Skip to main content

Advertisement

SpringerLink
Log in

Optimal indication of neoadjuvant chemoradiotherapy for pancreatic cancer

  • Original Article
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Purpose

Much attention has been paid to preoperative treatment as a new strategy especially for borderline resectable pancreatic cancer (BRPC). The purpose of this study was to define the optimal indication of neoadjuvant chemoradiotherapy (NACRT) for pancreatic cancer.

Methods

We analyzed consecutive 184 patients who had undergone pancreatic resection in Nara Medical University Hospital. Resectability status was classified by NCCN guidelines. Full-dose gemcitabine with concurrent radiation was used as NACRT. We evaluated 85 patients treated with NACRT in comparison with 99 patients without NACRT as control.

Results

The regimen of NACRT was well tolerated and feasible. The perioperative outcomes were almost comparable. The postoperative complications were significantly less frequent in NACRT group than non-NACRT group. The pathological effects on both resectable and borderline tumors were favorable in NACRT group compared to non-NACRT group. The overall survival of resectable pancreatic cancer was significantly better than that of BRPC regardless of whether the patients were treated with or without NACRT. The prognosis of the patients with NACRT in resectable tumors was significantly better than without, while there was no significant difference in BRPC. Furthermore, multivariate analysis of various factors in the patients with NACRT identified resectability status and completion of adjuvant chemotherapy as independent prognostic factors.

Conclusions

NACRT did not improve the prognosis of the patients with BRPC, although it induced substantial pathological antitumor effect. In contrast, the prognosis of resectable pancreatic cancer treated with NACRT was favorable. Therefore, resectable pancreatic cancer may be good indication for multimodal treatment including NACRT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ma J, Siegel R, Jemal A (2013) Pancreatic cancer death rates by race among US men and women, 1970–2009. J Natl Cancer Inst 105(22):1694–1700

    Article  PubMed  Google Scholar 

  2. Egawa S, Toma H, Ohigashi H et al (2012) Japan pancreatic cancer registry; 30th year anniversary: Japan pancreas society. Pancreas 41(7):985–992

    Article  PubMed  Google Scholar 

  3. Ueno H, Ioka T, Ikeda M et al (2013) Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol 31(13):1640–1648

    Article  CAS  PubMed  Google Scholar 

  4. Moore MJ, Goldstein D, Hamm J et al (2007) Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25(15):1960–1966

    Article  CAS  PubMed  Google Scholar 

  5. Conroy T, Desseigne F, Ychou M et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364(19):1817–1825

    Article  CAS  PubMed  Google Scholar 

  6. Von Hoff DD, Ervin T, Arena FP et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369(18):1691–1703

    Article  Google Scholar 

  7. Ferrone CR, Brennan MF, Gonen M et al (2008) Pancreatic adenocarcinoma: the actual 5-year survivors. J Gastrointest Surg 12(4):701–706

    Article  PubMed  Google Scholar 

  8. Schnelldorfer T, Ware AL, Sarr MG et al (2008) Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? Ann Surg 247(3):456–462

    Article  PubMed  Google Scholar 

  9. Oettle H, Post S, Neuhaus P et al (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297(3):267–277

    Article  CAS  PubMed  Google Scholar 

  10. Ueno H, Kosuge T, Matsuyama Y et al (2009) A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer. Br J Cancer 101(6):908–915

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Heinrich S, Pestalozzi B, Lesurtel M et al (2011) Adjuvant gemcitabine versus NEOadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study). BMC Cancer 11:346

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Paulson AS, Tran Cao HS, Tempero MA et al (2013) Therapeutic advances in pancreatic cancer. Gastroenterology 144(6):1316–1326

    Article  CAS  PubMed  Google Scholar 

  13. Heinemann V, Haas M, Boeck S (2013) Neoadjuvant treatment of borderline resectable and non-resectable pancreatic cancer. Ann Oncol 24(10):2484–2492

    Article  CAS  PubMed  Google Scholar 

  14. Katz MH, Marsh R, Herman JM et al (2013) Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol 20(8):2787–2795

    Article  PubMed  Google Scholar 

  15. Bockhorn M, Uzunoglu FG, Adham M et al (2014) Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 155(6):977–988

    Article  PubMed  Google Scholar 

  16. Motoi F, Ishida K, Fujishima F 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. Ann Surg Oncol 20(12):3794–3801

    Article  PubMed  Google Scholar 

  17. Takahashi H, Ohigashi H, Gotoh K et al (2013) Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg 258(6):1040–1050

    Article  PubMed  Google Scholar 

  18. Katz MH, Crane CH, Varadhachary G (2014) Management of borderline resectable pancreatic cancer. Semin Radiat Oncol 24(2):105–112

    Article  PubMed  Google Scholar 

  19. Rose JB, Rocha FG, Alseidi A et al (2014) Extended neoadjuvant chemotherapy for borderline resectable pancreatic cancer demonstrates promising postoperative outcomes and survival. Ann Surg Oncol 21(5):1530–1537

    Article  PubMed  Google Scholar 

  20. Sho M, Akahori T, Tanaka T et al (2013) Pathological and clinical impact of neoadjuvant chemoradiotherapy using full-dose gemcitabine and concurrent radiation for resectable pancreatic cancer. J Hepatobiliary Pancreat Sci 20(2):197–205

    Article  PubMed  Google Scholar 

  21. Sho M, Tanaka T, Yamada T et al (2011) Novel postoperative adjuvant strategy prevents early hepatic recurrence after resection of pancreatic cancer. J Hepatobiliary Pancreat Sci 18(2):235–239

    Article  PubMed  Google Scholar 

  22. Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17(6):1471–1474

    Article  PubMed  Google Scholar 

  23. Sobin LH, Gospodarowicz MK, Wittekind C (2009) TNM classification of malignant tumours, 7th edn. Wiley-Liss, New York

    Google Scholar 

  24. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) 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 92(3):205–216

    Article  CAS  PubMed  Google Scholar 

  25. Evans DB, Varadhachary GR, Crane CH et al (2008) Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol 26(21):3496–3502

    Article  CAS  PubMed  Google Scholar 

  26. Bassi C, Dervenis C, Butturini G et al (2005) Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 138(1):8–13

    Article  PubMed  Google Scholar 

  27. Wente MN, Veit JA, Bassi C et al (2007) Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery 142(1):20–25

    Article  PubMed  Google Scholar 

  28. Varadhachary GR (2011) Preoperative therapies for resectable and borderline resectable pancreatic cancer. J Gastrointest Oncol 2(3):136–142

    PubMed Central  PubMed  Google Scholar 

  29. Festa V, Andriulli A, Valvano MR et al (2013) Neoadjuvant chemo-radiotherapy for patients with borderline resectable pancreatic cancer: a meta-analytical evaluation of prospective studies. JOP 14(6):618–625

    PubMed  Google Scholar 

  30. Laurence JM, Tran PD, Morarji K et al (2011) A systematic review and meta-analysis of survival and surgical outcomes following neoadjuvant chemoradiotherapy for pancreatic cancer. J Gastrointest Surg 15(11):2059–2069

    Article  PubMed  Google Scholar 

  31. Kato K, Yamada S, Sugimoto H et al (2009) Prognostic factors for survival after extended pancreatectomy for pancreatic head cancer: influence of resection margin status on survival. Pancreas 38(6):605–612

    Article  PubMed  Google Scholar 

  32. Truty MJ, Thomas RM, Katz MH et al (2012) Multimodality therapy offers a chance for cure in patients with pancreatic adenocarcinoma deemed unresectable at first operative exploration. J Am Coll Surg 215(1):41–51

    Article  PubMed Central  PubMed  Google Scholar 

  33. Sahora K, Kuehrer I, Schindl M et al (2011) NeoGemTax: gemcitabine and docetaxel as neoadjuvant treatment for locally advanced nonmetastasized pancreatic cancer. World J Surg 35(7):1580–1589

    Article  PubMed  Google Scholar 

  34. Patel M, Hoffe S, Malafa M et al (2011) Neoadjuvant GTX chemotherapy and IMRT-based chemoradiation for borderline resectable pancreatic cancer. J Surg Oncol 104(2):155–161

    Article  PubMed Central  PubMed  Google Scholar 

  35. McClaine RJ, Lowy AM, Sussman JJ et al (2009) Neoadjuvant therapy may lead to successful surgical resection and improved survival in patients with borderline resectable pancreatic cancer. HPB (Oxford) 12(1):73–79

    Article  Google Scholar 

  36. Landry J, Catalano PJ, Staley C et al (2010) Randomized phase II study of gemcitabine plus radiotherapy versus gemcitabine, 5-fluorouracil, and cisplatin followed by radiotherapy and 5-fluorouracil for patients with locally advanced, potentially resectable pancreatic adenocarcinoma. J Surg Oncol 101(7):587–592

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Murakami Y, Uemura K, Sudo T et al (2010) Number of metastatic lymph nodes, but not lymph node ratio, is an independent prognostic factor after resection of pancreatic carcinoma. J Am Coll Surg 211(2):196–204

    Article  PubMed  Google Scholar 

  38. Christians KK, Tsai S, Mahmoud A et al (2014) Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment paradigm? Oncologist 19(3):266–274

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Ferrone CR, Marchegiani G, Hong TS et al (2015) Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg 261(1):12–17

    Article  PubMed  Google Scholar 

  40. Boone BA, Steve J, Krasinskas AM et al (2013) Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer. J Surg Oncol 108(4):236–241

    Article  CAS  PubMed  Google Scholar 

  41. Araujo RL, Gaujoux S, Huguet F et al (2013) Does pre-operative chemoradiation for initially unresectable or borderline resectable pancreatic adenocarcinoma increase post-operative morbidity? A case-matched analysis. HPB (Oxford) 15(8):574–580

    Article  Google Scholar 

  42. Takahashi H, Ogawa H, Ohigashi H et al (2011) Preoperative chemoradiation reduces the risk of pancreatic fistula after distal pancreatectomy for pancreatic adenocarcinoma. Surgery 150(3):547–556

    Article  PubMed  Google Scholar 

  43. Cheng TY, Sheth K, White RR et al (2006) Effect of neoadjuvant chemoradiation on operative mortality and morbidity for pancreaticoduodenectomy. Ann Surg Oncol 13(1):66–74

    Article  PubMed  Google Scholar 

  44. Valle JW, Palmer D, Jackson R 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. J Clin Oncol 32(6):504–512

    Article  PubMed  Google Scholar 

Download references

Conflicts of interest

None.

Authors’ contributions

• Study conception and design

Masayuki Sho, Chiho Ohbayashi, Masatoshi Hasegawa, Kimihiko Kichikawa, Yoshiyuki Nakajima

• Acquisition of data

Masayuki Sho, Takahiro Akahori, Toshihiro Tanaka, Shoichi Kinoshita, Minako Nagai, Satoshi Nishiwada, Tetsuro Tamamoto, Hideyuki Nishiofuku

• Analysis and interpretation of data

Masayuki Sho, Takahiro Akahori, Toshihiro Tanaka, Shoichi Kinoshita, Minako Nagai, Satoshi Nishiwada, Tetsuro Tamamoto, Hideyuki Nishiofuku

• Drafting of manuscript

Masayuki Sho

• Critical revision of manuscript

Masayuki Sho, Chiho Ohbayashi, Masatoshi Hasegawa, Kimihiko Kichikawa, Yoshiyuki Nakajima

Author information

Authors and Affiliations

  1. Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan

    Masayuki Sho, Takahiro Akahori, Shoichi Kinoshita, Minako Nagai, Satoshi Nishiwada & Yoshiyuki Nakajima

  2. Department of Radiology, Nara Medical University, Kashihara, Nara, Japan

    Toshihiro Tanaka, Hideyuki Nishiofuku & Kimihiko Kichikawa

  3. Department of Radiation Oncology, Nara Medical University, Kashihara, Nara, Japan

    Tetsuro Tamamoto & Masatoshi Hasegawa

  4. Department of Diagnostic Pathology, Nara Medical University, Kashihara, Nara, Japan

    Chiho Ohbayashi

Authors
  1. Masayuki Sho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takahiro Akahori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toshihiro Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shoichi Kinoshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Minako Nagai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Satoshi Nishiwada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tetsuro Tamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hideyuki Nishiofuku
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chiho Ohbayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Masatoshi Hasegawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kimihiko Kichikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yoshiyuki Nakajima
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masayuki Sho.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sho, M., Akahori, T., Tanaka, T. et al. Optimal indication of neoadjuvant chemoradiotherapy for pancreatic cancer. Langenbecks Arch Surg 400, 477–485 (2015). https://doi.org/10.1007/s00423-015-1304-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-015-1304-0

Keywords

Search

Navigation