EGFR R521K Polymorphism Is Not a Major Determinant of Clinical Cetuximab Resistance in Head and Neck Cancer.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are among the most abundant malignancies worldwide. Patients with recurrent/metastatic disease undergo combination chemotherapy containing cetuximab, the monoclonal antibody used against the epidermal growth factor receptor (EGFR). Cetuximab augments the effect of chemotherapy; however, a significant number of patients show therapy resistance. The mechanism of resistance is yet to be unveiled, although extracellular alterations of the receptor have been reported, and their role in cetuximab failure has been proposed. AIMS: Here, we investigate possible effects of the multi-exon deletion variant (EGFRvIII), and the single nucleotide polymorphism EGFR R521K on cetuximab efficacy. RESULTS: Our results show that in HNSCC patients, the EGFRvIII allele frequency is under 1%; therefore, it cannot lead to common resistance. EGFR R521K, present in 42% of the patients, is investigated in vitro in four HNSCC cell lines (two wild-type and two heterozygous for EGFR R521K). While no direct effect is found to be related to the EGFR status, cells harboring R521K show a reduced sensitivity in ADCC experiments and in vivo xenograft experiments. However, this preclinical difference is not reflected in the progression-free or overall survival of HNSCC patients. Furthermore, NK cell and macrophage presence in tumors is not related to EGFR R521K. DISCUSSION: Our results suggest that EGFR R521K, unlike reported previously, is unable to cause cetuximab resistance in HNSCC patients; therefore, its screening before therapy selection is not justifiable.

The territorial distribution of amputations in healthcare and social context in Hungary in 2016­2017. / [Az amputációk területi gyakorisága társadalmi és ellátórendszeri összefüggésben Magyarországon 2016-2017-ben].

Introduction and aim: Peripheral artery disease and lower extremity artery disease occur in 4 to 6% of the population. In Hungary, the number of major amputations was 6798 in the observed period. With timely and appropriate treatment, the number of leg amputations (30-day mortality: 20%, 2-year mortality: 40-60%) can be effectively reduced. The purpose of this study is to identify the territorial differences within Hungary with regard to the care pathways of these diseases. Method: We performed a retrospective data analysis of the peripheral vascular treatment using 2015-2017 claim data of the National Health Insurance Fund of Hungary. Territorial differences in mortality rates were examined by descriptive statistics. Correlation analysis was performed to describe any relationship between mortality rates and other factors. Results: The subregional level analysis (n = 175) revealed 4 times differences across the country proving that high domestic amputation rates are partially due to the extreme amputation rates in 30 percent of the subregions. Multiple stratified regression analysis revealed that the proportion of districts where endovascular therapy is not available (n = 159), the university education level of the population (ß1 = -0.13, 95% CI: -0.18 to -0.09) and the proportion of those over 65 years of age (ß1 = 0.14, 95% CI: 0.03-0.24) were significantly associated with amputation rate. In districts with available endovascular therapy (n = 14), age distribution of population (ß1 = 0.7, 95% CI: 0.42-0.98) was associated with the frequency of amputations. Conclusion: Regional and social disparities in incidence, prevalence and mortality rates significantly vary greatly across Hungary, but also provider capacities (with relevant competencies) influence strongly the development and progression of the disease. Orv Hetil. 2020; 161(18): 744-755.

Clinical Effectiveness and Cost-Effectiveness of Oral-Health Promotion in Dental Caries Prevention among Children: Systematic Review and Meta-Analysis.

The objective of this study was to evaluate the clinical effectiveness and cost-effectiveness of oral-health promotion programs (OHPPs) aiming to improve children's knowledge of favorable oral health behavior to lower decayed/-missing/-filled teeth (DMFT) while reducing the financial cost on health institutions. An electronic search was performed in seven databases. Studies were restricted to human interventions published in English. The search study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, and the risk of bias was assessed based on the Drummonds Checklist. A total of 1072 references were found. Among these, 19 full texts were included. Most studies had a strong quality. The overall pooled impact of OHPPs estimates children suffering from DMFT/S to have 81% lower odds of participating in OHPP (95% CI 61-90%, I2: 98.3%, p = 0). Furthermore, the program was shown to be effective at lowering the cost in 97 out of 100 OHPPs (95% CI 89-99%, I2: 99%, p = 0). Three subgroups analyses (age groups, study countries, studies of the last five years) were performed to evaluate the influence modification on the pooled effect. A comprehensive analysis of the OHPPs confirmed a reduction effect on child DMFT, hence, lowering the financial burden of dental-care treatment on health institutions.