Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Translational Research Support Section, National Cancer Center Hospital East, Kashiwa, Japan.
Am Soc Clin Oncol Educ Book. 2021 Mar;41:1-8. doi: 10.1200/EDBK_321247.
Gastric cancer is a major global health burden, especially when patients are diagnosed with recurrent or metastatic gastric cancer. Despite recent advances in treatment options with palliative chemotherapy, the median overall survival of patients with gastric cancer remains within 1 or 2 years after the diagnosis of metastatic disease. Gastric cancer is significantly more prevalent in eastern Asia (e.g., Japan and Korea). Next-generation sequencing (NGS) is rapidly being adopted as part of clinical practice in Korea and Japan, especially in patients with gastric cancer. Approximately 10% to 15% of the patients with gastric cancer who undergo NGS of their tumor specimen are allocated to target-matched clinical trials in Japan and Korea. In Japan and Korea, a cell-free DNA NGS panel is also actively being investigated as an alternative NGS test for patients with gastric cancer, which may reflect the tumor heterogeneity of gastric cancer. In Japan and Korea, multiple biomarkers, such as HER2, mismatch repair, Epstein-Barr virus, PD-L1 (combined positive score), EGFR, FGFR2, and CLDN18.2, are routinely assessed through immunohistochemistry or in situ hybridization before initiation of the first-line treatment in all patients with gastric cancer. Most tertiary cancer centers in Korea routinely perform HER2, mismatch repair, Epstein-Barr virus, and PD-L1 NGS before palliative chemotherapy in patients with gastric cancer. Biomarker evaluation for all patients with metastatic gastric cancer enables clinicians to identify available biomarker-based clinical trials early during the course of treatment, which expands treatment opportunities while patients are medically fit for clinical trials, if available. Comprehensive genomic profiling using a tissue or circulating tumor DNA NGS panel is considered necessary during second-line or subsequent treatment. It is hoped that a comprehensive molecular profiling strategy will facilitate greater use of precision medicine through molecularly targeted therapies for patients with gastric cancer in the near future.
胃癌是一个全球性的重大健康负担，尤其是当患者被诊断为复发性或转移性胃癌时。尽管近年来姑息性化疗治疗选择有所进展，但转移性疾病诊断后，胃癌患者的中位总生存期仍在 1 年或 2 年内。胃癌在东亚（如日本和韩国）更为普遍。下一代测序（NGS）正在迅速被采纳为韩国和日本临床实践的一部分，特别是在胃癌患者中。大约 10%至 15%接受肿瘤标本 NGS 检测的胃癌患者被分配到日本和韩国的靶向匹配临床试验中。在日本和韩国，一种游离细胞 DNA NGS 面板也被积极研究作为胃癌的替代 NGS 检测方法，这可能反映了胃癌的肿瘤异质性。在日本和韩国，多种生物标志物，如 HER2、错配修复、EB 病毒、PD-L1（综合阳性评分）、EGFR、FGFR2 和 CLDN18.2，在所有胃癌患者开始一线治疗之前，通常通过免疫组织化学或原位杂交进行评估。韩国的大多数三级癌症中心在为胃癌患者进行姑息性化疗之前，通常会对 HER2、错配修复、EB 病毒和 PD-L1 NGS 进行检测。对所有转移性胃癌患者进行生物标志物评估可使临床医生在治疗过程中尽早识别出可用的基于生物标志物的临床试验，如果有临床试验机会，这可扩大治疗机会。在二线或后续治疗中，使用组织或循环肿瘤 DNA NGS 面板进行全面的基因组分析被认为是必要的。人们希望在不久的将来，通过针对胃癌患者的分子靶向治疗，全面的分子分析策略将促进更多地使用精准医学。
