@article{895902da405d4303bc46ec77f3d77f62,
title = "Smad4 Loss Correlates with Higher Rates of Local and Distant Failure in Pancreatic Adenocarcinoma Patients Receiving Adjuvant Chemoradiation",
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.",
keywords = "DPC4, SMAD4, adjuvant therapy, chemoradiation therapy, pancreatic ductal adenocarcinoma, survival outcomes",
author = "Herman, {Joseph M.} and Jabbour, {Salma K.} and Lin, {Steven H.} and Deek, {Matthew P.} and Hsu, {Charles C.} and Fishman, {Elliot K.} and Sinae Kim and Cameron, {John L.} and Marina Chekmareva and Laheru, {Daniel A.} and Narang, {Amol K.} and Pawlik, {Timothy M.} and Hruban, {Ralph H.} and Wolfgang, {Christopher L.} and Iacobuzio-Donahue, {Christine A.}",
note = "Funding Information: Key Words: SMAD4, DPC4, pancreatic ductal adenocarcinoma, chemoradiation therapy, survival outcomes, adjuvant therapy From the *Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX; †Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert, Wood Johnson Medical School, Rutgers University, New Brunswick, NJ; ‡Department of Radiation Oncology and Molecular Radiation Sciences, The Sol Goldman, Pancreatic Cancer Research Center, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD; §Department of Radiation Oncology, University of Arizona Cancer Center, Tucson, AZ ||Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD; ¶Department of Biostatistics, School of Public Health, Rutgers University; Biometrics Division, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ; #Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD; **Department of Pathology, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ; ††Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD; ‡‡Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH; §§Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD; and ||||Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY. Received for publication April 7, 2017; accepted December 6, 2017. Address correspondence to: Joseph M. Herman, MD, Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (e‐mail: JMHerman@mdanderson.org). This study was supported by the GI SPORE grant, NCI CA 6, and Biorespository at the Rutgers Cancer Institute of New Jersey. The authors declare no conflict of interest. Copyright {\textcopyright} 2018 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/MPA.0000000000000985 Publisher Copyright: {\textcopyright} Wolters Kluwer Health, Inc. All rights reserved.",
year = "2018",
month = feb,
day = "1",
doi = "10.1097/MPA.0000000000000985",
language = "English (US)",
volume = "47",
pages = "208--212",
journal = "Pancreas",
issn = "0885-3177",
publisher = "Lippincott Williams and Wilkins",
number = "2",
}