had higher rates of R0 resection with prolonged median PFS and OS compared with any patient needing combination chemotherapy with radiotherapy.
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Affiliation(s)
- Gregory P. Botta
- Division of Hematology/Oncology, Department of Medicine, Moores Cancer CenterUniversity of California San DiegoLa JollaCaliforniaUSA
- Division of Medical OncologyScripps MD Anderson Cancer CenterLa JollaCaliforniaUSA
- Scripps Research Translational InstituteLa JollaCaliforniaUSA
| | - Tridu R. Huynh
- Division of Hematology/Oncology, Department of Medicine, Moores Cancer CenterUniversity of California San DiegoLa JollaCaliforniaUSA
- Scripps Research Translational InstituteLa JollaCaliforniaUSA
- Division of Internal MedicineScripps Clinic/Green HospitalLa JollaCaliforniaUSA
| | | | - Alexander Agelidis
- Scripps Research Translational InstituteLa JollaCaliforniaUSA
- Division of Internal MedicineScripps Clinic/Green HospitalLa JollaCaliforniaUSA
| | - Randolph Schaffer
- Division of Hepatopancreatobiliary SurgeryScripps MD Anderson Cancer CenterLa JollaCaliforniaUSA
| | - Ray Lin
- Division of Radiation OncologyScripps MD Anderson Cancer CenterLa JollaCaliforniaUSA
| | - Darren Sigal
- Division of Medical OncologyScripps MD Anderson Cancer CenterLa JollaCaliforniaUSA
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Nitschke C, Markmann B, Walter P, Badbaran A, Tölle M, Kropidlowski J, Belloum Y, Goetz MR, Bardenhagen J, Stern L, Tintelnot J, Schönlein M, Sinn M, van der Leest P, Simon R, Heumann A, Izbicki JR, Pantel K, Wikman H, Uzunoglu FG. Peripheral and Portal Venous KRAS ctDNA Detection as Independent Prognostic Markers of Early Tumor Recurrence in Pancreatic Ductal Adenocarcinoma. Clin Chem 2023; 69:295-307. [PMID: 36644936 DOI: 10.1093/clinchem/hvac214] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 11/17/2022] [Indexed: 01/17/2023]
Abstract
BACKGROUND KRAS circulating tumor DNA (ctDNA) has shown biomarker potential for pancreatic ductal adenocarcinoma (PDAC) but has not been applied in clinical routine yet. We aim to improve clinical applicability of ctDNA detection in PDAC and to study the impact of blood-draw site and time point on the detectability and prognostic role of KRAS mutations. METHODS 221 blood samples from 108 PDAC patients (65 curative, 43 palliative) were analyzed. Baseline peripheral and tumor-draining portal venous (PV), postoperative, and follow-up blood were analyzed and correlated with prognosis. RESULTS Significantly higher KRAS mutant detection rates and copy numbers were observed in palliative compared to curative patients baseline blood (58.1% vs 24.6%; P = 0.002; and P < 0.001). Significantly higher KRAS mutant copies were found in PV blood compared to baseline (P < 0.05) samples. KRAS detection in pre- and postoperative and PV blood were significantly associated with shorter recurrence-free survival (all P < 0.015) and identified as independent prognostic markers. KRAS ctDNA status was also an independent unfavorable prognostic factor for shorter overall survival in both palliative and curative cohorts (hazard ratio [HR] 4.9, P = 0.011; HR 6.9, P = 0.008). CONCLUSIONS KRAS ctDNA detection is an independent adverse prognostic marker in curative and palliative PDAC patients-at all sites of blood draw and a strong follow-up marker. The most substantial prognostic impact was seen for PV blood, which could be an effective novel tool for identifying prognostic borderline patients-guiding future decision-making on neoadjuvant treatment despite anatomical resectability. In addition, higher PV mutant copy numbers contribute to an improved technical feasibility.
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Affiliation(s)
- Christine Nitschke
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
- Mildred Scheel Cancer Career Center, Hamburg 20246, Germany
- Institute of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Benedikt Markmann
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
- Institute of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Philipp Walter
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
- Institute of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Anita Badbaran
- Clinic for Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Marie Tölle
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
- Institute of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Jolanthe Kropidlowski
- Institute of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Yassine Belloum
- Institute of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Mara R Goetz
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Jan Bardenhagen
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Louisa Stern
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Joseph Tintelnot
- II. Medical Clinic and Polyclinic (Oncology), University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Martin Schönlein
- II. Medical Clinic and Polyclinic (Oncology), University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Marianne Sinn
- II. Medical Clinic and Polyclinic (Oncology), University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Paul van der Leest
- Department of Pathology, University Medical Center, University of Groningen, Groningen 9700 RB, Netherlands
| | - Ronald Simon
- Institute of Pathology, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Asmus Heumann
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Jakob R Izbicki
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Klaus Pantel
- Institute of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Harriet Wikman
- Institute of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Faik G Uzunoglu
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg 20246, Germany
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Thalji SZ, Kamgar M, George B, Aldakkak M, Christians KK, Clarke CN, Erickson BA, Hall WA, Tolat PP, Smith ZL, Evans DB, Tsai S. CA19-9 Response to First-Line Neoadjuvant FOLFIRINOX and Second-Line Gemcitabine/Nab-Paclitaxel for Patients with Operable Pancreatic Cancer. Ann Surg Oncol 2023; 30:3013-3021. [PMID: 36788189 DOI: 10.1245/s10434-022-13055-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 12/22/2022] [Indexed: 02/16/2023]
Abstract
BACKGROUND Response to second-line (2L) neoadjuvant therapy for operable pancreatic cancer (PC) is understudied. This study examined carbohydrate antigen 19-9 (CA19-9) response to first-line (1L) and 2L chemotherapy. METHODS The study identified patients with operable PC and elevated CA19-9 (≥ 35 U/mL with total bilirubin < 2 mg/dL) who received 1L FOLFIRINOX (FFX). The patients were restaged after 2 months and based on response, received additional FFX or gemcitabine/nab-paclitaxel (GnP) as part of total neoadjuvant therapy. Response was defined as a decrease in tumor size on computed tomography (CT) imaging or a decline in CA19-9 of 50% or more and preserved performance status. RESULTS For operable PC with an elevated CA19-9, 108 patients received 1L FFX. After 2 months of chemotherapy, the decision was made to continue FFX (FFX ≥ FFX) for 76 (70%) of the 108 patients and switch to GnP (FFX ≥ GnP)) for 32 (30%) of the patients. Of the 32 FFX ≥ GnP patients, 27 had no evidence of radiographic or biochemical (CA19-9) response to 1L FFX. Of these 27 patients, 26 (96%) demonstrated a response to 2L GnP. After 4 months of chemotherapy, 62 (82%) of the 76 FFX ≥ FFX patients had a CA19-9 response compared with 31 (97%) of the 32 FFX ≥ GnP patients (p = 0.04). CONCLUSIONS Lack of biochemical response to 2 months of 1L FFX may identify a subgroup of patients with a very high rate of response to 2L GnP, emphasizing the importance of assessing treatment response at 2-month intervals.
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Affiliation(s)
- Sam Z Thalji
- Department of Surgery, Division of Surgical Oncology, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Mandana Kamgar
- Department of Medicine, Division of Medical Oncology, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Ben George
- Department of Medicine, Division of Medical Oncology, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Mohammed Aldakkak
- Department of Surgery, Division of Surgical Oncology, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Kathleen K Christians
- Department of Surgery, Division of Surgical Oncology, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Callisia N Clarke
- Department of Surgery, Division of Surgical Oncology, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Beth A Erickson
- Department of Radiation Oncology, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI, USA
| | - William A Hall
- Department of Radiation Oncology, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Parag P Tolat
- Department of Radiology, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Zachary L Smith
- Department of Medicine, Division of Gastroenterology and Hepatology, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Douglas B Evans
- Department of Surgery, Division of Surgical Oncology, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Susan Tsai
- Department of Surgery, Division of Surgical Oncology, LaBahn Pancreatic Cancer Program, Medical College of Wisconsin, Milwaukee, WI, USA.
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Lee B, Yoon YS, Kang M, Park Y, Lee E, Jo Y, Lee JS, Lee HW, Cho JY, Han HS. Validation of the Anatomical and Biological Definitions of Borderline Resectable Pancreatic Cancer According to the 2017 International Consensus for Survival and Recurrence in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Upfront Surgery. Ann Surg Oncol 2023; 30:3444-3454. [PMID: 36695994 DOI: 10.1245/s10434-022-13043-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 11/14/2022] [Indexed: 01/26/2023]
Abstract
BACKGROUND The International Consensus Criteria (ICC) (2017) redefined patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) according to anatomical, biological, and conditional aspects. However, these new criteria have not been validated comprehensively. The aim of this retrospective cohort study was to validate the anatomical and biological definitions of BR-PDAC for oncological outcomes in patients with resectable (R) and BR-PDAC undergoing upfront surgery. METHODS A total of 404 patients who underwent upfront surgery for R- and BR-PDAC from 2004 to 2020 were included. The patients were classified according to the ICC as follows: resectable (R) (n = 259), anatomical borderline (BR-A) (n = 43), biological borderline (BR-B) (n = 81), and anatomical and biologic borderline (BR-AB) (n = 21). RESULTS Compared with the R and BR-B groups, the BR-A and BR-AB groups had higher postoperative complication rates (16.5% and 27.2% vs 32.5% and 33.4%; P < 0.001) and significantly lower R0 resection rates (85.7% and 80.2% vs 65.1% and 61.9%; P = 0.003). In contrast, compared with the R and BR-A groups, the BR-B (32.1%) and BR-AB (57.1%) groups had higher early recurrence rates (within postoperative 6 months) (16.5% and 25.6% vs 32.1% and 57.1%; P < 0.001) and significantly lower 3-year recurrence-free survival rates (36.1% and 20.7% vs 12.1% and 7.8%; P < 0.001). CONCLUSION Anatomically defined BR-PDAC was associated with a higher risk of margin-positive resection and postoperative complication rates, while biologically defined BR-PDAC was associated with higher early recurrence rates and lower survival rates. Thus, the anatomical and biological definitions are useful in predicting the prognosis and determining the usefulness of neoadjuvant therapy.
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Affiliation(s)
- Boram Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea.
| | - MeeYoung Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Yeshong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Eunhye Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Yeongsoo Jo
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Jun Suh Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
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41
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Kim HS, Lee M, Han Y, Kang JS, Kang YH, Sohn HJ, Kwon W, Lee DH, Jang JY. Role of neoadjuvant treatment in resectable pancreatic cancer according to vessel invasion and increase of CA19-9 levels. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2023. [PMID: 36652346 DOI: 10.1002/jhbp.1302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 12/22/2022] [Accepted: 12/26/2022] [Indexed: 01/19/2023]
Abstract
BACKGROUND/PURPOSE The efficacy of neoadjuvant treatment (NAT) for resectable pancreatic cancer remains debatable, particularly in patients with portal vein (PV)/superior mesenteric vein (SMV) contact and elevated serum carbohydrate antigen (CA) 19-9. This study investigated the clinical significance of PV/SMV contact and CA19-9 levels, and the role of NAT in resectable pancreatic cancer. METHODS A total of 775 patients who underwent surgery for resectable pancreatic cancer between 2007 and 2018 were included. Propensity score-matched (PSM) analysis (1:3) was performed based on tumor size, lymph node enlargement, and PV/SMV contact. Subgroup analyses were performed according to PV/SMV contact and CA19-9 level. RESULTS Among the patients, 52 underwent NAT and 723 underwent upfront surgery. After PSM, NAT group showed better survival than upfront surgery group (median 30.0 vs 22.0 months, P = .047). In patients with PV/SMV contact, NAT tended to have better survival (30.0 vs 22.0 months, P = .069). CA19-9 >150 U/mL was a poor prognostic factor, with NAT showing a significant survival difference compared with upfront surgery (34.0 vs 18.0 months, P = .004). CONCLUSIONS Neoadjuvant treatment showed better survival than upfront surgery in resectable pancreatic cancer. In patients with PV/SMV contact or CA19-9 >150 U/mL, NAT showed a survival difference compared to upfront surgery; therefore, NAT could be considered in these patients.
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Affiliation(s)
- Hyeong Seok Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Surgery, Goodjang Hospital, Seoul, Republic of Korea
| | - Mirang Lee
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jae Seung Kang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Yoon Hyung Kang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hee Ju Sohn
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Surgery, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Republic of Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Dong Ho Lee
- Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
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Ono Y, Inoue Y, Ito H, Sasaki T, Takeda T, Ozaka M, Sasahira N, Hiratsuka M, Matsueda K, Oba A, Sato T, Saiura A, Takahashi Y. Analysis of prognostic factors for borderline resectable pancreatic cancer after neoadjuvant chemotherapy: the importance of CA19-9 decrease in patients with elevated pre-chemotherapy CA19-9 levels. HPB (Oxford) 2023; 25:100-108. [PMID: 36280425 DOI: 10.1016/j.hpb.2022.09.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 07/09/2022] [Accepted: 09/28/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) is widely used to treat borderline resectable pancreatic cancer. This study aimed to evaluate the serum carbohydrate antigen (CA)19-9 response, in association with survival, after four cycles of NAC-gemcitabine plus nab-paclitaxel. METHODS From 2015 to 2018, patients with borderline resectable pancreatic cancer were treated with NAC. Patients were stratified into two groups after excluding CA19-9 non-secretor: Group L (CA19-9 ≥2 and ≤500 U/mL) and Group H (CA19-9 >500 U/mL). The CA19-9 decrease during NAC was evaluated as a response of NAC and was assessed in association with survival concomitant with other prognosis factors. RESULTS Eighty-seven patients were evaluated (Group L: n = 43, Group H: n = 44). In intention-to-treat-based analysis, Group L exhibited significantly better progression-free survival (PFS) than Group H (median PFS: 24 vs 14months). In resection cohort, no correlation was detected between the CA19-9 decrease and survival in Group L. In Group H, the CA19-9 decrease ≤80% was associated with unfavorable survival in multivariate analysis [Hazard ratio: 4.738 (P = 0.007)]. CONCLUSION In patients with pre-treatment CA19-9 >500 U/mL, the CA19-9 decrease ≤80% was strongly associated with poor survival and new strategy should be reconsidered for these patients.
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Affiliation(s)
- Yoshihiro Ono
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Inoue
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hiromichi Ito
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takashi Sasaki
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tsuyoshi Takeda
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masato Ozaka
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naoki Sasahira
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Makiko Hiratsuka
- Department of Diagnostic Imaging, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kiyoshi Matsueda
- Department of Diagnostic Imaging, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Atsushi Oba
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takafumi Sato
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akio Saiura
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yu Takahashi
- Division of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
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de Jesus VHF, Riechelmann RP. Current Treatment of Potentially Resectable Pancreatic Ductal Adenocarcinoma: A Medical Oncologist's Perspective. Cancer Control 2023; 30:10732748231173212. [PMID: 37115533 PMCID: PMC10155028 DOI: 10.1177/10732748231173212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 03/01/2023] [Accepted: 04/06/2023] [Indexed: 04/29/2023] Open
Abstract
Pancreatic cancer has traditionally been associated with a dismal prognosis, even in early stages of the disease. In recent years, the introduction of newer generation chemotherapy regimens in the adjuvant setting has improved the survival of patients treated with upfront resection. However, there are multiple theoretical advantages to deliver early systemic therapy in patients with localized pancreatic cancer. So far, the evidence supports the use of neoadjuvant therapy for patients with borderline resectable pancreatic cancer. The benefit of this treatment sequence for patients with resectable disease remains elusive. In this review, we summarize the data on adjuvant therapy for pancreatic cancer and describe which evidence backs the use of neoadjuvant therapy. Additionally, we address important issues faced in clinical practice when treating patients with localized pancreatic cancer.
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44
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Fawaz A, Abdel-Rahman O. Borderline Resectable Pancreatic Cancer: Challenges for Clinical Management. Cancer Manag Res 2022; 14:3589-3598. [PMID: 36597515 PMCID: PMC9805723 DOI: 10.2147/cmar.s340719] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 12/07/2022] [Indexed: 12/29/2022] Open
Abstract
Background Pancreatic ductal adenocarcinoma (PDAC) remains a significant worldwide health problem with a poor prognosis. A borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) is a tumor with limited vascular involvement that is technically resectable but with a high risk of positive margins (R1 resection). Objective To identify the current challenges that exist in the management of BR-PDAC. Methods A review of the literature was conducted to identify articles discussing the definitions and management of BR-PDAC. Key Findings Several anatomic definitions of BR-PDAC exist, and there is significant heterogeneity in their utilization across published trials. To improve the odds of a margin negative (R0) resection, a neoadjuvant treatment approach involving chemotherapy with or without radiation is currently preferred. While supporting the efficacy of a neoadjuvant approach in BR-PDAC, the largest published randomized trials have utilized older gemcitabine-based regimens. Recently published Phase II evidence and meta-analyses have supported the use of modern multi-agent regimens such as FOLFIRINOX. The utility of adding radiation to a chemotherapy backbone remains in question. Due to remnant fibrosis and edema following neoadjuvant therapy, accurately selecting patients for resection based on a restaging CT scan is challenging. Furthermore, the role of adjuvant therapy in BR-PDAC patients receiving neoadjuvant therapy needs to be defined. Conclusion Though progress has been made, the optimal management of BR-PDAC is uncertain. Phase III trials utilizing modern chemotherapeutic regimens are needed to establish a standard of care.
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Affiliation(s)
- Ali Fawaz
- Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Omar Abdel-Rahman
- Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
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45
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Ren W, Xourafas D, Ashley SW, Clancy TE. Predicting Surgical Margins in Patients With Borderline Resectable and Locally Advanced Pancreatic Cancer Undergoing Resection. Am Surg 2022; 88:2899-2906. [PMID: 33861651 DOI: 10.1177/00031348211011129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Many patients with borderline resectable/locally advanced pancreatic ductal adenocarcinoma (borderline resectable [BR]/locally advanced [LA] pancreatic ductal adenocarcinoma [PDAC]) undergoing resection will have positive resection margins (R1), which is associated with poor prognosis. It might be useful to preoperatively predict the margin (R) status. METHODS Data from patients with BR/LA PDAC who underwent a pancreatectomy between 2008 and 2018 at Brigham and Women's Hospital were retrospectively reviewed. Logistic regression analysis was used to evaluate the association between R status and relevant preoperative factors. Significant predictors of R1 resection on univariate analysis (P < .1) were entered into a stepwise selection using the Akaike information criterion to define the final model. RESULTS A total of 142 patients with BR/LA PDAC were included in the analysis, 60(42.3%) had R1 resections. In stepwise selection, the following factors were identified as positive predictors of an R1 resection: evidence of lymphadenopathy at diagnosis (OR = 2.06, 95% CI: 0.99-4.36, P = .056), the need for pancreaticoduodenectomy (OR = 3.81, 96% CI: 1.15-15.70, P = .040), extent of portal vein/superior mesenteric vein involvement at restaging (<180°, OR = 3.57, 95% CI: 1.00-17.00, P = .069, ≥180°, OR = 7,32, 95% CI: 1.75-39.87, P = .010), stable CA 19-9 serum levels (less than 50% decrease from diagnosis to restaging, OR = 2.27, 95% CI: 0.84-6.36 P = .107), and no preoperative FOLFIRINOX (OR = 2.17, 95% CI: 0.86-5.64, P = .103). The prognostic nomogram based on this model yielded a probability of achieving an R1 resection ranging from <5% (0 factors) to >70% (all 5 factors). CONCLUSIONS Relevant preoperative clinicopathological characteristics accurately predict positive resection margins in patients with BR/LA PDAC before resection. With further development, this model might be used to preoperatively guide surgical decision-making in patients with BR/LA PDAC.
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Affiliation(s)
- Weizheng Ren
- Department of Hepatopancreatobiliary Surgery, 104607First Center of General Hospital of People's Liberation Army, Beijing, China
- Department of Surgery, 1861Brigham and Women's Hospital, Boston, MA, USA
- 1811Harvard Medical School, Boston, MA, USA
| | - Dimitrios Xourafas
- Department of Surgery, 1861Brigham and Women's Hospital, Boston, MA, USA
- 1811Harvard Medical School, Boston, MA, USA
| | - Stanley W Ashley
- Department of Surgery, 1861Brigham and Women's Hospital, Boston, MA, USA
- 1811Harvard Medical School, Boston, MA, USA
| | - Thomas E Clancy
- Department of Surgery, 1861Brigham and Women's Hospital, Boston, MA, USA
- 1811Harvard Medical School, Boston, MA, USA
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Hank T, Hinz U, Reiner T, Malleo G, König AK, Maggino L, Marchegiani G, Kaiser J, Paiella S, Binco A, Salvia R, Hackert T, Bassi C, Büchler MW, Strobel O. A Pretreatment Prognostic Score to Stratify Survival in Pancreatic Cancer. Ann Surg 2022; 276:e914-e922. [PMID: 33914468 DOI: 10.1097/sla.0000000000004845] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE The aim of this study was to develop and validate a pretreatment prognostic score in pancreatic cancer (PDAC). BACKGROUND Pretreatment prognostication in PDAC is important for treatment decisions but remains challenging. Available prognostic tools are derived from selected cohorts of patients who underwent resection, excluding up to 20% of patients with exploration only, and do not adequately reflect the pretreatment scenario. METHODS Patients undergoing surgery for PDAC in Heidelberg from July 2006 to June 2014 were identified from a prospective database. Pretreatment parameters were extracted from the database and the laboratory information system. Parameters independently associated with overall survival by uni- and multivariable analyses were used to build a prognostic score. A contemporary cohort from Verona was used for external validation. RESULTS In 1197 patients, multiple pretreatment parameters were associated with overall survival by univariable analyses. American Society of Anesthesiology classification, carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen, C-reactive protein, albumin, and platelet count were independently associated with survival and were used to create the Heidelberg Prognostic Pancreatic Cancer (HELPP)-score. The HELPP-score was closely associated with overall survival (median survival between 31.3 and 4.8 months; 5-year survival rates between 35% and 0%) and was able to stratify survival in subgroups with or without resection as well as in CA19-9 nonsecretors. In the resected subgroup the HELPP-score stratified survival independently of pathological prognostic factors. The HELPP-score was externally validated and was superior to CA19-9 in both the development and validation cohorts. CONCLUSION The HELPP-score is a readily available prognostic tool based on pretreatment routine parameters to stratify survival in PDAC independently of resection status and pathological tumor stage.
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Affiliation(s)
- Thomas Hank
- Department of General, Visceral and Transplantation Surgery, Heidelberg, University Hospital, Heidelberg, Germany
| | - Ulf Hinz
- Department of General, Visceral and Transplantation Surgery, Heidelberg, University Hospital, Heidelberg, Germany
| | - Thomas Reiner
- Department of General, Visceral and Transplantation Surgery, Heidelberg, University Hospital, Heidelberg, Germany
| | - Giuseppe Malleo
- Department of General, and Pancreatic Surgery, The Verona Pancreas Institute, University of Verona, Hospital Trust, Verona, Italy
| | - Anna-Katharina König
- Department of General, Visceral and Transplantation Surgery, Heidelberg, University Hospital, Heidelberg, Germany
| | - Laura Maggino
- Department of General, and Pancreatic Surgery, The Verona Pancreas Institute, University of Verona, Hospital Trust, Verona, Italy
| | - Giovanni Marchegiani
- Department of General, and Pancreatic Surgery, The Verona Pancreas Institute, University of Verona, Hospital Trust, Verona, Italy
| | - Jörg Kaiser
- Department of General, Visceral and Transplantation Surgery, Heidelberg, University Hospital, Heidelberg, Germany
| | - Salvatore Paiella
- Department of General, and Pancreatic Surgery, The Verona Pancreas Institute, University of Verona, Hospital Trust, Verona, Italy
| | - Alessandra Binco
- Department of General, and Pancreatic Surgery, The Verona Pancreas Institute, University of Verona, Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Department of General, and Pancreatic Surgery, The Verona Pancreas Institute, University of Verona, Hospital Trust, Verona, Italy
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, Heidelberg, University Hospital, Heidelberg, Germany
| | - Claudio Bassi
- Department of General, and Pancreatic Surgery, The Verona Pancreas Institute, University of Verona, Hospital Trust, Verona, Italy
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery, Heidelberg, University Hospital, Heidelberg, Germany
| | - Oliver Strobel
- Department of General, Visceral and Transplantation Surgery, Heidelberg, University Hospital, Heidelberg, Germany
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Hata T, Chiba K, Mizuma M, Masuda K, Ohtsuka H, Nakagawa K, Morikawa T, Hayashi H, Motoi F, Unno M. Levels of tumor markers CEA/CA 19-9 in serum and peritoneal lavage predict postoperative recurrence in patients with pancreatic cancer. Ann Gastroenterol Surg 2022; 6:862-872. [PMID: 36338582 PMCID: PMC9628216 DOI: 10.1002/ags3.12597] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 06/18/2022] [Indexed: 12/24/2022] Open
Abstract
Aim This study aimed to clarify the usefulness of tumor markers from peritoneal lavage in selecting patients with a high risk of recurrence and predicting site-specific recurrence in patients with pancreatic cancer. Methods The levels of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 (sCEA/sCA 19-9) and paired peritoneal lavage CEA and CA 19-9 (pCEA/pCA 19-9) were measured in 90 patients with pancreatic cancer who underwent surgery. Using the cutoff values determined by maximally selected rank statistics for disease-free survival (DFS), the risk of recurrence and its patterns were evaluated in combination with different markers and different test specimens. Results In univariate and multivariate analysis, an elevated pCA 19-9 level (>1.3 U/mL) was an independent prognostic marker for both DFS (hazard ratio [HR], 2.391; P = .018) and overall survival (HR, 3.194; P = .033). Combination analyses contributed to further stratification of a very high risk of recurrence. Of the 58 patients with resectable pancreatic cancer who underwent curative resection, elevated pCA19-9 was also associated with inferior DFS and overall survival (OS). Patients with elevated pCA 19-9 levels were more likely to have an earlier onset of peritoneal recurrence than those with normal pCA 19-9 levels (P = .048, Gehan-Breslow-Wilcoxon test). Conclusion pCA 19-9 is a reliable marker for predicting postoperative recurrence in patients with pancreatic cancer after surgery. Further risk stratification can be achieved by using combination assays. The combination of pCA 19-9 and sCA19-9 also serves as a predictor of recurrence site-specific recurrence.
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Affiliation(s)
- Tatsuo Hata
- Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan
| | - Kazuharu Chiba
- Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan
| | - Masamichi Mizuma
- Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan
| | - Kunihiro Masuda
- Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan
| | - Hideo Ohtsuka
- Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan
| | - Kei Nakagawa
- Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan
| | - Takanori Morikawa
- Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan
| | | | - Fuyuhiko Motoi
- Department of Surgery IYamagata University Graduate School of Medical ScienceYamagataJapan
| | - Michiaki Unno
- Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan
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Seufferlein T, Mayerle J, Böck S, Brunner T, Ettrich TJ, Grenacher L, Gress TM, Hackert T, Heinemann V, Kestler A, Sinn M, Tannapfel A, Wedding U, Uhl W. S3-Leitlinie zum exokrinen Pankreaskarzinom – Langversion 2.0 – Dezember 2021 – AWMF-Registernummer: 032/010OL. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e812-e909. [PMID: 36368658 DOI: 10.1055/a-1856-7346] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
| | | | - Stefan Böck
- Medizinische Klinik und Poliklinik III, Universitätsklinikum München, Germany
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz, Austria
| | | | | | - Thomas Mathias Gress
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Germany
| | - Thilo Hackert
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsklinikum, Heidelberg, Germany
| | - Volker Heinemann
- Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Campus Grosshadern, München, Germany
| | | | - Marianne Sinn
- Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik und Poliklinik II Onkologie Hämatologie, Hamburg, Germany
| | | | | | - Waldemar Uhl
- Allgemein- und Viszeralchirurgie, St Josef-Hospital, Bochum, Germany
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Bachellier P, Addeo P, Averous G, Dufour P. Resection of pancreatic adenocarcinomas with synchronous liver metastases: A retrospective study of prognostic factors for survival. Surgery 2022; 172:1245-1250. [PMID: 35422325 DOI: 10.1016/j.surg.2022.03.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 02/16/2022] [Accepted: 03/02/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND This study aimed to evaluate the results of synchronous liver resection for metastatic pancreatic ductal adenocarcinomas and to identify prognostic factors for overall survival. METHODS We retrospectively reviewed clinical data from patients who underwent the synchronous resection of pancreatic adenocarcinoma with liver metastases. Cox analyses were used to identify factors prognostic of overall survival. RESULTS Of the 92 patients included in this study, preoperative chemotherapy was administered to 52 patients. The median overall survival was 18.26 months (95% confidence interval: 14.7-22.7) (from diagnosis) and 12.68 months (95% confidence interval: 9.5-15.57) from surgery; overall survival at 1, 3, and 5 years was 70%, 10%, and 0%, respectively. Twenty-eight patients (30.4%) had median overall survival >18 months after surgery. The median overall survival from diagnosis was longer in patients undergoing preoperative treatment (22.7 vs 13.8 months; P = .01) but similar after surgery (12.6 vs 13.8 months; P = .86). Multivariate Cox analysis found CA19-9 levels <500 kU/L (hazard ratio: 0.35; 95% confidence interval: 0.17-0.70; P = .003), R0 resection (hazard ratio: 0.46; 95% confidence interval: 0.24-0.88; P = .020), and adjuvant chemotherapy (hazard ratio: 0.39; 95% confidence interval: 0.17-0.88; P = .024) as independent prognostic factors for overall survival. CONCLUSION Survival after resection of oligometastatic liver disease remains limited, reflecting the dismal prognosis of metastatic disease even after aggressive treatment. Preresection CA19-9 serum levels represent a useful tool for patient selection, and administration of adjuvant chemotherapy has a major impact on overall survival. Large comparative studies with exclusive chemotherapy are needed to validate this approach and to identify optimal candidates.
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Affiliation(s)
- Philippe Bachellier
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, France
| | - Pietro Addeo
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, France.
| | - Gerlinde Averous
- Department of Pathology, University of Strasbourg, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, France
| | - Patrick Dufour
- Department of Oncology, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, France
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Moon D, Kim H, Han Y, Byun Y, Choi Y, Kang J, Kwon W, Jang JY. Preoperative carbohydrate antigen 19-9 and standard uptake value of positron emission tomography-computed tomography as prognostic markers in patients with pancreatic ductal adenocarcinoma. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2022; 29:1133-1141. [PMID: 33063453 DOI: 10.1002/jhbp.845] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 08/30/2020] [Accepted: 09/20/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Among various prognostic factors of pancreatic cancer, preoperative clinical information is obtained by imaging modality. This study aimed to evaluate clinical usefulness of preoperative carbohydrate antigen and preoperative standard uptake value in 18F-fluorodeoxyglucose positron emission tomography as predictive biological markers for resectable pancreatic ductal adenocarcinoma. METHODS A total of 189 patients with PDAC who underwent preoperative PET-computed tomography were evaluated. Patients underwent neoadjuvant chemotherapy, and R2 resection was excluded. The correlation between SUVmax and clinicopathologic parameters was analyzed. The C-tree statistical method was used to estimate cutoff values of logCA19-9 and SUVmax for survival rate. A multivariate analysis was conducted to identify prognostic factors for overall survival. RESULTS The median duration of OS was 26 months, and the 5-year survival rate was 22.4%. The optimal cutoff values for CA19-9 level was 150 U/mL and SUVmax was 5.5. When subjects were divided into three groups according to the combination of CA19-9 level and SUVmax from C-tree (high-risk group, CA19-9 > 150 U/mL and SUVmax > 5.5; intermediate-risk group, CA19-9 ≤ 150 U/mL and SUVmax > 5.5 or CA19-9 > 150 U/mL and SUVmax ≤ 5.5; and low-risk group, CA19-9 ≤ 150 U/mL and SUVmax ≤ 5.5), there was a significant 5YSR difference (5.6%, 24.3%, and 36.5%, P < .001). The multivariate analysis revealed high SUVmax, high preoperative CA19-9 level, venous invasion, and adjuvant chemotherapy were prognostic factors of OS. CONCLUSIONS CA19-9 and SUVmax are strong prognostic biological factors in resectable PDAC. Moreover, patients with high CA19-9 level and SUVmax are not indicated for upfront surgery.
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Affiliation(s)
- Dokyoon Moon
- Departments of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hongbeom Kim
- Departments of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Youngmin Han
- Departments of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yoonhyeong Byun
- Departments of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yoojin Choi
- Departments of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jaeseung Kang
- Departments of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Departments of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jin-Young Jang
- Departments of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
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