Abstract
Background/purpose
The therapeutic options available as preoperative strategies for resectable pancreatic cancer have received worldwide attention. We have recently introduced neoadjuvant chemoradiotherapy (NACRT) to achieve local control and possibly complete cure. In this study, we have retrospectively evaluated its impact on pathology and the perioperative clinical course in addition to its safety.
Methods
Sixty-one patients who received full-dose gemcitabine (1000 mg/m2) preoperatively with concurrent radiation (50 or 54 Gy) were evaluated. Seventy-one patients who received no preoperative therapy served as controls. Perioperative outcomes, postoperative complications, immunonutritional status, and the performance of adjuvant chemotherapy were compared.
Results
Fifty-nine patients (97 %) completed NACRT. Toxicity was acceptable and the regimen was feasible as outpatient treatment. The perioperative outcomes were closely comparable to control. The rate of pancreatic fistula was lower and hospital stay was shorter in the NACRT group. The rate of lymph node metastasis and stage was lower in the NACRT group. Furthermore, R0 resection could be achieved in 92 % of patients treated with NACRT. Nutritional status decreased after NACRT and further deteriorated during adjuvant chemotherapy. The initiation of postoperative chemotherapy was delayed in the NACRT group.
Conclusions
Our current protocol of neoadjuvant chemoradiotherapy is feasible and substantially improves the pathology. However, it has some detrimental effects on postoperative nutritional status and performance of adjuvant chemotherapy. Furthermore, it should be noted that there is a possibility of arterial complications.
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References
Traverso LW. Pancreatic cancer: surgery alone is not sufficient. Surg Endosc. 2006;20(Suppl 2):S446–9.
Schnelldorfer T, Ware AL, Sarr MG, Smyrk TC, Zhang L, Qin R, et al. Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? Ann Surg. 2008;247:456–62.
Ferrone CR, Brennan MF, Gonen M, Coit DG, Fong Y, Chung S, et al. Pancreatic adenocarcinoma: the actual 5-year survivors. J Gastrointest Surg. 2008;12:701–6.
Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine vs. observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297:267–77.
Ueno H, Kosuge T, Matsuyama Y, Yamamoto J, Nakao A, Egawa S, et al. 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. 2009;101:908–15.
Satoi S, Yanagimoto H, Toyokawa H, Takahashi K, Matsui Y, Kitade H, et al. Surgical results after preoperative chemoradiation therapy for patients with pancreatic cancer. Pancreas. 2009;38:282–8.
Satoi S, Toyokawa H, Yanagimoto H, Yamamoto T, Kamata M, Ohe C, et al. Neo-adjuvant chemoradiation therapy using S-1 followed by surgical resection in patients with pancreatic cancer. J Gastrointest Surg. 2012;16:748–792.
Takahashi H, Ohigashi H, Ishikawa O, Eguchi H, Gotoh K, Yamada T, et al. Serum CA19-9 alterations during preoperative gemcitabine-based chemoradiation therapy for resectable invasive ductal carcinoma of the pancreas as an indicator for therapeutic selection and survival. Ann Surg. 2010;251:461–9.
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;35:1580–9.
Piperdi M, McDade TP, Shim JK, Piperdi B, Kadish SP, Sullivan ME, et al. A neoadjuvant strategy for pancreatic adenocarcinoma increases the likelihood of receiving all components of care: lessons from a single-institution database. HPB (Oxford). 2010;12:204–10.
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;104:155–61.
Ohigashi H, Ishikawa O, Eguchi H, Takahashi H, Gotoh K, Yamada T, et al. 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.
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). 2009;12:73–9.
Heinrich S, Schafer M, Weber A, Hany TF, Bhure U, Pestalozzi BC, et al. Neoadjuvant chemotherapy generates a significant tumor response in resectable pancreatic cancer without increasing morbidity: results of a prospective phase II trial. Ann Surg. 2008;248:1014–22.
Heinrich S, Pestalozzi BC, Schafer M, Weber A, Bauerfeind P, Knuth A, et al. Prospective phase II trial of neoadjuvant chemotherapy with gemcitabine and cisplatin for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26:2526–31.
Heinrich S, Pestalozzi B, Lesurtel M, Berrevoet F, Laurent S, Delpero JR, et al. Adjuvant gemcitabine versus neoadjuvant gemcitabine/oxaliplatin plus adjuvant gemcitabine in resectable pancreatic cancer: a randomized multicenter phase III study (NEOPAC study). BMC Cancer. 2011;11:346.
Gillen S, Schuster T, Meyer Zum Buschenfelde 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.
Evans DB, Varadhachary GR, Crane CH, Sun CC, Lee JE, Pisters PW, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26:3496–502.
Cheng TY, Sheth K, White RR, Ueno T, Hung CF, Clary BM, et al. Effect of neoadjuvant chemoradiation on operative mortality and morbidity for pancreaticoduodenectomy. Ann Surg Oncol. 2006;13:66–74.
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. 2011.
Andriulli A, Festa V, Botteri E, Valvano MR, Koch M, Bassi C, et al. Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies. Ann Surg Oncol. 2011.
Sho M, Tanaka T, Yamada T, Nomi T, Akahori T, Doh J, et al. Novel postoperative adjuvant strategy prevents early hepatic recurrence after resection of pancreatic cancer. J Hepatobiliary Pancreat Sci. 2011;18:235–9 (discussion 239–40).
National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology. Pancreatic adenocarcinoma. Version1.2012.
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. 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;92:205–16.
Evans DB, Rich TA, Byrd DR, Cleary KR, Connelly JH, Levin B, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992;127:1335–9.
Kanda M, Fujii T, Kodera Y, Nagai S, Takeda S, Nakao A. Nutritional predictors of postoperative outcome in pancreatic cancer. Br J Surg. 2011;98:268–74.
Wente MN, Veit JA, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, et al. Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery. 2007;142:20–5.
Bassi C, Dervenis C, Butturini G, Fingerhut A, Yeo C, Izbicki J, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005;138:8–13.
Landry J, Catalano PJ, Staley C, Harris W, Hoffman J, Talamonti M, et al. 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. 2010;101:587–92.
Talamonti MS, Small W Jr, Mulcahy MF, Wayne JD, Attaluri V, Colletti LM, et al. A multi-institutional phase II trial of preoperative full-dose gemcitabine and concurrent radiation for patients with potentially resectable pancreatic carcinoma. Ann Surg Oncol. 2006;13:150–8.
Takahashi H, Ogawa H, Ohigashi H, Gotoh K, Yamada T, Ohue M, et al. Preoperative chemoradiation reduces the risk of pancreatic fistula after distal pancreatectomy for pancreatic adenocarcinoma. Surgery. 2011;150:547–56.
Schafer M, Heinrich S, Pfammatter T, Clavien PA. Management of delayed major visceral arterial bleeding after pancreatic surgery. HPB (Oxford). 2011;13:132–8.
Murono S, Nakanishi Y, Inoue D, Ozaki K, Kondo S, Wakisaka N, et al. Pseudoaneurysm of the lingual artery after concurrent intra-arterial chemotherapy with radiotherapy for advanced tongue cancer. Head Neck. 2011;33:1230–2.
Murakami Y, Uemura K, Sudo T, Hayashidani Y, Hashimoto Y, Nakashima A, et al. Number of metastatic lymph nodes, but not lymph node ratio, is an independent prognostic factor after resection of pancreatic carcinoma. J Am Coll Surg. 2010;211:196–204.
Kato K, Yamada S, Sugimoto H, Kanazumi N, Nomoto S, Takeda S, et al. Prognostic factors for survival after extended pancreatectomy for pancreatic head cancer: influence of resection margin status on survival. Pancreas. 2009;38:605–12.
Kondo S, Katoh H, Hirano S, Ambo Y, Tanaka E, Okushiba S, et al. Results of radical distal pancreatectomy with en bloc resection of the celiac artery for locally advanced cancer of the pancreatic body. Langenbecks Arch Surg. 2003;388:101–6.
Yamaguchi K, Noshiro H, Shimizu S, Morisaki T, Chijiiwa K, Tanaka M. Long-term and short-term survivors after pancreatectomy for pancreatic cancer. Int Surg. 2000;85:71–6.
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Sho, M., Akahori, T., Tanaka, T. et al. Pathological and clinical impact of neoadjuvant chemoradiotherapy using full-dose gemcitabine and concurrent radiation for resectable pancreatic cancer. J Hepatobiliary Pancreat Sci 20, 197–205 (2013). https://doi.org/10.1007/s00534-012-0532-8
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DOI: https://doi.org/10.1007/s00534-012-0532-8