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Circulating tumor DNA before and after surgical resection in patients with peritoneal carcinomatosis.
Background: Analysis of cell-free DNA (cfDNA) using next generation sequencing (NGS) may be a useful tool for the detection and monitoring of alterations present in circulating tumor DNA (ctDNA). To date, most analyses of ctDNA have been performed on patients with locally advanced or widely metastatic disease. Patients with peritoneal carcinomatosis present unique diagnostic, prognostic and therapeutic challenges. We sought to explore pre- and postoperative ctDNA detection rates and correlation with outcomes in patients with peritoneal carcinomatosis in whom surgery was planned. Methods: Patients referred for surgical resection of peritoneal carcinomatosis underwent pre- and postoperative ctDNA analysis using NGS of plasma cfDNA (68 genes, Guardant Health, a CLIA-licensed lab). Results: Forty-five patients have undergone preoperative ctDNA testing (26 [57.8%] women; median age, 54 years). Diagnoses included: 36 (80.0%) patients with appendix cancer; 6 (13.3%), colorectal; 1 (2.2%) each of small bowel, cholangiocarcinoma, and peritoneal mesothelioma. Thirty-two patients (71.1%) underwent curative-intent tumor resection; while 13 (28.9%) underwent palliative-intent surgery. Fourteen patients (31.1%) had detectable preoperative ctDNA alterations, most frequently in the following genes: TP53 (23.8% of all preoperative alterations detected), KRAS (19.0%), GNAS (9.5%), and TERT(9.5%). Fifty-two percent (12/23) of patients that have undergone postoperative ctDNA testing (median 2.9 weeks after surgery; range, 1.1 to 21.3 weeks) had a detectable postoperative ctDNA alteration. Two patients had different genetic alterations detected than those found preoperatively, and 2 of 14 patients (14.2%) who had preoperative alterations showed no alterations postoperatively. Conclusions: A significant proportion of patients with peritoneal carcinomatosis referred for surgical intervention have detectable ctDNA alterations before and after surgery. Further study of potential association between clinical outcome and quantity of ctDNA and the presence of postoperative ctDNA alterations, as well as correlations with tissue NGS are ongoing and will be included in the final data presentation.