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Barreto SG, Strobel O, Salvia R, Marchegiani G, Wolfgang CL, Werner J, Ferrone CR, Abu Hilal M, Boggi U, Butturini G, Falconi M, Fernandez-Del Castillo C, Friess H, Fusai GK, Halloran CM, Hogg M, Jang JY, Kleeff J, Lillemoe KD, Miao Y, Nagakawa Y, Nakamura M, Probst P, Satoi S, Siriwardena AK, Vollmer CM, Zureikat A, Zyromski NJ, Asbun HJ, Dervenis C, Neoptolemos JP, Büchler MW, Hackert T, Besselink MG, Shrikhande SV. Complexity and Experience Grading to Guide Patient Selection for Minimally Invasive Pancreatoduodenectomy: An International Study Group for Pancreatic Surgery (ISGPS) Consensus. Ann Surg 2025; 281:417-429. [PMID: 39034920 DOI: 10.1097/sla.0000000000006454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/23/2024]
Abstract
OBJECTIVE To develop a universally accepted complexity and experience grading system to guide the safe implementation of robotic and laparoscopic minimally invasive pancreatoduodenectomy (MIPD). BACKGROUND Despite the perceived advantages of MIPD, its global adoption has been slow due to the inherent complexity of the procedure and challenges to acquiring surgical experience. Its wider adoption must be undertaken with an emphasis on appropriate patient selection according to adequate surgeon and center experience. METHODS The International Study Group for Pancreatic Surgery (ISGPS) developed a complexity and experience grading system to guide patient selection for MIPD based on an evidence-based review and a series of discussions. RESULTS The ISGPS complexity and experience grading system for MIPD is subclassified into patient-related risk factors and provider experience-related variables. The patient-related risk factors include anatomic (main pancreatic and common bile duct diameters), tumor-specific (vascular contact), and conditional (obesity and previous complicated upper abdominal surgery/disease) factors, all incorporated in an A-B-C classification, graded as no, a single, and multiple risk factors. The surgeon and center experience-related variables include surgeon total MIPD experience (cutoffs 40 and 80) and center annual MIPD volume (cutoffs 10 and 30), all also incorporated in an A-B-C classification. CONCLUSIONS This ISGPS complexity and experience grading system for robotic and laparoscopic MIPD may enable surgeons to optimally select patients after duly considering specific risk factors known to influence the complexity of the procedure. This grading system will likely allow for a thoughtful and stepwise implementation of MIPD and facilitate a fair comparison of outcomes between centers and countries.
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Affiliation(s)
- S George Barreto
- Department of Surgery, Flinders Medical Centre, Bedford Park, Adelaide, South Australia, Australia
- College of Medicine and Public Health, Flinders University, Bedford Park, Adelaide, South Australia, Australia
| | - Oliver Strobel
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Roberto Salvia
- Department of Surgery, The Pancreas Institute, Verona University Hospital, Verona, Italy
| | - Giovanni Marchegiani
- Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padua, Padua, Italy
| | | | - Jens Werner
- Department of General, Visceral and Transplant Surgery, University Hospital, LMU Munich, Munich, Germany
| | | | | | - Ugo Boggi
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
| | - Giovanni Butturini
- Department of Hepatopancreatobiliary Surgery, Pederzoli Hospital, Peschiera del Garda, Verona, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy
| | | | - Helmut Friess
- Department of Surgery, School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - Giuseppe K Fusai
- Department of Surgery, HPB and Liver Transplant Unit, Royal Free London NHS Foundation Trust, London, UK
| | - Christopher M Halloran
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | - Melissa Hogg
- Department of HPB Surgery, University of Chicago, Northshore, Chicago, IL
| | - Jin-Young Jang
- Department of General Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jorg Kleeff
- Department of Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale), Martin-Luther University Halle-Wittenberg, Germany
| | - Keith D Lillemoe
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Yi Miao
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, China
- Pancreas Institute, Nanjing Medical University, China
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University
| | - Yuichi Nagakawa
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Pascal Probst
- Department of Surgery, Cantonal Hospital Thurgau, Frauenfeld, Switzerland
| | - Sohei Satoi
- Department of Surgery, Kansai Medical University, Osaka, Japan
- Division of Surgical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | | | - Charles M Vollmer
- Department of Surgery, School of Medicine, University of Pennsylvania Perelman, Philadelphia, PA
| | - Amer Zureikat
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Nicholas J Zyromski
- Department of Surgery, School of Medicine, Indiana University, Indianapolis, IN
| | - Horacio J Asbun
- Division of Hepatobiliary and Pancreas Surgery, Miami Cancer Institute, Miami, FL
| | | | - John P Neoptolemos
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Botton-Champalimaud Pancreatic Cancer Centre, Champalimaud Foundation, Lisbon, Portugal
| | - Markus W Büchler
- Botton-Champalimaud Pancreatic Cancer Centre, Champalimaud Foundation, Lisbon, Portugal
| | - Thilo Hackert
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
- Cancer Center Amsterdam, the Netherlands
| | - Shailesh V Shrikhande
- Department of Gastrointestinal and HPB Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, MH, India
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Ocuin LM. Management of Localized Intrahepatic Cholangiocarcinoma: What Exactly is the 'Evidence'? Ann Surg Oncol 2024; 31:7676-7678. [PMID: 39103689 DOI: 10.1245/s10434-024-16023-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 07/29/2024] [Indexed: 08/07/2024]
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Drake J, Anaya DA, Fleming JB, Denbo JW. Surgery for Borderline Resectable Pancreatic Ductal Adenocarcinoma: Preoperative Planning, Technical Considerations, and Building a Program. Surg Clin North Am 2024; 104:1031-1048. [PMID: 39237162 DOI: 10.1016/j.suc.2024.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/07/2024]
Abstract
Pancreaticoduodenectomy, first described in 1935, has subsequently been refined over decades into the operation performed today for tumors of the pancreatic head and periampullary region. For years following Whipple's first publication, tumors found to be inseparable from the surrounding vasculature were considered locoregionally advanced and unresectable. Fortner began performing regional pancreatectomy with routine enbloc resection of the portal vein/superior mesenteric vein in an attempt to address high local recurrence rates and high rates of aborted operations due to vascular involvement.
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Affiliation(s)
- Justin Drake
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA
| | - Daniel A Anaya
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA; Division GI Surgery
| | - Jason B Fleming
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA; Department of Surgery, UT Southwestern Medical Center
| | - Jason W Denbo
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.
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Schouten TJ, van Goor IWJM, Dorland GA, Besselink MG, Bonsing BA, Bosscha K, Brosens LAA, Busch OR, Cirkel GA, van Dam RM, Festen S, Groot Koerkamp B, van der Harst E, de Hingh IHJT, Intven MPW, Kazemier G, Liem MSL, van Lienden KP, Los M, de Meijer VE, Patijn GA, Schreinemakers JMJ, Stommel MWJ, van Tienhoven GJ, Verdonk RC, Verkooijen HM, van Santvoort HC, Molenaar IQ, Daamen LA. The Value of Biological and Conditional Factors for Staging of Patients with Resectable Pancreatic Cancer Undergoing Upfront Resection: A Nationwide Analysis. Ann Surg Oncol 2024; 31:4956-4965. [PMID: 38386198 PMCID: PMC11236903 DOI: 10.1245/s10434-024-15070-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 01/31/2024] [Indexed: 02/23/2024]
Abstract
BACKGROUND Novel definitions suggest that resectability status for pancreatic ductal adenocarcinoma (PDAC) should be assessed beyond anatomical criteria, considering both biological and conditional factors. This has, however, yet to be validated on a nationwide scale. This study evaluated the prognostic value of biological and conditional factors for staging of patients with resectable PDAC. PATIENTS AND METHODS A nationwide observational cohort study was performed, including all consecutive patients who underwent upfront resection of National Comprehensive Cancer Network resectable PDAC in the Netherlands (2014-2019) with complete information on preoperative carbohydrate antigen (CA) 19-9 and Eastern Cooperative Oncology Group (ECOG) performance status. PDAC was considered biologically unfavorable (RB+) if CA19-9 ≥ 500 U/mL and favorable (RB-) otherwise. ECOG ≥ 2 was considered conditionally unfavorable (RC+) and favorable otherwise (RC-). Overall survival (OS) was assessed using Kaplan-Meier and Cox-proportional hazard analysis, presented as hazard ratios (HRs) with 95% confidence interval (CI). RESULTS Overall, 688 patients were analyzed with a median overall survival (OS) of 20 months (95% CI 19-23). OS was 14 months (95% CI 10 months-median not reached) in 20 RB+C+ patients (3%; HR 1.61, 95% CI 0.86-2.70), 13 months (95% CI 11-15) in 156 RB+C- patients (23%; HR 1.86, 95% CI 1.50-2.31), and 21 months (95% CI 12-41) in 47 RB-C+ patients (7%; HR 1.14, 95% CI 0.80-1.62) compared with 24 months (95% CI 22-27) in 465 patients with RB-C- PDAC (68%; reference). CONCLUSIONS Survival after upfront resection of anatomically resectable PDAC is worse in patients with CA19-9 ≥ 500 U/mL, while performance status had no impact. This supports consideration of CA19-9 in preoperative staging of resectable PDAC.
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Affiliation(s)
- Thijs J Schouten
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
| | - Iris W J M van Goor
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
- Department of Radiation Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Galina A Dorland
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
| | - Marc G Besselink
- Amsterdam UMC, Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Bert A Bonsing
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Koop Bosscha
- Department of Surgery, Jeroen Bosch Hospital, Den Bosch, The Netherlands
| | - Lodewijk A A Brosens
- Department of Pathology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Olivier R Busch
- Amsterdam UMC, Department of Surgery, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Geert A Cirkel
- Department of Medical Oncology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
- Department of Medical Oncology, Meander Medical Center, Amersfoort, The Netherlands
| | - Ronald M van Dam
- Department of Surgery, Maastricht UMC+,, Maastricht, The Netherlands
- GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
- Department of General and Visceral Surgery, University Hospital Aachen, Aachen, Germany
| | | | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | | | - Ignace H J T de Hingh
- GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Martijn P W Intven
- Department of Radiation Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Geert Kazemier
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University, Amsterdam, The Netherlands
| | - Mike S L Liem
- Department of Surgery, Medical Spectrum Twente, Enschede, The Netherlands
| | - Krijn P van Lienden
- Department of Interventional Radiology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - Maartje Los
- Department of Medical Oncology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - Vincent E de Meijer
- Department of Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Gijs A Patijn
- Department of Surgery, Isala Clinics, Zwolle, The Netherlands
| | | | - Martijn W J Stommel
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Geert Jan van Tienhoven
- Cancer Center Amsterdam, Amsterdam, The Netherlands
- Amsterdam UMC, Department of Radiation Oncology, location University of Amsterdam, Amsterdam, The Netherlands
| | - Robert C Verdonk
- Department of Gastroenterology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands
| | - Helena M Verkooijen
- Imaging Division, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Hjalmar C van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
| | - I Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands
| | - Lois A Daamen
- Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht University, Utrecht, The Netherlands.
- Imaging Division, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
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Saúde-Conde R, El Ghali B, Navez J, Bouchart C, Van Laethem JL. Total Neoadjuvant Therapy in Localized Pancreatic Cancer: Is More Better? Cancers (Basel) 2024; 16:2423. [PMID: 39001485 PMCID: PMC11240662 DOI: 10.3390/cancers16132423] [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: 05/15/2024] [Revised: 06/24/2024] [Accepted: 06/24/2024] [Indexed: 07/16/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge in oncology due to its advanced stage upon diagnosis and limited treatment options. Surgical resection, the primary curative approach, often results in poor long-term survival rates, leading to the exploration of alternative strategies like neoadjuvant therapy (NAT) and total neoadjuvant therapy (TNT). While NAT aims to enhance resectability and overall survival, there appears to be potential for improvement, prompting consideration of alternative neoadjuvant strategies integrating full-dose chemotherapy (CT) and radiotherapy (RT) in TNT approaches. TNT integrates chemotherapy and radiotherapy prior to surgery, potentially improving margin-negative resection rates and enabling curative resection for locally advanced cases. The lingering question: is more always better? This article categorizes TNT strategies into six main groups based on radiotherapy (RT) techniques: (1) conventional chemoradiotherapy (CRT), (2) the Dutch PREOPANC approach, (3) hypofractionated ablative intensity-modulated radiotherapy (HFA-IMRT), and stereotactic body radiotherapy (SBRT) techniques, which further divide into (4) non-ablative SBRT, (5) nearly ablative SBRT, and (6) adaptive ablative SBRT. A comprehensive analysis of the literature on TNT is provided for both borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC), with detailed sections for each.
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Affiliation(s)
- Rita Saúde-Conde
- Digestive Oncology Department, Hôpitaux Universitaires de Bruxelles (HUB), Université Libre de Bruxelles, 1070 Brussels, Belgium;
| | - Benjelloun El Ghali
- Department of Radiation Oncology, Hôpitaux Universitaires de Bruxelles (HUB), Institut Jules Bordet, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium; (B.E.G.); (C.B.)
| | - Julie Navez
- Department of Abdominal Surgery and Transplantation, Hôpitaux Universitaires de Bruxelles (HUB), Hopital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium;
| | - Christelle Bouchart
- Department of Radiation Oncology, Hôpitaux Universitaires de Bruxelles (HUB), Institut Jules Bordet, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium; (B.E.G.); (C.B.)
| | - Jean-Luc Van Laethem
- Digestive Oncology Department, Hôpitaux Universitaires de Bruxelles (HUB), Université Libre de Bruxelles, 1070 Brussels, Belgium;
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6
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Brown ZJ, Shannon AH, Cloyd JM. Neoadjuvant therapy for localized pancreatic ductal adenocarcinoma. Minerva Surg 2024; 79:315-325. [PMID: 38385797 DOI: 10.23736/s2724-5691.23.10150-x] [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: 02/23/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor with poor prognosis and rising incidence globally. Multimodal therapy that includes surgical resection and chemotherapy with or without radiation offers the best chance for optimal outcomes. The development of established criteria for anatomic staging of local primary tumors into potentially resectable (PR), borderline resectable (BR), and locally advanced (LA) has greatly clarified the optimal treatment strategies. While upfront surgical resection was traditionally the recommended approach for localized PDAC, increasingly neoadjuvant therapy (NT) is recommended prior to surgery. Whereas NT can lead to downstaging that facilitates surgical resection for BR/LA cancers, NT also enhances patient selection for surgery, improves margin-negative resection rates, and increases the odds of completing multimodality therapy for all patients with PDAC. Herein, we review the rationale for NT for localized PDAC and summarize existing and ongoing literature.
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Affiliation(s)
- Zachary J Brown
- Department of Surgery, Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Alexander H Shannon
- Department of Surgery, Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Jordan M Cloyd
- Department of Surgery, Ohio State University Wexner Medical Center, Columbus, OH, USA -
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Milella M. Stage Classification and Prognosis Assessment in Localized Pancreatic Cancer: It Takes Two to Tango. J Clin Oncol 2024; 42:1331-1334. [PMID: 38315951 DOI: 10.1200/jco.23.02494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 12/15/2023] [Accepted: 12/18/2023] [Indexed: 02/07/2024] Open
Affiliation(s)
- Michele Milella
- Section of Innovation Biomedicine-Oncology Area, Department of Engineering for Innovation Medicine (DIMI), University of Verona, Verona, Italy
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8
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Dekker EN, van Dam JL, Janssen QP, Besselink MG, DeSilva A, Doppenberg D, van Eijck CHJ, Nasar N, O'Reilly EM, Paniccia A, Prakash LR, Tzeng CWD, Verkolf EMM, Wei AC, Zureikat AH, Katz MHG, Groot Koerkamp B. Improved Clinical Staging System for Localized Pancreatic Cancer Using the ABC Factors: A TAPS Consortium Study. J Clin Oncol 2024; 42:1357-1367. [PMID: 38315954 DOI: 10.1200/jco.23.01311] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 10/03/2023] [Accepted: 11/14/2023] [Indexed: 02/07/2024] Open
Abstract
PURPOSE Previous studies suggest that besides anatomy (A: resectable, borderline resectable [BR], or locally advanced [LA]) also biologic (B: carbohydrate antigen 19-9 [CA 19-9]) and conditional (C: performance status) factors should be considered when staging patients with localized pancreatic ductal adenocarcinoma (PDAC). The prognostic value of the combined ABC factors has not been quantitatively validated. METHODS In this retrospective cohort study, we evaluated patients with localized PDAC treated with initial (modified) fluorouracil with leucovorin, irinotecan, and oxaliplatin ([m]FOLFIRINOX) at five high-volume pancreatic cancer centers in the United States and the Netherlands (2012-2019). Multivariable Cox proportional hazards analysis was used to investigate the impact of the ABC factors for overall survival (OS). RESULTS Overall, 1,835 patients with localized PDAC were included. Tumor stage at diagnosis was potentially resectable in 346 (18.9%), BR in 531 (28.9%), and LA in 958 (52.2%) patients. The baseline CA 19-9 was >500 U/mL in 559 patients (32.5%). Performance status was ≥1 in 1,110 patients (60.7%). Independent poor prognostic factors for OS were BR disease (hazard ratio [HR], 1.26 [95% CI, 1.06 to 1.50]), LA disease (HR, 1.71 [95% CI, 1.45 to 2.02]), CA 19-9 >500 U/mL (HR, 1.36 [95% CI, 1.21 to 1.52]), and WHO performance status ≥1 (HR, 1.31 [95% CI, 1.16 to 1.47]). Patients were assigned 1 point for each poor ABC factor and 2 points for LA disease. The median OS for patients with score 0-4 was 49.7, 29.9, 22.0, 19.1, and 14.9 months with corresponding 5-year OS rates of 47.0%, 28.9%, 19.2%, 9.3%, and 4.8%, respectively. CONCLUSION The ABC factors of tumor anatomy, CA 19-9, and performance status at diagnosis were independent prognostic factors for OS in patients with localized PDAC treated with initial (m)FOLFIRINOX. Staging of patients with localized PDAC at diagnosis should be based on anatomy, CA 19-9, and performance status.
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Affiliation(s)
- Esther N Dekker
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Jacob L van Dam
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Quisette P Janssen
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Annissa DeSilva
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Deesje Doppenberg
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Amsterdam, the Netherlands
| | | | - Naaz Nasar
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Eileen M O'Reilly
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Alessandro Paniccia
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Laura R Prakash
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Eva M M Verkolf
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Alice C Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Amer H Zureikat
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Matthew H G Katz
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
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9
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Dias E Silva D, Chung V. Neoadjuvant treatment for pancreatic cancer: Controversies and advances. Cancer Treat Res Commun 2024; 39:100804. [PMID: 38508132 DOI: 10.1016/j.ctarc.2024.100804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 02/28/2024] [Accepted: 03/02/2024] [Indexed: 03/22/2024]
Abstract
Despite the advancements in the treatment of localized pancreatic cancer, several unresolved issues persist in clinical practice, especially in the neoadjuvant setting. These include determining the criteria for selecting patients for treatment, identifying the most effective chemotherapy regimens, understanding the role of radiotherapy, and accurately assessing how patients respond to treatment. Current strategies for assessing patients before surgery involve thoroughly evaluating their overall health status, analyzing tumor markers, and using advanced imaging techniques. However, existing methods for staging the disease still have limitations when it comes to accurately detecting metastatic cancer. The ongoing debate between performing surgery upfront or administering neoadjuvant therapy highlights the need for robust clinical evidence to guide treatment decisions effectively. This review analyzes the evidence regarding controversial topics in neoadjuvant pancreatic cancer treatment and discusses further research efforts to enhance patient outcomes. To improve the outcomes found with surgery alone, multimodal treatment with chemotherapy.
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Affiliation(s)
| | - Vincent Chung
- City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, United States.
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10
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Labori KJ, Bratlie SO, Andersson B, Angelsen JH, Biörserud C, Björnsson B, Bringeland EA, Elander N, Garresori H, Grønbech JE, Haux J, Hemmingsson O, Liljefors MG, Myklebust TÅ, Nymo LS, Peltola K, Pfeiffer P, Sallinen V, Sandström P, Sparrelid E, Stenvold H, Søreide K, Tingstedt B, Verbeke C, Öhlund D, Klint L, Dueland S, Lassen K. Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol 2024; 9:205-217. [PMID: 38237621 DOI: 10.1016/s2468-1253(23)00405-3] [Citation(s) in RCA: 40] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 11/19/2023] [Accepted: 11/20/2023] [Indexed: 02/12/2024]
Abstract
BACKGROUND In patients undergoing resection for pancreatic cancer, adjuvant modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improves overall survival compared with alternative chemotherapy regimens. We aimed to compare the efficacy and safety of neoadjuvant FOLFIRINOX with the standard strategy of upfront surgery in patients with resectable pancreatic ductal adenocarcinoma. METHODS NORPACT-1 was a multicentre, randomised, phase 2 trial done in 12 hospitals in Denmark, Finland, Norway, and Sweden. Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, and had a resectable tumour of the pancreatic head radiologically strongly suspected to be pancreatic adenocarcinoma. Participants were randomly assigned (3:2 before October, 2018, and 1:1 after) to the neoadjuvant FOLFIRINOX group or upfront surgery group. Patients in the neoadjuvant FOLFIRINOX group received four neoadjuvant cycles of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h on day 1 of each 14-day cycle), followed by surgery and adjuvant chemotherapy. Patients in the upfront surgery group underwent surgery and then received adjuvant chemotherapy. Initially, adjuvant chemotherapy was gemcitabine plus capecitabine (gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of each 28-day cycle and capecitabine 830 mg/m2 twice daily for 3 weeks with 1 week of rest in each 28-day cycle; four cycles in the neoadjuvant FOLFIRINOX group, six cycles in the upfront surgery group). A protocol amendment was subsequently made to permit use of adjuvant modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 over 46 h on day 1 of each 14-day cycle; eight cycles in the neoadjuvant FOLFIRINOX group, 12 cycles in the upfront surgery group). Randomisation was performed with a computerised algorithm that stratified for each participating centre and used a concealed block size of two to six. Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was overall survival at 18 months. Analyses were done in the intention-to-treat (ITT) and per-protocol populations. Safety was assessed in all patients who were randomly assigned and received at least one cycle of neoadjuvant or adjuvant therapy. This trial is registered with ClinicalTrials.gov, NCT02919787, and EudraCT, 2015-001635-21, and is ongoing. FINDINGS Between Feb 8, 2017, and April 21, 2021, 77 patients were randomly assigned to receive neoadjuvant FOLFIRINOX and 63 to undergo upfront surgery. All patients were included in the ITT analysis. For the per-protocol analysis, 17 (22%) patients were excluded from the neoadjuvant FOLFIRINOX group (ten did not receive neoadjuvant therapy, four did not have pancreatic ductal adenocarcinoma, and three received another neoadjuvant regimen), and eight (13%) were excluded from the upfront surgery group (seven did not have pancreatic ductal adenocarcinoma and one did not undergo surgical exploration). 61 (79%) of 77 patients in the neoadjuvant FOLFIRINOX group received neoadjuvant therapy. The proportion of patients alive at 18 months by ITT was 60% (95% CI 49-71) in the neoadjuvant FOLFIRINOX group versus 73% (62-84) in the upfront surgery group (p=0·032), and median overall survival by ITT was 25·1 months (95% CI 17·2-34·9) versus 38·5 months (27·6-not reached; hazard ratio [HR] 1·52 [95% CI 1·00-2·33], log-rank p=0·050). The proportion of patients alive at 18 months in per-protocol analysis was 57% (95% CI 46-67) in the neoadjuvant FOLFIRINOX group versus 70% (55-83) in the upfront surgery group (p=0·14), and median overall survival in per-protocol population was 23·0 months (95% CI 16·2-34·9) versus 34·4 months (19·4-not reached; HR 1·46 [95% CI 0·99-2·17], log-rank p=0·058). In the safety population, 42 (58%) of 73 patients in the neoadjuvant FOLFIRINOX group and 19 (40%) of 47 patients in the upfront surgery group had at least one grade 3 or worse adverse event. 63 (82%) of 77 patients in the neoadjuvant group and 56 (89%) of 63 patients in the upfront surgery group had resection (p=0·24). One sudden death of unknown cause and one COVID-19-related death occurred after the first cycle of neoadjuvant FOLFIRINOX. Adjuvant chemotherapy was initiated in 51 (86%) of 59 patients with resected pancreatic ductal adenocarcinoma in the neoadjuvant FOLFIRINOX group and 44 (90%) of 49 patients with resected pancreatic ductal adenocarcinoma in the upfront surgery group (p=0·56). Adjuvant modified FOLFIRINOX was given to 13 (25%) patients in the neoadjuvant FOLFIRINOX group and 19 (43%) patients in the upfront surgery group. During adjuvant chemotherapy, neutropenia (11 [22%] patients in the neoadjuvant FOLFIRINOX group and five [11%] in the upfront surgery group) was the most common grade 3 or worse adverse event. INTERPRETATION This phase 2 trial did not show a survival benefit from neoadjuvant FOLFIRINOX in resectable pancreatic ductal adenocarcinoma compared with upfront surgery. Implementation of neoadjuvant FOLFIRINOX was challenging. Future trials on treatment sequencing in resectable pancreatic ductal adenocarcinoma should be biomarker driven. FUNDING Norwegian Cancer Society, South Eastern Norwegian Health Authority, The Sjöberg Foundation, and Helsinki University Hospital Research Grants.
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Affiliation(s)
- Knut Jørgen Labori
- Department of Hepato Pancreato Biliary Surgery, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | - Svein Olav Bratlie
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Surgery, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Bodil Andersson
- Department of Clinical Sciences Lund, Surgery, Lund University and Skåne University Hospital, Lund, Sweden
| | - Jon-Helge Angelsen
- Department of Gastrointestinal Surgery, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Christina Biörserud
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Surgery, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Bergthor Björnsson
- Department of Surgery in Linköping, Linköping University, Linköping, Sweden; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Erling Audun Bringeland
- Department of Gastrointestinal Surgery, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Nils Elander
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK
| | - Herish Garresori
- Department of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway
| | - Jon Erik Grønbech
- Department of Gastrointestinal Surgery, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Johan Haux
- Department of Oncology, Skaraborg Hospital Skövde, Skövde, Sweden; School of Health Sciences, University of Skövde, Skövde, Sweden
| | - Oskar Hemmingsson
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
| | - Maria Gustafsson Liljefors
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Tor Åge Myklebust
- Department of Registration, Cancer Registry of Norway, Oslo, Norway; Department of Research and Innovation, Møre and Romsdal Hospital Trust, Ålesund, Norway
| | - Linn Såve Nymo
- Department of Gastrointestinal Surgery, University Hospital of North Norway, Tromsø, Norway; Institute of Clinical Medicine, The Arctic University of Norway, Tromsø, Norway
| | - Katriina Peltola
- Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland
| | - Per Pfeiffer
- Department of Medical Oncology, Odense University Hospital, Odense, Denmark
| | - Ville Sallinen
- Gastroenterological Surgery/ Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | - Per Sandström
- Department of Surgery in Linköping, Linköping University, Linköping, Sweden; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Ernesto Sparrelid
- Division of Surgery and Oncology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Helge Stenvold
- Department of Oncology, University Hospital of North Norway, Tromsø, Norway
| | - Kjetil Søreide
- Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway
| | - Bobby Tingstedt
- Department of Clinical Sciences Lund, Surgery, Lund University and Skåne University Hospital, Lund, Sweden
| | - Caroline Verbeke
- Department of Pathology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Daniel Öhlund
- Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden; Department of Radiation Sciences, Umeå University, Umeå, Sweden
| | - Leif Klint
- Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Oncology, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Svein Dueland
- Department of Oncology, Oslo University Hospital, Oslo, Norway
| | - Kristoffer Lassen
- Department of Hepato Pancreato Biliary Surgery, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, The Arctic University of Norway, Tromsø, Norway
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11
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Boyev A, Prakash LR, Chiang YJ, Newhook TE, Bruno ML, Arvide EM, Dewhurst WL, Kim MP, Ikoma N, Lee JE, Snyder RA, Tzeng CWD, Katz MHG, Maxwell JE. Elevated CA 19-9 is associated with worse survival in patients with resected ampullary adenocarcinoma. Surg Oncol 2023; 51:101994. [PMID: 37742542 DOI: 10.1016/j.suronc.2023.101994] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 08/31/2023] [Accepted: 09/17/2023] [Indexed: 09/26/2023]
Abstract
BACKGROUND The prognostic utility of Carbohydrate Antigen 19-9 (CA 19-9) and Carcinoembryonic Antigen (CEA) in ampullary adenocarcinoma is unclear. We sought to evaluate the association between initial tumor marker levels and survival in patients with resected ampullary adenocarcinoma. METHODS This was a single-institution, retrospective cohort study of consecutive patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma from 1999 to 2021. CA 19-9 was assessed after biliary decompression. Contal and O'Quigley method determined optimal biomarker cutoff levels which were correlated with overall survival (OS) using the Kaplan-Meier method and Cox Proportional Hazards Regression. RESULTS A total of 180 patients underwent pancreatoduodenectomy. Patients with CA 19-9 >100 U/mL had a shorter median OS (28 vs. 132 months, p < 0.001) compared to patients with CA 19-9 ≤ 100 U/mL at diagnosis. Survival was similar between pancreaticobiliary and intestinal tumor subtypes when CA 19-9 was >100 U/mL (OS:25 vs. 33 months, p = 0.415). By Cox regression analysis, CA 19-9 >100 U/mL was independently associated with worse OS (HR 2.8, p = 0.001). CONCLUSIONS Preoperative CA 19-9 >100 U/mL was associated with shorter OS in patients with resected ampullary adenocarcinoma. CA 19-9 may be useful when counseling patients about prognosis or when considering the role of perioperative systemic therapy.
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Affiliation(s)
- Artem Boyev
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Laura R Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yi-Ju Chiang
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Timothy E Newhook
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Morgan L Bruno
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Elsa M Arvide
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Whitney L Dewhurst
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael P Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rebecca A Snyder
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jessica E Maxwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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12
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de Jesus VHF, Peixoto RD, Ribeiro HSDC, Pinheiro RN, Oliveira AF, Anghinoni M, Torres SM, Boff MF, Weschenfelder R, Prolla G, Riechelmann RP. Current clinical practice in the management of Brazilian patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). J Surg Oncol 2023. [PMID: 37795658 DOI: 10.1002/jso.27453] [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: 08/30/2023] [Accepted: 09/11/2023] [Indexed: 10/06/2023]
Abstract
BACKGROUND AND OBJECTIVES We aimed to describe the routine clinical practice of physicians involved in the treatment of patients with localized pancreatic ductal adenocarcinoma (PDAC) in Brazil. METHODS Physicians were invited through email and text messages to participate in an electronic survey sponsored by the Brazilian Gastrointestinal Tumor Group (GTG) and the Brazilian Society of Surgical Oncology (SBCO). We evaluated the relationship between variable categories numerically with false discovery rate-adjusted Fisher's exact test p values and graphically with Multiple Correspondence Analysis. RESULTS Overall, 255 physicians answered the survey. Most (52.5%) were medical oncologists, treated patients predominantly in the private setting (71.0%), and had access to multidisciplinary tumor boards (MTDTB; 76.1%). Medical oncologists were more likely to describe neoadjuvant therapy as beneficial in the resectable setting and surgeons in the borderline resectable setting. Most physicians would use information on risk factors for early recurrence, frailty, and type of surgery to decide treatment strategy. Doctors working predominantly in public institutions were less likely to have access to MTDTB and to consider FOLFIRINOX the most adequate regimen in the neoadjuvant setting. CONCLUSIONS Considerable differences exist in the management of localized PDAC, some of them possibly explained by the medical specialty, but also by the funding source of health care.
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Affiliation(s)
- Victor Hugo Fonseca de Jesus
- Medical Oncology Unit, Grupo Oncolínicas Florianópolis, Florianópolis, Santa Catarina, Brazil
- Medical Oncology Department, Centro de Pesquisas Oncológicas (CEPON), Florianópolis, Santa Catarina, Brazil
- Post-Graduate Program, A.C. Camargo Cancer, São Paulo, Sao Paulo, Brazil
| | - Renata D'Alpino Peixoto
- Medical Oncology Unit, Grupo Oncoclínicas/Centro Paulista de Oncologia, São Paulo, São Paulo, Brazil
| | | | | | | | - Marciano Anghinoni
- Surgical Oncology Unit, Centro de Oncologia do Paraná (Oncoville), Curitiba, Paraná, Brazil
| | - Silvio Melo Torres
- Department of Abdominal Surgery, A.C. Camargo Cancer, São Paulo, São Paulo, Brazil
| | - Márcio Fernando Boff
- Surgical Oncology Unit, Hospital Mãe de Deus, Porto Alegre, Rio Grande do Sul, Brazil
| | - Rui Weschenfelder
- Department of Medical Oncology, Hospital Moinho de Vento, Porto Alegre, Rio Grande do Sul, Brazil
| | - Gabriel Prolla
- Grupo Oncoclínicas Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Rachel P Riechelmann
- Department of Medical Oncology, A.C. Camargo Cancer, São Paulo, São Paulo, Brazil
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13
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Ferrari C, Leon P, Falconi M, Boggi U, Piardi T, Sulpice L, Cavaliere D, Rosso E, Chirica M, Ravazzoni F, Memeo R, Pessaux P, De Blasi V, Mascherini M, De Cian F, Navarro F, Panaro F. Multi-visceral resection for left-sided pancreatic ductal adenocarcinoma: a multicenter retrospective analysis from European countries. Langenbecks Arch Surg 2023; 408:386. [PMID: 37776339 DOI: 10.1007/s00423-023-03110-0] [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: 03/12/2023] [Accepted: 09/14/2023] [Indexed: 10/02/2023]
Abstract
BACKGROUND Due to delayed diagnosis and a lower surgical indication rate, left-sided pancreatic ductal adenocarcinoma (PDAC) is often associated with a poor prognosis in comparison to pancreatic head tumors. Multi-visceral resections (MVR) associated with distal pancreatectomy could be proposed for patients presenting with locally infiltrating disease. METHODS We retrospectively analyzed a multi-centric cohort of left-sided PDAC patients operated on from 2009 to 2020. Thirteen European high-volume HPB centers participated in this study. We analyzed patients who underwent distal pancreatectomy (DP) associated with MVR and compared them to standard DP patients. RESULTS Among 258 patients treated curatively for PDAC of the body and tail, 28 patients successfully underwent MVR. A longer operative time was observed in the MVR group (295 min +/- 74 vs. 250 min +/- 96, p= 0.248). The post-operative complication rate was comparable between the two groups (46.4% in the MVR group vs. 62.2% in the control group, p= 0.108). The incidence of positive margin (R1) was similar between the two groups (28.6% vs. 26.6%; p=0.827). After a median follow-up of 25 (9-111) months, overall survival was comparable between the two groups (p= 0.519). CONCLUSIONS Multi-visceral resection in left-sided pancreatic ductal adenocarcinoma is safe and feasible and should be considered in selected cases as it seems to provide acceptable surgical and oncological outcomes.
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Affiliation(s)
- Cecilia Ferrari
- HPB and Transplant Unit, University of Montpellier, Montpellier, France.
- Ospedale Policlinico San Martino, Genova, Italy.
| | - Piera Leon
- HPB and Transplant Unit, University of Montpellier, Montpellier, France
| | - Massimo Falconi
- Chirurgia Pancreatica, IRCCS Ospedale San Raffaele, Milano, Italy
| | - Ugo Boggi
- Chirurgia HPB e Trapianto di Fegato, Ospedale Cisanello, Università degli Studi di Pisa, Pisa, Italy
| | | | | | | | - Edoardo Rosso
- Department of Surgery, Istituto Fondazione Poliambulanza, Brescia, Italy
| | | | | | | | | | - Vito De Blasi
- Service de Chirurgie Générale et Mini-Invasive, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg
| | | | | | - Francis Navarro
- HPB and Transplant Unit, University of Montpellier, Montpellier, France
| | - Fabrizio Panaro
- HPB and Transplant Unit, University of Montpellier, Montpellier, France
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14
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Doppenberg D, van Dam JL, Han Y, Bonsing BA, Busch OR, Festen S, van der Harst E, de Hingh IH, Homs MYV, Kwon W, Lee M, Lips DJ, de Meijer VE, Molenaar IQ, Nuyttens JJ, Patijn GA, van Roessel S, van der Schelling GP, Suker M, Versteijne E, de Vos-Geelen J, Wilmink JW, van Eijck CHJ, van Tienhoven G, Jang JY, Besselink MG, Groot Koerkamp B. Predictive value of baseline serum carbohydrate antigen 19-9 level on treatment effect of neoadjuvant chemoradiotherapy in patients with resectable and borderline resectable pancreatic cancer in two randomized trials. Br J Surg 2023; 110:1374-1380. [PMID: 37440421 PMCID: PMC10480034 DOI: 10.1093/bjs/znad210] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 04/06/2023] [Accepted: 06/13/2023] [Indexed: 07/15/2023]
Abstract
BACKGROUND Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers. METHODS In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test. RESULTS Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501). CONCLUSION Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice.
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Affiliation(s)
- Deesje Doppenberg
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands
- Cancer Centre Amsterdam, Amsterdam, the Netherlands
- Department of Radiation Oncology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands
| | - Jacob L van Dam
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Youngmin Han
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Bert A Bonsing
- Department of Surgery, Leiden University Medical Centre, Leiden, the Netherlands
| | - Olivier R Busch
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands
- Cancer Centre Amsterdam, Amsterdam, the Netherlands
| | | | | | - Ignace H de Hingh
- Department of Surgery, Catherina Hospital, Eindhoven, the Netherlands
| | - Marjolein Y V Homs
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Wooil Kwon
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Mirang Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Daan J Lips
- Department of Surgery, Medisch Spectrum Twente, Enschede, the Netherlands
| | - Vincent E de Meijer
- Department of Surgery, University of Groningen and University Medical Centre Groningen, Groningen, the Netherlands
| | - I Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Centre Utrecht, University of Utrecht, Utrecht, the Netherlands
| | - Joost J Nuyttens
- Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Gijs A Patijn
- Department of Surgery, Isala Oncology Centre, Zwolle, the Netherlands
| | - Stijn van Roessel
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands
- Cancer Centre Amsterdam, Amsterdam, the Netherlands
| | | | - Mustafa Suker
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Eva Versteijne
- Cancer Centre Amsterdam, Amsterdam, the Netherlands
- Department of Radiation Oncology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands
| | - Judith de Vos-Geelen
- Department of Internal Medicine, Division of Medical Oncology, GROW, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Johanna W Wilmink
- Cancer Centre Amsterdam, Amsterdam, the Netherlands
- Department of Medical Oncology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands
| | | | - Geertjan van Tienhoven
- Cancer Centre Amsterdam, Amsterdam, the Netherlands
- Department of Radiation Oncology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands
| | - Jin-Young Jang
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, Location University of Amsterdam, Amsterdam, the Netherlands
- Cancer Centre Amsterdam, Amsterdam, the Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
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15
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Jain AJ, Maxwell JE, Katz MHG, Snyder RA. Surgical Considerations for Neoadjuvant Therapy for Pancreatic Adenocarcinoma. Cancers (Basel) 2023; 15:4174. [PMID: 37627202 PMCID: PMC10453019 DOI: 10.3390/cancers15164174] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 08/04/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease process with a 5-year survival rate of only 11%. Neoadjuvant therapy in patients with localized pancreatic cancer has multiple theoretical benefits, including improved patient selection for surgery, early delivery of systemic therapy, and assessment of response to therapy. Herein, we review key surgical considerations when selecting patients for neoadjuvant therapy and curative-intent resection. Accurate determination of resectability at diagnosis is critical and should be based on not only anatomic criteria but also biologic and clinical criteria to determine optimal treatment sequencing. Borderline resectable or locally advanced pancreatic cancer is best treated with neoadjuvant therapy and resection, including vascular resection and reconstruction when appropriate. Lastly, providing nutritional, prehabilitation, and supportive care interventions to improve patient fitness prior to surgical intervention and adequately address the adverse effects of therapy is critical.
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Affiliation(s)
| | | | | | - Rebecca A. Snyder
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (A.J.J.)
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16
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Cassese G, Han HS, Yoon YS, Lee JS, Lee B, Cubisino A, Panaro F, Troisi RI. Role of neoadjuvant therapy for nonmetastatic pancreatic cancer: Current evidence and future perspectives. World J Gastrointest Oncol 2023; 15:911-924. [PMID: 37389109 PMCID: PMC10302990 DOI: 10.4251/wjgo.v15.i6.911] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/17/2023] [Accepted: 04/24/2023] [Indexed: 06/14/2023] Open
Abstract
Pancreatic adenocarcinoma (PDAC) is one of the most common and lethal human cancers worldwide. Surgery followed by adjuvant chemotherapy offers the best chance of a long-term survival for patients with PDAC, although only approximately 20% of the patients have resectable tumors when diagnosed. Neoadjuvant chemotherapy (NACT) is recommended for borderline resectable pancreatic cancer. Several studies have investigated the role of NACT in treating resectable tumors based on the recent advances in PDAC biology, as NACT provides the potential benefit of selecting patients with favorable tumor biology and controls potential micro-metastases in high-risk patients with resectable PDAC. In such challenging cases, new potential tools, such as ct-DNA and molecular targeted therapy, are emerging as novel therapeutic options that may improve old paradigms. This review aims to summarize the current evidence regarding the role of NACT in treating non-metastatic pancreatic cancer while focusing on future perspectives in light of recent evidence.
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Affiliation(s)
- Gianluca Cassese
- Department of Clinical Medicine and Surgery, Division of Minimally Invasive HPB Surgery and Transplantation Service, Federico II University Hospital, Naples 80131, Italy
| | - Ho-Seong Han
- Department of Surgery, Seoul National University College of Medicine, Seongnam 13620, Gyeonggi-do, South Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University College of Medicine, Seongnam 13620, Gyeonggi-do, South Korea
| | - Jun Suh Lee
- Department of Surgery, Seoul National University College of Medicine, Seongnam 13620, Gyeonggi-do, South Korea
| | - Boram Lee
- Department of Surgery, Seoul National University College of Medicine, Seongnam 13620, Gyeonggi-do, South Korea
| | - Antonio Cubisino
- Department of HPB Surgery and Transplantation, Beaujon Hospital, Clichy 92110, France
| | - Fabrizio Panaro
- Department of Digestive Surgery and Liver Transplantation, CHU Montpellier, Montpellier 34100, France
| | - Roberto Ivan Troisi
- Department of Clinical Medicine and Surgery, Division of Minimally Invasive HPB Surgery and Transplantation Service, Federico II University Hospital, Naples 80131, Italy
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17
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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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18
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Donovan EC, Prakash LR, Chiang YJ, Bruno ML, Maxwell JE, Ikoma N, Tzeng CWD, Katz MHG, Lee JE, Kim MP. Incidence of Postoperative Complications Following Pancreatectomy for Pancreatic Cystic Lesions or Pancreatic Cancer. J Gastrointest Surg 2023; 27:319-327. [PMID: 36443557 PMCID: PMC11921787 DOI: 10.1007/s11605-022-05534-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 10/15/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND In contrast to pancreatic ductal adenocarcinoma (PDAC), the risks of pancreatectomy for mucinous pancreatic cysts (MCs) are balanced against the putative goal of removing potentially malignant tumors. Despite undergoing similar operations, different rates of perioperative complications and morbidity between MC and PDAC patient populations may affect recommendations for resection. We therefore sought to compare the rates of postoperative complications between patients undergoing pancreatectomies for MCs or PDAC. METHODS A prospectively maintained institutional database was used to identify patients who underwent surgical resection for MCs or PDAC from July 2011 to August 2019. Patient demographics, complications, and perioperative data were compared between groups. RESULTS A total of 103 patients underwent surgical resection for MCs and 428 patients underwent resection for PDAC. Combined major 90-day postoperative complications were similar between MC and PDAC patients undergoing pancreaticoduodenectomy (PD, 32.5% vs. 20.0%, p = 0.068) or distal pancreatectomy (DP, 30.2% vs. 20.5%, p = 0.172). The most frequent complications were postoperative pancreatic fistula (POPF), abscess, and postoperative bleeding. The incidence of 90-day ISGPS Grade B/C POPF was higher in cyst patients undergoing PD (17.5% vs. 4.1%, p = 0.003) but not DP (25.4% vs. 20.5%, p = 0.473). No significant differences in operative time or length of stay between MCs and PDAC cohorts were observed. CONCLUSIONS POPFs occur more frequently and at higher grades in patients undergoing PD for MCs than for PDAC and should inform patient selection. Accordingly, the perioperative management of MC patients undergoing PD should emphasize POPF risk mitigation.
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Affiliation(s)
- Eileen C Donovan
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Laura R Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yi-Ju Chiang
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Morgan L Bruno
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jessica E Maxwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael P Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Department of Genetics, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, FCT17.6006, Unit 1484, Houston, TX, 77030, USA.
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19
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Lee B, Yoon YS, Kang M, Park Y, Lee E, Jo Y, Lee JS, Lee HW, Cho JY, Han HS. Validation of the Anatomical and Biological Definitions of Borderline Resectable Pancreatic Cancer According to the 2017 International Consensus for Survival and Recurrence in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Upfront Surgery. Ann Surg Oncol 2023; 30:3444-3454. [PMID: 36695994 DOI: 10.1245/s10434-022-13043-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Accepted: 11/14/2022] [Indexed: 01/26/2023]
Abstract
BACKGROUND The International Consensus Criteria (ICC) (2017) redefined patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) according to anatomical, biological, and conditional aspects. However, these new criteria have not been validated comprehensively. The aim of this retrospective cohort study was to validate the anatomical and biological definitions of BR-PDAC for oncological outcomes in patients with resectable (R) and BR-PDAC undergoing upfront surgery. METHODS A total of 404 patients who underwent upfront surgery for R- and BR-PDAC from 2004 to 2020 were included. The patients were classified according to the ICC as follows: resectable (R) (n = 259), anatomical borderline (BR-A) (n = 43), biological borderline (BR-B) (n = 81), and anatomical and biologic borderline (BR-AB) (n = 21). RESULTS Compared with the R and BR-B groups, the BR-A and BR-AB groups had higher postoperative complication rates (16.5% and 27.2% vs 32.5% and 33.4%; P < 0.001) and significantly lower R0 resection rates (85.7% and 80.2% vs 65.1% and 61.9%; P = 0.003). In contrast, compared with the R and BR-A groups, the BR-B (32.1%) and BR-AB (57.1%) groups had higher early recurrence rates (within postoperative 6 months) (16.5% and 25.6% vs 32.1% and 57.1%; P < 0.001) and significantly lower 3-year recurrence-free survival rates (36.1% and 20.7% vs 12.1% and 7.8%; P < 0.001). CONCLUSION Anatomically defined BR-PDAC was associated with a higher risk of margin-positive resection and postoperative complication rates, while biologically defined BR-PDAC was associated with higher early recurrence rates and lower survival rates. Thus, the anatomical and biological definitions are useful in predicting the prognosis and determining the usefulness of neoadjuvant therapy.
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Affiliation(s)
- Boram Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea.
| | - MeeYoung Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Yeshong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Eunhye Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Yeongsoo Jo
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Jun Suh Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, Gyeonggi-do, Korea
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20
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de Jesus VHF, Riechelmann RP. Current Treatment of Potentially Resectable Pancreatic Ductal Adenocarcinoma: A Medical Oncologist's Perspective. Cancer Control 2023; 30:10732748231173212. [PMID: 37115533 PMCID: PMC10155028 DOI: 10.1177/10732748231173212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 03/01/2023] [Accepted: 04/06/2023] [Indexed: 04/29/2023] Open
Abstract
Pancreatic cancer has traditionally been associated with a dismal prognosis, even in early stages of the disease. In recent years, the introduction of newer generation chemotherapy regimens in the adjuvant setting has improved the survival of patients treated with upfront resection. However, there are multiple theoretical advantages to deliver early systemic therapy in patients with localized pancreatic cancer. So far, the evidence supports the use of neoadjuvant therapy for patients with borderline resectable pancreatic cancer. The benefit of this treatment sequence for patients with resectable disease remains elusive. In this review, we summarize the data on adjuvant therapy for pancreatic cancer and describe which evidence backs the use of neoadjuvant therapy. Additionally, we address important issues faced in clinical practice when treating patients with localized pancreatic cancer.
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21
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Routine neoadjuvant chemotherapy for all patients with resectable pancreatic ductal adenocarcinoma? A review of the evidence. Curr Opin Pharmacol 2022; 67:102305. [PMID: 36223686 DOI: 10.1016/j.coph.2022.102305] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 09/07/2022] [Accepted: 09/12/2022] [Indexed: 01/25/2023]
Abstract
Pancreatic ductal adenocarcinoma is an aggressive malignancy that carries a poor prognosis because the majority of patients present with locally advanced or metastatic disease. However, even patients who are fortunate enough to present with resectable disease are often plagued by high recurrence rates. While adjuvant chemotherapy has been shown to decrease the risk of recurrence after surgery, post operative complications and poor performance status after surgery prevent up to 50% of patients from receiving it. Given the benefits of neoadjuvant therapy in patients with borderline resectable disease, it is understandable that neoadjuvant therapy has been steadily increasing in patients with resectable cancers as well. In this review paper, we highlight the rational and existing evidence of using neoadjuvant therapy in all patients with resectable pancreatic adenocarcinoma.
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22
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DiPeri TP, Newhook TE, Prakash LR, Ikoma N, Maxwell JE, Kim MP, Lee JE, Katz MH, Tzeng CWD. Prognostic significance of preoperative and postoperative CA 19-9 normalization in pancreatic adenocarcinoma treated with neoadjuvant therapy or surgery first. J Surg Oncol 2022; 126:1021-1027. [PMID: 35726394 PMCID: PMC9547830 DOI: 10.1002/jso.26989] [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: 04/27/2022] [Revised: 06/08/2022] [Accepted: 06/11/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND Normal(ization) of serum carbohydrate 19-9 (CA19-9) before/after surgery has not been compared in patients with pancreatic adenocarcinoma (PDAC) treated with neoadjuvant therapy (NT) versus surgery-first (SF). METHODS Characteristics for patients with PDAC who underwent resection from July 2011 to October 2018 were collected. Patients with pre-/postoperative CA19-9, bilirubin <2 mg/dL, and initial CA19-9 > 1 U/ml were included. Overall survival (OS) and recurrence-free survival (RFS) were compared by pre-/postoperative CA19-9. RESULTS In patients receiving NT, normal pre/postoperative CA19-9 ("NTnl/nl ") was associated with median RFS and OS (26 and 77mo), followed by those who normalized after surgery ("NTabnl/nl " 16 and 44mo). For SF patients, normal pre-/postoperative CA19-9 ("SFnl/nl ") was associated with median RFS and OS (115 and not estimable mo), followed by those who normalized after resection ("SFabnl/nl " 18 and 49mo). Groups "NTabnl/abnl " and "SFabnl/abnl " with elevated CA19-9 both before and after resection had the worst median RFS and OS durations. CONCLUSIONS While a normal(ized) postoperative CA19-9 may result in similar survival as preoperative normal(ization), postoperative normalization failed to occur in nearly 30% of SF patients. NT should be considered in patients presenting with elevated CA19-9. If considering SF, ideal patients may include those with normal CA19-9 at presentation.
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Affiliation(s)
- Timothy P. DiPeri
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston TX
| | - Timothy E. Newhook
- Department of Surgical Oncology, 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
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston TX
| | - Jessica E. 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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23
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Landa K, Schmitz R, Farrow NE, Rushing C, Niedzwiecki D, Cerullo M, Herbert GS, Shah KN, Zani S, Blazer DG, Allen PJ, Lidsky ME. Surgical resection is associated with improved long-term survival of patients with resectable pancreatic head cancer compared to multiagent chemotherapy. HPB (Oxford) 2022; 24:1153-1161. [PMID: 34987008 DOI: 10.1016/j.hpb.2021.12.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 12/02/2021] [Accepted: 12/13/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Standard of care for resectable pancreatic cancer is a combination of surgical resection (SR) and multiagent chemotherapy (MCT). We aim to determine whether SR or MCT is associated with superior survival for patients receiving only single-modality therapy. METHODS Patients with stage I-IIb pancreatic head adenocarcinoma who received either MCT or SR were identified in the NCDB (2013-2015). Following a piecewise approach to estimating hazards over the course of follow-up, conditional overall survival (OS) at 30, 60, and 90 days after treatment initiation was estimated using landmark analyses. RESULTS 3103 patients received MCT alone (60.3%) and 2043 underwent SR alone (39.7%). SR had an OS disadvantage at 30 (HR 3.99, 95% CI 3.12-5.11) and 60 days (HR 1.85, 95% CI 1.4-2.45), but an OS advantage after 90 days (HR 0.59, 95% CI 0.55-0.64). In a landmark analysis conditioned on 90 days survival post treatment initiation, median OS was improved for SR (17.0 vs. 12.2 months, p < 0.0001); SR improved 3-year OS by 21.3% (p < 0.05), despite patients being older (median 72 vs. 67 years, p < 0.0001) with higher Charlson-Deyo comorbidity scores (≥2: 11.2 vs. 8.6%, p = 0.006). CONCLUSION For patients with resectable pancreatic cancer, SR is associated with superior long-term survival compared to MCT.
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Affiliation(s)
- Karenia Landa
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Robin Schmitz
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
| | - Norma E Farrow
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Christel Rushing
- Department of Biostatistics & Bioinformatics, Duke University, Durham, NC 27710, USA
| | - Donna Niedzwiecki
- Department of Biostatistics & Bioinformatics, Duke University, Durham, NC 27710, USA
| | - Marcelo Cerullo
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Garth S Herbert
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Kevin N Shah
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Sabino Zani
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Dan G Blazer
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Peter J Allen
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Michael E Lidsky
- Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
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24
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Oba A, Del Chiaro M, Satoi S, Kim SW, Takahashi H, Yu J, Hioki M, Tanaka M, Kato Y, Ariake K, Wu YHA, Inoue Y, Takahashi Y, Hackert T, Wolfgang CL, Besselink MG, Schulick RD, Nagakawa Y, Isaji S, Tsuchida A, Endo I. New criteria of resectability for pancreatic cancer: A position paper by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS). JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2022; 29:725-731. [PMID: 34581016 DOI: 10.1002/jhbp.1049] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 08/28/2021] [Accepted: 09/01/2021] [Indexed: 12/15/2022]
Abstract
The symposium "New criteria of resectability for pancreatic cancer" was held during the 33nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) in 2021 to discuss the potential modifications that could be made in the current resectability classification. The meeting focused on setting the foundation for developing a new prognosis-based resectability classification that is based on the tumor biology and the response to neoadjuvant treatment (NAT). The symposium included selected experts from Western and Eastern high-volume centers who have discussed their concept of resectability status through published literature. During the symposium, presenters reported new resectability classifications from their respective institutions based on tumor biology, conditional status, pathology, and genetics, in addition to anatomical tumor involvement. Interestingly, experts from all the centers reached the agreement that anatomy alone is insufficient to define resectability in the current era of effective NAT. On behalf of the JSHBPS, we would like to summarize the content of the conference in this position paper. We also invite global experts as internal reviewers of this paper for intercontinental cooperation in creating an up-to-date, prognosis-based resectability classification that reflects the trends of contemporary clinical practice.
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Affiliation(s)
- Atsushi Oba
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA
| | - Sohei Satoi
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA
- Department Surgery, Kansai Medical University, Osaka, Japan
| | - Sun-Whe Kim
- Department Surgery, Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Korea
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Jun Yu
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Masayoshi Hioki
- Department of Surgery, Fukuyama City Hospital, Hiroshima, Japan
| | - Masayuki Tanaka
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Yoshiyasu Kato
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kyohei Ariake
- Department of Surgery, Tohoku University, Sendai, Japan
| | - Y H Andrew Wu
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Yosuke Inoue
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yu Takahashi
- Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Germany
| | | | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Richard D Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA
| | - Yuichi Nagakawa
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Shuji Isaji
- Director of Mie University Graduate School of Medicine, Tsu, Japan
| | - Akihiko Tsuchida
- Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School Medicine, Yokohama, Japan
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25
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Ermiah E, Eddfair M, Abdulrahman O, Elfagieh M, Jebriel A, Al‑Sharif M, Assidi M, Buhmeida A. Prognostic value of serum CEA and CA19‑9 levels in pancreatic ductal adenocarcinoma. Mol Clin Oncol 2022; 17:126. [PMID: 35832472 PMCID: PMC9264325 DOI: 10.3892/mco.2022.2559] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 02/10/2022] [Indexed: 11/10/2022] Open
Abstract
The present study investigated the associations of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels with clinicopathological variables and survival outcomes in Libyan patients with pancreatic ductal adenocarcinoma (PDAC). The clinicopathological variables of 123 patients with PDAC registered at the National Cancer Institute in Misurata, Libya, between 2010 and 2018 were retrospectively analyzed. Blood samples from these patients were analyzed for serum CEA and CA19-9 levels before treatment by electrochemiluminescence immunoassay (double antibody sandwich ELISA) on a Roche cobas e 602 modules. The relationships between CA19-9 and CEA serum levels with clinicopathologic variables and survival outcomes were analyzed using the Kaplan-Meier method, log-rank test and Cox regression analyzes. Cut-off values for serum CEA and CA19-9 levels were 5 ng/ml and 400 U/ml, respectively. The median serum levels of all patients with PDAC for CEA and CA19-9 were 8 ng/ml (1.1-377 ng/ml) and 389 U/ml (1-10,050 U/ml), respectively. Tumors with higher serum CEA and CA19-9 levels were found in 63 and 48% of patients, respectively. Higher CEA and CA19-9 serum levels were significantly associated with more indicators of a malignant phenotype, including a surgically unresectable tumor, unevaluable lymph nodes, advanced stages and distant metastases. Regarding survival, patients with higher serum levels of the biomarkers CEA and CA19-9 had shorter overall survival rates (P<0.016 and (P<0.014, log-rank, respectively) and lower disease-free survival rates (P<0.002 and P<0.0001, log-rank, respectively). The present study demonstrated significant clinical and prognostic value of serum levels of biomarkers CEA and CA19-9 for Libyan patients with PDAC. Moreover, patients with PDAC with higher serum CEA and CA19-9 levels had more aggressive tumors, higher rates of disease recurrence and shorter overall survival rates and thus required more vigilant follow-up. Further multinational studies with larger PDAC cohorts are warranted to confirm these findings in terms of improved clinical decision making, more effective management and improved survival.
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Affiliation(s)
- Eramah Ermiah
- Medical Research Unit, National Cancer Institute, Misurata 051, Libya
| | - Mona Eddfair
- Department of Medical Oncology, National Cancer Institute, Misurata 051, Libya
| | - Othman Abdulrahman
- Department of Medical Oncology, National Cancer Institute, Misurata 051, Libya
| | - Mohamed Elfagieh
- Department of Surgery, National Cancer Institute, Misurata 051, Libya
| | - Abdalla Jebriel
- Department of Medical Oncology, National Cancer Institute, Misurata 051, Libya
| | - Mona Al‑Sharif
- Department of Biology College of Science, University of Jeddah, Jeddah 21589, Saudi Arabia
| | - Mourad Assidi
- Medical Laboratory Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Abdelbaset Buhmeida
- Centre of Excellence in Genomic Medicine Research, King Abdul‑Aziz University, Jeddah 21589, Saudi Arabia
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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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Labori KJ. Short-Course or Total Neoadjuvant Chemotherapy in Resectable and Borderline Resectable Pancreatic Cancer - Current Status and Future Perspectives. Front Surg 2022; 9:839339. [PMID: 35548190 PMCID: PMC9082635 DOI: 10.3389/fsurg.2022.839339] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 02/28/2022] [Indexed: 12/27/2022] Open
Abstract
Neoadjuvant therapy improves overall survival compared with a surgery-first approach in patients with borderline resectable pancreatic cancer (BRPC). Evidence of higher quality is required to determine whether neoadjuvant therapy has potential benefits and improves survival for patients with resectable pancreatic cancer (RPC). Most randomized controlled trials (RCTs) have explored short-course neoadjuvant chemotherapy (SNT), but total neoadjuvant chemotherapy (TNT) is now the experimental arm of ongoing RCTs. This article reviews the current status of SNT and TNT in RPC and BRPC, and provides perspectives of future challenges and research directions in this field.
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Affiliation(s)
- Knut Jørgen Labori
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Janssen QP, van Dam JL, Doppenberg D, Prakash LR, van Eijck CHJ, Jarnagin WR, O’ Reilly EM, Paniccia A, Besselink MG, Katz MHG, Tzeng CWD, Wei AC, Zureikat AH, Groot Koerkamp B. FOLFIRINOX as Initial Treatment for Localized Pancreatic Adenocarcinoma: A Retrospective Analysis by the Trans-Atlantic Pancreatic Surgery Consortium. J Natl Cancer Inst 2022; 114:695-703. [PMID: 35157075 PMCID: PMC9086789 DOI: 10.1093/jnci/djac018] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 10/27/2021] [Accepted: 01/14/2022] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Large pragmatic studies of patients who received 5-fluorouracil with leucovorin, irinotecan, and oxaliplatin ([m]FOLFIRINOX) as initial treatment for localized pancreatic ductal adenocarcinoma (PDAC) are lacking. This study aimed to provide realistic estimates of oncologic outcomes in these patients. METHODS This international retrospective cohort study included all consecutive patients presenting with localized PDAC who received at least 1 cycle of (m)FOLFIRINOX as initial treatment in 5 referral centers from the United States and the Netherlands (2012-2019). Primary outcome was median overall survival (OS), calculated from the date of tissue diagnosis, assessed using Kaplan-Meier estimates. Log-rank test was used to compare OS between groups. A Cox proportional hazards regression model was used to assess prognostic baseline factors for OS. All statistical tests were 2-sided. RESULTS Overall, 1835 patients were included, of whom 958 (52.2%) had locally advanced (LA), 531 (28.9%) had borderline resectable (BR), and 346 (18.9%) had potentially resectable (PR) PDAC. The median number of (m)FOLFIRINOX cycles was 6 (interquartile range = 4-8). Subsequent treatment included second chemotherapy (12.9%), radiotherapy (49.0%), and resection (37.9%). The resection rate was 17.6% for LA, 53.1% for BR, and 70.5% for PR PDAC (P < .001). The margin-negative resection rate (>1 mm) was 55.2% for LA, 62.6% for BR, and 79.2% for PR PDAC (P < .001). The median OS was 18.7 months (95% confidence interval [CI] = 17.7 to 19.9 months) for LA, 23.2 months (95% CI = 21.0 to 25.7 months) for BR, and 31.2 months (95% CI = 26.2 to 36.6 months) for PR PDAC (P < .001). The median OS for 695 patients who underwent a resection was 38.3 months (95% CI = 36.1 to 42.0 months). Independent prognostic factors at baseline for worse OS were more advanced stage, worse performance status, baseline carbohydrate antigen (CA) 19-9 > 500 U/mL, and body mass index ≤18.5 kg/m2. CONCLUSIONS This large international cohort study provides realistic estimates of resection rates and survival in patients with LA, BR, and PR PDAC who started (m)FOLFIRINOX treatment in PDAC referral centers.
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Affiliation(s)
- Quisette P Janssen
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jacob L van Dam
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Deesje Doppenberg
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Laura R Prakash
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Casper H J van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Eileen M O’ Reilly
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alessandro Paniccia
- Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Matthew H G Katz
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Alice C Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Amer H Zureikat
- Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
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Iterative Changes in Risk-Stratified Pancreatectomy Clinical Pathways and Accelerated Discharge After Pancreaticoduodenectomy. J Gastrointest Surg 2022; 26:1054-1062. [PMID: 35023033 DOI: 10.1007/s11605-021-05235-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 12/08/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Previous implementation of risk-stratified pancreatectomy clinical pathways (RSPCPs) decreased length of stay (LOS) following pancreaticoduodenectomy (PD). This study's primary aim was to measure the association of iterative RSPCP revisions with accelerated discharge and early postoperative outcomes. METHODS This is a retrospective cohort study of a prospectively maintained surgical database (10/2016-9/2020). In February 2019, revised RSPCPs were implemented with earlier nasogastric tube (NGT) removal (postoperative day [POD] 1 for low risk; POD 2 for high risk) and updated drain fluid amylase cutoffs for POD 1/POD 3 removal. Perioperative outcomes between original and revised pathways were compared. Predictors of accelerated discharge (defined as ≤ POD 5 for low risk; ≤ POD 6 for high risk) were identified. RESULTS There were 233 (36% high risk) patients in original and 131 (32% high risk) in revised RSPCPs. After revision, the rate of POD 1 NGT removal was higher while POD ≤ 3 drain removal was similar. Median LOS decreased for low risk (5 vs. 6 days, p = 0.011) and high risk (6 vs. 9 days, p = 0.005) with no increase in delayed gastric emptying, postoperative pancreatic fistula, or readmissions. With POD 1 NGT removal, diet tolerance was earlier without increased NGT reinsertions. In low-risk patients, younger age, POD 1 NGT removal, and POD ≤ 3 drain removal were independent predictors of accelerated discharge. In high-risk patients, POD 1 NGT removal and POD ≤ 3 drain removal were independent predictors of accelerated discharge. CONCLUSIONS Following iterative revisions in RSPCPs, LOS after PD decreased further without increasing readmissions, and NGTs were removed earlier without increased reinsertions. Early NGT and drain removal are modifiable practices within RSPCPs that are associated with accelerated discharge.
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Oppliger FA, Prakash LR, Newhook TE, Chiang YJ, Ikoma N, Maxwell JE, Kim MP, Vauthey JN, Lee JE, Katz MH, Tzeng CWD. AJCC 8th edition pathologic nodal staging of resected pancreatic adenocarcinoma predicts survival regardless of treatment sequencing. Surg Oncol 2021; 40:101673. [PMID: 34894620 DOI: 10.1016/j.suronc.2021.101673] [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: 07/23/2021] [Revised: 09/29/2021] [Accepted: 11/14/2021] [Indexed: 10/19/2022]
Abstract
OBJECTIVE The primary aim was to compare overall survival (OS) between neoadjuvant therapy (NT) and surgery-first (SF) patients with pancreatic adenocarcinoma (PDAC) by nodal stage using the American Joint Commission on Cancer 8th Edition (AJCC8). BACKGROUND Rates of nodal positivity are consistently lower following NT versus SF sequencing. It's unclear whether post-NT nodal stage (ypNx) has similar survival compared to SF (pNx) using AJCC8. METHODS This is a single-institution retrospective cohort study with routine consideration of NT. Patients undergoing PDAC resection from 2010 to 2018 were analyzed and OS compared by nodal stage using AJCC8. RESULTS Of 450 total patients, 24% were treated with SF and 76% NT. SF patients had potentially resectable disease in 97% of the cases, whereas NT patients had more advanced clinical stages at diagnosis: borderline resectable 34%, locally advanced 5%. NT patients had higher rates of node-negativity (52.4% vs 22.7%) and lower rates of pathologic N2 disease (19.1% vs 43.6%) vs. SF (p < 0.001). For each pathologic nodal stage, SF and NT groups had similar 5-year OS [pN0/ypN0 52.7% vs. 53.6%, p = 0.723], [pN1/ypN1 37.0% vs. 36.7%, p = 0.872], and [pN2/ypN2 16.6% vs. 21.0%, p = 0.508]. CONCLUSIONS AJCC8 stratifies outcomes for each post-NT nodal stage similar to SF counterparts. Despite presenting with more advanced clinical stage, NT patients had lower rates of nodal metastases yet comparable OS when stratified by final nodal status. These data provide both hope for patients with obvious radiographic nodal disease at presentation and further support for considering NT sequencing for most patients diagnosed with localized PDAC.
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Affiliation(s)
- Federico A Oppliger
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Laura R Prakash
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Timothy E Newhook
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yi-Ju Chiang
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jessica E Maxwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael P Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jean-Nicolas Vauthey
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Matthew H Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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31
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Schizas D, Koumpoura A, Galari M, Economopoulou P, Vailas M, Sotiropoulou M, Dimitroulis D, Maroulis I, Felekouras E. A personalized approach to pancreatic ductal adenocarcinoma and its application in surgical practice. Per Med 2021; 18:613-627. [PMID: 34676789 DOI: 10.2217/pme-2021-0031] [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: 11/21/2022]
Abstract
Pancreatic duct adenocarcinoma is an aggressive tumor which constitutes the fourth leading cause of cancer-related mortality in the USA. Despite the fact that surgery is an integral part of treatment, 5-year survival rates remain unfavorable, partly because of the complex genetic background, delayed diagnosis and also the absence of effective therapeutic approaches. To optimize surgery's results in recent years, the use of patients' genetic profile has been implemented through classification into subtypes; subtypes based on mutations which could efficiently lead oncologists to the path of targeted novel neoadjuvant regimens. This approach aims to achieve the most effective selection of patients undergoing surgery, to increase the number of potentially resectable tumors and also control micro-metastases, aiming to extend overall survival.
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Affiliation(s)
- Dimitrios Schizas
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Alkmini Koumpoura
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Meropi Galari
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Panagiota Economopoulou
- Oncology Unit, Second Propaideutic Department of Internal Medicine, National & Kapodistrian University of Athens, Attikon University Hospital, Athens, 12462, Greece
| | - Michail Vailas
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Maria Sotiropoulou
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Dimitrios Dimitroulis
- Second Propaedeutic Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
| | - Ioannis Maroulis
- Department of Surgery, University of Patras, University Hospital of Patras, Rio, 26504, Greece
| | - Evangelos Felekouras
- First Department of Surgery, National & Kapodistrian University of Athens, Laikon General Hospital, Athens, 11527, Greece
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Cloyd JM, Shen C, Santry H, Bridges J, Dillhoff M, Ejaz A, Pawlik TM, Tsung A. Disparities in the Use of Neoadjuvant Therapy for Resectable Pancreatic Ductal Adenocarcinoma. J Natl Compr Canc Netw 2021; 18:556-563. [PMID: 32380462 DOI: 10.6004/jnccn.2019.7380] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Accepted: 11/25/2019] [Indexed: 12/27/2022]
Abstract
BACKGROUND Current guidelines support either immediate surgical resection or neoadjuvant therapy (NT) for patients with resectable pancreatic ductal adenocarcinoma (PDAC). However, which patients are selected for NT and whether disparities exist in the use of NT for PDAC are not well understood. METHODS Using the National Cancer Database from 2004 through 2016, the clinical, demographic, socioeconomic, and hospital-related characteristics of patients with stage I/II PDAC who underwent immediate surgery versus NT followed by surgery were compared. RESULTS Among 58,124 patients who underwent pancreatectomy, 8,124 (14.0%) received NT whereas 50,000 (86.0%) did not. Use of NT increased significantly throughout the study period (from 3.5% in 2004 to 26.4% in 2016). Multivariable logistic regression analysis showed that travel distance, education level, hospital facility type, clinical T stage, tumor size, and year of diagnosis were associated with increased use of NT, whereas comorbidities, uninsured/Medicaid status, South/West geography, left-sided tumor location, and increasing age were associated with immediate surgery (all P<.001). Based on logistic regression-derived interaction factors, the association between NT use and median income, education level, Midwest location, clinical T stage, and clinical N stage significantly increased over time (all P<.01). CONCLUSIONS In addition to traditional clinicopathologic factors, several demographic, socioeconomic, and hospital-related factors are associated with use of NT for PDAC. Because NT is used increasingly for PDAC, efforts to reduce disparities will be critical in improving outcomes for all patients with pancreatic cancer.
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Affiliation(s)
- Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, and the Center for Surgical Health Assessment, Research, and Policy, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Chengli Shen
- Division of Surgical Oncology, Department of Surgery, and the Center for Surgical Health Assessment, Research, and Policy, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Heena Santry
- Division of Surgical Oncology, Department of Surgery, and the Center for Surgical Health Assessment, Research, and Policy, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - John Bridges
- Division of Surgical Oncology, Department of Surgery, and the Center for Surgical Health Assessment, Research, and Policy, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Mary Dillhoff
- Division of Surgical Oncology, Department of Surgery, and the Center for Surgical Health Assessment, Research, and Policy, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Aslam Ejaz
- Division of Surgical Oncology, Department of Surgery, and the Center for Surgical Health Assessment, Research, and Policy, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, and the Center for Surgical Health Assessment, Research, and Policy, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Allan Tsung
- Division of Surgical Oncology, Department of Surgery, and the Center for Surgical Health Assessment, Research, and Policy, The Ohio State University Wexner Medical Center, Columbus, Ohio
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Rieser CJ, Narayanan S, Bahary N, Bartlett DL, Lee KK, Paniccia A, Smith K, Zureikat AH. Optimal management of patients with operable pancreatic head cancer: A Markov decision analysis. J Surg Oncol 2021; 124:801-809. [PMID: 34231222 DOI: 10.1002/jso.26589] [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: 04/15/2021] [Accepted: 06/11/2021] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Neoadjuvant therapy (NAT) is an emerging strategy for operable pancreatic ductal adenocarcinoma (PDAC). While NAT increases multimodal therapy completion, it risks functional decline and treatment dropout. We used decision analysis to determine optimal management of localized PDAC and consider risks faced by elderly patients. METHODS A Markov cohort decision analysis model evaluated treatment options for a 60-year-old patient with resectable PDAC: (1) upfront pancreaticoduodenectomy or (2) NAT. One-way and probabilistic sensitivity analyses were performed. A subanalysis considered the scenario of a 75-year-old patient. RESULTS For the base case, NAT offered an incremental survival gain of 4.6 months compared with SF (overall survival: 26.3 vs. 21.7 months). In one-way sensitivity analyses, findings were sensitive to recurrence-free survival for NAT patients undergoing adjuvant, probability of completing NAT, and probability of being resectable at exploration after NAT. On probabilistic analysis, NAT was favored in a majority of trials (97%) with a median survival benefit of 5.1 months. In altering the base case for the 75-year-old scenario, NAT had a survival benefit of 3.8 months. CONCLUSIONS This analysis demonstrates a significant benefit to NAT in patients with localized PDAC. This benefit persists even in the elderly cohort.
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Affiliation(s)
- Caroline J Rieser
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Sowmya Narayanan
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Nathan Bahary
- Department of Medical Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - David L Bartlett
- AHN Cancer Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA
| | - Kenneth K Lee
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Alessandro Paniccia
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Kenneth Smith
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Amer H Zureikat
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Yoon MS, Lee HS, Kang CM, Lee WJ, Keum J, Sung MJ, Kim SS, Park MS, Jo JH, Chung MJ, Park JY, Park SW, Song SY, Hwang HK, Bang S. Response to Neoadjuvant Therapy and Prognosis in Patients with Resectable Pancreatic Cancer: A Propensity Score Matching Analysis. Gut Liver 2021; 16:118-128. [PMID: 34140428 PMCID: PMC8761915 DOI: 10.5009/gnl20301] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 03/12/2021] [Accepted: 03/15/2021] [Indexed: 11/18/2022] Open
Abstract
Background/Aims Controversy regarding the effectiveness of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC) still exists. Here, we aimed to identify the potential benefits of neoadjuvant therapy followed by surgery for resectable PDAC. Methods We reviewed radiologically resectable PDAC patients who received resection with curative intent at a tertiary hospital in South Korea between January 2012 and August 2019. A total of 202 patients underwent curative resection for resectable PDAC 167 underwent surgical resection first during this period, and 35 received neoadjuvant chemotherapy/chemoradiation therapy followed by surgery. Resectable PDAC patients were subdivided, and 13 propensity score matching (PSM) was performed to reduce selection bias. Results Compared with the group that received surgery first, the group that received neoadjuvant treatment followed by surgery had significantly smaller tumors (22.0 mm vs 27.0 mm, p=0.004), a smaller proportion of patients with postoperative pathologic T stage (p=0.026), a smaller proportion of patients with lymphovascular invasion (20.0% vs 40.7%, p=0.022), and a larger proportion of patients with negative resection margins (74.3% vs 51.5%, p=0.049). After PSM, the group that received neoadjuvant therapy had a significantly longer progression-free survival than those in the group that underwent surgery first (29.6 months vs 15.1 months, p=0.002). Overall survival was not significantly different between the two groups after PSM analysis. Conclusions We observed significantly better surgical outcomes and progression-free survival with the addition of neoadjuvant therapy to the management of resectable PDAC. However, despite PSM, there was still selection bias due to the use of different regimens between the groups receiving surgery first and neoadjuvant therapy. Large homogeneous samples are needed in the future prospective studies.
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Affiliation(s)
- Min Sung Yoon
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hee Seung Lee
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Chang Moo Kang
- Division of Gastroenterology, Department of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Woo Jung Lee
- Division of Gastroenterology, Department of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jiyoung Keum
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Min Je Sung
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Seung-Seob Kim
- Division of Gastroenterology, Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Mi-Suk Park
- Division of Gastroenterology, Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Hyun Jo
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Moon Jae Chung
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jeong Youp Park
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Woo Park
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Si Young Song
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Ho Kyoung Hwang
- Division of Gastroenterology, Department of Hepatobiliary and Pancreatic Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Seungmin Bang
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Brown ZJ, Cloyd JM. Trends in the utilization of neoadjuvant therapy for pancreatic ductal adenocarcinoma. J Surg Oncol 2021; 123:1432-1440. [PMID: 33831253 DOI: 10.1002/jso.26384] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 12/18/2020] [Accepted: 01/05/2021] [Indexed: 12/12/2022]
Abstract
For patients with localized pancreatic cancer, neoadjuvant therapy (NT) is increasingly delivered before surgery to maximize the receipt of multimodality therapy and the odds of a margin-negative resection. Three decades of refining the use of NT have led to its acceptance as a valid treatment approach for pancreatic adenocarcinoma. In this review, we discuss the rationale for and recent global trends in the utilization of NT for patients with pancreatic cancer.
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Affiliation(s)
- Zachary J Brown
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
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Gaskill CE, Maxwell J, Ikoma N, Kim MP, Tzeng CW, Lee JE, Katz MHG. History of preoperative therapy for pancreatic cancer and the MD Anderson experience. J Surg Oncol 2021; 123:1414-1422. [PMID: 33831256 DOI: 10.1002/jso.26394] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 01/18/2021] [Indexed: 12/11/2022]
Abstract
Systemic chemotherapy improves the survival of patients who undergo pancreatectomy, but whether chemotherapy should be delivered before or after surgery remains debated. At The University of Texas MD Anderson Cancer Center, localized pancreatic ductal adenocarcinoma (PDAC) has been preferentially treated with preoperative therapy-a practice supported by a robust history of institutional and national trials. In the following review, we discuss the historical use of perioperative therapy, our experience with it at MD Anderson Cancer Center and internationally, and the future of treatment and trials for PDAC.
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Affiliation(s)
- Cameron E Gaskill
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jessica Maxwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Michael P Kim
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ching-Wei Tzeng
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jeffrey E Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Ushida Y, Inoue Y, Ito H, Oba A, Mise Y, Ono Y, Sato T, Saiura A, Takahashi Y. High CA19-9 level in resectable pancreatic cancer is a potential indication of neoadjuvant treatment. Pancreatology 2021; 21:130-137. [PMID: 33303373 DOI: 10.1016/j.pan.2020.11.026] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 11/25/2020] [Accepted: 11/30/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Previous studies on borderline resectable (BR) pancreatic cancer (PC) included patients with heterogenous preoperative states; however, the definition of resectability for PC has evolved. We aimed to investigate the prognostic factors for PC other than anatomical resectability in those who underwent upfront resection and discuss the optimal treatment strategy for PC. METHODS We retrospectively examined 431 patients who underwent upfront surgery with curative intent between 2007 and 2014. The association between clinical characteristics and survival outcomes was assessed by stratifying patients according to risk factors. The patients were categorized into four groups based on anatomical (resectable [R]/BR) and biological features (CA19-9 ≤500/>500 U/mL): anatomical R with CA19-9 ≤500 U/mL (favorable-R); anatomical BR with CA19-9 ≤500 U/mL (favorable-BR); anatomical R with CA19-9 >500 U/mL (risky-R); and anatomical BR with CA19-9 >500 U/mL (risky-BR). RESULTS Overall, 320 and 111 patients had anatomical R- and BR-PC, respectively. A modified Glasgow prognostic score = 2 (hazard ratio [HR]: 1.73), NLR>5 (hazard ratio [HR]: 1.54), CA19-9 >500 U/mL (HR: 1.86), and anatomical BR (HR: 1.38) were independent prognostic factors for overall survival. The risky-R group had likely worse prognosis (16 months vs. 19 months, P = 0.0605) and a significantly higher early recurrence rate (36% vs 18%, P = 0.0231) than the favorable-BR group. CONCLUSIONS It is essential to stratify and distinguish PC patients at a high risk of worse prognosis. Risky-R was an unfavorable prognostic factor and should thus be considered in the decision-making for treatment with neoadjuvant chemotherapy, in addition to anatomical BR-PC.
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Affiliation(s)
- Yuta Ushida
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Yosuke Inoue
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan.
| | - Hiromichi Ito
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Atsushi Oba
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Yoshihiro Mise
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan; Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Hospital, 3-1-3, Hongo, Bunkyo-ku, Tokyo, 113-8431, Japan
| | - Yoshihiro Ono
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Takafumi Sato
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan
| | - Akio Saiura
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan; Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Hospital, 3-1-3, Hongo, Bunkyo-ku, Tokyo, 113-8431, Japan
| | - Yu Takahashi
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan
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da Costa WL, Tran Cao HS, Sheetz KH, Gu X, Norton EC, Massarweh NN. Comparative Effectiveness of Neoadjuvant Therapy and Upfront Resection for Patients with Resectable Pancreatic Adenocarcinoma: An Instrumental Variable Analysis. Ann Surg Oncol 2020; 28:3186-3195. [PMID: 33174146 DOI: 10.1245/s10434-020-09327-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 10/17/2020] [Indexed: 12/31/2022]
Abstract
BACKGROUND Neoadjuvant therapy (NAT) is increasingly being used in the management of patients with resectable pancreatic ductal adenocarcinoma (PDAC); however, there is a lack of evidence regarding the benefit among these patients. OBJECTIVE The aim of this study was to evaluate overall survival (OS) in PDAC patients with resectable disease treated with NAT or upfront resection through instrumental variable (IV) analysis. DESIGN A national cohort study of resectable PDAC patients in the National Cancer Data Base (2007-2015) treated with either upfront surgery or resection after NAT. Using multivariable modeling and IV methods, OS was compared between those treated with NAT and upfront resection. The IV was hospital-level NAT utilization in the most recent year prior to treatment. RESULTS The cohort included 16,666 patients (14,012 upfront resection; 2654 NAT) treated at 779 hospitals. Among those treated with upfront resection, 59.9% received any adjuvant therapy. NAT patients had higher median (27.9 months, 95% confidence interval [CI] 26.2-29.1) and 5-year OS (24.1%, 95% CI 21.9-26.3%) compared with those treated with upfront surgery (median 21.2 months, 95% CI 20.7-21.6; 5-year survival 20.9%, 95% CI 20.1-21.7%). After multivariable modeling, NAT was associated with an approximately 20% decrease in the risk of death (hazard ratio [HR] 0.78, 95% CI 0.73-0.84), and this effect was magnified in the IV analysis (HR 0.61, 95% CI 0.47-0.79). CONCLUSIONS In patients with resectable PDAC, NAT is associated with improved survival relative to upfront resection. Given the benefits of multimodality therapy and the challenges in receiving adjuvant therapy, consideration should be given to treating all PDAC patients with NAT.
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Affiliation(s)
- Wilson Luiz da Costa
- Department of Medicine, Epidemiology, and Population Sciences, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
| | - Hop S Tran Cao
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kyle H Sheetz
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Xiangjun Gu
- Department of Medicine, Epidemiology, and Population Sciences, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
| | - Edward C Norton
- Department of Health Management and Policy, University of Michigan, Ann Arbor, MI, USA.,Department of Economics, University of Michigan, Ann Arbor, MI, USA
| | - Nader N Massarweh
- Center for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey VA Medical Center, Houston, TX, USA.,Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
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Kim JK, DePeralta DK, Ogami T, Denbo JW, Pimiento J, Hodul PJ, Malafa MP, Kim DW, Fleming JB, Powers BD. Cancer outcomes are independent of preoperative CA 19-9 in anatomically resectable pancreatic ductal adenocarcinoma: A retrospective cohort analysis. J Surg Oncol 2020; 122:1074-1083. [PMID: 32673436 DOI: 10.1002/jso.26103] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Accepted: 06/08/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND OBJECTIVES Current guidelines recommend neoadjuvant therapy for pancreatic ductal adenocarcinoma (PDAC) patients with anatomically resectable tumors but elevated CA 19-9. However, this recommendation is based on data from anatomically resectable and borderline resectable PDAC patients. Therefore, we analyzed the association of preoperative CA 19-9 with oncologic outcomes in a cohort of anatomically resectable PDAC patients. METHODS A single-institution PDAC database from 2007 to 2015 included patients who underwent guideline-based staging and were anatomically resectable. Patients with bilirubin above 1.5 after decompression, nonsecretors of CA 19-9, and borderline resectable patients were excluded. Statistical analysis included frequency testing and regression modeling for recurrence and survival. RESULTS One hundred forty-four PDAC patients were identified; 16 (11.1%) had elevated preoperative CA 19-9 ≥ 1000. A CA 19-9 level ≥1000 was not associated with demographic, clinical, or pathological factors. After adjustment for potential confounders, CA 19-9 levels (continuous, median, 500 U/mL, or 1000 U/mL cut-offs) were not associated with recurrence or overall survival (OS). CONCLUSIONS Although guidelines recommend CA 19-9 to determine the management of anatomically resectable PDAC patients, CA 19-9 was not associated with recurrence or OS in this cohort. Our findings do not suggest that CA 19-9 alone should determine the PDAC treatment strategy.
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Affiliation(s)
- Joon Kyung Kim
- Morsani College of Medicine, University of South Florida, Tampa, Florida
| | - Danielle K DePeralta
- School of Medicine, Northwell Health, Hofstra University, New Hyde Park, New York
| | - Takuya Ogami
- Morsani College of Medicine, University of South Florida, Tampa, Florida
| | - Jason W Denbo
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida
| | - Jose Pimiento
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida
| | - Pamela J Hodul
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida
| | - Mokenge P Malafa
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida
| | - Dae W Kim
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida
| | - Jason B Fleming
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida
| | - Benjamin D Powers
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida
- Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida
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Capello M, Fahrmann JF, Rios Perez MV, Vykoukal JV, Irajizad E, Tripathi SC, Roife D, Bantis LE, Kang Y, Kundnani DL, Xu H, Prakash LR, Long JP, Katayama H, Fleury A, Ferri-Borgogno S, Baluya DL, Dennison JB, Aguilar-Bonavides C, Casabar JP, Celiktas M, Do KA, Fiehn O, Maitra A, Wang H, Feng Z, Chiao PJ, Katz MH, Fleming JB, Hanash SM. CES2 Expression in Pancreatic Adenocarcinoma Is Predictive of Response to Irinotecan and Is Associated With Type 2 Diabetes. JCO Precis Oncol 2020; 4:426-436. [PMID: 35050739 PMCID: PMC10860959 DOI: 10.1200/po.19.00330] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/16/2020] [Indexed: 12/18/2022] Open
Abstract
PURPOSE The combination chemotherapy of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) has provided clinically meaningful improvement for pancreatic ductal adenocarcinoma (PDAC). We previously uncovered a role for the serine hydrolase carboxylesterase 2 (CES2) in mediating intratumoral activation of the prodrug irinotecan, a constituent of FOLFIRINOX. We aimed to further test the predictive value of CES2 for response to irinotecan using patient-derived xenograft (PDX) models and to elucidate the determinants of CES2 expression and response to FOLFIRINOX treatment among patients with PDAC. METHODS PDXs were engrafted subcutaneously into nude mice and treated for 4 weeks with either saline control or irinotecan. CES2 and hepatocyte nuclear factor 4 alpha (HNF4A) expression in PDAC tissues was evaluated by immunohistochemical and Western blot analysis. Kaplan-Meier and Cox regression analyses were applied to assess the association between overall survival and hemoglobin A1C (HbA1C) levels in patients who underwent neoadjuvant FOLFIRINOX treatment. RESULTS High CES2 activity in PDAC PDXs was associated with increased sensitivity to irinotecan. Integrated gene expression, proteomic analyses, and in vitro genetic experiments revealed that nuclear receptor HNF4A, which is upregulated in diabetes, is the upstream transcriptional regulator of CES2 expression. Elevated CES2 protein expression in PDAC tissues was positively associated with a history of type 2 diabetes (odds ratio, 4.84; P = .02). High HbA1C levels were associated with longer overall survival in patients who received neoadjuvant FOLFIRINOX treatment (P = .04). CONCLUSION To our knowledge, we provide, for the first time, evidence that CES2 expression is associated with a history of type 2 diabetes in PDAC and that elevated HbA1C, by predicting tumor CES2 expression, may represent a novel marker for stratifying patients most likely to respond to FOLFIRINOX therapy.
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Affiliation(s)
- Michela Capello
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Johannes F. Fahrmann
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Mayrim V. Rios Perez
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jody V. Vykoukal
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ehsan Irajizad
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Satyendra C. Tripathi
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - David Roife
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Leonidas E. Bantis
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
- Department of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, KS
| | - Ya’an Kang
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Deepali L. Kundnani
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Hanwen Xu
- Department of Clinical Cancer Prevention, 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
| | - James P. Long
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Hiroyuki Katayama
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Alia Fleury
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Sammy Ferri-Borgogno
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Dodge L. Baluya
- Center for Radiation Oncology Research, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jennifer B. Dennison
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Clemente Aguilar-Bonavides
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Julian P. Casabar
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Muge Celiktas
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Kim-Anh Do
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Oliver Fiehn
- University of California Davis Genome Center–Metabolomics, University of California, Davis, CA
| | - Anirban Maitra
- Department of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, KS
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Huamin Wang
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ziding Feng
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Paul J. Chiao
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Matthew H. Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jason B. Fleming
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, FL
| | - Samir M. Hanash
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX
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van Manen L, Groen JV, Putter H, Pichler M, Vahrmeijer AL, Bonsing BA, Mieog JSD. Stage-Specific Value of Carbohydrate Antigen 19-9 and Carcinoembryonic Antigen Serum Levels on Survival and Recurrence in Pancreatic Cancer: A Single Center Study and Meta-Analysis. Cancers (Basel) 2020; 12:cancers12102970. [PMID: 33066393 PMCID: PMC7602123 DOI: 10.3390/cancers12102970] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 10/12/2020] [Accepted: 10/12/2020] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Pancreatic cancer is one of the most aggressive cancers with a poor survival. Only the minority of patients can be treated by extensive surgery, which is associated with high morbidity. Therefore it could be helpful to identify which patients are at risk of early recurrence and associated poor survival in order to optimize treatment strategies for individual patients. Serum tumor markers, which are readily available and easily implicated in the clinical workflow, are such additional tools. In this study, tumor markers carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been studied and results have been compared with existing literature by performing a systematic literature search, as current literature is lacking a complete overview of the prognostic value of both markers. Elevated CA19-9 serum level appear to be an independent prognostic factor for poor survival and early recurrence in pancreatic adenocarcinoma patients, whereas the prognostic value of CEA is disputable. Abstract This study aimed to determine the stage-specific prognostic value of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) serum levels at diagnosis on overall survival (OS) and time to local recurrence or distant metastases in patients with pancreatic ductal adenocarcinoma (PDAC). Consecutive PDAC patients, discussed at multidisciplinary team meetings from 2013 through 2017, were reviewed. Prognostic factors were stage-specific (resection vs. advanced PDAC) evaluated in Cox proportional hazard models. Additionally, a systematic literature search and meta-analysis was performed, as current literature is lacking a complete overview of used cut-off values and the added value of CEA as prognostic marker. In the retrospective cohort, elevated CA19-9 (>305 kU/L) level was independently associated with poor OS (Hazard ratio (HR): 1.72(1.31–2.26)) and early recurrence (HR: 1.74(1.06–2.86)), whereas CEA was not significantly associated. The meta-analysis showed that both elevated CA19-9 and CEA serum levels were predictors for poor OS (pooled HR: 1.29(1.17–1.42) and HR: 1.51(1.33–1.73), respectively). In the resected cohort, elevated CA19-9 level was significantly associated with early recurrence (pooled HR: 2.41(1.77–3.29)), whereas CEA was not. Elevated CA19-9 serum level appear to be an independent prognostic factor for poor OS and early recurrence in PDAC patients, whereas the prognostic value of CEA is disputable.
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Affiliation(s)
- Labrinus van Manen
- Department of Surgery, Leiden University Medical Center, 2300RC Leiden, The Netherlands; (L.v.M.); (J.V.G.); (A.L.V.); (B.A.B.)
| | - Jesse V. Groen
- Department of Surgery, Leiden University Medical Center, 2300RC Leiden, The Netherlands; (L.v.M.); (J.V.G.); (A.L.V.); (B.A.B.)
| | - Hein Putter
- Department of Medical Statistics, Leiden University Medical Center, 2300RC Leiden, The Netherlands;
| | - Martin Pichler
- Division of Clinical Oncology, Medical University of Graz, 8036 Graz, Austria;
| | - Alexander L. Vahrmeijer
- Department of Surgery, Leiden University Medical Center, 2300RC Leiden, The Netherlands; (L.v.M.); (J.V.G.); (A.L.V.); (B.A.B.)
| | - Bert A. Bonsing
- Department of Surgery, Leiden University Medical Center, 2300RC Leiden, The Netherlands; (L.v.M.); (J.V.G.); (A.L.V.); (B.A.B.)
| | - J. Sven D. Mieog
- Department of Surgery, Leiden University Medical Center, 2300RC Leiden, The Netherlands; (L.v.M.); (J.V.G.); (A.L.V.); (B.A.B.)
- Correspondence: ; Tel.: +31-71-529-9143; Fax: +31-71-526-6770
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Müller PC, Frey MC, Ruzza CM, Nickel F, Jost C, Gwerder C, Hackert T, Z'graggen K, Kessler U. Neoadjuvant Chemotherapy in Pancreatic Cancer: An Appraisal of the Current High-Level Evidence. Pharmacology 2020; 106:143-153. [PMID: 32966993 DOI: 10.1159/000510343] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 07/20/2020] [Indexed: 01/11/2023]
Abstract
At the time of diagnosis, only about 20% of patients with pancreatic ductal adenocarcinoma (PDAC) have resectable disease. PDAC treatment necessitates a multidisciplinary approach, and adjuvant chemotherapy after upfront resection is an established means of preventing recurrence. Neoadjuvant chemotherapy (NAT), originally introduced to downstage tumor size, is nowadays more frequently used for selection of patients with favorable tumor biology and to control potential micrometastases. While NAT is routinely applied in locally advanced (LA) PDAC, there is increasing evidence demonstrating benefits of NAT in borderline resectable (BR) PDAC. The concept of NAT has recently been tested in resectable PDAC, but to date NAT has been restricted to clinical trials, as the data are limited and no clear benefits have yet been shown in this patient group. This review summarizes the current evidence for NAT in resectable, BR, and LA PDAC, with a focus on high-level evidence and randomized controlled trials.
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Affiliation(s)
- Philip C Müller
- Department of Surgery, Hirslanden Klinik Beau-Site, Bern, Switzerland.,Swiss Pancreas Center, Hirslanden Klinik Beau-Site, Bern, Switzerland
| | - Michael C Frey
- Swiss Pancreas Center, Hirslanden Klinik Beau-Site, Bern, Switzerland.,Department of Pediatric Surgery, University Hospital Bern, University of Bern, Bern, Switzerland
| | - Claudio M Ruzza
- Department of Surgery, Hirslanden Klinik Beau-Site, Bern, Switzerland.,Swiss Pancreas Center, Hirslanden Klinik Beau-Site, Bern, Switzerland
| | - Felix Nickel
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Christian Jost
- Swiss Pancreas Center, Hirslanden Klinik Beau-Site, Bern, Switzerland.,Department of Gastroenterology, Hirslanden Klinik Beau-Site, Bern, Switzerland
| | - Christoph Gwerder
- Swiss Pancreas Center, Hirslanden Klinik Beau-Site, Bern, Switzerland.,Department of Oncology, Hirslanden Klinik Beau-Site, Bern, Switzerland
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Kaspar Z'graggen
- Department of Surgery, Hirslanden Klinik Beau-Site, Bern, Switzerland, .,Swiss Pancreas Center, Hirslanden Klinik Beau-Site, Bern, Switzerland,
| | - Ulf Kessler
- Department of Surgery, Hirslanden Klinik Beau-Site, Bern, Switzerland.,Swiss Pancreas Center, Hirslanden Klinik Beau-Site, Bern, Switzerland.,Department of Pediatric Surgery, University Hospital Bern, University of Bern, Bern, Switzerland
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Truty MJ. Commentary: Two papers, 2 tumor types, same conclusion. Surgery 2020; 168:1019-1020. [PMID: 32896374 DOI: 10.1016/j.surg.2020.07.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 07/30/2020] [Indexed: 11/18/2022]
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Reduced and Normalized Carbohydrate Antigen 19-9 Concentrations after Neoadjuvant Chemotherapy Have Comparable Prognostic Performance in Patients with Borderline Resectable and Locally Advanced Pancreatic Cancer. J Clin Med 2020; 9:jcm9051477. [PMID: 32423123 PMCID: PMC7291310 DOI: 10.3390/jcm9051477] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 05/12/2020] [Accepted: 05/13/2020] [Indexed: 02/06/2023] Open
Abstract
Background: The association between optimal carbohydrate antigen (CA) 19-9 concentration after neoadjuvant chemotherapy (NACT) and prognosis has not been confirmed in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). Methods: This retrospective study included 122 patients with BRPC and 103 with LAPC who underwent surgery after NACT between 2012 and 2019 in a tertiary referral center. Prognostic models were established based on relative difference of the CA 19-9 (RDC), with their prognostic performance compared using C-index and Akaike information criterion (AIC). Results: CA 19-9 concentrations of 37–1000 U/mL before NACT showed prognostic significance in patients with BRPC and LAPC (hazard ratio [HR]: 0.262; 95% confidence interval [CI]: 0.092–0.748; p = 0.012). Prognostic models in this subgroup showed that RDC was independently prognostic of better overall survival (HR: 0.262; 95% CI: 0.093–0.739; p = 0.011) and recurrence free survival (HR: 0.299; 95% CI: 0.140–0.642; p = 0.002). The prognostic performances of RDC (C-index: 0.653; AIC: 227.243), normalization of CA 19-9 after NACT (C-index: 0.625; AIC: 230.897) and surgery (C-index: 0.613; AIC: 233.114) showed no significant differences. Conclusion: RDC was independently associated with better prognosis after NACT in patients with BRPC or LAPC. Decreased CA19-9 after NACT was a prognostic indicator of better survival and recurrence, as was normalization of CA 19-9 after both NACT and surgery.
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Extrapancreatic Nerve Plexus Invasion on Imaging Predicts Poor Survival After Upfront Surgery for Anatomically Resectable Pancreatic Cancer. Pancreas 2020; 49:675-682. [PMID: 32433406 DOI: 10.1097/mpa.0000000000001547] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES This study aimed to analyze the risk factors for poor survival of the patients with anatomically resectable pancreatic ductal adenocarcinoma (PDAC), focusing on detailed computed tomography (CT) findings of tumor extent to the peripancreatic tissue. METHODS The study included 192 patients who underwent upfront pancreaticoduodenectomy for anatomically resectable PDAC. Preoperative CT images were rereviewed by an experienced radiologist for the pattern of tumor extension to the surrounding tissue: biliary, duodenal, serosal, retroperitoneal, portal venous, arterial, extrapancreatic nerve plexus, and other-organ invasion. Imaging findings and other clinical data that could be obtained before surgery were evaluated for their association with a shorter disease-specific survival (DSS) and recurrence-free survival (RFS). RESULTS Of the 192 anatomically resectable PDAC patients, extrapancreatic nerve plexus invasion was observed on CT in 38 patients (20%), and this finding was independently associated with a shorter DSS (hazard ratio, 2.258; P < 0.001) and RFS (hazard ratio, 2.665; P < 0.001). The median survival of patients with and without extrapancreatic nerve plexus invasion on CT was 19.7 versus 38.5 months (P < 0.001). CONCLUSIONS Extrapancreatic nerve plexus invasion was shown as an only CT finding associated with a shorter DSS and RFS after upfront surgery for the patients with anatomically resectable PDAC.
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A contemporary evidence basis for neoadjuvant chemotherapy in upfront resectable pancreatic adenocarcinoma: a systematic review of the literature. JOURNAL OF PANCREATOLOGY 2020. [DOI: 10.1097/jp9.0000000000000037] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Sugimoto M, Takahashi N, Farnell MB, Smyrk TC, Truty MJ, Nagorney DM, Smoot RL, Chari ST, Carter RE, Kendrick ML. Survival benefit of neoadjuvant therapy in patients with non-metastatic pancreatic ductal adenocarcinoma: A propensity matching and intention-to-treat analysis. J Surg Oncol 2019; 120:976-984. [PMID: 31452208 DOI: 10.1002/jso.25681] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 08/12/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND OBJECTIVES Conclusive evidence in favor of neoadjuvant therapy for those with non-metastatic pancreatic ductal adenocarcinoma (PDAC) is still lacking. The objective of this study was to evaluate the survival benefit of neoadjuvant therapy vs upfront surgery for patients with non-metastatic PDAC. METHODS The study involved 565 patients undergoing neoadjuvant therapy or upfront surgery as the primary treatment for PDAC. Propensity score matching was performed between the neoadjuvant therapy group (NAT group) and the upfront surgery group (UFS group) using 20 clinical variables at diagnosis. Overall survival and surgical pathology were compared between the two treatment groups on an intent-to-treat basis. RESULTS In the matched cohort, the NAT group (n = 91) had a longer median overall survival than the UFS group (n = 91) (23.1 months vs 18.5 months, P = .043). The rate of patients undergoing surgical resection was lower in the NAT group (58% vs 80%, P = .001). Regarding surgical pathology, the NAT group had smaller tumor size (2.8 cm vs 4.0 cm, P = .001), lower incidence of positive surgical margins (8% vs 30%, P < .002), and less lymph node metastasis (45% vs 78%, P < .001). CONCLUSIONS The strategy of neoadjuvant therapy before surgical resection appears to offer pathologic effect and survival benefit for the patients presenting with non-metastatic PDAC.
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Affiliation(s)
- Motokazu Sugimoto
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, Minnesota
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa, Japan
| | | | - Michael B Farnell
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, Minnesota
| | - Thomas C Smyrk
- Division of Pathology, Mayo Clinic, Rochester, Minnesota
| | - Mark J Truty
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, Minnesota
| | - David M Nagorney
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, Minnesota
| | - Rory L Smoot
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, Minnesota
| | - Suresh T Chari
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Rickey E Carter
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Michael L Kendrick
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, Minnesota
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Vicente D, Lee AJ, Hall CS, Lucci A, Lee JE, Kim MP, Katz MH, Hurd MW, Maitra A, Rhim, MD AD, Tzeng CWD. Circulating Tumor Cells and Transforming Growth Factor Beta in Resected Pancreatic Adenocarcinoma. J Surg Res 2019; 243:90-99. [DOI: 10.1016/j.jss.2019.04.090] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 04/05/2019] [Accepted: 04/30/2019] [Indexed: 12/22/2022]
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Abstract
The aim of this study was to evaluate outcomes of patients with resectable pancreatic adenocarcinoma (PDAC) who underwent neoadjuvant chemotherapy. The MEDLINE and PubMed databases were searched to identify relevant original articles investigating neoadjuvant therapy in resectable PDAC. Qualitative analyses were performed to investigate patient selection, disease stage, impact on perioperative outcomes, and cost-effectiveness. Forty-three studies met inclusion criteria for this review. Neoadjuvant chemotherapy for upfront resectable PDAC is cost-effective, safe, may result in lower stage disease and has potential survival advantages. With proper patient selection, neoadjuvant chemotherapy is an appropriate approach for upfront resectable PDAC. Nevertheless, the risk for disease progression and losing a curative surgical window highlights the need for appropriate patient identification, further discovery of superior biomarkers or molecular profiles representative of positive treatment response, and additional prospective comparative study.
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Vreeland TJ, McAllister F, Javadi S, Prakash LR, Fogelman DR, Ho L, Varadhachary G, Aloia TA, Vauthey JN, Lee JE, Kim MP, Katz MHG, Tzeng CWD. Benefit of Gemcitabine/Nab-Paclitaxel Rescue of Patients With Borderline Resectable or Locally Advanced Pancreatic Adenocarcinoma After Early Failure of FOLFIRINOX. Pancreas 2019; 48:837-843. [PMID: 31210666 PMCID: PMC7309587 DOI: 10.1097/mpa.0000000000001345] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVES Neoadjuvant therapy (NT) is used for advanced pancreatic ductal adenocarcinoma (PDAC). No clear guidelines exist for switching therapies when patients do not respond to initial NT. We sought to characterize patients who underwent early switch from FOLFIRINOX to gemcitabine/nab-paclitaxel (GA) as NT for PDAC. METHODS We identified patients at a single institution switched from FOLFIRINOX to GA within the first 4 months of NT for PDAC during 2012-2017. We compared clinicopathologic data and oncologic outcomes. RESULTS Of 25 patients who met the criteria, 21 showed a serologic or radiographic response to GA; 11 (52%) reached resection. Responders had decreased carbohydrate antigen (CA) 19-9 levels from pretreatment to post-GA (P = 0.036). Resected responders had significantly decreased CA 19-9 comparing preswitch to post-GA (P = 0.048). The only predictor of GA response was prechemotherapy CA 19-9 of less than1000 U/mL (P = 0.021). Predictors of reaching resection were head/uncinate tumor (P = 0.010) and presenting stage lower than locally advanced (P = 0.041). CONCLUSIONS When patients do not respond to neoadjuvant FOLFIRINOX, early switch to GA should be considered. Future efforts should be directed toward identifying markers that will allow correct choice of initial therapy rather than attempting to rescue patients who respond poorly to first-line therapy.
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Affiliation(s)
- Timothy J Vreeland
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Florencia McAllister
- Department of Clinical Cancer Prevention, Department of Gastrointestinal Medical Oncology, Clinical Cancer Genetics Program, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Sanaz Javadi
- Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Laura R. Prakash
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX
| | - David R Fogelman
- Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Linus Ho
- Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Gauri Varadhachary
- Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX
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