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Neo-adjuvant Chemoradiation Therapy Using S-1 Followed by Surgical Resection in Patients with Pancreatic Cancer

  • Original Article
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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Objective

The aim of this study was to compare short-term surgical results in pancreatic cancer patients who underwent surgical resection after neo-adjuvant chemoradiation therapy (NACRT) using S-1.

Methods

The study population comprised 77 patients with pancreatic cancer between 2006 and 2010. Out of 34 patients who underwent staging laparoscopy between 2008 and 2010, 31 patients without occult distant organ metastasis underwent chemoradiation and of whom 30 underwent pancreatectomy (NACRT group). Of the other 43 patients, 36 underwent surgical resection in 2006–2008, followed by adjuvant therapy (adjuvant group). The primary endpoint was frequency of pathological curative resection (R0).

Results

The new regimen of NACRT was feasible and safe. Twenty-eight of 30 (93%) patients in the NACRT group had R0 resection, which was significantly higher than in the adjuvant group (21 of 36 patients, 58%, p = 0.005). The number and extent of metastatic lymph nodes in the NACRT group (1 (0–25), N0/1; 18 of 38) was significantly lower than in the adjuvant group (2 (0–19), N0/1; 23 of 30), p = 0.0363). The frequency of intractable ascites in the NACRT group (eight of 30) was significantly higher than in the adjuvant group (two of 36, p = 0.035).

Conclusion

Neo-adjuvant chemoradiation therapy using S-1 followed by pancreatectomy can improve the rate of pathologically curative resection and reduces the number and extent of lymph node metastasis.

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References

  1. Takai S, Satoi S, Toyokawa H, Yanagimoto H, Sugimoto N, Tsuji K, Araki H, Matsui Y, Imamura A, Kwon AH, Kamiyama Y. Clinicopathologic evaluation after resection for ductal adenocarcinoma of the pancreas: a retrospective, single-institution experience. Pancreas. 2003;26:243–9.

    Article  PubMed  CAS  Google Scholar 

  2. Conlon KC, Klimstra DS, Brennan MF. Long term survival after curative resection for pancreatic ductal adenocarcinoma. Ann Surg. 1996;223:273–279.

    Article  PubMed  CAS  Google Scholar 

  3. Adham M, Jaeck D, Le Borgne J, Oussoultzouglou E, Chenard-Neu MP, Mosnier JF, Scoazec JY, Mornex F, Partensky C. Long-term survival (5–20 years) after pancreatectomy for pancreatic ductal adenocarcinoma: a series of 30 patients collected from 3 institutions. Pancreas. 2008;37:352–7.

    Article  PubMed  Google Scholar 

  4. Schnelldorfer T, Ware AL, Sarr MG, Smyrk TC, Zhang L, Qin R, Gullerud RE, Donohue JH, Nagorney DM, Farnell MB. Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? Ann Surg. 2008;247:456–62.

    Article  PubMed  Google Scholar 

  5. Han SS, Jang JY, Kim SW, Kim WH, Lee KU, Park YH. Analysis of long-term survivors after surgical resection for pancreatic cancer. Pancreas 2006;32:271–5.

    Article  PubMed  Google Scholar 

  6. Bradley III EL. Long-term survival after pancreatoduodenectomy for ductal adenocarcinoma. The emperor has no clothes? Pancreas 2008;37:349–351.

    Article  PubMed  Google Scholar 

  7. Traverso LW. Pancreatic cancer: surgery alone is not sufficient. Surg Endosc. 2006;20:446–9.

    Article  Google Scholar 

  8. Crane CH, Varadhachary G, Pisters PW, Evans DB, Wolff RA. Future chemoradiation strategies in pancreatic cancer. Semin Oncol. 2007;34:335–46.

    Article  PubMed  CAS  Google Scholar 

  9. Takai S, Satoi S, Yanagimoto H, Toyokawa H, Takahashi K, Terakawa N, Araki H, Matsui Y, Sohgawa M, Kamiyama Y. Neoadjuvant chemoradiation in patients with potentially resectable pancreatic cancer. Pancreas 2008;36:e26-32.

    Article  PubMed  Google Scholar 

  10. Satoi S, Yanagimoto H, Toyokawa H, Takahashi K, Matsui Y, Kitade H, Mergental H, Tanigawa N, Takai S, Kwon AH. Surgical results following pre-operative chemoradiation therapy for patients with pancreatic cancer. Pancreas. 2009,38:282–8.

    Article  PubMed  CAS  Google Scholar 

  11. Satoi S, Yanagimoto H, Toyokawa H, Yamamoto T, Hirooka S, Yui R, Yamaki S, Matsui Y, Kitade H, Tanigawa N, Takai S, A-Hon Kwon. Long-term results of surgical resection following pre-operative chemoradiation in patients with pancreatic cancer. Pancreas 2011; in press.

  12. Ikeda M, Okusaka T, Ito Y, Ueno H, Morizane C, Furuse J, Ishii H, Kawashima M, Kagami Y, Ikeda H. A phase I trial of S-1 with concurrent radiotherapy for locally advanced pancreatic cancer. Brit J Cancer 2007;96:1650–1655.

    Article  PubMed  CAS  Google Scholar 

  13. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology, ver 1. Fort Washington: NCCN; 2011.

  14. Appleby LH. The celiac axis in the expansion of the operation for gastric carcinoma. Cancer 1953;6:704–7.

    Article  PubMed  CAS  Google Scholar 

  15. Hirano S, Kondo S, Hara T, Ambo Y, Tanaka E, Shichinohe T, Suzuki O, Hazama K. Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic body cancer: long-term results. Ann Surg. 2007;246:46–51.

    Article  PubMed  Google Scholar 

  16. Sobin L, Wittekind C, eds. TNM classification of malignant tumors. 6th ed. New York: Wiley-Liss; 2002.

    Google Scholar 

  17. Japan Pancreas Society. The general rules for clinical and pathological management of carcinoma of the pancreas, 6th ed. Tokyo: Kanehara; 2009.

    Google Scholar 

  18. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–216.

    Article  PubMed  CAS  Google Scholar 

  19. Evans DB, Rich TA, Byrd DR, Cleary KR, Connelly JH, Levin B, Charnsangavej C, Fenoglio CJ, Ames FC. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg 1992;127:1335–1339.

    Article  PubMed  CAS  Google Scholar 

  20. Raut CP, Tseng JF, Sun C, et al. Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg. 2007;246:52–60.

    Article  PubMed  Google Scholar 

  21. Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Büchler MW; European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004;350:1200–1210.

    Article  PubMed  CAS  Google Scholar 

  22. Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007;297:267–277.

    Article  PubMed  CAS  Google Scholar 

  23. Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, Wente MN, Izbicki JR, Friess H, Lerch MM, Dervenis C, Oláh A, Butturini G, Doi R, Lind PA, Smith D, Valle JW, Palmer DH, Buckels JA, Thompson J, McKay CJ, Rawcliffe CL, Büchler MW; European Study Group for Pancreatic Cancer. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010;304:1073–81.

    Google Scholar 

  24. Gillen S, Schuster T, Meyer Zum Büschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 2010;7:e1000267.

    Article  PubMed  Google Scholar 

  25. Katz MH, Wang H, Fleming JB, Sun CC, Hwang RF, Wolff RA, Varadhachary G, Abbruzzese JL, Crane CH, Krishnan S, Vauthey JN, Abdalla EK, Lee JE, Pisters PW, Evans DB. Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma. Ann Surg Oncol. 2009;16:836–47.

    Article  PubMed  Google Scholar 

  26. Evans DB, Varadhachary GR, Crane CH, Sun CC, Lee JE, Pisters PW, Vauthey JN, Wang H, Cleary KR, Staerkel GA, Charnsangavej C, Lano EA, Ho L, Lenzi R, Abbruzzese JL, Wolff RA. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008,26:3496–3502.

    Article  PubMed  CAS  Google Scholar 

  27. Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Chen JS, Mizumoto K, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi A, Cheng L, Okusaka T. Randomized phase III study of gemcitabine plus S-1 (GS) versus S-1 versus gemcitabine (GEM) in unresectable advanced pancreatic cancer (PC) in Japan and Taiwan: GEST study. J Clin Oncol 29: 2011 (suppl; abstr 4007)

  28. Harada K, Kawaguchi S, Supriatno, Onoue T, Yoshida H, Sato M. Combined effects of the oral fluoropyrimidine anticancer agent, S-1 and radiation on human oral cancer cells. Oral Oncol 2004;40:713–719.

    Article  PubMed  CAS  Google Scholar 

  29. Nakata E, Fukushima M, Takai Y, Nemoto K, Ogawa Y, Nomiya T, Nakamura Y, Milas L, Yamada S. S-1, an oral fluoropyrimidine, enhances radiation response of DLD-1/FU human colon cancer xenografts resistant to 5-FU. Oncol Rep 2006;16:465–471.

    PubMed  CAS  Google Scholar 

  30. Shinchi H, Maemura K, Noma H, Mataki Y, Aikou T, Takao S. Phase-I trial of oral fluoropyrimidine anticancer agent (S-1) with concurrent radiotherapy in patients with unresectable pancreatic cancer. Brit J Cancer. 2007;96:1353–1357.

    PubMed  CAS  Google Scholar 

  31. Sudo K, Yamaguchi T, Ishihara T, Nakamura K, Shirai Y, Nakagawa A, Kawakami H, Uno T, Ito H, Saisho H. Phase I study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Int. J. Radiation Oncology Biol. Phys 2008;67:219–224.

    Google Scholar 

  32. Kim HM, Bang S, Park JY, Seong J, Song SY, Chung JB, Park SW. Phase II trial of S-1 and concurrent radiotherapy in patients with locally advanced pancreatic cancer. Cancer Chemother Pharmacol. 2009;63:535–541.

    Article  PubMed  CAS  Google Scholar 

  33. White RR, Hurwitz HI, Morse MA, Lee C, Anscher MS, Paulson EK, Gottfried MR, Baillie J, Branch MS, Jowell PS, McGrath KM, Clary BM, Pappas TN, Tyler DS. Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas. Ann Surg Oncol 2001; 8: 758–765.

    Article  PubMed  CAS  Google Scholar 

  34. Moutardier V, Magnin V, Turrini O, Viret F, Hennekinne-Mucci S, Gonçalves A, Pesenti C, Guiramand J, Lelong B, Giovannini M, Monges G, Houvenaeghel G, Delpero JR. Assessment of pathologic response after preoperative chemoradiotherapy and surgery in pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys 2004;60:437–443.

    Article  PubMed  Google Scholar 

  35. Le Scodan R, Mornex F, Girard N, Mercier C, Valette PJ, Ychou M, Bibeau F, Roy P, Scoazec JY, Partensky C. 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;20:1387–1396.

    Article  PubMed  Google Scholar 

  36. Ohigashi H, Ishikawa O, Eguchi H, Takahashi H, Gotoh K, Yamada T, Yano M, Nakaizumi A, Uehara H, Tomita Y, Nishiyama K. Feasibility and efficacy of combination therapy with preoperative full-dose gemcitabine, concurrent three-dimensional conformal radiation, surgery, and postoperative liver perfusion chemotherapy for T3-pancreatic cancer. Ann Surg 2009;250:88–95.

    Article  PubMed  Google Scholar 

  37. Turrini O, Ychou M, Moureau-Zabotto L, Rouanet P, Giovannini M, Moutardier V, Azria D, Delpero JR, Viret F. Neoadjuvant docetaxel-based chemoradiation for resectable adenocarcinoma of the pancreas: New neoadjuvant regimen was safe and provided an interesting pathologic response. Eur J Surg Oncol. 2010;36:987–92.

    Article  PubMed  CAS  Google Scholar 

  38. Stokes JB, Nolan NJ, Stelow EB, Walters DM, Weiss GR, de Lange EE, Rich TA, Adams RB, Bauer TW. Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer. Ann Surg Oncol. 2011;18:619–27.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Kansai Medical University, 2-3-1, Shin-machi, Hirakata City, Osaka, 573-1191, Japan

    Sohei Satoi, Hideyoshi Toyokawa, Hiroaki Yanagimoto, Tomohisa Yamamoto, Hiroaki Kitade, Kentaro Inoue, Yoichi Matsui & A-Hon Kwon

  2. Department of Radiology, Kansai Medical University, 2-3-1, Shin-machi, Hirakata City, Osaka, 573-1191, Japan

    Minoru Kamata & Noboru Tanigawa

  3. Department of Pathology, Kansai Medical University, 2-3-1, Shin-machi, Hirakata-City, Osaka, 573-1191, Japan

    Chisato Ohe, Noriko Sakaida & Yoshiko Uemura

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  1. Sohei Satoi
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Correspondence to Sohei Satoi.

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Satoi, S., Toyokawa, H., Yanagimoto, H. et al. Neo-adjuvant Chemoradiation Therapy Using S-1 Followed by Surgical Resection in Patients with Pancreatic Cancer. J Gastrointest Surg 16, 784–792 (2012). https://doi.org/10.1007/s11605-011-1795-0

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