Rohit Das1, Kevin McGrath2, Natalie Seiser3, Katelyn Smith4, Shikhar Uttam5, Randall E Brand2, Kenneth E Fasanella2, Asif Khalid2, Jennifer S Chennat2, Savreet Sarkaria2, Harkirat Singh2, Adam Slivka2, Herbert J Zeh6, Amer H Zureikat3, Melissa E Hogg7, Kenneth K Lee3, Alessandro Paniccia3, Melanie C Ongchin3, James F Pingpank3, Brian A Boone8, Anil K Dasyam9, Nathan Bahary2, Vikram C Gorantla2, John C Rhee2, Roby Thomas2, Susannah Ellsworth10, Michael S Landau4, N Paul Ohori4, Patrick Henn11, Susan Shyu4, Brian K Theisen12, Aatur D Singhi13. 1. Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address: dasr@upmc.edu. 2. Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 3. Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 4. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 5. Department of Computational and Systems Biology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 6. Department of Clinical Sciences, Surgery, University of Texas Southwestern, Dallas, Texas. 7. Department of Surgery, North Shore University Health System, Chicago, Illinois. 8. Department of Surgery, West Virginia University, Morgantown, West Virginia. 9. Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 10. Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. 11. Department of Pathology, University of Colorado Hospital, Aurora, Colorado. 12. Department of Pathology, Henry Ford Health System, Detroit, Michigan. 13. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Electronic address: singhiad@upmc.edu.
Abstract
BACKGROUND & AIMS: The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy were hypothesized to represent an improved marker of treatment response. METHODS: For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. RESULTS: Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r = 0.726, P < .001) and AJCC 8th edition T-stage (r = 0.586, P < .001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs 31%, P < .001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs 32%, P < .001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs 36%, P < .001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (P = .007). CONCLUSIONS: The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management.
BACKGROUND & AIMS: The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy were hypothesized to represent an improved marker of treatment response. METHODS: For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. RESULTS: Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r = 0.726, P < .001) and AJCC 8th edition T-stage (r = 0.586, P < .001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs 31%, P < .001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs 32%, P < .001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs 36%, P < .001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (P = .007). CONCLUSIONS: The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management.