Journal of Gastric Cancer最新文献

Neoadjuvant and perioperative therapy have emerged as promising strategies for managing locally advanced gastric cancer (LAGC). Landmark phase III studies, such as PRODIGY and RESOLVE, have established neoadjuvant chemotherapy as a viable therapeutic option in Asia. More recently, the MATTERHORN trial demonstrated the potential of incorporating immune checkpoint inhibitors (ICIs) into perioperative treatment. However, the use of fluorouracil, leucovorin, oxaliplatin, and docetaxel in Asian populations warrants careful consideration, given regional treatment standards and concerns regarding chemotherapy-related toxicities, including neutropenia. This review summarizes key perioperative trials and highlights the evolving role of ICIs while also addressing emerging evidence on targeted therapies in LAGC. Key considerations include assessment of treatment response, as the validity of pathological response as a surrogate endpoint for survival remains unclear; risk- and biomarker-driven patient selection; and unresolved questions regarding the necessity and optimal duration of postoperative therapy. Personalizing postoperative treatment based on prognostic and molecular markers-including clinical stage, pathological response, and circulating tumor DNA status-represents an important next step toward improving outcomes.

Despite the many advances in treatment methods for gastric cancer, it remains a leading cause of cancer-related mortality worldwide, with treatment outcomes intrinsically linked to the nutritional status of the patient. Malnutrition is a frequent and severe complication in patients with gastric cancer, arising from a confluence of factors including tumor-induced anorexia-cachexia syndrome, mechanical obstruction, and the metabolic stress of anti-cancer therapies including surgery and chemotherapy. Historically, nutritional support has often been a secondary consideration compared with surgical intervention or chemotherapy. However, a growing body of evidence has repositioned perioperative nutritional treatment as a cornerstone of comprehensive gastric cancer management. It is known that malnutrition can result in poorer clinical outcomes, including increased susceptibility to treatment-related toxicity, higher rates of postoperative complications, diminished quality of life, and a reduction in overall survival. Further, the paradigm shift toward proactive nutritional screening and assessment as standard clinical practice has allowed for timely and individualized prehabilitation. We conclude that advancements in nutritional science have fundamentally transformed gastric cancer management. The integration of tailored nutritional strategies throughout the journey of a patient from diagnosis through treatment and into survivorship is no longer just supportive, but a therapeutic modality in its own right. This symbiotic relationship emphasizes the necessity of a multidisciplinary approach, where oncologic and nutritional care are seamlessly interwoven to optimize patient outcomes and redefine the standards of gastric cancer treatment.

Conversion therapy enables curative-intent resection in patients with initially unresectable or metastatic cancers after effective systemic therapy. Recently, advances in systemic therapy with molecular targeted agents and immune checkpoint inhibitors (ICIs) have renewed clinical and research interest in this approach, particularly for metastatic gastric cancer (GC). This review aimed to summarize the international guidelines and expert consensus informed by contemporary evidence on conversion therapy for metastatic GC, emphasizing the central role of systemic therapy, the emergence of biomarker-driven strategies, and the optimal timing for surgical intervention. Key consensus statements (Bertinoro, OMEC, and KINGCA WEEK 2024) and pivotal studies covering the cytotoxic, targeted, and immunotherapy eras were reviewed, focusing on regimen selection, treatment duration, and prognostic determinants associated with surgical outcomes. According to global guidelines, conversion surgery is not yet standard of care but may be considered for biologically and clinically selected patients demonstrating a major response to systemic therapy. Retrospective and prospective studies have reported a median overall survival of 24-36 months in the cytotoxic era and >48 months in the ICI/targeted era among patients who underwent R0 resection. Emerging evidence supports approximately 6 months of preoperative systemic therapy, followed by R0 resection, and up to one year of postoperative maintenance therapy. Therefore, conversion surgery should be viewed as the culmination of effective systemic therapy rather than as a substitute. A biology-driven, multidisciplinary strategy integrating treatment response assessment and prognostic factor evaluation represents the next frontier in potentially curative management of metastatic GC.

Gastric cancer is a biologically heterogeneous disease. The advent of high-throughput multi-omic technologies has revolutionized our understanding of gastric cancer by deconstructing this heterogeneous entity into distinct and more homogeneous molecular subtypes. Early classifications based on gene expression, methylation, and histology have laid the groundwork for multi-omic frameworks proposed by The Cancer Genome Atlas and Asian Cancer Research Group, which established the foundation of modern molecular taxonomy. Subsequent integrative efforts, particularly the Consensus Genomic Subtypes (Super 6) model, have unified this collected information into clinically relevant subtypes that bridge prognostic stratification with treatment strategies. Established biomarkers such as human epidermal growth factor receptor 2 amplification, microsatellite instability, and programmed death-ligand 1 expression are now used clinically to guide treatment with targeted agents and immune checkpoint inhibitors. Emerging single-cell and spatial transcriptomic analyses have further refined this landscape by deconstructing tumor microenvironments and potential evolutionary trajectories associated with disease progression. This review examines the evolution of molecular classification systems for gastric cancer, highlights current consensus frameworks, and discusses how subtype-based stratification will transform clinical trial design and enable biomarker-driven precision therapy.

Gastric cancer remains a major global health burden, and accurate staging and response assessment are essential for optimal management. 2-[¹⁸F]-Fluoro-2-deoxy-D-glucose ([¹⁸F]FDG) positron emission tomography (PET)/computed tomography (CT) is widely used in oncology. However, it exhibits variable sensitivity in gastric cancer, particularly in poorly cohesive, mucinous, and signet ring cell carcinomas with low glucose metabolism. These limitations have prompted interest in fibroblast activation protein-targeted imaging, which visualizes the tumor stroma rather than the tumor cells. Radiolabeled fibroblast activation protein inhibitors (FAPIs) exhibit high tumor-to-background contrast and consistent uptake across histological subtypes, offering improved lesion detectability even in [¹⁸F]FDG-negative tumors. This review outlines the evolving role of PET/CT in gastric cancer, with a focus on [¹⁸F]FDG and FAPI tracers. Comparative evidence indicates that FAPI PET/CT enhances diagnostic accuracy, provides complementary information for evaluating treatment response, and offers potential theranostic applications. Further prospective studies are needed to establish standardized protocols and define the clinical impact of FAPI PET/CT.

Young-onset gastric cancer (YOGC) is an increasingly recognized subtype that challenges traditional assumptions about gastric cancer (GC) biology. Although the overall global incidence of GC continues to decline, the rising burden among individuals aged <40 years has reshaped clinical perceptions, highlighting YOGC as a distinct entity with unique drivers and unmet needs. It is frequently associated with diffuse-type histology and enrichment of genomically stable or microsatellite stable/epithelial-mesenchymal transition molecular subtypes, diverging from conventional late-onset diseases. Family history remains the strongest risk factor; however, most cases are sporadic, suggesting a multifactorial interplay between inherited susceptibility, environmental exposure, and early-life carcinogenic pathways. YOGC is also associated with a unique genetic and molecular profile with predominance of CDH1, RHOA, and CLDN18-ARHGAP alterations, aligned with low human epidermal growth factor 2 expression. Clinically, nonspecific symptoms and lack of screening recommendations often result in diagnosis at advanced stages. Thus, current treatment approaches largely mirror those designed for older patients. This review synthesizes evolving knowledge on the epidemiology, molecular and genetic landscape, and clinical behavior of YOGC. We emphasize opportunities to refine risk stratification, integrate hereditary cancer management, and adopt emerging tools, such as liquid biopsy, for early detection and disease monitoring. Ultimately, defining the biological foundations of YOGC may enable tailored interventions and improve prognosis in this increasingly relevant and understudied population.

Claudin 18.2 (CLDN18.2), a tight junction protein selectively expressed in normal gastric epithelium and widely retained during carcinogenesis, has emerged as a promising therapeutic target for advanced gastric cancer (AGC). SPOTLIGHT and GLOW trials evaluated the anti-CLDN18.2 monoclonal antibody (mAb) zolbetuximab in combination with first-line chemotherapy, and established CLDN18.2 as a therapeutic target, initiating a paradigm shift toward a biomarker-driven treatment approach in AGC. In addition, from zolbetuximab to a diverse pipeline of promising high-affinity mAbs, bispecific antibodies, antibody-drug conjugates and chimeric antigen receptor T cells, this target has established a new and highly effective therapeutic avenue for CLDN18.2-expressing AGC. Therefore, as research progresses, CLDN18.2-targeted therapy is poised to become a cornerstone of treatment across multiple disease stages and cancer types. This review describes the biological role of CLDN18.2 in normal gastric epithelium and gastric carcinogenesis and summarizes the current therapeutic landscape and future perspectives targeting CLDN18.2 in AGC.

Purpose: This study evaluated long-term trends in gastric cancer epidemiology and survival with a focus on conditional relative survival (CRS).

Materials and methods: Using the Korea Central Cancer Registry, we analyzed 665,184 patients who were newly diagnosed with gastric cancer between 1999 and 2022. The study period was divided into four intervals: Period I (1999-2005), Period II (2006-2011), Period III (2012-2017), and Period IV (2018-2022). Temporal trends in the incidence and mortality were assessed using crude and age-standardized rates. Relative survival was estimated using the Ederer II method, and the 5-year CRS was calculated according to the survival duration after diagnosis.

Results: The incidence of gastric cancer increased until 2011 and subsequently declined, with a marked decrease observed in 2020. Individuals aged ≥70 years consistently had the highest incidence rates. Mortality rates showed a sustained decline throughout the study period. The overall 5-year relative survival improved from 69.8% in Period II to 78.4% in Period IV. The 5-year CRS increased from 86.1% at 1 year after diagnosis to 96.3% at 5 years. Patients with localized stage maintained a 5-year CRS above 95% at 1 year after diagnosis, whereas those with regional and distant stages showed 5-year CRS that consistently remained below 95%.

Conclusions: The incidence and mortality rates of gastric cancer in Korea have declined over the past two decades, accompanied by improved survival outcomes. The CRS analysis suggests that long-term follow-up is warranted, with the optimal duration varying according to patient characteristics.

Hereditary diffuse gastric cancer (HDGC) is a dominantly inherited cancer syndrome characterized by the early onset of diffuse gastric cancer (DGC) and lobular breast cancer. HDGC is predominantly caused by germline truncating mutations in CDH1, which encodes the cell-cell adhesion protein, E-cadherin. Less frequent predisposing mutations are observed in the CTNNA1 gene that encodes α-catenin. E-cadherin and α-catenin are components of the epithelial adherens junction and play important roles in cell adhesion, signal transduction, and cell architecture maintenance. The first step in DGC initiation in carriers of pathogenic CDH1 and CTNNA1 variants is the inactivation of wildtype CDH1 or CTNNA1 alleles, leading to the development of intramucosal gastric signet ring cell carcinomas (SRCCs). In the case of CDH1 mutations, E-cadherin loss is associated with abnormal orientation of the mitotic spindle, which is believed to result in the displacement of dividing stem or progenitor cells out of the epithelial plane and into either the glandular lumen or lamina propria. Although these early stage pT1a SRCCs are generally indolent, they can acquire aggressive traits that precede a pattern of invasive growth. HDGC is clinically managed using an increasingly balanced approach involving endoscopic surveillance and prophylactic total gastrectomy. In this review, we discuss the range of predisposing germline HDGC variants and their effects, the mechanism of DGC initiation and growth, and current best practices for the diagnosis and management of this disease. Finally, we highlight emerging areas of research on the characterization, classification, and management of HDGC.