Skip to main content
SpringerLink
Log in
Book cover

Management of Localized Pancreatic Cancer pp 67–84Cite as

Delivery of Neoadjuvant Versus Adjuvant Therapy in Localized Pancreatic Cancer

  • Chapter
  • First Online:

  • 441 Accesses

Abstract

Cancer of the exocrine pancreas is a highly lethal malignancy. Approximately 53,670 people develop exocrine pancreatic cancer each year in the United States, and almost all are expected to die from the disease [1]. Worldwide, pancreatic cancer is the eighth leading cause of cancer deaths in men (138,100 deaths annually) and the ninth in women (127,900 deaths annually) [2]. It is the third leading cause of cancer-related death in the United States after recently eclipsing breast cancer-related mortality and is expected to become the second leading cause of cancer-related mortality in the United States in the next decade, second only to lung cancer [1].

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.

    Article  Google Scholar 

  2. Jemal A, et al. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    Article  Google Scholar 

  3. Allen PJ, et al. Multi-institutional Validation Study of the American Joint Commission on Cancer (8th edition) changes for T and N staging in patients with pancreatic adenocarcinoma. Ann Surg. 2017;265(1):185–91.

    Article  Google Scholar 

  4. Chun YS, Pawlik TM, Vauthey JN. 8th edition of the AJCC cancer staging manual: pancreas and hepatobiliary cancers. Ann Surg Oncol. 2018;25(4):845–7.

    Article  Google Scholar 

  5. Al-Hawary MM, et al. Pancreatic ductal adenocarcinoma radiology reporting template: consensus statement of the society of abdominal radiology and the american pancreatic association. Gastroenterology. 2014;146(1):291–304.e1.

    Article  Google Scholar 

  6. Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014;371(11):1039–49.

    Article  CAS  Google Scholar 

  7. Neoptolemos JP, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001;358(9293):1576–85.

    Article  CAS  Google Scholar 

  8. Neoptolemos JP, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350(12):1200–10.

    Article  CAS  Google Scholar 

  9. Oettle H, 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.

    Article  CAS  Google Scholar 

  10. Oettle H, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310(14):1473–81.

    Article  CAS  Google Scholar 

  11. Ueno H, et al. A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer. Br J Cancer. 2009;101(6):908–15.

    Article  CAS  Google Scholar 

  12. Neoptolemos JP, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010;304(10):1073–81.

    Article  CAS  Google Scholar 

  13. Valle JW, et al. Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. J Clin Oncol. 2014;32(6):504–12.

    Article  Google Scholar 

  14. Neoptolemos JP, 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.

    Article  CAS  Google Scholar 

  15. Conroy T, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379(25):2395–406.

    Article  CAS  Google Scholar 

  16. Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985;120(8):899–903.

    Article  CAS  Google Scholar 

  17. Klinkenbijl JH, et al. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg. 1999;230(6):776–82; discussion 782–4.

    Article  CAS  Google Scholar 

  18. Regine WF, 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.

    Article  CAS  Google Scholar 

  19. Regine WF, et al. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analysis of the U.S. Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011;18(5):1319–26.

    Article  Google Scholar 

  20. Gnerlich JL, et al. Microscopic margins and patterns of treatment failure in resected pancreatic adenocarcinoma. Arch Surg. 2012;147(8):753–60.

    Article  Google Scholar 

  21. Iacobuzio-Donahue CA, et al. 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.

    Article  CAS  Google Scholar 

  22. Spitz FR, et al. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol. 1997;15(3):928–37.

    Article  CAS  Google Scholar 

  23. Mayo SC, et al. Management of patients with pancreatic adenocarcinoma: national trends in patient selection, operative management, and use of adjuvant therapy. J Am Coll Surg. 2012;214(1):33–45.

    Article  Google Scholar 

  24. Evans DB, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3496–502.

    Article  CAS  Google Scholar 

  25. Varadhachary GR, 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.

    Article  CAS  Google Scholar 

  26. Miura JT, et al. Use of neoadjuvant therapy in patients 75 years of age and older with pancreatic cancer. Surgery. 2015;158(6):1545–55.

    Article  Google Scholar 

  27. Christians KK, et al. Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment paradigm? Oncologist. 2014;19(3):266–74.

    Article  CAS  Google Scholar 

  28. Raut CP, et al. Neoadjuvant therapy for resectable pancreatic cancer. Surg Oncol Clin N Am. 2004;13(4):639–61, ix.

    Article  Google Scholar 

  29. Takahashi H, et al. Preoperative chemoradiation reduces the risk of pancreatic fistula after distal pancreatectomy for pancreatic adenocarcinoma. Surgery. 2011;150(3):547–56.

    Article  Google Scholar 

  30. Willett CG, et al. Resection margins in carcinoma of the head of the pancreas. Implications for radiation therapy. Ann Surg. 1993;217(2):144–8.

    Article  CAS  Google Scholar 

  31. Cooper AB, et al. Does the use of neoadjuvant therapy for pancreatic adenocarcinoma increase postoperative morbidity and mortality rates? J Gastrointest Surg. 2015;19(1):80–6; discussion 86–7.

    Article  Google Scholar 

  32. Christians KK, et al. Survival of patients with resectable pancreatic cancer who received neoadjuvant therapy. Surgery. 2016;159(3):893–900.

    Article  Google Scholar 

  33. Winter JM, et al. Survival after resection of pancreatic adenocarcinoma: results from a single institution over three decades. Ann Surg Oncol. 2012;19(1):169–75.

    Article  Google Scholar 

  34. Andriulli A, et al. Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies. Ann Surg Oncol. 2012;19(5):1644–62.

    Article  Google Scholar 

  35. Assifi MM, et al. Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials. Surgery. 2011;150(3):466–73.

    Article  Google Scholar 

  36. 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.

    Article  Google Scholar 

  37. Casadei R, et al. Neoadjuvant chemoradiotherapy and surgery versus surgery alone in resectable pancreatic cancer: a single-center prospective, randomized, controlled trial which failed to achieve accrual targets. J Gastrointest Surg. 2015;19(10):1802–12.

    Article  Google Scholar 

  38. Golcher H, et al. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: results of the first prospective randomized phase II trial. Strahlenther Onkol. 2015;191(1):7–16.

    Article  Google Scholar 

  39. Mokdad AA, et al. Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer: a propensity score matched analysis. J Clin Oncol. 2017;35(5):515–22.

    Article  Google Scholar 

  40. Evans DB, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992;127(11):1335–9.

    Article  CAS  Google Scholar 

  41. Staley CA, et al. Preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for adenocarcinoma of the pancreatic head. Am J Surg. 1996;171(1):118–24; discussion 124–5.

    Article  CAS  Google Scholar 

  42. Pisters PW, et al. Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol. 1998;16(12):3843–50.

    Article  CAS  Google Scholar 

  43. Hoffman JP, et al. Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group Study. J Clin Oncol. 1998;16(1):317–23.

    Article  CAS  Google Scholar 

  44. White RR, et al. Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas. Ann Surg Oncol. 2001;8(10):758–65.

    Article  CAS  Google Scholar 

  45. Pisters PW, et al. Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome. J Clin Oncol. 2002;20(10):2537–44.

    Article  CAS  Google Scholar 

  46. Moutardier V, et al. Assessment of pathologic response after preoperative chemoradiotherapy and surgery in pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys. 2004;60(2):437–43.

    Article  Google Scholar 

  47. Talamonti MS, 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.

    Article  Google Scholar 

  48. Palmer DH, et al. A randomized phase 2 trial of neoadjuvant chemotherapy in resectable pancreatic cancer: gemcitabine alone versus gemcitabine combined with cisplatin. Ann Surg Oncol. 2007;14(7):2088–96.

    Article  Google Scholar 

  49. Heinrich S, et al. Prospective phase II trial of neoadjuvant chemotherapy with gemcitabine and cisplatin for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(15):2526–31.

    Article  CAS  Google Scholar 

  50. Le Scodan R, et al. Preoperative chemoradiation in potentially resectable pancreatic adenocarcinoma: feasibility, treatment effect evaluation and prognostic factors, analysis of the SFRO-FFCD 9704 trial and literature review. Ann Oncol. 2009;20(8):1387–96.

    Article  Google Scholar 

  51. O’Reilly EM, et al. A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma. Ann Surg. 2014;260(1):142–8.

    Article  Google Scholar 

  52. Kim SS, et al. Preoperative FOLFIRINOX for borderline resectable pancreatic cancer: is radiation necessary in the modern era of chemotherapy? J Surg Oncol. 2016;114(5):587–96.

    Article  CAS  Google Scholar 

  53. Katz MH, et al. 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):e161137.

    Article  Google Scholar 

  54. Takahashi H, et al. Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg. 2013;258(6):1040–50.

    Article  Google Scholar 

  55. Kim EJ, et al. A multi-institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer. Cancer. 2013;119(15):2692–700.

    Article  CAS  Google Scholar 

  56. Kang CM, et al. Potential contribution of preoperative neoadjuvant concurrent chemoradiation therapy on margin-negative resection in borderline resectable pancreatic cancer. J Gastrointest Surg. 2012;16(3):509–17.

    Article  Google Scholar 

  57. Barugola G, et al. Outcomes after resection of locally advanced or borderline resectable pancreatic cancer after neoadjuvant therapy. Am J Surg. 2012;203(2):132–9.

    Article  Google Scholar 

  58. Stokes JB, et al. Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer. Ann Surg Oncol. 2011;18(3):619–27.

    Article  Google Scholar 

  59. Chun YS, et al. Defining venous involvement in borderline resectable pancreatic cancer. Ann Surg Oncol. 2010;17(11):2832–8.

    Article  Google Scholar 

  60. McClaine RJ, et al. Neoadjuvant therapy may lead to successful surgical resection and improved survival in patients with borderline resectable pancreatic cancer. HPB (Oxford). 2010;12(1):73–9.

    Article  Google Scholar 

  61. Koprowski H, et al. Specific antigen in serum of patients with colon carcinoma. Science. 1981;212(4490):53–5.

    Article  CAS  Google Scholar 

  62. Koprowski H, et al. Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet. 1979;5(6):957–71.

    Article  CAS  Google Scholar 

  63. Galli C, Basso D, Plebani M. CA 19-9: handle with care. Clin Chem Lab Med. 2013;51(7):1369–83.

    Article  CAS  Google Scholar 

  64. Poruk KE, et al. Screening for pancreatic cancer: why, how, and who? Ann Surg. 2013;257(1):17–26.

    Article  Google Scholar 

  65. Poruk KE, et al. The clinical utility of CA 19-9 in pancreatic adenocarcinoma: diagnostic and prognostic updates. Curr Mol Med. 2013;13(3):340–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Zubarik R, et al. Screening for pancreatic cancer in a high-risk population with serum CA 19-9 and targeted EUS: a feasibility study. Gastrointest Endosc. 2011;74(1):87–95.

    Article  Google Scholar 

  67. Orntoft TF, et al. Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels. J Biol Chem. 1996;271(50):32260–8.

    Article  CAS  Google Scholar 

  68. Yu LC, et al. Correlation of a missense mutation in the human secretor alpha 1,2-fucosyltransferase gene with the Lewis(a+b+) phenotype: a potential molecular basis for the weak secretor allele (sew). Biochem J. 1995;312(Pt 2):329–32.

    Article  CAS  Google Scholar 

  69. Kannagi R. Carbohydrate antigen sialyl Lewis a--its pathophysiological significance and induction mechanism in cancer progression. Chang Gung Med J. 2007;30(3):189–209.

    PubMed  Google Scholar 

  70. Sanchez M, Gomes H, Marcus EN. Elevated CA 19-9 levels in a patient with Mirizzi syndrome: case report. South Med J. 2006;99(2):160–3.

    Article  Google Scholar 

  71. Scoggins CR, et al. Supra-elevated CA 19-9 in a benign hepatic cyst adenoma. HPB (Oxford). 2004;6(1):43–4.

    Article  CAS  Google Scholar 

  72. Berger AC, et al. Undetectable preoperative levels of serum CA 19-9 correlate with improved survival for patients with resectable pancreatic adenocarcinoma. Ann Surg Oncol. 2004;11(7):644–9.

    Article  Google Scholar 

  73. Park HD, et al. The relationship between Lewis/Secretor genotypes and serum carbohydrate antigen 19-9 levels in a Korean population. Korean J Lab Med. 2010;30(1):51–7.

    Article  CAS  Google Scholar 

  74. Bergquist JR, et al. Carbohydrate antigen 19-9 elevation in anatomically resectable, early stage pancreatic cancer is independently associated with decreased overall survival and an indication for neoadjuvant therapy: a National Cancer Database Study. J Am Coll Surg. 2016;223(1):52–65.

    Article  Google Scholar 

  75. Mirkin KA, Hollenbeak CS, Wong J. Prognostic impact of carbohydrate antigen 19-9 level at diagnosis in resected stage I-III pancreatic adenocarcinoma: a U.S. population study. J Gastrointest Oncol. 2017;8(5):778–88.

    Article  Google Scholar 

  76. Aldakkak M, et al. Pre-treatment carbohydrate antigen 19-9 does not predict the response to neoadjuvant therapy in patients with localized pancreatic cancer. HPB (Oxford). 2015;17(10):942–52.

    Article  Google Scholar 

  77. Williams JL, et al. CA19-9 normalization during pre-operative treatment predicts longer survival for patients with locally progressed pancreatic cancer. J Gastrointest Surg. 2016;20(7):1331–42.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pancreatic Cancer Program, Division of Hematology and Oncology, Department of Medicine, Phase 1 Clinical Trials Program, Froedtert and Medical College of Wisconsin, Milwaukee, WI, USA

    Ben George

  2. Pancreatic Cancer Program, Division of Hematology and Oncology, Department of Medicine, Froedtert and Medical College of Wisconsin, Clinical Cancer Center, Milwaukee, WI, USA

    Paul S. Ritch

Authors
  1. Ben George
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul S. Ritch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul S. Ritch .

Editor information

Editors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, The Medical College of Wisconsin, Milwaukee, WI, USA

    Susan Tsai

  2. Division of Medical Oncology, Department of Medicine, The Medical College of Wisconsin, Milwaukee, WI, USA

    Paul S. Ritch

  3. Department of Radiation Oncology, The Medical College of Wisconsin, Milwaukee, WI, USA

    Beth A. Erickson

  4. Department of Surgery, The Medical College of Wisconsin, Milwaukee, WI, USA

    Douglas B. Evans

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

George, B., Ritch, P.S. (2019). Delivery of Neoadjuvant Versus Adjuvant Therapy in Localized Pancreatic Cancer. In: Tsai, S., Ritch, P., Erickson, B., Evans, D. (eds) Management of Localized Pancreatic Cancer . Springer, Cham. https://doi.org/10.1007/978-3-319-98944-0_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-98944-0_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-98943-3

  • Online ISBN: 978-3-319-98944-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation