Smad4 Loss Correlates with Higher Rates of Local and Distant Failure in Pancreatic Adenocarcinoma Patients Receiving Adjuvant Chemoradiation

Joseph M. Herman, Salma K. Jabbour, Steven H. Lin, Matthew P. Deek, Charles C. Hsu, Elliot K. Fishman, Sinae Kim, John L. Cameron, Marina Chekmareva, Daniel A. Laheru, Amol K. Narang, Timothy M. Pawlik, Ralph H. Hruban, Christopher L. Wolfgang, Christine A. Iacobuzio-Donahue

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives The tumor suppressor gene SMAD4 (DPC4) is genetically inactivated in approximately half of pancreatic ductal adenocarcinomas (PDAs). We examined whether Smad4 tumor status was associated with outcomes after adjuvant chemoradiation (CRT) for resected PDAs. Methods Patients treated with adjuvant CRT were identified (N = 145). Smad4 status was determined by immunolabeling and graded as intact or lost. Kaplan-Meier method and multivariable competing risk analyses were performed. Results On multivariate competing risk analysis, Smad4 loss was associated with increased risk of local recurrence (LR) (hazard ratio, 2.37; 95% confidence interval, 1.10-5.11; P = 0.027), distant failure (DF) (hazard ratio, 1.71; 95% confidence interval, 1.03-2.83; P = 0.037), and synchronous LR and DF at first recurrence (14.9 % vs 5.3%, P = 0.07) compared with Smad4 intact cancers. Smad4 loss was not associated with median overall survival (22 vs 22 months; P = 0.63) or disease-free survival (lost [13.6 months] vs intact [13.5 months], P = 0.79). Conclusions After PDA resection and adjuvant CRT, Smad4 loss correlated with higher risk of LR and DF, but not with survival. Smad4 loss may help predict which surgical patients are at higher risk for failure after definitive management and may benefit from intensified adjuvant therapy.

Original languageEnglish (US)
Pages (from-to)208-212
Number of pages5
JournalPancreas
Volume47
Issue number2
DOIs
StatePublished - Feb 1 2018

Keywords

  • DPC4
  • SMAD4
  • adjuvant therapy
  • chemoradiation therapy
  • pancreatic ductal adenocarcinoma
  • survival outcomes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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