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Peritoneal Cell-Free Tumor DNA as Biomarker for Peritoneal Surface Malignancies

Abstract

Background

Disease burden in patients with peritoneal carcinomatosis (PC) is difficult to estimate. We evaluate whether peritoneal cell-free tumor DNA can be used as a measure of disease burden.

Patients and Methods

Malignant ascites or peritoneal lavage fluids were collected from patients with PC under approved IRB protocol. Cell-free DNA was extracted from peritoneal fluid. Droplet digital PCR (ddPCR) was performed using a commercially available KRAS G12/G13 screening kit. Mutant allele frequency (MAF) was calculated based on the numbers of KRAS wild-type and mutant droplets. Clinicopathological, treatment and outcome data were abstracted and correlated with MAF of cell-free KRAS mutant DNA.

Results

Cell-free KRAS mutant DNA was detected in 15/37 (40%) malignant peritoneal fluids with a MAF of 0.1% to 26.2%. While peritoneal cell-free KRAS mutant DNA was detected in all the patients with KRAS mutant tumors (N = 10), 3/16 (19%) patients with KRAS wild-type tumors also had peritoneal cell-free KRAS mutant DNA. We also found that 71% (5/7) of patients with disease amenable to cytoreductive surgery (CRS) had a MAF of < 1% (median: 0.5%, range: 0.1–4.7%), while 75% (6/8) of patients with unresectable disease had a MAF of > 1% (median: 4.4%, range: 0.1–26.2%).

Conclusions

This pilot proof-of-principle study suggests that peritoneal cell-free tumor DNA detected by ddPCR may enable prediction of disease burden and a measure of disease amenable to CRS in patients with PC.

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Acknowledgements

This study was supported by the Holden Comprehensive Cancer Center through funds from the National Cancer Institute of the National Institutes of Health under award no. P30 CA086862 for supporting the Molecular Epidemiology Resource Core. A.G.K. was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award no. T35 HL007485. A.M.M. was supported by the National Institutes of Health Free Radical and Radiation Biology T32 CA078586 training grant. H.R.S. was supported by the Iowa Center for Research by Undergraduates Fellowship Awards.

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Correspondence to Carlos H. F. Chan MD, PhD.

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Disclosure

P.M.K.: consultancy/advisory board (Taiho, Ipsen, Foundation Medicine, Natera); Honoraria (AstraZeneca, Foundation Medicine, Natera). Foundation Medicine, a company focusing on genomics and ctDNA in blood/tissue, is not directly related to the submitted work but to ctDNA testing. Natera, a company focusing on ctDNA for stage II/III colorectal cancer, is not directly related to the submitted work but to the field of liquid biopsies. All other authors declare that they have no conflicts of interest.

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Leick, K.M., Kazarian, A.G., Rajput, M. et al. Peritoneal Cell-Free Tumor DNA as Biomarker for Peritoneal Surface Malignancies. Ann Surg Oncol 27, 5065–5071 (2020). https://doi.org/10.1245/s10434-020-08832-9

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  • DOI: https://doi.org/10.1245/s10434-020-08832-9