| Sumario: | 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.
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