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

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Abstract

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.

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Authors

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Correspondence to Joel M. Baumgartner MD, MAS.

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Financial support

Funded in part by the National Cancer Institute (grant P30 CA023100) and the Joan and Irwin Jacobs Fund philanthropic fund. Study also funded in part by the Guardant Health (Guardant Health, Inc., Redwood City, CA). The project described was partially supported by the National Institutes of Health (grant TL1TR001443 of CTSA funding beginning August 13, 2015 and beyond). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Disclosures

Razelle Kurzrock discloses stock and other equity interests (IDbyDNA, CureMatch, Inc., and Soluventis); consulting or advisory role (Gaido, LOXO, X-Biotech, Actuate Therapeutics, Roche, NeoMed, Soluventis, and Pfizer); speaker’s fee (Roche); research Fundingf [Incyte, Genentech, Merck Serono, Pfizer, Sequenom, Foundation Medicine, Guardant Health, Grifols, Konica Minolta, DeBiopharm, Boerhringer Ingelheim, and OmniSeq (all institutional)]; board member (CureMatch, Inc). Paul Riviere discloses consulting fees from Peptide Logic, LLC. Richard Lanman is an employee of Guardant Health, Inc.

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Baumgartner, J.M., Riviere, P., Lanman, R.B. et al. Prognostic Utility of Pre- and Postoperative Circulating Tumor DNA Liquid Biopsies in Patients with Peritoneal Metastases. Ann Surg Oncol 27, 3259–3267 (2020). https://doi.org/10.1245/s10434-020-08331-x

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  • DOI: https://doi.org/10.1245/s10434-020-08331-x

Keywords

  • Cancer prognostication
  • Liquid biopsy
  • Cancer surveillance