Skip to main content
Top
Published in: Annals of Surgical Oncology 8/2011

01-08-2011 | Pancreatic Tumors

A Prospective Comparison of the Prognostic Value of Tumor- and Patient-Related Factors in Patients Undergoing Potentially Curative Surgery for Pancreatic Ductal Adenocarcinoma

Authors: Nigel B. Jamieson, MRCS, Simon M. Denley, MD, Jennifer Logue, MRCS, Douglas J. MacKenzie, MBChB, Alan K. Foulis, MD, Euan J. Dickson, MD, Clem W. Imrie, FRCS, Ross Carter, MD, Colin J. McKay, MD, Donald C. McMillan, PhD

Published in: Annals of Surgical Oncology | Issue 8/2011

Login to get access

Abstract

Background

Outcome prediction after resection with curative intent for pancreatic ductal adenocarcinoma remains a challenge. There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients undergoing resection for a variety of common solid tumors. Our aim was to prospectively evaluate the prognostic value of tumor- and patient-related factors including the systemic inflammatory response in patients undergoing potentially curative surgery for pancreatic ductal adenocarcinoma of the head of pancreas.

Methods

The prognostic impact of tumor factors such as stage and host factors, including the systemic inflammatory response (modified Glasgow Prognostic Score [mGPS]), were evaluated in a prospective study of 135 patients who underwent elective pancreaticoduodenectomy for pancreatic ductal adenocarcinoma from January 2002 to April 2009.

Results

In addition to the established tumor-related pathological factors (in particular margin involvement; hazard ratio [HR] 2.82, 95% confidence interval [CI] 1.65–4.84, P < 0.001), an elevated mGPS (HR 2.26, 95% CI 1.43–3.57, P < 0.001) was independently associated with lower overall survival after pancreaticoduodenectomy. Additionally, in an adjuvant therapy subgroup of 74 patients, both margin involvement and an elevated mGPS remained independently associated with reduced overall survival.

Conclusions

We have prospectively validated the influence of tumor-related and patient-related factors. Margin involvement and the preoperative mGPS were the most important determinants of overall survival in patients undergoing potentially curative pancreaticoduodenectomy. Furthermore, both had independent prognostic value in those patients receiving adjuvant chemotherapy. In the future, this may be considered a stratification factor for entry onto therapeutic trials.
Literature
1.
2.
go back to reference Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985–1995, using the National Cancer Database. J Am Coll Surg. 1999;189:1–7.PubMedCrossRef Sener SF, Fremgen A, Menck HR, Winchester DP. Pancreatic cancer: a report of treatment and survival trends for 100,313 patients diagnosed from 1985–1995, using the National Cancer Database. J Am Coll Surg. 1999;189:1–7.PubMedCrossRef
3.
go back to reference Luttges J, Schemm S, Vogel I, et al. The grade of pancreatic ductal carcinoma is an independent prognostic factor and is superior to the immunohistochemical assessment of proliferation. J Pathol. 2000;191:154–61.PubMedCrossRef Luttges J, Schemm S, Vogel I, et al. The grade of pancreatic ductal carcinoma is an independent prognostic factor and is superior to the immunohistochemical assessment of proliferation. J Pathol. 2000;191:154–61.PubMedCrossRef
4.
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.PubMedCrossRef 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.PubMedCrossRef
5.
go back to reference van Roest MH, Gouw AS, Peeters PM, et al. Results of pancreaticoduodenectomy in patients with periampullary adenocarcinoma: perineural growth more important prognostic factor than tumor localization. Ann Surg. 2008;248:97–103.PubMedCrossRef van Roest MH, Gouw AS, Peeters PM, et al. Results of pancreaticoduodenectomy in patients with periampullary adenocarcinoma: perineural growth more important prognostic factor than tumor localization. Ann Surg. 2008;248:97–103.PubMedCrossRef
6.
go back to reference Wagner M, Redaelli C, Lietz M, et al. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004;91:586–94.PubMedCrossRef Wagner M, Redaelli C, Lietz M, et al. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004;91:586–94.PubMedCrossRef
7.
go back to reference Winter JM, Cameron JL, Campbell KA, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg. 2006;10:1199–210.PubMedCrossRef Winter JM, Cameron JL, Campbell KA, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg. 2006;10:1199–210.PubMedCrossRef
8.
go back to reference Jamieson NB, Foulis AK, Oien KA, et al. Positive mobilization margins alone do not influence survival following pancreatico-duodenectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2010;251:1003–10.PubMedCrossRef Jamieson NB, Foulis AK, Oien KA, et al. Positive mobilization margins alone do not influence survival following pancreatico-duodenectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2010;251:1003–10.PubMedCrossRef
9.
go back to reference Colotta F, Allavena P, Sica A, et al. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30:1073–81.PubMedCrossRef Colotta F, Allavena P, Sica A, et al. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30:1073–81.PubMedCrossRef
10.
go back to reference Vakkila J, Lotze MT. Inflammation and necrosis promote tumour growth. Nat Rev Immunol. 2004;4:641–8.PubMedCrossRef Vakkila J, Lotze MT. Inflammation and necrosis promote tumour growth. Nat Rev Immunol. 2004;4:641–8.PubMedCrossRef
11.
go back to reference McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care. 2009;12:223–6.PubMedCrossRef McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care. 2009;12:223–6.PubMedCrossRef
12.
go back to reference Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;6:149–63.PubMedCrossRef Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;6:149–63.PubMedCrossRef
13.
go back to reference Vashist YK, Loos J, Dedow J, et al. Glasgow Prognostic Score is a predictor of perioperative and long-term outcome in patients with only surgically treated esophageal cancer. Ann Surg Oncol. doi:10.1245/s10434-010-1383-7. Vashist YK, Loos J, Dedow J, et al. Glasgow Prognostic Score is a predictor of perioperative and long-term outcome in patients with only surgically treated esophageal cancer. Ann Surg Oncol. doi:10.​1245/​s10434-010-1383-7.
14.
go back to reference McMillan DC, Crozier JE, Canna K, et al. Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis. 2007;22:881–6.PubMedCrossRef McMillan DC, Crozier JE, Canna K, et al. Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis. 2007;22:881–6.PubMedCrossRef
15.
go back to reference Ishizuka M, Nagata H, Takagi K, et al. Inflammation-based prognostic score is a novel predictor of postoperative outcome in patients with colorectal cancer. Ann Surg. 2007;246:1047–51.PubMedCrossRef Ishizuka M, Nagata H, Takagi K, et al. Inflammation-based prognostic score is a novel predictor of postoperative outcome in patients with colorectal cancer. Ann Surg. 2007;246:1047–51.PubMedCrossRef
16.
go back to reference Jamieson NB, Glen P, McMillan DC, et al. Systemic inflammatory response predicts outcome in patients undergoing resection for ductal adenocarcinoma head of pancreas. Br J Cancer. 2005;92:21–3.PubMedCrossRef Jamieson NB, Glen P, McMillan DC, et al. Systemic inflammatory response predicts outcome in patients undergoing resection for ductal adenocarcinoma head of pancreas. Br J Cancer. 2005;92:21–3.PubMedCrossRef
17.
go back to reference Glen P, Jamieson NB, McMillan DC, et al. Evaluation of an inflammation-based prognostic score in patients with inoperable pancreatic cancer. Pancreatology. 2006;6:450–3.PubMedCrossRef Glen P, Jamieson NB, McMillan DC, et al. Evaluation of an inflammation-based prognostic score in patients with inoperable pancreatic cancer. Pancreatology. 2006;6:450–3.PubMedCrossRef
18.
go back to reference Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448–54.PubMedCrossRef Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448–54.PubMedCrossRef
19.
go back to reference Monreal M, Fernandez-Llamazares J, Pinol M, et al. Platelet count and survival in patients with colorectal cancer—a preliminary study. Thromb Haemost. 1998;79:916–8.PubMed Monreal M, Fernandez-Llamazares J, Pinol M, et al. Platelet count and survival in patients with colorectal cancer—a preliminary study. Thromb Haemost. 1998;79:916–8.PubMed
20.
go back to reference Leitch EF, Chakrabarti M, Crozier JE, et al. Comparison of the prognostic value of selected markers of the systemic inflammatory response in patients with colorectal cancer. Br J Cancer. 2007;97:1266–70.PubMedCrossRef Leitch EF, Chakrabarti M, Crozier JE, et al. Comparison of the prognostic value of selected markers of the systemic inflammatory response in patients with colorectal cancer. Br J Cancer. 2007;97:1266–70.PubMedCrossRef
21.
go back to reference Kandemir EG, Mayadagli A, Karagoz B, et al. Prognostic significance of thrombocytosis in node-negative colon cancer. J Int Med Res. 2005;33:228–35.PubMed Kandemir EG, Mayadagli A, Karagoz B, et al. Prognostic significance of thrombocytosis in node-negative colon cancer. J Int Med Res. 2005;33:228–35.PubMed
22.
go back to reference Walsh SR, Cook EJ, Goulder F, et al. Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol. 2005;91:181–4.PubMedCrossRef Walsh SR, Cook EJ, Goulder F, et al. Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol. 2005;91:181–4.PubMedCrossRef
23.
go back to reference Smith RA, Bosonnet L, Raraty M, et al. Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma. Am J Surg. 2009;197:466–72.PubMedCrossRef Smith RA, Bosonnet L, Raraty M, et al. Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma. Am J Surg. 2009;197:466–72.PubMedCrossRef
24.
go back to reference Smith RA, Ghaneh P, Sutton R, et al. Prognosis of resected ampullary adenocarcinoma by preoperative serum CA19-9 levels and platelet-lymphocyte ratio. J Gastrointest Surg. 2008;12:1422–8.PubMedCrossRef Smith RA, Ghaneh P, Sutton R, et al. Prognosis of resected ampullary adenocarcinoma by preoperative serum CA19-9 levels and platelet-lymphocyte ratio. J Gastrointest Surg. 2008;12:1422–8.PubMedCrossRef
25.
go back to reference Neoptolemos JP, Stocken DD, Dunn JA, et al. Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial. Ann Surg. 2001;234:758–68.PubMedCrossRef Neoptolemos JP, Stocken DD, Dunn JA, et al. Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial. Ann Surg. 2001;234:758–68.PubMedCrossRef
26.
go back to reference Greene FL, Page DL, Fleming ID, et al. Exocrine pancreas. In: Greene FL, Page DL, Fleming ID, et al, editors. AJCC cancer staging manual, 6th ed. New York: Springer; 2002. p. 157–64. Greene FL, Page DL, Fleming ID, et al. Exocrine pancreas. In: Greene FL, Page DL, Fleming ID, et al, editors. AJCC cancer staging manual, 6th ed. New York: Springer; 2002. p. 157–64.
27.
go back to reference Royal College of Pathologists. Standards and minimum datasets for reporting cancers. minimum dataset for the histopathological reporting of pancreatic, ampulla of Vater and bile duct carcinoma. London: Royal College of Pathologists; 2002. Royal College of Pathologists. Standards and minimum datasets for reporting cancers. minimum dataset for the histopathological reporting of pancreatic, ampulla of Vater and bile duct carcinoma. London: Royal College of Pathologists; 2002.
28.
go back to reference Forrest LM, McMillan DC, McArdle CS, et al. Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer. 2003;89:1028–30.PubMedCrossRef Forrest LM, McMillan DC, McArdle CS, et al. Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer. 2003;89:1028–30.PubMedCrossRef
29.
go back to reference Hauser CA, Stockler MR, Tattersall MH. Prognostic factors in patients with recently diagnosed incurable cancer: a systematic review. Support Care Cancer. 2006;14:999–1011.PubMedCrossRef Hauser CA, Stockler MR, Tattersall MH. Prognostic factors in patients with recently diagnosed incurable cancer: a systematic review. Support Care Cancer. 2006;14:999–1011.PubMedCrossRef
30.
go back to reference Maltoni M, Caraceni A, Brunelli C, et al. Prognostic factors in advanced cancer patients: evidence-based clinical recommendations—a study by the Steering Committee of the European Association for Palliative Care. J Clin Oncol. 2005;23:6240–8.PubMedCrossRef Maltoni M, Caraceni A, Brunelli C, et al. Prognostic factors in advanced cancer patients: evidence-based clinical recommendations—a study by the Steering Committee of the European Association for Palliative Care. J Clin Oncol. 2005;23:6240–8.PubMedCrossRef
31.
go back to reference Ramsey S, Lamb GW, Aitchison M, et al. Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer. Cancer. 2007;109:205–12.PubMedCrossRef Ramsey S, Lamb GW, Aitchison M, et al. Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer. Cancer. 2007;109:205–12.PubMedCrossRef
32.
go back to reference Vigano A, Bruera E, Jhangri GS, et al. Clinical survival predictors in patients with advanced cancer. Arch Intern Med. 2000;160:861–8.PubMedCrossRef Vigano A, Bruera E, Jhangri GS, et al. Clinical survival predictors in patients with advanced cancer. Arch Intern Med. 2000;160:861–8.PubMedCrossRef
33.
go back to reference Chang DK, Johns AL, Merrett ND, et al. Margin clearance and outcome in resected pancreatic cancer. J Clin Oncol. 2009;27:2855–62.PubMedCrossRef Chang DK, Johns AL, Merrett ND, et al. Margin clearance and outcome in resected pancreatic cancer. J Clin Oncol. 2009;27:2855–62.PubMedCrossRef
34.
go back to reference Esposito I, Kleeff J, Bergmann F, et al. Most pancreatic cancer resections are R1 resections. Ann Surg Oncol. 2008;15:1651–60.PubMedCrossRef Esposito I, Kleeff J, Bergmann F, et al. Most pancreatic cancer resections are R1 resections. Ann Surg Oncol. 2008;15:1651–60.PubMedCrossRef
35.
go back to reference Verbeke CS, Leitch D, Menon KV, et al. Redefining the R1 resection in pancreatic cancer. Br J Surg. 2006;93:1232–7.PubMedCrossRef Verbeke CS, Leitch D, Menon KV, et al. Redefining the R1 resection in pancreatic cancer. Br J Surg. 2006;93:1232–7.PubMedCrossRef
36.
go back to reference Smith RA, Dajani K, Dodd S, et al. Preoperative resolution of jaundice following biliary stenting predicts more favourable early survival in resected pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2008;15:3138–46.PubMedCrossRef Smith RA, Dajani K, Dodd S, et al. Preoperative resolution of jaundice following biliary stenting predicts more favourable early survival in resected pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2008;15:3138–46.PubMedCrossRef
37.
go back to reference Halazun KJ, Aldoori A, Malik HZ, et al. Elevated preoperative neutrophil to lymphocyte ratio predicts survival following hepatic resection for colorectal liver metastases. Eur J Surg Oncol. 2008;34:55–60.PubMed Halazun KJ, Aldoori A, Malik HZ, et al. Elevated preoperative neutrophil to lymphocyte ratio predicts survival following hepatic resection for colorectal liver metastases. Eur J Surg Oncol. 2008;34:55–60.PubMed
38.
go back to reference Sewnath ME, Karsten TM, Prins MH, et al. A meta-analysis on the efficacy of preoperative biliary drainage for tumors causing obstructive jaundice. Ann Surg. 2002;236:17–27.PubMedCrossRef Sewnath ME, Karsten TM, Prins MH, et al. A meta-analysis on the efficacy of preoperative biliary drainage for tumors causing obstructive jaundice. Ann Surg. 2002;236:17–27.PubMedCrossRef
39.
go back to reference van der Gaag NA, Rauws EJA, van Eijick CHJ, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. 2010;362:130–7. van der Gaag NA, Rauws EJA, van Eijick CHJ, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. 2010;362:130–7.
40.
go back to reference Sharma R, Zucknick M, London R, et al. Systemic inflammatory response predicts prognosis in patients with advanced-stage colorectal cancer. Clin Colorectal Cancer. 2008;7:331–7.PubMedCrossRef Sharma R, Zucknick M, London R, et al. Systemic inflammatory response predicts prognosis in patients with advanced-stage colorectal cancer. Clin Colorectal Cancer. 2008;7:331–7.PubMedCrossRef
41.
go back to reference Kobayashi T, Teruya M, Kishiki T, et al. Inflammation-based prognostic score, prior to neoadjuvant chemoradiotherapy, predicts postoperative outcome in patients with esophageal squamous cell carcinoma. Surgery. 2008;144:729–35.PubMedCrossRef Kobayashi T, Teruya M, Kishiki T, et al. Inflammation-based prognostic score, prior to neoadjuvant chemoradiotherapy, predicts postoperative outcome in patients with esophageal squamous cell carcinoma. Surgery. 2008;144:729–35.PubMedCrossRef
42.
go back to reference Crozier JE, McKee RF, McArdle CS, et al. The presence of a systemic inflammatory response predicts poorer survival in patients receiving adjuvant 5-FU chemotherapy following potentially curative resection for colorectal cancer. Br J Cancer. 2006;94:1833–6.PubMedCrossRef Crozier JE, McKee RF, McArdle CS, et al. The presence of a systemic inflammatory response predicts poorer survival in patients receiving adjuvant 5-FU chemotherapy following potentially curative resection for colorectal cancer. Br J Cancer. 2006;94:1833–6.PubMedCrossRef
43.
go back to reference Ishizuka M, Nagata H, Takagi K, Kubota K. Influence of inflammation-based prognostic score on mortality of patients undergoing chemotherapy for far advanced or recurrent unresectable colorectal cancer. Ann Surg. 2009;250:268–72.PubMedCrossRef Ishizuka M, Nagata H, Takagi K, Kubota K. Influence of inflammation-based prognostic score on mortality of patients undergoing chemotherapy for far advanced or recurrent unresectable colorectal cancer. Ann Surg. 2009;250:268–72.PubMedCrossRef
44.
go back to reference Mantovani G, Maccio A, Madeddu C, et al. Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia. J Mol Med. 2010;88:85–92.PubMedCrossRef Mantovani G, Maccio A, Madeddu C, et al. Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia. J Mol Med. 2010;88:85–92.PubMedCrossRef
Metadata
Title
A Prospective Comparison of the Prognostic Value of Tumor- and Patient-Related Factors in Patients Undergoing Potentially Curative Surgery for Pancreatic Ductal Adenocarcinoma
Authors
Nigel B. Jamieson, MRCS
Simon M. Denley, MD
Jennifer Logue, MRCS
Douglas J. MacKenzie, MBChB
Alan K. Foulis, MD
Euan J. Dickson, MD
Clem W. Imrie, FRCS
Ross Carter, MD
Colin J. McKay, MD
Donald C. McMillan, PhD
Publication date
01-08-2011
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 8/2011
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-1560-3

Other articles of this Issue 8/2011

Annals of Surgical Oncology 8/2011 Go to the issue