Upper endoscopy, endoscopic ultrasound, contrast-enhanced computed tomography (CT) and positron emission tomography are the main tools for staging. In this review, the current status and possible future developments of perioperative chemotherapy or resectable GC are summarized. Advances in precision medicine and the role of immunotherapy have been the focus of GC treatment research. Since the onset of the fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT)4-AIO trial, perioperative FLOT administration has become the new standard of care for locally advanced gastric and gastroesophageal junction cancers. In Asia, Europe and Northern America adjuvant chemotherapy is administered after surgery after preoperative chemotherapy and surgery (perioperative chemotherapy) an in combination with radiotherapy (chemoradiotherapy), respectively. The administration modality and chemotherapy protocols differ between Eastern and Western countries. Adjuvant chemotherapy, chemoradiotherapy, and perioperative chemotherapy are different approaches that are proven to improve survival compared with surgery alone. Both EBV and MSI-H GC patients are highly responsive to immune checkpoint inhibitors (ICIs).ĭespite the significant progress in the therapeutic strategies and surgical techniques for GC in the last decade, the number of patients experiencing relapse and dying after being diagnosed with localized GC remains rather high, even in the early stages. MSI-high (MSI-H) GC is considered a distinct subtype and has higher mutation rates with unique DNA methylation patterns. However, patients with the GS subtype are characterized by poor chemotherapy benefit and worse prognosis. The EBV subtype has an excellent prognosis, whereas patients with the CIN subtype achieve the greatest benefit following adjuvant chemotherapy. TCGA identifies a comprehensive set of genetic changes associated with GC and further classifies GC into four subtypes: Chromosomal instability (CIN) (50%), microsatellite instability (MSI) (22%), genomically stable (GS) (20%), and Epstein-Barr virus-positive (EBV) tumors (9%). Recently, molecular classification systems were published by the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group, providing a molecular subtyping structure, as well as a guide to targeted agents. The WHO classification defines five different subtypes, i.e., papillary, tubular, mucinous, poorly cohesive, and mixed adenocarcinoma. According to the Lauren classification, GC is categorized into two subtypes: Intestinal and diffuse. Gastric cancer (GC) includes histologically heterogeneous and microscopically distinct cell types and can be classified using various systems such as the Lauren and the World Health Organization (WHO) classifications.
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