Gervaso Lorenzo, Bottiglieri Luca, Meneses-Medina Monica Isabel, Pellicori Stefania, Biffi Roberto, Fumagalli Romario Uberto, De Pascale Stefano, Sala Isabella, Bagnardi Vincenzo, Barberis Massimo, Cella Chiara Alessandra, Fazio Nicola
Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO IRCCS, Via Ripamonti 435, Milan, Italy.
Molecular Medicine Department, University of Pavia, Pavia, Italy.
Clin Transl Oncol. 2023 Nov;25(11):3287-3295. doi: 10.1007/s12094-023-03179-5. Epub 2023 Apr 21.
Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced gastric cancer (LAGC). Several biomarkers, including HER2 and MMR/MSI are crucial for treatment decisions in the advanced stage but, currently, no biomarkers can guide the choice of NAC in clinical practice. Our aim was to evaluate the role of MSI and HER2 status on clinical outcomes.
We retrospectively collected LAGC patients treated with NAC and surgery +/- adjuvant chemotherapy from 2006 to 2018. HER2 and MSI were assessed on endoscopic and surgical samples. Pathologic complete response (pCR) rate, overall survival (OS), and event-free survival (EFS) were estimated and evaluated for association with downstaging and MSI.
We included 76 patients, 8% were classified as MSI-H, entirely consistent between endoscopic and surgical samples. Six percent of patients were HER2 positive on endoscopic and 4% on surgical samples. Tumor downstaging was observed in 52.5% of cases, with three pCR (5.1%), none in MSI-H cancers. According to MSI status, event-free survival (EFS) and overall survival (OS) were higher for MSI-H patients to MSS [EFS not reached vs 30.0 months, p = 0.08; OS not reached vs 39.6 months, p = 0.10].
Our work confirms the positive prognostic effect of MSI-H in the curative setting of LAGC, not correlated with pathologic tumor downstaging. Prospective ad-hoc trial and tumor molecular profiling are eagerly needed.
新辅助化疗（NAC）显著改善了局部晚期胃癌（LAGC）患者的预后。包括HER2和错配修复/微卫星高度不稳定（MMR/MSI）在内的多种生物标志物对于晚期治疗决策至关重要，但目前尚无生物标志物可在临床实践中指导NAC的选择。我们的目的是评估MSI和HER2状态对临床结局的作用。
我们回顾性收集了2006年至2018年接受NAC及手术±辅助化疗的LAGC患者。在内镜和手术样本上评估HER2和MSI。估计并评估病理完全缓解（pCR）率、总生存期（OS）和无事件生存期（EFS）与降期和MSI的相关性。
我们纳入了76例患者，8%被分类为微卫星高度不稳定（MSI-H），内镜和手术样本结果完全一致。6%的患者在内镜样本上HER2呈阳性，手术样本上为4%。52.5%的病例观察到肿瘤降期，有3例pCR（5.1%），MSI-H癌症中无pCR病例。根据MSI状态，MSI-H患者的无事件生存期（EFS）和总生存期（OS）高于微卫星稳定（MSS）患者[EFS未达到 vs 30.0个月，p = 0.08；OS未达到 vs 39.6个月，p = 0.10]。
我们的研究证实了MSI-H在LAGC根治性治疗中的积极预后作用，与病理肿瘤降期无关。迫切需要进行前瞻性专项试验和肿瘤分子分析。
