TY - JOUR
T1 - Molecular Peritoneal Staging for Pancreatic Ductal Adenocarcinoma Using Mutant KRAS Droplet-Digital Polymerase Chain Reaction
T2 - Results of a Prospective Clinical Trial
AU - Yonkus, Jennifer A.
AU - Alva-Ruiz, Roberto
AU - Abdelrahman, Amro M.
AU - Leiting, Jennifer L.
AU - Schneider, Amber R.
AU - Grotz, Travis E.
AU - Cleary, Sean P.
AU - Smoot, Rory L.
AU - Nagorney, David M.
AU - Kendrick, Michael L.
AU - Kipp, Benjamin R.
AU - Truty, Mark J.
N1 - Funding Information:
We would like to acknowledge Jesse S Voss and Dragana Milosevic, in the Department of Laboratory Medicine and Pathology, for their contribution to this work. Virtual Abstract Created with BioRender.com with laparoscopy image for visual abstract obtained from Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014” WikiJournal of Medicine 1 (2). https://doi.org/10.15347/wjm/2014.010. ISSN 2002-4436.
Publisher Copyright:
© 2021 American College of Surgeons
PY - 2021/7
Y1 - 2021/7
N2 - Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with predilection for peritoneal dissemination. Accurate peritoneal staging is imperative for treatment recommendations, as one-third of patients develop peritoneal recurrence after resection. Because >90% of PDAC tumors harbor mutant KRAS (mKRAS), we sought to determine feasibility of mKRAS DNA detection in peritoneal lavage (PL) fluid using droplet-digital polymerase chain reaction (ddPCR) via a prospective trial. Study design: Patients with nonmetastatic PDAC undergoing staging laparoscopy with PL were included. PL fluid was sent for cytologic examination, CA19-9/CEA levels, and mKRAS ddPCR assay. Clinically positive laparoscopy was defined as gross metastases or positive cytology. PL mKRAS status was compared with gross findings, cytology, and CA19-9/CEA levels. Results: There were 136 patients enrolled; 70 of 136 (51%) patients received neoadjuvant therapy before PL, and 32 of 136 (24%) patients had clinically positive laparoscopy. Cytology was positive in 17 of 136 (13%) patients, and 22 of 136 (16%) patients had gross metastases. Of patients with gross metastases, only 8 of 22 (36%) had positive cytology; 97 of 136 (71%) patients had mKRAS in PL. PL mKRAS was present in 27 of 32 (84%) clinically positive laparoscopies, with higher mean copy number in clinically positive patients (643 vs 10, p = 0.02). Peritoneal mKRAS was positive in an additional 70 clinically negative patients. Conclusions: This prospective study establishes the feasibility of PL mKRAS detection. Clinically positive disease was identified in 1 in 4 staging laparoscopies. Although PL mKRAS was highly associated with clinically positive findings, many clinically negative laparoscopies had detectable PL mKRAS, suggesting that standard staging may be inadequate. Longer follow-up will elucidate utility of this promising molecular assay.
AB - Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with predilection for peritoneal dissemination. Accurate peritoneal staging is imperative for treatment recommendations, as one-third of patients develop peritoneal recurrence after resection. Because >90% of PDAC tumors harbor mutant KRAS (mKRAS), we sought to determine feasibility of mKRAS DNA detection in peritoneal lavage (PL) fluid using droplet-digital polymerase chain reaction (ddPCR) via a prospective trial. Study design: Patients with nonmetastatic PDAC undergoing staging laparoscopy with PL were included. PL fluid was sent for cytologic examination, CA19-9/CEA levels, and mKRAS ddPCR assay. Clinically positive laparoscopy was defined as gross metastases or positive cytology. PL mKRAS status was compared with gross findings, cytology, and CA19-9/CEA levels. Results: There were 136 patients enrolled; 70 of 136 (51%) patients received neoadjuvant therapy before PL, and 32 of 136 (24%) patients had clinically positive laparoscopy. Cytology was positive in 17 of 136 (13%) patients, and 22 of 136 (16%) patients had gross metastases. Of patients with gross metastases, only 8 of 22 (36%) had positive cytology; 97 of 136 (71%) patients had mKRAS in PL. PL mKRAS was present in 27 of 32 (84%) clinically positive laparoscopies, with higher mean copy number in clinically positive patients (643 vs 10, p = 0.02). Peritoneal mKRAS was positive in an additional 70 clinically negative patients. Conclusions: This prospective study establishes the feasibility of PL mKRAS detection. Clinically positive disease was identified in 1 in 4 staging laparoscopies. Although PL mKRAS was highly associated with clinically positive findings, many clinically negative laparoscopies had detectable PL mKRAS, suggesting that standard staging may be inadequate. Longer follow-up will elucidate utility of this promising molecular assay.
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U2 - 10.1016/j.jamcollsurg.2021.05.009
DO - 10.1016/j.jamcollsurg.2021.05.009
M3 - Article
C2 - 34022414
AN - SCOPUS:85106562666
SN - 1072-7515
VL - 233
SP - 73-80.e1
JO - Journal of the American College of Surgeons
JF - Journal of the American College of Surgeons
IS - 1
ER -