The majority of patients with localized pancreatic cancer (PC) who undergo surgery followed by adjuvant therapy will develop metastatic disease, suggesting that surgery alone is not sufficient for cure and micrometastases are present even when are not clinically detected. As such, the delivery of early systemic therapy may be a rational alternative to a surgery-first approach, in an effort to provide oncologic therapies which are commensurate with the disease stage, and improve surgical selection. This review details the rationale for a neoadjuvant approach to localized PC and provides specific recommendations for both pretreatment staging and treatment sequencing for patients with resectable and borderline resectable PC.
KeywordsPancreas CancerNeoadjuvant TherapyReview
Howlander, N.N.A., Krapcho, M., Garshell, J/, Miller, D., Altekruse, S.F., Kosary, C.L., Yu, M., Ruhl, J., Tatlovich, Z., Mariotto, A., Lewis, D.R., Chen, H.S., Feuer, E.J. and Cronin, K.A. (2015) SEER Cancer Statistics Review. 1975-2012. http://seer.cancer.gov/csr/1975_2012/
Sohal, D.P., Walsh, R.M., Ramanathan, R.K. and Khorana, A.A. (2014) Pancreatic Adenocarcinoma: Treating a Systemic Disease with Systemic Therapy. Journal of the National Cancer Institute, 10, dju011. http://dx.doi.org/10.1093/jnci/dju011
Casadei, R., Di Marco, M., Ricci, C., et al. (2015) Neoadjuvant Chemoradiotherapy and Surgery versus Surgery Alone in Resectable Pancreatic Cancer: A Single-Center Prospective, Randomized, Controlled Trial Which Failed to Achieve Accrual Targets. Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract; 19, 1802-1812. http://dx.doi.org/10.1007/s11605-015-2890-4
Golcher, H., Brunner, T.B., Witzigmann, H., et al. (2015) 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 Deutschen Rontgengesellschaft, 191, 7-16. http://dx.doi.org/10.1007/s00066-014-0737-7
Evans, D.B., Rich, T.A., Byrd, D.R., et al. (1992) Preoperative Chemoradiation and Pancreaticoduodenectomy for Adenocarcinoma of the Pancreas. Archives of Surgery, 127, 1335-1339. http://dx.doi.org/10.1001/archsurg.1992.01420110083017
Christians, K., Heimler, J.W., George, B., Ritch, P.S., Erickson, B.A., Johnston, F.M., Tolat, P.P., Foley, W.D., Evans, D.B. and Tsai, S. (2015) Survival of Patients with Resectable Pancreatic Cancer Receiving Neoadjuvant Therapy. 72nd Annual Meeting of the Central Surgical Society, 5-7 March 2015, Chicago. http://dx.doi.org/10.1016/j.surg.2015.09.018
Winter, J.M., Brennan, M.F., Tang, L.H., et al. (2012) Survival after Resection of Pancreatic Adenocarcinoma: Results from a Single Institution over Three Decades. Annals of Surgical Oncology, 19, 169-175. http://dx.doi.org/10.1245/s10434-011-1900-3
Appel, B.L., Tolat, P., Evans, D.B. and Tsai, S. (2012) Current Staging Systems for Pancreatic Cancer. Cancer Journal, 18, 539-549. http://dx.doi.org/10.1097/PPO.0b013e318278c5b5
Smeenk, H.G., van Eijck, C.H., Hop, W.C., et al. (2007) Long-Term Survival and Metastatic Pattern of Pancreatic and Periampullary Cancer after Adjuvant Chemoradiation or Observation: Long-Term Results of EORTC Trial 40891. Annals of Surgery, 246, 734-740. http://dx.doi.org/10.1097/SLA.0b013e318156eef3
Tepper, J., Nardi, G. and Sutt, H. (1976) Carcinoma of the Pancreas: Review of MGH Experience from 1963 to 1973. Analysis of Surgical Failure and Implications for Radiation Therapy. Cancer, 37, 1519-1524. http://dx.doi.org/10.1002/1097-0142(197603)37:3 3.0.CO;2-O
Van den Broeck, A., Sergeant, G., Ectors, N., Van Steenbergen, W., Aerts, R. and Topal, B. (2009) Patterns of Recurrence after Curative Resection of Pancreatic Ductal Adenocarcinoma. European Journal of Surgical Oncology, 35, 600-604. http://dx.doi.org/10.1016/j.ejso.2008.12.006
Westerdahl, J., Andren-Sandberg, A. and Ihse, I. (1993) Recurrence of Exocrine Pancreatic Cancer—Local or Hepatic? Hepatogastroenterology, 40, 384-387.
Kalser, M.H. and Ellenberg, S.S. (1985) Pancreatic Cancer. Adjuvant Combined Radiation and Chemotherapy Following Curative Resection. Archives of Surgery, 120, 899-903. http://dx.doi.org/10.1001/archsurg.1985.01390320023003
Klinkenbijl, J.H., Jeekel, J., Sahmoud, T., van Pel, R., Couvreur, M.L., Veenhof, C.H., et al. (1999) 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. Annals of Surgery, 230, 776-782. http://dx.doi.org/10.1097/00000658-199912000-00006
Neoptolemos, J.P., Stocken, D.D., Friess, H., Bassi, C., Dunn, J.A., Hickey, H., et al. (2004) A Randomized Trial of Chemoradiotherapy and Chemotherapy after Resection of Pancreatic Cancer. The New England Journal of Medicine, 350, 1200-1210. http://dx.doi.org/10.1056/NEJMoa032295
Oettle, H., Post, S., Neuhaus, P., Gellert, K., Langrehr, J., Ridwelski, K., et al. (2007) Adjuvant Chemotherapy with Gemcitabine vs Observation in Patients Undergoing Curative-Intent Resection of Pancreatic Cancer: A Randomized Controlled Trial. JAMA, 297, 267-277. http://dx.doi.org/10.1001/jama.297.3.267
Neoptolemos, J.P., Stocken, D.D., Bassi, C., Ghaneh, P., Cunningham, D., Goldstein, D., et al. (2010) Adjuvant Chemotherapy with Fluorouracil plus Folinic Acid vs Gemcitabine Following Pancreatic Cancer Resection: A Randomized Controlled Trial. JAMA, 304, 1073-1081. http://dx.doi.org/10.1001/jama.2010.1275
Valle, J.W., Palmer, D., Jackson, R., Cox, T., Neoptolemos, J.P., Ghaneh, P., et al. (2014) Optimal Duration and Timing of Adjuvant Chemotherapy after Definitive Surgery for Ductal Adenocarcinoma of the Pancreas: Ongoing Lessons from the ESPAC-3 Study. Journal of Clinical Oncology, 32, 504-512. http://dx.doi.org/10.1200/jco.2013.50.7657
Regine, W.F., Winter, K.W., Abrams, R., Safran, H., Hoffman, J.P., Konski, A., Benson, A.B., MacDonald, J.S., Willett, C.G. and Rich, T.A. (2006) RTOG 9704 a Phase III Study of Adjuvant Pre and Post Chemoradiation (CRT) 5-FU vs. Gemcitabine (G) for Resected Pancreatic Adenocarcinoma. Journal of Clinical Oncology, 24, 4007.
Regine, W.F., Winter, K.A., Abrams, R., Safran, H., Hoffman, J.P., Konski, A., et al. (2011) 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. Annals of Surgical Oncology, 18, 1319-1326. http://dx.doi.org/10.1245/s10434-011-1630-6
Abrams, R.A., Lowy, A.M., O’Reilly, E.M., Wolff, R.A., Picozzi, V.J. and Pisters, P.W. (2009) Combined Modality Treatment of Resectable and Borderline Resectable Pancreas Cancer: Expert Consensus Statement. Annals of Surgical Oncology, 16, 1751-1756. http://dx.doi.org/10.1245/s10434-009-0413-9
National Comprehensive Cancer Network (2011) NCCN Practice Guidelines: Pancreatic Adenocarcinoma.
Evans, D.B. and Wolff, R.A. (2011) Adjuvant Therapy for Pancreatic Cancer: A Logical Strategy in Search of Progress. Annals of Surgical Oncology, 18, 1224-1228. http://dx.doi.org/10.1245/s10434-011-1633-3
Tempero, M.A., Arnoletti, J.P., Behrman, S., et al. (2010) Pancreatic Adenocarcinoma. Journal of the National Comprehensive Cancer Network, 8, 972-1017.
Wu, W., He, J., Cameron, J.L., Makary, M., Soares, K., Ahuja, N., et al. (2014) The Impact of Postoperative Complications on the Administration of Adjuvant Therapy Following Pancreaticoduodenectomy for Adenocarcinoma. Annals of Surgical Oncology, 21, 2873-2881. http://dx.doi.org/10.1245/s10434-014-3722-6
Pilepich, M.V. and Miller, H.H. (1980) Preoperative Irradiation in Carcinoma of the Pancreas. Cancer, 46, 1945-1949. http://dx.doi.org/10.1002/1097-0142(19801101)46:9 3.0.CO;2-X
Takahashi, H., Ogawa, H., Ohigashi, H., Gotoh, K., Yamada, T., Ohue, M., et al. (2011) Preoperative Chemoradiation Reduces the Risk of Pancreatic Fistula after Distal Pancreatectomy for Pancreatic Adenocarcinoma. Surgery, 150, 547-556. http://dx.doi.org/10.1016/j.surg.2011.03.001
Raut, C.P., Evans, D.B., Crane, C.H., Pisters, P.W. and Wolff, R.A. (2004) Neoadjuvant Therapy for Resectable Pancreatic Cancer. Surgical Oncology Clinics of North America, 13, 639-661. http://dx.doi.org/10.1016/j.soc.2004.06.007
Willett, C.G., Lewandrowski, K., Warshaw, A.L., Efird, J. and Compton, C.C. (1993) Resection Margins in Carcinoma of the Head of the Pancreas. Implications for Radiation Therapy. Annals of Surgery, 217, 144-148. http://dx.doi.org/10.1097/00000658-199302000-00008
Pisters, P.W., Hudec, W.A., Lee, J.E., et al. (2000) Preoperative Chemoradiation for Patients with Pancreatic Cancer: Toxicity of Endobiliary Stents. Journal of Clinical Oncology, 18, 860-867.
Aadam, A.A., Evans, D.B., Khan, A., Oh, Y. and Dua, K. (2012) Efficacy and Safety of Self-Expandable Metal Stents for Biliary Decompression in Patients Receiving Neoadjuvant Therapy for Pancreatic Cancer: A Prospective Study. Gastrointestinal Endoscopy, 76, 67-75. http://dx.doi.org/10.1016/j.gie.2012.02.041
Varadhachary, G.R., Wolff, R.A., Crane, C.H., Sun, C.C., Lee, J.E., Pisters, P.W.T., et al. (2008) Preoperative Gemcitabine and Cisplatin Followed by Gemcitabine-Based Chemoradiation for Resectable Adenocarcinoma of the Pancreatic Head. Journal of Clinical Oncology, 26, 3487-3495. http://dx.doi.org/10.1200/jco.2007.15.8642
Talamonti, M.S., Small Jr., W., Mulcahy, M.F., Wayne, J.D., Attaluri, V., Colletti, L.M., et al. (2006) A Multi-Institutional Phase II Trial of Preoperative Full-Dose Gemcitabine and Concurrent Radiation for Patients with Potentially Resectable Pancreatic Carcinoma. Annals of Surgical Oncology, 13, 150-158. http://dx.doi.org/10.1245/ASO.2006.03.039
Tzeng, C.W., Tran Cao, H.S., Lee, J.E., et al. (2014) Treatment Sequencing for Resectable Pancreatic Cancer: Influence of Early Metastases and Surgical Complications on Multimodality Therapy Completion and Survival. Journal of Gastrointestinal Surgery, 18, 16-24.
Kim, E.J., Ben-Josef, E., Herman, J.M., Bekaii-Saab, T., Dawson, L.A., Griffith, K.A., et al. (2013) A Multi-Institutional Phase 2 Study of Neoadjuvant Gemcitabine and Oxaliplatin with Radiation Therapy in Patients with Pancreatic Cancer. Cancer, 119, 2692-2700. http://dx.doi.org/10.1002/cncr.28117
O’Reilly, E.M., Perelshteyn, A., Jarnagin, W.R., Schattner, M., Gerdes, H., Capanu, M., et al. (2014) A Single-Arm, Nonrandomized Phase II Trial of Neoadjuvant Gemcitabine and Oxaliplatin in Patients with Resectable Pancreas Adenocarcinoma. Annals of Surgery, 260, 142-148. http://dx.doi.org/10.1097/SLA.0000000000000251
Rose, J.B., Rocha, F.G., Alseidi, A., Biehl, T., Moonka, R., Ryan, J.A., Lin, B., Picozzi, V. and Helton, S. (2014) Extended Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer Demonstrates Promising Postoperative Outcomes and Survival. Annals of Surgical Oncology, 21, 1530-1537. http://dx.doi.org/10.1245/s10434-014-3486-z
Ferrone, C.R., Marchegiani, G., Hong, T.S., Ryan, D.P., Deshpande, V., McDonnell, E.I., et al. (2015) Radiological and Surgical Implications of Neoadjuvant Treatment with FOLFIRINOX for Locally Advanced and Borderline Resectable Pancreatic Cancer. Annals of Surgery, 261, 12-17. http://dx.doi.org/10.1097/SLA.0000000000000867
Evans, D.B., Varadhachary, G.R., Crane, C.H., Sun, C.C., Lee, J.E., Pisters, P.W.T., et al. (2008) Preoperative Gemcitabine-Based Chemoradiation for Patients with Resectable Adenocarcinoma of the Pancreatic Head. Journal of Clinical Oncology, 26, 3496-3502. http://dx.doi.org/10.1200/JCO.2007.15.8634
Christians, K., Heimler, J.W., George, B., Ritch, P.S., Erickson, B.A., Johnston, F.M., Tolat, P.P., Foley, W.D., Evans, D.B. and Tsai, S. Survival of Patients with Resectable Pancreatic Cancer Receiving Neoadjuvant Therapy. Surgery 2015.
Shibuya, K.C., Goel, V.K., Xiong, W., Sham, J.G., Pollack, S.M., Leahy, A.M., et al. (2014) Pancreatic Ductal Adenocarcinoma Contains an Effector and Regulatory Immune Cell Infiltrate That Is Altered by Multimodal Neoadjuvant Treatment. PLoS ONE, 9, e96565. http://dx.doi.org/10.1371/journal.pone.0096565
Conroy, T., Desseigne, F., Ychou, M., Bouché, O., Guimbaud, R., Bécouarn, Y., et al. (2011) FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer. The New England Journal of Medicine, 364, 1817-1825. http://dx.doi.org/10.1056/NEJMoa1011923
Von Hoff, D.D., Goldstein, D. and Renschler, M.F. (2014) Albumin-Bound Paclitaxel plus Gemcitabine in Pancreatic Cancer. The New England Journal of Medicine, 370, 479-480.
Mahaseth, H., Brutcher, E., Kauh, J., Hawk, N., Kim, S., Chen, Z., et al. (2013) Modified FOLFIRINOX Regimen with Improved Safety and Maintained Efficacy in Pancreatic Adenocarcinoma. Pancreas, 42, 1311-1315. http://dx.doi.org/10.1097/MPA.0b013e31829e2006
Christians, K.K., Tsai, S., Mahmoud, A., Ritch, P., Thomas, J.P., Wiebe, L., et al. (2014) Neoadjuvant FOLFIRINOX for Borderline Resectable Pancreas Cancer: A New Treatment Paradigm? The Oncologist, 19, 266-274. http://dx.doi.org/10.1634/theoncologist.2013-0273
University of Pittsburgh (2015) Phase II Neoadjuvant Chemotheraphy (Gemcitabine and Nab-Paclitaxel vs. mFOLFIRINOX) and Sterotatic Body Radiation Therapy for Borderline Resectable Pancreatic Cancer. https://clinicaltrials.gov/ct2/show/NCT02241551?term=02241551&rank=1
Medical College of Wisconsin (2015) Pancreas Cancer: Molecular Profiling as a Guide to Therapy before and after Surgery. ClinicalTrials.gov [Internet], National Library of Medicine (US), Bethesda.
Gillen, S., Schuster, T., Meyer Zum Buschenfelde, C., Friess, H. and Kleeff, J. (2010) Preoperative/Neoadjuvant Therapy in Pancreatic Cancer: A Systematic Review and Meta-Analysis of Response and Resection Percentages. PLoS Medicine, 7, e1000267. http://dx.doi.org/10.1371/journal.pmed.1000267
Katz, M.H., Pisters, P.W., Evans, D.B., Sun, C.C., Lee, J.E., Fleming, J.B., et al. (2008) Borderline Resectable Pancreatic Cancer: The Importance of This Emerging Stage of Disease. Journal of the American College of Surgeons, 206, 833-846. http://dx.doi.org/10.1016/j.jamcollsurg.2007.12.020
Patel, M., Hoffe, S., Malafa, M., Hodul, P., Klapman, J., Centeno, B., et al. (2011) Neoadjuvant GTX Chemotherapy and IMRT-Based Chemoradiation for Borderline Resectable Pancreatic Cancer. Journal of Surgical Oncology, 104, 155-161. http://dx.doi.org/10.1002/jso.21954
McClaine, R.J., Lowy, A.M., Sussman, J.J., Schmulewitz, N., Grisell, D.L. and Ahmad, S.A. (2010) Neoadjuvant Therapy May Lead to Successful Surgical Resection and Improved Survival in Patients with Borderline Resectable Pancreatic Cancer. HPB, 12, 73-79. http://dx.doi.org/10.1111/j.1477-2574.2009.00136.x
Stokes, J.B., Nolan, N.J., Stelow, E.B., Walters, D.M., Weiss, G.R., de Lange, E.E., Rich, T.A., Adams, R.B. and Bauer, T.W. (2011) Preoperative Capecitabine and Concurrent Radiation for Borderline Resectable Pancreatic Cancer. Annals of Surgical Oncology, 18, 619-627. http://dx.doi.org/10.1245/s10434-010-1456-7
Fine, R.L., Fogelman, D.R., Schreibman, S.M., Desai, M., Sherman, W., Strauss, J., Guba, S., Andrade, R. and Chabot, J. (2008) The Gemcitabine, Docetaxel, and Capecitabine (GTX) Regimen for Metastatic Pancreatic Cancer: A Retrospective Analysis. Cancer Chemotherapy and Pharmacology, 61, 167-175. http://dx.doi.org/10.1007/s00280-007-0473-0
Von Hoff, D.D., Ramanathan, R.K., Borad, M.J., Laheru, D.A., Smith, L.S., Wood, T.E., et al. (2011) Gemcitabine plus nab-Paclitaxel Is an Active Regimen in Patients with Advanced Pancreatic Cancer: A Phase I/II Trial. Journal of Clinical Oncology, 29, 4548-4554. http://dx.doi.org/10.1200/JCO.2011.36.5742
Pilgrim, C.H., Tsai, S., Tolat, P., Patel, P., Rilling, W., Evans, D.B. and Christians, K.K. (2014) Optimal Management of the Splenic Vein at the Time of Venous Resection for Pancreatic Cancer: Importance of the Inferior Mesenteric Vein. Journal of Gastrointestinal Surgery, 18, 917-921. http://dx.doi.org/10.1007/s11605-013-2428-6
Evans, D.B., George, B. and Tsai, S. (2015) Non-Metastatic Pancreatic Cancer: Resectable, Borderline Resectable, and Locally Advanced-Definitions of Increasing Importance for the Optimal Delivery of Multimodality Therapy. Annals of Surgical Oncology, 22, 3409-3413. http://dx.doi.org/10.1245/s10434-015-4649-2
Katz, M.H., Wang, H., Fleming, J.B., Sun, C.C., Hwang, R.F., Wolff, R.A., et al. (2009) Long-Term Survival after Multidisciplinary Management of Resected Pancreatic Adenocarcinoma. Annals of Surgical Oncology, 16, 836-847. http://dx.doi.org/10.1245/s10434-008-0295-2
Oettle, H., Neuhaus, P., Hochhaus, A., Hartmann, J.T., Gellert, K., Ridwelski, K., et al. (2013) Adjuvant Chemotherapy with Gemcitabine and Long-Term Outcomes among Patients with Resected Pancreatic Cancer: The CONKO-001 Randomized Trial. JAMA, 310, 1473-1481. http://dx.doi.org/10.1001/jama.2013.279201
Yeung, R.S., Weese, J.L., Hoffman, J.P., Solin, L.J., Paul, A.R., Engstrom, P.F., Litwin, S., Kowalyshyn, M.J. and Eisenberg, B.L. (1993) Neoadjuvant Chemoradiation in Pancreatic and Duodenal Carcinoma. A Phase II Study. Cancer, 72, 2124-2133. http://dx.doi.org/10.1002/1097-0142(19931001)72:7 3.0.CO;2-C
Pisters, P.W., Abbruzzese, J.L., Janjan, N.A., et al. (1998) Rapid-Fractionation Preoperative Chemoradiation, Pancreaticoduodenectomy, and Intraoperative Radiation Therapy for Resectable Pancreatic Adenocarcinoma. Journal of Clinical Oncology, 16, 3843-3850.
Hoffman, J.P., Lipsitz, S., Pisansky, T., Weese, J.L., Solin, L. and Benson III, A.B. (1998) Phase II Trial of Preoperative Radiation Therapy and Chemotherapy for Patients with Localized, Resectable Adenocarcinoma of the Pancreas: An Eastern Cooperative Oncology Group Study. Journal of Clinical Oncology, 16, 317-323.
White, R.R., Hurwitz, H.I., Morse, M.A., Lee, C., Anscher, M.S., Paulson, E.K., et al. (2001) Neoadjuvant Chemoradiation for Localized Adenocarcinoma of the Pancreas. Annals of Surgical Oncology, 8, 758-765. http://dx.doi.org/10.1007/s10434-001-0758-1
Pisters, P.W., Wolff, R.A., Janjan, N.A., Cleary, K.R., Charnsangavej, C., Crane, C.N., et al. (2002) Preoperative Paclitaxel and Concurrent Rapid-Fractionation Radiation for Resectable Pancreatic Adenocarcinoma: Toxicities, Histologic Response Rates, and Event-Free Outcome. Journal of Clinical Oncology, 20, 2537-2544. http://dx.doi.org/10.1200/JCO.2002.11.064
Moutardier, V., Magnin, V., Turrini, O., Viret, F., Hennekinne-Mucci, S., Goncalves, A., et al. (2004) Assessment of Pathologic Response after Preoperative Chemoradiotherapy and Surgery in Pancreatic Adenocarcinoma. International Journal of Radiation Oncology, Biology, Physics, 60, 437-443. http://dx.doi.org/10.1016/j.ijrobp.2004.04.004
Mornex, F., Girard, N., Delpero, J.R. and Partensky, C. (2005) Radiochemotherapy in the Management of Pancreatic Cancer—Part I: Neoadjuvant Treatment. Seminars in Radiation Oncology, 15, 226-234. http://dx.doi.org/10.1016/j.semradonc.2005.04.008
Turrini, O., Viret, F., Moureau-Zabotto, L., Guiramand, J., Moutardier, V., Lelong, B., et al. (2009) Neoadjuvant 5 Fluorouracil-Cisplatin Chemoradiation Effect on Survival in Patients with Resectable Pancreatic Head Adenocarcinoma: A Ten-Year Single Institution Experience. Oncology, 76, 413-419. http://dx.doi.org/10.1159/000215928
Le Scodan, R., Mornex, F., Girard, N., Mercier, C., Valette, P.-J., Ychou, M., et al. (2009) Preoperative Chemoradiation in Potentially Resectable Pancreatic Adenocarcinoma: Feasibility, Treatment Effect Evaluation and Prognostic Factors, Analysis of the SFRO-FFCD 9704 Trial and Literature Review. Annals of Oncology, 20, 1387-1396. http://dx.doi.org/10.1093/annonc/mdp015
Turrini, O., Ychou, M., Moureau-Zabotto, L., Rouanet, P., Giovannini, M., Moutardier, V., Azria, D., Delpero, J.-R. and Viret, F. (2010) Neoadjuvant Docetaxel-Based Chemoradiation for Resectable Adenocarcinoma of the Pancreas: New Neoadjuvant Regimen Was Safe and Provided an Interesting Pathologic Response. European Journal of Surgical Oncology, 36, 987-992. http://dx.doi.org/10.1016/j.ejso.2010.07.003
Kang, C.M., Chung, Y.E., Park, J.Y., Sung, J.S., Hwang, H.K., Choi, H.J., Kim, H., Song, S.Y. and Lee, W.J. (2012) Potential Contribution of Preoperative Neoadjuvant Concurrent Chemoradiation Therapy on Margin-Negative Resection in Borderline Resectable Pancreatic Cancer. Journal of Gastrointestinal Surgery, 16, 509-517. http://dx.doi.org/10.1007/s11605-011-1784-3
Artinyan, A., Anaya, D.A., McKenzie, S., Ellenhorn, J.D. and Kim, J. (2011) Neoadjuvant Therapy Is Associated with Improved Survival in Resectable Pancreatic Adenocarcinoma. Cancer, 117, 2044-2049. http://dx.doi.org/10.1002/cncr.25763
Lee, J.L., Kim, S.C., Kim, J.H., Lee, S.S., Kim, T.-W., Park, D.H., et al. (2012) Prospective Efficacy and Safety Study of Neoadjuvant Gemcitabine with Capecitabine Combination Chemotherapy for Borderline-Resectable or Unresectable Locally Advanced Pancreatic Adenocarcinoma. Surgery, 152, 851-862. http://dx.doi.org/10.1016/j.surg.2012.03.010
Sho, M., Akahori, T., Tanaka, T., Kinoshita, S., Tamamoto, T., Nomi, T., et al. (2013) Pathological and Clinical Impact of Neoadjuvant Chemoradiotherapy Using Full-Dose Gemcitabine and Concurrent Radiation for Resectable Pancreatic Cancer. Journal of Hepato-Biliary-Pancreatic Sciences, 20, 197-205. http://dx.doi.org/10.1007/s00534-012-0532-8
Pipas, J.M., Zaki, B.I., McGowan, M.M., Tsapakos, M.J., Ripple, G.H., Suriawinata, A.A., et al. (2012) Neoadjuvant Cetuximab, Twice-Weekly Gemcitabine, and Intensity-Modulated Radiotherapy (IMRT) in Patients with Pancreatic Adenocarcinoma. Annals of Oncology, 23, 2820-2827. http://dx.doi.org/10.1093/annonc/mds109
Arvold, N.D., Ryan, D.P., Niemierko, A., Blaszkowsky, L.S., Kwak, E.L., Wo, J.Y., et al. (2012) Long-Term Outcomes of Neoadjuvant Chemotherapy before Chemoradiation for Locally Advanced Pancreatic Cancer. Cancer, 118, 3026-3035. http://dx.doi.org/10.1002/cncr.26633
Barugola, G., Partelli, S., Crippa, S., Capelli, P., D’Onofrio, M., Pederzoli, P. and Falconi, M. (2012) Outcomes after Resection of Locally Advanced or Borderline Resectable Pancreatic Cancer after Neoadjuvant Therapy. American Journal of Surgery, 203, 132-139. http://dx.doi.org/10.1016/j.amjsurg.2011.03.008
Leone, F., Gatti, M., Massucco, P., Colombi, F., Sperti, E., Campanella, D., et al. (2013) 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, 119, 277-284. http://dx.doi.org/10.1002/cncr.27736
Van Buren II, G., Ramanathan, R.K., Krasinskas, A.M., Smith, R.P., Abood, G.J., Bahary, N., et al. (2013) Phase II Study of Induction Fixed-Dose Rate Gemcitabine and Bevacizumab Followed by 30 Gy Radiotherapy as Preoperative Treatment for Potentially Resectable Pancreatic Adenocarcinoma. Annals of Surgical Oncology, 20, 3787-3793. http://dx.doi.org/10.1245/s10434-013-3161-9
Motoi, F., Ishida, K., Fujishima, F., Ottomo, S., Oikawa, M., Okada, T., et al. (2013) Neoadjuvant Chemotherapy with Gemcitabine and S-1 for Resectable and Borderline Pancreatic Ductal Adenocarcinoma: Results from a Prospective Multi-Institutional Phase 2 Trial. Annals of Surgical Oncology, 20, 3794-3801. http://dx.doi.org/10.1245/s10434-013-3129-9
Cho, I.R., Chung, M.J., Bang, S., Park, S.W., Chung, J.B., Song, S.Y., et al. (2013) Gemcitabine Based Neoadjuvant Chemoradiotherapy Therapy in Patients with Borderline Resectable Pancreatic Cancer. Pancreatology, 13, 539-543. http://dx.doi.org/10.1016/j.pan.2013.07.064
Epelboym, I., DiNorcia, J., Winner, M., Lee, M.K., Lee, J.A., Schrope, B.A., Chabot, J.A. and Allendorf, J.D. (2014) Neoadjuvant Therapy and Vascular Resection during Pancreaticoduodenectomy: Shifting the Survival Curve for Patients with Locally Advanced Pancreatic Cancer. World Journal of Surgery, 38, 1184-1195. http://dx.doi.org/10.1007/s00268-013-2384-z
Blazer, M., Wu, C., Goldberg, R.M., Phillips, G., Schmidt, C., Muscarella, P., et al. (2014) Neoadjuvant Modified (m) FOLFIRINOX for Locally Advanced Unresectable (LAPC) and Borderline Resectable (BRPC) Adenocarcinoma of the Pancreas. Annals of Surgical Oncology, 22, 1153-1159.
Katz, M., Shi, Q., Ahmad, S.A., Herman, J.M., Marsh, R., Collisson, E.A., Schwartz, L.H., Martin, R.C.G., Conway, W.C., Truty, M., Kindler, H.L., Lowy, A.M., Philip, P.A., Bekaii-Saab, T.S., Cardin, D.B., LoConte, N.K. and Venook, A.P. (2015) Preoperative Modified FOLFIRINOX (mFOLFIRINOX) Followed by Chemoradiation (CRT) for Borderline Resectable (BLR) Pancreatic Cancer (PC): Initial Results from Alliance Trial A021101. Journal of Clinical Oncology, 33, Abstract No. 4008.