Neoadjuvant Therapy In Pancreatic Adenocarcinoma: A Meta-Analysis Of Phase II Trials

ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS 33.4. Neoadjuvant versus Initial Resection for Potentially Resectable Pancreatic Cancer: A Decision Model. J. P. VanHouten,1 G. P. Jackson,2 R. R. White3; 1Vanderbilt University Medical School, Nashville, TN; 2Vanderbilt University Medical Center, Nashville, TN; 3Duke University Medical Center, Durham, NC Introduction: The optimal treatment strategy for potentially resectable pancreatic cancer is controversial. Surgical resection is considered the only curative treatment, but neoadjuvant chemoradiotherapy may offer advantages for potentially resectable disease. A previously developed decision model for the treatment of potentially resectable pancreatic cancer suggested a slight benefit for neoadjuvant therapy. Methods: We updated this decision model with current literature. Initial therapeutic choices were surgery, preoperative chemotherapy and radiation, and no treatment; subsequent decisions offered a second intervention if not prohibited by complications or death. Payoffs were calculated as the median expected survival after treatment. The model incorporated utilities for time spent in treatment and recovery, but all utilities were set to 1 for this analysis. We gathered evidence for this model through a comprehensive MEDLINEÒ search. The probabilities of resectability and treatment complications, and the expected median survival after treatments were collected and weighted according to study size. The decision was analyzed, and one-way sensitivity analyses were performed for all probabilities and utilities. Results: Based on survival alone, neoadjuvant chemoradiation is slightly favored over initial surgery for the treatment of potentially resectable pancreatic cancer, with expected values of 17.9 months and 16.8 months, respectively. The decision is sensitive to the probability of mortality from neoadjuvant therapy and tumor resectability. Initial surgery is preferred when the mortality of neoadjuvant chemoradiation exceeds 13.1%. Neoadjuvant therapy is favored when the resectability on imaging after chemoradiation is greater than 70% or when the resectability at operation is greater than 10%. The decision was sensitive to the utility for the time spent in chemoradiation, with surgery being favored for utilities less than -0.8. Conclusions: The ideal treatment for potentially resectable pancreatic cancer remains controversial, although recent evidence supports a slight benefit for neoadjuvant therapy over initial surgery. Our model showed that the decision is sensitive to the probability of tumor resectability, with initial surgery being favored when resectability after neoadjuvant therapy fell below 70%. The decision is not sensitive to the rates of treatment morbidities or mortalities, unless the rate of death from neoadjuvant therapy exceeds 13.1%, which has not been observed in the literature. With only a small survival benefit of one treatment over another, patient preferences for health states during and after treatment are likely to play an important role in individual decisions. The decision was sensitive to the utility for the time spent in chemotherapy and radiation when this health state was considered worse than death. More research is needed on patient preferences and how they might influence such treatment decisions.

33.5. Neoadjuvant Therapy In Pancreatic Adenocarcinoma: A Meta-Analysis Of Phase II Trials. M. M. Assifi,1 X. Lu,2 G. Eibl,1 H. A. Reber,1 G. Li,2 O. J. Hines1; 1Department of Surgery, Los Angeles, CA; 2Department of Biostatistics, Los Angeles, CA Introduction: Neoadjuvant treatment has proven beneficial for many GI malignancies, but no phase III trials have been completed examining this approach in pancreatic cancer. Despite this, neoadjuvant treatment has become routine in some centers. This meta-analysis examines the best available phase II trials using neoadjuvant chemotherapy and radiation for resectable and

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borderline/unresectable pancreatic adenocarcinoma. Methods: Studies were identified using the Cochrane Central Register of Controlled Trials from 1960 to July 2010, and using a MEDLINE search. Only phase II trials that examined the effects of neoadjuvant chemotherapy and/or radiation on pancreatic cancer were included. Patients were divided into two groups: patients with initially resectable tumors (Group A), and patients with borderline/unresectable tumors (Group B). Primary outcome measures were rate of resection and survival. Pooled proportions and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 14 phase II clinical trials including 536 patients were analyzed. The agents used were largely gemcitabine or gemcitabine combinations including cisplatin, 5-FU, or mitomycin C, and 86% concurrently administered radiation. Following treatment, resectability was 65.8% (95% CI 55.4%-75.6%) compared with 31.6% in Group B (95% CI 14.0%-52.5%). Negative margins were achieved in 85.1% (95% CI 76.8-91.9%) of patients in Group A versus 62.2% (95% CI 29.9%-89.4%) patients in Group B. Only 6 out of 308 patients had a complete response. A significant partial response was observed in patients with borderline/ unresectable tumors; 31.8 (95% CI 24.2%-39.8%) in Group B, and 9.5% (95% CI 2.9%-19.4%) in Group A (p¼0.003). Progressive disease was seen in 17.0% (95% CI 11.9%-22.7) patients in Group A versus 21.8% (95% CI 10.1%-36.5%) in Group B (p¼0.006). Grade III/IV toxicity, local and distant recurrence were not significantly different between the two groups. Median survival in resected patients was 23 months (range 11.7-34) for Group A, and 22.3 months (range 18-26.3) for patients in Group B. An analysis of heterogeneity was performed using a general linear model to explore the causes of heterogeneity. Conclusions: From this initial pooled phase II data, neoadjuvant treatment appears to have some activity in patients with borderline/unresectable pancreatic adenocarcinoma. Nearly one-third of tumors initially deemed marginal for operative intervention were ultimately able to be resected following treatment. The survival rates from all patients in these studies were comparable to those reported in large surgical series that did not include neoadjuvant treatment. Until more effective targeted chemotherapeutics are developed, the only group of patients with pancreatic cancer that may benefit from neoadjuvant treatment are those with locally advanced disease.

33.6. 415 Patients With Adenosquamous Carcinoma Of The Pancreas: A Population-Based Analysis Of Prognosis and Survival. C. A. Boyd, K. M. Sheffield, J. BenarrochGampel, T. S. Riall; University of Texas-Medical Branch, Galveston, Texas Introduction: Adenosquamous carcinoma is a rare cancer of the pancreas, accounting for approximately 1-4% of exocrine pancreatic malignancies. Because of the uncommon nature of this tumor, our understanding of the disease and its prognosis comes mainly from small retrospective studies and case reports. Methods: Using Surveillance, Epidemiology, and End Results (SEER) database (1988 to 2007), we identified all patients with a diagnosis of adenosquamous or adenocarcinoma of the pancreas. The demographic factors, tumor characteristics, resection status, and long-term survival were compared between the groups. Results: A total of 415 patients with pancreatic adenosquamous carcinoma and 45,693 patients with adenocarcinoma were identified. The gender and race distributions were similar in the two groups. When compared to patients with adenocarcinoma, patients with adenosquamous carcinoma were less likely to have disease located in the head (44.6% vs 53.5%, P<0.0001) and more likely to have disease in the body or tail of the pancreas (29.2% vs 19%, P<0.0001). The stage distribution was similar between the two groups with approximately 60% of patients in