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Despite new therapeutic options, advanced gastric cancer remains associated with a poor prognosis compared with other cancers. Recent gains in the treatment of gastric cancer were accompanied by the identification of novel biomarkers associated with various cellular pathways and corresponding diagnostic technologies. It is expected that the standardization of clinical workflow and technological refinements in biomarker assessment will support greater personalization and further improve treatment outcomes. In this article, we review the current state of prognostic and predictive biomarkers in gastric cancer. [ABSTRACT FROM AUTHOR]

Background: In the phase 3 KEYNOTE-061 study (cutoff: 10/26/2017), pembrolizumab did not significantly prolong OS vs paclitaxel as second-line (2L) therapy in PD-L1 combined positive score (CPS) ≥ 1 gastric/GEJ cancer. We present results in CPS ≥ 1, ≥ 5, and ≥ 10 populations after two additional years of follow-up (cutoff: 10/07/2019). Methods: Patients were randomly allocated 1:1 to pembrolizumab 200 mg Q3W for ≤ 35 cycles or standard-dose paclitaxel. Primary endpoints: OS and PFS (CPS ≥ 1 population). HRs were calculated using stratified Cox proportional hazards models. Results: 366/395 patients (92.7%) with CPS ≥ 1 died. Pembrolizumab demonstrated a trend toward improved OS vs paclitaxel in the CPS ≥ 1 population (HR, 0.81); 24-month OS rates: 19.9% vs 8.5%. Pembrolizumab incrementally increased the OS benefit with PD-L1 enrichment (CPS ≥ 5: HR, 0.72, 24-month rate, 24.2% vs 8.8%; CPS ≥ 10: 0.69, 24-month rate, 32.1% vs 10.9%). There was no difference in median PFS among treatment groups (CPS ≥ 1: HR, 1.25; CPS ≥ 5: 0.98; CPS ≥ 10: 0.79). ORR (pembrolizumab vs paclitaxel) was 16.3% vs 13.6% (CPS ≥ 1), 20.0% vs 14.3% (CPS ≥ 5), and 24.5% vs 9.1% (CPS ≥ 10); median DOR was 19.1 months vs 5.2, 32.7 vs 4.8, and NR vs 6.9, respectively. Fewer treatment-related AEs (TRAEs) occurred with pembrolizumab than paclitaxel (53% vs 84%). Conclusion: In this long-term analysis, 2L pembrolizumab did not significantly improve OS but was associated with higher 24-month OS rates than paclitaxel. Pembrolizumab also increased OS benefit with PD-L1 enrichment among patients with PD-L1-positive gastric/GEJ cancer and led to fewer TRAEs than paclitaxel. Trial registration: ClinicalTrials.gov, NCT02370498 [ABSTRACT FROM AUTHOR]

Avelumab is a human anti-PD-L1 IgG1 monoclonal antibody that has shown antitumor activity in early phase studies in advanced/metastatic gastric/gastroesophageal junction cancer, including as first-line maintenance therapy. Here, we describe the design of JAVELIN Gastric 100 (NCT02625610), an open-label, Phase III trial. A total of 499 patients with locally advanced/metastatic HER2- gastric/gastroesophageal junction cancer adenocarcinoma, who had achieved at least stable disease following 12 weeks of first-line oxaliplatin/fluoropyrimidine chemotherapy, have been randomized 1:1 to receive avelumab maintenance therapy or continue chemotherapy. The primary objective is to demonstrate superior overall survival in all randomized patients or in the PD-L1+ population. Secondary objectives are to demonstrate superiority for progression-free survival and objective response rate, compare quality of life measures, and determine safety. [ABSTRACT FROM AUTHOR]

Avelumab is a human anti-PD-L1 IgG1 monoclonal antibody that has shown antitumor activity in early phase studies in advanced/metastatic gastric/gastroesophageal junction cancer, including as first-line maintenance therapy. Here, we describe the design of JAVELIN Gastric 100 (NCT02625610), an open-label, Phase III trial. A total of 499 patients with locally advanced/metastatic HER2- gastric/gastroesophageal junction cancer adenocarcinoma, who had achieved at least stable disease following 12 weeks of first-line oxaliplatin/fluoropyrimidine chemotherapy, have been randomized 1:1 to receive avelumab maintenance therapy or continue chemotherapy. The primary objective is to demonstrate superior overall survival in all randomized patients or in the PD-L1+ population. Secondary objectives are to demonstrate superiority for progression-free survival and objective response rate, compare quality of life measures, and determine safety. [ABSTRACT FROM AUTHOR]

Aims We evaluated and compared the safety and efficacy of sunitinib in Asian and non-Asian patients with metastatic renal cell carcinoma enrolled in a previously reported global expanded access program. Methods Previously treated and treatment-naïve patients received open-label sunitinib at a starting dose of 50 mg/day for 4 weeks, followed by 2 weeks off treatment, in repeated 6-week cycles. Safety was assessed regularly, tumor measurements were performed per local practice, and survival data collected where possible. Results Data were available for 212 Asian patients from Asian sites ( Asian- A), 113 Asian patients from non- Asian sites (Asian- O) and 4046 non-Asian patients. The most common grade 3/4 treatment-related adverse events were neutropenia, thrombocytopenia, hand-foot syndrome, diarrhea, asthenia and fatigue. The incidence of many adverse events was greater in Asian-A than in Asian- O or non-Asian patients. Sunitinib efficacy was comparable between Asian and non- Asian patients, with an objective response rate of 18% versus 14%; median progression-free survival of 8.7 versus 10.9 months; and overall survival of 18.9 versus 18.4 months, respectively. Conclusions Sunitinib demonstrated tolerable safety and similar efficacy in Asian and non- Asian patients. Geographic differences in the reported frequency of specific adverse events were noted across Asian patients. [ABSTRACT FROM AUTHOR]

Background: Irinotecan plus intravenous 5-fluorouracil (5-FU) with leucovorin is effective against gastrointestinal cancer. S-1 is an oral fluoropyrimidine derivative and has a high response rate of about 40% for patients with advanced gastric cancer (AGC). We evaluated the antitumor activity and toxicities of an S-1 and irinotecan combination as a first-line therapy for patients with AGC. Methods: Patients with histologically confirmed unresectable or metastatic AGC were treated with S-1 40 mg/m2 PO twice daily on days 1–14 and irinotecan 150 mg/m2 i.v. on day 1 every 3 weeks until disease progression or unacceptable toxicities resulted. Results: A total of 45 patients were enrolled between September 2005 and March 2007. After a median of seven cycles of chemotherapy (range: 1–20, total: 350), 42 and 44 patients were evaluable for response and toxicity, respectively. On the intention-to-treat analysis, the overall response rate was 48.9% (95% C.I. 34.3–63.5%). The median time to progression was 5.7 months (95% C.I. 4.3–7.1) and the median overall survival was 10.4 months (95% C.I. 6.1–14.7). The commonly observed grade 3/4 adverse events were neutropenia (29.5% of patients) and vomiting (13.6%). Conclusion: An S-1 and irinotecan combination chemotherapy is active and tolerable as a first-line therapy for AGC. [ABSTRACT FROM AUTHOR]

The article presents case study of a 61-year-old woman on chronic haemodialysis due to the membranoproliferative glomerulonephritis. She was admitted with sudden headaches and irregular involuntary movements. It also discusses few cases of reversible posterior leukoencephalopathy syndrome, which refers to a clinicoradiologic entity characterized by headache, altered mentality, cortical visual disturbance, seizure and transient vasogenic oedema.

In recent years, a number of studies have clearly pointed out the nutritional benefits of fish consumption. However, some concerns about potential health risks derived from contaminants found in fish have also been raised. Therefore, balancing adequately the risks and benefits of fish consumption is currently a health key issue. As tuna fish represents a large part of the traditional food in some countries, the possible impact of tuna fish consumption on public health was investigated. Hepatic damages following consumption of tuna fish white (ordinary) or red (dark) muscle were evaluated in rat. Under our experimental conditions, feeding the animals for 60 days with white or, more markedly, red tuna meat resulted in 1) an elevated uric acid level in blood, 2) an accumulation of lead in liver, 3) an atrophy of liver, 4) an increase in plasma aspartate aminotransferase and alanine aminotransferase activities, and 5) an oxidative stress in liver including an increased level of lipids peroxidation and enhanced activities of superoxide dismutase, catalase and glutathione peroxidase. In addition, liver histology revealed several abnormalities. These alterations could be attributed to both lead accumulation and high purine levels in tuna meat. We conclude that attention should be paid to a possible health impact of frequent and important consumption of tuna fish meat, especially the dark one. [ABSTRACT FROM AUTHOR]

Purpose of Review: Gastric adenocarcinoma is the fifth most common and the third most lethal cancer worldwide. Surgery is the only chance of cure, but recurrence is common, even with complete resection. Recent Findings: Advances in diagnosis and staging, genomic classification, surgical resection and treatment of peritoneal disease, systemic chemotherapy and chemoradiation, and targeted and immune therapies have led to the current multidisciplinary approach to gastric adenocarcinoma. Summary: Treatment of gastric cancer is rapidly evolving in an effort to combat this challenging disease. [ABSTRACT FROM AUTHOR]