Adjuvant Radiotherapy in Patients With Pancreatic Adenocarcinoma. Is It Still Appealing in Clinical Trials? A Meta-analysis and Review of the Literature

Abstract

Aim. Pancreatic adenocarcinoma is a lifethreatening disease with a rising frequency and the fourth leading cause of cancer death. This review aimed to assess the impact of postoperative radiotherapy through a meta-analysis of prospective randomized studies. Materials and Methods: Six studies met the inclusion criteria and were analyzed to calculate the cumulative risk of death (hazard ratio) in patients affected by pancreatic cancer treated with or without radiotherapy. Higgins' index was used to determine heterogeneity in betweenstudy variability and, subsequently, the random-effects model was applied according to DerSimonian and Laird. Results: Eight hundred and thirty-seven patients were analyzed (418 in the control arm and 419 in the treatment one), the hazard ratio for death after randomization was 0.92 (p=0.560, 95% confidence interval=0.70-1.22). When scrutinizing these studies, only one out of six showed a statistically significant benefit due to the addition of radiotherapy in the postoperative setting. Conclusion: We conclude that the use of adjuvant radiotherapy is not beneficial in treating all patients affected by pancreatic cancer but only for a subset of cases with potential residual local disease.Pancreatic cancer is expected to become the second cause of cancer-related death in the next decade; due to its aggressiveness and the early onset of distant metastases, it holds a poor prognosis, and no more than 7% of all patients survive 5 years following diagnosis (1-5). Despite the latest advances in cancer treatment, surgery still represents the only strategy with curative intent; but even after resection, the 5-year survival rate for all resected patients ranges between 14% and 27% (6-9).Since the 1980s, the role of radiotherapy in pancreatic cancer has been investigated through prospective phase 3 trials with controversial findings (10,11). While some studies showed a limited benefit using radiotherapy after surgery, other experiences did not indicate any benefit or reported a detrimental effect (10,11). Currently, despite considerable efforts, the clinical impact of adjuvant radiotherapy in patients with pancreatic cancer is still not clear. Furthermore, considering that several clinical trials were carried out more than 30 years ago, new clinical studies with state-of-the-art technology are required to assess the real impact of adjuvant radiotherapy in this setting (12). However, two more major issues must be addressed before planning further studies: the role of the persistence of cancer cells and the selection of patients suitable for postoperative 4697 This article is freely accessible online.

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