Frequency and outcomes of BRAF alterations identified by liquid biopsy in metastatic, non-colorectal gastrointestinal cancers.

Background Impact of BRAF V600E mutations (BRAF V600E), a poor prognostic factor in metastatic colorectal cancer, is lacking in non-CRC gastrointestinal (GI) cancers including pancreatic (PDAC), gastric/gastroesophageal (GEA), hepatocellular carcinoma (HCC), and cholangiocarcinoma (CCA). Due to tumo...

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Published in:Oncologist Vol. 30; no. 3; pp. 1 - 10
Main Authors: Mahipal, Amit, Bucheit, Leslie, Zhang, Nicole, Barnett, Reagan M, Storandt, Michael H, Chakrabarti, Sakti
Format: research tables/charts Journal Article
Published: Oxford University Press / USA Mar2025
Online Access:View this record in EBSCOhost
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      dt: Mar2025
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      pub: Oxford University Press / USA
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        10.1093/oncolo/oyaf044
        184296452
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        atl: Frequency and outcomes of BRAF alterations identified by liquid biopsy in metastatic, non-colorectal gastrointestinal cancers.
      aug:
        au:
          Mahipal, Amit
          Bucheit, Leslie
          Zhang, Nicole
          Barnett, Reagan M
          Storandt, Michael H
          Chakrabarti, Sakti
        affil: University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, United States
      sug:
        subj:
          Gastrointestinal Neoplasms Drug Therapy
          Transferases
          Gastrointestinal Neoplasms Diagnosis
          Liquid Biopsy
          Mutation
          Decision Making, Clinical
          Human
          Genomics
          Chi Square Test
          Overall Survival
          Gastrointestinal Neoplasms Prognosis
          Outcome Assessment
          Descriptive Statistics
          DNA
          Gastrointestinal Neoplasms Epidemiology
      ab: Background Impact of BRAF V600E mutations (BRAF V600E), a poor prognostic factor in metastatic colorectal cancer, is lacking in non-CRC gastrointestinal (GI) cancers including pancreatic (PDAC), gastric/gastroesophageal (GEA), hepatocellular carcinoma (HCC), and cholangiocarcinoma (CCA). Due to tumor-agnostic approvals for patients with BRAF V600E, understanding the frequency and impact of BRAF alterations across non-CRC GI cancers is essential for clinical decision-making. Methods Patients with PDAC, GEA, HCC, or CCA who had cell-free DNA detected on Guardant360 (Guardant Health) from 2020 to 2023 were queried. Prevalence of characterized BRAF genomic alterations (GA) was calculated; GAs were grouped by class (Class I/II/III). The Chi-squared test assessed differences between cancer types. A subset of patients had outcomes analysis using GuardantINFORM, a real-world clinicogenomic database, to derive real-world overall survival (rwOS). Results Of 32 480 included patients, BRAF GAs were identified in 4.4%; 19% were BRAF V600E (0.81% prevalence overall). CCA had the highest rate of BRAF GAs and BRAF V600E (P  < .01); HCC and GEA had the highest rates of BRAF class II/III alterations. There were no significant differences in rwOS by alteration class or cancer type; numeric differences were observed by alteration class. Few patients were treated with BRAF inhibitors (2.2%). Prevalence of co-occurring alterations was unique by cancer type. Conclusions Frequency of BRAF GAs, including BRAF V600E, in non-CRC GI cancers detected by liquid biopsy is similar to tissue-based rates and can be reliably used to assess BRAF status. BRAF GAs have mixed prognostic implications on survival for patients with non-CRC GI malignancies that warrant further exploration.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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