Abstract B80: Stroma in pancreatic cancer: Automated quantification and its prognostic significance
Authors: Torphy Robert J. , Naim Rashid , Midkiff Bentley , Volmar Keith , Collisson Eric , Yeh Jen Jen 
Published: December 2016

Abstract
Tumor stroma (TS) is a cardinal component of pancreatic ductal adenocarcinoma (PDAC); it comprises 60 to 90% of tumor volume and is an emerging treatment target. There are conflicting reports of the role that TS plays in disease progression and its prognostic significance. The objective of this study was to develop a high-throughput, operator independent method for objectively quantifying TS density (TSD) and to evaluate the prognostic significance of TSD in resected tumors.
Tissue sections of primary tumor from 126 patients undergoing pancreaticoduodenectomy for PDAC from 1979 to 2008 and followed by observation only were stained with hematoxylin and eosin (H&E). Sections were digitally uploaded and location of tumor was annotated using ImageScope. Annotated images were imported to Definiens Architect. By training on representative areas, an algorithm was created to segment the tissue into different regions-of-interest (ROI): tumor epithelium, TS, and inflammatory infiltrate. Next, the algorithm was used to quantify the above described ROIs in each tissue section. TSD was calculated as tumor stroma area over total tumor area. A cox proportional hazards model was used to compare overall survival (OS) and recurrence free survival (RFS) vs TSD controlling for age, sex, tumor grade, T, N, and overall stage, smoking status, and American Society of Anesthesia (ASA) physical classification score.
Median TSD was 0.637. High TSD was significantly associated with RFS (p=0.043) and OS (p=0.037). In the low TSD group, median RFS and OS was 8.9 months and 11.5 months, respectively. In the high TSD group, median RFS and OS was 13.9 and 18.3 months, respectively. In this cohort, 18 patients were identified with an OS greater than 5 years. This cohort had a higher median TSD of 0.71. After excluding those with a survival greater than 5 years, there was still a trend toward high TSD and worse OS (p=0.052).
Our novel automated algorithm for quantification of TSD allows for high throughput, reproducible, and objective analysis of H&E stained PDAC slides. The median TSD in our study obtained using our novel algorithm was 0.637, in agreement with prior manual descriptions of PDAC tumors having a TSD of greater than 60%. We also found high TSD to be a positive independent prognostic variable in resected tumors in patients not receiving adjuvant therapy. Further understanding of the balance of TS in restraining tumor progression vs impeding chemotherapeutic delivery is needed to successfully manipulate stroma in the treatment of PDAC.
Citation Format: Robert J. Torphy, Rashid Naim, Bentley Midkiff, Keith Volmar, Eric Collisson, Jen Jen Yeh.{Authors}. Stroma in pancreatic cancer: Automated quantification and its prognostic significance. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B80.