Abstract
Neoadjuvant therapy represents an increasingly used strategy in pancreatic cancer, and this means that more pancreatic resections need to be evaluated for therapy effect. Several grading systems have been proposed for the histological assessment of tumor regression in pre-treated patients with pancreatic cancer, but issues like practical application, level of agreement and prognostic significance are still debated. To date, a standardized and widely accepted score has not been established yet. In this study, two pathologists with expertise in pancreatic cancer used 4 of the most frequently reported systems (College of American Pathologists, Evans, MD Anderson, and Hartman) to evaluate tumor regression in 29 locally advanced pancreatic cancers previously treated with modified FOLFIRINOX regimen, to establish the level of agreement between pathologists and to determine their potential prognostic value. Cases were additionally evaluated with a fifth grading system inspired to the Dworak score, normally used for colo-rectal cancer, to identify an alternative, relevant option. Results obtained for current grading systems showed different levels of agreement, and they often proved to be very subjective and inaccurate. In addition, no significant correlation was observed with survival. Interestingly, Dworak score showed a higher degree of concordance and a significant correlation with overall survival in individual assessments. These data reflect the need to re-evaluate grading systems for pancreatic cancer to establish a more reproducible and clinically relevant score.
Highlights
Pancreatic cancer (PC) is the third leading cause of cancer-related death in the United States, with 45,750 projected deaths in 2019 and it is expected to become the second leading cause within few years [1]
After histological evaluation of surgical specimens, 22 cases were diagnosed as ductal adenocarcinoma (PDAC), 5 as adenocarcinoma derived from intraductal pancreatic mucinous neoplasia (IPMN), and 1 as adenosquamous carcinoma; in 1 case, cancer histotype was not assessed due to the small number of neoplastic cells left after neoadjuvant treatment
According to our daily experience, particular attention should be paid to peripheral areas where residual tumor can be often detected, especially the duodenal wall, around the main mesenteric vessels and in peripancreatic lymph nodes. This is the second study, after the one proposed by Kalimuthu et al to assess the level of agreement between pathologists in reporting tumor regression grade (TRG) in pancreatic cancer
Summary
Pancreatic cancer (PC) is the third leading cause of cancer-related death in the United States, with 45,750 projected deaths in 2019 and it is expected to become the second leading cause within few years [1]. Upfront treatment with chemotherapy with or without radiation therapy and subsequent evaluation for surgery represents an increasingly used strategy in borderline resectable (BR) and locally advanced pancreatic cancer (LAPC) and has shown interesting results even in resectable disease [3,4,5]. Even in the absence of a clear survival benefit upfront medical treatment in LAPC seems to add a significant benefit in terms of downstaging of primary carcinoma, reduction of the risk of positive margins (R1) after histological evaluation, and of local recurrence [6,7,8]. The combination of 5-fluorouracil, oxaliplatin, and irinotecan (FOLFIRINOX) has been associated with notable results in terms of response rate, conversion to surgery and overall survival in different case series [9]
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