Top

Published in:

01-01-2014 | 2013 SSAT Plenary Presentation

Treatment Sequencing for Resectable Pancreatic Cancer: Influence of Early Metastases and Surgical Complications on Multimodality Therapy Completion and Survival

Authors: Ching-Wei D. Tzeng, Hop S. Tran Cao, Jeffrey E. Lee, Peter W. T. Pisters, Gauri R. Varadhachary, Robert A. Wolff, James L. Abbruzzese, Christopher H. Crane, Douglas B. Evans, Huamin Wang, Daniel E. Abbott, Jean-Nicolas Vauthey, Thomas A. Aloia, Jason B. Fleming, Matthew H. G. Katz

Published in: Journal of Gastrointestinal Surgery | Issue 1/2014

Abstract

Barriers to multimodality therapy (MMT) completion among patients with resectable pancreatic adenocarcinoma include early cancer progression and postoperative major complications (PMC). We sought to evaluate the influence of these factors on MMT completion rates of patients treated with neoadjuvant therapy (NT) and surgery-first (SF) approaches. We evaluated all operable patients treated for clinically resectable pancreatic head adenocarcinoma at our institution from 2002 to 2007. Rates of MMT completion, 90-day PMC, and overall survival (OS) were evaluated. Ninety-five of 115 (83 %) NT and 29/50 (58 %) SF patients completed MMT. Patients who completed MMT lived longer than those who did not (36 vs. 11 months, p < 0.001). The most common reason that NT (11 %) and SF (26 %) patients failed to complete MMT was early disease progression. The rates of PMC among NT and SF patients were similar. Among SF patients, 69 % with no PMC completed MMT versus 29 % after PMC (p = 0.040). PMC were associated with decreased OS in SF patients but not in NT patients. The impact of early cancer progression and PMC upon completion of MMT is reduced by delivery of nonoperative therapies prior to pancreaticoduodenectomy. NT sequencing is a practical treatment strategy, particularly for patients at high biological or perioperative risk.

Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 1985;120(8):899–903.PubMedCrossRef

Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, Bassi C, Falconi M, Pederzoli P, Dervenis C, Fernandez-Cruz L, Lacaine F, Pap A, Spooner D, Kerr DJ, Friess H, Buchler MW. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 2001;358(9293):1576–1585.PubMedCrossRef

Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Buchler MW. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004;350(12):1200–1210.PubMedCrossRef

Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007;297(3):267–277.PubMedCrossRef

Tzeng CW, Fleming JB, Lee JE, Xiao L, Pisters PW, Vauthey JN, Abdalla EK, Wolff RA, Varadhachary GR, Fogelman DR, Crane CH, Balachandran A, Katz MH. Defined clinical classifications are associated with outcome of patients with anatomically resectable pancreatic adenocarcinoma treated with neoadjuvant therapy. Ann Surg Oncol 2012;19(6):2045–2053.PubMedCrossRef

Evans DB, Varadhachary GR, Crane CH, Sun CC, Lee JE, Pisters PW, Vauthey JN, Wang H, Cleary KR, Staerkel GA, Charnsangavej C, Lano EA, Ho L, Lenzi R, Abbruzzese JL, Wolff RA. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol 2008;26(21):3496–3502.PubMedCrossRef

Varadhachary GR, Wolff RA, Crane CH, Sun CC, Lee JE, Pisters PW, Vauthey JN, Abdalla E, Wang H, Staerkel GA, Lee JH, Ross WA, Tamm EP, Bhosale PR, Krishnan S, Das P, Ho L, Xiong H, Abbruzzese JL, Evans DB. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol 2008;26(21):3487–3495.PubMedCrossRef

Hsu CC, Herman JM, Corsini MM, Winter JM, Callister MD, Haddock MG, Cameron JL, Pawlik TM, Schulick RD, Wolfgang CL, Laheru DA, Farnell MB, Swartz MJ, Gunderson LL, Miller RC. Adjuvant chemoradiation for pancreatic adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic collaborative study. Ann Surg Oncol 2010;17(4):981–990.PubMedCentralPubMedCrossRef

Pancreatic adenocarcinoma Version 2.2012. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) 2012.

10.

Bilimoria KY, Bentrem DJ, Ko CY, Tomlinson JS, Stewart AK, Winchester DP, Talamonti MS. Multimodality therapy for pancreatic cancer in the U.S.: utilization, outcomes, and the effect of hospital volume. Cancer 2007;110(6):1227–1234.PubMedCrossRef

11.

Katz MH, Wang H, Fleming JB, Sun CC, Hwang RF, Wolff RA, Varadhachary G, Abbruzzese JL, Crane CH, Krishnan S, Vauthey JN, Abdalla EK, Lee JE, Pisters PW, Evans DB. Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma. Annals of surgical oncology 2009;16(4):836–847.PubMedCentralPubMedCrossRef

12.

Sinn M, Striefler JK, Sinn BV, Sallmon D, Bischoff S, Stieler JM, Pelzer U, Bahra M, Neuhaus P, Dorken B, Denkert C, Riess H, Oettle H. Does long-term survival in patients with pancreatic cancer really exist?-Results from the CONKO-001 study. J Surg Oncol 2013.

13.

Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zulke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H. Adjuvant Chemotherapy With Gemcitabine and Long-term Outcomes Among Patients With Resected Pancreatic Cancer: The CONKO-001 Randomized Trial. JAMA 2013;310(14):1473–1481.PubMedCrossRef

14.

Aloia TA, Lee JE, Vauthey JN, Abdalla EK, Wolff RA, Varadhachary GR, Abbruzzese JL, Crane CH, Evans DB, Pisters PW. Delayed recovery after pancreaticoduodenectomy: a major factor impairing the delivery of adjuvant therapy? J Am Coll Surg 2007;204(3):347–355.PubMedCrossRef

15.

Tzeng CW, Fleming JB, Lee JE, Wang X, Pisters PW, Vauthey JN, Varadhachary G, Wolff RA, Katz MH. Yield of clinical and radiographic surveillance in patients with resected pancreatic adenocarcinoma following multimodal therapy. HPB (Oxford) 2012;14(6):365–372.PubMedCentralPubMedCrossRef

16.

Hwang RF, Wang H, Lara A, Gomez H, Chang T, Sieffert N, Moon Y, Ram S, Zimmerman S, Lee JH, Pisters PW, Tamm EP, Fleming JB, Abbruzzese JL, Evans DB. Development of an integrated biospecimen bank and multidisciplinary clinical database for pancreatic cancer. Annals of surgical oncology 2008;15(5):1356–1366.PubMedCrossRef

17.

Katz MH, Fleming JB, Bhosale P, Varadhachary G, Lee JE, Wolff R, Wang H, Abbruzzese J, Pisters PW, Vauthey JN, Charnsangavej C, Tamm E, Crane CH, Balachandran A. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer 2012;118(23):5749–5756.PubMedCrossRef

18.

Katz MH, Pisters PW, Evans DB, Sun CC, Lee JE, Fleming JB, Vauthey JN, Abdalla EK, Crane CH, Wolff RA, Varadhachary GR, Hwang RF. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg 2008;206(5):833–846; discussion 846–838.PubMedCrossRef

19.

Varadhachary GR, Tamm EP, Abbruzzese JL, Xiong HQ, Crane CH, Wang H, Lee JE, Pisters PW, Evans DB, Wolff RA. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol 2006;13(8):1035–1046.PubMedCrossRef

20.

Pisters PW, Hudec WA, Hess KR, Lee JE, Vauthey JN, Lahoti S, Raijman I, Evans DB. Effect of preoperative biliary decompression on pancreaticoduodenectomy-associated morbidity in 300 consecutive patients. Ann Surg 2001;234(1):47–55.PubMedCrossRef

21.

Zhao Q, Rashid A, Gong Y, Katz MH, Lee JE, Wolf R, Balachandran A, Varadhachary GR, Pisters PW, Wang H, Gomez HF, Abbruzzese JL, Fleming JB. Pathologic complete response to neoadjuvant therapy in patients with pancreatic ductal adenocarcinoma is associated with a better prognosis. Ann Diagn Pathol 2012;16(1):29–37.PubMedCrossRef

22.

Tzeng CW, Abbott DE, Cantor SB, Fleming JB, Lee JE, Pisters PW, Varadhachary GR, Abbruzzese JL, Wolff RA, Ahmad SA, Katz MH. Frequency and Intensity of Postoperative Surveillance After Curative Treatment of Pancreatic Cancer: A Cost-Effectiveness Analysis. Ann Surg Oncol 2013.

23.

Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibanes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg 2009;250(2):187–196.PubMedCrossRef

24.

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240(2):205–213.PubMedCrossRef

25.

Winter JM, Brennan MF, Tang LH, D'Angelica MI, Dematteo RP, Fong Y, Klimstra DS, Jarnagin WR, Allen PJ. Survival after resection of pancreatic adenocarcinoma: results from a single institution over three decades. Ann Surg Oncol 2012;19(1):169–175.PubMedCrossRef

26.

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(7):1681–1690.PubMedCrossRef

27.

Lewis R, Drebin JA, Callery MP, Fraker D, Kent TS, Gates J, Vollmer CM, Jr. A contemporary analysis of survival for resected pancreatic ductal adenocarcinoma. HPB (Oxford) 2013;15(1):49–60.PubMedCentralPubMedCrossRef

28.

Ferrone CR, Pieretti-Vanmarcke R, Bloom JP, Zheng H, Szymonifka J, Wargo JA, Thayer SP, Lauwers GY, Deshpande V, Mino-Kenudson M, Fernandez-del Castillo C, Lillemoe KD, Warshaw AL. Pancreatic ductal adenocarcinoma: long-term survival does not equal cure. Surgery 2012;152(3 Suppl 1):S43–49.PubMedCentralPubMedCrossRef

29.

Hartwig W, Strobel O, Hinz U, Fritz S, Hackert T, Roth C, Buchler MW, Werner J. CA19-9 in Potentially Resectable Pancreatic Cancer: Perspective to Adjust Surgical and Perioperative Therapy. Ann Surg Oncol 18 2012.

30.

Khuri SF, Henderson WG, DePalma RG, Mosca C, Healey NA, Kumbhani DJ. Determinants of long-term survival after major surgery and the adverse effect of postoperative complications. Ann Surg 2005;242(3):326–341; discussion 341–323.PubMed

31.

Matsuda A, Matsumoto S, Seya T, Matsutani T, Kishi T, Yokoi K, Wang P, Uchida E. Does Postoperative Complication Have a Negative Impact on Long-Term Outcomes Following Hepatic Resection for Colorectal Liver Metastasis?: A Meta-Analysis. Ann Surg Oncol 2013.

32.

Howard TJ, Krug JE, Yu J, Zyromski NJ, Schmidt CM, Jacobson LE, Madura JA, Wiebke EA, Lillemoe KD. A margin-negative R0 resection accomplished with minimal postoperative complications is the surgeon's contribution to long-term survival in pancreatic cancer. J Gastrointest Surg 2006;10(10):1338–1345; discussion 1345–1336.PubMedCrossRef

33.

Kamphues C, Bova R, Schricke D, Hippler-Benscheidt M, Klauschen F, Stenzinger A, Seehofer D, Glanemann M, Neuhaus P, Bahra M. Postoperative complications deteriorate long-term outcome in pancreatic cancer patients. Ann Surg Oncol 2012;19(3):856–863.PubMedCrossRef

34.

Greenblatt DY, Kelly KJ, Rajamanickam V, Wan Y, Hanson T, Rettammel R, Winslow ER, Cho CS, Weber SM. Preoperative factors predict perioperative morbidity and mortality after pancreaticoduodenectomy. Ann Surg Oncol 2011;18(8):2126–2135.PubMedCrossRef

35.

Callery MP, Pratt WB, Kent TS, Chaikof EL, Vollmer CM, Jr. A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J Am Coll Surg 2013;216(1):1–14.PubMedCrossRef

36.

Hill JS, Zhou Z, Simons JP, Ng SC, McDade TP, Whalen GF, Tseng JF. A simple risk score to predict in-hospital mortality after pancreatic resection for cancer. Ann Surg Oncol 2010;17(7):1802–1807.PubMedCrossRef

37.

Pratt W, Joseph S, Callery MP, Vollmer CM, Jr. POSSUM accurately predicts morbidity for pancreatic resection. Surgery 2008;143(1):8–19.PubMedCrossRef

38.

Bilimoria KY, Bentrem DJ, Ko CY, Stewart AK, Winchester DP, Talamonti MS. National failure to operate on early stage pancreatic cancer. Ann Surg 2007;246(2):173–180.PubMedCrossRef

39.

Strasberg SM, Linehan DC, Hawkins WG. The accordion severity grading system of surgical complications. Ann Surg 2009;250(2):177–186.PubMedCrossRef

Title: Treatment Sequencing for Resectable Pancreatic Cancer: Influence of Early Metastases and Surgical Complications on Multimodality Therapy Completion and Survival
Authors: Ching-Wei D. Tzeng
Hop S. Tran Cao
Jeffrey E. Lee
Peter W. T. Pisters
Gauri R. Varadhachary
Robert A. Wolff
James L. Abbruzzese
Christopher H. Crane
Douglas B. Evans
Huamin Wang
Daniel E. Abbott
Jean-Nicolas Vauthey
Thomas A. Aloia
Jason B. Fleming
Matthew H. G. Katz
Publication date: 01-01-2014
Publisher: Springer US
Published in: Journal of Gastrointestinal Surgery / Issue 1/2014
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-013-2412-1

At a glance: The STEP trials

Springer Medicine

Treatment Sequencing for Resectable Pancreatic Cancer: Influence of Early Metastases and Surgical Complications on Multimodality Therapy Completion and Survival

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2014

Perineal Wound Healing Following Ileoanal Pouch Excision

Laparoscopic Heller Myotomy Can Be Used As Primary Therapy for Esophageal Achalasia Regardless of Age

Impact of Thoracic Recurrent Laryngeal Node Dissection: 508 Patients with Tri-Incisional Esophagectomy

Modern Chemotherapy Mitigates Adverse Prognostic Effect of Regional Nodal Metastases in Stage IV Colorectal Cancer

Morbidity and Mortality after Pancreaticoduodenectomy in Patients with Borderline Resectable Type C Clinical Classification

Idiopathic Pulmonary Fibrosis and Gastroesophageal Reflux. Implications for Treatment