RESUMO
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.
Assuntos
DNA Tumoral Circulante , Neoplasias Esofágicas , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Neoplasias Gástricas , Humanos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Idoso , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , AdultoRESUMO
In the last two decades, the incidence of gastroesophageal junction (GEJ) adenocarcinomas (AC) has increased, in part due to the increasing prevalence of obesity and untreated gastroesophageal reflux disease (GERD). Esophageal and GEJ cancers have become one of the leading causes of cancer deaths worldwide due to its aggressive nature. While the mainstay of treatment for locally advanced gastroesophageal cancers (GECs) remains surgery, several studies have now shown that multimodality approach yields better outcomes. GEJ cancers have historically been included both in esophageal cancer as well as gastric cancer trials. Therefore, both approaches, neoadjuvant chemoradiation (CRT) or perioperative chemotherapy are considered standard treatment options. thereon the same token, there yet remains a debate for the 'gold standard' treatment of locally advanced GEJ cancers. The landmark trials, fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT) and ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS), have shown similar improvements in overall survival (OS) and disease-free survival (DFS) for patients with resectable locoregional GEJ cancers. In this review, the authors attempt to highlight the historical evolution of current standard treatments and provide a sneak peek into the future of treatment of GEJ cancers. Several factors must be borne in mind when making the optimal choice for a patient. Some of these include surgical candidacy, tolerance to chemotherapy, eligibility for radiation (RT) as well as institutional preferences.