Intact SMAD-4 is a predictor of increased locoregional recurrence in upfront resected pancreas cancer receiving adjuvant therapy.

BACKGROUND

Previous reports suggest that intact SMAD4 expression is associated with a locally aggressive pancreas cancer phenotype. The objectives of this work were to determine the frequency of intact SMAD4 and its association with patterns of recurrence in patients with upfront resected pancreas cancer receiving adjuvant therapy.

METHODS

A tissue microarray was constructed using resected specimens from patients who underwent upfront surgery and adjuvant gemcitabine with no neoadjuvant treatment for pancreas cancer. SMAD4 expression was determined by immunohistochemical staining. Associations of SMAD4 expression and clinicopathologic parameters with clinical outcomes were evaluated using Cox proportional hazard models.

RESULTS

One hundred twenty-seven patients were included with a median follow up of 5.7 years. Most patients had stage ≥ pT3 tumors (75%) and pN1 (68%). All patients received adjuvant gemcitabine, and 79% of patients received adjuvant chemoradiotherapy. Ten (8%) patients had intact SMAD4 expression. Grade was the only clinicopathologic parameter statistically associated with SMAD4 expression (P=0.05). Median overall survival was 2.1 years. On univariate analysis, SMAD4 expression was associated with increased locoregional recurrence (hazard ratio 7.0, P<0.01, 95% confidence interval: 2.8-18.0) but not distant recurrence (P=0.06) or overall survival (P=0.73). On multivariable analysis, SMAD4 expression (hazard ratio 9.6, P<0.01, 95% confidence interval: 3.7-24.8) and adjuvant chemoradiotherapy (hazard ratio 0.3, P=0.01, 95% confidence interval: 0.1-0.8) were associated with higher and lower locoregional recurrence, respectively.

CONCLUSIONS

In patients with upfront resected pancreas cancer, SMAD4 expression was associated with an increased risk of locoregional recurrence. Prospective evaluation of the frequency of SMAD4 expression and validation of its predictive utility is warranted.

Informations de copyright

2021 Journal of Gastrointestinal Oncology. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-21-55). SPC declares Olympus consulting and Ethicon educational events. ROK declares his wife is a senior technical product manager for GE Healthcare. KWM declares ongoing grant support for clinical trial and global medical education programs. None of these grants are relevant to the manuscript. DO declares grants for clinical trial operations and protocol delivery from Mayo Clinic and Astra Zeneca. No direct financial relationship. TTS declares that he provides strategic and scientific recommendations as a member of the Advisory Board and speaker for Novocure, Inc., which is not in any way associated with the content or disease site as presented in this manuscript. AHT declares grants from AACR-PanCAN, Lutsgarten Foundation for Pancreatic Cancer Research, National Institute of General Medical Sciences, National Cancer Institute, and Dorothy G. Hoefer Foundation for Pancreatic Cancer Research, is a grant reviewer at National Institute of Health, National Cancer Institute, Department of Defense, and PanCAN, and is a Vice Chair at PanCAN Career Development Award Scientific Review Committee. The other authors have no conflicts of interest to declare.