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The Management of Locally Advanced Nonmetastatic Pancreas Cancer

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Current and Emerging Therapies in Pancreatic Cancer

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Abstract

At the time of diagnosis of pancreatic cancer, greater than half of patients have metastatic disease, and less than 20% of patients are resectable. The remaining 30–40% of patients present with borderline resectable (BR) or locally advanced unresectable pancreatic cancer (LAPC). Recently endorsed by the NCCN, the Intergroup definition of BR and LAPC has been developed to promote multicenter collaboration and to standardize future clinical trials.

For this subset of patients, neoadjuvant therapy (NT) has become standard treatment with the primary purpose of tumor downstaging so that a margin-free, R0 resection may be possible. Current treatment strategies in BR and LAPC, gemcitabine combinations and FOLFIRINOX, derive from the success of regimens used in metastatic pancreatic cancer. Further trials are needed to evaluate the efficacy of chemoradiation with these new chemotherapy regimens.

Upon completion of NT, the decision to proceed with resection has traditionally been determined by radiologic imaging. However, radiologic response is not an accurate predictor of resectability, and all patients should undergo an attempt at resection after NT, in the absence of systemic progression.

Due to limitations of current imaging modalities to accurately distinguish continued tumor involvement from downstaged desmoplastic reaction, en bloc vascular resections are frequently performed for patients with BR and LAPC who proceed to surgery. Although venous resections have been demonstrated to be feasible and safe, arterial resections are associated with unfavorable surgical and prognostic outcomes.

Medical progress continues to be outpaced by pancreatic cancer’s rising mortality rate. Targeted therapy, genomic profiling, and immunotherapy are prospective adjuncts to bridge the gap between modest advancements in medicine and the aggressive nature of pancreatic cancer. Future breakthroughs in the treatment of metastatic pancreatic cancer may carry over promises of more effective systemic therapies to downstage patients with advanced nonmetastatic disease.

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Abbreviations

AGEO:

Association des Gastro-Entérologues Oncologues

AHPBA:

Americas Hepato-Pancreato-Biliary Association

BR:

Borderline resectable

CA:

Celiac artery/axis

CI:

Confidence interval

CRT:

Chemoradiation therapy

CT:

Computed tomography

DP:

Distal pancreatectomy

DP-CAR:

Distal pancreatectomy and splenectomy with celiac artery resection

ECOG:

Eastern Cooperative Oncology Group

EGFR:

Epidermal growth factor receptor

ERCP:

Endoscopic retrograde cholangiopancreatography

EUS:

Endoscopic ultrasound

FDG-PET/CT:

Combined positron emission tomography/computed tomography using 18-fluorodeoxyglucose

FNA:

Fine needle aspiration

FOLFIRINOX:

Folinic acid, fluorouracil, irinotecan, and oxaliplatin

HA:

Hepatic artery

LAPC:

Locally advanced pancreatic cancer

MDACC:

MD Anderson Cancer Center

MDCT:

Multi-detector computed tomography

mFOLFIRINOX:

Modified FOLFIRINOX

MRI:

Magnetic resonance imaging

NCCN:

National Comprehensive Cancer Network

NT:

Neoadjuvant therapy

OR:

Odds ratio

OS:

Overall survival

PV:

Portal vein

RECIST:

Response Evaluation Criteria in Solid Tumors

SBRT:

Stereotactic body radiation therapy

SEMS:

Self-expanding metal stents

SMA:

Superior mesenteric artery

SMV:

Superior mesenteric vein

SSAT:

Society for Surgery of the Alimentary Tract

SSO:

Society of Surgical Oncology

TNM:

Tumor-node-metastasis

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.

    Article  PubMed  Google Scholar 

  2. Sohn TA, Yeo CJ, Cameron JL, Koniaris L, Kaushal S, Abrams RA, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4(6):567–79.

    Article  CAS  PubMed  Google Scholar 

  3. Edge SB, Compton CC. The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.

    Article  PubMed  Google Scholar 

  4. 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  PubMed  Google Scholar 

  5. Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol. 2009;16(7):1727–33.

    Article  PubMed  Google Scholar 

  6. Ishikawa O, Ohigashi H, Imaoka S, Furukawa H, Sasaki Y, Fujita M, et al. Preoperative indications for extended pancreatectomy for locally advanced pancreas cancer involving the portal vein. Ann Surg. 1992;215(3):231–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Katz MH, Marsh R, Herman JM, Shi Q, Collison E, Venook AP, et al. Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol. 2013;20(8):2787–95.

    Article  PubMed  PubMed Central  Google Scholar 

  8. DS L, 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.

    Article  Google Scholar 

  9. Wong JC, Lu DS. Staging of pancreatic adenocarcinoma by imaging studies. Clin Gastroenterol Hepatol. 2008;6(12):1301–8.

    Article  PubMed  Google Scholar 

  10. Legmann P, Vignaux O, Dousset B, Baraza AJ, Palazzo L, Dumontier I, et al. Pancreatic tumors: comparison of dual-phase helical CT and endoscopic sonography. AJR Am J Roentgenol. 1998;170(5):1315–22.

    Article  CAS  PubMed  Google Scholar 

  11. Pietryga JA, Morgan DE. Imaging preoperatively for pancreatic adenocarcinoma. J Gastrointest Oncol. 2015;6(4):343–57.

    PubMed  PubMed Central  Google Scholar 

  12. Prokesch RW, Chow LC, Beaulieu CF, Bammer R, Jeffrey RB Jr. Isoattenuating pancreatic adenocarcinoma at multi-detector row CT: secondary signs. Radiology. 2002;224(3):764–8.

    Article  PubMed  Google Scholar 

  13. Xia BT, Ahmad SA. Clinical considerations for pancreatic cancer. Semin Roentgenol. 2016;51(2):74–81.

    Article  PubMed  Google Scholar 

  14. Makarawo TP, Negussie E, Malde S, Tilak J, Gayagoy J, Watson J, et al. Water as a contrast medium: a re-evaluation using the multidetector-row computed tomography. Am Surg. 2013;79(7):728–33.

    PubMed  Google Scholar 

  15. Kim JH, Park SH, ES Y, Kim MH, Kim J, Byun JH, et al. Visually isoattenuating pancreatic adenocarcinoma at dynamic-enhanced CT: frequency, clinical and pathologic characteristics, and diagnosis at imaging examinations. Radiology. 2010;257(1):87–96.

    Article  PubMed  Google Scholar 

  16. Koelblinger C, Ba-Ssalamah A, Goetzinger P, Puchner S, Weber M, Sahora K, et al. Gadobenate dimeglumine-enhanced 3.0-T MR imaging versus multiphasic 64-detector row CT: prospective evaluation in patients suspected of having pancreatic cancer. Radiology. 2011;259(3):757–66.

    Article  PubMed  Google Scholar 

  17. Bipat S, Phoa SS, van Delden OM, Bossuyt PM, Gouma DJ, Lameris JS, et al. Ultrasonography, computed tomography and magnetic resonance imaging for diagnosis and determining resectability of pancreatic adenocarcinoma: a meta-analysis. J Comput Assist Tomogr. 2005;29(4):438–45.

    Article  PubMed  Google Scholar 

  18. Kauhanen SP, Komar G, Seppanen MP, Dean KI, Minn HR, Kajander SA, et al. A prospective diagnostic accuracy study of 18F-fluorodeoxyglucose positron emission tomography/computed tomography, multidetector row computed tomography, and magnetic resonance imaging in primary diagnosis and staging of pancreatic cancer. Ann Surg. 2009;250(6):957–63.

    Article  PubMed  Google Scholar 

  19. Roy A, Kim M, Hawes R, Varadarajulu S. Changing trends in tissue acquisition in malignant pancreatic neoplasms. J Gastroenterol Hepatol. 2016;31(2):501–5.

    Article  PubMed  Google Scholar 

  20. Matsuyama M, Ishii H, Kuraoka K, Yukisawa S, Kasuga A, Ozaka M, et al. Ultrasound-guided vs endoscopic ultrasound-guided fine-needle aspiration for pancreatic cancer diagnosis. World J Gastroenterol. 2013;19(15):2368–73.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ikezawa K, Uehara H, Sakai A, Fukutake N, Imanaka K, Ohkawa K, et al. Risk of peritoneal carcinomatosis by endoscopic ultrasound-guided fine needle aspiration for pancreatic cancer. J Gastroenterol. 2013;48(8):966–72.

    Article  CAS  PubMed  Google Scholar 

  22. Ngamruengphong S, Swanson KM, Shah ND, Wallace MB. Preoperative endoscopic ultrasound-guided fine needle aspiration does not impair survival of patients with resected pancreatic cancer. Gut. 2015;64(7):1105–10.

    Article  PubMed  Google Scholar 

  23. Tempero MA, Arnoletti JP, Behrman SW, Ben-Josef E, Benson AB 3rd, Casper ES, et al. Pancreatic adenocarcinoma, version 2.2012: featured updates to the NCCN guidelines. J Natl Compr Cancer Netw. 2012;10(6):703–13.

    Article  CAS  Google Scholar 

  24. Cooper AB, Tzeng CW, Katz MH. Treatment of borderline resectable pancreatic cancer. Curr Treat Options in Oncol. 2013;14(3):293–310.

    Article  Google Scholar 

  25. Adams MA, Anderson MA, Myles JD, Khalatbari S, Scheiman JM. Self-expanding metal stents (SEMS) provide superior outcomes compared to plastic stents for pancreatic cancer patients undergoing neoadjuvant therapy. J Gastrointest Oncol. 2012;3(4):309–13.

    PubMed  PubMed Central  Google Scholar 

  26. Soderlund C, Linder S. Covered metal versus plastic stents for malignant common bile duct stenosis: a prospective, randomized, controlled trial. Gastrointest Endosc. 2006;63(7):986–95.

    Article  PubMed  Google Scholar 

  27. Aadam AA, Evans DB, Khan A, Oh Y, Dua K. Efficacy and safety of self-expandable metal stents for biliary decompression in patients receiving neoadjuvant therapy for pancreatic cancer: a prospective study. Gastrointest Endosc. 2012;76(1):67–75.

    Article  PubMed  Google Scholar 

  28. Kang CM, Chung YE, Park JY, Sung JS, Hwang HK, Choi HJ, 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  PubMed  Google Scholar 

  29. Takahashi H, Ohigashi H, Gotoh K, Marubashi S, Yamada T, Murata M, et al. Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg. 2013;258(6):1040–50.

    Article  PubMed  Google Scholar 

  30. 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  PubMed  Google Scholar 

  31. 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  PubMed  PubMed Central  Google Scholar 

  32. 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(1):12–7.

    Article  PubMed  PubMed Central  Google Scholar 

  33. 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  PubMed  Google Scholar 

  34. Katz MH, Shi Q, Ahmad SA, Herman JM, Marsh RW, Collisson E, 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  PubMed  PubMed Central  Google Scholar 

  35. Faris JE, Blaszkowsky LS, McDermott S, Guimaraes AR, Szymonifka J, Huynh MA, et al. FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital cancer center experience. Oncologist. 2013;18(5):543–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hosein PJ, Macintyre J, Kawamura C, Maldonado JC, Ernani V, Loaiza-Bonilla A, et al. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012;12:199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Boone BA, Steve J, Krasinskas AM, Zureikat AH, Lembersky BC, Gibson MK, et al. Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer. J Surg Oncol. 2013;108(4):236–41.

    Article  CAS  PubMed  Google Scholar 

  38. Gunturu KS, Yao X, Cong X, Thumar JR, Hochster HS, Stein SM, et al. FOLFIRINOX for locally advanced and metastatic pancreatic cancer: single institution retrospective review of efficacy and toxicity. Med Oncol. 2013;30(1):361.

    Article  PubMed  Google Scholar 

  39. Marthey L, Sa-Cunha A, Blanc JF, Gauthier M, Cueff A, Francois E, et al. FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicenter prospective observational cohort. Ann Surg Oncol. 2015;22(1):295–301.

    Article  CAS  PubMed  Google Scholar 

  40. Sadot E, Doussot A, O'Reilly EM, Lowery MA, Goodman KA, Do RK, et al. FOLFIRINOX induction therapy for stage 3 pancreatic adenocarcinoma. Ann Surg Oncol. 2015;22(11):3512–21.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, et al. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016;17(6):801–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouche O, et al. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol. 2008;19(9):1592–9.

    Article  CAS  PubMed  Google Scholar 

  43. Hackert T, Sachsenmaier M, Hinz U, Schneider L, Michalski CW, Springfeld C, et al. Locally advanced pancreatic cancer: Neoadjuvant therapy with Folfirinox results in Resectability in 60% of the patients. Ann Surg. 2016;264(3):457–63.

    Article  PubMed  Google Scholar 

  44. Mahaseth H, Brutcher E, Kauh J, Hawk N, Kim S, Chen Z, et al. Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. Pancreas. 2013;42(8):1311–5.

    Article  CAS  PubMed  Google Scholar 

  45. Nanda RH, El-Rayes B, Maithel SK, Landry J. Neoadjuvant modified FOLFIRINOX and chemoradiation therapy for locally advanced pancreatic cancer improves resectability. J Surg Oncol. 2015;111(8):1028–34.

    Article  CAS  PubMed  Google Scholar 

  46. Stein SM, James ES, Deng Y, Cong X, Kortmansky JS, Li J, et al. Final analysis of a phase II study of modified FOLFIRINOX in locally advanced and metastatic pancreatic cancer. Br J Cancer. 2016;114(7):809–12.

    Article  CAS  PubMed Central  Google Scholar 

  47. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.

    Article  Google Scholar 

  48. Olowokure O, Torregroza-Sanchez MP, Bedoya-Apraez ID. Gemcitabine plus nab-paclitaxel with chemoradiation in locally advanced pancreatic cancer (LAPC). J Gastrointest Oncol. 2013;4(2):E16–8.

    PubMed  PubMed Central  Google Scholar 

  49. Leone F, Gatti M, Massucco P, Colombi F, Sperti E, Campanella D, et al. Induction gemcitabine and oxaliplatin therapy followed by a twice-weekly infusion of gemcitabine and concurrent external-beam radiation for neoadjuvant treatment of locally advanced pancreatic cancer: a single institutional experience. Cancer. 2013;119(2):277–84.

    Article  CAS  PubMed  Google Scholar 

  50. 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  PubMed  PubMed Central  Google Scholar 

  51. Morganti AG, Massaccesi M, La Torre G, Caravatta L, Piscopo A, Tambaro R, et al. A systematic review of resectability and survival after concurrent chemoradiation in primarily unresectable pancreatic cancer. Ann Surg Oncol. 2010;17(1):194–205.

    Article  PubMed  Google Scholar 

  52. Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, 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(17):1844–53.

    Article  CAS  PubMed  Google Scholar 

  53. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.

    Article  CAS  PubMed  Google Scholar 

  54. 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.

    Article  PubMed  Google Scholar 

  55. Harrison LE, Klimstra DS, Brennan MF. Isolated portal vein involvement in pancreatic adenocarcinoma. A contraindication for resection? Ann Surg. 1996;224(3):342–7. discussion 7-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Koniaris LG, Staveley-O'Carroll KF, Zeh HJ, Perez E, Jin XL, Maley WR, et al. Pancreaticoduodenectomy in the presence of superior mesenteric venous obstruction. J Gastrointest Surg. 2005;9(7):915–21.

    Article  PubMed  Google Scholar 

  57. Yekebas EF, Bogoevski D, Cataldegirmen G, Kunze C, Marx A, Vashist YK, et al. En bloc vascular resection for locally advanced pancreatic malignancies infiltrating major blood vessels: perioperative outcome and long-term survival in 136 patients. Ann Surg. 2008;247(2):300–9.

    Article  PubMed  Google Scholar 

  58. Bockhorn M, Burdelski C, Bogoevski D, Sgourakis G, Yekebas EF, Izbicki JR. Arterial en bloc resection for pancreatic carcinoma. Br J Surg. 2011;98(1):86–92.

    Article  CAS  PubMed  Google Scholar 

  59. Mollberg N, Rahbari NN, Koch M, Hartwig W, Hoeger Y, Buchler MW, et al. Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis. Ann Surg. 2011;254(6):882–93.

    Article  PubMed  Google Scholar 

  60. Takahashi H, Akita H, Tomokuni A, Kobayashi S, Ohigashi H, Fijiwara Y, et al. Preoperative gemcitabine-based Chemoradiation therapy for borderline Resectable pancreatic cancer: impact of venous and arterial involvement status on surgical outcome and pattern of recurrence. Ann Surg. 2016;264(6):1091–7.

    Article  PubMed  Google Scholar 

  61. Appleby LH. The coeliac axis in the expansion of the operation for gastric carcinoma. Cancer. 1953;6(4):704–7.

    Article  CAS  PubMed  Google Scholar 

  62. Liu B. Modified Appleby operation in treatment of distal pancreatic cancer. Hepatobiliary Pancreat Dis Int. 2003;2(4):622–5.

    PubMed  Google Scholar 

  63. Nakamura T, Hirano S, Noji T, Asano T, Okamura K, Tsuchikawa T, et al. Distal Pancreatectomy with en bloc celiac Axis resection (modified Appleby procedure) for locally advanced pancreatic body cancer: a single-center review of 80 consecutive patients. Ann Surg Oncol. 2016;23:969.

    Article  PubMed  Google Scholar 

  64. Hirano S, Kondo S, Hara T, Ambo Y, Tanaka E, Shichinohe T, et al. Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic body cancer: long-term results. Ann Surg. 2007;246(1):46–51.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Baumgartner JM, Krasinskas A, Daouadi M, Zureikat A, Marsh W, Lee K, et al. Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic adenocarcinoma following neoadjuvant therapy. J Gastrointest Surg. 2012;16(6):1152–9.

    Article  PubMed  Google Scholar 

  66. Peters NA, Javed AA, Cameron JL, Makary MA, Hirose K, Pawlik TM, et al. Modified Appleby procedure for pancreatic adenocarcinoma: does improved Neoadjuvant therapy warrant such an aggressive approach? Ann Surg Oncol. 2016;23:3757.

    Article  PubMed  Google Scholar 

  67. Beane JD, House MG, Pitt SC, Kilbane EM, Hall BL, Parmar AD, et al. Distal pancreatectomy with celiac axis resection: what are the added risks? HPB (Oxford). 2015;17(9):777–84.

    Article  Google Scholar 

  68. Frank TS, Sun X, Zhang Y, Yang J, Fisher WE, Gingras MC, et al. Genomic profiling guides the choice of molecular targeted therapy of pancreatic cancer. Cancer Lett. 2015;363(1):1–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Diep CH, Munoz RM, Choudhary A, Von Hoff DD, Han H. Synergistic effect between erlotinib and MEK inhibitors in KRAS wild-type human pancreatic cancer cells. Clin Cancer Res. 2011;17(9):2744–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010;33(8):828–33.

    Article  CAS  PubMed  Google Scholar 

  71. Mehta VK, Fisher G, Ford JA, Poen JC, Vierra MA, Oberhelman H, et al. Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas. J Gastrointest Surg. 2001;5(1):27–35.

    Article  CAS  PubMed  Google Scholar 

  72. Brown KM, Siripurapu V, Davidson M, Cohen SJ, Konski A, Watson JC, et al. Chemoradiation followed by chemotherapy before resection for borderline pancreatic adenocarcinoma. Am J Surg. 2008;195(3):318–21.

    Article  CAS  PubMed  Google Scholar 

  73. McClaine RJ, Lowy AM, Sussman JJ, Schmulewitz N, Grisell DL, Ahmad SA. 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 

  74. 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.

    Article  PubMed  Google Scholar 

  75. Patel M, Hoffe S, Malafa M, Hodul P, Klapman J, Centeno B, et al. Neoadjuvant GTX chemotherapy and IMRT-based chemoradiation for borderline resectable pancreatic cancer. J Surg Oncol. 2011;104(2):155–61.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Chuong MD, Hayman TJ, Patel MR, Russell MS, Malafa MP, Hodul PJ, et al. Comparison of 1-, 2-, and 3-dimensional tumor response assessment after Neoadjuvant GTX-RT in borderline-Resectable pancreatic cancer. Gastrointest Cancer Res. 2011;4(4):128–34.

    PubMed  PubMed Central  Google Scholar 

  77. Rose JB, Rocha FG, Alseidi A, Biehl T, Moonka R, Ryan JA, et al. Extended neoadjuvant chemotherapy for borderline resectable pancreatic cancer demonstrates promising postoperative outcomes and survival. Ann Surg Oncol. 2014;21(5):1530–7.

    Article  PubMed  Google Scholar 

  78. Rashid OM, Pimiento JM, Gamenthaler AW, Nguyen P, Ha TT, Hutchinson T, et al. Outcomes of a clinical pathway for borderline Resectable pancreatic cancer. Ann Surg Oncol. 2016;23(4):1371–9.

    Article  PubMed  Google Scholar 

  79. Pipas JM, Barth RJ Jr, Zaki B, Tsapakos MJ, Suriawinata AA, Bettmann MA, et al. Docetaxel/gemcitabine followed by gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma. Ann Surg Oncol. 2005;12(12):995–1004.

    Article  PubMed  Google Scholar 

  80. Massucco P, Capussotti L, Magnino A, Sperti E, Gatti M, Muratore A, et al. Pancreatic resections after chemoradiotherapy for locally advanced ductal adenocarcinoma: analysis of perioperative outcome and survival. Ann Surg Oncol. 2006;13(9):1201–8.

    Article  PubMed  Google Scholar 

  81. Small W Jr, Berlin J, Freedman GM, Lawrence T, Talamonti MS, Mulcahy MF, et al. Full-dose gemcitabine with concurrent radiation therapy in patients with nonmetastatic pancreatic cancer: a multicenter phase II trial. J Clin Oncol. 2008;26(6):942–7.

    Article  CAS  PubMed  Google Scholar 

  82. Turrini O, Viret F, Moureau-Zabotto L, Guiramand J, Moutardier V, Lelong B, et al. Neoadjuvant chemoradiation and pancreaticoduodenectomy for initially locally advanced head pancreatic adenocarcinoma. Eur J Surg Oncol. 2009;35(12):1306–11.

    Article  CAS  PubMed  Google Scholar 

  83. 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.

    Article  PubMed  Google Scholar 

  84. 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.

    Article  PubMed  Google Scholar 

  85. Arvold ND, Ryan DP, Niemierko A, Blaszkowsky LS, Kwak EL, Wo JY, et al. Long-term outcomes of neoadjuvant chemotherapy before chemoradiation for locally advanced pancreatic cancer. Cancer. 2012;118(12):3026–35.

    Article  PubMed  Google Scholar 

  86. Peddi PF, Lubner S, McWilliams R, Tan BR, Picus J, Sorscher SM, et al. Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma. JOP. 2012;13(5):497–501.

    PubMed  Google Scholar 

  87. Lee JL, Kim SC, Kim JH, Lee SS, Kim TW, Park DH, 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.

    Article  PubMed  Google Scholar 

  88. Barugola G, Partelli S, Crippa S, Capelli P, D'Onofrio M, Pederzoli P, 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  PubMed  Google Scholar 

  89. Moorcraft SY, Khan K, Peckitt C, Watkins D, Rao S, Cunningham D, et al. FOLFIRINOX for locally advanced or metastatic pancreatic ductal adenocarcinoma: the Royal Marsden experience. Clin Colorectal Cancer. 2014;13(4):232–8.

    Article  PubMed  Google Scholar 

  90. Addeo P, Rosso E, Fuchshuber P, Oussoultzoglou E, De Blasi V, Simone G, et al. Resection of borderline Resectable and locally advanced pancreatic adenocarcinomas after Neoadjuvant chemotherapy. Oncology. 2015;89(1):37–46.

    Article  CAS  PubMed  Google Scholar 

  91. Krishnan S, Rana V, Janjan NA, Varadhachary GR, Abbruzzese JL, Das P, et al. Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy. Cancer. 2007;110(1):47–55.

    Article  PubMed  Google Scholar 

  92. Wilkowski R, Boeck S, Ostermaier S, Sauer R, Herbst M, Fietkau R, et al. Chemoradiotherapy with concurrent gemcitabine and cisplatin with or without sequential chemotherapy with gemcitabine/cisplatin vs chemoradiotherapy with concurrent 5-fluorouracil in patients with locally advanced pancreatic cancer--a multi-centre randomised phase II study. Br J Cancer. 2009;101(11):1853–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, et al. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an eastern cooperative Oncology group trial. J Clin Oncol. 2011;29(31):4105–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Habermehl D, Kessel K, Welzel T, Hof H, Abdollahi A, Bergmann F, et al. Neoadjuvant chemoradiation with gemcitabine for locally advanced pancreatic cancer. Radiat Oncol. 2012;7:28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, The University of Cincinnati Medical Center, 231 Albert Sabin Way, ML 0558, SRU Room 1466, Cincinnati, OH, 45267-0558, USA

    Brent T. Xia M.D., Young Kim M.D. & Syed A. Ahmad M.D.

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  1. Brent T. Xia M.D.
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  2. Young Kim M.D.
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  3. Syed A. Ahmad M.D.
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Correspondence to Syed A. Ahmad M.D. .

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Editors and Affiliations

  1. Mayo Clinic Cancer Center, Scottsdale, Arizona, USA

    Tanios Bekaii-Saab

  2. Winship Cancer Institute, Emory University, Atlanta, Georgia, USA

    Bassel El-Rayes

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Xia, B.T., Kim, Y., Ahmad, S.A. (2018). The Management of Locally Advanced Nonmetastatic Pancreas Cancer. In: Bekaii-Saab, T., El-Rayes, B. (eds) Current and Emerging Therapies in Pancreatic Cancer . Springer, Cham. https://doi.org/10.1007/978-3-319-58256-6_10

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