Resection Status, Age and Nodal Involvement Determine Survival among Patients Receiving Adjuvant Chemoradiotherapy in Pancreatic Adenocarcinoma
Abstract
Context Pancreas cancer can potentially be cured by resection, but the role of adjuvant chemotherapy and/or chemoradiation has been controversial. Objectives To better define clinicopathological factors that may serve as predictive and/or prognostic variables. Patients Between 1984 and 2006, we retrospectively analyzed 91 patients with pancreas cancer treated with pancreaticoduodenectomy or total pancreatectomy followed by adjuvant 5-fluorouracil-based chemoradiation at the University of Pennsylvania. Final pathological coding including margin status was confirmed by a pathologist. Interventions Patients were treated with 48.6 to 63.0 Gy, and 96.7% completed their prescribed radiation dose. Main outcome measures The prognostic significance of demographic factors, stage, year of surgery, tumor location, grade, resection status, and number of positive lymph nodes on overall survival were examined. Results With a median follow-up of 6.5 years, the overall median survival was 2.3 years (95% CI 1.5-3.2 years), and the 5-year overall survival was 28.9%. In multivariate analysis, completeness of resection (P<0.001), fewer number of positive lymph nodes (0 vs. 1-2 vs. 3 or more) (P=0.004), and age less than, or equal to, 60 years (P=0.006) were all independently associated with improved overall survival. The overall survival reported in this study compares favorably with the results of other single-institution studies and with the RTOG 97-04 trial. Conclusions Adjuvant 5-FU-based chemoradiation following radical pancreatectomy can be delivered safely and results in comparatively good overall survival. The results of this analysis underscore the importance of resection status, number of involved lymph nodes and patient age as prognostic characteristics. These factors may be considered stratification variables for future post-pancreatectomy adjuvant therapy trials.
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Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 1985; 120:899-903. [PMID 4015380]
Whittington R, Bryer MP, Haller DG, Solin LJ, Rosato EF. Adjuvant therapy of resected adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys 1991; 21:1137-43. [PMID 1938511]
Neuhaus P, Riess H, Post S, Gellert K, Ridwelski K, Schramm H, et al. CONKO-001: Final results of the randomized, prospective, multicenter phase III trial of adjuvant chemotherapy with gemcitabine versus observation in patients with resected pancreatic cancer. J Clin Oncol 2008; 26(15 Suppl):LBA4504.
Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, 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. [PMID 17227978]
Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004; 350:1200-10. [PMID 15028824]
Cardenes HR, Powell M, Loehrer PJ, Wagner LI, Cella DF, Brell J, et al. E4201: Randomized phase II study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with locally advanced, unresectable, pancreatic cancer (LAPC): Quality-of-life (QOL) analysis. J Clin Oncol 2009; 27(15 Suppl):4627.
Abrams RA. Comment on 'adjuvant therapy in pancreatic cancer: a critical appraisal'. Drugs 2007; 67:2481-5. [PMID 18034585]
Abrams RA, Lillemoe KD, Piantadosi S. Continuing controversy over adjuvant therapy of pancreatic cancer. Lancet 2001; 358:1565-6. [PMID 11716876]
Choti MA. Adjuvant therapy for pancreatic cancer--the debate continues. N Engl J Med 2004; 350:1249-51. [PMID 15028829]
Garofalo MC, Regine WF, Tan MT. On statistical reanalysis, the EORTC trial is a positive trial for adjuvant chemoradiation in pancreatic cancer. Ann Surg 2006; 244:332-3. [PMID 16858208]
Koshy MC, Landry JC, Cavanaugh SX, Fuller CD, Willett CG, Abrams RA, et al. A challenge to the therapeutic nihilism of ESPAC-1. Int J Radiat Oncol Biol Phys 2005; 61:965-6. [PMID 15752874]
Oettle H, Neuhaus P. Adjuvant therapy in pancreatic cancer: a critical appraisal. Drugs 2007; 67:2293-310. [PMID 17983252]
Chang DK, Johns AL, Merrett ND, Gill AJ, Colvin EK, Scarlett CJ, et al. Margin clearance and outcome in resected pancreatic cancer. J Clin Oncol 2009; 27:2855-62. [PMID 19398572]
Corsini MM, Miller RC, Haddock MG, Donohue JH, Farnell MB, Nagorney DM, et al. Adjuvant radiotherapy and chemotherapy for pancreatic carcinoma: the Mayo Clinic experience (1975-2005). J Clin Oncol 2008; 26:3511-6. [PMID 18640932]
Herman JM, Swartz MJ, Hsu CC, Winter J, Pawlik TM, Sugar E, et al. Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital. J Clin Oncol 2008; 26:3503-10. [PMID 18640931]
Fortner JG, Klimstra DS, Senie RT, Maclean BJ. Tumor size is the primary prognosticator for pancreatic cancer after regional pancreatectomy. Ann Surg 1996; 223:147-53. [PMID 8597508]
Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg 1993; 165:68-72. [PMID 8380315]
Neoptolemos JP, Stocken DD, Dunn JA, Almond J, Beger HG, Pederzoli P, 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. [PMID 11729382]
Wenger FA, Peter F, Zieren J, Steiert A, Jacobi CA, Müller JM. Prognosis factors in carcinoma of the head of the pancreas. Dig Surg 2000; 17:29-35. [PMID 10720829]
Klinkenbijl JH, Jeekel J, Sahmoud T, van Pel R, Couvreur ML, Veenhof CH, et al. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg 1999; 230:776-82. [PMID 10615932]
Picozzi VJ, Traverso LW, O'Reilly EM, Greeno E, Martin RC, Wilfond LS, et al. ACOSOG Z05031: Report on a multicenter, phase II trial for adjuvant therapy of resected pancreatic cancer using cisplatin, 5-FU, and alpha-interferon. J Clin Oncol 2008; 26(15 Suppl):4505. ]
Picozzi VJ, Kozarek RA, Traverso LW. Interferon-based adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic adenocarcinoma. Am J Surg 2003; 185:476-80. [PMID 12727570]
Wilson VC, Guo M, Hampshire M, O'Dwyer P, Sun W, Drebin J, et al. Aggressive supportive care improves outcomes in the combined modality treatment of pancreatic and duodenal cancer. Int J Radiat Oncol Biol Phys 2007; 69:S278-9.
Van Laethem J, Hammel P, Mornex F, Azria D, Van Tienhoven G, Peeters M, et al. Adjuvant chemotherapy alone versus chemoradiation after curative resection for pancreatic cancer : feasibility results of a randomised EORTC/FFCD/GERCOR phase II/III study (40013/22012/0304). J Clin Oncol 2008; 26(15 Suppl):4514.
Berger AC, Garcia M Jr, Hoffman JP, Regine WF, Abrams RA, Safran H, 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. [PMID 19029412]
Boeck S, Schulz C, Stieber P, Holdenrieder S, Weckbach S, Heinemann V. Assessing prognosis in metastatic pancreatic cancer by the serum tumor marker CA 19-9: pretreatment levels or kinetics during chemotherapy? Onkologie 2007; 30:39-42. [PMID 17264524]
Boeck S, Stieber P, Holdenrieder S, Wilkowski R, Heinemann V. Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer. Oncology 2006; 70:255-64. [PMID 16899980]
Ferrone CR, Finkelstein DM, Thayer SP, Muzikansky A, Fernandez-delCastillo C, Warshaw AL. Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma. J Clin Oncol 2006; 24:2897-902. [PMID 16782929]
Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer 1987; 59:2006-10. [PMID 3567862]
Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, et al. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA 2008; 299:1019-26. [PMID 18319412]
Sohn TA, Yeo CJ, Cameron JL, Koniaris L, Kaushal S, Abrams RA, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg 2000; 4:567-79. [PMID 11307091]
Whittington R, Neuberg D, Tester WJ, Benson AB 3rd, Haller DG. Protracted intravenous fluorouracil infusion with radiation therapy in the management of localized pancreaticobiliary carcinoma: a phase I Eastern Cooperative Oncology Group Trial. J Clin Oncol 1995; 13:227-32. [PMID 7799024]
Yeo CJ, Abrams RA, Grochow LB, Sohn TA, Ord SE, Hruban RH, et al. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 1997; 225:621-33. [PMID 9193189]
Copyright (c) 2014 Drew Moghanaki, Rosemarie Mick, Emma Elizabeth Furth, Davendra Sohal, Patricia M Salmon, Ali Behbahani, Alicia K Morgans, Seth M Miller, Bruce J Giantonio, Richard W Whittington, Daniel G Haller, Ernest F Rosato, John P Plastaras
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