Prognostic Utility of Pre- and Postoperative Circulating Tumor DNA Liquid Biopsies in Patients with Peritoneal Metastases.

Autor: Baumgartner JM; Department of Surgery, Division of Surgical Oncology, University of California, San Diego, La Jolla, CA, USA. j1baumgartner@ucsd.edu., Riviere P; Center for Personalized Cancer Therapy, University of California, San Diego, La Jolla, CA, USA., Lanman RB; Guardant Health, Inc., Redwood City, CA, USA., Kelly KJ; Department of Surgery, Division of Surgical Oncology, University of California, San Diego, La Jolla, CA, USA., Veerapong J; Department of Surgery, Division of Surgical Oncology, University of California, San Diego, La Jolla, CA, USA., Lowy AM; Department of Surgery, Division of Surgical Oncology, University of California, San Diego, La Jolla, CA, USA., Kurzrock R; Center for Personalized Cancer Therapy, University of California, San Diego, La Jolla, CA, USA.
Jazyk: angličtina
Zdroj: Annals of surgical oncology [Ann Surg Oncol] 2020 Sep; Vol. 27 (9), pp. 3259-3267. Date of Electronic Publication: 2020 Aug 06.
DOI: 10.1245/s10434-020-08331-x
Abstrakt: Background: Circulating tumor DNA (ctDNA) is a promising technology for treatment selection, prognostication, and surveillance after definitive therapy. Its use in the perioperative setting for patients with metastatic disease has not been well studied. We characterize perioperative plasma ctDNA and its association with progression-free survival (PFS) in patients undergoing surgery for peritoneal metastases.
Patients and Methods: We recruited 71 patients undergoing surgery for peritoneal metastases and evaluated their plasma with a targeted 73-gene ctDNA next-generation sequencing test before and after surgery. The association between perioperative ctDNA, as well as other patient factors, and PFS was evaluated by Cox regression.
Results: ctDNA was detectable in 28 patients (39.4%) preoperatively and in 37 patients (52.1%) postoperatively. Patients with high ctDNA [maximum somatic variant allele fraction (MSVAF) > 0.25%] had worse PFS than those with low MSVAF (< 0.25%) in both the pre- and postoperative settings (median 4.8 vs. 19.3 months, p < 0.001, and 9.2 vs.15.0 months, p = 0.049, respectively; log-rank test). On multivariate analysis, high-grade histology [hazard ratio (HR) 3.42, p = 0.001], incomplete resection (HR 2.35, p = 0.010), and high preoperative MSVAF (HR 3.04, p = 0.001) were associated with worse PFS. Patients with new postoperative alterations in the context of preoperative alteration(s) also had a significantly shorter PFS compared with other groups (HR 4.28, p < 0.001).
Conclusions: High levels of perioperative ctDNA and new postoperative ctDNA alterations in the context of preoperative alterations predict worse outcomes in patients undergoing resection for peritoneal metastases. This may highlight a role for longitudinal ctDNA surveillance in this population.
Databáze: MEDLINE
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