Heckl Steffen M, Behrens Hans-Michael, Ebert Ulrike, Ulase Dita, Richter Florian, Becker Thomas, Letsch Anne, Röcken Christoph
Department of Pathology, Christian-Albrechts-University, University Hospital Schleswig-Holstein, Arnold-Heller-Str. 3, Building U33, 24105, Kiel, Germany.
Department of Internal Medicine II, Christian-Albrechts-University, University Hospital Schleswig-Holstein, Kiel, Germany.
Gastric Cancer. 2025 May 16. doi: 10.1007/s10120-025-01624-8.
Since the FLOT4 gastric cancer (GC) trial, the use of adjuvant chemotherapy has been perceived as limited and its added value questioned. We wanted to objectify this perception and reassess the value of adjuvant chemotherapy in a real-world setting.
In our retrospective cohort study we analyzed real-world data from 147 patients with GC or cancer of the gastroesophageal junction (AEG) who received perioperative FLOT. Data originated from clinical care at the university hospital, local hospitals and medical practices. Clinicopathologic data, survival outcomes, and targetable biomarkers were analyzed.
Median overall survival (OS) and tumor specific survival (TSS) were 19.4 ± 2.9 and 19.9 ± 3.1 months, respectively. 84.4% completed all cycles of neoadjuvant chemotherapy. The pathological complete response rate was 11.8%. Adjuvant chemotherapy was initiated in only 42.9%. Survival rates of patients with marked tumor regression (TRG1) were not improved by adjuvant chemotherapy. Conversely, patients with partial histopathologic response (TRG2) showed a marked trend and those with minimal histopathologic response (TRG3) showed a significantly longer survival with any number of adjuvant chemotherapy cycles (OS: 22.3 ± 2.6 months versus 8.7 ± 2.4 months, p = 0.005; TSS: 22.3 ± 4.5 months versus 8.7 ± 2.4 months, p = 0.016). Targetable biomarkers PD-L1, Claudin 18.2, HER2 and microsatellite instability were detected in 53.4%, 26.2%, 7.8%, and 3.9% of the TRG2/3 patient subset, respectively.
In the real-world setting, adjuvant chemotherapy proved to be a critical turning point of the FLOT regimen. It should be sought-even in a reduced form-in patients with TRG2/3.
自FLOT4胃癌（GC）试验以来，辅助化疗的应用被认为有限，其附加价值也受到质疑。我们希望客观验证这一认知，并在真实世界环境中重新评估辅助化疗的价值。
在我们的回顾性队列研究中，我们分析了147例接受围手术期FLOT治疗的GC或胃食管交界癌（AEG）患者的真实世界数据。数据来源于大学医院、当地医院和医疗实践中的临床护理。分析了临床病理数据、生存结果和可靶向生物标志物。
中位总生存期（OS）和肿瘤特异性生存期（TSS）分别为19.4±2.9个月和19.9±3.1个月。84.4%的患者完成了新辅助化疗的所有周期。病理完全缓解率为11.8%。仅42.9%的患者开始了辅助化疗。辅助化疗并未改善肿瘤显著消退（TRG1）患者的生存率。相反，部分组织病理学缓解（TRG2）的患者显示出明显的趋势，而组织病理学缓解最小（TRG3）的患者在接受任何周期的辅助化疗后生存期显著延长（OS：22.3±2.6个月对8.7±2.4个月，p = 0.005；TSS：22.3±4.5个月对8.7±2.4个月，p = 0.016）。在TRG2/3患者亚组中，分别有53.4%、26.2%、7.8%和3.9%的患者检测到可靶向生物标志物PD-L1、Claudin 18.2、HER2和微卫星不稳定性。
在真实世界环境中，辅助化疗被证明是FLOT方案的关键转折点。对于TRG2/3的患者，即使是简化形式的辅助化疗也应采用。
