Preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for adenocarcinoma of the pancreatic head

BACKGROUND: Local recurrence in the bed of the resected pancreas is the most common site of tumor recurrence following a standard pancreaticoduodenectomy (PD) for adenocarcinoma of the pancreatic head. In an attempt to improve local and regional disease control and thereby enhance the quality and length of survival in patients undergoing potentially curative PD, we have used a protocol of preoperative multi-modality therapy. PATIENTS AND METHODS: All patients were treated with external-beam radiation (30.0 or 50.4 Gy) and concomitant 5-fluorouracil (300 mg/m² per day) prior to PD. Electron-beam intraoperative radiation therapy was given to the bed of the resected pancreas before reconstruction. Patients were assessed for recurrence by physical examination, chest roentgenography, and computed tomography scan performed at 3-month intervals following treatment. RESULTS: Thirty-nine patients completed all therapy; 1 perioperative death occurred. Thirty-eight tumor recurrences have been documented in 29 patients at a median of 11 months from the date of diagnosis; 23 patients died of disease. The liver was the most frequent site of recurrence, and liver metastases were a component of treatment failure in 53% of patients. Isolated local or peritoneal recurrences were documented in only 4 patients (11%). The only significant clinical or pathologic variable predictive of local-regional recurrence was a previous laparotomy and intra-operative biopsy. The median survival of all 39 patients was 19 months, and the 4-year actuarial survival rate was 19%. CONCLUSIONS: Preoperative chemoradiation, PD, and electron-beam intraoperative radiation therapy for adenocarcinoma of the pancreatic head have resulted in improved local-regional tumor control, with distant metastatic disease becoming the predominant site of tumor recurrence. Future treatment stategies should incorporate effective multimodality therapy for local-regional disease as demonstrated in this study. Major improvements in overall survival will likely await the development of systemic or regional therapy for liver metastases.