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 Table of Contents  
COMMENTARY
Year : 2017  |  Volume : 6  |  Issue : 9  |  Page : 76-78

The borderline resectable and locally advanced pancreatic ductal adenocarcinoma: Definition


Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

Date of Submission12-Jul-2017
Date of Acceptance31-Aug-2017
Date of Web Publication29-Dec-2017

Correspondence Address:
Dr. Assaad M Soweid
Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut
Lebanon
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/eus.eus_66_17

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How to cite this article:
Soweid AM. The borderline resectable and locally advanced pancreatic ductal adenocarcinoma: Definition. Endosc Ultrasound 2017;6, Suppl S3:76-8

How to cite this URL:
Soweid AM. The borderline resectable and locally advanced pancreatic ductal adenocarcinoma: Definition. Endosc Ultrasound [serial online] 2017 [cited 2020 Jan 23];6, Suppl S3:76-8. Available from: http://www.eusjournal.com/text.asp?2017/6/9/76/221935




  Introduction Top


Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer death in the United States with around 50,000 incident cases and 40,000 deaths in 2015.[1] Despite the tremendous recent advances in diagnostic and therapeutic interventions, the 5-year survival rate remains dismal at approximately 5%. At initial presentation, the majority of patients (50%–55%) have metastatic disease while only 20% have resectable disease.[2],[3] The remaining 25%–30% of patients present with either borderline resectable (BR) or locally advanced (LA) disease.[2],[4] In both BR-PDAC and LA-PDAC, the tumor is localized to the pancreas but adheres to or invades adjacent vascular structures, including the celiac axis (CA) vessels, superior mesenteric artery (SMA), superior mesenteric vein (SMV), and portal vein (PV). Patients with BR-PDAC and LA-PDAC represent a unique subset of patients with PDAC who are not candidates for primary surgical resection. Identification of such patients requires a team of experts in the fields of gastroenterology/endosonography and radiology (computed tomography, magnetic resonance imaging). This identification is vital for the planning of a potentially curative multimodality treatment that relies on chemotherapy, radiotherapy (RT), and surgery. The objective of treatment for BR-PDAC is to achieve tumor downstaging to facilitate margin-negative (R0) resection, while that for LA-PDAC is local disease control with improvement of survival.


  BR-PDAC Top


Over the past decade, the concept of “BR” PDAC has emerged to describe a distinct spectrum of patients ranging from “resectable” to LA disease, for whom a microscopically margin-positive (R1) resection is considered relatively more likely, primarily due to the relationship between the primary pancreatic tumor and the surrounding blood vessels. Unfortunately, both anatomic and imaging criteria to define “borderline resectability” are not yet universally agreed upon, with several classification systems proposed in the literature and considerable variability among medical institutions. Thus, as a result of: the lack of consensus regarding the definition, the relatively small numbers of patients in this category, and the paucity of dedicated clinical trials; accurate evidence-based diagnostic categorization and treatment selection for this subgroup of patients remains a major challenge.

Hence, although there is no consensus regarding the definition, BR-PDAC is often defined as a tumor confined to the pancreatic bed with limited involvement of the adjacent vascular structures where vascular reconstruction options are feasible.[4] However, there is not yet a universally accepted definition in the oncology community regarding the extent of vascular involvement that would be amenable to reconstruction.[5],[6] More specifically, according to the Society of Surgical Oncology/American Hepato-Pancreato-Biliary Association/Society for Surgery of the Alimentary Tract consensus definition, which had been incorporated into the National Comprehensive Cancer Network (NCCN) guidelines, BR tumors have: (a) no distant metastases; (b) venous involvement of the SMV/PV with or without impingement and narrowing of the lumen; (c) short segment venous occlusion but with suitable vessel proximal and distal to occlusion, allowing for safe resection and reconstruction; (d) gastroduodenal artery (GDA) encasement up to the hepatic artery (HA) with either short segment encasement or direct abutment of HA, without extension to the CA; and (e) tumor abutment of the SMA not to exceed 180° of the circumference.[5],[6],[7],[8] To complicate matters further, there is even internal conflict within the individual consensus statements. For example, it is noted in the 2016 NCCN guidelines that there is disagreement among various panelists regarding the second celiac criterion (>180° contact without involvement of the aorta and with intact and uninvolved GDA), which some would deem unresectable.[7],[9]

A growing body of evidence suggests that the BR group may particularly benefit from neoadjuvant therapy to increase the likelihood of a margin-negative (R0) resection. Recent data have revealed that PDAC patients with involvement of the adjacent mesenteric vessels who were undergoing R0 resections had the same survival outcomes as those who underwent resection for primarily resectable PDAC.[10],[11] The main challenge in the surgical management of BR-PDAC is the high rate of positive margins at the reconstructed vessel segments, leading to high risk of local and systemic recurrence.[12] Selection of patients who will benefit from neoadjuvant therapy or upfront surgical resection is a particularly challenging task that is highly dependent on the expertise of the multidisciplinary team members.


  LA-PDAC Top


On the other hand, LA-PDAC is often defined as the involvement of the CA or the encasement of >180° of the SMA (T4) and/or involvement of SMV/PV with no reconstruction options, irrespective of nodal involvement, provided that no distant metastasis exists outside the pancreatic bed.[13] Historically, BR-PDAC has been included in trials that involved LA-PDAC patients.

The median overall survival ranges from 5.5 to 22 months (LA-PDAC around 16 months, whereas BR-PDAC rarely reaches 2 years).[3],[13],[14],[15],[16],[17] Optimal treatment for BR-PDAC is still controversial with regard to the type, dose, and regimen of chemotherapy, use of RT, RT field and dose, and sequence of the multimodality treatment approach. The chance of surgical resection in patients with LA-PDAC is <5%. LA-PDAC is often treated with combination chemotherapy or combined chemoradiation therapy. These approaches have not shown any improvement in survival.[16],[17]


  Conclusions Top


It is very important to recognize and closely follow the evolving imaging criteria for defining BR and LA disease given their profound implications for treatment strategy, follow-up recommendations, and overall prognosis.



 
  References Top

1.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5-29.  Back to cited text no. 1
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2.
Stathis A, Moore MJ. Advanced pancreatic carcinoma: Current treatment and future challenges. Nat Rev Clin Oncol 2010;7:163-72.  Back to cited text no. 2
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3.
Stokes JB, Nolan NJ, Stelow EB, et al. Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer. Ann Surg Oncol 2011;18:619-27.  Back to cited text no. 3
[PUBMED]    
4.
Varadhachary GR, Tamm EP, Abbruzzese JL, et al. Borderline resectable pancreatic cancer: Definitions, management, and role of preoperative therapy. Ann Surg Oncol 2006;13:1035-46.  Back to cited text no. 4
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5.
Callery MP, Chang KJ, Fishman EK, et al. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: Expert consensus statement. Ann Surg Oncol 2009;16:1727-33.  Back to cited text no. 5
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6.
Shaib WL, Ip A, Cardona K, et al. Contemporary management of borderline resectable and locally advanced unresectable pancreatic cancer. Oncologist 2016;21:178-87.  Back to cited text no. 6
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7.
Gilbert JW, Wolpin B, Clancy T, et al. Borderline resectable pancreatic cancer: Conceptual evolution and current approach to image-based classification. Ann Oncol 2017;28:2067-76.  Back to cited text no. 7
    
8.
Lopez NE, Prendergast C, Lowy AM. Borderline resectable pancreatic cancer: Definitions and management. World J Gastrointest Oncol 2014;20:10740-51.  Back to cited text no. 8
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9.
NCCN. Pancreatic Adenocarcinoma. Ver. 1. 2016. Available from: http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. [Last accesssed on 2017 Jul 01].  Back to cited text no. 9
    
10.
Shinchi H, Takao S, Noma H, et al. Length and quality of survival after external-beam radiotherapy with concurrent continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2002;53:146-50.  Back to cited text no. 10
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11.
Cohen SJ, Dobelbower R Jr., Lipsitz S, et al. Arandomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern cooperative oncology group study E8282. Int J Radiat Oncol Biol Phys 2005;62:1345-50.  Back to cited text no. 11
    
12.
Sultana A, Smith CT, Cunningham D, et al. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J Clin Oncol 2007;25:2607-15.  Back to cited text no. 12
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13.
McCracken JD, Ray P, Heilbrun LK, et al. 5-fluorouracil, methyl-CCNU, and radiotherapy with or without testolactone for localized adenocarcinoma of the exocrine pancreas: A southwest oncology group study. Cancer 1980;46:1518-22.  Back to cited text no. 13
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14.
Mahaseth H, Brutcher E, Kauh J, et al. Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. Pancreas 2013;42:1311-5.  Back to cited text no. 14
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15.
Hammel P, Huguet F, van Laethem JL, et al. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA 2016;315:1844-53.  Back to cited text no. 15
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16.
Blazer M, Wu C, Goldberg RM, et al. Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Ann Surg Oncol 2015;22:1153-9.  Back to cited text no. 16
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17.
Faris JE, Blaszkowsky LS, McDermott S, et al. FOLFIRINOX in locally advanced pancreatic cancer: The massachusetts general hospital cancer center experience. Oncologist 2013;18:543-8.  Back to cited text no. 17
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This article has been cited by
1 Consensus in determining the resectability of locally progressed pancreatic ductal adenocarcinoma – results of the Conko-007 multicenter trial
U. A. Wittel,D. Lubgan,M. Ghadimi,O. Belyaev,W. Uhl,W. O. Bechstein,R. Grützmann,W. M. Hohenberger,A. Schmid,L. Jacobasch,R. S. Croner,A. Reinacher-Schick,U. T. Hopt,A. Pirkl,H. Oettle,R. Fietkau,H. Golcher
BMC Cancer. 2019; 19(1)
[Pubmed] | [DOI]



 

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  Introduction
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