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Neoadjuvant Chemoradiation for Operable Pancreatic Cancer: The Importance of Local Disease Control

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Pancreatic Cancer

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Abstract

Pancreatic cancer (PC) is one of the most neuroinvasive tumors of the gastrointestinal tract, and perineural invasion is associated with high rates of local-regional recurrence. Historically, the goal of local-regional control in patients with PC has largely been secondary to the prevention of metastatic disease progression. However, with improving systemic therapies, patients are now experiencing unprecedented survivals and are living long enough to be susceptible to local recurrence. Such local recurrences usually occur in the neural tissue enveloping the celiac artery, superior mesenteric artery, or hepatic artery. The use of neoadjuvant chemoradiation has been effective in decreasing perineural invasion and may be particularly effective when given preoperatively prior to the immune suppressive effects of surgery and the hypoxic tissue disruption that occurs following pancreatectomy. This chapter focuses on the rationale and importance of neoadjuvant radiation therapy in the treatment of localized, potentially operable PC and provides an introduction to current neoadjuvant radiation therapy techniques, including intensity modulated radiation therapy and stereotactic body radiation therapy.

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References

  1. Sohal DP, Walsh RM, Ramanathan RK, Khorana AA. Pancreatic adenocarcinoma: treating a systemic disease with systemic therapy. J Natl Cancer Inst. 2014;106(3):dju011.

    Article  Google Scholar 

  2. Pancreatic Adenocarcinoma. NCCN clinical practice guidelines in Oncology (NCCN Guidelines) 2017; http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf.

  3. Merkow RP, Bilimoria KY, Tomlinson JS, et al. Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg. 2014;260(2):372–7.

    Article  Google Scholar 

  4. Wu W, He J, Cameron JL, et al. The impact of postoperative complications on the administration of adjuvant therapy following pancreaticoduodenectomy for adenocarcinoma. Ann Surg Oncol. 2014;21(9):2873–81.

    Article  Google Scholar 

  5. Tsai S, Erickson BA, Dua K, Ritch PS, Tolat P, Evans DB. Evolution of the management of resectable pancreatic cancer. J Oncol Pract. 2016;12(9):772–8.

    Article  Google Scholar 

  6. Evans DB, Varadhachary GR, Crane CH, 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 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Varadhachary GR, Tamm EP, Crane C, Evans DB, Wolff RA. Borderline resectable pancreatic cancer. Curr Treat Options Gastroenterol. 2005;8(5):377–84.

    Article  Google Scholar 

  10. Evans DB, Erickson BA, Ritch P. Borderline resectable pancreatic cancer: definitions and the importance of multimodality therapy. Ann Surg Oncol. 2010;17(11):2803–5.

    Article  Google Scholar 

  11. Evans DB, George B, Tsai S. Non-metastatic pancreatic cancer: resectable, borderline resectable, and locally advanced-definitions of increasing importance for the optimal delivery of multimodality therapy. Ann Surg Oncol. 2015;22(11):3409–13.

    Article  Google Scholar 

  12. Christians KK, Pilgrim CH, Tsai S, et al. Arterial resection at the time of pancreatectomy for cancer. Surgery. 2014;155(5):919–26.

    Article  Google Scholar 

  13. Liebl F, Demir IE, Mayer K, et al. The impact of neural invasion severity in gastrointestinal malignancies: a clinicopathological study. Ann Surg. 2014;260(5):900–7; discussion 907–908.

    Article  Google Scholar 

  14. Batsakis JG. Nerves and neurotropic carcinomas. Ann Otol Rhinol Laryngol. 1985;94(4 Pt 1):426–7.

    CAS  PubMed  Google Scholar 

  15. Schorn S, Demir IE, Haller B, et al. The influence of neural invasion on survival and tumor recurrence in pancreatic ductal adenocarcinoma – a systematic review and meta-analysis. Surg Oncol. 2017;26(1):105–15.

    Article  Google Scholar 

  16. Takahashi T, Ishikura H, Motohara T, Okushiba S, Dohke M, Katoh H. Perineural invasion by ductal adenocarcinoma of the pancreas. J Surg Oncol. 1997;65(3):164–70.

    Article  CAS  Google Scholar 

  17. Chatterjee D, Katz MH, Rashid A, et al. Perineural and intraneural invasion in posttherapy pancreaticoduodenectomy specimens predicts poor prognosis in patients with pancreatic ductal adenocarcinoma. Am J Surg Pathol. 2012;36(3):409–17.

    Article  Google Scholar 

  18. Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261(1):12–7.

    Article  Google Scholar 

  19. Demir IE, Boldis A, Pfitzinger PL, et al. Investigation of Schwann cells at neoplastic cell sites before the onset of cancer invasion. J Natl Cancer Inst. 2014;106(8): dju184, https://doi.org/10.1093/jnci/dju184.

  20. Secq V, Leca J, Bressy C, et al. Stromal SLIT2 impacts on pancreatic cancer-associated neural remodeling. Cell Death Dis. 2015;6:e1592.

    Article  CAS  Google Scholar 

  21. Gil Z, Cavel O, Kelly K, et al. Paracrine regulation of pancreatic cancer cell invasion by peripheral nerves. J Natl Cancer Inst. 2010;102(2):107–18.

    Article  CAS  Google Scholar 

  22. Liebig C, Ayala G, Wilks JA, Berger DH, Albo D. Perineural invasion in cancer: a review of the literature. Cancer. 2009;115(15):3379–91.

    Article  CAS  Google Scholar 

  23. Groot VP, Rezaee N, Wu W, et al. Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2017:1.

    Google Scholar 

  24. Dholakia AS, Kumar R, Raman SP, et al. Mapping patterns of local recurrence after pancreaticoduodenectomy for pancreatic adenocarcinoma: a new approach to adjuvant radiation field design. Int J Radiat Oncol Biol Phys. 2013;87(5):1007–15.

    Article  Google Scholar 

  25. Christians KK, Tsai S, Tolat PP, Evans DB. Critical steps for pancreaticoduodenectomy in the setting of pancreatic adenocarcinoma. J Surg Oncol. 2013;107(1):33–8.

    Article  Google Scholar 

  26. Kharofa J, Tsai S, Kelly T, et al. Neoadjuvant chemoradiation with IMRT in resectable and borderline resectable pancreatic cancer. Radiother Oncol. 2014;113(1):41–6.

    Article  Google Scholar 

  27. Roland CL, Yang AD, Katz MH, et al. Neoadjuvant therapy is associated with a reduced lymph node ratio in patients with potentially resectable pancreatic cancer. Ann Surg Oncol. 2015;22(4):1168–75.

    Article  Google Scholar 

  28. Chatterjee D, Rashid A, Wang H, et al. Tumor invasion of muscular vessels predicts poor prognosis in patients with pancreatic ductal adenocarcinoma who have received neoadjuvant therapy and pancreaticoduodenectomy. Am J Surg Pathol. 2012;36(4):552–9.

    Article  Google Scholar 

  29. Bakst RL, Lee N, He S, et al. Radiation impairs perineural invasion by modulating the nerve microenvironment. PLoS One. 2012;7(6):e39925.

    Article  CAS  Google Scholar 

  30. Iacobuzio-Donahue CA, Fu B, Yachida S, 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 

  31. Verbeke CS. Resection margins in pancreatic cancer. Pathologe. 2013;34(Suppl 2):241–7.

    Article  Google Scholar 

  32. Katz MH, Wang H, Balachandran A, et al. Effect of neoadjuvant chemoradiation and surgical technique on recurrence of localized pancreatic cancer. J Gastrointest Surg. 2012;16(1):68–78; discussion 78–69.

    Article  Google Scholar 

  33. Reese AS, Lu W, Regine WF. Utilization of intensity-modulated radiation therapy and image-guided radiation therapy in pancreatic cancer: is it beneficial? Semin Radiat Oncol. 2014;24(2):132–9.

    Article  Google Scholar 

  34. Abelson JA, Murphy JD, Minn AY, et al. Intensity-modulated radiotherapy for pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys. 2012;82(4):e595–601.

    Article  Google Scholar 

  35. Bittner MI, Grosu AL, Brunner TB. Comparison of toxicity after IMRT and 3D-conformal radiotherapy for patients with pancreatic cancer – a systematic review. Radiother Oncol. 2015;114(1):117–21.

    Article  Google Scholar 

  36. Lee KJ, Yoon HI, Chung MJ, et al. A comparison of gastrointestinal toxicities between intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for pancreatic cancer. Gut Liver. 2016;10(2):303–9.

    Article  Google Scholar 

  37. Yovino S, Maidment BW 3rd, Herman JM, et al. Analysis of local control in patients receiving IMRT for resected pancreatic cancers. Int J Radiat Oncol Biol Phys. 2012;83(3):916–20.

    Article  Google Scholar 

  38. Petit SF, Wu B, Kazhdan M, et al. Increased organ sparing using shape-based treatment plan optimization for intensity modulated radiation therapy of pancreatic adenocarcinoma. Radiother Oncol. 2012;102(1):38–44.

    Article  Google Scholar 

  39. Heerkens HD, Hall WA, Li XA, et al. Recommendations for MRI-based contouring of gross tumor volume and organs at risk for radiation therapy of pancreatic cancer. Pract Radiat Oncol. 2017;7(2):126–36.

    Article  CAS  Google Scholar 

  40. Wang LS, Shaikh T, Handorf EA, Hoffman JP, Cohen SJ, Meyer JE. Dose escalation with a vessel boost in pancreatic adenocarcinoma treated with neoadjuvant chemoradiation. Pract Radiat Oncol. 2015;5(5):e457–63.

    Article  Google Scholar 

  41. Huang X, Knoble JL, Zeng M, et al. Neoadjuvant gemcitabine chemotherapy followed by concurrent IMRT simultaneous boost achieves high R0 resection in borderline resectable pancreatic cancer patients. PLoS One. 2016;11(12):e0166606.

    Article  Google Scholar 

  42. Krishnan S, Chadha AS, Suh Y, et al. Focal radiation therapy dose escalation improves overall survival in locally advanced pancreatic cancer patients receiving induction chemotherapy and consolidative chemoradiation. Int J Radiat Oncol Biol Phys. 2016;94(4):755–65.

    Article  Google Scholar 

  43. Ben-Josef E, Schipper M, Francis IR, et al. A phase I/II trial of intensity modulated radiation (IMRT) dose escalation with concurrent fixed-dose rate gemcitabine (FDR-G) in patients with unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys. 2012;84(5):1166–71.

    Article  Google Scholar 

  44. Combs SE, Habermehl D, Kessel K, et al. Intensity modulated radiotherapy as neoadjuvant chemoradiation for the treatment of patients with locally advanced pancreatic cancer. Outcome analysis and comparison with a 3D-treated patient cohort. Strahlenther Onkol. 2013;189(9):738–44.

    Article  CAS  Google Scholar 

  45. Lo SS, Fakiris AJ, Chang EL, et al. Stereotactic body radiation therapy: a novel treatment modality. Nat Rev Clin Oncol. 2010;7(1):44–54.

    Article  Google Scholar 

  46. Koong AC, Le QT, Ho A, et al. Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2004;58(4):1017–21.

    Article  Google Scholar 

  47. Herman JM, Chang DT, Goodman KA, et al. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer. 2015;121(7):1128–37.

    Article  CAS  Google Scholar 

  48. Petrelli F, Comito T, Ghidini A, Torri V, Scorsetti M, Barni S. Stereotactic body radiation therapy for locally advanced pancreatic cancer: a systematic review and pooled analysis of 19 trials. Int J Radiat Oncol Biol Phys. 2017;97(2):313–22.

    Article  Google Scholar 

  49. Chuong MD, Springett GM, Freilich JM, 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.

    Article  Google Scholar 

  50. Hoyer M, Roed H, Sengelov L, et al. Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma. Radiother Oncol. 2005;76(1):48–53.

    Article  Google Scholar 

  51. Schellenberg D, Goodman KA, Lee F, et al. Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2008;72(3):678–86.

    Article  CAS  Google Scholar 

  52. Chang JY, Senan S, Paul MA, et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol. 2015;16(6):630–7.

    Article  Google Scholar 

  53. Mahadevan A, Jain S, Goldstein M, et al. Stereotactic body radiotherapy and gemcitabine for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2010;78(3):735–42.

    Article  Google Scholar 

  54. Polistina F, Costantin G, Casamassima F, et al. Unresectable locally advanced pancreatic cancer: a multimodal treatment using neoadjuvant chemoradiotherapy (gemcitabine plus stereotactic radiosurgery) and subsequent surgical exploration. Ann Surg Oncol. 2010;17(8):2092–101.

    Article  Google Scholar 

  55. Gurka MK, Collins SP, Slack R, et al. Stereotactic body radiation therapy with concurrent full-dose gemcitabine for locally advanced pancreatic cancer: a pilot trial demonstrating safety. Radiat Oncol. 2013;8:44.

    Article  Google Scholar 

  56. Schellenberg D, Kim J, Christman-Skieller C, et al. Single-fraction stereotactic body radiation therapy and sequential gemcitabine for the treatment of locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2011;81(1):181–8.

    Article  Google Scholar 

  57. Lominska CE, Unger K, Nasr NM, Haddad N, Gagnon G. Stereotactic body radiation therapy for reirradiation of localized adenocarcinoma of the pancreas. Radiat Oncol. 2012;7:74.

    Article  Google Scholar 

  58. Koong AC, Christofferson E, Le QT, et al. Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer. Int J Radiat Oncol. 2005;63(2):320–3.

    Article  Google Scholar 

  59. Chang DT, Schellenberg D, Shen J, et al. Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas. Cancer. 2009;115(3):665–72.

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Pancreatic Cancer Program, Department of Surgery, The Medical College of Wisconsin, Milwaukee, WI, USA

    Chad A. Barnes

  2. Pancreatic Cancer Program, Department of Surgery, MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA

    Susan Tsai & Douglas B. Evans

  3. Pancreatic Cancer Program, Radiation Oncology, The Medical College of Wisconsin, Milwaukee, WI, USA

    William A. Hall & Beth A. Erickson

Authors
  1. Chad A. Barnes
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  2. Susan Tsai
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  3. William A. Hall
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  4. Beth A. Erickson
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  5. Douglas B. Evans
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Corresponding author

Correspondence to Douglas B. Evans .

Editor information

Editors and Affiliations

  1. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany

    John P. Neoptolemos

  2. Division of Research Department of Surgery and Genomic Sciences and Precision Medicine Center (GSPMC), Medical College of Wisconsin, Milwaukee, Wisconsin, USA

    Raul Urrutia

  3. Division of Medical Oncology, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA

    James L. Abbruzzese

  4. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany

    Markus W. Büchler

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Barnes, C.A., Tsai, S., Hall, W.A., Erickson, B.A., Evans, D.B. (2018). Neoadjuvant Chemoradiation for Operable Pancreatic Cancer: The Importance of Local Disease Control. In: Neoptolemos, J., Urrutia, R., Abbruzzese, J., Büchler, M. (eds) Pancreatic Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7193-0_95

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