Skip to main content
Top
Published in: Journal of Gastrointestinal Surgery 7/2016

01-07-2016 | Original Article

CA19-9 Normalization During Pre-operative Treatment Predicts Longer Survival for Patients with Locally Progressed Pancreatic Cancer

Authors: Jennifer L. Williams, Brian E. Kadera, Andrew H. Nguyen, V. Raman Muthusamy, Zev A. Wainberg, O. Joe Hines, Howard A. Reber, Timothy R. Donahue

Published in: Journal of Gastrointestinal Surgery | Issue 7/2016

Login to get access

Abstract

Background

Compared to the widely adopted 2–4 months of pre-operative therapy for patients with borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC), our institution tends to administer a longer duration before considering surgical resection. Using this unique approach, the aim of this study was to determine pre-operative variables associated with survival.

Methods

Records from patients with BR/LA PDAC who underwent attempt at surgical resection from 1992–2014 were reviewed.

Results

After a median duration of 6 months of pre-operative treatment, 109 patients with BR/LA PDAC (BR 63, LA 46) were explored; 93 (85.3 %) underwent pancreatectomy. Those who received at least 6 months of pre-operative treatment had longer median overall survival (OS) than those who received less (52.8 vs. 32.1 months, P = 0.044). On multivariate analysis, pre-operative treatment duration was the strongest predictor of survival (hazard ratio (HR) 4.79, P = 0.043). However, OS was similar in those whose CA19-9 normalized regardless of whether they received more or less than 6 months of chemotherapy (71.4 vs. 101.8 months, P = 0.930).

Conclusions

Pre-operative CA19-9 decline can guide treatment duration in patients with BR/LA PDAC. We endorse 6 months of therapy except in those patients whose values normalize, where surgery can be considered after a shorter course.
Appendix
Available only for authorised users
Literature
2.
go back to reference Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 2014;74:2913-21.CrossRefPubMed Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 2014;74:2913-21.CrossRefPubMed
3.
go back to reference Katz MH, Pisters PW, Evans DB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg 2008;206:833-48.CrossRefPubMed Katz MH, Pisters PW, Evans DB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg 2008;206:833-48.CrossRefPubMed
4.
go back to reference Malafa MP. Defining borderline resectable pancreatic cancer: emerging consensus for an old challenge. J Natl Compr Canc Netw 2015;13:501-4.PubMed Malafa MP. Defining borderline resectable pancreatic cancer: emerging consensus for an old challenge. J Natl Compr Canc Netw 2015;13:501-4.PubMed
5.
go back to reference Callery MP, Chang KJ, Fishman EK, et al. 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, et al. 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 Capussotti L, Massucco P, Ribero D, et al. Extended lymphadenectomy and vein resection for pancreatic head cancer: outcomes and implications for therapy. Arch Surg 2003;138:1316-22.CrossRefPubMed Capussotti L, Massucco P, Ribero D, et al. Extended lymphadenectomy and vein resection for pancreatic head cancer: outcomes and implications for therapy. Arch Surg 2003;138:1316-22.CrossRefPubMed
7.
go back to reference van Geenen RC, ten Kate FJ, de Wit LT, et al. Segmental resection and wedge excision of the portal or superior mesenteric vein during pancreatoduodenectomy. Surgery 2001;129:158-63.CrossRefPubMed van Geenen RC, ten Kate FJ, de Wit LT, et al. Segmental resection and wedge excision of the portal or superior mesenteric vein during pancreatoduodenectomy. Surgery 2001;129:158-63.CrossRefPubMed
8.
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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
9.
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.CrossRefPubMed Winter JM, Cameron JL, Campbell KA, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg 2006;10:1199-210.CrossRefPubMed
10.
go back to reference Katz MH, Wang H, Fleming JB, et al. Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma. Ann Surg Oncol 2009;16:836-47.CrossRefPubMedPubMedCentral Katz MH, Wang H, Fleming JB, et al. Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma. Ann Surg Oncol 2009;16:836-47.CrossRefPubMedPubMedCentral
11.
go back to reference Abrams RA, Lowy AM, O’Reilly EM, et al. Combined modality treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol 2009;16:1751-6.CrossRefPubMed Abrams RA, Lowy AM, O’Reilly EM, et al. Combined modality treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol 2009;16:1751-6.CrossRefPubMed
12.
go back to reference Stokes JB, Nolan NJ, Stelow EB, et al. Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer. Ann Surg Oncol 2011;18:619-27.CrossRefPubMed Stokes JB, Nolan NJ, Stelow EB, et al. Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer. Ann Surg Oncol 2011;18:619-27.CrossRefPubMed
13.
go back to reference Katz MH, Fleming JB, Bhosale P, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer 2012;118:5749-56.CrossRefPubMed Katz MH, Fleming JB, Bhosale P, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer 2012;118:5749-56.CrossRefPubMed
14.
go back to reference Takahashi H, Ohigashi H, Gotoh K, et al. Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg 2013;258:1040-50.CrossRefPubMed Takahashi H, Ohigashi H, Gotoh K, et al. Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg 2013;258:1040-50.CrossRefPubMed
15.
go back to reference Cho IR, Chung MJ, Bang S, et al. Gemcitabine based neoadjuvant chemoradiotherapy therapy in patients with borderline resectable pancreatic cancer. Pancreatology 2013;13:539-43.CrossRefPubMed Cho IR, Chung MJ, Bang S, et al. Gemcitabine based neoadjuvant chemoradiotherapy therapy in patients with borderline resectable pancreatic cancer. Pancreatology 2013;13:539-43.CrossRefPubMed
16.
go back to reference Rose JB, Rocha FG, Alseidi A, et al. Extended neoadjuvant chemotherapy for borderline resectable pancreatic cancer demonstrates promising postoperative outcomes and survival. Ann Surg Oncol 2014;21:1530-7.CrossRefPubMed Rose JB, Rocha FG, Alseidi A, et al. Extended neoadjuvant chemotherapy for borderline resectable pancreatic cancer demonstrates promising postoperative outcomes and survival. Ann Surg Oncol 2014;21:1530-7.CrossRefPubMed
17.
go back to reference Takeda Y, Nakamori S, Eguchi H, et al. Neoadjuvant gemcitabine-based accelerated hyperfractionation chemoradiotherapy for patients with borderline resectable pancreatic adenocarcinoma. Jpn J Clin Oncol 2014;44:1172-80.CrossRefPubMed Takeda Y, Nakamori S, Eguchi H, et al. Neoadjuvant gemcitabine-based accelerated hyperfractionation chemoradiotherapy for patients with borderline resectable pancreatic adenocarcinoma. Jpn J Clin Oncol 2014;44:1172-80.CrossRefPubMed
18.
go back to reference Mellon EA, Hoffe SE, Springett GM, et al. Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma. Acta Oncol 2015;54:979-85.CrossRefPubMed Mellon EA, Hoffe SE, Springett GM, et al. Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma. Acta Oncol 2015;54:979-85.CrossRefPubMed
19.
go back to reference Aristu J, Cañón R, Pardo F, et al. Surgical resection after preoperative chemoradiotherapy benefits selected patients with unresectable pancreatic cancer. Am J Clin Oncol 2003;26:30-6.CrossRefPubMed Aristu J, Cañón R, Pardo F, et al. Surgical resection after preoperative chemoradiotherapy benefits selected patients with unresectable pancreatic cancer. Am J Clin Oncol 2003;26:30-6.CrossRefPubMed
20.
go back to reference Sa Cunha A, Rault A, Laurent C, et al. Surgical resection after radiochemotherapy in patients with unresectable adenocarcinoma of the pancreas. J Am Coll Surg 2005;201:359-65.CrossRefPubMed Sa Cunha A, Rault A, Laurent C, et al. Surgical resection after radiochemotherapy in patients with unresectable adenocarcinoma of the pancreas. J Am Coll Surg 2005;201:359-65.CrossRefPubMed
21.
go back to reference Allendorf JD, Lauerman M, Bill A, et al. Neoadjuvant chemotherapy and radiation for patients with locally unresectable pancreatic adenocarcinoma: feasibility, efficacy, and survival. J Gastrointest Surg 2008;12:91-100.CrossRefPubMed Allendorf JD, Lauerman M, Bill A, et al. Neoadjuvant chemotherapy and radiation for patients with locally unresectable pancreatic adenocarcinoma: feasibility, efficacy, and survival. J Gastrointest Surg 2008;12:91-100.CrossRefPubMed
22.
go back to reference Bickenbach KA, Gonen M, Tang LH, et al. Downstaging in pancreatic cancer: a matched analysis of patients resected following systemic treatment of initially locally unresectable disease. Ann Surg Oncol 2012;19:1663-9.CrossRefPubMed Bickenbach KA, Gonen M, Tang LH, et al. Downstaging in pancreatic cancer: a matched analysis of patients resected following systemic treatment of initially locally unresectable disease. Ann Surg Oncol 2012;19:1663-9.CrossRefPubMed
23.
go back to reference Strobel O, Berens V, Hinz U, et al. Resection after neoadjuvant therapy for locally advanced, “unresectable” pancreatic cancer. Surgery 2012;152:S33-42.CrossRefPubMed Strobel O, Berens V, Hinz U, et al. Resection after neoadjuvant therapy for locally advanced, “unresectable” pancreatic cancer. Surgery 2012;152:S33-42.CrossRefPubMed
24.
go back to reference Ben-Josef E, Schipper M, Francis IR, et al. A phase I/II trial of intensity modulated radiation (IMRT) dose escalation with concurrent fixed-dose rate gemcitabine (FDR-G) in patients with unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2012;84:1166-71.CrossRefPubMedPubMedCentral Ben-Josef E, Schipper M, Francis IR, et al. A phase I/II trial of intensity modulated radiation (IMRT) dose escalation with concurrent fixed-dose rate gemcitabine (FDR-G) in patients with unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2012;84:1166-71.CrossRefPubMedPubMedCentral
25.
26.
go back to reference Donahue TR, Isacoff WH, Hines OJ, et al. Downstaging chemotherapy and alteration in the classic computed tomography/magnetic resonance imaging signs of vascular involvement in patients with pancreaticobiliary malignant tumors: influence on patient selection for surgery. Arch Surg 2011;146:836-43.CrossRefPubMed Donahue TR, Isacoff WH, Hines OJ, et al. Downstaging chemotherapy and alteration in the classic computed tomography/magnetic resonance imaging signs of vascular involvement in patients with pancreaticobiliary malignant tumors: influence on patient selection for surgery. Arch Surg 2011;146:836-43.CrossRefPubMed
27.
go back to reference Kadera BE, Sunjaya DB, Isacoff WH, et al. Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival. JAMA Surg 2014;149:145-53.CrossRefPubMed Kadera BE, Sunjaya DB, Isacoff WH, et al. Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival. JAMA Surg 2014;149:145-53.CrossRefPubMed
28.
go back to reference Washington K, Berlin J, Branton P, et al. Protocol for the Examination of Specimens From Patients with Carcinoma of the Exocrine Pancreas Version 3.2.0.0. Northfield, IL: College of American Pathologists;2012:1-18. Washington K, Berlin J, Branton P, et al. Protocol for the Examination of Specimens From Patients with Carcinoma of the Exocrine Pancreas Version 3.2.0.0. Northfield, IL: College of American Pathologists;2012:1-18.
29.
go back to reference Dholakia AS, Hacker-Prietz A, Wild AT, et al. Resection of borderline resectable pancreatic cancer after neoadjuvant chemoradiation does not depend on improved radiographic appearance of tumor-vessel relationships. J Radiat Oncol 2013;2:413-425.CrossRefPubMedPubMedCentral Dholakia AS, Hacker-Prietz A, Wild AT, et al. Resection of borderline resectable pancreatic cancer after neoadjuvant chemoradiation does not depend on improved radiographic appearance of tumor-vessel relationships. J Radiat Oncol 2013;2:413-425.CrossRefPubMedPubMedCentral
30.
go back to reference Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47.CrossRefPubMed Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47.CrossRefPubMed
31.
go back to reference Berger AC, Garcia M Jr, Hoffman JP, et al. Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: a prospective validation by RTOG 9704. J Clin Oncol 2008;26:5918-22.CrossRefPubMedPubMedCentral Berger AC, Garcia M Jr, Hoffman JP, et al. Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: a prospective validation by RTOG 9704. J Clin Oncol 2008;26:5918-22.CrossRefPubMedPubMedCentral
32.
go back to reference Tzeng CW, Balachandran A, Ahmad M, et al. Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer. HPB (Oxford) 2014;16:430-8.CrossRef Tzeng CW, Balachandran A, Ahmad M, et al. Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer. HPB (Oxford) 2014;16:430-8.CrossRef
33.
go back to reference Combs SE, Habermehl D, Kessel KA, et al. Prognostic impact of CA 19-9 on outcome after neoadjuvant chemoradiation in patients with locally advanced pancreatic cancer. Ann Surg Oncol 2014;21:2801-7.CrossRefPubMed Combs SE, Habermehl D, Kessel KA, et al. Prognostic impact of CA 19-9 on outcome after neoadjuvant chemoradiation in patients with locally advanced pancreatic cancer. Ann Surg Oncol 2014;21:2801-7.CrossRefPubMed
34.
go back to reference Kim TH, Han SS, Park SJ, et al. CA 19-9 level as indicator of early distant metastasis and therapeutic selection in resected pancreatic cancer. Int J Radiat Oncol Biol Phys 2011;81:743-8.CrossRef Kim TH, Han SS, Park SJ, et al. CA 19-9 level as indicator of early distant metastasis and therapeutic selection in resected pancreatic cancer. Int J Radiat Oncol Biol Phys 2011;81:743-8.CrossRef
35.
go back to reference Yoo T, Lee WJ, Woo SM, et al. Pretreatment carbohydrate antigen 19-9 level indicates tumor response, early distant metastasis, overall survival, and therapeutic selection in localized and unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2011;81:623-30.CrossRef Yoo T, Lee WJ, Woo SM, et al. Pretreatment carbohydrate antigen 19-9 level indicates tumor response, early distant metastasis, overall survival, and therapeutic selection in localized and unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2011;81:623-30.CrossRef
36.
go back to reference Iacobuzio-Donahue CA, Fu B, Yachida S, et al.: DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 2009;27:1806-13.CrossRefPubMedPubMedCentral Iacobuzio-Donahue CA, Fu B, Yachida S, et al.: DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 2009;27:1806-13.CrossRefPubMedPubMedCentral
37.
go back to reference Kannagi R. Carbohydrate antigen sialyl Lewis a--its pathophysiological significance and induction mechanism in cancer progression. Chang Gung Med J. 2007;30:189-209.PubMed Kannagi R. Carbohydrate antigen sialyl Lewis a--its pathophysiological significance and induction mechanism in cancer progression. Chang Gung Med J. 2007;30:189-209.PubMed
Metadata
Title
CA19-9 Normalization During Pre-operative Treatment Predicts Longer Survival for Patients with Locally Progressed Pancreatic Cancer
Authors
Jennifer L. Williams
Brian E. Kadera
Andrew H. Nguyen
V. Raman Muthusamy
Zev A. Wainberg
O. Joe Hines
Howard A. Reber
Timothy R. Donahue
Publication date
01-07-2016
Publisher
Springer US
Published in
Journal of Gastrointestinal Surgery / Issue 7/2016
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-016-3149-4

Other articles of this Issue 7/2016

Journal of Gastrointestinal Surgery 7/2016 Go to the issue