Journal of Clinical Oncology, Vol 15, 928-937, Copyright © 1997 by American Society of Clinical Oncology

ARTICLES

Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas

FR Spitz, JL Abbruzzese, JE Lee, PW Pisters, AM Lowy, CJ Fenoglio, KR Cleary, NA Janjan, MS Goswitz, TA Rich and DB Evans
Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

PURPOSE: The effects of preoperative versus postoperative fluorouracil (5-FU)-based chemotherapy and irradiation on treatment toxicity, duration of treatment, tumor recurrence, and survival were compared in patients who underwent potentially curative therapy for adenocarcinoma of the pancreatic head during a 5-year period. METHODS: From July 1990 to July 1995, 142 patients with localized adenocarcinoma of the pancreatic head deemed resectable on the basis of radiographic images were treated with curative intent using a multimodality approach involving either preoperative or postoperative chemoradiation. Patients with biopsy confirmation of adenocarcinoma and a low-density mass in the pancreatic head identified by computed tomography (CT) received preoperative chemoradiation. Patients without a mass on CT or in whom the preoperative biopsy was negative underwent pancreaticoduodenectomy with planned postoperative chemoradiation. Protocol-based preoperative chemoradiation consisted of external-beam irradiation at a dose of 50.4 Gy (standard fractionation; 1.8 Gy/d, 5 d/wk) or 30 Gy (rapid fractionation; 3 Gy/d, 5 d/wk) combined with continuous infusion 5-FU (300 mg/m2/d, 5 d/wk). Postoperative chemoradiation combined 50.4 Gy of external-beam irradiation (standard fractionation) with continuous- infusion 5-FU. RESULTS: No patient who received preoperative chemoradiation experienced a delay in surgery because of chemoradiation toxicity, but six of 25 eligible patients (24%) did not receive postoperative chemoradiation because of delayed recovery after pancreaticoduodenectomy. No significant differences in toxicities from chemoradiation were observed between groups. Patients treated with rapid-fractionation preoperative chemoradiation had a significantly (P < .01) shorter duration of treatment (median, 62.5 days) compared with patients who received postoperative chemoradiation (median, 98.5 days) or standard-fractionation preoperative chemoradiation (median, 91.0 days). At a median followup of 19 months, no significant differences in survival were observed between treatment groups. No patient who received preoperative chemoradiation and pancreaticoduodenectomy experienced a local recurrence; peritoneal (regional) recurrence occurred in 10% of these patients. Local or regional recurrence occurred in 21% of patients who received pancreaticoduodenectomy and postoperative chemoradiation. CONCLUSION: Delivery of preoperative and postoperative chemoradiation in patients who underwent potentially curative pancreaticoduodenectomy for adenocarcinoma of the pancreatic head resulted in similar treatment toxicity, patterns of tumor recurrence, and survival. Rapid-fractionation preoperative chemoradiation ensured the delivery of all components of therapy to all eligible patients with a significantly shorter duration of treatment than with standard-fractionation chemoradiation given either before or after pancreaticoduodenectomy. Prolonged recovery after pancreaticoduodenectomy prevents the delivery of postoperative adjuvant chemoradiation in up to one fourth of eligible patients.

This article has been cited by other articles:

				R. A. Wolff, G. R. Varadhachary, and D. B. Evans Adjuvant Therapy for Adenocarcinoma of the Pancreas: Analysis of Reported Trials and Recommendations for Future Progress Ann. Surg. Oncol., October 1, 2008; 15(10): 2773 - 2786. [Abstract] [Full Text] [PDF]

				D. B. Evans, G. R. Varadhachary, C. H. Crane, C. C. Sun, J. E. Lee, P. W.T. Pisters, J.-N. Vauthey, H. Wang, K. R. Cleary, G. A. Staerkel, et al. Preoperative Gemcitabine-Based Chemoradiation for Patients With Resectable Adenocarcinoma of the Pancreatic Head J. Clin. Oncol., July 20, 2008; 26(21): 3496 - 3502. [Abstract] [Full Text] [PDF]

				H. Furukawa, K. Uesaka, and N. Boku Treatment Decision Making in Pancreatic Adenocarcinoma: Multidisciplinary Team Discussion With Multidetector-Row Computed Tomography Arch Surg, March 1, 2008; 143(3): 275 - 280. [Abstract] [Full Text] [PDF]

				A. Sa Cunha, A. Rault, C. Beau, C. Laurent, D. Collet, and B. Masson A Single-Institution Prospective Study of Laparoscopic Pancreatic Resection Arch Surg, March 1, 2008; 143(3): 289 - 295. [Abstract] [Full Text] [PDF]

				W. Small Jr, J. Berlin, G. M. Freedman, T. Lawrence, M. S. Talamonti, M. F. Mulcahy, A. B. Chakravarthy, A. A. Konski, M. M. Zalupski, P. A. Philip, et al. Full-Dose Gemcitabine With Concurrent Radiation Therapy in Patients With Nonmetastatic Pancreatic Cancer: A Multicenter Phase II Trial J. Clin. Oncol., February 20, 2008; 26(6): 942 - 947. [Abstract] [Full Text] [PDF]

				D. H. Palmer, D. D. Stocken, H. Hewitt, C. E. Markham, A. B. Hassan, P. J. Johnson, J. A. C. Buckels, and S. R. Bramhall A Randomized Phase 2 Trial of Neoadjuvant Chemotherapy in Resectable Pancreatic Cancer: Gemcitabine Alone Versus Gemcitabine Combined with Cisplatin Ann. Surg. Oncol., July 1, 2007; 14(7): 2088 - 2096. [Abstract] [Full Text] [PDF]

				R. R. White, M. W. Kattan, J. C. Haney, B. M. Clary, T. N. Pappas, D. S. Tyler, and M. F. Brennan Evaluation of Preoperative Therapy for Pancreatic Cancer Using a Prognostic Nomogram Ann. Surg. Oncol., November 1, 2006; 13(11): 1485 - 1492. [Abstract] [Full Text] [PDF]

				P. Massucco, L. Capussotti, A. Magnino, E. Sperti, M. Gatti, A. Muratore, E. Sgotto, P. Gabriele, and M. Aglietta Pancreatic Resections after Chemoradiotherapy for Locally Advanced Ductal Adenocarcinoma: Analysis of Perioperative Outcome and Survival Ann. Surg. Oncol., September 1, 2006; 13(9): 1201 - 1208. [Abstract] [Full Text] [PDF]

				G. R. Varadhachary, E. P. Tamm, J. L. Abbruzzese, H. Q. Xiong, C. H. Crane, H. Wang, J. E. Lee, P. W. T. Pisters, D. B. Evans, and R. A. Wolff Borderline Resectable Pancreatic Cancer: Definitions, Management, and Role of Preoperative Therapy Ann. Surg. Oncol., August 1, 2006; 13(8): 1035 - 1046. [Abstract] [Full Text] [PDF]

				M Hartel, F F di Mola, F Selvaggi, G Mascetta, M N Wente, K Felix, N A Giese, U Hinz, P Di Sebastiano, M W Buchler, et al. Vanilloids in pancreatic cancer: potential for chemotherapy and pain management Gut, April 1, 2006; 55(4): 519 - 528. [Abstract] [Full Text] [PDF]

				M. S. Talamonti, W. Small Jr., M. F. Mulcahy, J. D. Wayne, V. Attaluri, L. M. Colletti, M. M. Zalupski, J. P. Hoffman, G. M. Freedman, T. J. Kinsella, et al. A Multi-Institutional Phase II Trial of Preoperative Full-Dose Gemcitabine and Concurrent Radiation for Patients With Potentially Resectable Pancreatic Carcinoma Ann. Surg. Oncol., February 1, 2006; 13(2): 150 - 158. [Abstract] [Full Text] [PDF]

				J. Hoffman Does Prior Adjuvant Chemoradiotherapy Lead to a Safer Pancreatoduodenectomy? Ann. Surg. Oncol., January 1, 2006; 13(1): 7 - 9. [Full Text] [PDF]

				T.-Y. Cheng, K. Sheth, R. R. White, T. Ueno, C.-F. Hung, B. M. Clary, T. N. Pappas, and D. S. Tyler Effect of Neoadjuvant Chemoradiation on Operative Mortality and Morbidity for Pancreaticoduodenectomy Ann. Surg. Oncol., January 1, 2006; 13(1): 66 - 74. [Abstract] [Full Text] [PDF]

				J. M. Pipas, R. J. Barth Jr., B. Zaki, M. J. Tsapakos, A. A. Suriawinata, M. A. Bettmann, J. M. Cates, G. H. Ripple, J. E. Sutton, S. R. Gordon, et al. Docetaxel/Gemcitabine Followed by Gemcitabine and External Beam Radiotherapy in Patients With Pancreatic Adenocarcinoma Ann. Surg. Oncol., December 1, 2005; 12(12): 995 - 1004. [Abstract] [Full Text] [PDF]

				G. Y. Yang, T. D. Wagner, M. Fuss, and C. R. Thomas Jr. Multimodality Approaches for Pancreatic Cancer CA Cancer J Clin, November 1, 2005; 55(6): 352 - 367. [Abstract] [Full Text] [PDF]

				H. Ohigashi, O. Ishikawa, H. Eguchi, Y. Sasaki, T. Yamada, S. Noura, K. Murata, K. Takachi, I. Miyashiro, Y. Doki, et al. Feasibility and Efficacy of Combination Therapy With Preoperative and Postoperative Chemoradiation, Extended Pancreatectomy, and Postoperative Liver Perfusion Chemotherapy for Locally Advanced Cancers of the Pancreatic Head Ann. Surg. Oncol., August 1, 2005; 12(8): 629 - 636. [Abstract] [Full Text] [PDF]

				D. P. Ryan, C. Fernandez-del Castillo, C. G. Willett, W. R. Brugge, D. Sahani, and E. F. Brachtel Case 20-2005 - A 58-Year-Old Man with Locally Advanced Pancreatic Cancer N. Engl. J. Med., June 30, 2005; 352(26): 2734 - 2741. [Full Text] [PDF]

				R. R. White, H. B. Xie, M. R. Gottfried, B. G. Czito, H. I. Hurwitz, M. A. Morse, G. C. Blobe, E. K. Paulson, J. Baillie, M. S. Branch, et al. Significance of Histological Response to Preoperative Chemoradiotherapy for Pancreatic Cancer Ann. Surg. Oncol., March 1, 2005; 12(3): 214 - 221. [Abstract] [Full Text] [PDF]

				A. G. Morganti, M. G. Brizi, G. Macchia, G. Sallustio, G. Costamagna, S. Alfieri, G. C. Mattiucci, V. Valentini, L. Natale, F. Deodato, et al. The Prognostic Effect of Clinical Staging in Pancreatic Adenocarcinoma Ann. Surg. Oncol., February 1, 2005; 12(2): 145 - 151. [Abstract] [Full Text] [PDF]

				M. G. Schlieman, H. S. Ho, and R. J. Bold Utility of Tumor Markers in Determining Resectability of Pancreatic Cancer Arch Surg, September 1, 2003; 138(9): 951 - 956. [Abstract] [Full Text] [PDF]

				J. P. Neoptolemos, D. Cunningham, H. Friess, C. Bassi, D. D. Stocken, D. M. Tait, J. A. Dunn, C. Dervenis, F. Lacaine, H. Hickey, et al. Adjuvant therapy in pancreatic cancer: historical and current perspectives Ann. Onc., May 1, 2003; 14(5): 675 - 692. [Abstract] [Full Text] [PDF]

				K. C. Conlon and R. L. McMahon Minimally Invasive Surgery in the Diagnosis and Treatment of Upper Gastrointestinal Tract Malignancy Ann. Surg. Oncol., October 1, 2002; 9(8): 725 - 737. [Full Text] [PDF]

				J. D. Wayne, E. K. Abdalla, R. A. Wolff, C. H. Crane, P. W.T. Pisters, and D. B. Evans Localized Adenocarcinoma of the Pancreas: The Rationale for Preoperative Chemoradiation Oncologist, February 1, 2002; 7(1): 34 - 45. [Abstract] [Full Text] [PDF]

				R. R. White, H. I. Hurwitz, M. A. Morse, C. Lee, M. S. Anscher, E. K. Paulson, M. R. Gottfried, J. Baillie, M. S. Branch, P. S. Jowell, et al. Neoadjuvant Chemoradiation for Localized Adenocarcinoma of the Pancreas Ann. Surg. Oncol., December 1, 2001; 8(10): 758 - 765. [Abstract] [Full Text] [PDF]

				R. A. Wolff, D. B. Evans, D. M. Gravel, R. Lenzi, P. W. T. Pisters, J. E. Lee, N. A. Janjan, C. Charnsangavej, and J. L. Abbruzzese Phase I Trial of Gemcitabine Combined with Radiation for the Treatment of Locally Advanced Pancreatic Adenocarcinoma Clin. Cancer Res., August 1, 2001; 7(8): 2246 - 2253. [Abstract] [Full Text] [PDF]

				T. M. Breslin, K. R. Hess, D. B. Harbison, M. E. Jean, K. R. Cleary, A. P. Dackiw, R. A. Wolff, J. L. Abbruzzese, N. A. Janjan, C. H. Crane, et al. Neoadjuvant Chemoradiotherapy for Adenocarcinoma of the Pancreas: Treatment Variables and Survival Duration Ann. Surg. Oncol., March 1, 2001; 8(2): 123 - 132. [Abstract] [Full Text] [PDF]

				P. W. T. Pisters, W. A. Hudec, J. E. Lee, I. Raijman, S. Lahoti, N. A. Janjan, T. A. Rich, C. H. Crane, R. Lenzi, R. A. Wolff, et al. Preoperative Chemoradiation for Patients With Pancreatic Cancer: Toxicity of Endobiliary Stents J. Clin. Oncol., February 14, 2000; 18(4): 860 - 860. [Abstract] [Full Text] [PDF]

				H. J. Wanebo, A. S. Glicksman, M. P. Vezeridis, J. Clark, L. Tibbetts, R. J. Koness, and A. Levy Preoperative Chemotherapy, Radiotherapy, and Surgical Resection of Locally Advanced Pancreatic Cancer Arch Surg, January 1, 2000; 135(1): 81 - 87. [Abstract] [Full Text] [PDF]

				H. Kuniyasu, L. M. Ellis, D. B. Evans, J. L. Abbruzzese, C. J. Fenoglio, C. D. Bucana, K. R. Cleary, E. Tahara, and I. J. Fidler Relative Expression of E-Cadherin and Type IV Collagenase Genes Predicts Disease Outcome in Patients with Resectable Pancreatic Carcinoma Clin. Cancer Res., January 1, 1999; 5(1): 25 - 33. [Abstract] [Full Text] [PDF]

				D. P. Ryan and M. L. Grossbard Pancreatic Cancer: Local Success and Distant Failure Oncologist, June 1, 1998; 3(3): 178 - 188. [Abstract] [Full Text]