• Journal of Digestive Cancer Research
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• 제10권1호
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• pp.22-30
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• 2022

Immune checkpoint inhibition has been established as a new treatment option for various types of carcinoma, and many clinical trials are being actively conducted as a treatment for advanced or metastatic gastric cancer, either as a monotherapy with an immune checkpoint inhibitor or as a combination therapy with standard chemotherapy. In the CheckMate-649 clinical trial to confirm the efficacy of the combination of nivolumab and chemotherapy (FP) in advanced gastric cancer and gastroesophageal junction cancer, nivolumab group showed improvement in overall survival in programmed death ligand 1-positive cancer patients compared with placebo group. Also, the combination therapy of pembrolizumab, trastuzumab and chemotherapy (FP) in first-line treatment was tested through the KEYNOTE-811 trial. The pembrolizumab group showed 22.7% of improvement in objective response rate compared with placebo group. Accordingly, the combination of nivolumab/pembrolizumab with standard chemotherapy was approved for the first-line treatment. In KEYNOTE-059 trials for patients with progressive disease after at least two lines of chemotherapy, pembrolizumab monotherapy showed improvement in objective response rate and overall survival, and the use of pembrolizumab was approved for the third-line or more treatment. In this article, we review the result of clinical trials related to immune checkpoint inhibitors that have been recently introduced in the treatment of gastric cancer.

• Journal of Digestive Cancer Research
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• 제6권1호
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• pp.16-24
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• 2018

위암은 최근에 균일한 성격의 단일 질환이 아니라, 매우 이질적인 질환으로 인식되고 있다. 수술이 불가능한 진행성 또는 전이성 위암의 경우 일반적으로 완치가 불가능하며 항암치료를 하지 않는 경우 중앙 생존기간이 3-6개월 정도로 알려져 있다. 따라서 항암치료를 하는 경우가 최선의 지지 치료에 비하여 삶의 질이나 생명연장의 측면에서 우월함을 이미 여러 연구를 통해서 확인되고 있다. 지난 기간 동안 다양한 항암치료가 진행성 위암의 치료에 적용되었고, 최근에 여러 표적 치료와 면역치료가 도입되고 있으나, 여전히 다른 암종에 비하여 진행성 위암환자에서는 현저한 생명연장은 아직 저조하고 답보 상태에 있다. 그러나 향후 위암의 분자생물학적인 특성이 자세히 알려지면서 이러한 어려움들은 극복될 것으로 기대된다.

• Journal of Gastric Cancer
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• 제22권4호
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• pp.408-417
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• 2022

Purpose: Treatment options are limited after the failure of first-and second-line treatments in patients with HER2⁺ metastatic gastric cancer (mGC). The present study aimed to explore the efficacy, safety, and prognostic factors of apatinib efficacy as a third-line therapy for patients with human epithelial growth factor receptor 2-positive (HER2⁺) mGC. Materials and Methods: A total of 59 HER2⁺ mGC patients who received apatinib as third-line therapy were retrospectively enrolled in this two-center, single-arm, cohort study; the clinical response, survival data, and adverse events were retrieved. Results: The median progression-free survival (PFS) was 5.2 months (95% confidence interval [CI], 3.9-6.5), and the median overall survival (OS) was 8.2 months (95% CI, 6.6-9.8) Furthermore, forward stepwise multivariate Cox regression analysis showed that a higher Eastern Cooperative Oncology Group performance status score and multiple metastases were independently correlated with decreased PFS and OS (both P<0.05). The main adverse events were leukopenia (45.8%), hypertension (44.1%), thrombocytopenia (39.0%), hand-foot syndrome (37.3%), and elevated transaminase (33.9%). Grade 3 adverse events mainly included hypertension (5.1%) and neutropenia (5.1%); grade 4 adverse events did not occur. Conclusions: Apatinib is efficient and well tolerated in patients with HER2⁺ mGC as a third-line treatment, suggesting that it may be a candidate of choice for these patients.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.553-556
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• 2013

Background: This study was designed to examine changing trends in localization of gastric cancer in Turkey in recent years. Materials and Methods: A total of 796 adult patients with newly diagnosed, histologically proven adenocarcinomas, treated and followed up at our oncology center between 2000-2011, were examined retrospectively. In all cases tumor localization were identified and recorded with clinicopathological features. Results: The median age was 58 with a range between 22-90 for the 552 men and 244 women. Median follow up was 12 months (1-276) and median overall survival was also 12 months (11.5-12.4). There was a trend for a change in tumor localization from distal to proximal. Survival of patients was low with advanced T and N stage tumours. Positive surgical margins, lymphovascular invasion, perineural invasion, cardioesophageal localization were predisposition factors for metastatic disease in gastric cancer. There was no relation between age or sex and histopathological type of gastric cancer. Conclusions: There is a trend in our country for a change in gastric tumour localization from distal to proximal, with clear significance for treatment choices.

• Journal of Gastric Cancer
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• 제22권4호
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• pp.273-305
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• 2022

Gastric cancer (GC) is one of the most common lethal malignant neoplasms worldwide, with limited treatment options for both locally advanced and/or metastatic conditions, resulting in a dismal prognosis. Although the widely used morphological classifications may be helpful for endoscopic or surgical treatment choices, they are still insufficient to guide precise and/or personalized therapy for individual patients. Recent advances in genomic technology and high-throughput analysis may improve the understanding of molecular pathways associated with GC pathogenesis and aid in the classification of GC at the molecular level. Advances in next-generation sequencing have enabled the identification of several genetic alterations through single experiments. Thus, understanding the driver alterations involved in gastric carcinogenesis has become increasingly important because it can aid in the discovery of potential biomarkers and therapeutic targets. In this article, we review the molecular classifications of GC, focusing on The Cancer Genome Atlas (TCGA) classification. We further describe the currently available biomarker-targeted therapies and potential biomarker-guided therapies. This review will help clinicians by providing an inclusive understanding of the molecular pathology of GC and may assist in selecting the best treatment approaches for patients with GC.

• Journal of Gastric Cancer
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• 제23권2호
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• pp.289-302
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• 2023

Purpose: Liver metastasis (LM) is reported in approximately 40% of patients with advanced/metastatic gastric/gastroesophageal junction adenocarcinoma (metastatic esophagogastric adenocarcinoma; mGEA) and is associated with a worse prognosis. This post-hoc analysis from the RAINBOW trial reported the efficacy, safety, and biomarker outcomes of ramucirumab and paclitaxel combination treatment (RAM+PAC) in patients with (LM+) and without (LM-) LM at baseline. Materials and Methods: Patients (n=665) were randomly assigned on a 1:1 basis to receive either RAM+PAC (LM+: 150, LM-: 180) or placebo and paclitaxel (PL+PAC) (LM+: 138, LM-: 197). The overall survival (OS) and progression-free survival (PFS) were evaluated using stratified Kaplan-Meier and Cox regression models. The correlation of dichotomized biomarkers (VEGF-C, D; VEGFR-1,2) with efficacy in the LM+ versus LM- subgroups was analyzed using the Cox regression model with reported interaction P-values. Results: The presence of LM was associated with earlier progression than those without LM, particularly in patients receiving PL+PAC (hazard ratio [HR], 1.68). RAM+PAC treatment improved OS and PFS irrespective of LM status but showed greater improvement in LM+ than that in LM- (OS HR, 0.71 [LM+] vs. 0.88 [LM-]; PFS HR, 0.47 [LM+] vs. 0.76 [LM-]). Treatment-emergent adverse events were similar between patients with and without LM. No predictive relationship was observed between biomarker levels (VEGF-C, D; VEGFR-1,2) and efficacy outcome (OS, PFS) (all interaction P-values >0.05). Conclusions: RAM provided a significant benefit, irrespective of LM status; however, its effect was numerically stronger in patients with LM. Therefore, RAM+PAC is a clinically meaningful therapeutic option for patients with mGEA and LM.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3703-3708
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• 2015

Background: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with colorectal, lung, gastric cancer, pancreatic and metastatic renal cell carcinoma. We here evaluated whether preoperative NLR is an independent prognostic factor for non-metastatic renal cell carcinoma (RCC). Materials and Methods: Data from 327 patients who underwent curative or palliative nephrectomy were evaluated retrospectively. In preoperative blood routine examination, neutrophils and lymphocytes were obtained. The predictive value of NLR for non-metastatic RCC was analyzed. Results: The NLR of 327 patients was $2.72{\pm}2.25$. NLR <1.7 and NLR ${\geq}1.7$ were classified as low and high NLR groups, respectively. Chi-square test showed that the preoperative NLR was significantly correlated with the tumor size (P=0.025), but not with the histological subtype (P=0.095)and the pT stage (P=0.283). Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. Effects of NLR on OS (P=0.007) and DFS (P=0.011) were significant. To evaluate the independent prognostic significance of NLR, multivariate COX regression models were applied and identified increased NLR as an independent prognostic factor for OS (P=0.015), and DFS (P=0.019). Conclusions: Regarding patient survival, an increased NLR represented an independent risk factor, which might reflect a higher risk for severe cardiovascular and other comorbidities. An elevated blood NLR may be a biomarker of poor OS and DFS in patients with non-metastatic RCC.

• Journal of Gastric Cancer
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• 제20권1호
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• pp.95-105
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• 2020

Purpose: Gastric cancer is a highly metastatic malignant tumor, often characterized by chemoresistance and high mortality. In the present study, we aimed to investigate the role of B-cell lymphoma 3 (Bcl-3) protein on cell migration and chemosensitivity of gastric cancer. Materials and Methods: The gastric cancer cell lines, AGS and NCI-N87, were used for the in vitro studies and the in vivo studies were performed using BALB/c nude mice. Western blotting, wound healing assay, Cell Counting Kit-8 assay, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to evaluate the role of Bcl-3 in gastric cancer. Results: We found that the protein expression of hypoxia (HYP)-inducible factor-1α and Bcl-3 were markedly upregulated under hypoxic conditions in both AGS and NCI-N87 cells in a time-dependent manner. Interestingly, small interfering RNA-mediated knockdown of Bcl-3 expression affected the migration and chemosensitivity of the gastric cancer cells. AGS and NCI-N87 cells transfected with si-RNA-Bcl-3 (si-Bcl-3) showed significantly reduced migratory ability and increased chemosensitivity to oxaliplatin, 5-fluorouracil, and irinotecan. In addition, si-Bcl-3 restored the autophagy induced by HYP. Further, the protective role of si-Bcl-3 on the gastric cancer cells could be reversed by the autophagy inducer, rapamycin. Importantly, the in vivo xenograft tumor experiments showed similar results. Conclusions: Our present study reveals that Bcl-3 knockdown inhibits cell migration and chemoresistance of gastric cancer cells through restoring HYP-induced autophagy.

• Journal of Gastric Cancer
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• 제2권4호
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• pp.184-190
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• 2002

Clinical application of positron emission tomography (PET) is rapidly increasing for the detection and staging of cancer at whole-body studies performed with the glucose analogue tracer 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG). Although FDG PET cannot match the anatomic resolution of conventional imaging techniques in gastrointestinal and abdominal organs, it is particularly useful for identification and characterization of whole body at the same time. FDG PET can show foci of metastatic disease that may not be apparent at conventional anatomic imaging and can aid in the characterization of indeterminate soft-tissue masses. Most gastrointestinal cancer need to surgical management. FDG PET can improve the selection of patients for surgical treatment and thereby reduce the morbidity and mortality associated with inappropriate surgery. FDG PET is also useful for the early detection of recurrence and the monitoring of therapeutic effect. The gastrointestinal cancers, such as gastroesophageal cancer, colorectal cancer, liver cancer and pancreatic cancer, are common malignancies in Korea. PET is one of the most promising and useful methodology for the management of gastric cancer as well as other gastrointestinal cancers.

• Journal of Gastric Cancer
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• 제4권4호
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• pp.277-281
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• 2004

조기위암은 림프절 전이에 상관없이 위점막이나 점막하층까지 암이 국한된 것으로 정의된다. 진행성 위암에 동반된 간전이율은 $5\~12\%$이나 조기위암에 동반된 간전이는 드물다. 64세 여자 환자나 상복부 통증을 주소로 성빈센트 병원에 내원하여 시행한 위내시경 검사에서 위전정부에 폴립형 종괴가 있었으나 간전이 소견은 없었다. 수술 시 간에 단일 전이가 발견되었으며, 2군 림프절을 포함하여 원위부 아전절제술과 전이된 간이 절제술을 시행하였다. 조직검사에서 위전정부의 종괴는 선종의 일부에 선암성 변화가 있었고 이는 위점막에 국한되어 있었으며, 절제된 간은 선암의 소견을 보였다. 저자들은 조기위암에 동반된 간전이 1예를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.