title: Validation of a Proposed Tumor Regression Grading Scheme for Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy as a Prognostic Indicator for Survival.
abstract: 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.
authors.affiliation: Departments of *Pathology †Surgical Oncology §Gastrointestinal Medical Oncology ‡Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Lee
authors.forename: Matthew H G
authors.initials: MH
authors.lastname: Katz
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Manonmani
authors.initials: M
authors.lastname: Sundar
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Gauri R
authors.initials: GR
authors.lastname: Varadhachary
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Jason B
authors.initials: JB
authors.lastname: Fleming
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
authors.forename: Huamin
authors.initials: H
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D016577:Pancreaticoduodenectomy; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis