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Neoadjuvant Chemoradiation for Localized Pancreatic Cancer

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Management of Localized Pancreatic Cancer

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Abstract

Pancreatic cancer is a deadly malignancy with extremely poor outcomes. Central to the management of patients with pancreatic cancer is surgical resection. The role of neoadjuvant or adjuvant therapies in conjunction with surgical resection is well established. The optimal sequencing of these therapies remains controversial. While historically patients with pancreatic cancer were managed with a surgery-first approach, the oncologic rationale for this management strategy has been examined, and questioned, for decades. This is primarily secondary to high rates of positive margins, nodal positivity, and local recurrence associated with a surgery-first approach. Furthermore, successful completion of adjuvant therapy is challenging with a surgery-first approach, making progress with novel adjuvant treatment strategies problematic. Neoadjuvant therapy represents an important advance in the management of patients with pancreatic cancer. Patients managed with neoadjuvant therapy have lower rates of margin positivity, lower rates of node positivity, higher rates of treatment completion, and lower rates of local recurrence as compared to patients managed with a surgery-first approach. In this chapter, we present the rationale for neoadjuvant therapy in pancreatic cancer along with supporting evidence. Evolving data examining the role for varying neoadjuvant treatment strategies is summarized. Select ongoing neoadjuvant clinical trials are also summarized. Finally, we present future directions in need of additional investigation for patients undergoing neoadjuvant therapy.

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References

  1. 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.

    Article  CAS  Google Scholar 

  2. Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, 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 

  3. Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016;388(10041):248–57.

    Article  CAS  Google Scholar 

  4. Ghaneh P, Kleeff J, Halloran CM, Raraty M, Jackson R, Melling J, et al. The impact of positive resection margins on survival and recurrence following resection and adjuvant chemotherapy for pancreatic ductal adenocarcinoma. Ann Surg. 2019;269(3):520–9.

    Article  Google Scholar 

  5. Available from: http://www.isrctn.com/ISRCTN89500674.

  6. Herman JM, Swartz MJ, Hsu CC, Winter J, Pawlik TM, Sugar E, et al. Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital. J Clin Oncol. 2008;26(21):3503–10.

    Article  Google Scholar 

  7. Corsini MM, Miller RC, Haddock MG, Donohue JH, Farnell MB, Nagorney DM, et al. Adjuvant radiotherapy and chemotherapy for pancreatic carcinoma: the Mayo Clinic experience (1975–2005). J Clin Oncol. 2008;26(21):3511–6.

    Article  Google Scholar 

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

    Article  Google Scholar 

  9. 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):3496–502.

    Article  CAS  Google Scholar 

  10. Evans DB, Rich TA, Byrd DR, Cleary KR, Connelly JH, Levin B, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992;127(11):1335–9.

    Article  CAS  Google Scholar 

  11. Pisters PW, Abbruzzese JL, Janjan NA, Cleary KR, Charnsangavej C, Goswitz MS, 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 

  12. Pisters PW, Wolff RA, Janjan NA, Cleary KR, Charnsangavej C, Crane CN, 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 

  13. 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.

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  15. Mokdad AA, Minter RM, Zhu H, Augustine MM, Porembka MR, Wang SC, 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 

  16. Papavasiliou P, Chun YS, Hoffman JP. How to define and manage borderline resectable pancreatic cancer. Surg Clin North Am. 2013;93(3):663–74.

    Article  Google Scholar 

  17. 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 

  18. 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; discussion 46–8.

    Article  Google Scholar 

  19. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.

    Article  CAS  Google Scholar 

  20. Christians KK, Tsai S, Mahmoud A, Ritch P, Thomas JP, Wiebe L, et al. Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment paradigm? Oncologist. 2014;19(3):266–74.

    Article  CAS  Google Scholar 

  21. 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.

    Article  CAS  Google Scholar 

  22. 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.

    Article  Google Scholar 

  23. Petrelli F, Coinu A, Borgonovo K, Cabiddu M, Ghilardi M, Lonati V, et al. FOLFIRINOX-based neoadjuvant therapy in borderline resectable or unresectable pancreatic cancer: a meta-analytical review of published studies. Pancreas. 2015;44(4):515–21.

    Article  CAS  Google Scholar 

  24. Katz MHG, Ou FS, Herman JM, Ahmad SA, Wolpin B, Marsh R, et al. Alliance for clinical trials in oncology (ALLIANCE) trial A021501: preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas. BMC Cancer. 2017;17(1):505.

    Article  Google Scholar 

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

    Article  Google Scholar 

  26. 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.

    Article  Google Scholar 

  27. Palta M. Gemcitabine/Nab-Paclitaxel with HIGRT in resectablepancreatic cancer 2017. Available from: https://clinicaltrials.gov/ct2/show/NCT02318095?term=palta&cond=Pancreatic+Cancer&rank=1.

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

    Article  Google Scholar 

  29. Huang X, Knoble JL, Zeng M, Aguila FN, Patel T, Chambers LW, 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 

  30. Kim EJ, Ben-Josef E, Herman JM, Bekaii-Saab T, Dawson LA, Griffith KA, 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 

  31. Hong TS, Ryan DP, Borger DR, Blaszkowsky LS, Yeap BY, Ancukiewicz M, et al. A phase 1/2 and biomarker study of preoperative short course chemoradiation with proton beam therapy and capecitabine followed by early surgery for resectable pancreatic ductal adenocarcinoma. Int J Radiat Oncol Biol Phys. 2014;89(4):830–8.

    Article  CAS  Google Scholar 

  32. Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731–40.

    Article  CAS  Google Scholar 

  33. Doi R, Imamura M, Hosotani R, Imaizumi T, Hatori T, Takasaki K, et al. Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: final results of a randomized multi-institutional trial. Surg Today. 2008;38(11):1021–8.

    Article  Google Scholar 

  34. Golcher H, Brunner TB, Witzigmann H, Marti L, Bechstein WO, Bruns C, 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. Strahlentherapie und Onkologie : Organ der DeutschenRontgengesellschaft [et al]. 2015;191(1):7–16.

    Google Scholar 

  35. Versteijne E, van Eijck CH, Punt CJ, Suker M, Zwinderman AH, Dohmen MA, et al. Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC trial): study protocol for a multicentre randomized controlled trial. Trials. 2016;17(1):127.

    Article  Google Scholar 

  36. Tachezy M, Gebauer F, Petersen C, Arnold D, Trepel M, Wegscheider K, et al. Sequential neoadjuvantchemoradiotherapy (CRT) followed by curative surgery vs. primary surgery alone for resectable, non-metastasized pancreatic adenocarcinoma: NEOPA- a randomized multicenter phase III study (NCT01900327, DRKS00003893, ISRCTN82191749). BMC Cancer. 2014;14:411.

    Article  Google Scholar 

  37. 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 

  38. Jaffray DA. Image-guided radiotherapy: from current concept to future perspectives. Nat Rev Clin Oncol. 2012;9(12):688–99.

    Article  CAS  Google Scholar 

  39. Hall WA, Heerkens HD, Paulson ES, Meijer GJ, Kotte AN, Knechtges P, et al. Pancreatic gross tumor volume contouring on computed tomography (CT) compared with magnetic resonance imaging (MRI): results of an international contouring conference. Pract Radiat Oncol. 2018;8(2):107–15.

    Article  Google Scholar 

  40. Dholakia AS, Kumar R, Raman SP, Moore JA, Ellsworth S, McNutt T, 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 

  41. Heerkens HD, Hall WA, Li XA, Knechtges P, Dalah E, Paulson ES, 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 

  42. Hall WA, Mikell JL, Mittal P, Colbert L, Prabhu RS, Kooby DA, et al. Tumor size on abdominal MRI versus pathologic specimen in resected pancreatic adenocarcinoma: implications for radiation treatment planning. Int J Radiat Oncol Biol Phys. 2013;86(1):102–7.

    Article  Google Scholar 

  43. Shaib WL, Hawk N, Cassidy RJ, Chen Z, Zhang C, Brutcher E, et al. A phase 1 study of stereotactic body radiation therapy dose escalation for borderline resectable pancreatic cancer after modified FOLFIRINOX (NCT01446458). Int J Radiat Oncol Biol Phys. 2016;96(2):296–303.

    Article  Google Scholar 

  44. Krishnan S, Chadha AS, Suh Y, Chen HC, Rao A, Das P, 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 

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

    Article  Google Scholar 

  46. Bittner MI, Grosu AL, Brunner TB. Comparison of toxicity after IMRT and 3D-conformal radiotherapy for patients with pancreatic cancer - a systematic review. RadiotherOncol: Journal of the European Society for Therapeutic Radiology and Oncology. 2015;114(1):117–21.

    Google Scholar 

  47. Lee KJ, Yoon HI, Chung MJ, Park JY, Bang S, Park SW, et al. A comparison of gastrointestinal toxicities between intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for pancreatic cancer. GutLiver. 2016;10(2):303–9.

    Google Scholar 

  48. Hoffman JP, Lipsitz S, Pisansky T, Weese JL, Solin L, Benson AB 3rd. 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 

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Authors and Affiliations

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

    William A. Hall & Beth A. Erickson

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  1. William A. Hall
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  2. Beth A. Erickson
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Correspondence to William A. Hall .

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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

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Hall, W.A., Erickson, B.A. (2019). Neoadjuvant Chemoradiation for 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_8

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  • DOI: https://doi.org/10.1007/978-3-319-98944-0_8

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