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Wang J, Lyu SC, Cui SP, Huang JC, Wang HX, Hu B, He Q, Lang R. Utilizing bifurcated allogeneic vein grafts: a novel approach for preventing sinistral portal hypertension following pancreaticoduodenectomy. A 10-year before and after study. Int J Surg 2025; 111:9-19. [PMID: 38995182 PMCID: PMC11745578 DOI: 10.1097/js9.0000000000001944] [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: 04/05/2024] [Accepted: 06/30/2024] [Indexed: 07/13/2024]
Abstract
BACKGROUND Sinistral portal hypertension (SPH) may occur in patients with pancreatic carcinoma after pancreaticoduodenectomy (PD) with spleno-mesenterico-portal (S-M-P) confluence resection. This study aimed to evaluate outcomes with bifurcated allogeneic vein replacement in the prevention of SPH in pancreatic carcinoma patients. MATERIALS AND METHODS A total of 81 patients were included. The authors retrospectively collected clinicopathological data from 66 patients underwent PD with S-M-P confluence resection in our hospital from January 2011 to December 2021, compared the correlation between different venous reconstruction methods using log-rank tests and clinical outcomes through univariate and multivariate analyses. Secondly, the authors prospectively collected clinical data and outcomes of 15 patients who underwent splenic vein reconstruction from January 2021 to January 2023. RESULTS In the retrospective study, 43 cases received reconstruction by bifurcated allogeneic vein (Reconstruction group) and 23 cases received simply SV ligation (Ligation group). The preoperative platelet counts and spleen volume were similar between two groups ( P >0.05). Nevertheless, at 1 month, 3 months and 6 months after operation, the related indexes of SPH such as platelet count, spleen volume, spleen volume ratio and esophagogastric varices (EGV) grade in Reconstruction group were better than those in Ligation group ( P <0.05). 6 months after surgery, the incidence of SPH in Ligation group was significantly higher than in Reconstruction group (36.4% vs. 8.1%, respectively). In the prospective study, the incidence of SPH in patients undergoing SV reconstruction was 6.7% (1/15). CONCLUSIONS Without compromising surgical outcomes, reconstruction of the S-M-P confluence by bifurcated allogeneic vein is a better method to avoid SPH in patients with advanced pancreatic carcinoma.
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Affiliation(s)
- Jing Wang
- Department of Thoracic Surgery, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
- Mass General Cancer Cennter, Mass General Brigham, Harvard Medical School
| | - Shao-cheng Lyu
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Song-ping Cui
- Department of Thoracic Surgery, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Jin-can Huang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Han-xuan Wang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Bin Hu
- Department of Thoracic Surgery, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Qiang He
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Ren Lang
- Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
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Hoffman D, Ganjouei AA, Hernandez FR, Ifuku K, Miller P, Glencer A, Corvera C, Kirkwood K, Alseidi A, Adam M, Maker A, Hirose K, Hirose R, Nakakura EK. Graft choice in pancreatectomy with vascular resection: equivalent safety in selected patients. J Gastrointest Surg 2024; 28:1799-1804. [PMID: 39181231 DOI: 10.1016/j.gassur.2024.08.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Revised: 06/17/2024] [Accepted: 08/17/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND Pancreatic cancer is the third leading cause of cancer-related death in the United States, with surgical resection being the only option for long-term survival. The ability to manage vascular involvement has expanded the pool of patients who are able to undergo resection with curative intent. However, not all vascular involvements can be detected preoperatively. This study aimed to investigate the patterns of vascular resection and methods of repair or reconstruction METHODS: This was a single-center retrospective review of adult patients undergoing pancreatectomy with vascular involvement at a tertiary care referral hospital between 2010 and 2022. The primary endpoint was graft thrombosis within 90 days. RESULTS A total of 147 patients were included in the study. Of note, 21.8% of patients were not suspected of having vascular involvement preoperatively. Moreover, 68.0% of patients required vascular reconstruction, whereas the remaining 32.0% of patients underwent repair (either primary repair or patch angioplasty). Most patients who underwent reconstruction underwent primary end-to-end anastomosis (63.0%), with 19 patients requiring autologous interposition grafts and 16 patients requiring CryoVein interposition grafts. Univariate analysis found no clinical or technical predictors of early or 90-day thrombosis, including graft choice. In addition, 30- and 90-day mortalities occurred in 1 and 7 patients, respectively. CONCLUSION Pancreatectomy with vascular resection can be performed with low mortality in carefully selected patients. Unsuspected vascular involvement is relatively common (1 in 5). If autologous graft is not readily available, CryoVein is a safe alternative with similar perioperative outcomes.
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Affiliation(s)
- Daniel Hoffman
- Department of Surgery, University of California, San Francisco, CA, United States
| | - Amir Ashraf Ganjouei
- Department of Surgery, University of California, San Francisco, CA, United States
| | | | - Kelli Ifuku
- Department of Surgery, University of California, San Francisco, CA, United States
| | - Phoebe Miller
- Department of Surgery, University of California, San Francisco, CA, United States
| | - Alexa Glencer
- Department of Surgery, University of California, San Francisco, CA, United States
| | - Carlos Corvera
- Department of Surgery, University of California, San Francisco, CA, United States; Section of Hepatopancreaticobiliary Surgery, Division of Surgical Oncology, Department of Surgery, University of California, San Francisco, CA, United States
| | - Kimberly Kirkwood
- Department of Surgery, University of California, San Francisco, CA, United States; Section of Hepatopancreaticobiliary Surgery, Division of Surgical Oncology, Department of Surgery, University of California, San Francisco, CA, United States
| | - Adnan Alseidi
- Department of Surgery, University of California, San Francisco, CA, United States; Section of Hepatopancreaticobiliary Surgery, Division of Surgical Oncology, Department of Surgery, University of California, San Francisco, CA, United States
| | - Mohamed Adam
- Department of Surgery, University of California, San Francisco, CA, United States; Section of Hepatopancreaticobiliary Surgery, Division of Surgical Oncology, Department of Surgery, University of California, San Francisco, CA, United States
| | - Ajay Maker
- Department of Surgery, University of California, San Francisco, CA, United States
| | - Kenzo Hirose
- Department of Surgery, University of California, San Francisco, CA, United States; UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, United States
| | - Ryutaro Hirose
- Department of Surgery, University of California, San Francisco, CA, United States; UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, United States; Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, CA, United States
| | - Eric K Nakakura
- Department of Surgery, University of California, San Francisco, CA, United States; Section of Hepatopancreaticobiliary Surgery, Division of Surgical Oncology, Department of Surgery, University of California, San Francisco, CA, United States; UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, United States.
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Cortiana V, Vallabhaneni H, Gambill J, Nadar S, Itodo K, Park CH, Leyfman Y. Advancing Pancreatic Cancer Surgical Treatments and Proposal of New Approaches. Cancers (Basel) 2024; 16:2848. [PMID: 39199619 PMCID: PMC11352325 DOI: 10.3390/cancers16162848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 08/13/2024] [Accepted: 08/13/2024] [Indexed: 09/01/2024] Open
Abstract
Pancreatic cancer is a significant challenge in oncology due to its aggressive nature and complex management, leading to high mortality rates and a dismally low 5-year survival rate. Approximately 85% of cases manifest as adenocarcinoma, while endocrine tumors constitute less than 5%. Borderline resectable and locally advanced pancreatic cancers are particularly difficult to treat due to vascular involvement, which complicates complete resections and increases morbidity. Various therapeutic modalities aim to overcome these challenges and improve patient outcomes. Traditionally, upfront surgery was the standard for resectable tumors, with multimodal chemotherapy being central to treatment. Understanding surgical anatomy is pivotal in enhancing surgical outcomes and patient survival. Resectability challenges are several when seeking to achieve R0 resections, particularly for borderline resectable tumors. Various classification systems-the MD Anderson criteria, the NCCN criteria, the AHPA/SSAT/SSO consensus statement, and the Alliance definition-assess tumor involvement with major blood vessels, with the first of these systems being broadly accepted. Vascular staging integration is also important, with the Ishikawa staging system using preoperative imaging to assess venous involvement. Furthermore, neoadjuvant therapy enhances treatment effectiveness by addressing micro-metastatic disease early, increasing R0 resection chances, and downstaging tumors for optimal surgery. Insights from the Fox Chase Cancer Center's neoadjuvant treatment approach highlight the importance of a multidisciplinary strategy when advancing therapy and improving patient prognosis. This commentary, inspired by Dr. Sanjay S. Reddy's Keynote Conference during MedNews week, highlights current advancements and ongoing challenges in the treatment of pancreatic cancer, emphasizing the need for a comprehensive, multidisciplinary approach to improve outcomes.
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Affiliation(s)
- Viviana Cortiana
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy
| | | | | | - Soumiya Nadar
- Tbilisi State Medical University, 0186 Tbilisi, Georgia
| | - Kennedy Itodo
- Nigerian Institute for Trypanosomiasis Research Jos, Kaduna PMB 2077, Nigeria
| | | | - Yan Leyfman
- Icahn School of Medicine at Mount Sinai South Nassau, Oceanside, NY 11572, USA;
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Riviere D, van den Boezem PB, Besselink MG, van Laarhoven CJ, Kooby DA, Vollmer CM, Davidson BR, Gurusamy KS. Minimally invasive versus open pancreatoduodenectomy in benign, premalignant, and malignant disease. Cochrane Database Syst Rev 2024; 7:CD014017. [PMID: 39056402 PMCID: PMC11274036 DOI: 10.1002/14651858.cd014017] [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] [Indexed: 07/28/2024]
Abstract
OBJECTIVES This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of laparoscopic or robot-assisted pancreatoduodenectomy versus open pancreatoduodenectomy for people with benign, premalignant, and malignant disease.
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Affiliation(s)
- Deniece Riviere
- Department of Medical Imaging, Radboud University Medical Center Nijmegen, Nijmegen, Netherlands
| | | | - Marc G Besselink
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | | | - David A Kooby
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Charles M Vollmer
- Department of Gastrointestinal Surgery, University of Pennsylvania, Philadelphia, PA, USA
| | - Brian R Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
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He J, Lv N, Yang Z, Luo Y, Zhong W, Wu C. Comparing upfront surgery with neoadjuvant treatments in patients with resectable, borderline resectable or locally advanced pancreatic cancer: a systematic review and network meta-analysis of randomized clinical trials. Int J Surg 2024; 110:3900-3909. [PMID: 38935819 PMCID: PMC11175811 DOI: 10.1097/js9.0000000000001313] [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: 11/02/2023] [Accepted: 02/25/2024] [Indexed: 06/29/2024]
Abstract
BACKGROUND The aim was to explore the optimal neoadjuvant therapy strategy for resectable, borderline resectable, and locally advanced pancreatic cancer, in order to provide a theoretical basis for the development of new neoadjuvant treatment protocols for clinical use. PATIENTS AND METHODS The authors reviewed literature titles and abstracts comparing three treatment strategies (neoadjuvant chemoradiotherapy, neoadjuvant chemotherapy, and upfront surgery) in PubMed, Embase, The Cochrane Library, Web of Science from 2009 to 2023 to estimate relative odds ratios for resection rate and hazard ratios (HRs) for overall survival (OS) in all include trials. RESULTS A total of nine studies involving 889 patients were included in the analysis. The treatment methods included upfront surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy followed by surgery. The network meta-analysis results demonstrated that neoadjuvant chemoradiotherapy followed by surgery was an effective approach in improving OS for resectable and borderline resectable pancreatic cancer (RPC) patients compared to upfront surgery (HR: 0.79, 95% CI: 0.64-0.98) and neoadjuvant chemotherapy (HR: 0.79, 95% CI: 0.64-0.98). Additionally, neoadjuvant chemoradiotherapy significantly increased the margin negative resection (R0) rate and pathological negative lymph node (pN0) rate in patients with resectable and borderline RPC. However, it is worth noting that neoadjuvant chemoradiotherapy increased the risk of grade 3 or higher treatment-related adverse events, including in patients with locally advanced pancreatic cancer. CONCLUSIONS The current evidence suggests that neoadjuvant chemoradiotherapy followed by surgery is the optimal choice for treating patients with resectable and borderline RPC. Future research should focus on optimizing neoadjuvant chemoradiotherapy regimens to effectively improve OS while reducing the occurrence of adverse events.
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Affiliation(s)
| | | | | | | | | | - Chunli Wu
- Department of Radiation Oncology, The Fourth Affiliated Hospital of China Medical University, Liaoning, China
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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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Vehviläinen S, Kuuliala A, Udd M, Nurmi A, Peltola K, Haglund C, Kylänpää L, Seppänen H. Cholangitis and Interruptions of Neoadjuvant Chemotherapy Associate with Reduced Overall and Progression-Free Survival in Pancreatic Cancer. Ann Surg Oncol 2024; 31:2621-2631. [PMID: 38153645 PMCID: PMC10908635 DOI: 10.1245/s10434-023-14793-6] [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: 04/05/2023] [Accepted: 12/06/2023] [Indexed: 12/29/2023]
Abstract
BACKGROUND Interrupting chemotherapy may explain the reduced overall survival (OS) in patients with pancreatic cancer (PC) with cholangitis. Endoscopic biliary decompression (BD) with metallic stents results in fewer chemotherapy interruptions and a lower cholangitis rate compared with plastic stents. We aimed to determine the impact of cholangitis, neoadjuvant treatment (NAT) interruptions and biliary stent choice on PC patients' survival. METHODS We conducted a retrospective analysis of 162 patients with cancer of the head of the pancreas undergoing pancreatoduodenectomy after NAT and BD documenting progression-free survival (PFS) and OS. Data on BD, cholangitis, stent type, surgical radicality, and chemotherapy were collected. Survival was estimated based on the Kaplan-Meier method by using the log-rank test and multivariate Cox regression analysis. RESULTS Median OS and PFS for patients with cholangitis (n = 33, 20%) were 26 and 8 months (95% confidence interval [CI] 20-32 and 5-10 months), respectively, compared with 36 and 17 months (95% CI 31-41 and 12-21 months; p < 0.001 for OS; p = 0.002 for PFS) for patients without cholangitis. Among patients without NAT interruptions median OS and PFS were 35 and 17 months (95% CI 31-40 and 12-21 months), falling to 26 and 7 months (95% CI 18-30 and 5-10 months) among those who experienced an NAT interruption caused by biliary stent failure (n = 26, 16%) (p = 0.039 for OS; p < 0.001 for PFS). We found no difference in OS or PFS between stent types. CONCLUSIONS Cholangitis and NAT interruptions reduce OS and PFS among PC patients.
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Affiliation(s)
- Sini Vehviläinen
- Department of Gastrointestinal Surgery, Meilahti Hospital, Helsinki University Hospital, Helsinki, Finland.
- Translational Cancer Medicine Research Programme, University of Helsinki, Helsinki, Finland.
| | - Antti Kuuliala
- Bacteriology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Marianne Udd
- Department of Gastrointestinal Surgery, Meilahti Hospital, Helsinki University Hospital, Helsinki, Finland
- Translational Cancer Medicine Research Programme, University of Helsinki, Helsinki, Finland
| | - Anna Nurmi
- Department of Gastrointestinal Surgery, Meilahti Hospital, Helsinki University Hospital, Helsinki, Finland
- Translational Cancer Medicine Research Programme, University of Helsinki, Helsinki, Finland
| | - Katriina Peltola
- Department of Oncology, Helsinki University Hospital, Helsinki, Finland
| | - Caj Haglund
- Department of Gastrointestinal Surgery, Meilahti Hospital, Helsinki University Hospital, Helsinki, Finland
- Translational Cancer Medicine Research Programme, University of Helsinki, Helsinki, Finland
| | - Leena Kylänpää
- Department of Gastrointestinal Surgery, Meilahti Hospital, Helsinki University Hospital, Helsinki, Finland
- Translational Cancer Medicine Research Programme, University of Helsinki, Helsinki, Finland
| | - Hanna Seppänen
- Department of Gastrointestinal Surgery, Meilahti Hospital, Helsinki University Hospital, Helsinki, Finland
- Translational Cancer Medicine Research Programme, University of Helsinki, Helsinki, Finland
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Shouman MA, Fuchs F, Walter F, Corradini S, Westphalen CB, Vornhülz M, Beyer G, Andrade D, Belka C, Niyazi M, Rogowski P. Stereotactic body radiotherapy for pancreatic cancer - A systematic review of prospective data. Clin Transl Radiat Oncol 2024; 45:100738. [PMID: 38370495 PMCID: PMC10873666 DOI: 10.1016/j.ctro.2024.100738] [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: 10/01/2023] [Revised: 01/05/2024] [Accepted: 01/26/2024] [Indexed: 02/20/2024] Open
Abstract
Purpose This systematic review aims to comprehensively summarize the current prospective evidence regarding Stereotactic Body Radiotherapy (SBRT) in various clinical contexts for pancreatic cancer including its use as neoadjuvant therapy for borderline resectable pancreatic cancer (BRPC), induction therapy for locally advanced pancreatic cancer (LAPC), salvage therapy for isolated local recurrence (ILR), adjuvant therapy after radical resection, and as a palliative treatment. Special attention is given to the application of magnetic resonance-guided radiotherapy (MRgRT). Methods Following PRISMA guidelines, a systematic review of the Medline database via PubMed was conducted focusing on prospective studies published within the past decade. Data were extracted concerning study characteristics, outcome measures, toxicity profiles, SBRT dosage and fractionation regimens, as well as additional systemic therapies. Results and conclusion 31 studies with in total 1,571 patients were included in this review encompassing 14 studies for LAPC, 9 for neoadjuvant treatment, 2 for adjuvant treatment, 2 for ILR, with an additional 4 studies evaluating MRgRT. In LAPC, SBRT demonstrates encouraging results, characterized by favorable local control rates. Several studies even report conversion to resectable disease with substantial resection rates reaching 39%. The adoption of MRgRT may provide a solution to the challenge to deliver ablative doses while minimizing severe toxicities. In BRPC, select prospective studies combining preoperative ablative-dose SBRT with modern induction systemic therapies have achieved remarkable resection rates of up to 80%. MRgRT also holds potential in this context. Adjuvant SBRT does not appear to confer relevant advantages over chemotherapy. While prospective data for SBRT in ILR and for palliative pain relief are limited, they corroborate positive findings from retrospective studies.
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Affiliation(s)
- Mohamed A Shouman
- Department of Radiation Oncology, University Hospital LMU, Munich, Germany
- Bavarian Cancer Research Center (BZKF), Munich, Germany
| | - Frederik Fuchs
- Department of Radiation Oncology, University Hospital LMU, Munich, Germany
| | - Franziska Walter
- Department of Radiation Oncology, University Hospital LMU, Munich, Germany
| | - Stefanie Corradini
- Department of Radiation Oncology, University Hospital LMU, Munich, Germany
| | - C Benedikt Westphalen
- Department of Medicine III and Comprehensive Cancer Center (CCC Munich LMU), University Hospital LMU, Munich, Germany
| | - Marlies Vornhülz
- Bavarian Cancer Research Center (BZKF), Munich, Germany
- Department of Internal Medicine II, LMU University Hospital, Munich, Germany
| | - Georg Beyer
- Bavarian Cancer Research Center (BZKF), Munich, Germany
- Department of Internal Medicine II, LMU University Hospital, Munich, Germany
| | - Dorian Andrade
- Department of General, Visceral, and Transplant Surgery, University Hospital LMU, Munich, Germany
| | - Claus Belka
- Department of Radiation Oncology, University Hospital LMU, Munich, Germany
- Bavarian Cancer Research Center (BZKF), Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
| | - Maximilian Niyazi
- Department of Radiation Oncology, University Hospital LMU, Munich, Germany
- Department of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany
- German Cancer Consortium (DKTK), Partner Site Tübingen, Germany
| | - Paul Rogowski
- Department of Radiation Oncology, University Hospital LMU, Munich, Germany
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Pedrazzoli S. Currently Debated Topics on Surgical Treatment of Pancreatic Ductal Adenocarcinoma: A Narrative Review on Surgical Treatment of Borderline Resectable, Locally Advanced, and Synchronous or Metachronous Oligometastatic Tumor. J Clin Med 2023; 12:6461. [PMID: 37892599 PMCID: PMC10607532 DOI: 10.3390/jcm12206461] [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: 09/06/2023] [Revised: 09/29/2023] [Accepted: 10/04/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND Previously considered inoperable patients (borderline resectable, locally advanced, synchronous oligometastatic or metachronous pancreatic adenocarcinoma (PDAC)) are starting to become resectable thanks to advances in chemo/radiotherapy and the reduction in operative mortality. METHODS This narrative review presents a chosen literature selection, giving a picture of the current state of treatment of these patients. RESULTS Neoadjuvant therapy (NAT) is generally recognized as the treatment of choice before surgery. However, despite the increased efficacy, the best pathological response is still limited to 10.9-27.9% of patients. There are still limited data on the selection of possible NAT responders and how to diagnose non-responders early. Multidetector computed tomography has high sensitivity and low specificity in evaluating resectability after NAT, limiting the resection rate of resectable patients. Ca 19-9 and Positron emission tomography are giving promising results. The prediction of early recurrence after a radical resection of synchronous or metachronous metastatic PDAC, thus identifying patients with poor prognosis and saving them from a resection of little benefit, is still ongoing, although some promising data are available. CONCLUSION In conclusion, high-level evidence demonstrating the benefit of the surgical treatment of such patients is still lacking and should not be performed outside of high-volume centers with interdisciplinary teams of surgeons and oncologists.
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10
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Wu VS, Elshami M, Stitzel HJ, Lee JJ, Hue JJ, Kyasaram RK, Hardacre JM, Ammori JB, Winter JM, Selfridge JE, Mohamed A, Chakrabarti S, Bajor D, Mahipal A, Ocuin LM. Why the Treatment Sequence Matters: Interplay Between Chemotherapy Cycles Received, Cumulative Dose Intensity, and Survival in Resected Early-stage Pancreas Cancer. Ann Surg 2023; 278:e677-e684. [PMID: 37071769 DOI: 10.1097/sla.0000000000005830] [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: 04/20/2023]
Abstract
OBJECTIVE To define the optimal threshold of perioperative chemotherapy completion and relative dose intensity (RDI) for patients with resected pancreatic ductal adenocarcinoma (PDAC). BACKGROUND Many patients who undergo pancreatectomy for PDAC fail to initiate or complete recommended perioperative chemotherapy. The association between the amount of perioperative chemotherapy received and overall survival (OS) is not well-defined. METHODS Single-institution analysis of 225 patients who underwent pancreatectomy for stage I/II PDAC (2010-2021). Associations between OS, chemotherapy cycles completed, and RDI were analyzed. RESULTS Regardless of treatment sequence, completion of ≥67% of recommended cycles was associated with improved OS compared with no chemotherapy [median OS: 34.5 vs 18.1 months; hazard ratio (HR): 0.43; 95% CI: 0.25-0.74] and <67% of cycles (median OS: 17.9 months; HR: 0.39; 95% CI: 0.24-0.64). A near-linear relationship existed between cycles completed and the RDI received (β = 0.82). A median RDI of 56% corresponded to the completion of 67% of cycles. Receipt of ≥56% RDI was associated with improved OS compared with no chemotherapy (median OS: 35.5 vs 18.1 months; HR: 0.44; 95% CI: 0.23-0.84) and <56% RDI (median OS: 27.2 months; HR: 0.44; 95% CI: 0.20-0.96). Neoadjuvant chemotherapy is associated with increased odds of receiving ≥67% of recommended cycles (odds ratio: 2.94; 95% CI: 1.45-6.26) and ≥56% RDI (odds ratio: 4.47; 95% CI: 1.72-12.50). CONCLUSIONS Patients with PDAC who received ≥67% of recommended chemotherapy cycles or ≥56% cumulative RDI had improved OS. Neoadjuvant therapy was associated with increased odds of receiving ≥67% of cycles and ≥56% cumulative RDI and should be considered in all patients with resectable PDAC.
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Affiliation(s)
- Victoria S Wu
- Case Western Reserve University School of Medicine, Cleveland, OH
| | - Mohamedraed Elshami
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Henry J Stitzel
- Case Western Reserve University School of Medicine, Cleveland, OH
| | - Jonathan J Lee
- Case Western Reserve University School of Medicine, Cleveland, OH
| | - Jonathan J Hue
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Ravi K Kyasaram
- Department of Cancer Informatics, University Hospitals Cleveland Medical Center/Seidman Cancer Center, Cleveland, OH
| | - Jeffrey M Hardacre
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - John B Ammori
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Jordan M Winter
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - Jennifer Eva Selfridge
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH
| | - Amr Mohamed
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH
| | - Sakti Chakrabarti
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH
| | - David Bajor
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH
| | - Amit Mahipal
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH
| | - Lee M Ocuin
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH
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Tachezy M, Gebauer F, Yekebas E, Izbicki JR. Failure of a Multi-Centric Clinical Trial Investigating Neoadjuvant Radio-Chemotherapy in Resectable Pancreatic Carcinoma (NEOPA-NCT01900327)-Which Lessons Are Learnt? Cancers (Basel) 2023; 15:4262. [PMID: 37686537 PMCID: PMC10487154 DOI: 10.3390/cancers15174262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 07/28/2023] [Accepted: 07/31/2023] [Indexed: 09/10/2023] Open
Abstract
BACKGROUND A significant number of clinical trials must be prematurely discontinued due to recruitment failure, and only a small fraction publish results and a failure analysis. Based on our experience on conducting the NEOPA trial on neoadjuvant radiochemotherapy for resectable and borderline resectable pancreatic carcinoma (NCT01900327-funded by the German Federal Ministry of Education and Research-BMBF), we performed an analysis of potential reasons for recruitment failure and general problems in conducting clinical trials in Germany. METHODS Systematic analysis of environmental factors, trial history, conducting and funding in the background of the published literature. RESULTS The recruitment failure was based on various study-specific conceptional and local environmental aspects and in peculiarities of the German surgical study culture. General reservations against a neo-adjuvant study concept combined with game changing scientific progresses during the long-lasting planning and funding phase have led to a reduced interest in the trial design and recruitment. CONCLUSIONS Trial planning and conducting should be focused, professionalized and financed on a national basis. Individual interests must be subordinated to reach the goal to perform more relevant and successful clinical trials in Germany. Bureaucratic processes must be further fastened between a trial idea and the start of a study.
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Affiliation(s)
- Michael Tachezy
- Department of General, Visceral and Thoracic Surgery, University-Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; (F.G.); (E.Y.); (J.R.I.)
| | - Florian Gebauer
- Department of General, Visceral and Thoracic Surgery, University-Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; (F.G.); (E.Y.); (J.R.I.)
- Department of General and Visceral Surgery, HELIOS University Hospital Wuppertal, 42283 Wuppertal, Germany
| | - Emre Yekebas
- Department of General, Visceral and Thoracic Surgery, University-Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; (F.G.); (E.Y.); (J.R.I.)
| | - Jakob Robert Izbicki
- Department of General, Visceral and Thoracic Surgery, University-Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; (F.G.); (E.Y.); (J.R.I.)
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12
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Chen EY, Kardosh A, Nabavizadeh N, Foster B, Mayo SC, Billingsley KG, Gilbert EW, Lanciault C, Grossberg A, Bensch KG, Maynard E, Anderson EC, Sheppard BC, Thomas CR, Lopez CD, Vaccaro GM. Phase 2 study of preoperative chemotherapy with nab-paclitaxel and gemcitabine followed by chemoradiation for borderline resectable or node-positive pancreatic ductal adenocarcinoma. Cancer Med 2023; 12:12986-12995. [PMID: 37132281 PMCID: PMC10315770 DOI: 10.1002/cam4.5971] [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: 12/28/2022] [Revised: 03/30/2023] [Accepted: 04/10/2023] [Indexed: 05/04/2023] Open
Abstract
BACKGROUND Neoadjuvant treatment with nab-paclitaxel and gemcitabine for potentially operable pancreatic adenocarcinoma has not been well studied in a prospective interventional trial and could down-stage tumors to achieve negative surgical margins. METHODS A single-arm, open-label phase 2 trial (NCT02427841) enrolled patients with pancreatic adenocarcinoma deemed to be borderline resectable or clinically node-positive from March 17, 2016 to October 5, 2019. Patients received preoperative gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on Days 1, 8, 15, every 28 days for two cycles followed by chemoradiation with 50.4 Gy intensity-modulated radiation over 28 fractions with concurrent fluoropyrimidine chemotherapy. After definitive resection, patients received four additional cycles of gemcitabine and nab-paclitaxel. The primary endpoint was R0 resection rate. Other endpoints included treatment completion rate, resection rate, radiographic response rate, survival, and adverse events. RESULTS Nineteen patients were enrolled, with the majority having head of pancreas primary tumors, both arterial and venous vasculature involvement, and clinically positive nodes on imaging. Among them, 11 (58%) underwent definitive resection and eight of 19 (42%) achieved R0 resection. Disease progression and functional decline were primary reasons for deferring surgical resection after neoadjuvant treatment. Pathologic near-complete response was observed in two of 11 (18%) resection specimens. Among the 19 patients, the 12-month progression-free survival was 58%, and 12-month overall survival was 79%. Common adverse events were alopecia, nausea, vomiting, fatigue, myalgia, peripheral neuropathy, rash, and neutropenia. CONCLUSION Gemcitabine and nab-paclitaxel followed by long-course chemoradiation represents a feasible neoadjuvant treatment strategy for borderline resectable or node-positive pancreatic cancer.
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Affiliation(s)
- Emerson Y. Chen
- Division of Hematology and Medical OncologyOregon Health & Science University, Knight Cancer InstitutePortlandOregonUSA
| | - Adel Kardosh
- Division of Hematology and Medical OncologyOregon Health & Science University, Knight Cancer InstitutePortlandOregonUSA
| | - Nima Nabavizadeh
- Department of Radiation MedicineOregon Health & Science UniversityPortlandOregonUSA
| | - Bryan Foster
- Department of Diagnostic RadiologyOregon Health & Science UniversityPortlandOregonUSA
| | - Skye C. Mayo
- Division of Surgical OncologyOregon Health & Science University, Knight Cancer InstitutePortlandOregonUSA
| | | | - Erin W. Gilbert
- Division of Gastrointestinal and General SurgeryOregon Health & Science UniversityPortlandOregonUSA
| | | | - Aaron Grossberg
- Department of Radiation MedicineOregon Health & Science UniversityPortlandOregonUSA
| | | | | | - Eric C. Anderson
- Division of Hematology and Medical OncologyOregon Health & Science University, Knight Cancer InstitutePortlandOregonUSA
| | - Brett C. Sheppard
- Division of Gastrointestinal and General SurgeryOregon Health & Science UniversityPortlandOregonUSA
| | - Charles R. Thomas
- Department of Radiation MedicineOregon Health & Science UniversityPortlandOregonUSA
- Radiation OncologyGeisel School of Medicine at Dartmouth and Dartmouth Cancer CenterNew HampshireLebanonUSA
| | - Charles D. Lopez
- Division of Hematology and Medical OncologyOregon Health & Science University, Knight Cancer InstitutePortlandOregonUSA
| | - Gina M. Vaccaro
- Division of Hematology and Medical OncologyOregon Health & Science University, Knight Cancer InstitutePortlandOregonUSA
- Providence Cancer InstitutePortlandOregonUSA
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13
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Nagakawa Y, Jang JY, Kawai M, Kim SC, Inoue Y, Matsuyama R, Heo JS, Honda M, Sugiura T, Ohtsuka M, Mizuno S, Kwon W, Uemura K, Han HS, Sugimoto M, Okano K, Nakamura M, Wada K, Kumamoto Y, Osakae H, Tsuchida A, Yoon YS, Park JS, Yamaue H, Endo I. Surgical Outcomes of Pancreatectomy with Resection of the Portal Vein and/or Superior Mesenteric Vein and Jejunal Vein for Pancreatic Head Cancer: A Multicenter Study. Ann Surg 2023; 277:e1081-e1088. [PMID: 34913900 DOI: 10.1097/sla.0000000000005330] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE The aim of this study was to investigate the safety and survival benefits of portal vein and/or superior mesenteric vein (PV/SMV) resection with jejunal vein resection (JVR) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA Few studies have shown the surgical outcome and survival of pancreatic resection with JVR, and treatment strategies for patients with PDAC suspected of jejunal vein (JV) infiltration remain unclear. METHODS In total, 1260 patients who underwent pancreatectomy with PV/ SMV resection between 2013 and 2016 at 50 facilities were included; treatment outcomes were compared between the PV/SMV group (PV/ SMV resection without JVR; n = 824), PV/SMV-J1 V group (PV/SMV resection with first jejunal vein resection; n = 394), and PV/SMV-J2,3 V group (PV/SMV resection with second jejunal vein or later branch resection; n = 42). RESULTS Postoperative complications and mortality did not differ between the three groups. The postoperative complication rate associated with PV/ SMV reconstruction was 11.9% in PV/SMV group, 8.6% in PV/SMV-J1 V group, and 7.1% in PV/SMV-J2,3V group; there were no significant differences among the three groups. Overall survival did not differ between PV/SMV and PV/SMV-J1 V groups (median survival; 29.2 vs 30.9 months, P = 0.60). Although PV/SMV-J2,3 V group had significantly shorter survival than PV/SMV group who underwent upfront surgery ( P = 0.05), no significant differences in overall survival of patients who received preoperative therapy. Multivariate survival analysis revealed that adjuvant therapy and R0 resection were independent prognostic factors in all groups. CONCLUSION PV/SMV resection with JVR can be safely performed and may provide satisfactory overall survival with the pre-and postoperative adjuvant therapy.
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Affiliation(s)
- Yuichi Nagakawa
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Jin-Young Jang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Manabu Kawai
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Song Cheol Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yosuke Inoue
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Ryusei Matsuyama
- Department of Hepatobiliary-pancreatic surgery, Japanese Foundation for Cancer Research, Cancer Institute Hospital, Tokyo, Japan
| | - Jin Seok Heo
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Masayuki Honda
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shugo Mizuno
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Mie, Japan
| | - Wooil Kwon
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kenichiro Uemura
- Department of Surgery, institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul, Korea
| | - Motokazu Sugimoto
- Department of Hepatobiliary-Pancreatic Surgery, National Cancer Center Hospital East, Chiba, Japan
| | - Keiichi Okano
- Department of Gastroenterologi-cal Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Keita Wada
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Yusuke Kumamoto
- Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.; and
| | - Hiroaki Osakae
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Akihiko Tsuchida
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul, Korea
| | - Joon Seong Park
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hiroki Yamaue
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Itaru Endo
- Department of Hepatobiliary-pancreatic surgery, Japanese Foundation for Cancer Research, Cancer Institute Hospital, Tokyo, Japan
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14
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Yabushita Y, Matsuyama R, Miyake K, Homma Y, Kumamoto T, Misumi T, Hata M, Yamanaka S, Fujii S, Endo I. Outcomes of neoadjuvant gemcitabine plus S-1 and radiation therapy for borderline resectable pancreatic cancer. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2023; 30:493-502. [PMID: 36178433 DOI: 10.1002/jhbp.1245] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 08/15/2022] [Accepted: 08/25/2022] [Indexed: 04/28/2023]
Abstract
BACKGROUND The efficacy of multidisciplinary treatment, including neoadjuvant treatment, in borderline resectable pancreatic cancer (BRPC) remains unclear. We assessed the efficacy of neoadjuvant chemoradiotherapy with gemcitabine and tegafu/gimearcil/oteracil (S-1) for BRPC. METHODS In a single center, nonrandomized prospective study, neoadjuvant chemoradiotherapy (NACRT) with gemcitabine plus S-1 was administered for BRPC (no. B090312028) in 122 patients enrolled between 2009 and 2015. Gemcitabine plus S-1 comprised gemcitabine on days 8 and 15, and daily S-1 on days 1-14. After two courses of gemcitabine plus S-1, 30 Gy radiotherapy was administered in 10 fractions with S-1. RESULTS Eighty-four and 38 patients had BR-PV and BR-A, respectively. No deaths occurred during NACRT. Ninety-four patients (77%) underwent resection with curative intent. R0 resection was performed in 91% of resected cases. Patients who underwent post-NACRT resection had better overall survival than did patients without resection (mean survival time [MST]: 24.7 vs 9.6 months, 5-year-survival rate (5 years): 30.3% vs 0%, P < .001). Adjuvant chemotherapy was administered in 73% of patients. MST and 5-year survival rate of the patients treated with NACRT followed by resection and adjuvant chemotherapy were 29.6 months and 34.3%, respectively. CONCLUSIONS Neoadjuvant chemoradiotherapy with gemcitabine and S-1 can be safely administered in BRPC and may require adjuvant chemotherapy. CLINICAL TRIAL REGISTRATION NUMBER This study was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) UMIN000006782.
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Affiliation(s)
- Yasuhiro Yabushita
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Ryusei Matsuyama
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Kentaro Miyake
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Yuki Homma
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Takafumi Kumamoto
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
| | - Toshihiro Misumi
- Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, Japan
| | - Masaharu Hata
- Department of Radiation Oncology, Yokohama City University School of Medicine, Yokohama, Japan
| | - Shoji Yamanaka
- Department of Pathology, Yokohama City University Hospital, Yokohama, Japan
| | - Satoshi Fujii
- Department of Pathology, Yokohama City University Hospital, Yokohama, Japan
- Department of Molecular Pathology, Yokohama City University School of Medicine, Yokohama, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan
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15
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Newhook TE, Vreeland TJ, Griffin JF, Tidwell RSS, Prakash LR, Koay EJ, Ludmir EB, Smaglo BG, Pant S, Overman M, Wolff RA, Ikoma N, Maxwell J, Kim MP, Lee JE, Katz MHG, Tzeng CWD. Prognosis Associated With CA19-9 Response Dynamics and Normalization During Neoadjuvant Therapy in Resected Pancreatic Adenocarcinoma. Ann Surg 2023; 277:484-490. [PMID: 36649067 DOI: 10.1097/sla.0000000000005184] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To characterize associations between carbohydrate antigen 19-9 (CA19-9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND Although normalization of CA19-9 during NT is associated with improved outcomes following PDAC resection, we hypothesize that CA19-9 dynamics during NT can improve prognostication. METHODS Characteristics for patients with PDAC undergoing NT (July 2011-October 2018) with ≥3 CA19-9 results (bilirubin<2mg/dL) were collected and grouped by CA19-9 dynamics. Nonproducers (<1 U/ml) were excluded, and normal was ≤35 U/ml. Postresection survival was compared among groups. RESULTS Of 431 patients, 166 had eligible CA19-9 values. Median baseline CA19-9 was 98 U/ml. Overall 2-year postresection recurrence-free survival (RFS) and overall survival (OS) were 37% and 63%, respectively. Patients with normalization (53%) had improved 2-year RFS (47% vs. 28%, P = 0.01) and OS (75% vs. 49%, P = 0.01). CA19-9 dynamics during NT were analyzed by shape, direction, and normalization creating response types ("A-B-C-D-E"). Type A was "Always" decreasing to normalization, B "Bidirectional" with eventual normalization, C "Consistently" normal, D any "Decrease" without normalization, and E "Elevating" without normalization. Types A and B responses were associated with the longest postresection 2-year RFS (51% and 56%) and OS (75% and 92%, respectively) whereas Types D and E had the worst outcomes. After adjusting for node-positivity, perineural invasion, and margin-positivity, CA19-9 response types were independently associated with both RFS and OS, and predicted outcomes are better than CA19-9 normalization alone (likelihood ratio test RFS P < 0.001, OS P = 0.01). CONCLUSIONS This novel A-B-C-D-E classification of CA19-9 dynamics during NT was associated with postresection outcomes more precisely than CA19-9 normalization alone.
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Affiliation(s)
- Timothy E Newhook
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | | | - Rebecca S S Tidwell
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Laura R Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Eugene J Koay
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ethan B Ludmir
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Brandon G Smaglo
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Shubham Pant
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Michael Overman
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Robert A Wolff
- Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jessica Maxwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Michael P Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
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16
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Toesca DAS, Susko M, von Eyben R, Baclay JRM, Pollom EL, Jeffrey RB, Poullos PD, Poultsides GA, Fisher GA, Visser BC, Koong AC, Feng M, Chang DT. Validation of a Resectability Scoring System for Prediction of Pancreatic Adenocarcinoma Surgical Outcomes. Ann Surg Oncol 2023; 30:3479-3488. [PMID: 36792768 DOI: 10.1245/s10434-023-13120-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 01/02/2023] [Indexed: 02/17/2023]
Abstract
BACKGROUND The most used pancreatic cancer (PC) resectability criteria are descriptive in nature or based solely on dichotomous degree of involvement (< 180° or > 180°) of vessels, which allows for a high degree of subjectivity and inconsistency. METHODS Radiographic measurements of the circumferential degree and length of tumor contact with major peripancreatic vessels were retrospectively obtained from pre-treatment multi-detector computed tomography (MDCT) images from PC patients treated between 2001 and 2015 at two large academic institutions. Arterial and venous scores were calculated for each patient, then tested for a correlation with tumor resection and R0 resection. RESULTS The analysis included 466 patients. Arterial and venous scores were highly predictive of resection and R0 resection in both the training (n = 294) and validation (n = 172) cohorts. A recursive partitioning tree based on arterial and venous score cutoffs developed with the training cohort was able to stratify patients of the validation cohort into discrete groups with distinct resectability probabilities. A refined recursive partitioning tree composed of three resectability groups was generated, with probabilities of resection and R0 resection of respectively 94 and 73% for group A, 61 and 35% for group B, and 4 and 2% for group C. This resectability scoring system (RSS) was highly prognostic, predicting median overall survival times of 27, 18.9, and 13.5 months respectively for patients in RSS groups A, B, and C (p < 0.001). CONCLUSIONS The proposed RSS was highly predictive of resection, R0 resection, and prognosis for patients with PC when tested against an external dataset.
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Affiliation(s)
- Diego A S Toesca
- Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, AZ, USA
| | - Matthew Susko
- Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA
| | - Rie von Eyben
- Department of Radiation Oncology, Stanford Cancer Institute, 875 Blake Wilbur Drive MC5847, Stanford, CA, 94305, USA
| | - J Richelsyn M Baclay
- Department of Radiation Oncology, Stanford Cancer Institute, 875 Blake Wilbur Drive MC5847, Stanford, CA, 94305, USA
| | - Erqi L Pollom
- Department of Radiation Oncology, Stanford Cancer Institute, 875 Blake Wilbur Drive MC5847, Stanford, CA, 94305, USA
| | - R Brooke Jeffrey
- Department of Radiology, Stanford Cancer Institute, Stanford, CA, USA
| | - Peter D Poullos
- Department of Radiology, Stanford Cancer Institute, Stanford, CA, USA
| | | | - George A Fisher
- Department of Medical Oncology, Stanford Cancer Institute, Stanford, CA, USA
| | - Brendan C Visser
- Department of Surgery, Stanford Cancer Institute, Stanford, CA, USA
| | - Albert C Koong
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Mary Feng
- Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA
| | - Daniel T Chang
- Department of Radiation Oncology, Stanford Cancer Institute, 875 Blake Wilbur Drive MC5847, Stanford, CA, 94305, USA. .,Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
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17
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Ghaneh P, Palmer D, Cicconi S, Jackson R, Halloran CM, Rawcliffe C, Sripadam R, Mukherjee S, Soonawalla Z, Wadsley J, Al-Mukhtar A, Dickson E, Graham J, Jiao L, Wasan HS, Tait IS, Prachalias A, Ross P, Valle JW, O'Reilly DA, Al-Sarireh B, Gwynne S, Ahmed I, Connolly K, Yim KL, Cunningham D, Armstrong T, Archer C, Roberts K, Ma YT, Springfeld C, Tjaden C, Hackert T, Büchler MW, Neoptolemos JP. Immediate surgery compared with short-course neoadjuvant gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable pancreatic cancer (ESPAC5): a four-arm, multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol 2023; 8:157-168. [PMID: 36521500 DOI: 10.1016/s2468-1253(22)00348-x] [Citation(s) in RCA: 145] [Impact Index Per Article: 72.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 10/10/2022] [Accepted: 10/11/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND Patients with borderline resectable pancreatic ductal adenocarcinoma have relatively low resection rates and poor survival despite the use of adjuvant chemotherapy. The aim of our study was to establish the feasibility and efficacy of three different types of short-course neoadjuvant therapy compared with immediate surgery. METHODS ESPAC5 (formerly known as ESPAC-5f) was a multicentre, open label, randomised controlled trial done in 16 pancreatic centres in two countries (UK and Germany). Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, biopsy proven pancreatic ductal adenocarcinoma in the pancreatic head, and were staged as having a borderline resectable tumour by contrast-enhanced CT criteria following central review. Participants were randomly assigned by means of minimisation to one of four groups: immediate surgery; neoadjuvant gemcitabine and capecitabine (gemcitabine 1000 mg/m2 on days 1, 8, and 15, and oral capecitabine 830 mg/m2 twice a day on days 1-21 of a 28-day cycle for two cycles); neoadjuvant FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, folinic acid given according to local practice, and fluorouracil 400 mg/m2 bolus injection on days 1 and 15 followed by 2400 mg/m2 46 h intravenous infusion given on days 1 and 15, repeated every 2 weeks for four cycles); or neoadjuvant capecitabine-based chemoradiation (total dose 50·4 Gy in 28 daily fractions over 5·5 weeks [1·8 Gy per fraction, Monday to Friday] with capecitabine 830 mg/m2 twice daily [Monday to Friday] throughout radiotherapy). Patients underwent restaging contrast-enhanced CT at 4-6 weeks after neoadjuvant therapy and underwent surgical exploration if the tumour was still at least borderline resectable. All patients who had their tumour resected received adjuvant therapy at the oncologist's discretion. Primary endpoints were recruitment rate and resection rate. Analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN, 89500674, and is complete. FINDINGS Between Sept 3, 2014, and Dec 20, 2018, from 478 patients screened, 90 were randomly assigned to a group (33 to immediate surgery, 20 to gemcitabine plus capecitabine, 20 to FOLFIRINOX, and 17 to capecitabine-based chemoradiation); four patients were excluded from the intention-to-treat analysis (one in the capecitabine-based chemoradiotherapy withdrew consent before starting therapy and three [two in the immediate surgery group and one in the gemcitabine plus capecitabine group] were found to be ineligible after randomisation). 44 (80%) of 55 patients completed neoadjuvant therapy. The recruitment rate was 25·92 patients per year from 16 sites; 21 (68%) of 31 patients in the immediate surgery and 30 (55%) of 55 patients in the combined neoadjuvant therapy groups underwent resection (p=0·33). R0 resection was achieved in three (14%) of 21 patients in the immediate surgery group and seven (23%) of 30 in the neoadjuvant therapy groups combined (p=0·49). Surgical complications were observed in 29 (43%) of 68 patients who underwent surgery; no patients died within 30 days. 46 (84%) of 55 patients receiving neoadjuvant therapy were available for restaging. Six (13%) of 46 had a partial response. Median follow-up time was 12·2 months (95% CI 12·0-12·4). 1-year overall survival was 39% (95% CI 24-61) for immediate surgery, 78% (60-100) for gemcitabine plus capecitabine, 84% (70-100) for FOLFIRINOX, and 60% (37-97) for capecitabine-based chemoradiotherapy (p=0·0028). 1-year disease-free survival from surgery was 33% (95% CI 19-58) for immediate surgery and 59% (46-74) for the combined neoadjuvant therapies (hazard ratio 0·53 [95% CI 0·28-0·98], p=0·016). Three patients reported local disease recurrence (two in the immediate surgery group and one in the FOLFIRINOX group). 78 (91%) patients were included in the safety set and assessed for toxicity events. 19 (24%) of 78 patients reported a grade 3 or worse adverse event (two [7%] of 28 patients in the immediate surgery group and 17 [34%] of 50 patients in the neoadjuvant therapy groups combined), the most common of which were neutropenia, infection, and hyperglycaemia. INTERPRETATION Recruitment was challenging. There was no significant difference in resection rates between patients who underwent immediate surgery and those who underwent neoadjuvant therapy. Short-course (8 week) neoadjuvant therapy had a significant survival benefit compared with immediate surgery. Neoadjuvant chemotherapy with either gemcitabine plus capecitabine or FOLFIRINOX had the best survival compared with immediate surgery. These findings support the use of short-course neoadjuvant chemotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma. FUNDING Cancer Research UK.
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Affiliation(s)
- Paula Ghaneh
- Department Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
| | - Daniel Palmer
- Department Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | - Silvia Cicconi
- Department Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK; Swiss Tropical and Public Health Institute, Allschwil, Switzerland; Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland
| | - Richard Jackson
- Department Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | | | - Charlotte Rawcliffe
- Department Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | | | | | | | | | | | | | - Janet Graham
- Beatson West of Scotland Cancer Centre, Glasgow, UK
| | | | | | | | | | - Paul Ross
- Guy's and St Thomas'Hospital, London, UK
| | - Juan W Valle
- University of Manchester, The Christie, Manchester, UK
| | | | | | | | | | | | | | | | | | | | | | | | | | - Christine Tjaden
- University Hospital Heidelberg Department of Surgery, Heidelberg, Germany
| | - Thilo Hackert
- University Hospital Heidelberg Department of Surgery, Heidelberg, Germany
| | - Markus W Büchler
- University Hospital Heidelberg Department of Surgery, Heidelberg, Germany
| | - John P Neoptolemos
- Department Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK; University Hospital Heidelberg Department of Surgery, Heidelberg, Germany
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18
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Sardar M, Recio-Boiles A, Mody K, Karime C, Chandana SR, Mahadevan D, Starr J, Jones J, Borad M, Babiker H. Pharmacotherapeutic options for pancreatic ductal adenocarcinoma. Expert Opin Pharmacother 2022; 23:2079-2089. [PMID: 36394449 DOI: 10.1080/14656566.2022.2149322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy projected to be the 2nd leading cause of cancer related death in the USA by 2030. This manuscript discusses current and evolving treatment approaches in patients with pancreatic cancer. AREAS COVERED PDAC is classified as: a) resectable, b) borderline resectable, c) unresectable (locally advanced and metastatic). The standard of care for patients who present with resectable pancreatic adenocarcinoma is six months of adjuvant modified (m) FOLFIRINOX, gemcitabine plus capecitabine, or single agent gemcitabine. For many reasons, there has been a paradigm shift to employing neoadjuvant chemotherapy. For resectable and borderline resectable patients, we generally start with systemic therapy and reevaluate resectability with subsequent scans specifically when the tumor is located in the head or body of the pancreas. Combined chemoradiation therapy can be employed in select patients. The standard of care for metastatic PDAC is FOLFIRINOX or gemcitabine and nab-paclitaxel. Germline and somatic genomic profiling should be obtained in all patients. Patients with a germline BRCA mutation can receive upfront gemcitabine and cisplatin. EXPERT OPINION Thorough understanding of molecular pathogenesis in PDAC has opened various therapeutic avenues. We remain optimistic that future treatment modalities such as targeted therapies, cellular therapies and immunotherapy will further improve survival in PDAC.
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Affiliation(s)
- Muhammad Sardar
- Division of Hematology-Oncology, Department of Medicine, University of Arizona Cancer Center, Tucson, Az, USA
| | - Alejandro Recio-Boiles
- Division of Hematology-Oncology, Department of Medicine, University of Arizona Cancer Center, Tucson, Az, USA
| | - Kabir Mody
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Jacksonville, FL, USA
| | | | | | - Daruka Mahadevan
- Division of Hematology and Oncology, Department of Medicine, University of Texas, San Antonio, Texas, USA
| | - Jason Starr
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Jacksonville, FL, USA
| | - Jeremy Jones
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Jacksonville, FL, USA
| | - Mitesh Borad
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Phoenix, AZ, USA
| | - Hani Babiker
- Division of Hematology-Oncology, Department of Medicine, Mayo Clinic Cancer Center, Jacksonville, FL, USA
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19
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Zhang JY, Ding JM, Zhou Y, Jing X. Nine-year survival of a 60-year-old woman with locally advanced pancreatic cancer under repeated open approach radiofrequency ablation: A case report. World J Clin Cases 2022; 10:11845-11852. [PMID: 36405299 PMCID: PMC9669842 DOI: 10.12998/wjcc.v10.i32.11845] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 06/18/2022] [Accepted: 10/12/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Radiofrequency ablation (RFA) is gaining popularity as an additional therapy for pancreatic ductal adenocarcinoma. RFA appears to be an attractive treatment option for patients with unresectable, locally advanced and nonmetastatic pancreatic cancer.
CASE SUMMARY A 60-year-old woman with 2 mo intermittent upper abdominal pains was admitted to hospital. She had undergone radical gastrectomy (Billroth II) for gastric antral cancer. Contrast-enhanced computed tomography (CECT) and abdominal ultrasound displayed a primary tumor in the neck of the pancreas. Pathological examination showed that the lesion was a pancreatic ductal adenocarcinoma. According to the results of the imaging, open approach RFA was selected to treat the primary tumor. Eight months later, CECT follow-up revealed local recurrence of the tumor, and another open RFA was performed. Although there is evidence that RFA for recurrence of other cancers such as hepatocellular carcinoma may prolong patient survival, it remains unclear whether repeat RFA for local recurrence of pancreatic cancer is feasible. The patient continued to enjoy 9 years of life following the first RFA.
CONCLUSION RFA of locally advanced, nonresectable, nonmetastatic, pancreatic tumor is characterized by feasibility-based treatment giving rise to tumor reduction based on improvement of quality of life.
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Affiliation(s)
- Jia-Yi Zhang
- Department of Ultrasound, The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, China
| | - Jian-Min Ding
- Department of Ultrasound, Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin 300170, China
| | - Yan Zhou
- Department of Ultrasound, Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin 300170, China
| | - Xiang Jing
- Department of Ultrasound, Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin 300170, China
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Barrak D, Villano AM, Moslim MA, Hopkins SE, Lefton MD, Ruth K, Reddy SS. Total Neoadjuvant Treatment for Pancreatic Ductal Adenocarcinoma Is Associated With Limited Lymph Node Yield but Improved Ratio. J Surg Res 2022; 280:543-550. [PMID: 36096019 DOI: 10.1016/j.jss.2022.08.002] [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: 08/26/2021] [Revised: 07/09/2022] [Accepted: 08/16/2022] [Indexed: 10/14/2022]
Abstract
INTRODUCTION The lymph node yield (LNY) and lymph node ratio (LNR) of nodal metastases following pancreatoduodenectomy (PD) have been reported as prognostic parameters in patients with pancreatic ductal adenocarcinoma (PDAC). However, they have not been compared in the setting of various neoadjuvant therapy modalities. METHODS A single institutional retrospective study identified 134 patients diagnosed with resectable, BLR- and LA-PDAC who underwent PD at Fox Chase Cancer Center between 2010 and 2019. Patients were categorized based on first-line treatment as follows: surgery first (SF), total neoadjuvant therapy (TNT), and single modality neoadjuvant therapy (SMNT). The histopathological reports of the surgical specimens were examined to obtain LNY and determine the counts of lymph nodes with metastases. Subsequently, LNR was calculated as the number of positive lymph nodes divided by the number of lymph nodes examined. RESULTS Overall, 49, 38, 27, 12, and 8 patients underwent SF approach, SMNT, incomplete TNT, induction TNT, and consolidation TNT, respectively. There was no difference in R0 resection and vascular resection between the groups (P = 0.096 and 0.794, respectively). The median counts of LNY were 22, 15, 21, 11.5, and 10, respectively (P < 0.001). The average LNR was 0.16, 0.07, 0.03, 0.02, and 0.02, respectively (P < 0.001). There were statistically significant differences in overall survival in the TNT groups (log-rank test P = 0.030). CONCLUSIONS PDAC patients who undergo the TNT modality exhibit lower LNY and improved LNR compared with the SF approach and SMNT neoadjuvant therapy groups. This is likely explained by the increased treatment response and lymph node obliteration associated with the TNT approach. Our results question the minimal requirement of 11-18 harvested lymph nodes for PD following TNT.
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Affiliation(s)
- Dany Barrak
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Anthony M Villano
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Maitham A Moslim
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Steven E Hopkins
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Max D Lefton
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Karen Ruth
- Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, Pennsylvania
| | - Sanjay S Reddy
- Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
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21
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Villano AM, O’Halloran E, Goel N, Ruth K, Barrak D, Lefton M, Reddy SS. Total neoadjuvant therapy is associated with improved overall survival and pathologic response in pancreatic adenocarcinoma. J Surg Oncol 2022; 126:502-512. [PMID: 35476892 PMCID: PMC9340441 DOI: 10.1002/jso.26906] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 04/10/2022] [Accepted: 04/18/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Few studies have evaluated outcomes of total neoadjuvant therapy (TNT) compared with single modality neoadjuvant therapy (SMNT) or surgery first (SF) for pancreatic ductal adenocarcinoma (PDAC). METHODS A single-institution retrospective review of PDAC patients who underwent pancreatectomy was conducted (1993-2019). Overall survival (OS) estimates from diagnosis and from surgery were determined using Kaplan-Meier methods; Cox proportional hazards models adjusted for covariates. RESULTS Surgery was performed upfront (SF) in 168 (46.9%), while 111 (31.0%) had chemotherapy or chemoradiation before resection (SMNT), and 79 (22.1%) underwent TNT (chemotherapy and chemoradiation). Resection margins were more frequently R0 in the TNT group (86.1%) compared with SMNT (64.0%) and SF (72%) (p < 0.001). Complete pathologic response was more common in the TNT group (10.1%) compared with SMNT (3.6%) or SF (0.6%) (p = 0.001), resulting in prolonged survival (median OS = 100.2 months). TNT patients demonstrated longer median OS from surgery (33.6 months) compared with SF (19.1 months) and SMNT (17.4 months) (p = 0.010), which persisted after controlling for covariates. CONCLUSIONS TNT is associated with more frequent complete pathologic response, a higher rate of margin negative resection, and prolonged OS as compared with SF or SMNT. Additional studies to identify subgroups that derive the greatest benefit are warranted.
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Affiliation(s)
- Anthony M. Villano
- Division of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA
| | - Eileen O’Halloran
- Division of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA
| | - Neha Goel
- Division of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA
| | - Karen Ruth
- Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, PA
| | - Dany Barrak
- Division of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA
| | - Max Lefton
- Division of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA
| | - Sanjay S. Reddy
- Division of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA
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22
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Katz MHG, Shi Q, Meyers J, Herman JM, Chuong M, Wolpin BM, Ahmad S, Marsh R, Schwartz L, Behr S, Frankel WL, Collisson E, Leenstra J, Williams TM, Vaccaro G, Venook A, Meyerhardt JA, O’Reilly EM. Efficacy of Preoperative mFOLFIRINOX vs mFOLFIRINOX Plus Hypofractionated Radiotherapy for Borderline Resectable Adenocarcinoma of the Pancreas: The A021501 Phase 2 Randomized Clinical Trial. JAMA Oncol 2022; 8:1263-1270. [PMID: 35834226 PMCID: PMC9284408 DOI: 10.1001/jamaoncol.2022.2319] [Citation(s) in RCA: 164] [Impact Index Per Article: 54.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 04/27/2022] [Indexed: 01/10/2023]
Abstract
Importance National guidelines endorse treatment with neoadjuvant therapy for borderline resectable pancreatic ductal adenocarcinoma (PDAC), but the optimal strategy remains unclear. Objective To compare treatment with neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) with or without hypofractionated radiation therapy with historical data and establish standards for therapy in borderline resectable PDAC. Design, Setting, and Participants This prospective, multicenter, randomized phase 2 clinical trial conducted from February 2017 to January 2019 among member institutions of National Clinical Trials Network cooperative groups used standardized quality control measures and included 126 patients, of whom 70 (55.6%) were registered to arm 1 (systemic therapy; 54 randomized, 16 following closure of arm 2 at interim analysis) and 56 (44.4%) to arm 2 (systemic therapy and sequential hypofractionated radiotherapy; all randomized before closure). Data were analyzed by the Alliance Statistics and Data Management Center during September 2021. Interventions Arm 1: 8 treatment cycles of mFOLFIRINOX (oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2; leucovorin, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2) over 46 hours, administered every 2 weeks. Arm 2: 7 treatment cycles of mFOLFIRINOX followed by stereotactic body radiotherapy (33-40 Gy in 5 fractions) or hypofractionated image-guided radiotherapy (25 Gy in 5 fractions). Patients without disease progression underwent pancreatectomy, which was followed by 4 cycles of treatment with postoperative FOLFOX6 (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; bolus fluorouracil, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2 over 46 hours). Main Outcomes and Measures Each treatment arm's 18-month overall survival (OS) rate was compared with a historical control rate of 50%. A planned interim analysis mandated closure of either arm for which 11 or fewer of the first 30 accrued patients underwent margin-negative (R0) resection. Results Of 126 patients, 62 (49%) were women, and the median (range) age was 64 (37-83) years. Among the first 30 evaluable patients enrolled to each arm, 17 patients in arm 1 (57%) and 10 patients in arm 2 (33%) had undergone R0 resection, leading to closure of arm 2 but continuation to full enrollment in arm 1. The 18-month OS rate of evaluable patients was 66.7% (95% CI, 56.1%-79.4%) in arm 1 and 47.3% (95% CI 35.8%-62.5%) in arm 2. The median OS of evaluable patients in arm 1 and arm 2 was 29.8 (95% CI, 21.1-36.6) months and 17.1 (95% CI, 12.8-24.4) months, respectively. Conclusions and Relevance This randomized clinical trial found that treatment with neoadjuvant mFOLFIRINOX alone was associated with favorable OS in patients with borderline resectable PDAC compared with mFOLFIRINOX treatment plus hypofractionated radiotherapy; thus, mFOLFIRINOX represents a reference regimen in this setting. Trial Registration ClinicalTrials.gov Identifier: NCT02839343.
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Affiliation(s)
| | - Qian Shi
- Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, Minnesota
| | - Jeff Meyers
- Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, Minnesota
| | - Joseph M. Herman
- Northwell Cancer Institute, National Cancer Institute Community Oncology Research Program, Manhasset, New York
| | | | | | - Syed Ahmad
- University of Cincinnati, Cincinnati, Ohio
| | - Robert Marsh
- NorthShore University Health System, Evanston, Illinois
| | | | | | - Wendy L. Frankel
- The Ohio State University Arthur G James Cancer Hospital, Columbus
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23
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Stevens L, Brown ZJ, Zeh R, Monsour C, Wells-Di Gregorio S, Santry H, Ejaz AM, Pawlik TM, Cloyd JM. Characterizing the patient experience during neoadjuvant therapy for pancreatic ductal adenocarcinoma: A qualitative study. World J Gastrointest Oncol 2022; 14:1175-1186. [PMID: 35949220 PMCID: PMC9244990 DOI: 10.4251/wjgo.v14.i6.1175] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 04/01/2022] [Accepted: 05/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Neoadjuvant therapy (NT) has increasingly been utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). It is the recommended approach for borderline resectable (BR) and locally advanced (LA) cancers and an increasingly utilized option for potentially resectable (PR) disease. Despite its increased use, little research has focused on patient-centered metrics among patients undergoing NT, including patient experiences, preferences, and recommendations. A better understanding of all aspects of the patient experience during NT may identify opportunities to design interventions aimed at improving quality of life; it may also facilitate the completion of NT and receipt of surgery, ultimately optimizing long-term outcomes. AIM To understand the experience of patients initiating and receiving NT to identify opportunities to improve neoadjuvant cancer care delivery. METHODS Semi-structured interviews of patients with localized PDAC during NT were conducted to explore their experience initiating and receiving NT. Interviews took place between August 2020 and October 2021. Due to the descriptive nature of the research, questions were open ended. Interviews were conducted over the phone, audio recorded and then transcribed. All interviews were coded by two independent researchers using NVivo 12, iteratively identifying themes until thematic saturation was achieved. An integrative approach to qualitative analysis was used, utilizing both inductive and deductive methods. RESULTS A total of 12 patients with localized PDAC were interviewed. Patients with BR (n = 7), PR (n = 2), and LA (n = 3) cancers participated in the study. All patients indicated that choosing NT was the doctor's recommendation, while most reported not being familiar with the concept of NT (n = 11) and that NT was presented as the only option (n = 8). Five themes describing the patient experience emerged: physical symptoms, emotional symptoms, coping mechanisms, access to care, and life factors. The most commonly cited recommendation for improving the experience of NT was improved education before and during NT (n = 7). Patients highlighted the need for more information on the rationale behind choosing NT prior to surgery, the anticipated surgery and its likelihood of surgery occurring after NT, as well as general information prior to starting NT treatment. The need for seeing different members of the healthcare team, including ancillary services was also frequently cited as a recommendation for improving the experience of NT (n = 5). CONCLUSION This study provides a framework to allow for a better understanding of the PDAC patient experience during NT and highlights opportunities to improve quality and quantity of life outcomes.
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Affiliation(s)
- Lena Stevens
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Zachary J Brown
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Ryan Zeh
- Department of General Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States
| | - Christina Monsour
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Sharla Wells-Di Gregorio
- Department of Psychiatry, Center for Palliative Care, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Heena Santry
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Aslam M Ejaz
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Timothy Michael Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
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Gray S, de Liguori Carino N, Radhakrishna G, Lamarca A, Hubner RA, Valle JW, McNamara MG. Clinical challenges associated with utility of neoadjuvant treatment in patients with pancreatic ductal adenocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1198-1208. [PMID: 35264307 DOI: 10.1016/j.ejso.2022.02.014] [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: 01/04/2022] [Revised: 02/03/2022] [Accepted: 02/10/2022] [Indexed: 11/22/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an increasingly common cancer with a persistently poor prognosis, and only approximately 20% of patients are clearly anatomically resectable at diagnosis. Historically, a paucity of effective therapy made it inappropriate to forego the traditional gold standard of upfront surgery in favour of neoadjuvant treatment; however, modern combination chemotherapy regimens have made neoadjuvant therapy increasingly viable. As its use has expanded, the rationale for neoadjuvant therapy has evolved from one of 'downstaging' to one of early treatment of micro-metastases and selection of patients with favourable tumour biology for resection. Defining resectability in PDAC is problematic; multiple differing definitions exist. Multidisciplinary input, both in initial assessment of resectability and in supervision of multimodality therapy, is therefore advised. European and North American guidelines recommend the use of neoadjuvant chemotherapy in borderline resectable (BR)-PDAC. Similar regimens may be applied in locally advanced (LA)-PDAC with the aim of improving potential access to curative-intent resection, but appropriate patient selection is key due to significant rates of recurrence after excision of LA disease. Upfront surgery and adjuvant chemotherapy remain standard-of-care in clearly resectable PDAC, but multiple trials evaluating the use of neoadjuvant therapy in this and other localised settings are ongoing.
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Affiliation(s)
- Simon Gray
- Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester, M20 4BX, United Kingdom
| | - Nicola de Liguori Carino
- Regional Hepato-Pancreato-Biliary Unit, Manchester Royal Infirmary, Oxford Rd, Manchester, M13 9WL, United Kingdom
| | - Ganesh Radhakrishna
- Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester, M20 4BX, United Kingdom
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester, M20 4BX, United Kingdom; Division of Cancer Sciences, University of Manchester, Oxford Rd, Manchester, M13 9PL, United Kingdom
| | - Richard A Hubner
- Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester, M20 4BX, United Kingdom; Division of Cancer Sciences, University of Manchester, Oxford Rd, Manchester, M13 9PL, United Kingdom
| | - Juan W Valle
- Division of Cancer Sciences, University of Manchester, Oxford Rd, Manchester, M13 9PL, United Kingdom; Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester, M20 4BX, United Kingdom
| | - Mairéad G McNamara
- Division of Cancer Sciences, University of Manchester, Oxford Rd, Manchester, M13 9PL, United Kingdom; Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Rd, Manchester, M20 4BX, United Kingdom.
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25
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Schreiber L, Zeh R, Monsour C, Ejaz A, Tsung A, Pawlik TM, Miller E, Noonan A, Krishna SG, Santry H, Cloyd JM. Multi-specialty physician perspectives on barriers and facilitators to the use of neoadjuvant therapy for pancreatic ductal adenocarcinoma. HPB (Oxford) 2022; 24:833-840. [PMID: 34764009 PMCID: PMC9035472 DOI: 10.1016/j.hpb.2021.10.010] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 10/15/2021] [Accepted: 10/19/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Neoadjuvant therapy (NT) is increasingly utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). Given the importance of completing multimodality therapy, the purpose of this qualitative study was to characterize physician perspectives on barriers and facilitators to delivering NT. METHODS A purposive sample of surgical, medical, and radiation oncologists participated in semi-structured interviews. Interviews were transcribed and coded by 3 independent researchers, iteratively identifying themes until saturation was achieved. RESULTS Participants (n = 27) were heterogeneous in specialty, years of experience, practice setting, gender, and geography. The most commonly cited advantage of NT was the ability to downstage patients. The most commonly cited barriers included lack of access and limited evidence. Patient preference for immediate surgery was frequently cited as a barrier, but most participants felt that patients eventually understood the treatment recommendation after informed discussion. Recommendations to enhance the delivery of NT included improved patient education, communication, and better evidence. CONCLUSION In this qualitative study, indications for, barriers to, and opportunities to improve the delivery of NT for localized PDAC were identified. These results highlight the need for better evidence and protocol standardization for NT as well as methods of improving care coordination, communication, and education to improve patient-centered outcomes.
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Affiliation(s)
- Lena Schreiber
- Department of Surgery, The Ohio State University Wexner Medical Center, 410 W 10th Ave, Columbus, OH, 43210, USA
| | - Ryan Zeh
- Department of Surgery, The Ohio State University Wexner Medical Center, 410 W 10th Ave, Columbus, OH, 43210, USA
| | - Christina Monsour
- Department of Surgery, The Ohio State University Wexner Medical Center, 410 W 10th Ave, Columbus, OH, 43210, USA
| | - Aslam Ejaz
- Department of Surgery, The Ohio State University Wexner Medical Center, 410 W 10th Ave, Columbus, OH, 43210, USA
| | - Allan Tsung
- Department of Surgery, The Ohio State University Wexner Medical Center, 410 W 10th Ave, Columbus, OH, 43210, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, 410 W 10th Ave, Columbus, OH, 43210, USA
| | - Eric Miller
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, 410 W 10th Ave, Columbus, OH, 43210, USA
| | - Anne Noonan
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, 410 W 10th Ave, Columbus, OH, 43210, USA
| | - Somashekar G Krishna
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, 410 W 10th Ave, Columbus, OH, 43210, USA
| | - Heena Santry
- Department of Surgery, The Ohio State University Wexner Medical Center, 410 W 10th Ave, Columbus, OH, 43210, USA
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, 410 W 10th Ave, Columbus, OH, 43210, USA.
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26
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Nehme F, Lee JH. Preoperative biliary drainage for pancreatic cancer. Dig Endosc 2022; 34:428-438. [PMID: 34275165 DOI: 10.1111/den.14081] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 07/15/2021] [Indexed: 12/15/2022]
Abstract
Pancreatic adenocarcinoma is currently one of the leading causes of cancer-related morbidity and mortality with dismal long term survival after diagnosis. Nearly 85% of pancreatic cancer patients present with advanced disease precluding curative surgical resection. In those who are candidates for surgery, preoperative biliary drainage (PBD) has been developed since the 1960s in order to improve surgical outcomes. While obstructive jaundice in resectable pancreatic cancer has been traditionally treated before surgical resection in all patients, data over the past decade demonstrated increased perioperative complications and morbidity with systematic PBD compared to direct surgery. With new evidence of potential adverse events, the role of routine PBD is being reassessed. Current indications for PBD include cholangitis, delayed surgery, and relief of jaundice in patients planned to receive neoadjuvant therapy (NAT). NAT is being increasingly utilized in borderline resectable as well as resectable pancreatic cancer and a higher proportion of patients with likely require PBD in the future. The evidence for endoscopic retrograde cholangiopancreatography as first line for PBD is robust with supporting data from endoscopic ultrasound assisted biliary drainage. Self-expanding metal stent was shown to be cost-effective in recent studies without increase in morbidity compared to plastic stents in this setting. In this review, we will summarize the current evidence for PBD in patients with pancreatic cancer.
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Affiliation(s)
- Fredy Nehme
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - Jeffrey H Lee
- Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, USA
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Kim K, Gaddam S, Liu Q. Pathogenesis, Epidemiology, and Prognosis of Pancreatic Adenocarcinomas. HEPATO-PANCREATO-BILIARY MALIGNANCIES 2022:461-481. [DOI: 10.1007/978-3-030-41683-6_28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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The impact of chemotherapy sequencing on resectable pancreatic cancer by stage. Surg Oncol 2021; 40:101694. [PMID: 34973593 DOI: 10.1016/j.suronc.2021.101694] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 11/30/2021] [Accepted: 12/11/2021] [Indexed: 11/23/2022]
Abstract
INTRODUCTION While chemotherapy is an important therapeutic modality for pancreatic cancer (PDAC), the optimal sequence of chemotherapy to surgery remains unclear. Further, the precise added benefit of including chemotherapy at each (especially early) stage has not been quantified. METHODS The National Cancer Database (NCDB) was queried for patients with PDAC who underwent pancreaticoduodenectomy between 2004 and 2016. Cox multivariable and Kaplan-Meier survival analyses were performed for disease-specific survival (DSS) and overall survival (OS) after correcting for confounders. Permutations of chemotherapy/surgery were compared: preoperative only (NCT), postoperative only (ACT), pre- and post-operative (perioperative, PCT), and no therapy (NoT). RESULTS 22975 patients met inclusion criteria. 13944(61%) received ACT, 1793(8%) received NCT and 946(4%) received PCT, while 6292(27%) did not receive chemotherapy. Log-rank test showed inferior survival in the NoT group compared to NCT, ACT, and PCT. Compared to the NoT group, PCT had the lowest rate of death (HR 0.704, p < 0.001) followed by NCT (HR 0.721, p < 0.001) and ACT (HR 0.759, p < 0.001).). CONCLUSION PDAC patients receiving chemotherapy, independent of their stage, will result in better DSS and OS. NCT should be given consideration for resectable disease including early stage PDAC and ideally complemented with postoperative chemotherapy. While there was a trend towards improved survival for PCT, NCT and ACT are reasonable options for stages IB-III.
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Evolving pancreatic cancer treatment: From diagnosis to healthcare management. Crit Rev Oncol Hematol 2021; 169:103571. [PMID: 34923121 DOI: 10.1016/j.critrevonc.2021.103571] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 12/13/2021] [Indexed: 12/12/2022] Open
Abstract
The prognosis of pancreatic ductal adenocarcinoma is still the worst among solid tumors. In this review, a panel of experts addressed the main unanswered questions about the clinical management of this disease, with the aim of providing practical decision support for physicians. On the basis of the evidence available from the literature, the main topics concerning pancreatic cancer are discussed: the diagnosis, as the need for a pathological characterization and the role for germ-line and somatic molecular profiling; the therapeutic management of resectable disease, as the role of upfront surgery or neoadjuvant chemotherapy, the post-operative restaging and the optimal timing foradjuvant chemotherapy, the management of the borderline resectable and locally advanced disease; the metastatic disease and the role of surgery for the management of patients with isolated metastasis and the use of biomarkers of metastatic potential; the role of supportive care and the healthcare management of pancreatic ductal adenocarcinoma.
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Han L, Song X. Lutein induces an inhibitory effect on the malignant progression of pancreatic adenocarcinoma by targeting BAG3/cholesterol homeostasis. J Biochem Mol Toxicol 2021; 36:e22958. [PMID: 34783111 DOI: 10.1002/jbt.22958] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 09/07/2021] [Accepted: 10/26/2021] [Indexed: 11/06/2022]
Abstract
Pancreatic adenocarcinoma (PDAC) is a fatal malignancy and patients with PDAC are mostly diagnosed at advanced stages. Lutein is a natural compound that belongs to the non-vitamin A carotenoids family and has presented antitumor effects on multiple cancer types. However, the function of lutein in PDAC and the mechanisms are not reported. Here, we explored the role of lutein in PDAC progression. Bioinformatic analysis identified that lutein is correlated with PDAC. Lutein suppressed the proliferation, migration, and invasion of PANC-1 cells. The upregulated genes in PDAC patients were identified and the overlap analysis predicted BAG3 as one target of lutein. Lutein repressed BAG3 expression and bioinformatics analysis predicted the interaction between lutein and BAG3. The inhibitory effects of lutein on PANC-1 cell proliferation, migration, and invasion are reversed by overexpression of BAG3. GSEA analysis identified that cholesterol homeostasis as one of the downstream signaling pathways of BAG3. In conclusion, lutein induced an inhibitory effect on the malignant progression of PDAC by targeting BAG3/cholesterol homeostasis. Lutein may be applied as a promising candidate for PDAC therapy.
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Affiliation(s)
- Lulu Han
- Department of Neurology Ward 3, The Fifth People's Hospital of Jinan, Jinan, Shandong, P.R. China
| | - Xiaoming Song
- Department of Gerontology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, P.R. China
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Development of a MicroRNA Signature Predictive of Recurrence and Survival in Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2021; 13:cancers13205168. [PMID: 34680317 PMCID: PMC8534163 DOI: 10.3390/cancers13205168] [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: 08/19/2021] [Revised: 09/30/2021] [Accepted: 10/06/2021] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Optimal patient selection for radiotherapy in pancreatic cancer is unestablished and may be improved with molecular profiling. To this end, we developed and validated a microRNA signature that predicted for worse locoregional recurrence and overall survival in patients with resectable pancreatic cancer. In a separate cohort of patients with borderline resectable and locally advanced pancreatic cancer, this risk signature was also predictive of worse locoregional recurrence, distant recurrence, and overall survival. Additionally, borderline resectable or locally advanced patients who had high risk score and did not receive radiation had worse outcomes compared to patients who either had low risk score or received radiation, irrespective of risk score. This risk signature may be useful in assessing patient prognosis and tailor therapy in patients with resectable, borderline resectable, or locally advanced pancreatic cancer, but requires further study. Abstract Background: Optimal patient selection for radiotherapy in pancreatic ductal adenocarcinoma (PDAC) is unestablished. Molecular profiling may select patients at high risk for locoregional recurrence (LRR) who would benefit from radiation. Methods: We included resectable pancreatic cancer (R-PDAC) patients, divided into training and validation cohorts, treated among three institutions with surgery and adjuvant chemotherapy, and borderline resectable or locally advanced pancreatic cancer (BR/LA-PDAC) patients treated with chemotherapy with or without radiation at the primary study institution. We isolated RNA from R-PDAC surgical specimens. Using NanoString, we identified miRNAs differentially expressed between normal and malignant pancreatic tissue. ElasticNet regression identified two miRNAs most predictive of LRR in the training cohort, miR-181b/d and miR-575, which were used to generate a risk score (RS). We evaluated the association of the median-dichotomized RS with recurrence and overall survival (OS). Results: We identified 183 R-PDAC and 77 BR/LA-PDAC patients with median follow up of 37 months treated between 2001 and 2014. On multivariable analysis of the R-PDAC training cohort (n = 90), RS was associated with worse LRR (HR = 1.34; 95%CI 1.27–11.38; p = 0.017) and OS (HR = 2.89; 95%CI 1.10–4.76; p = 0.027). In the R-PDAC validation cohort, RS was associated with worse LRR (HR = 2.39; 95%CI 1.03–5.54; p = 0.042), but not OS (p = 0.087). For BR/LA-PDAC, RS was associated with worse LRR (HR = 2.71; 95%CI 1.14–6.48; p = 0.025), DR (HR = 1.93; 95%CI 1.10–3.38; p = 0.022), and OS (HR = 1.97; 95%CI 1.17–3.34; p = 0.011). Additionally, after stratifying by RS and receipt of radiation in BR/LA-PDAC patients, high RS patients who did not receive radiation had worse LRR (p = 0.018), DR (p = 0.006), and OS (p < 0.001) compared to patients with either low RS or patients who received radiation, irrespective of RS. Conclusions: RS predicted worse LRR and OS in R-PDAC and worse LRR, DR, and OS in BR/LA-PDAC. This may select patients who would benefit from radiation and should be validated prospectively.
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Use of FOLFIRINOX or Nab-Paclitaxel Plus Gemcitabine for the Treatment of Locally Advanced Pancreatic Adenocarcinoma: A Single Institution Observational Study. Cancers (Basel) 2021; 13:cancers13194939. [PMID: 34638422 PMCID: PMC8508515 DOI: 10.3390/cancers13194939] [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: 08/30/2021] [Revised: 09/24/2021] [Accepted: 09/27/2021] [Indexed: 11/16/2022] Open
Abstract
Simple Summary We performed a retrospective analysis to evaluate the effect of treatment with FOLFIRINOX (FFN) or Nab-paclitaxel plus gemcitabine (GemNab) in patients with locally advanced (LA) pancreatic adenocarcinoma (PDAC). Forty-eight percent of patients treated with FFN became eligible for radical resection, and twenty-two percent of patients receiving GemNab underwent surgery after neoadjuvant treatment. FFN treatment was associated with a better overall survival, compared with GemNab (mOS 85.1 vs. 54.3 weeks, FFN and GemNab, respectively; HR = 0.54; p = 0.0109). We found different toxicity profiles between the two chemotherapy regimens. Future randomized clinical trials are mandatory to clarify the best treatment in patients with LA PDAC. Abstract Patients with locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) do not present distant metastases but are not eligible for surgery upfront. Chemotherapy regimens, such as FOLFIRINOX (FFN) or nab-paclitaxel plus gemcitabine (GemNab) in combination with loco-regional treatments are generally used in this setting. However, the best treatment choice is unknown. We retrospectively analyzed the information of 225 patients with stage II–III PDAC treated at our institution between October 2011 and December 2020. A total of 94 patients with LA PDAC who are non-eligible for surgery upfront received neoadjuvant FFN or GemNab. Of the 67 patients receiving FFN, 28 (41.8%) underwent surgery after neoadjuvant therapy. Of the 27 patients treated with GemNab, 6 (22.2%) became eligible for resection. The median overall survival (OS) was 85.1 weeks and 54.3 weeks in the FFN and GemNab groups, respectively (HR = 0.54, p = 0.0109). The median OS was 189.7 weeks and 76.4 weeks in the resected and unresected cohorts, respectively (HR = 0.25, p < 0.0001). Neutropenia (37.3%), anemia (6.0%), and diarrhea (6.0%) in the FFN group and neutropenia (22.2%) and thrombocytopenia (18.5%) in the GemNab groups were the most frequent grade 3–4 side effects. Higher rates of thrombocytosis (p < 0.0001) and peripheral edema (p < 0.0001) were observed in the GemNab group. Our results suggest that the use of FFN is associated with more favorable clinical outcomes than GemNab for patients with LA PDAC. Future randomized and controlled clinical trials are needed to further elucidate the role of these regimens and loco-regional treatments in this setting.
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Mavros MN, Moris D, Karanicolas PJ, Katz MHG, O'Reilly EM, Pawlik TM. Clinical Trials of Systemic Chemotherapy for Resectable Pancreatic Cancer: A Review. JAMA Surg 2021; 156:663-672. [PMID: 33787841 DOI: 10.1001/jamasurg.2021.0149] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
IMPORTANCE Adjuvant chemotherapy is the standard of care for resected pancreatic ductal adenocarcinoma (PDAC) based on level 1 evidence, but some studies suggest that a neoadjuvant approach (which is standard for borderline resectable PDAC) may be preferable for upfront resectable PDAC. An in-depth review was conducted of all randomized clinical trials that investigated neoadjuvant and adjuvant treatment of patients with resectable or resected PDAC, focusing on trial design, characteristics of enrolled population, and long-term outcomes. OBSERVATIONS The existing resectable PDAC trials have good internal validity but variable applicability because of their restrictive eligibility criteria. In these trials, overall survival is the criterion standard end point, but disease-free survival is more feasible, proximate, and specific to the assigned intervention (at the cost of subjective outcome assessment) and thus an acceptable end point in certain contexts. The prolonged survival in the PRODIGE 24 trial highlights both the success of mFOLFIRINOX (modified fluorouracil, leucovorin, irinotecan, and oxaliplatin) and the importance of patient selection. Neoadjuvant and perioperative trials have shown promising preliminary results; however, the number of patients who are not subsequently eligible for surgery reflects the limitations of this approach. Head-to-head comparisons of neoadjuvant and adjuvant treatments are limited to date in Western countries. Precision oncology with genomic and somatic testing for actionable mutations has promising preliminary results and may refine the management of PDAC, although the implications for early-stage disease and neoadjuvant therapy are unknown. CONCLUSIONS AND RELEVANCE This review found that adjuvant chemotherapy with mFOLFIRINOX is currently the standard of care in fit patients with resected PDAC; however, the role of neoadjuvant treatment is expanding. Precision oncology may help individualize the treatment regimen and sequence and improve outcomes. Enrollment of patients with resectable PDAC in clinical trials is strongly encouraged.
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Affiliation(s)
- Michail N Mavros
- Department of Surgery, University of Arkansas for Medical Sciences, Little Rock
| | - Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, North Carolina
| | - Paul J Karanicolas
- Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
- Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
| | - Eileen M O'Reilly
- Division of Gastrointestinal Medical Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- Department of Medicine, Weill Cornell Medical College, New York, New York
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus
- Deputy Editor, JAMA Surgery
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Kamarajah SK, Chatzizacharias N, Hodson J, Marcon F, Kalisvaart M, Punia P, Ting Ma Y, Dasari B, Marudanayagam R, Sutcliffe RP, Muiesan P, Mirza DF, Isaac J, Roberts KJ. Intention to treat outcomes among patients with pancreatic cancer treated using International Study Group on Pancreatic Surgery recommended pathways for resectable and borderline resectable disease. ANZ J Surg 2021; 91:1549-1557. [PMID: 33576568 DOI: 10.1111/ans.16643] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Revised: 01/21/2021] [Accepted: 01/22/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND The International Study Group on Pancreatic Surgery recommends upfront surgery for resectable pancreatic cancer or borderline resectable-venous (BR-V) disease and neoadjuvant therapy (NAT) among those with arterial involvement (BR-A or locally advanced, LA). Though neoadjuvant therapy (NAT) is a promising strategy, outcomes are rarely reported on intention-to-treat (ITT) basis. This study presents ITT outcomes where pathways to surgery were in line with International Study Group on Pancreatic Surgery guidelines. METHODS Patients recommended for potentially curative treatment with PDAC between 2012 and 2017 (n = 345) were classified as resectable, BR-A/BR-V or LA, according to NCCN criteria. The primary outcome was overall survival. Secondary outcomes were resection rates, positive margins and toxicity among patients receiving NAT. RESULTS At surgery, the resection rates were 78% (172/221), 65% (35/54) and 54% (21/39) for those with resectable, BR-V and BR-A/LA disease, respectively (P < 0.0001). The median survival of those resected in the BR-A/LA cohort was 31 months. However, on an ITT basis, there was no significant difference in survival between resectable, BR-V and BR-A/LA disease (median: 19 versus 15 versus 19 months; P = 0.585). On review, some 31 (44%) patients of the BR-A/LA cohort either did not receive or did not complete NAT. CONCLUSION To realize benefits of NAT, more patients need to complete NAT and to undergo resection. Upfront resection for BR-V disease is associated with equivalent outcomes to upfront surgery for resectable disease or NAT for BR-A/LA disease. Strategies to increase the proportion of patients who complete NAT and undergo resection are needed.
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Affiliation(s)
- Sivesh K Kamarajah
- Department of Pancreatic Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | | | - James Hodson
- Institute of Translational Medicine, University of Birmingham, Birmingham, UK
| | - Francesca Marcon
- Department of Pancreatic Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Marit Kalisvaart
- Department of Pancreatic Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Pankaj Punia
- Department of Oncology, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Yuk Ting Ma
- Department of Oncology, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Bobby Dasari
- Department of Pancreatic Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Ravi Marudanayagam
- Department of Pancreatic Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Robert P Sutcliffe
- Department of Pancreatic Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Paolo Muiesan
- Department of Pancreatic Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Darius F Mirza
- Department of Pancreatic Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - John Isaac
- Department of Pancreatic Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Keith J Roberts
- Department of Pancreatic Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, UK
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
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Nappo G, Donisi G, Zerbi A. Borderline resectable pancreatic cancer: Certainties and controversies. World J Gastrointest Surg 2021; 13:516-528. [PMID: 34194610 PMCID: PMC8223708 DOI: 10.4240/wjgs.v13.i6.516] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 04/09/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is currently a well-recognized entity, characterized by some specific anatomic, biological and conditional features: It includes patients with a stage of disease intermediate between the resectable and the locally advanced ones. The term BR identifies a tumour with an aggressive biological behaviour, on which a neoadjuvant approach instead of an upfront surgery one should be preferred, in order to obtain a radical resection (R0) and to avoid an early recurrence after surgery. Even if during the last decades several studies on this topic have been published, some aspects of BR-PDAC still represent a matter of debate. The aim of this review is to critically analyse the available literature on this topic, particularly focusing on: The problem of the heterogeneity of definition of BR-PDAC adopted, leading to a misinterpretation of published data; its current management (neoadjuvant vs upfront surgery); which neoadjuvant regimen should be preferably adopted; the problem of radiological restaging and the determination of resectability after neoadjuvant therapy; the post-operative outcomes after surgery; and the role and efficacy of adjuvant treatment for resected patients that already underwent neoadjuvant therapy.
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Affiliation(s)
- Gennaro Nappo
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano 20089, Italy
| | - Greta Donisi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano 20089, Italy
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano 20089, Italy
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Zhang Y, Huang ZX, Song B. Role of imaging in evaluating the response after neoadjuvant treatment for pancreatic ductal adenocarcinoma. World J Gastroenterol 2021; 27:3037-3049. [PMID: 34168406 PMCID: PMC8192284 DOI: 10.3748/wjg.v27.i22.3037] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/08/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Despite the development of multimodality treatments, including surgical resection, radiotherapy, and chemotherapy, the long-term prognosis of patients with PDAC remains poor. Recently, the introduction of neoadjuvant treatment (NAT) has made more patients amenable to surgery, increasing the possibility of R0 resection, treatment of occult micro-metastasis, and prolongation of overall survival. Imaging plays a vital role in tumor response evaluation after NAT. However, conventional imaging modalities such as multidetector computed tomography have limited roles in the assessment of tumor resectability after NAT for PDAC because of the similar appearance of tissue fibrosis and tumor infiltration. Perfusion computed tomography, using blood perfusion as a biomarker, provides added value in predicting the histopathologic response of PDAC to NAT by reflecting the changes in tumor matrix and fibrosis content. Other imaging technologies, including diffusion-weighted imaging of magnetic resonance imaging and positron emission tomography, can reveal the tumor response by monitoring the structural changes in tumor cells and functional metabolic changes in tumors after NAT. In addition, with the renewed interest in data acquisition and analysis, texture analysis and radiomics have shown potential for the early evaluation of the response to NAT, thus improving patient stratification to achieve accurate and intensive treatment. In this review, we briefly introduce the application and value of NAT in resectable and unresectable PDAC. We also summarize the role of imaging in evaluating the response to NAT for PDAC, as well as the advantages, limitations, and future development directions of current imaging techniques.
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Affiliation(s)
- Yun Zhang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Zi-Xing Huang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Nagaria TS, Wang H, Chatterjee D, Wang H. Pathology of Treated Pancreatic Ductal Adenocarcinoma and Its Clinical Implications. Arch Pathol Lab Med 2021; 144:838-845. [PMID: 32023088 DOI: 10.5858/arpa.2019-0477-ra] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/27/2019] [Indexed: 11/06/2022]
Abstract
CONTEXT.— Preoperative neoadjuvant therapy has been increasingly used to treat patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant therapy often induces extensive fibrosis in tumor, adjacent pancreatic parenchyma, and peripancreatic tissue. Histopathologic evaluations and histologic tumor response grading (HTRG) of posttherapy pancreatectomy specimens are very difficult and challenging. Studies on prognostic significance of posttherapy pathologic staging, optimal system for HTRG, and other pathologic parameters in treated PDAC patients are limited. OBJECTIVE.— This review is to provide a timely update of the prognostic values of posttherapy pathologic staging, HTRG, and other pathologic parameters in PDAC patients who received neoadjuvant therapy and pancreas resection. DATA SOURCES.— Systemic review of major studies on pathologic evaluation and its clinicopathologic implications in treated PDAC patients. CONCLUSIONS.— Systemic pathologic examination, histologic tumor regression grading, pathologic evaluation of the margins, tumor involvement of superior mesenteric vein/portal vein, accurate pathologic staging, and reporting of posttherapy pancreatectomy specimens provide highly valuable prognostic information for postoperative patient care. Our findings suggest for the first time that tumor size of 1.0 cm, instead of 2.0 cm, is a better cutoff for ypT2 in PDAC patients. The newly proposed 3-tier MD Anderson HTRG system not only has proved to be an independent prognostic marker for PDAC patients who received neoadjuvant therapy and pancreatectomy, but also improves interobserver agreement among pathologists in evaluation of tumor response. This grading system should be considered in future editions of the College of American Pathologists protocol for PDAC.
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Affiliation(s)
- Teddy Sutardji Nagaria
- From the Departments of Anatomical Pathology (Drs Nagaria and Huamin Wang), Gastrointestinal Medical Oncology (Dr Hua Wang), and Translational Molecular Pathology (Dr Huamin Wang), The University of Texas MD Anderson Cancer Center, Houston; and the Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri (Dr Chatterjee)
| | - Hua Wang
- From the Departments of Anatomical Pathology (Drs Nagaria and Huamin Wang), Gastrointestinal Medical Oncology (Dr Hua Wang), and Translational Molecular Pathology (Dr Huamin Wang), The University of Texas MD Anderson Cancer Center, Houston; and the Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri (Dr Chatterjee)
| | - Deyali Chatterjee
- From the Departments of Anatomical Pathology (Drs Nagaria and Huamin Wang), Gastrointestinal Medical Oncology (Dr Hua Wang), and Translational Molecular Pathology (Dr Huamin Wang), The University of Texas MD Anderson Cancer Center, Houston; and the Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri (Dr Chatterjee)
| | - Huamin Wang
- From the Departments of Anatomical Pathology (Drs Nagaria and Huamin Wang), Gastrointestinal Medical Oncology (Dr Hua Wang), and Translational Molecular Pathology (Dr Huamin Wang), The University of Texas MD Anderson Cancer Center, Houston; and the Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri (Dr Chatterjee)
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Patel SH, Katz MHG, Ahmad SA. The Landmark Series: Preoperative Therapy for Pancreatic Cancer. Ann Surg Oncol 2021; 28:4104-4129. [PMID: 34047859 DOI: 10.1245/s10434-021-10075-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 04/12/2021] [Indexed: 12/13/2022]
Abstract
The surgical treatment of pancreas ductal adenocarcinoma (PDAC) is plagued by high rates of distant recurrences despite complete resection, highlighting the importance of systemic therapy. Historically, patients with PDAC have been treated with postoperative therapy, but this sequencing strategy can be associated with the inability to complete therapy due to perioperative complications and prolonged recovery. In addition, a subset of patients progress early, irrespective of whether surgery is performed, highlighting the systemic nature of this disease. Preoperative therapy has increasingly been utilized in clinical practice, but studies examining its benefits are limited. In this Landmark Series, we will review seminal studies for resectable and borderline resectable PDAC.
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Affiliation(s)
- Sameer H Patel
- Department of Surgery and the Division of Surgical Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
| | - Matthew H G Katz
- Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Syed A Ahmad
- Department of Surgery and the Division of Surgical Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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Pancreatic Cancer: "Whether to Cross the Border"? Indian J Surg Oncol 2021; 12:235-237. [PMID: 34295062 DOI: 10.1007/s13193-021-01341-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 04/29/2021] [Indexed: 10/21/2022] Open
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40
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He C, Sun S, Zhang Y, Li S. Identification of Circulating Biomarkers and Construction of a Prognostic Signature for Survival Prediction in Locally Advanced Pancreatic Cancer After Irreversible Electroporation. J Inflamm Res 2021; 14:1689-1699. [PMID: 33953596 PMCID: PMC8091593 DOI: 10.2147/jir.s307884] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 04/14/2021] [Indexed: 12/14/2022] Open
Abstract
Background Irreversible electroporation (IRE) is a novel treatment for locally advanced pancreatic cancer (LAPC), but the predictive factors, based on cytokines and immunocytes of survival, are still lacking. This study aimed to establish a risk model based on cytokines and immunocytes for LAPC patients undergoing IRE treatment. Patients and Methods Peripheral blood samples were obtained from 31 LAPC patients and 8 healthy control subjects before IRE. The phenotypes of lymphocytes were analyzed by flow cytometry, and the cytokines were evaluated with Luminex microarray assay. Least absolute shrinkage and selection operator (LASSO) and Cox regression were applied to assess the prognostic factors for overall survival (OS) and progression-free survival (PFS). A receiver operating characteristic (ROC) curve and a concordance index (C-index) were used to compare the abilities to predict survival rates. Results The relationship between multiple cytokines and clinical factors was evaluated and their prognostic value was compared. The five best predictors for OS and PFS, including CA19-9, CD3+CD4+ T cells, CD3+CD8+ T cells, IL-17A, and TNF-α were selected and incorporated into a new immune panel. A risk model based on this immune panel was established and exhibited significantly higher values of C-indexes and AUC for OS and PFS prediction as compared with tumor marker score and TNM stage system. Conclusion We presented a risk model based on a microarray assay of cytokines and lymphocytes for LAPC patients after receiving IRE treatment for the first time. The established risk model showed relatively good performance in survival prediction and was able to facilitate tailed patient management in clinical practice.
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Affiliation(s)
- Chaobin He
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China
| | - Shuxin Sun
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China
| | - Yu Zhang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, People's Republic of China
| | - Shengping Li
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China
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Sánchez Morales G, Moguel Valladares R, Flores Maza J, Clemente Gutiérrez U, Sánchez-García Ramos E, Domínguez Rosado I, Chan Núñez L. Pancreatic ductal adenocarcinoma: Eleven years of experience at a tertiary care hospital center. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2021. [DOI: 10.1016/j.rgmxen.2020.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Perri G, Prakash L, Wang H, Bhosale P, Varadhachary GR, Wolff R, Fogelman D, Overman M, Pant S, Javle M, Koay E, Herman J, Kim M, Ikoma N, Tzeng CW, Lee JE, Katz MHG. Radiographic and Serologic Predictors of Pathologic Major Response to Preoperative Therapy for Pancreatic Cancer. Ann Surg 2021; 273:806-813. [PMID: 31274655 PMCID: PMC7703852 DOI: 10.1097/sla.0000000000003442] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE We sought to identify potential radiologic and serologic markers of pancreatic tumor response to therapy, using pathologic major response (pMR) as the objective endpoint. BACKGROUND We previously demonstrated that a pMR to preoperative therapy, defined as detection of <5% viable cancer cells in the surgical specimen on histopathological analysis, is an important prognostic factor for patients with pancreatic ductal adenocarcinoma (PDAC). METHODS Pretreatment and posttreatment computed tomography scans of consecutive patients who received preoperative chemotherapy and/or (chemo)radiation before pancreatectomy for PDAC between January 2010 and December 2018 were rereviewed. Response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, other radiographic changes in tumor size and anatomic extent, and posttreatment CA 19-9 levels were compared between patients who did and did not have a pMR on final histopathologic analysis of their surgical specimens. RESULTS A total of 290 patients with localized PDAC underwent pancreatectomy between 2010 and 2018 after receiving preoperative chemotherapy (n = 36; 12%), (chemo)radiation (n = 87; 30%), or both (n = 167; 58%). Among them, 28 (10%) experienced pMR, including 9 (3.1%) who experienced pathologic complete response. On multivariable logistic regression, low posttreatment CA 19-9 level, RECIST partial response, and reduction in tumor volume were confirmed to be independently associated with pMR (P < 0.01). CONCLUSIONS We identified serologic and radiographic indicators of pMR that could help inform the delivery of preoperative therapy to patients with PDAC.
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Affiliation(s)
- Giampaolo Perri
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Laura Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Huamin Wang
- Department of Anatomic Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Priya Bhosale
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Gauri R Varadhachary
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Robert Wolff
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - David Fogelman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Michael Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Shubham Pant
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Milind Javle
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Eugene Koay
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Joseph Herman
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Michael Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ching-Wei Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
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Garcia-Ochoa C, McArthur E, Skaro A, Leslie K, Hawel J. Pre-operative stenting and complications following pancreatoduodenectomy for pancreatic cancer: an analysis of the ACS-NSQIP registry. Surg Endosc 2020; 35:6604-6611. [PMID: 33237466 DOI: 10.1007/s00464-020-08160-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 11/15/2020] [Indexed: 11/24/2022]
Abstract
BACKGROUND Historically, pre-operative biliary stenting has been associated with higher infectious complication rates following pancreatoduodenectomy. However, alleviation of biliary obstruction is necessary for consideration of pre-operative chemotherapy, which may improve disease-free survival, or for mitigation of symptoms while awaiting surgery. Our aim is to compare contemporary post-operative complication risk among patients with pre-operative endoscopic retrograde cholangiopancreatography (ERCP) stenting compared to those without. METHODS Patients who underwent a pancreatoduodenectomy for pancreatic cancer with biliary obstruction within the ACS-NSQIP registry from 2014 to 2017 were identified. The primary outcome was to compare the risk of 30-day complication (composite outcome) between patients with and without pre-operative ERCP stenting. Propensity score matching was used to ensure balanced baseline characteristics and log-binomial regression models were used to estimate risk ratios for overall perioperative complication between groups. RESULTS From 6073 patients with obstructive jaundice undergoing pancreatoduodenectomy for pancreatic cancer, 92% (5564) were eligible for the study. After performing a propensity score matching on 20 baseline characteristics, 952 patients without stenting were matched to up to four patients who received pre-operative ERCP stenting (n = 3467) for a matched cohort of 4419. A total of 1901 (55%) patients with pre-operative ERCP stenting experienced a post-operative complication compared to 501 (53%) patients without stenting (risk ratio 1.04, 95% CI 0.97-1.11, p = 0.23). CONCLUSION Pre-operative ERCP stenting was not associated with an increased risk of post-operative complication in patients undergoing pancreatoduodenectomy with obstructive jaundice. Biliary stenting may be safely considered for symptom relief and to potentially facilitate pre-operative chemotherapy for pancreatic cancer.
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Affiliation(s)
- Carlos Garcia-Ochoa
- Department of General Surgery, London Health Sciences Centre, London, ON, Canada. .,Department of General Surgery, University of Ottawa, Ottawa, ON, Canada. .,Victoria Hospital, London Health Sciences Centre, 800 Commissioners Road East Room E2-213, Zone E, London, ON, N6A 5W9, Canada.
| | | | - Anton Skaro
- Department of General Surgery, London Health Sciences Centre, London, ON, Canada.,Department of Liver Transplantation, London Health Sciences Centre, London, ON, Canada
| | - Ken Leslie
- Department of General Surgery, London Health Sciences Centre, London, ON, Canada
| | - Jeff Hawel
- Department of General Surgery, London Health Sciences Centre, London, ON, Canada
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Trinh KV, Fischer DA, Gardner TB, Smith KD. Outcomes of Neoadjuvant Chemoradiation With and Without Systemic Chemotherapy in Resectable and Borderline Resectable Pancreatic Adenocarcinoma. Front Oncol 2020; 10:1461. [PMID: 33042792 PMCID: PMC7525017 DOI: 10.3389/fonc.2020.01461] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 07/09/2020] [Indexed: 01/01/2023] Open
Abstract
Introduction: Neoadjuvant therapy is increasingly being used for localized pancreatic adenocarcinoma. While there is evidence supporting neoadjuvant systemic chemotherapy as well as chemoradiation, more evidence is needed to determine whether systemic chemotherapy with chemoradiation offers benefits over chemoradiation alone. This study compares the outcomes of neoadjuvant chemoradiation therapy with and without systemic chemotherapy in resectable and borderline resectable pancreatic cancers. Methods: This retrospective study evaluated patients with resectable and borderline resectable pancreatic adenocarcinoma who completed neoadjuvant chemoradiation therapy with and without systemic chemotherapy prior to surgical resection. 149 patients met inclusion criteria, with 75 having resectable cancer and 74 having borderline resectable cancer. Outcomes included recurrence free and overall survival rates at 6, 12, and 36 months. Results: In resectable pancreatic carcinoma, 72% of patients treated with chemoradiation alone achieved 1 year recurrence free survival compared to 78% of patients treated with systemic chemotherapy and chemoradiation (p = 0.55). 28% of patients treated with chemoradiation alone had 3 years recurrence free survival compared to 31% of patients who received systemic and chemoradiation therapy (p = 0.75). In both treatment groups, 92% of patients lived past 1 year (p = 0.92), and 44% of patients survived at least 3 years (p = 0.95). In borderline resectable pancreatic carcinoma, 50% of patients treated with chemoradiation alone achieved 1 year recurrence free survival compared to 70% of patients treated with systemic chemotherapy and chemoradiation (p = 0.079). The 3 years recurrence free survival was 26 and 29% for the chemoradiation alone group and the systemic chemotherapy plus chemoradiation group, respectively (p = 0.85). There was no significant difference in 1 year overall survival: 85% of patients treated with chemoradiation alone survived compared to 92% of patients treated with systemic chemotherapy and chemoradiation (p = 0.32). Both groups had 41% 3 years overall survival (p = 0.96). Discussion: In resectable and borderline resectable pancreatic adenocarcinoma, there was no significant difference in overall or recurrence free survival between patients treated with chemoradiation with and without systemic chemotherapy. Our findings suggest that systemic neoadjuvant chemotherapy with chemoradiation and chemoradiation alone are efficacious treatments for localized pancreatic carcinoma. This brings into question whether more effective systemic chemotherapy is necessary to increase survival benefit.
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Affiliation(s)
- Katherine V Trinh
- Department of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States
| | - Dawn A Fischer
- Department of General Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States
| | - Timothy B Gardner
- Department of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States
| | - Kerrington D Smith
- Department of General Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States
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Radiographic patterns of first disease recurrence after neoadjuvant therapy and surgery for patients with resectable and borderline resectable pancreatic cancer. Surgery 2020; 168:440-447. [DOI: 10.1016/j.surg.2020.04.031] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 04/15/2020] [Accepted: 04/15/2020] [Indexed: 12/16/2022]
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Affiliation(s)
- Kristin N Kelly
- Division of Surgical Oncology, Dewitt-Daughtry Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 Northwest 14th Street, CRB, 4th Floor, Miami, FL 33136, USA
| | - Francisco I Macedo
- Department of Surgery, North Florida Regional Medical Center, University of Central Florida College of Medicine, Gainesville, FL, USA
| | - Nipun B Merchant
- Division of Surgical Oncology, Dewitt-Daughtry Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 Northwest 14th Street, CRB, 4th Floor, Miami, FL 33136, USA.
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Distal pancreas-coeliac axis resection with preoperative selective embolization of the coeliac axis: a single high-volume centre experience. Langenbecks Arch Surg 2020; 405:635-645. [PMID: 32683485 DOI: 10.1007/s00423-020-01919-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Accepted: 06/24/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Patients with ductal adenocarcinoma in the body and/or tail of the pancreas with involvement of the common hepatic artery and/or celiac axis have until recently been considered unresectable. In selected cases, distal pancreatectomy (DP) with en bloc celiac axis resection (DP-CAR) may be an option to achieve R0 resection. METHODS Patients with tumours in the body and/or tail of the pancreas locally advanced with involvement of the common hepatic artery and/or celiac axis, with no distant metastases, were evaluated for DP-CAR procedures. Preoperative embolization was performed 10-14 days prior to surgery to enhance collateral arterial supply for the liver and stomach. RESULTS A total of 21 patients went through DP-CAR of whom 15 were preoperatively embolized. R0 resection vas achieved in 76% of the patients comparable to our standard distal pancreatectomies. The DP-CAR patients had a significant longer postoperative hospital stay, but no difference in major complications, including pancreatic fistulas compared with our standard distal pancreatectomies. No 30 nor 90 days postoperative mortality were recorded. Median survival in patients who underwent DP and DP-CAR procedures was 24.0 and 23.5 months, respectively (P > 0.5). CONCLUSION Outcomes after DP-CAR are comparable to standard distal pancreatectomies. DP-CAR after preoperative embolization is feasible and may in selected patients be a good option for treating patients with tumours in the body and/or tail of the pancreas with central arterial involvement.
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Sánchez Morales GE, Moguel Valladares RA, Flores Maza J, Gutiérrez UC, Sánchez-García Ramos E, Domínguez Rosado I, Chan Núñez LC. Pancreatic ductal adenocarcinoma: Eleven years of experience at a tertiary care hospital center. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2020; 86:118-124. [PMID: 32616358 DOI: 10.1016/j.rgmx.2020.04.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Revised: 03/27/2020] [Accepted: 04/01/2020] [Indexed: 12/17/2022]
Abstract
INTRODUCTION AND AIM Pancreatic cancer is considered one of the most aggressive solid tumors. In Mexico, it is the twelfth cause of cancer, with 4,489 cases diagnosed annually, and accounts for 4.9% of oncologic deaths. The aim of our study was to describe the clinical and epidemiologic characteristics of the patients diagnosed with pancreatic cancer spanning an 11-year period at the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán". METHODS A retrospective, cross-sectional study was conducted that included 479 patients diagnosed with pancreatic cancer, within the time frame of 2003-2013. The documented findings were summarized through descriptive statistics. RESULTS Of the patients with pancreatic ductal adenocarcinoma, 50.9% were women, and the mean patient age at diagnosis was 61.5 years. A total of 48.4% of the cases were diagnosed at clinical stage IV, 12.9% presented with clinical stage III, and 25.0% had localized disease. Surgery was performed on 37.5% of the patients, the most frequent of which was pancreatoduodenectomy. The surgical mortality rate was 5.5%. CONCLUSION The clinical characteristics in our study group were similar to those described in the literature. However, the number of candidates for surgical treatment was higher than that reported in other hospitals and the percentage of borderline tumors was lower. Those differences, respectively, are possibly associated with the nature of our referral center and the prolonged intervals between diagnosis and treatment that result in the loss of potential surgical patients.
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Affiliation(s)
- G E Sánchez Morales
- Departamento de Cirugía General, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, México
| | - R A Moguel Valladares
- Departamento de Cirugía General, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, México
| | - J Flores Maza
- Departamento de Cirugía General, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, México
| | - U Clemente Gutiérrez
- Departamento de Cirugía General, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, México
| | - E Sánchez-García Ramos
- Departamento de Cirugía General, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, México
| | - I Domínguez Rosado
- Departamento de Cirugía General, Servicio de Cirugía Hepatopancreatobiliar, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, México
| | - L C Chan Núñez
- Departamento de Cirugía General, Servicio de Cirugía Hepatopancreatobiliar, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Ciudad de México, México.
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Mas L, Schwarz L, Bachet JB. Adjuvant chemotherapy in pancreatic cancer: state of the art and future perspectives. Curr Opin Oncol 2020; 32:356-363. [PMID: 32541325 DOI: 10.1097/cco.0000000000000639] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW The modalities of management of resectable pancreatic ductal adenocarcinoma (PDAC) have evolved in recent years with new practice guidelines on adjuvant chemotherapy and results of randomized phase III trials. The aim of this review is to describe the state of the art in this setting and to highlight future possible perspectives. RECENT FINDINGS Resectable PDAC is the tumor without vascular contact or a limited venous contact without vein irregularity. Several pathologic and biologic robust prognostic factors such as an R0 resection defined by a margin at least 1 mm have been validated. In phase III trials, the doublet gemcitabine-capecitabine provided a statistically significant, albeit modest overall survival benefit, but failed to show an improvement in relapse-free survival. Similarly, gemcitabine plus nab-paclitaxel did not increase disease-free survival. Modified FOLFIRINOX led to improved disease-free survival, overall survival, and metastasis-free survival, with acceptable toxicity. In the future, prognostic and/or predictive biomarkers could lead the optimization of therapeutic strategies and neoadjuvant treatment could become a standard of care in PDAC. SUMMARY After curative intent resection, modified FOLFIRINOX is the standard of care in adjuvant in fit patients with PDAC. Others regimens (monotherapy or gemcitabine-based) are an option in unfit patients.
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Affiliation(s)
- Léo Mas
- Department of Hepato-gastroenterology, Groupe Hospitalier Pitié Salpêtrière, Paris
| | - Lilian Schwarz
- Department of Digestive Surgery, Rouen University Hospital
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Normandie University, UNIROUEN, UMR 1245 INSERM, Rouen University Hospital, Rouen
| | - Jean-Baptiste Bachet
- Department of Hepato-gastroenterology, Groupe Hospitalier Pitié Salpêtrière, Paris
- Sorbonne University, UPMC University, Paris, France
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Abstract
OBJECTIVES Locally advanced pancreatic cancer (LAPC) is managed with multimodality therapy. We aim to evaluate the outcome of single-modality radiation therapy for LAPC. METHODS Locally advanced pancreatic cancer patients were identified between 2004 and 2013 using the National Cancer Database excluding patients who received chemotherapy or surgery. RESULTS A total of 6590 patients were included. The mean age was 73.5 (range, 28-90) years, 83.2% were white, and 54.4% were female. Tumors of 4 cm or greater (>T3 stage) accounted for 52.7%. The median radiation dose was 39.6 Gy. Stereotactic body radiation (SBRT) delivered to 64 patients and external-beam/intensity modulated radiotherapy in 416 patients. Radiation therapy was associated with improved overall survival (OS) compared with no treatment in univariate and multivariable analyses. The medians OS for patients who received SBRT, external-beam/intensity modulated radiotherapy, or no radiation were 8.6, 6.7, and 3.4 months, respectively (P < 0.001). There is a significant difference in 12-month OS for the SBRT cohort (31.9%; 95% confidence interval [CI], 20.9%-43.5%) compared with patients who received no radiation (15.1%; 95% CI, 14.2%-16.0%), and on multivariable analysis (hazard ratio, 0.50; 95% CI, 0.38-0.65; P < 0.001). CONCLUSIONS The current study suggests potential benefit for radiation therapy alone in comparison with no treatment in LAPC.
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