Skip to main content
Top
Published in: Annals of Surgical Oncology 4/2015

01-04-2015 | Pancreatic Tumors

Improved Long-Term Outcomes After Resection of Pancreatic Adenocarcinoma: A Comparison Between Two Time Periods

Authors: Pablo E. Serrano, MD, MPH, MSc, Sean P. Cleary, MD, MPH, MSc, Neesha Dhani, MD, Peter T. W. Kim, MD, Paul D. Greig, MD, Kenneth Leung, MD, Carol-Anne Moulton, MD, PhD, Steven Gallinger, MD, MSc, Alice C. Wei, MD, CM, MSc

Published in: Annals of Surgical Oncology | Issue 4/2015

Login to get access

Abstract

Background

Despite reduced perioperative mortality and routine use of adjuvant therapy following pancreatectomy for pancreatic ductal adenocarcinoma (PDAC), improvement in long-term outcome has been difficult to ascertain. This study compares outcomes in patients undergoing resection for PDAC within a single, high-volume academic institution over two sequential time periods.

Methods

Retrospective review of patients with resected PDAC, in two cohorts: period 1 (P1), 1991–2000; and period 2 (P2), 2001–2010. Univariate and multivariate analyses using the Cox proportional hazards model were performed to determine prognostic factors associated with long-term survival. Survival was evaluated using Kaplan–Meier analyses.

Results

A total of 179 pancreatectomies were performed during P1 and 310 during P2. Perioperative mortality was 6.7 % (12/179) in P1 and 1.6 % (5/310) in P2 (p = 0.003). P2 had a greater number of lymph nodes resected (17 [0–50] vs. 7 [0–31]; p < 0.001), and a higher lymph node positivity rate (69 % [215/310] vs. 58 % [104/179]; p = 0.021) compared with P1. The adjuvant therapy rate was 30 % (53/179) in P1 and 63 % (195/310) in P2 (p < 0.001). By multivariate analysis, node and margin status, tumor grade, adjuvant therapy, and time period of resection were independently associated with overall survival (OS) for both time periods. Median OS was 16 months (95 % confidence interval [CI] 14–20) in P1 and 27 months (95 % CI 24–30) in P2 (p < 0.001).

Conclusions

Factors associated with improved long-term survival remain comparable over time. Short- and long-term survival for patients with resected PDAC has improved over time due to decreased perioperative mortality and increased use of adjuvant therapy, although the proportion of 5-year survivors remains small.
Appendix
Available only for authorised users
Literature
1.
go back to reference Begg CB, Cramer LD, Hoskins WJ, Brennan MF. Impact of hospital volume on operative mortality for major cancer surgery. JAMA. 1998;280:1747–51.CrossRefPubMed Begg CB, Cramer LD, Hoskins WJ, Brennan MF. Impact of hospital volume on operative mortality for major cancer surgery. JAMA. 1998;280:1747–51.CrossRefPubMed
2.
go back to reference Ghaferi AA, Osborne NH, Birkmeyer JD, Dimick JB. Hospital characteristics associated with failure to rescue from complications after pancreatectomy. J Am Coll Surg. 2010;211:325–30.CrossRefPubMed Ghaferi AA, Osborne NH, Birkmeyer JD, Dimick JB. Hospital characteristics associated with failure to rescue from complications after pancreatectomy. J Am Coll Surg. 2010;211:325–30.CrossRefPubMed
3.
go back to reference Ghaferi AA, Birkmeyer JD, Dimick JB. Variation in hospital mortality associated with inpatient surgery. N Engl J Med. 2009;361:1368–75.CrossRefPubMed Ghaferi AA, Birkmeyer JD, Dimick JB. Variation in hospital mortality associated with inpatient surgery. N Engl J Med. 2009;361:1368–75.CrossRefPubMed
4.
go back to reference McNulty NJ, Francis IR, Platt JF, Cohan RH, Korobkin M, Gebremariam A. Multi–detector row helical CT of the pancreas: effect of contrast-enhanced multiphasic imaging on enhancement of the pancreas, peripancreatic vasculature, and pancreatic adenocarcinoma. Radiology. 2001;220:97–102.CrossRefPubMed McNulty NJ, Francis IR, Platt JF, Cohan RH, Korobkin M, Gebremariam A. Multi–detector row helical CT of the pancreas: effect of contrast-enhanced multiphasic imaging on enhancement of the pancreas, peripancreatic vasculature, and pancreatic adenocarcinoma. Radiology. 2001;220:97–102.CrossRefPubMed
5.
go back to reference Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol. 2009;16:1727–33.CrossRefPubMed Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol. 2009;16:1727–33.CrossRefPubMed
6.
go back to reference House MG, Yeo CJ, Cameron JL, et al. Predicting resectability of periampullary cancer with three-dimensional computed tomography. J Gastrointest Surg. 2004;8:280–8.CrossRefPubMed House MG, Yeo CJ, Cameron JL, et al. Predicting resectability of periampullary cancer with three-dimensional computed tomography. J Gastrointest Surg. 2004;8:280–8.CrossRefPubMed
7.
go back to reference Neoptolemos JP, Stocken DD, Bassi C, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010;304:1073–81.CrossRefPubMed Neoptolemos JP, Stocken DD, Bassi C, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010;304:1073–81.CrossRefPubMed
8.
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;297:267–77.CrossRefPubMed 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;297:267–77.CrossRefPubMed
9.
go back to reference Kalser MH, Ellenberg SS. Pancreatic cancer: adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985;120:899–903.CrossRefPubMed Kalser MH, Ellenberg SS. Pancreatic cancer: adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985;120:899–903.CrossRefPubMed
10.
go back to reference Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350:1200–10.CrossRefPubMed Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350:1200–10.CrossRefPubMed
11.
go back to reference Winter JM, Brennan MF, Tang LH, et al. Survival after resection of pancreatic adenocarcinoma: results from a single institution over three decades. Ann Surg Oncol. 2012;19:169–75.CrossRefPubMed Winter JM, Brennan MF, Tang LH, et al. Survival after resection of pancreatic adenocarcinoma: results from a single institution over three decades. Ann Surg Oncol. 2012;19:169–75.CrossRefPubMed
12.
go back to reference He J, Ahuja N, Makary MA, et al. 2564 resected periampullary adenocarcinomas at a single institution: trends over three decades. HPB (Oxford). 2014;16:83–90.CrossRef He J, Ahuja N, Makary MA, et al. 2564 resected periampullary adenocarcinomas at a single institution: trends over three decades. HPB (Oxford). 2014;16:83–90.CrossRef
13.
14.
go back to reference Riall TS, Nealon WH, Goodwin JS, Zhang D, Kuo YF, Townsend CM Jr, et al. Pancreatic cancer in the general population: Improvements in survival over the last decade. J Gastrointest Surg. 2006;10:1212–23; discussion 1223-1214. Riall TS, Nealon WH, Goodwin JS, Zhang D, Kuo YF, Townsend CM Jr, et al. Pancreatic cancer in the general population: Improvements in survival over the last decade. J Gastrointest Surg. 2006;10:1212–23; discussion 1223-1214.
15.
go back to reference Sohal DP, Walsh RM, Ramanathan RK, Khorana AA. Pancreatic adenocarcinoma: treating a systemic disease with systemic therapy. J Natl Cancer Inst. 2014;106:dju011. Sohal DP, Walsh RM, Ramanathan RK, Khorana AA. Pancreatic adenocarcinoma: treating a systemic disease with systemic therapy. J Natl Cancer Inst. 2014;106:dju011.
16.
go back to reference Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310:1473–81.CrossRefPubMed Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310:1473–81.CrossRefPubMed
17.
go back to reference Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.CrossRefPubMed Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.CrossRefPubMed
18.
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;369:1691–03.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;369:1691–03.CrossRef
19.
go back to reference Yu XJ. Nab-paclitaxel combined with gemcitabine as adjuvant therapy for pancreatic cancer after curative resection (No) [ClinicalTrials.gov identifier NCT02023021]. US National Institutes of Health, ClinicalTrials.gov. http://www.clinicaltrials.gov. Yu XJ. Nab-paclitaxel combined with gemcitabine as adjuvant therapy for pancreatic cancer after curative resection (No) [ClinicalTrials.gov identifier NCT02023021]. US National Institutes of Health, ClinicalTrials.gov. http://​www.​clinicaltrials.​gov.
20.
go back to reference UNICANCER. Trial comparing adjuvant chemotherapy with gemcitabine versus mFolfirinox to treat resected pancreatic adenocarcinoma. [ClinicalTrials.gov identifier NCT01526135]. US National Institutes of Health, ClinicalTrials.gov. http://www.clinicaltrials.gov. UNICANCER. Trial comparing adjuvant chemotherapy with gemcitabine versus mFolfirinox to treat resected pancreatic adenocarcinoma. [ClinicalTrials.gov identifier NCT01526135]. US National Institutes of Health, ClinicalTrials.gov. http://​www.​clinicaltrials.​gov.
21.
go back to reference Kim EJ, Ben-Josef E, Herman JM, et al. A multi-institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer. Cancer. 2013;119:2692–700.CrossRefPubMedCentralPubMed Kim EJ, Ben-Josef E, Herman JM, et al. A multi-institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer. Cancer. 2013;119:2692–700.CrossRefPubMedCentralPubMed
22.
go back to reference Barugola G, Partelli S, Crippa S, Capelli P, D’Onofrio M, Pederzoli P, et al. Outcomes after resection of locally advanced or borderline resectable pancreatic cancer after neoadjuvant therapy. Am J Surg. 2012;203:,132–39.CrossRefPubMed Barugola G, Partelli S, Crippa S, Capelli P, D’Onofrio M, Pederzoli P, et al. Outcomes after resection of locally advanced or borderline resectable pancreatic cancer after neoadjuvant therapy. Am J Surg. 2012;203:,132–39.CrossRefPubMed
23.
go back to reference Katz MH, Marsh R, Herman JM et al. Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol. 2013;20:2787–95.CrossRefPubMed Katz MH, Marsh R, Herman JM et al. Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol. 2013;20:2787–95.CrossRefPubMed
24.
go back to reference Leone F, Gatti M, Massucco P, et al. Induction gemcitabine and oxaliplatin therapy followed by a twice-weekly infusion of gemcitabine and concurrent external-beam radiation for neoadjuvant treatment of locally advanced pancreatic cancer: a single institutional experience. Cancer. 2013;119:277–84.CrossRefPubMed Leone F, Gatti M, Massucco P, et al. Induction gemcitabine and oxaliplatin therapy followed by a twice-weekly infusion of gemcitabine and concurrent external-beam radiation for neoadjuvant treatment of locally advanced pancreatic cancer: a single institutional experience. Cancer. 2013;119:277–84.CrossRefPubMed
25.
go back to reference Edge SB, Byrd DR, Compton CC, et al. Exocrine and endocrine pancreas. AJCC cancer staging manual. 7th ed. New York: Springer; 2010:241–49. Edge SB, Byrd DR, Compton CC, et al. Exocrine and endocrine pancreas. AJCC cancer staging manual. 7th ed. New York: Springer; 2010:241–49.
26.
go back to reference Sobin LG, Wittekind C. TNM classification of malignant tumours. 7th ed. Oxford: Wiley; 2010. Sobin LG, Wittekind C. TNM classification of malignant tumours. 7th ed. Oxford: Wiley; 2010.
27.
go back to reference Mills M. Introducing survival and event history analysis. 2011:81–93. Mills M. Introducing survival and event history analysis. 2011:81–93.
28.
go back to reference Simons JP, Ng SC, McDade TP, Zhou Z, Earle CC, Tseng JF. Progress for resectable pancreatic [corrected] cancer? A population-based assessment of US practices. Cancer. 2010;116:1681–90.CrossRefPubMed Simons JP, Ng SC, McDade TP, Zhou Z, Earle CC, Tseng JF. Progress for resectable pancreatic [corrected] cancer? A population-based assessment of US practices. Cancer. 2010;116:1681–90.CrossRefPubMed
29.
go back to reference Langer B. Role of volume outcome data in assuring quality in HPB surgery. HPB (Oxford). 2007;9:330–4.CrossRef Langer B. Role of volume outcome data in assuring quality in HPB surgery. HPB (Oxford). 2007;9:330–4.CrossRef
30.
go back to reference Marcaccio M, LB, Rumble B, Hunter A; Expert Panel on HPB Surgical Oncology. Hepatic, pancreatic and biliary tract (HPB) surgical oncology standards. 2006. http://www.cancercare.on.ca. Accessed 2 Oct 2014. Marcaccio M, LB, Rumble B, Hunter A; Expert Panel on HPB Surgical Oncology. Hepatic, pancreatic and biliary tract (HPB) surgical oncology standards. 2006. http://​www.​cancercare.​on.​ca. Accessed 2 Oct 2014.
31.
go back to reference Simunovic M, Urbach D, Major D, et al. Assessing the volume-outcome hypothesis and region-level quality improvement interventions: pancreas cancer surgery in two Canadian provinces. Ann Surg Oncol. 2010;17:2537–44.CrossRefPubMed Simunovic M, Urbach D, Major D, et al. Assessing the volume-outcome hypothesis and region-level quality improvement interventions: pancreas cancer surgery in two Canadian provinces. Ann Surg Oncol. 2010;17:2537–44.CrossRefPubMed
32.
go back to reference Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4:567–79.CrossRefPubMed Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4:567–79.CrossRefPubMed
33.
go back to reference Tomlinson JS, Jain S, Bentrem DJ, et al. Accuracy of staging node-negative pancreas cancer: a potential quality measure. Arch Surg. 2007;142:767–74; discussion 773-764. Tomlinson JS, Jain S, Bentrem DJ, et al. Accuracy of staging node-negative pancreas cancer: a potential quality measure. Arch Surg. 2007;142:767–74; discussion 773-764.
34.
go back to reference Slidell MB, Chang DC, Cameron JL, et al. Impact of total lymph node count and lymph node ratio on staging and survival after pancreatectomy for pancreatic adenocarcinoma: a large, population-based analysis. Ann Surg Oncol. 2008;15:165–74.CrossRefPubMed Slidell MB, Chang DC, Cameron JL, et al. Impact of total lymph node count and lymph node ratio on staging and survival after pancreatectomy for pancreatic adenocarcinoma: a large, population-based analysis. Ann Surg Oncol. 2008;15:165–74.CrossRefPubMed
35.
go back to reference Riediger H, Keck T, Wellner U, zur Hausen A, Adam U, Hopt UT, et al. The lymph node ratio is the strongest prognostic factor after resection of pancreatic cancer. J Gastrointest Surg. 2009;13:1337–44. Riediger H, Keck T, Wellner U, zur Hausen A, Adam U, Hopt UT, et al. The lymph node ratio is the strongest prognostic factor after resection of pancreatic cancer. J Gastrointest Surg. 2009;13:1337–44.
36.
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;358:1576–85.CrossRefPubMed Neoptolemos JP, Dunn JA, Stocken DD, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001;358:1576–85.CrossRefPubMed
37.
go back to reference Lim JE, Chien MW, Earle CC. Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients. Ann Surg. 2003;237:74–85.CrossRefPubMedCentralPubMed Lim JE, Chien MW, Earle CC. Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients. Ann Surg. 2003;237:74–85.CrossRefPubMedCentralPubMed
38.
go back to reference Valle JW, Palmer D, Jackson R, et al. 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. 2014;32:504–12.CrossRefPubMed Valle JW, Palmer D, Jackson R, et al. 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. 2014;32:504–12.CrossRefPubMed
Metadata
Title
Improved Long-Term Outcomes After Resection of Pancreatic Adenocarcinoma: A Comparison Between Two Time Periods
Authors
Pablo E. Serrano, MD, MPH, MSc
Sean P. Cleary, MD, MPH, MSc
Neesha Dhani, MD
Peter T. W. Kim, MD
Paul D. Greig, MD
Kenneth Leung, MD
Carol-Anne Moulton, MD, PhD
Steven Gallinger, MD, MSc
Alice C. Wei, MD, CM, MSc
Publication date
01-04-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 4/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-014-4196-2

Other articles of this Issue 4/2015

Annals of Surgical Oncology 4/2015 Go to the issue