医学
微卫星不稳定性
癌症
肿瘤科
内科学
DNA错配修复
围手术期
生物标志物
胃食管交界处
免疫检查点
疾病
腺癌
免疫疗法
结直肠癌
外科
等位基因
生物化学
化学
微卫星
基因
作者
Matthew R. Strickland,Eric Lander,Michael K. Gibson,David H. Ilson,Jaffer A. Ajani,Samuel J. Klempner
出处
期刊:Journal of The National Comprehensive Cancer Network
日期:2024-04-01
卷期号:22 (3)
标识
DOI:10.6004/jnccn.2023.7103
摘要
Esophageal, gastroesophageal junction, and gastric adenocarcinomas, referred to collectively as gastroesophageal adenocarcinomas (GEAs), are a major cause of global cancer-related mortality. Our increasing molecular understanding has led to the addition of biomarker-directed approaches to defined subgroups and has improved survival in selected patients, such as those with HER2 and Claudin18.2 overexpression. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, including GEA, but biomarkers beyond PD-L1 expression are lacking. Mismatch repair deficiency and/or high microsatellite instability (dMMR/MSI-H) is observed in 8% to 22% of nonmetastatic GEA, and 3% to 5% of patients with metastatic disease. dMMR/MSI-H tumors are associated with more favorable prognosis and significant benefit from ICIs, although some heterogeneity exists. The activity of ICIs in advanced dMMR/MSI-H cancer is seen across lines of therapy and should be recommended in the frontline setting. In patients with nonmetastatic dMMR/MSI-H cancer, increasing evidence suggests that perioperative and adjuvant chemotherapy may not provide benefit to the dMMR/MSI-H subgroup. The activity of perioperative chemotherapy-free immune checkpoint regimens in patients with nonmetastatic dMMR/MSI-H cancer is highly promising and underscores the need to identify this unique subgroup. We recommend MMR/MSI testing for all patients with GEA at diagnosis, and review the key rationale and clinical management implications for patient with dMMR/MSI-H tumors across disease stages.
科研通智能强力驱动
Strongly Powered by AbleSci AI