The risk of delaying adjuvant therapy, combined with small published experiences of successful pancreatic resection following external-beam radiation therapy, prompted us to initiate a study in which chemoradiation was given before pancreaticoduodenectomy for patients with potentially resectable adenocarcinoma of the pancreas.

The use of preoperative chemoradiation is supported by the following considerations:

because radiation therapy and chemotherapy will be given first, delayed recovery from surgery will have no effect on the delivery of multimodality therapy, a frequent problem in postoperative adjuvant therapy studies.

the high frequency of margin-positive resections recently reported supports the concern that the retroperitoneal margin of excision, even when negative, may be only a few millimeters (surgery alone may therefore be an inadequate strategy for local tumor control),

patients with disseminated disease evident on restaging studies after chemoradiation will not be subjected to laparotomy, and

preoperative chemoradiation may prevent peritoneal tumor cell implantation due to the manipulation of surgery.

We recently evaluated survival and patterns of tumor recurrence in patients treated with preoperative chemoradiation, surgery, and electron-beam intraoperative radiation therapy (EB-IORT) for adenocarcinoma of the pancreatic head. The median survival of all 39 patients was 19 months, with a median follow-up of 19 months. Thirty-eight of 39 patients were evaluable for patterns of treatment failure. Tumor recurrence was documented in 29 patients at a median of 11 months (range, 5 to 48 months) from the date of diagnosis. The median time to death after diagnosis of tumor recurrence was 3 months. Overall, there have been 38 recurrences in 29 patients: 8 (21%) were local-regional (pancreatic bed and/or peritoneal cavity), and 30 (79%) were distant (lung, liver, and/or bone). The liver was the most frequent site of tumor recurrence, and liver metastases were a component of treatment failure in 53% of all patients (70% of patients who recurred). Fourteen patients (37%) had liver metastases as their only site of recurrence. Isolated local or peritoneal recurrences were documented in only 4 patients (11%). The combination of chemoradiation, pancreaticoduodenectomy, and EB-IORT has altered patterns of treatment failure compared with surgery alone or other multimodality management regimens. The improvement in local-regional control demonstrated in our study was seen despite the fact that 14 of 38 evaluated patients had undergone laparotomy with tumor manipulation and biopsy prior to referral to our institution. If these 14 patients were excluded, only 2 patients (8%) would have experienced local or peritoneal recurrence as any component of treatment failure.

Future multimodality treatment schemas build upon this experience and attempt to shorten overall treatment time and reduce toxicity by combining more effective radiation sensitizing agents with systemic therapies designed to attack the unique biologic properties of pancreatic cancer.