Preoperative chemoradiation in adenocarcinoma of the pancreas. A single centre experience advocating a new treatment strategy☆
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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Cited by (54)
The impact of neoadjuvant therapy on the histopathological features of pancreatic ductal adenocarcinoma – A systematic review and meta-analysis
2017, Cancer Treatment ReviewsCitation Excerpt :One of the most relevant prognostic factors of overall survival and tumor recurrence in PDAC is the R0-status, i.e. tumor-free, surgical resection margin. In our meta-analysis, 28 studies [8,9,11–13,28,29,31,33–39,41–43,45–48,52–56] with a total of 10,141 patients could be identified meeting all inclusion criteria for the meta-analysis of R0 status after NTx versus upfront surgery. NTx was performed in 2276 patients (22%) and 83% (N = 1888) were classified as R0 in contrast to 73% (N = 5766) with upfront surgery.
Trends in the use of pre-operative radiation for adenocarcinoma of the pancreas in the United States
2015, HPBCitation Excerpt :If a clinical trial is not an option, the NCCN guidelines recommend either chemoradiation or chemotherapy alone as appropriate post-operative adjuvant therapy.9 While the utility of post-operative radiation has been questioned, several single-institutional studies have reported the outcomes and potential benefits of pre-operative chemoradiation.10-14 Current NCCN guidelines recommend pre-operative adjuvant therapy as an appropriate option for those with borderline resectable disease and acknowledge that many NCCN member institutions now prefer this approach for borderline resectable patients.
Pancreaticoduodenectomy following chemoradiotherapy for locally advanced adenocarcinoma of the pancreatic head
2013, HPBCitation Excerpt :Treatment with postoperative chemotherapy in patients who have received preoperative CRT may decrease the distant recurrence rate and more significantly increase overall and disease‐free survival. Although surgery remains the standard curative therapy for resectable pancreatic cancer, very similar rates of survival were observed in the two treatment groups assessed in this study, which is in agreement with previous studies.[18,23,30] Although it is important to note that the patients who underwent PD after preoperative CRT represented a selected subset of patients, this observation may suggest a defect in selecting patients who have been treated with radical surgery alone.
CA 19-9 level as indicator of early distant metastasis and therapeutic selection in resected pancreatic cancer
2011, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :In recent studies of preoperative CRT for pancreatic cancer (26, 27), 13–20% of patients who were diagnosed with localized and resectable disease at preoperative CRT avoided resection because of the occurrence of distant disease at restaging after preoperative CRT. In part because of the selection effect, preoperative treatment strategies have improved the surgical outcome of pancreatic cancer, with a 5-year survival rate of 36–53% (26–32). However, a significant number of patients will still develop recurrent disease immediately after preoperative CRT and subsequent surgical resection.
Neoadjuvant therapy in resectable pancreatic cancer: A promising curative method to improve prognosis
2022, World Journal of Gastrointestinal Oncology
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The study ISRCTN78805636/NCT00335543 was supported by a grant of the German Cancer Aid and the Tumorzentrum Erlangen-Nürnberg.
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Was supported by a grant of the German Cancer Aid.