Circulating Tumor DNA is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis

• Published in: Annals of surgical oncology 2023-01, Vol.30 (1), p.278-284
• Main Authors: Sullivan, Brittany G., Lo, Angelina, Yu, Jingjing, Gonda, Amber, Dehkordi-Vakil, Farideh, Dayyani, Farshid, Senthil, Maheswari
• Format: Article
• Language: English
• Subjects: Cancer; Circulating Tumor DNA - genetics; Gastric cancer; Gastrointestinal Neoplasms - diagnosis; Gastrointestinal Neoplasms - genetics; Gastrointestinal Oncology; Gene frequency; Genomic analysis; Genomics; Humans; Medicine; Medicine & Public Health; Metastases; Metastasis; Mutation; Oncology; Patients; Peritoneum; Retrospective Studies; Surgery; Surgical Oncology; Tumors; Vascularization
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-022-12399-y

Introduction Tumor agnostic circulating tumor DNA (ctDNA) is routinely used to guide treatment decisions in gastrointestinal (GI) cancers, especially metastatic cancers. The amount of ctDNA detected in plasma is affected by stage, tumor burden, and tumor vascularization. We hypothesized that peritoneal carcinomatosis (PC) is associated with lower ctDNA levels than other metastatic sites in GI cancers due to the plasma–peritoneal barrier. Methods We conducted a retrospective analysis of patients with stage II–IV GI cancers treated at our institution between 2015 and 2020 with available panel-based ctDNA results (Guardant 360 TM ). ctDNA analysis was performed on early and pretreatment samples. We compared the reported maximum variant allele frequency (mVAF) of somatic mutations across metastatic sites. Results Of the 279 patients with GI cancers (colorectal, upper GI, pancreaticobiliary), 212 had stage IV disease (PC: n  = 61; visceral metastases: n  = 138; other metastases: n  = 13). Mean mVAF increased with increasing stages of disease (stage II: 3.6 ± 7; stage III: 6.4 ± 10; stage IV: 28.0 ± 51; p