Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas

Background: Improved resectability is a major theoretical benefit of preope rative chemoradiation for pancreatic cancer. Since 1994, patients at Duke U niversity Medical Center with locally advanced pancreatic cancer have been treated with multimodality preoperative therapy. The purpose of this study was to review our experience with preoperative therapy for locally advanced pancreatic cancer and determine if an aggressive neoadjuvant regimen would -not only downstage these tumors pathologically but also improve the odds o f complete surgical resection. Methods: The charts of 25 patients treated with neoadjuvant chemoradiation at Duke University Medical Center with biopsy-proven, locally advanced aden ocarcinoma of the pancreas were reviewed. Tumors were defined as locally ad vanced based on radiographic or intraoperative evidence of disease that abu ts the superior mesenteric artery or Vein (n = 22) or involves lymph nodes that are within the proposed radiation field (n = 3). All 25 patients recei ved external beam radiotherapy (median dose 4500 cGy) in daily fractions of 180 cGy over 5 weeks. All patients concurrently received 5-fluorouracil (F U), and many also received mitomycin C or cisplatin, or both. Patients were given a 3- to 4-week break before a restaging computed tomographic (CT) sc an was performed. Three patients were not restaged: one died from metastati c disease; one was reclassified as having a neuroendocrine tumor; and one w as lost to follow-up. Results: On restaging after neoadjuvant therapy, 64% of patients had stable or decreased primary tumor size. Radiographically, two patients appeared p otentially resectable, and seven others developed evidence of metastatic di sease. Eight patients underwent exploration, but only five could be resecte d, Of the five patients resected, only one had negative margins and negativ e lymph nodes. This patient had significant pancreatitis on initial explora tion. After neoadjuvant therapy, be had a complete response radiographicall y, and there was no residual cancer in his resection specimen. Pathologic e xamination of the other resection specimens suggested that despite signific ant tumor fibrosis, malignant cells persist even at the periphery of the le sions. Conclusion: Although neoadjuvant chemoradiation has many theoretical advant ages in managing pancreatic malignancy, true pathologic downstaging of loca lly advanced lesions into tumors that can be removed with negative nodes an d margins appears to be a rare event with currently used therapeutic regime ns.