Preoperative chemoradiation in adenocarcinoma of the pancreas. A single centre experience advocating a new treatment strategy

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Abstract

Aims

To evaluate a single centre's experience with pancreatic carcinoma focused on preoperative chemoradiation therapy (CRT) for treatment of locally advanced pancreatic carcinoma. The aim of the present analysis was to evaluate the median overall survival time (OS) after preoperative CRT and to compare it with OS after primary resection of pancreatic carcinoma. In conclusion a new treatment strategy was developed using multimodality treatment for pancreatic carcinoma deemed to be resectable by CT-scan.

Patients and methods

Between 1995 and 2003, 302 patients with ductal adenocarcinoma of the pancreatic head and body were recorded prospectively and OS was analysed with regard to therapy.

Results

Fifty-eight patients were resected without any pretreatment and had an OS of 21 months. Twenty-one patients with initially unresectable tumours underwent CRT followed by resection and had an OS of 54 months, which was not significantly different from primary resection (p = 0.315). Lymph node metastasis was significantly reduced after CRT (p = 0.0029). OS for patients whose tumours could not be resected was 3–10 months, depending on tumour stage and consecutive therapy.

Conclusion

CRT pretreatment was effective in locally advanced pancreatic carcinoma and resulted in resection of tumours otherwise staged as non-resectable. This experience led to a randomized trial for patients who by CT are staged to have resectable cancer of the pancreatic head with the intent to increase curative resectability and survival by neoadjuvant CRT (ISRCTN78805636/NCT00335543).

Introduction

Ductal adenocarcinoma of the pancreas is associated with an extremely poor prognosis. The overall median survival time is about 3–5 months including all stages. The only chance for long term survival is curative resection of the tumour with a median survival time of 11–17 months and 5-year survival rates of 10–23% in experienced centres.1, 2, 3, 4 Less than 20–25% of all patients are eligible for resection. Most of the tumours are diagnosed after metastatic dissemination. Many tumours are irresectable due to circumferential invasion of the major peripancreatic vessels and the mesenteric root. Palliative therapy either by chemotherapy or chemoradiation therapy (CRT) increases survival only by a few months: median survival up to 6.4 months for patients with distant metastasis treated with chemotherapy5, 6 and up to 9–15 months for patients without distant metastases undergoing CRT.1, 7 Even after potentially curative resection survival is usually limited by local recurrences and/or distant metastatic spread of the tumour in the further course of disease.

In a monocentric study, Snady et al.8 demonstrated that patients with primarily non-resectable pancreatic tumours had a better outcome when their tumours could be resected after preoperative CRT than patients who underwent resection of their pancreatic tumour without preoperative therapy. Median survival time could be significantly increased from 14.0 months to 23.6 months after neoadjuvant CRT. This was surprising because patients undergoing primary surgery were expected to have a better prognosis due to smaller tumours.8

This promising report prompted us to review the outcome of patients with pancreatic carcinoma treated at our institution focusing on the value of preoperative chemoradiation. A new treatment strategy was developed to improve the prognosis of patients with newly diagnosed pancreatic carcinoma.

Section snippets

Selection of patients and patient characteristics

All patients with pancreatic carcinoma who presented themselves at the Department of Surgery, University of Erlangen, since the introduction of CRT in pancreatic carcinoma in 1995 were prospectively registered in the clinical cancer registry of the department. Patients with cancer of the pancreatic tail and other entities such as cystadenocarcinomas or neuroendocrine tumours were excluded. Only patients presenting with ductal pancreatic carcinoma of the head and body (n = 302) between 1995 and

Patients with tumour resection

Seventy-nine patients underwent partial or subtotal duodenopancreatectomy with a standardized lymphadenectomy (paraaortic nodes, nodes at the hepatoduodenal ligament, nodes around celiac trunk, nodes at least right and dorsal to the superior mesenteric artery, with the majority including a circular lymph node dissection around the superior mesenteric artery to the origin of the middle colic artery). Reconstruction was usually achieved by one jejunal loop with anastomosis of the pancreatic

Discussion

The first evidence for prolonged survival after preoperative CRT and resection at our institution resulted from a phase II-study (single dose 1.8 Gy, total dose 50.4 Gy, boost to 55.8 Gy; concurrent 5-FU/mitomycin).12 In our experience and in other publications CRT is not associated with higher toxicity or an increased rate of postoperative complications.14 These results could be confirmed in this study in comparison to patients who underwent primary resection. Patients undergoing preoperative CRT

Conflicts of interest

None.

Acknowledgement

We thank Mrs. L. Reindl for proofreading the manuscript.

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    The study ISRCTN78805636/NCT00335543 was supported by a grant of the German Cancer Aid and the Tumorzentrum Erlangen-Nürnberg.

    1

    Was supported by a grant of the German Cancer Aid.

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