Abstract
ObjectivesThe objective of this study was to investigate the role of genetic status of DPC4 in recurrence patterns of resected pancreatic ductal adenocarcinoma (PDAC).MethodsBetween April 2004 and December 2011, data on patients undergoing surgical resection for PDAC were reviewed. Genetic status of DPC4 was determined and correlated to recurrence patterns and clinical outcomes.ResultsAnalysis of 641 patients revealed that genetic status of DPC4 was associated with overall survival and was highly correlated with recurrence patterns, as inactivation of the DPC4 gene was the strongest predictor of metastatic recurrence (odds ratio = 4.28). Treatment modalities for recurrent PDAC included chemotherapy alone and concurrent chemotherapy along with local control. For both locoregional and metastatic recurrence, local control resulted in improved survival; however, for groups subdivided according to recurrence patterns and genetic status of DPC4, local control contributed to improved survival in locoregional recurrences of patients with expressed DPC4, while chemotherapy alone was sufficient for others.ConclusionsGenetic status of DPC4 contributes to the recurrence patterns following pancreatectomy, and patients with an initially expressed DPC4 gene receive a greater benefit from intensive local control for locoregional recurrence. The DPC4 gene, therefore, may aid the establishment of treatment strategies for initial adjuvant treatment or for recurrent PDAC.
Highlights
Advances in understanding the molecular underpinnings of pancreatic ductal adenocarcinoma (PDAC) have begun to contribute to the development of new approaches to clinical management of this devastating cancer
Analysis of 641 patients revealed that genetic status of DPC4 was associated with overall survival and was highly correlated with recurrence patterns, as inactivation of the DPC4 gene was the strongest predictor of metastatic recurrence
Treatment modalities for recurrent PDAC included chemotherapy alone and concurrent chemotherapy along with local control. For both locoregional and metastatic recurrence, local control resulted in improved survival; for groups subdivided according to recurrence patterns and genetic status of DPC4, local control contributed to improved survival in locoregional recurrences of patients with expressed DPC4, while chemotherapy alone was sufficient for others
Summary
Advances in understanding the molecular underpinnings of pancreatic ductal adenocarcinoma (PDAC) have begun to contribute to the development of new approaches to clinical management of this devastating cancer. These investigators performed rapid autopsies on patients with documented pancreatic cancer and found that the histological features and patterns of failure were correlated with the genetic status of DPC4 (i.e., locally destructive tumors in patients with an expressed DPC4 gene vs distant metastasis in patients with an inactivated DPC4 gene) Based on these findings, Iacobuzio–Donahue and colleagues concluded that determination of the status of DPC4 upon initial diagnosis may aid the stratification of patients into treatment regimens related to local control versus systemic therapy; further follow-up prospective studies designed to confirm and extend this finding were proposed
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