Circulating tumor DNA molecular analyses and real-world evidence outcomes of FGFR2 amplified gastroesophageal cancers Journal Article
| Authors: | Shariff, B.; Barnett, R. M.; Dayyani, F.; Maron, S. B.; McGriskin, R.; Klempner, S.; Donderici, E. Y.; Zhang, N.; Masannat, J.; Drusbosky, L. M.; Mehta, R. |
| Article Title: | Circulating tumor DNA molecular analyses and real-world evidence outcomes of FGFR2 amplified gastroesophageal cancers |
| Abstract: | Purpose: In addition to the existing biomarkers HER2 and PD-L1, FGFR2b has become an area of interest for the development of new targeted-based treatment. Given that clinical evaluation of FGFR2 targeted therapy is underway, we sought to elucidate the genomic landscape of FGFR2amp in gastroesophageal cancer (GEC) using a circulating tumor DNA (ctDNA) platform. Materials and Methods: We retrospectively evaluated the Guardant Health database from 2017 to 2022 for patients with GECs with Guardant360 ctDNA next-generation sequencing (NGS) performed. We assessed co-occurring genetic alterations for patients who harbored FGFR2amp versus FGFR2null. We also explored real-world evidence database with Guardant Health, publicly available genomic databases (MSK cohort using cBioPortal), and pooled clinical data from large-volume cancer centers for FGFR2amp GECs. Results: Less than 4% of patients with GEC in the Guardant Health database were identified to be FGFR2amp. The most commonly co-occurring gene mutations were TP53, CTNNB1, CDH1, and RHOA. Upon interrogation of the MSK cohort, these same genes were not significant on tissue NGS in the FGFR2amp cohort of GEC. In the pooled institutional cohort, we noted that FGFR2amp tumors were most commonly involving the gastroesophageal junction (GEJ). The overall survival of these patients was noted at 13.1 months. Conclusion: FGFR2 is a validated target in GECs, and the contexture of FGFR2amp will be important in defining patient subgroups with responses to FGFR2-directed therapy. Using ctDNA to provide a more detailed genomic landscape in patients with GECs will allow the advancement of targeted therapy in the near future for these aggressive cancers. © The Author(s) 2024. |
| Keywords: | adult; cancer survival; clinical article; human tissue; aged; middle aged; retrospective studies; gene mutation; gene sequence; overall survival; sequence analysis; genetics; mutation; validation process; cancer staging; adenocarcinoma; gene; gene amplification; epidermal growth factor receptor 2; evidence based practice; pathology; retrospective study; protein p53; uvomorulin; tumor marker; histology; blood; stomach cancer; rhoa guanine nucleotide binding protein; multivariate analysis; esophagus cancer; stomach neoplasms; esophagus tumor; esophageal neoplasms; fibroblast growth factor receptor 2; receptor, fibroblast growth factor, type 2; stomach tumor; programmed death 1 ligand 1; landscape; molecularly targeted therapy; copy number variation; nucleophosmin; clinical outcome; gastroesophageal cancer; demographics; gastroesophageal junction; procedures; high throughput sequencing; ctnnb1 gene; high-throughput nucleotide sequencing; rhoa gene; humans; human; male; female; article; circulating tumor dna; fgfr2 protein, human; liquid biopsy; biomarkers, tumor; real-world data; elixhauser comorbidity index; fgfr2 amplification |
| Journal Title: | The Oncologist |
| Volume: | 29 |
| Issue: | 8 |
| ISSN: | 1083-7159 |
| Publisher: | Oxford University Press |
| Date Published: | 2024-08-01 |
| Start Page: | 672 |
| End Page: | 680 |
| Language: | English |
| DOI: | 10.1093/oncolo/oyae061 |
| PUBMED: | 38902956 |
| PROVIDER: | scopus |
| PMCID: | PMC11299948 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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