Katie M Leick1, Austin G Kazarian1, Maheen Rajput2, Ann Tomanek-Chalkley1, Ann Miller1, Hannah R Shrader1, Ashley McCarthy3, Kristen L Coleman3, Pashtoon M Kasi3,4, Carlos H F Chan5,6. 1. Department of Surgery, University of Iowa, Iowa City, IA, USA. 2. Department of Radiology, University of Iowa, Iowa City, IA, USA. 3. Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. 4. Internal Medicine, University of Iowa, Iowa City, IA, USA. 5. Department of Surgery, University of Iowa, Iowa City, IA, USA. carloshfchan@gmail.com. 6. Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. carloshfchan@gmail.com.
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.
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.
Authors: Enrico M Pasqual; Serena Bertozzi; Stefano Bacchetti; Ambrogio P Londero; Stefano M M Basso; Davide A Santeufemia; Giovanni Lo Re; Franco Lumachi Journal: Anticancer Res Date: 2014-05 Impact factor: 2.480
Authors: Iris Van't Erve; Koen P Rovers; Alexander Constantinides; Karen Bolhuis; Emma Ce Wassenaar; Robin J Lurvink; Clément J Huysentruyt; Petur Snaebjornsson; Djamila Boerma; Daan van den Broek; Tineke E Buffart; Max J Lahaye; Arend Gj Aalbers; Niels Fm Kok; Gerrit A Meijer; Cornelis Ja Punt; Onno Kranenburg; Ignace Hjt de Hingh; Remond Ja Fijneman Journal: J Pathol Clin Res Date: 2021-02-26