Preoperative CA 19-9 level is an important prognostic factor in patients with pancreatic adenocarcinoma treated with surgical resection and adjuvant concurrent chemoradiotherapy.

OBJECTIVES: To evaluate preoperative CA 19-9 level as a prognostic factor in patients with resected adenocarcinoma of the pancreas. METHODS: We retrospectively reviewed the cases of consecutive patients with pancreatic adenocarcinoma who had CA 19-9 measured preoperatively and underwent potentially curative resection at Mayo Clinic from September 1995 to January 2005. Patients who died within 30 days of resection were excluded. RESULTS: Search of our database identified 226 consecutive patients who met all the inclusion criteria. Adjuvant therapy was concurrent chemoradiotherapy (CCRT) in 122 patients, CCRT followed by chemotherapy in 23 patients, chemotherapy alone in 6 patients, and none in 69 patients. Median follow-up for surviving patients was 2.1 years. Median survival in all patients was 1.6 years. Patients with a high preoperative CA 19-9 level (defined as ≥180 U/mL) had a greater chance of having pathologic T3-T4 disease (P=0.03), positive lymph nodes (P=0.01), and histologic grade 3 or 4 (P=0.02). In multivariate analysis, a high preoperative CA 19-9 level (P=0.006) and R1-R2 margin status (P=0.03) were associated with decreased survival. Overall survival was increased for patients who received adjuvant CCRT (vs. those who did not; P=0.002) and for patients with high preoperative CA 19-9 level who received adjuvant CCRT (vs. those who did not; P<0.001). CONCLUSIONS: In patients with resected adenocarcinoma of the pancreas, high preoperative CA 19-9 level was associated with adverse pathologic features and poorer survival. Adjuvant CCRT was associated with a significant survival benefit in patients with high preoperative CA 19-9 but not in those with low CA 19-9.

Mayo Clinic experience with very rare exocrine pancreatic neoplasms.

OBJECTIVES: Limited data are available to guide the management of very rare exocrine neoplasms of the pancreas (VREP). Available evidence suggests that VREP have different risk factors and prognoses from those of adenocarcinoma of the pancreas. The primary objectives for this study were to determine the survival, comorbidities, and response to treatment of patients seen at Mayo Clinic with VREP. METHODS: We reviewed patients from 1975 to 2005 who had VREP and compared them to patients with adenocarcinomas that were matched for TNM, grade, and decade of treatment. RESULTS: Sixty-six patients with VREP were identified. The most commonly identified neoplasms were acinar cell carcinoma (n = 15), small cell carcinoma (n = 12), and squamous cell carcinoma (n = 8). Abdominal discomfort and jaundice were the most common presenting symptoms. The median overall survival for patients with VREP, 10.4 months (range, 3.7-23 months), was better than that for matched controls, 8.2 months (range, 4-15.4 months) (P = 0.01). There was no difference in the survival of patients with stage 4 disease between cases, 8 months (range, 2.3-21.8 months), and controls, 6.7 months (range, 2.3-10.8 months) (P = 0.17). CONCLUSIONS: We present one of the largest series of VREP to date. The overall survival of all patients with VREP was better than matched controls, but no statistical difference was seen between the groups with stage 4 disease.

Adjuvant chemoradiation for pancreatic adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic collaborative study.

BACKGROUND: Survival for pancreatic ductal adenocarcinoma is low, the role of adjuvant therapy remains controversial, and recent data suggest adjuvant chemoradiation (CRT) may decrease survival compared with surgery alone. Our goal was to examine efficacy of adjuvant CRT in resected pancreatic adenocarcinoma compared with surgery alone. MATERIALS AND METHODS: Patients with pancreatic adenocarcinoma at Johns Hopkins Hospital (n = 794, 1993-2005) and Mayo Clinic (n = 478, 1985-2005) following resection who were observed (n = 509) or received adjuvant 5-FU based CRT (median dose 50.4 Gy; n = 583) were included. Cox survival and propensity score analyses assessed associations with overall survival. Matched-pair analysis by treatment group (1:1) based on institution, age, sex, tumor size/stage, differentiation, margin, and node positivity with N = 496 (n = 248 per treatment arm) was performed. RESULTS: Median survival was 18.8 months. Overall survival (OS) was longer among recipients of CRT versus surgery alone (median survival 21.1 vs. 15.5 months, P < .001; 2- and 5-year OS 44.7 vs. 34.6%; 22.3 vs. 16.1%, P < .001). Compared with surgery alone, adjuvant CRT improved survival in propensity score analysis for all patients by 33% (P < .001), with improved survival when stratified by age, margin, node, and T-stage (RR = 0.57-0.75, P < .05). Matched-pair analysis demonstrated OS was longer with CRT (21.9 vs. 14.3 months median survival; 2- and 5-year OS 45.5 vs. 31.4%; 25.4 vs. 12.2%, P < .001). CONCLUSIONS: Adjuvant CRT is associated with improved survival after pancreaticoduodenectomy. Adjuvant CRT was not associated with decreased survival in any risk group, even in propensity score and matched-pair analyses. Further studies evaluating adjuvant chemotherapy compared with adjuvant chemoradiation are needed to determine the most effective combination of systemic and local-regional therapy to achieve optimal survival results.

Review of adjuvant radiochemotherapy for resected pancreatic cancer and results from Mayo Clinic for the 5th JUCTS symposium.

PURPOSE: To present an overview of Phase III trials in adjuvant therapy for pancreatic cancer and review outcomes at the Mayo Clinic after adjuvant radiochemotherapy (RT/CT) for resected pancreatic cancer. METHODS AND MATERIALS: A literature review and a retrospective review of 472 patients who underwent an R0 resection for T1-3N0-1M0 invasive carcinoma of the pancreas from 1975 to 2005 at the Mayo Clinic, Rochester, MN. Patients with metastatic or unresectable disease at the time of surgery, positive surgical margins, or indolent tumors and those treated with intraoperative radiotherapy were excluded from the analysis. Median radiotherapy dose was 50.4 Gy in 28 fractions, with 98% of patients receiving concurrent 5-fluorouracil- based chemotherapy. RESULTS: Median follow-up was 2.7 years. Median overall survival (OS) was 1.8 years. Median OS after adjuvant RT/CT was 2.1 vs. 1.6 years for surgery alone (p = 0.001). The 2-y OS was 50% vs. 39%, and 5-y was 28% vs. 17% for patients receiving RT/CT vs. surgery alone. Univariate and multivariate analysis revealed that adverse prognostic factors were positive lymph nodes (risk ratio [RR] 1.3, p < 0.001) and high histologic grade (RR 1.2, p < 0.001). T3 tumor status was found significant on univariate analysis only (RR 1.1, p = 0.07). CONCLUSIONS: Results from recent clinical trials support the use of adjuvant chemotherapy in resected pancreatic cancer. The role of radiochemotherapy in adjuvant treatment of pancreatic cancer remains a topic of debate. Results from the Mayo Clinic suggest improved outcomes after the administration of adjuvant radiochemotherapy after a complete resection of invasive pancreatic malignancies.

Evidence-based guidelines for adjuvant therapy for resected adenocarcinoma of the pancreas.

Pancreatic cancer, the fourth most common cause of cancer deaths, has a five-year survival rate of 5% or less. Surgical removal of the tumor may improve survival, but survival remains poor even in optimally resected patients. The best adjuvant therapy for patients with resected pancreatic cancer is not clear. Surgical resection followed by chemoradiation and maintenance chemotherapy has been considered the most beneficial treatment for improving survival, but more recent studies have suggested that chemotherapy alone is more effective. The purpose of this article is to review randomized controlled studies of adjuvant chemoradiation or chemotherapy alone in the treatment of resected pancreatic cancer and to determine the optimal adjuvant therapy after curative resection with negative or microscopically positive margins. The outcomes of interest were overall survival and disease-free survival. The results indicate that chemoradiation is an acceptable option for adjuvant treatment. Three of the four randomized controlled trials suggest that adjuvant chemoradiation for resected pancreatic cancer improves overall survival. Adding gemcitabine to the chemoradiation regimen also confers increased disease-free survival. Providers counseling patients regarding treatment options for resected pancreatic cancer should continue to recommend adjuvant therapy--a combination of chemotherapy including gemcitabine and radiotherapy--for appropriately selected patients.

Adjuvant radiotherapy and chemotherapy for pancreatic carcinoma: the Mayo Clinic experience (1975-2005).

PURPOSE: To determine prognostic factors and impact of adjuvant chemotherapy (CT) and radiotherapy (RT) on overall survival (OS) after resection of pancreatic adenocarcinoma. PATIENTS AND METHODS: We performed a retrospective review 472 consecutive patients who underwent complete resection with negative margins (R0) for invasive carcinoma (T1-3N0-1M0) of the pancreas between 1975 and 2005 at the Mayo Clinic in Rochester, MN. Exclusion criteria included metastatic or unresectable disease at surgery, positive surgical margins, and indolent tumor types (islet cell tumors and mucinous cystadenocarcinoma). Median RT dose was 50.4 Gy in 28 fractions; 98% of RT patients also received concurrent fluorouracil-based CT. RESULTS: Six patients died within 30 days of surgery. For the 466 surviving patients, median follow-up was 32.4 months; median OS was 21.6 months. Median OS after adjuvant CT-RT was 25.2 versus 19.2 months after no adjuvant therapy (P = .001). Two-year OS was 50% versus 39%, and 5-year OS was 28% versus 17%. Adverse prognostic factors identified by univariate and multivariate analysis included positive lymph nodes (risk ratio [RR] = 1.3; P < .001), high histologic grade (RR = 1.2; P < .001), and no adjuvant therapy (RR = 1.3; P < .001). Tumor extension beyond the pancreas was an adverse prognostic factor by univariate analysis alone (P = .03). Patients receiving adjuvant therapy had more adverse prognostic factors than those not receiving adjuvant therapy (P = .001). CONCLUSION: This study represents one of the largest, single-institution, retrospective reviews of adjuvant therapy in patients after R0 resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CT-RT.