Tara M. Breslin, Nora A. Janjan, Jeffrey E. Lee, Peter W. T. Pisters, Robert A. Wolff, James L. Abbruzzese, Douglas B. Evans

Pancreatic Tumor Study Group: Departments of Surgical Oncology (TMB, JEL, PWTP, DBE), Radiation Oncology (NAJ), and Gastrointestinal Oncology and Digestive Diseases (RAW, JLA), The University of Texas M. D. Anderson Cancer Center, Houston, TX

Received 6/4/98 Accepted 5/5/98

2. INTRODUCTION

Clinical research in pancreatic adenocarcinoma at the University of Texas M. D. Anderson Cancer Center (MDACC) has focused on the development of treatment strategies to improve local-regional tumor control, minimize treatment related toxicity, and maximize survival duration for patients with potentially resectable disease.

Patients who undergo pancreaticoduodenectomy alone for adenocarcinoma of the pancreatic head or uncinate process have a median survival of 12 months, and a high incidence of local tumor recurrence (50% - 80%) due to the common finding of positive margins following pathologic evaluation of pancreaticoduodenectomy specimens (1). The available prospective and retrospective data suggests improved survival duration and local regional tumor control when pancreaticoduodenectomy is combined with 5-FU–based chemoradiation as shown in table 1 (2-8). However, the morbidity and prolonged recovery associated with pancreaticoduodenectomy frequently prevents the timely delivery of postoperative chemoradiation (8,9). The risk of delaying postoperative adjuvant chemoradiation, combined with small published experiences of successful pancreatic resection following radiation therapy alone, prompted investigators at the MDACC to initiate studies in which chemoradiation was given before pancreaticoduodenectomy for patients with potentially resectable adenocarcinoma of the pancreas. The preoperative use of chemoradiation is supported by the following considerations: 1) The high frequency of positive-margin resections recently reported supports the concern that the retroperitoneal margin of excision, even when negative, may be only a few millimeters (10); surgery alone may therefore be an inadequate strategy for local tumor control. 2) Patients with disseminated disease evident on restaging studies after chemoradiation will not be subjected to laparotomy. 3) Because radiation therapy and chemotherapy will be given first, delayed postoperative recovery will have no effect on the delivery of multimodality therapy. 4) The preoperative delivery of chemoradiation does not increase perioperative morbidity or mortality in patients who undergo pancreaticoduodenectomy and in fact, recent data suggests that preoperative chemoradiation may decrease the incidence of pancreaticojejunal anastomotic fistula the most common complication following pancreaticoduodenectomy(11).

Abbreviations: EBRT, external-beam radiation therapy; 5-FU, 5-fluorouracil; Mito-C, mitomycin C.*All patients underwent a pancreatectomy with curative intent.

Critical to the accurate analysis of preoperative or postoperative adjuvant therapy is the incorporation of a standardized approach to patient selection (pretreatment staging), operative technique, and pathologic evaluation of surgical specimens. Standardization of these important variables is necessary to make accurate comparisons between treatment groups. Lack of precise definitions of patient groups has made much of the available data on the use of multimodality therapy for pancreatic cancer difficult to interpret. Therefore, we will briefly outline the radiographic staging, surgical technique, and pathologic evaluation of the resected specimen which are critical to the conduct of clinical trials examining the use of innovative multimodality therapies. This review will focus on current and future neoadjuvant chemoradiation strategies for patients with potentially resectable adenocarcinoma of the pancreas.