Gervaso Lorenzo, Pellicori Stefania, Cella Chiara A, Bagnardi Vincenzo, Lordick Florian, Fazio Nicola
Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Milan, Lombardia, Italy.
Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milano, Lombardia Italy.
Ther Adv Med Oncol. 2021 Sep 1;13:17588359211029559. doi: 10.1177/17588359211029559. eCollection 2021.
Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced resectable gastric cancer but, despite important progresses, relapse-related death remains a major challenge. Therefore, it appears crucial to understand which patients will benefit from peri-operative treatment. Biomarkers such as human epidermal growth factor receptor-2 (HER2), microsatellite instability (MSI), and Epstein-Barr Virus (EBV) have been widely studied; however, they do not yet guide the choice of perioperative treatment in clinical practice. We performed a narrative review, including 23 studies, addressing the value of tissue- or blood-based biomarkers in the neoadjuvant setting. Ten studies (43.5%) were prospective, and more than half were conducted in East-Asia. Biomarkers were evaluated only post-NAC (on surgical samples or blood) in seven studies (30.4%), only pre-NAC (on endoscopic specimens or blood) in 10 studies (43.5%), and both pre- and post-NAC (26.1%) in six studies. Among the high variety of investigated biomarkers, some of these including MSI-H or enzymatic profile (as TS, UGT1A1, MTHFR, ERCC or XRCC) showed promising results and deserve to be assessed in methodologically sound clinical trials. The identification of molecular biomarkers in patients treated with NAC for locally advanced resectable gastric or EGJ cancer remains crucial.
新辅助化疗（NAC）显著改善了局部晚期可切除胃癌患者的预后，但尽管取得了重要进展，复发相关死亡仍然是一个重大挑战。因此，了解哪些患者将从围手术期治疗中获益显得至关重要。诸如人表皮生长因子受体2（HER2）、微卫星不稳定性（MSI）和爱泼斯坦-巴尔病毒（EBV）等生物标志物已得到广泛研究；然而，它们在临床实践中尚未能指导围手术期治疗的选择。我们进行了一项叙述性综述，纳入23项研究，探讨基于组织或血液的生物标志物在新辅助治疗中的价值。10项研究（43.5%）为前瞻性研究，超过一半的研究在东亚地区进行。7项研究（30.4%）仅在新辅助化疗后（对手术样本或血液）评估生物标志物，10项研究（43.5%）仅在新辅助化疗前（对内镜标本或血液）评估，6项研究（26.1%）在新辅助化疗前后均进行评估。在众多研究的生物标志物中，其中一些包括微卫星高度不稳定（MSI-H）或酶谱（如胸苷合成酶、尿苷二磷酸葡萄糖醛酸基转移酶1A1、亚甲基四氢叶酸还原酶、切除修复交叉互补基因或X射线修复交叉互补蛋白）显示出有前景的结果，值得在方法学合理的临床试验中进行评估。对于接受新辅助化疗治疗局部晚期可切除胃癌或食管胃交界部癌的患者，鉴定分子生物标志物仍然至关重要。
