Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128, Padua, Italy.
Medical Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
J Cancer Res Clin Oncol. 2023 Aug;149(9):6601-6611. doi: 10.1007/s00432-023-04636-y. Epub 2023 Feb 16.
FLOT regimen is the standard perioperative treatment in Western countries for patients with locally advanced gastric (GC) or gastroesophageal junction cancer (GEJC). High microsatellite instability (MSI-H) and Mismatch Repair deficient (dMMR) demonstrated a favorable prognostic role and a concomitant negative predictive impact on the benefit of perioperative 5-fluorouracil-based doublets; however, its role in pts receiving FLOT chemotherapy is still unclear.
This is a retrospective, multicenter observational study of 265 pts with GC/GEJC treated with perioperative FLOT regimen in 11 Italian oncology centers between January 2017 to December 2021 and analyzed for microsatellite status.
The MSI-H phenotype was found in 27 (10.2%) of 265 analyzed tumors. Compared to microsatellite stable (MSS) and Mismatch Repair proficient (pMMR) cases, MSI-H/dMMR were more frequently female (48.1% vs. 27.3%, p = 0.0424), elderly pts (age > 70 years, 44.4% vs. 13.4%, p = 0.0003), Laurens's intestinal type (62.5% vs. 36.1%, p = 0.02) and pts with a primary location tumor in the antrum (37 vs. 14.3%, p = 0.0004). A statistically significant difference in the rate of pathologically negative lymph node emerged (63% vs 30.7%, p = 0.0018). Compared to the MSS/pMMR tumor population, the MSI-H/dMMR subgroup had a better DFS (median not reached [NR] vs. 19.5 [15.59-23.59] mos, p = 0.031) and OS (median NR vs. 34.84 [26.68-47.60] mos, p = 0.0316).
These real-world data confirm that FLOT treatment is effective in daily clinical practice for locally advanced GC/GEJC, also in the MSI-H/dMMR subgroup. It also showed a higher rate of nodal status downstaging and a better outcome of MSI-H/dMMR pts in comparison to MSS/pMMR.
FLOT 方案是西方国家局部晚期胃（GC）或胃食管交界处癌（GEJC）患者围手术期的标准治疗方案。高度微卫星不稳定（MSI-H）和错配修复缺陷（dMMR）显示出有利的预后作用，并对围手术期基于 5-氟尿嘧啶的双药治疗的获益产生了伴随的负面预测影响；然而，其在接受 FLOT 化疗的患者中的作用仍不清楚。
这是一项回顾性、多中心观察性研究，纳入了 2017 年 1 月至 2021 年 12 月期间在意大利 11 个肿瘤中心接受围手术期 FLOT 方案治疗的 265 例 GC/GEJC 患者，并对微卫星状态进行了分析。
在分析的 265 例肿瘤中，发现 MSI-H 表型 27 例（10.2%）。与微卫星稳定（MSS）和错配修复功能正常（pMMR）病例相比，MSI-H/dMMR 患者更多为女性（48.1%比 27.3%，p=0.0424）、老年患者（>70 岁，44.4%比 13.4%，p=0.0003）、Laurens 肠型（62.5%比 36.1%，p=0.02）和肿瘤原发部位在胃窦部（37%比 14.3%，p=0.0004）的患者更为常见。在病理阴性淋巴结的检出率方面存在统计学显著差异（63%比 30.7%，p=0.0018）。与 MSS/pMMR 肿瘤人群相比，MSI-H/dMMR 亚组的 DFS 更好（中位无进展生存期未达到[NR]比 19.5[15.59-23.59]个月，p=0.031），OS 更好（中位 NR 比 34.84[26.68-47.60]个月，p=0.0316）。
这些真实世界的数据证实，FLOT 治疗在局部晚期 GC/GEJC 的临床实践中也是有效的，即使在 MSI-H/dMMR 亚组中也是如此。与 MSS/pMMR 相比，它还显示出更高的淋巴结状态降级率和 MSI-H/dMMR 患者更好的结局。
