Top

Published in:

01-05-2015 | Original Article

Optimal indication of neoadjuvant chemoradiotherapy for pancreatic cancer

Authors: Masayuki Sho, Takahiro Akahori, Toshihiro Tanaka, Shoichi Kinoshita, Minako Nagai, Satoshi Nishiwada, Tetsuro Tamamoto, Hideyuki Nishiofuku, Chiho Ohbayashi, Masatoshi Hasegawa, Kimihiko Kichikawa, Yoshiyuki Nakajima

Published in: Langenbeck's Archives of Surgery | Issue 4/2015

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.

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):1694–1700CrossRefPubMed

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

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):1640–1648CrossRefPubMed

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):1960–1966CrossRefPubMed

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

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):1691–1703CrossRef

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

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

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):267–277CrossRefPubMed

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):908–915CrossRefPubMedCentralPubMed

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 11:346CrossRefPubMedCentralPubMed

12.

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

13.

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

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):2787–2795CrossRefPubMed

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):977–988CrossRefPubMed

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):3794–3801CrossRefPubMed

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):1040–1050CrossRefPubMed

18.

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

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):1530–1537CrossRefPubMed

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):197–205CrossRefPubMed

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):235–239CrossRefPubMed

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):1471–1474CrossRefPubMed

23.

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

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):205–216CrossRefPubMed

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):3496–3502CrossRefPubMed

26.

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

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):20–25CrossRefPubMed

28.

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

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):618–625PubMed

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):2059–2069CrossRefPubMed

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):605–612CrossRefPubMed

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):41–51CrossRefPubMedCentralPubMed

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):1580–1589CrossRefPubMed

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):155–161CrossRefPubMedCentralPubMed

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):73–79CrossRef

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):587–592CrossRefPubMedCentralPubMed

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):196–204CrossRefPubMed

38.

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

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):12–17CrossRefPubMed

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):236–241CrossRefPubMed

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):574–580CrossRef

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):547–556CrossRefPubMed

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):66–74CrossRefPubMed

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):504–512CrossRefPubMed

Title: Optimal indication of neoadjuvant chemoradiotherapy for pancreatic cancer
Authors: Masayuki Sho
Takahiro Akahori
Toshihiro Tanaka
Shoichi Kinoshita
Minako Nagai
Satoshi Nishiwada
Tetsuro Tamamoto
Hideyuki Nishiofuku
Chiho Ohbayashi
Masatoshi Hasegawa
Kimihiko Kichikawa
Yoshiyuki Nakajima
Publication date: 01-05-2015
Publisher: Springer Berlin Heidelberg
Published in: Langenbeck's Archives of Surgery / Issue 4/2015
Print ISSN: 1435-2443
Electronic ISSN: 1435-2451
DOI: https://doi.org/10.1007/s00423-015-1304-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Optimal indication of neoadjuvant chemoradiotherapy for pancreatic cancer

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2015

Incidence and risk factors for symptomatic venous thromboembolism following cholecystectomy

Aortic morphometry at endograft position as assessed by 3D image analysis affects risk of type I endoleak formation after TEVAR

Clinicopathological features of hepatocellular carcinoma in patients with nonalcoholic fatty liver disease

Delirium in fast-track colonic surgery

Mortality after thyroid surgery, insignificant or still an issue?

Significant reduction in the incidence of small bowel obstruction and ventral hernia after laparoscopic compared to open segmental colorectal resection