A19: Circulating Tumor DNA Is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis

Saturday, March 12, 2022

8:11 AM – 8:19 AM CST

Location: Coronado

Abstract Presenter(s)

Brittany G. Sullivan, MD

Resident
University of California - Irvine General Surgery
Long Beach, California, United States

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Participants should be aware of the following financial/non-financial relationships:

Brittany G. Sullivan, MD: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Introduction:

Tumor agnostic, circulating tumor DNA (ctDNA) is routinely used to guide treatment decisions in gastrointestinal (GI) cancers, especially metastatic cancers. Since the amount of ctDNA detected in plasma is affected by tumor burden and tumor vascularization, the sensitivity of ctDNA will be influenced by the type of metastasis. Particularly, peritoneal carcinomatosis (PC) due to the plasma peritoneal barrier, is likely associated with lower ctDNA levels than other metastatic sites in GI cancers. We sought to analyze and compare ctDNA levels in patients with GI peritoneal carcinomatosis and visceral metastasis.

Methods:

We conducted a retrospective analysis of patients with stage II-IV GI cancers treated at our institution between 2015 to 2020 with available panel-based ctDNA results (Guardant 360 ^TM). ctDNA analysis was performed on early and pre- treatment samples. We compared the reported maximum variant allele frequency (mVAF) of somatic mutations across metastatic sites with the Kruskal-Wallis test.

Results:

Of the 295 patients with GI cancers (colorectal, upper GI, pancreaticobiliary), 228 had stage IV disease (PC n=61; visceral met n=138; other met n=14). Mean mVAF increased with increasing stages of disease (Stage II: 3.6 ± 7, Stage III: 6.4 ± 10, Stage IV: 28.0 ± 51; p< 0.01). Among patients with stage IV disease, PC was associated with nearly 2.5 fold lower mean ctDNA levels compared to visceral metastases, independent of primary tumor site (PC only: 14.2 ± 42, PC+ visceral met: 23.2 ± 44, and visceral met only: 36.7 ± 44; p< 0.01). In a subset of patients (n=27), matched pair analysis of genomic alterations (GA) showed that in 56% of patients there were no concordance between plasma and tissue GA detected and in an additional 26%, no pathogenic mutations were detected in plasma despite being detected in tumor.

Conclusions:

PC of GI origin is associated with significantly lower ctDNA levels compared to visceral metastasis. Caution is warranted when interpreting ctDNA results from patients with PC due to lower sensitivity for detecting actionable mutations.

Learning Objectives:

Upon completion, participants will be able to identify what cancer features affects the amount of ctDNA found in plasma.
Upon completion, participants will be able to define what stage of cancer is associated with the highest amount of ctDNA.
Upon completion, participants will recognize that peritoneal carcinomatosis is associated with lower levels of ctDNA and lower identifiable genomic alterations when compared to tissue samples.