Advertisement

Pancreatic Cancer pp 1001-1020 | Cite as

Borderline Resectable Pancreatic Cancer

  • Gauri R. Varadhachary
Reference work entry

Abstract

Rigorous criteria are essential to define resectability of PDAC, which allows for accurate pretreatment staging and planning stage-specific therapy. Tumors of borderline resectability have emerged as a distinct subset, and these patients are at a high risk for margin positive resection. The intergroup criteria for BRPC includes: (1) an interface between the tumor and SMV–PV ≥180° of the vein circumference; (2) short-segment occlusion of the SMV–PV with normal vein above and below the obstruction amenable to resection and reconstruction; (3) short-segment interface of any degree between tumor and HA with normal artery proximal and distal to the interface amenable to arterial resection and reconstruction; and (4) interface between the tumor and SMA and/or CA measuring <180° of the circumference of the artery. Two multicytotoxic regimens approved for metastatic disease, 5-flurouracil with oxaliplatin and irinotecan (FOLFIRINOX) and gemcitabine with nab-paclitaxel (Gem-nabP), are incorporated in the preoperative management of BRPC in many centers although high-level evidence data on these regimens in the neoadjuvant setting are not yet available. Those with radiographic stability or regression and an improvement in serum tumor markers (CA19-9) may proceed to pancreatectomy and may require vascular resection and reconstruction. Prospective clinical trials with well-defined eligibility will help determine the treatment strategies. Additionally, prognostic and predictive biomarkers are urgently needed in therapy planning.

Keywords

Pancreatic adenocarcinoma preoperative chemotherapy neoadjuvant borderline resectable biomarkers 

References

  1. 1.
    Cloyd JM, Katz MH, Prakash L, Varadhachary GR, Wolff RA, Shroff RT, et al. Preoperative therapy and pancreatoduodenectomy for pancreatic ductal adenocarcinoma: a 25-year single-institution experience. J Gastrointest Surg. 2017;21(1):164–74.CrossRefGoogle Scholar
  2. 2.
    Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389(10073):1011–24.CrossRefGoogle Scholar
  3. 3.
    Katz MH, Wang H, Fleming JB, Sun CC, Hwang RF, Wolff RA, et al. Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma. Ann Surg Oncol. 2009;16(4):836–47.CrossRefGoogle Scholar
  4. 4.
    Neoptolemos JP, Stocken DD, Dunn JA, Almond J, Beger HG, Pederzoli P, et al. Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial. Ann Surg. 2001;234(6):758–68.CrossRefGoogle Scholar
  5. 5.
    Tamm EP, Loyer EM, Faria S, Raut CP, Evans DB, Wolff RA, et al. Staging of pancreatic cancer with multidetector CT in the setting of preoperative chemoradiation therapy. Abdom Imaging. 2006;31(5):568–74.CrossRefGoogle Scholar
  6. 6.
    Varadhachary GR, Tamm EP, Abbruzzese JL, Xiong HQ, Crane CH, Wang H, et al. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol. 2006;13(8):1035–46.CrossRefGoogle Scholar
  7. 7.
    Katz MH, Pisters PW, Evans DB, Sun CC, Lee JE, Fleming JB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008;206(5):833–46.CrossRefGoogle Scholar
  8. 8.
    Chun YS, Milestone BN, Watson JC, Cohen SJ, Burtness B, Engstrom PF, et al. Defining venous involvement in borderline resectable pancreatic cancer. Ann Surg Oncol. 2010;17(11):2832–8.CrossRefGoogle Scholar
  9. 9.
  10. 10.
    National Comprehensive Cancer Network (NCCN). https://www.nccn.org/professionals/physician_gls/PDF/pancreatic.pdf. Accessed 31 Mar 2017.
  11. 11.
    Lopez NE, Prendergast C, Lowy AM. Borderline resectable pancreatic cancer: definitions and management. World J Gastroenterol. 2014;20(31):10740–51.CrossRefGoogle Scholar
  12. 12.
    Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.CrossRefGoogle Scholar
  13. 13.
    Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, et al. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol. 2011;29(34):4548–54.CrossRefGoogle Scholar
  14. 14.
    Faria SC, Tamm EP, Loyer EM, Szklaruk J, Choi H, Charnsangavej C. Diagnosis and staging of pancreatic tumors. Semin Roentgenol. 2004;39(3):397–11.CrossRefGoogle Scholar
  15. 15.
    Ferrone CR, Finkelstein DM, Thayer SP, Muzikansky A, Fernandez-delCastillo C, Warshaw AL. Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma. J Clin Oncol. 2006;24(18):2897–02.CrossRefGoogle Scholar
  16. 16.
    Fuhrman GM, Charnsangavej C, Abbruzzese JL, Cleary KR, Martin RG, Fenoglio CJ, et al. Thin-section contrast-enhanced computed tomography accurately predicts the resectability of malignant pancreatic neoplasms. Am J Surg. 1994;167(1):104–11. discussion 11–13CrossRefGoogle Scholar
  17. 17.
    Zhong L, Li L, Yao QY. Preoperative evaluation of pancreaticobiliary tumor using MR multi-imaging techniques. World J Gastroenterol. 2005;11(24):3756–61.CrossRefGoogle Scholar
  18. 18.
    Tamm E, Charnsangavej C, Szklaruk J. Advanced 3-D imaging for the evaluation of pancreatic cancer with multidetector CT. Int J Gastrointest Cancer. 2001;30(1–2):65–71.CrossRefGoogle Scholar
  19. 19.
    Pisters PW, Lee JE, Vauthey JN, Charnsangavej C, Evans DB. Laparoscopy in the staging of pancreatic cancer. Br J Surg. 2001;88(3):325–37.CrossRefGoogle Scholar
  20. 20.
    Schmidt J, Fraunhofer S, Fleisch M, Zirngibl H. Is peritoneal cytology a predictor of unresectability in pancreatic carcinoma? Hepatogastroenterology. 2004;51(60):1827–31.PubMedGoogle Scholar
  21. 21.
    Raut CP, Grau AM, Staerkel GA, Kaw M, Tamm EP, Wolff RA, et al. Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration in patients with presumed pancreatic cancer. J Gastrointest Surg. 2003;7(1):118–26.CrossRefGoogle Scholar
  22. 22.
    Loyer EM, David CL, Dubrow RA, Evans DB, Charnsangavej C. Vascular involvement in pancreatic adenocarcinoma: reassessment by thin-section CT. Abdom Imaging. 1996;21(3):202–6.CrossRefGoogle Scholar
  23. 23.
    Lu DS, Reber HA, Krasny RM, Kadell BM, Sayre J. Local staging of pancreatic cancer: criteria for unresectability of major vessels as revealed by pancreatic-phase, thin-section helical CT. AJR Am J Roentgenol. 1997;168(6):1439–43.CrossRefGoogle Scholar
  24. 24.
    Saldinger PF, Reilly M, Reynolds K, Raptopoulos V, Chuttani R, Steer ML, Matthews JB. Is CT angiography sufficient for prediction of resectability of periampullary neoplasms? J Gastrointest Surg. 2000;4(3):233–7.CrossRefGoogle Scholar
  25. 25.
    Valls C, Andia E, Sanchez A, Fabregat J, Pozuelo O, Quintero JC, et al. Dual-phase helical CT of pancreatic adenocarcinoma: assessment of resectability before surgery. AJR Am J Roentgenol. 2002;178(4):821–6.CrossRefGoogle Scholar
  26. 26.
    Tseng JF, Raut CP, Lee JE, Pisters PW, Vauthey JN, Abdalla EK, et al. Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg. 2004;8(8):935–50.CrossRefGoogle Scholar
  27. 27.
    Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001;358(9293):1576–85.CrossRefGoogle Scholar
  28. 28.
    Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350(12):1200–10.CrossRefGoogle Scholar
  29. 29.
    Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297(3):267–77.CrossRefGoogle Scholar
  30. 30.
    Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, et al. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008;299(9):1019–26.CrossRefGoogle Scholar
  31. 31.
    Evans DB, Varadhachary GR, Crane CH, Sun CC, Lee JE, Pisters PW, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3496–02.CrossRefGoogle Scholar
  32. 32.
    Talamonti MS, Small W Jr, Mulcahy MF, Wayne JD, Attaluri V, Colletti LM, et al. A multi-institutional phase II trial of preoperative full-dose gemcitabine and concurrent radiation for patients with potentially resectable pancreatic carcinoma. Ann Surg Oncol. 2006;13(2):150–8.CrossRefGoogle Scholar
  33. 33.
    Varadhachary GR, Wolff RA, Crane CH, Sun CC, Lee JE, Pisters PW, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3487–95.CrossRefGoogle Scholar
  34. 34.
    White RR, Tyler DS. Neoadjuvant therapy for pancreatic cancer: the Duke experience. Surg Oncol Clin N Am. 2004;13(4):675–84, ix–x.CrossRefGoogle Scholar
  35. 35.
    Katz MH, Fleming JB, Bhosale P, Varadhachary G, Lee JE, Wolff R, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer. 2012;118(23):5749–56.CrossRefGoogle Scholar
  36. 36.
    Chun YS, et al. Defining venous involvement in borderline resectable pancreatic cancer. Ann Surg Oncol. 2010;17(11):2832–8.CrossRefGoogle Scholar
  37. 37.
    Stokes JB, Nolan NJ, Stelow EB, Walters DM, Weiss GR, de Lange EE, et al. Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer. Ann Surg Oncol. 2011;18(3):619–27.CrossRefGoogle Scholar
  38. 38.
    Chuong MD, Springett GM, Freilich JM, Park CK, Weber JM, Mellon EA, et al. Stereotactic body radiation therapy for locally advanced and borderline resectable pancreatic cancer is effective and well tolerated. Int J Radiat Oncol Biol Phys. 2013;86(3):516–22.CrossRefGoogle Scholar
  39. 39.
    Paniccia A, Edil BH, Schulick RD, Byers JT, Meguid C, Gajdos C, et al. Neoadjuvant FOLFIRINOX application in borderline resectable pancreatic adenocarcinoma: a retrospective cohort study. Medicine (Baltimore). 2014;93(27):e198.CrossRefGoogle Scholar
  40. 40.
    Blazer M, Wu C, Goldberg RM, Phillips G, Schmidt C, Muscarella P, et al. Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Ann Surg Oncol. 2015;22(4):1153–9.CrossRefGoogle Scholar
  41. 41.
    Gillen S, et al. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7(4):e1000267.CrossRefGoogle Scholar
  42. 42.
    Sahora K, Kuehrer I, Eisenhut A, Akan B, Koellblinger C, Goetzinger P, et al. NeoGemOx: gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer. Surgery. 2011;149(3):311–20.CrossRefGoogle Scholar
  43. 43.
    Sahora K, Kuehrer I, Schindl M, Koelblinger C, Goetzinger P, Gnant M. NeoGemTax: gemcitabine and docetaxel as neoadjuvant treatment for locally advanced nonmetastasized pancreatic cancer. World J Surg. 2011;35(7):1580–9.CrossRefGoogle Scholar
  44. 44.
    Lee JL, et al. Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma. Surgery. 2012;152(5):851–62.CrossRefGoogle Scholar
  45. 45.
    Mizuma M, et al. Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma: a prospective, multi-institutional, phase II trial. Ann Surg Oncol. 2013;20(12):3794–801.CrossRefGoogle Scholar
  46. 46.
    Mehta VK, et al. Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas. J Gastrointest Surg. 2001;5(1):27–35.CrossRefGoogle Scholar
  47. 47.
    Landry J, Catalano PJ, Staley C, Harris W, Hoffman J, Talamonti M, et al. Randomized phase II study of gemcitabine plus radiotherapy versus gemcitabine, 5-fluorouracil, and cisplatin followed by radiotherapy and 5-fluorouracil for patients with locally advanced, potentially resectable pancreatic adenocarcinoma. J Surg Oncol. 2010 Jun 1;101(7):587–92.CrossRefGoogle Scholar
  48. 48.
    Takahashi H, et al. Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg. 2013;258(6):1040–50.CrossRefGoogle Scholar
  49. 49.
    Hattori M, et al. Neoadjuvant chemoradiotherapy with S-1 in patients with borderline resectable pancreatic cancer. J Clin Oncol. 2014;32(3), suppl, 302CrossRefGoogle Scholar
  50. 50.
    Suker* M, Beumer* BR, Sadot E, Marthey L, Faris JE, Mellon EA. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016;17(6):801–10.CrossRefGoogle Scholar
  51. 51.
    Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261:12–7.CrossRefGoogle Scholar
  52. 52.
    Katz MH, Shi Q, Ahmad SA, Herman JM, Marsh Rde W, Collisson E. Preoperative modified FOLFIRINOX treatment followed by capecitabine-based chemoradiation for borderline resectable pancreatic cancer: alliance for clinical trials in oncology trial A021101. JAMA Surg. 2016;151(8):1–8.CrossRefGoogle Scholar
  53. 53.
    Nywening TM, Wang-Gillam A, Sanford DE, Belt BA, Panni RZ, Cusworth BM, et al. Targeting tumor-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Lancet Oncol. 2016;17(5):651–62.CrossRefGoogle Scholar
  54. 54.
    Boulay BR, Parepally M. Managing malignant biliary obstruction in pancreas cancer: choosing the appropriate strategy. World J Gastroenterol. 2014;20(28):9345–53.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Wasan SM, Ross WA, Staerkel GA, Lee JH. Use of expandable metallic biliary stents in resectable pancreatic cancer. Am J Gastroenterol. 2005;100(9):2056–61.CrossRefGoogle Scholar
  56. 56.
    Boulay BR, Gardner TB, Gordon SR. Occlusion rate and complications of plastic biliary stent placement in patients undergoing neoadjuvant chemoradiotherapy for pancreatic cancer with malignant biliary obstruction. J Clin Gastroenterol. 2010;44(6):452–5.PubMedGoogle Scholar
  57. 57.
    Kitano M, Yamashita Y, Tanaka K. Covered self-expandable metal stents with an anti-migration system improve patency duration without increased complications compared with uncovered stents for distal biliary obstruction caused by pancreatic carcinoma: a randomized multicenter trial. Am J Gastroenterol. 2013;108(11):1713–22.CrossRefGoogle Scholar
  58. 58.
    Silver JK, Baima J. Cancer prehabilitation: an opportunity to decrease treatment-related morbidity, increase cancer treatment options, and improve physical and psychological health outcomes. Am J Phys Med Rehabil. 2013;92(8):715–27.CrossRefGoogle Scholar
  59. 59.
    Li C, Carli F, Lee L, Charlebois P, Stein B, Liberman AS, et al. Impact of a trimodal prehabilitation program on functional recovery after colorectal cancer surgery: a pilot study. Surg Endosc. 2013;27(4):1072–82.CrossRefGoogle Scholar
  60. 60.
    Mayo NE, Feldman L, Scott S, Zavorsky G, Kim DJ, Charlebois P, et al. Impact of preoperative change in physical function on postoperative recovery: argument supporting prehabilitation for colorectal surgery. Surgery. 2011;150(3):505–14.CrossRefGoogle Scholar
  61. 61.
    de Paleville DT, Topp RV, Swank AM. Effects of aerobic training prior to and during chemotherapy in a breast cancer patient: a case study. J Strength Cond Res. 2007;21(2):635–7.PubMedGoogle Scholar
  62. 62.
    Tzeng CW, Katz MH, Fleming JB, Lee JE, Pisters PW, Holmes HM, et al. Morbidity and mortality after pancreaticoduodenectomy in patients with borderline resectable type C clinical classification. J Gastrointest Surg. 2014;18(1):146–55.CrossRefGoogle Scholar
  63. 63.
    Gerstenhaber F, Grossman J, Lubezky N, Itzkowitz E, Nachmany I, Sever R, et al. Pancreaticoduodenectomy in elderly adults: is it justified in terms of mortality, long-term morbidity, and quality of life? J Am Geriatr Soc. 2013;61(8):1351–7.CrossRefGoogle Scholar
  64. 64.
    Frakes JM, Strom T, Springett GM, Hoffe SE, Balducci L, Hodul P, et al. Resected pancreatic cancer outcomes in the elderly. J Geriatr Oncol. 2015;6(2):127–32.CrossRefGoogle Scholar
  65. 65.
    Miura JT, Krepline AN, George B, Ritch PS, Erickson BA, Johnston FM, et al. Neoadjuvant therapy for pancreatic cancer in patients older than age 75. J Clin Oncol. 2014;32(3):1545–55.Google Scholar
  66. 66.
    Cassinotto C, Mouries A, Lafourcade JP, Terrebonne E, Belleannée G, Blanc JF, et al. Locally advanced pancreatic adenocarcinoma: reassessment of response with CT after neoadjuvant chemotherapy and radiation therapy. Radiology. 2014;273(1):108–16.CrossRefGoogle Scholar
  67. 67.
    Du Y, Zhou X, Huang Z, Qiu T, Wang J, Zhu W, et al. Meta-analysis of the prognostic value of smad4 immunohistochemistry in various cancers. PLoS One. 2014;9(10):e110182.CrossRefGoogle Scholar
  68. 68.
    Iacobuzio-Donahue CA, Fu B, Yachida S, Luo M, Abe H, Henderson CM. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol. 2009;27(11):1806–13.CrossRefGoogle Scholar
  69. 69.
    Boone BA, Sabbaghian S, Zenati M, Marsh JW, Moser AJ, Zureikat AH, et al. Loss of SMAD4 staining in pre-operative cell blocks is associated with distant metastases following pancreaticoduodenectomy with venous resection for pancreatic cancer. J Surg Oncol. 2014;110(2):171–5.CrossRefGoogle Scholar
  70. 70.
    Koay EJ, Amer AM, Baio FE, Ondari AO, Fleming JB. Toward stratification of patients with pancreatic cancer: past lessons from traditional approaches and future applications with physical biomarkers. Cancer Lett. 2016;381(1):237–43.CrossRefGoogle Scholar
  71. 71.
    Koay EJ, Baio FE, Ondari A, Truty MJ, Cristini V, Thomas RM, et al. Intra-tumoral heterogeneity of gemcitabine delivery and mass transport in human pancreatic cancer. Phys Biol. 2014;11(6):065002.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Gastrointestinal Medical OncologyUniversity of Texas, M.D. Anderson Cancer CenterHoustonUSA

Personalised recommendations