Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Division of Hematology and Oncology, Department of Internal Medicine, Hanyang University Guri Hospital, Guri, South Korea.
Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Pathol Res Pract. 2020 Apr;216(4):152878. doi: 10.1016/j.prp.2020.152878. Epub 2020 Feb 13.
Recurrent FGFR2 amplification is observed in gastroesophageal cancers but clinical implications are unknown. We investigated the association of FGFR2 amplification with cytotoxic chemotherapy outcome in gastroesophageal cancer (GC) patients.
Between 2016 and 2018, we identified 1045 metastatic GC patients who received palliative fluoropyrimidine/platinum-based chemotherapy and underwent tumor genomic profiling at a tertiary hospital in Korea and two US cancer centers. We retrospectively identified FGFR2-amplified cases and abstracted clinicopathologic features and treatment outcomes. Cox proportional hazard regression model was used to evaluate the variables that demonstrated effects on progression free and overall survival PFS and OS. Descriptive statistics were used to correlate level of FGFR2 copy number amplification CNA and clinicopathological parameters.
The incidence of FGFR2-amplified GC was 4.0 %. A total of 42 FGFR2-amplified GC patients were included and divided into high and lower FGFR2 amplification values. Fifteen patients had an FGFR2 CNA greater than 30, and 27 had a CNA of 30 or less. There was no significant differences between age, sex, tumor localization, Lauren classification, or tumor staging. After a median follow-up duration of 11.4 months, patients with high FGFR2 amplification had significantly poorer median PFS (3.2 vs. 4.8 months, hazard ratio (HR) 2.08, 95 % CI, 1.03-4.22, P = 0.042) and significantly shorter median OS (10.1 vs. 26.3 months, HR 2.99, 95 % CI = 1.05-8.49, P = 0.040) than the low FGFR2 amplification group.
Recurrent FGFR2 amplification was observed in roughly 4.0 % of GC patients. High FGFR2 amplification was significantly associated with poor progression free survival and overall survival in GC patients. Clinical studies of FGFR2-directed therapies are warranted and should consider stratification by FGFR2 CNA.
FGFR2 扩增在胃食管癌症中经常观察到，但临床意义尚不清楚。我们研究了 FGFR2 扩增与胃食管癌症（GC）患者细胞毒性化疗结果的关联。
在 2016 年至 2018 年期间，我们在韩国的一家三级医院和两家美国癌症中心鉴定了 1045 名接受姑息性氟嘧啶/铂类化疗的转移性 GC 患者，并对其肿瘤基因组进行了分析。我们回顾性地确定了 FGFR2 扩增病例，并提取了临床病理特征和治疗结果。使用 Cox 比例风险回归模型来评估对无进展生存期（PFS）和总生存期（OS）有影响的变量。描述性统计用于关联 FGFR2 拷贝数扩增（CNA）的水平和临床病理参数。
FGFR2 扩增 GC 的发生率为 4.0%。共纳入 42 例 FGFR2 扩增 GC 患者，并分为高和低 FGFR2 扩增值。15 例患者的 FGFR2 CNA 大于 30，27 例患者的 CNA 为 30 或更低。年龄、性别、肿瘤定位、Lauren 分类或肿瘤分期之间无显著差异。在中位随访 11.4 个月后，高 FGFR2 扩增患者的中位 PFS（3.2 与 4.8 个月，风险比（HR）2.08，95%CI，1.03-4.22，P=0.042）和中位 OS（10.1 与 26.3 个月，HR 2.99，95%CI=1.05-8.49，P=0.040）显著短于低 FGFR2 扩增组。
大约 4.0%的 GC 患者中存在复发性 FGFR2 扩增。高 FGFR2 扩增与 GC 患者无进展生存期和总生存期的不良显著相关。需要进行 FGFR2 靶向治疗的临床研究，并且应该考虑根据 FGFR2 CNA 进行分层。
