Journal of Clinical Oncology, Vol 16, 3843-3850, Copyright © 1998 by American Society of Clinical Oncology

ARTICLES

Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma

PW Pisters, JL Abbruzzese, NA Janjan, KR Cleary, C Charnsangavej, MS Goswitz, TA Rich, I Raijman, RA Wolff, R Lenzi, JE Lee and DB Evans
University of Texas M.D. Anderson Cancer Center Pancreatic Tumor Study Group, Houston 77030, USA. ppisters@notes.mdacc.tmc.edu

PURPOSE: To evaluate the toxicities, radiographic and pathologic responses, and event-free outcomes with combined modality treatment that involves preoperative rapid-fractionation chemoradiation, pancreaticoduodenectomy, and electron-beam intraoperative radiation therapy (EB-IORT) for patients with resectable pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients with radiographically resectable localized adenocarcinoma of the pancreatic head were entered onto a preoperative protocol that consisted of a 2-week course of fluorouracil (5-FU) 300 mg/m2 daily 5 days per week and concomitant rapid-fractionation radiation 30 Gy, 3 Gy daily 5 days per week. Radiographic restaging was performed 4 weeks after chemoradiation, and patients with localized disease underwent pancreaticoduodenectomy with EB-IORT 10 to 15 Gy. RESULTS: Thirty-five patients were entered onto the study and completed chemoradiation, 34 (97%) as outpatients. Three patients (9%) experienced grade 3 nausea and vomiting; no other grade 3 or 4 toxicities were observed. Of the 27 patients taken to surgery, 20 patients (74%) underwent pancreaticoduodenectomy with EB-IORT. All patients had a less than grade III pathologic response to preoperative chemoradiation. At a median follow-up of 37 months, the 3-year survival rate in patients who underwent combined modality therapy was 23%. CONCLUSION: Combined modality treatment with preoperative rapid- fractionation chemoradiation, pancreaticoduodenectomy, and EB-IORT is associated with minimal toxicity and excellent locoregional control. This represents one approach to maximize the proportion of patients who receive all components of combined modality therapy and avoids the toxicity of pancreaticoduodenectomy in patients found to have metastatic disease at the time of restaging.

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]

				G. R. Varadhachary, R. A. Wolff, C. H. Crane, C. C. Sun, J. E. Lee, P. W.T. Pisters, J.-N. Vauthey, E. Abdalla, H. Wang, G. A. Staerkel, et al. Preoperative Gemcitabine and Cisplatin Followed by Gemcitabine-Based Chemoradiation for Resectable Adenocarcinoma of the Pancreatic Head J. Clin. Oncol., July 20, 2008; 26(21): 3487 - 3495. [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]

				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]

				A. S. Caudle, J. E. Tepper, B. F. Calvo, M. O. Meyers, L. K. Goyal, W. G. Cance, and H. J. Kim Complications Associated with Neoadjuvant Radiotherapy in the Multidisciplinary Treatment of Retroperitoneal Sarcomas Ann. Surg. Oncol., February 1, 2007; 14(2): 577 - 582. [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]

				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]

				P. W. T. Pisters, R. A. Wolff, N. A. Janjan, K. R. Cleary, C. Charnsangavej, C. N. Crane, R. Lenzi, J. Nicolas Vauthey, J. E. Lee, J. L. Abbruzzese, et al. Preoperative Paclitaxel and Concurrent Rapid-Fractionation Radiation for Resectable Pancreatic Adenocarcinoma: Toxicities, Histologic Response Rates, and Event-Free Outcome J. Clin. Oncol., May 15, 2002; 20(10): 2537 - 2544. [Abstract] [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. A. Wolff Neoadjuvant Chemoradiation for Localized Adenocarcinoma of the Pancreas: Great Logic, Grim Reality Ann. Surg. Oncol., December 1, 2001; 8(10): 747 - 748. [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]

				C. J. McGinn, M. M. Zalupski, I. Shureiqi, J. M. Robertson, F. E. Eckhauser, D. C. Smith, D. Brown, G. Hejna, M. Strawderman, D. Normolle, et al. Phase I Trial of Radiation Dose Escalation With Concurrent Weekly Full-Dose Gemcitabine in Patients With Advanced Pancreatic Cancer J. Clin. Oncol., November 15, 2001; 19(22): 4202 - 4208. [Abstract] [Full Text]

				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]

				H. Ohigashi, O. Ishikawa, Y. Sasaki, T. Yamada, H. Furukawa, S. Imaoka, T. Kasugai, S. Ishiguro, K. Ueda, Y. Miyoshi, et al. K-ras Point Mutation in the Nerve Plexuses Around the Superior Mesenteric Artery in Resectable Adenocarcinoma of the Pancreatic Head: Distribution Pattern and Related Factors Arch Surg, December 1, 2000; 135(12): 1450 - 1455. [Abstract] [Full Text] [PDF]