TY - JOUR
T1 - Prospective Study of Perioperative Circulating Tumor DNA Dynamics in Patients Undergoing Hepatectomy for Colorectal Liver Metastases
AU - Newhook, Timothy E.
AU - Overman, Michael J.
AU - Chun, Yun Shin
AU - Dasari, Arvind
AU - Tzeng, Ching Wei D.
AU - Cao, Hop S.Tran
AU - Raymond, Victoria
AU - Parseghian, Christine
AU - Johnson, Benny
AU - Nishioka, Yujiro
AU - Kawaguchi, Yoshikuni
AU - Uppal, Abhineet
AU - Vreeland, Timothy J.
AU - Jaimovich, Ariel
AU - Arvide, Elsa M.
AU - Cristo, Jenilette V.
AU - Wei, Steven H.
AU - Raghav, Kanwal P.
AU - Morris, Van K.
AU - Lee, Jeffrey E.
AU - Kopetz, Scott
AU - Vauthey, Jean Nicolas
N1 - Publisher Copyright:
© 2022 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2023/5/1
Y1 - 2023/5/1
N2 - Objective: To evaluate the association of perioperative ctDNA dynamics on outcomes after hepatectomy for CLM. Summary Background Data: Prognostication is imprecise for patients undergoing hepatectomy for CLM, and ctDNA is a promising biomarker. However, clinical implications of perioperative ctDNA dynamics are not well established. Methods: Patients underwent curative-intent hepatectomy after preoperative chemotherapy for CLM (2013-2017) with paired prehepatectomy/postoperative ctDNA analyses via plasma-only assay. Positivity was determined using a proprietary variant classifier. Primary endpoint was recurrence-free survival (RFS). Median follow-up was 55 months. Results: Forty-eight patients were included. ctDNA was detected before and after surgery (ctDNA+/+) in 14 (29%), before but not after surgery (ctDNA+/-) in 19 (40%), and not at all (ctDNA-/-) in 11 (23%). Adverse tissue somatic mutations were detected in TP53 (n = 26; 54%), RAS (n = 23; 48%), SMAD4 (n = 5; 10%), FBXW7 (n = 3; 6%), and BRAF (n = 2; 4%). ctDNA+/+ was associated with worse RFS (median: ctDNA+/+, 6.0 months; ctDNA+/-, not reached; ctDNA-/-, 33.0 months; P = 0.001). Compared to ctDNA+/+, ctDNA+/- was associated with improved RFS [hazard ratio (HR) 0.24 (95% confidence interval (CI) 0.1-0.58)] and overall survival [HR 0.24 (95% CI 0.08-0.74)]. Adverse somatic mutations were not associated with survival. After adjustment for prehepatectomy chemotherapy, synchronous disease, and ≥2 CLM, ctDNA+/- and ctDNA-/- were independently associated with improved RFS compared to ctDNA+/+ (ctDNA+/-: HR 0.21, 95% CI 0.08-0.53; ctDNA-/-: HR 0.21, 95% CI 0.08-0.56). Conclusions: Perioperative ctDNA dynamics are associated with survival, identify patients with high recurrence risk, and may be used to guide treatment decisions and surveillance after hepatectomy for patients with CLM.
AB - Objective: To evaluate the association of perioperative ctDNA dynamics on outcomes after hepatectomy for CLM. Summary Background Data: Prognostication is imprecise for patients undergoing hepatectomy for CLM, and ctDNA is a promising biomarker. However, clinical implications of perioperative ctDNA dynamics are not well established. Methods: Patients underwent curative-intent hepatectomy after preoperative chemotherapy for CLM (2013-2017) with paired prehepatectomy/postoperative ctDNA analyses via plasma-only assay. Positivity was determined using a proprietary variant classifier. Primary endpoint was recurrence-free survival (RFS). Median follow-up was 55 months. Results: Forty-eight patients were included. ctDNA was detected before and after surgery (ctDNA+/+) in 14 (29%), before but not after surgery (ctDNA+/-) in 19 (40%), and not at all (ctDNA-/-) in 11 (23%). Adverse tissue somatic mutations were detected in TP53 (n = 26; 54%), RAS (n = 23; 48%), SMAD4 (n = 5; 10%), FBXW7 (n = 3; 6%), and BRAF (n = 2; 4%). ctDNA+/+ was associated with worse RFS (median: ctDNA+/+, 6.0 months; ctDNA+/-, not reached; ctDNA-/-, 33.0 months; P = 0.001). Compared to ctDNA+/+, ctDNA+/- was associated with improved RFS [hazard ratio (HR) 0.24 (95% confidence interval (CI) 0.1-0.58)] and overall survival [HR 0.24 (95% CI 0.08-0.74)]. Adverse somatic mutations were not associated with survival. After adjustment for prehepatectomy chemotherapy, synchronous disease, and ≥2 CLM, ctDNA+/- and ctDNA-/- were independently associated with improved RFS compared to ctDNA+/+ (ctDNA+/-: HR 0.21, 95% CI 0.08-0.53; ctDNA-/-: HR 0.21, 95% CI 0.08-0.56). Conclusions: Perioperative ctDNA dynamics are associated with survival, identify patients with high recurrence risk, and may be used to guide treatment decisions and surveillance after hepatectomy for patients with CLM.
KW - circulating tumor DNA
KW - colorectal liver metastases
KW - ctDNA
KW - hepatectomy
KW - recurrence
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U2 - 10.1097/SLA.0000000000005461
DO - 10.1097/SLA.0000000000005461
M3 - Article
C2 - 35797554
AN - SCOPUS:85152294861
SN - 0003-4932
VL - 277
SP - 813
EP - 820
JO - Annals of surgery
JF - Annals of surgery
IS - 5
ER -