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Published in: Annals of Surgical Oncology 13/2018

01-12-2018 | Pancreatic Tumors

Resectable Distal Pancreas Cancer: Time to Reconsider the Role of Upfront Surgery

Authors: Daniel W. Nelson, DO, Shu-Ching Chang, PhD, Gary Grunkemeier, PhD, Ahmed N. Dehal, MD, David Y. Lee, MD, Trevan D. Fischer, MD, L. Andrew DiFronzo, MD, Victoria V. O’Connor, MD

Published in: Annals of Surgical Oncology | Issue 13/2018

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Abstract

Background

Neoadjuvant chemotherapy (NAC) is increasingly utilized to optimize survival in proximal pancreatic adenocarcinoma. However, few studies have explored the impact of NAC in distal pancreas cancer.

Methods

Patients with resectable pancreatic adenocarcinoma of the body or tail treated with either upfront pancreatectomy or NAC followed by surgery were identified in the 2006–2014 National Cancer Database. Trends in utilization, predictors of use, and impact of NAC on overall survival were determined.

Results

Of 1485 patients, 176 (11.9%) received NAC. Use of NAC increased from 9.3% in 2006 to 16.9% in 2013 [odds ratio 1.14; 95% confidence interval (CI) 1.05–1.24; p = 0.001]. NAC patients were younger, had higher clinical stage, and preoperative CA 19-9 levels (all p < 0.05). After adjustment for patient-, tumor-, and treatment-related factors, increased clinical stage was the greatest independent predictor of neoadjuvant approach (p < 0.001). On multivariable analysis, survival benefit from NAC did not reach threshold of significance (95% CI 0.66–1.04; p = 0.10) for the entire cohort. However, NAC was associated with a significant survival advantage in clinical stage III with a 51% decreased yearly risk of death (adjusted hazard ratio 0.49; 95% CI 0.25–0.98; p = 0.04). A trend towards improved survival with NAC was observed among stage IIA (p = 0.09) and IIB (p = 0.07) patients.

Conclusions

Neoadjuvant chemotherapy is associated with improved overall survival in Stage III distal pancreatic adenocarcinoma and shows promise in earlier stage disease. However, only a small percentage of patients receive NAC. Prospective evaluation of NAC in distal pancreatic adenocarcinoma is warranted based on these findings.
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Literature
2.
go back to reference Wong J, Solomon NL, Hsueh CT. Neoadjuvant treatment for resectable pancreatic adenocarcinoma. World J Clin Oncol. 2016;7(1):1–8.CrossRef Wong J, Solomon NL, Hsueh CT. Neoadjuvant treatment for resectable pancreatic adenocarcinoma. World J Clin Oncol. 2016;7(1):1–8.CrossRef
3.
go back to reference Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985;120(8):899–903.CrossRef Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985;120(8):899–903.CrossRef
4.
go back to reference Neoptolemos JP, Dunn JA, Stocken DD, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001;358(9293):1576–85.CrossRef Neoptolemos JP, Dunn JA, Stocken DD, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001;358(9293):1576–85.CrossRef
5.
go back to reference Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297(3):267–77.CrossRef Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297(3):267–77.CrossRef
6.
go back to reference Regine WF, Winter KA, Abrams RA, et al. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008;299(9):1019–26.CrossRef Regine WF, Winter KA, Abrams RA, et al. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008;299(9):1019–26.CrossRef
7.
go back to reference Merkow RP, Bilimoria KY, Tomlinson JS, et al. Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg. 2014;260(2):372–7.CrossRef Merkow RP, Bilimoria KY, Tomlinson JS, et al. Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg. 2014;260(2):372–7.CrossRef
8.
go back to reference Tang K, Lu W, Qin W, Wu Y. Neoadjuvant therapy for patients with borderline resectable pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. Pancreatology. 2016;16(1):28–37.CrossRef Tang K, Lu W, Qin W, Wu Y. Neoadjuvant therapy for patients with borderline resectable pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. Pancreatology. 2016;16(1):28–37.CrossRef
9.
go back to reference Palmer DH, Stocken DD, Hewitt H, et al. A randomized phase 2 trial of neoadjuvant chemotherapy in resectable pancreatic cancer: gemcitabine alone versus gemcitabine combined with cisplatin. Ann Surg Oncol. 2007;14(7):2088–96.CrossRef Palmer DH, Stocken DD, Hewitt H, et al. A randomized phase 2 trial of neoadjuvant chemotherapy in resectable pancreatic cancer: gemcitabine alone versus gemcitabine combined with cisplatin. Ann Surg Oncol. 2007;14(7):2088–96.CrossRef
10.
go back to reference Heinrich S, Schafer M, Weber A, 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(6):1014–22.CrossRef Heinrich S, Schafer M, Weber A, 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(6):1014–22.CrossRef
11.
go back to reference O’Reilly EM, Perelshteyn A, Jarnagin WR, et al. A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma. Ann Surg. 2014;260(1):142–8.CrossRef O’Reilly EM, Perelshteyn A, Jarnagin WR, et al. A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma. Ann Surg. 2014;260(1):142–8.CrossRef
12.
go back to reference Lutfi W, Talamonti MS, Kantor O, et al. Perioperative chemotherapy is associated with a survival advantage in early stage adenocarcinoma of the pancreatic head. Surgery. 2016;160(3):714–24.CrossRef Lutfi W, Talamonti MS, Kantor O, et al. Perioperative chemotherapy is associated with a survival advantage in early stage adenocarcinoma of the pancreatic head. Surgery. 2016;160(3):714–24.CrossRef
13.
go back to reference Mirkin KA, Hollenbeak CS, Wong J. Survival impact of neoadjuvant therapy in resected pancreatic cancer: A Prospective Cohort Study involving 18,332 patients from the National Cancer Data Base. Int J Surg. 2016;34:96–102.CrossRef Mirkin KA, Hollenbeak CS, Wong J. Survival impact of neoadjuvant therapy in resected pancreatic cancer: A Prospective Cohort Study involving 18,332 patients from the National Cancer Data Base. Int J Surg. 2016;34:96–102.CrossRef
14.
go back to reference Mokdad AA, Minter RM, Zhu H, et al. Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer: a propensity score matched analysis. J Clin Oncol. 2017;35(5):515–22.CrossRef Mokdad AA, Minter RM, Zhu H, et al. Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer: a propensity score matched analysis. J Clin Oncol. 2017;35(5):515–22.CrossRef
15.
go back to reference Shubert CR, Bergquist JR, Groeschl RT, et al. Overall survival is increased among stage III pancreatic adenocarcinoma patients receiving neoadjuvant chemotherapy compared to surgery first and adjuvant chemotherapy: an intention to treat analysis of the National Cancer Database. Surgery. 2016;160(4):1080–96.CrossRef Shubert CR, Bergquist JR, Groeschl RT, et al. Overall survival is increased among stage III pancreatic adenocarcinoma patients receiving neoadjuvant chemotherapy compared to surgery first and adjuvant chemotherapy: an intention to treat analysis of the National Cancer Database. Surgery. 2016;160(4):1080–96.CrossRef
16.
go back to reference Youngwirth LM, Nussbaum DP, Thomas S, et al. Nationwide trends and outcomes associated with neoadjuvant therapy in pancreatic cancer: an analysis of 18 243 patients. J Surg Oncol. 2017;116(2):127–32.CrossRef Youngwirth LM, Nussbaum DP, Thomas S, et al. Nationwide trends and outcomes associated with neoadjuvant therapy in pancreatic cancer: an analysis of 18 243 patients. J Surg Oncol. 2017;116(2):127–32.CrossRef
17.
go back to reference Mirkin KA, Hollenbeak CS, Gusani NJ, Wong J. Trends in utilization of neoadjuvant therapy and short-term outcomes in resected pancreatic cancer. Am J Surg. 2017;214(1):80–8.CrossRef Mirkin KA, Hollenbeak CS, Gusani NJ, Wong J. Trends in utilization of neoadjuvant therapy and short-term outcomes in resected pancreatic cancer. Am J Surg. 2017;214(1):80–8.CrossRef
18.
go back to reference 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(4):e1000267.CrossRef 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(4):e1000267.CrossRef
19.
go back to reference Winchester DP, Stewart AK, Bura C, Jones RS. The National Cancer Data Base: a clinical surveillance and quality improvement tool. J Surg Oncol. 2004;85(1):1–3.CrossRef Winchester DP, Stewart AK, Bura C, Jones RS. The National Cancer Data Base: a clinical surveillance and quality improvement tool. J Surg Oncol. 2004;85(1):1–3.CrossRef
20.
go back to reference Giobbie-Hurder A, Gelber RD, Regan MM. Challenges of guarantee-time bias. J Clin Oncol. 2013;31(23):2963–9.CrossRef Giobbie-Hurder A, Gelber RD, Regan MM. Challenges of guarantee-time bias. J Clin Oncol. 2013;31(23):2963–9.CrossRef
21.
go back to reference Dafni U. Landmark analysis at the 25-year landmark point. Circ Cardiovasc Qual Outcomes. 2011;4(3):363–71.CrossRef Dafni U. Landmark analysis at the 25-year landmark point. Circ Cardiovasc Qual Outcomes. 2011;4(3):363–71.CrossRef
22.
go back to reference Murakami Y, Uemura K, Sudo T, et al. Early initiation of adjuvant chemotherapy improves survival of patients with pancreatic carcinoma after surgical resection. Cancer Chemother Pharmacol. 2013;71(2):419–29.CrossRef Murakami Y, Uemura K, Sudo T, et al. Early initiation of adjuvant chemotherapy improves survival of patients with pancreatic carcinoma after surgical resection. Cancer Chemother Pharmacol. 2013;71(2):419–29.CrossRef
23.
go back to reference Aloia TA, Lee JE, Vauthey JN, et al. Delayed recovery after pancreaticoduodenectomy: a major factor impairing the delivery of adjuvant therapy? J Am Coll Surg. 2007;204(3):347–55.CrossRef Aloia TA, Lee JE, Vauthey JN, et al. Delayed recovery after pancreaticoduodenectomy: a major factor impairing the delivery of adjuvant therapy? J Am Coll Surg. 2007;204(3):347–55.CrossRef
24.
go back to reference Reni M, Balzano G, Zanon S, et al. Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial. Lancet Gastroenterol Hepatol. 2018;3(6):413–23.CrossRef Reni M, Balzano G, Zanon S, et al. Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial. Lancet Gastroenterol Hepatol. 2018;3(6):413–23.CrossRef
25.
go back to reference Artinyan A, Soriano PA, Prendergast C, Low T, Ellenhorn JD, Kim J. The anatomic location of pancreatic cancer is a prognostic factor for survival. HPB (Oxford). 2008;10(5):371–6.CrossRef Artinyan A, Soriano PA, Prendergast C, Low T, Ellenhorn JD, Kim J. The anatomic location of pancreatic cancer is a prognostic factor for survival. HPB (Oxford). 2008;10(5):371–6.CrossRef
26.
go back to reference Winner M, Goff SL, Chabot JA. Neoadjuvant therapy for non-metastatic pancreatic ductal adenocarcinoma. Semin Oncol. 2015;42(1):86–97.CrossRef Winner M, Goff SL, Chabot JA. Neoadjuvant therapy for non-metastatic pancreatic ductal adenocarcinoma. Semin Oncol. 2015;42(1):86–97.CrossRef
27.
go back to reference Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.CrossRef Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.CrossRef
28.
go back to reference Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.CrossRef Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.CrossRef
29.
go back to reference Golcher H, Brunner TB, Witzigmann H, et al. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: results of the first prospective randomized phase II trial. Strahlenther Onkol. 2015;191(1):7–16.CrossRef Golcher H, Brunner TB, Witzigmann H, et al. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: results of the first prospective randomized phase II trial. Strahlenther Onkol. 2015;191(1):7–16.CrossRef
30.
go back to reference Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3496–502.CrossRef Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3496–502.CrossRef
31.
go back to reference Varadhachary GR, Wolff RA, Crane CH, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3487–95.CrossRef Varadhachary GR, Wolff RA, Crane CH, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3487–95.CrossRef
Metadata
Title
Resectable Distal Pancreas Cancer: Time to Reconsider the Role of Upfront Surgery
Authors
Daniel W. Nelson, DO
Shu-Ching Chang, PhD
Gary Grunkemeier, PhD
Ahmed N. Dehal, MD
David Y. Lee, MD
Trevan D. Fischer, MD
L. Andrew DiFronzo, MD
Victoria V. O’Connor, MD
Publication date
01-12-2018
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 13/2018
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-6765-2

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