Treatment of potentially resectable disease
TUMORS OF THE PANCREATIC BODY AND TAIL
Because adenocarcinomas of the pancreatic body and tail do not cause obstruction of the intrapancreatic portion of the common bile duct, early diagnosis is rare; virtually all patients have locally advanced or metastatic disease at the time of diagnosis. CT provides an excellent assessment of the relationship of the tumor to the celiac axis and the SMA origin. Arterial encasement is present in most patients, except for the anecdotal patient who presents with upper gastrointestinal hemorrhage resulting from sinistral hypertension secondary to splenic vein occlusion by a small tumor. In the rare patient who appears to have resectable disease (no arterial encasement and no extrapancreatic disease), laparoscopy before laparotomy is a logical approach because peritoneal metastases are frequently found. The scant data available regarding surgical resection confirm the short survival and poor prognosis in this subgroup of patients. Further, the high 30-day hospital mortality rate (43%; 6 of 14 patients with adenocarcinoma) reported in a study from the Department of Veterans Affairs hospitals suggests that many of the patients taken to surgery have advanced disease and a poor performance status. Accurate preoperative imaging and a selective approach to surgical therapy will minimize treatment-related morbidity and mortality and maximize the length and quality of patient survival.
TREATMENT OF POTENTIALLY RESECTABLE DISEASE
PREOPERATIVE AND POSTOPERATIVE CHEMORADIATION
External-beam radiation therapy (EBRT) and concomitant 5-FU chemotherapy (chemoradiation) were shown to prolong survival in patients with locally advanced adenocarcinoma of the pancreas. Those data were the foundation for a prospective randomized study of adjuvant chemoradiation (500 mg/m2 /d 5-FU for 6 days and 40 Gy of radiation) following pancreaticoduodenectomy conducted by the Gastrointestinal Tumor Study Group (GITSG); that trial also demonstrated a survival advantage from multimodality therapy compared with resection alone. However, because of a prolonged recovery, 5 (24%) of the 21 patients in the adjuvant chemoradiation arm could not begin chemoradiation until more than 10 weeks after pancreaticoduodenectomy.
Further, published studies advocating postoperative adjuvant chemoradiation are prone to selection bias; the patients likely to be considered for protocol entry are those who recover rapidly from surgery and have a good performance status.
The slow patient accrual of postoperative adjuvant therapy studies and the positive correlation of survival with performance status in the GITSG trial validate this concern. A similar selection bias is likely in effect when attempts are made to retrospectively compare patients who received postoperative adjuvant chemoradiation with patients who were treated only with pancreaticoduodenectomy. However, recently reported data from Yeo and colleagues at Johns Hopkins University add further support to the use of multimodality therapy. Those investigators reviewed all patients who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreatic head during a 4-year period. Fifty-six patients received adjuvant chemoradiation, and 22 underwent pancreaticoduodenectomy alone. Despite the chemoradiation group containing a larger percentage of patients with aneuploid tumors, median survival for that group was 20 months compared with 12 months for the group who received surgery alone.
A survival advantage was also demonstrated for patients treated with adjuvant combination chemotherapy alone (5-FU, doxorubicin, mitomycin C) after pancreatectomy. Median survival was 23 months in the 30 patients randomized to receive adjuvant therapy compared with 11 months in the 31 patients treated with surgery alone. Forty-six additional patients were ineligible following surgery, attesting to the difficulty in performing multiinstitution protocol-based research following a complex surgical procedure such as pancreaticoduodenectomy. The toxicity of the surgery and chemotherapy was significant; only 24 of 30 patients received chemotherapy, and only 13 of these received all 6 planned courses of chemotherapy. A previous pilot study of adjuvant 5-FU, doxorubicin, and mitomycin C, using a different schedule of administration, found similar toxicity and therefore questioned the use of adjuvant combination chemotherapy, of even moderate toxicity, after pancreatectomy.