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

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 u...

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Veröffentlicht in:Annals of surgical oncology 2020-12, Vol.27 (13), p.5065-5071
Hauptverfasser: Leick, Katie M., Kazarian, Austin G., Rajput, Maheen, Tomanek-Chalkley, Ann, Miller, Ann, Shrader, Hannah R., McCarthy, Ashley, Coleman, Kristen L., Kasi, Pashtoon M., Chan, Carlos H. F.
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Sprache:eng
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Zusammenfassung: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: 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.
ISSN:1068-9265
1534-4681
DOI:10.1245/s10434-020-08832-9