• Timothy E Newhook, Michael J Overman, Yun Shin Chun, Arvind Dasari, TzengChing-Wei DCDDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX., CaoHop S TranHSTDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX., Victoria Raymond, Christine Parseghian, Benny Johnson, Yujiro Nishioka, Yoshikuni Kawaguchi, Abhineet Uppal, Timothy J Vreeland, Ariel Jaimovich, Elsa M Arvide, Jenilette V Cristo, Steven H Wei, Kanwal P Raghav, Van K Morris, Jeffrey E Lee, Scott Kopetz, and Jean-Nicolas Vauthey.
• Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
• Ann. Surg. 2023 May 1; 277 (5): 813820813-820.

ObjectiveTo evaluate the association of perioperative ctDNA dynamics on outcomes after hepatectomy for CLM.Summary Background DataPrognostication 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.MethodsPatients 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.ResultsForty-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).ConclusionsPerioperative 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.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

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