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Validation of a Proposed Tumor Regression Grading Scheme for Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy as a Prognostic Indicator for Survival

Lee, Sun Mi MD; Katz, Matthew H.G. MD; Liu, Li MD, PhD; Sundar, Manonmani MD; Wang, Hua MD, PhD; Varadhachary, Gauri R. MD; Wolff, Robert A. MD; Lee, Jeffrey E. MD; Maitra, Anirban MD, PhD; Fleming, Jason B. MD; Rashid, Asif MD, PhD; Wang, Huamin MD, PhD

The American Journal of Surgical Pathology: December 2016 - Volume 40 - Issue 12 - p 1653–1660
doi: 10.1097/PAS.0000000000000738
Original Articles
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Neoadjuvant therapy has been increasingly used to treat patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Although the College of American Pathologists (CAP) grading scheme for tumor response in posttherapy specimens has been used, its clinical significance has not been validated. Previously, we proposed a 3-tier histologic tumor regression grading (HTRG) scheme (HTRG 0, no viable tumor; HTRG 1, <5% viable tumor cells; HTRG 2, ≥5% viable tumor cells) and showed that the 3-tier HTRG scheme correlated with prognosis. In this study, we sought to validate our proposed HTRG scheme in a new cohort of 167 consecutive PDAC patients who completed neoadjuvant therapy and pancreaticoduodenectomy. We found that patients with HTRG 0 or 1 were associated with a lower frequency of lymph node metastasis (P=0.004) and recurrence (P=0.01), lower ypT (P<0.001) and AJCC stage (P<0.001), longer disease-free survival (DFS, P=0.004) and overall survival (OS, P=0.02) than those with HTRG 2. However, there was no difference in either DFS or OS between the groups with CAP grade 2 and those with CAP grade 3 (P>0.05). In multivariate analysis, HTRG grade 0 or 1 was an independent prognostic factor for better DFS (P=0.03), but not OS. Therefore we validated the proposed HTRG scheme from our previous study. The proposed HTRG scheme is simple and easy to apply in practice by pathologists and might be used as a successful surrogate for longer DFS in patients with potentially resectable PDAC who completed neoadjuvant therapy and surgery.

Departments of *Pathology

Surgical Oncology

§Gastrointestinal Medical Oncology

Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX

Conflicts of Interest and Source of Funding: Supported by the National Institutes of Health grant (1R01 CA196941-01A1) and Khalifa Bin Zayed Al Nahyan Foundation Institute for Pancreatic Cancer Research at The University of Texas MD Anderson Cancer Center. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Huamin Wang, MD, PhD, Department of Pathology, Unit 085, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 (e-mail: hmwang@mdanderson.org).

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