Published in:
01-12-2020 | Peritoneal Cancer | Translational Research
Peritoneal Cell-Free Tumor DNA as Biomarker for Peritoneal Surface Malignancies
Authors:
Katie M. Leick, MD, MS, Austin G. Kazarian, BS, Maheen Rajput, MD, Ann Tomanek-Chalkley, BS, Ann Miller, PhD, Hannah R. Shrader, BA, BS, Ashley McCarthy, BS, MPH, Kristen L. Coleman, PhD, Pashtoon M. Kasi, MD, MS, Carlos H. F. Chan, MD, PhD
Published in:
Annals of Surgical Oncology
|
Issue 13/2020
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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.