The role of chemoradiotherapy and immunotherapy in stage III NSCLC.

Locally advanced non-small lung cancer encompasses a diverse range of tumors. In the last few years, the treatment of stage III unresectable non-small lung cancer has evolved significantly. The PACIFIC trial opened a new therapeutic era in the treatment of locally advanced NSCLC, establishing durvalumab consolidation therapy as the new standard of care worldwide. A careful evaluation of this type of lung cancer and a discussion of the management of these patients within a multidisciplinary team represents a crucial step in defining the best treatment strategy for each patient. For unresectable stage III NSCLC, definitive concurrent chemoradiotherapy (CCRT) was historically recommended as a treatment with a 5-year survival rate ranging from 20% to 30%. The PACIFIC study conducted in 2017 compared the use of chemoradiotherapy and maintenance therapy with the anti-PD-L1 monoclonal antibody durvalumab to a placebo in patients with locally advanced NSCLC who had not experienced disease progression. The study was prospective, randomized, and phase III. The administration of this medication in patients with locally advanced non-small cell lung cancer (NSCLC) has demonstrated a notable improvement in overall survival. Multiple clinical trials are currently exploring various immune checkpoint inhibition regimens to enhance the treatment efficacy in patients with stage III cancer. Our goal is to offer an up-to-date summary of the planned clinical trials for treatment options, focusing on the significant obstacles and prospects in the post-PACIFIC era.

Recurrence Patterns after Radiotherapy for Glioblastoma with [(11)C]methionine Positron Emission Tomography-Guided Irradiation for Target Volume Optimization.

11C methionine (11C-MET) is increasingly being used in addition to contrast-enhanced MRI to plan for radiotherapy of patients with glioblastomas. This study aimed to assess the recurrence pattern quantitatively. Glioblastoma patients undergoing 11C-MET PET examination before primary radiotherapy from 2018 to 2023 were included in the analysis. A clinical target volume was manually created and fused with MRI-based gross tumor volumes and MET PET-based biological target volume. The recurrence was noted as an area of contrast enhancement on the first MRI scan, which showed progression. The recurrent tumor was identified on the radiological MR images in terms of recurrent tumor volume, and recurrences were classified as central, in-field, marginal, or ex-field tumors. We then compared the MET-PET-defined biological target volume with the MRI-defined recurrent tumor volume regarding spatial overlap (the Dice coefficient) and the Hausdorff distance. Most recurrences occurred locally within the primary tumor area (64.8%). The mean Hausdorff distance was 39.4 mm (SD 32.25), and the mean Dice coefficient was 0.30 (SD 0.22). In patients with glioblastoma, the analysis of the recurrence pattern has been mainly based on FET-PET. Our study confirms that the recurrence pattern after gross tumor volume-based treatment contoured by MET-PET is consistent with the FET-PET-based treatment described in the literature.

Flow Cytometry-Based Assay to Detect Alpha Galactosidase Enzymatic Activity at the Cellular Level.

BACKGROUND: Fabry disease is a progressive, X chromosome-linked lysosomal storage disorder with multiple organ dysfunction. Due to the absence or reduced activity of alpha-galactosidase A (AGAL), glycosphingolipids, primarily globotriaosyl-ceramide (Gb3), concentrate in cells. In heterozygous women, symptomatology is heterogenous and currently routinely used fluorometry-based assays measuring mean activity mostly fail to uncover AGAL dysfunction. The aim was the development of a flow cytometry assay to measure AGAL activity in individual cells. METHODS: Conventional and multispectral imaging flow cytometry was used to detect AGAL activity. Specificity was validated using the GLA knockout (KO) Jurkat cell line and AGAL inhibitor 1-deoxygalactonojirimycin. The GLA KO cell line was generated via CRISPR-Cas9-based transfection, validated with exome sequencing, gene expression and substrate accumulation. RESULTS: Flow cytometric detection of specific AGAL activity is feasible with fluorescently labelled Gb3. In the case of Jurkat cells, a substrate concentration of 2.83 nmol/mL and 6 h of incubation are required. Quenching of the aspecific exofacial binding of Gb3 with 20% trypan blue solution is necessary for the specific detection of lysosomal substrate accumulation. CONCLUSION: A flow cytometry-based assay was developed for the quantitative detection of AGAL activity at the single-cell level, which may contribute to the diagnosis of Fabry patients.

Sex-specific cardiovascular remodeling leads to a divergent sex-dependent development of heart failure in aged hypertensive rats.

INTRODUCTION: The prevalence of heart failure with preserved ejection fraction (HFpEF) is continuously rising and predominantly affects older women often hypertensive and/or obese or diabetic. Indeed, there is evidence on sex differences in the development of HF. Hence, we studied cardiovascular performance dependent on sex and age as well as pathomechanisms on a cellular and molecular level. METHODS: We studied 15-week- and 1-year-old female and male hypertensive transgenic rats carrying the mouse Ren-2 renin gene (TG) and compared them to wild-type (WT) controls at the same age. We tracked blood pressure and cardiac function via echocardiography. After sacrificing the 1-year survivors we studied vascular smooth muscle and endothelial function. Isolated single skinned cardiomyocytes were used to determine passive stiffness and Ca2+-dependent force. In addition, Western blots were applied to analyse the phosphorylation status of sarcomeric regulatory proteins, titin and of protein kinases AMPK, PKG, CaMKII as well as their expression. Protein kinase activity assays were used to measure activities of CaMKII, PKG and angiotensin-converting enzyme (ACE). RESULTS: TG male rats showed significantly higher mortality at 1 year than females or WT male rats. Left ventricular (LV) ejection fraction was specifically reduced in male, but not in female TG rats, while LV diastolic dysfunction was evident in both TG sexes, but LV hypertrophy, increased LV ACE activity, and reduced AMPK activity as evident from AMPK hypophosphorylation were specific to male rats. Sex differences were also observed in vascular and cardiomyocyte function showing different response to acetylcholine and Ca2+-sensitivity of force production, respectively cardiomyocyte functional changes were associated with altered phosphorylation states of cardiac myosin binding protein C and cardiac troponin I phosphorylation in TG males only. Cardiomyocyte passive stiffness was increased in TG animals. On a molecular level titin phosphorylation pattern was altered, though alterations were sex-specific. Thus, also the reduction of PKG expression and activity was more pronounced in TG females. However, cardiomyocyte passive stiffness was restored by PKG and CaMKII treatments in both TG sexes. CONCLUSION: Here we demonstrated divergent sex-specific cardiovascular adaptation to the over-activation of the renin-angiotensin system in the rat. Higher mortality of male TG rats in contrast to female TG rats was observed as well as reduced LV systolic function, whereas females mainly developed HFpEF. Though both sexes developed increased myocardial stiffness to which an impaired titin function contributes to a sex-specific molecular mechanism. The functional derangements of titin are due to a sex-specific divergent regulation of PKG and CaMKII systems.

Stereotactic body radiotherapy in lung cancer: a contemporary review.

The treatment of early stage non-small cell lung cancer (NSCLC) has improved enormously in the last two decades. Although surgery is not the only choice, lobectomy is still the gold standard treatment type for operable patients. For inoperable patients stereotactic body radiotherapy (SBRT) should be offered, reaching very high local control and overall survival rates. With SBRT we can precisely irradiate small, well-defined lesions with high doses. To select the appropriate fractionation schedule it is important to determine the size, localization and extent of the lung tumor. The introduction of novel and further developed planning (contouring guidelines, diagnostic image application, planning systems) and delivery techniques (motion management, image guided radiotherapy) led to lower rates of side effects and more conformal target volume coverage. The purpose of this study is to summarize the current developments, randomised studies, guidelines about lung SBRT, with emphasis on the possibility of increasing local control and overall rates in "fit," operable patients as well, so SBRT would be eligible in place of surgery.

[External radiation therapy of primary central nervous system tumors - current trends and practice]. / A primer központi idegrendszeri tumorok konvencionális külso sugárkezelése ­ aktuális trendek és gyakorlat.

The family of primary central nervous system (CNS) tumors is a highly heterogeneous group of diseases. In the complex care of CNS tumors, in addition to surgical and systemic treatments, modern external beam radiation therapy (EBRT) plays a prominent role. This summary article provides an overview of the current indications related to EBRT, diagnostic procedures, contouring, planning, and radiation therapy techniques and applications that can be used in daily routine for adults' most common primary CNS tumors.

LINAC-based SBRT in treating early-stage NSCLC patients-single institution experience and survival data analysis.

Aim: This single institute prospective study aimed to evaluate the feasibility of LINAC-based stereotactic body radiotherapy (SBRT) in treating patients with early-stage non-small cell lung cancer (NSLSC). We focused on the survival data with the local and distant control profiles and the cancer- and non-cancer-specific survival. Treatment-related side effects were also collected and analyzed. Methods: Patients with early-stage NSCLC between January 2018 and October 2021 were included in our prospective study; a total of 77 patients receiving LINAC-based SBRT were analyzed. All patients had pretreatment multidisciplinary tumor board decisions on SBRT. The average patient age was 68.8 years (median: 70 years, range: 52-82); 70 patients were in ECOG 0 status (91%), while seven patients were in ECOG 1-2 status (9%). 52% of the patients (40) had histologically verified NSCLC, and the other 48% were verified based on PETCT results. We applied the SBRT scheme 8 x 7.5 Gy for central tumors (74%) or 4 x 12 Gy for peripheral tumors (26%). Results: The mean follow-up time was 25.4 months (median 23, range 18-50). The Kaplan-Meier estimation for overall survival in patients receiving LINAC-based SBRT was 41.67 months. Of the 77 patients treated by SBRT, death was reported for 17 patients (9 cases cancer-specific, 8 cases non-cancer specific reason). The mean local tumor control was 34.25 months (range 8.4-41), and the mean systemic control was 24.24 months (range 7-25). During the treatments, no Grade I-II were reported; in 30 cases, Grade I non-symptomatic treatment-related lung fibrosis and two asymptomatic rib fractures were reported. Conclusion: In the treatment of early-stage NSCLC, LINAC-based SBRT can be a feasible alternative to surgery. Although we reported worse OS data in our patient cohort compared to the literature, the higher older average age and the initial worse general condition (ECOG1-2) in our patient cohort appear to be the reason for this difference. With the comparable local control and survival data and the favorable side effect profile, SBRT might be preferable over surgery in selected cases.

Occupational Stress Levels among Radiologists and Radiographers in Hungary during the COVID-19 Era.

The COVID-19 pandemic has heightened stress levels, potentially affecting the occupational wellbeing of radiographers and radiologists. Our study aimed to assess occupational stress levels within the radiology department and identify contributing factors. A cross-sectional survey was conducted between September and November 2022, with participants comprising radiographers and radiologists affiliated with the Hungarian Society of Radiographers and the Hungarian Society of Radiologists. The online survey collected socio-demographic and COVID-19 data, and the participants completed an effort-reward imbalance questionnaire. The analysis of 406 responses revealed significantly higher effort-reward imbalance (ERI) levels among the radiologists compared to the radiographers (p < 0.05). The healthcare professionals with over 30 years of experience exhibited significantly lower ERI levels than those with 1-9 years, 10-19 years, or 20-29 years of experience (p < 0.05). Additionally, the individuals aged 31-40 demonstrated higher ERI levels compared to their counterparts aged 19-30, 41-50, and over 51 (p < 0.05). The respondents cohabiting with a spouse/partner reported significantly higher stress levels than their single colleagues (p < 0.05), while the dog owners exhibited significantly lower ERI levels (p < 0.05). Elevated occupational stress highlights specific groups requiring targeted interventions to reduce stress and mitigate burnout among radiologists and radiographers.

Sleep Quality and Perceived Stress among Health Science Students during Online Education-A Single Institution Study.

Recently, online education has been gaining prominence in university life. Our survey aimed to examine sleep quality and perceived stress levels among students at the University of Pécs Faculty of Health Sciences. A cross-sectional, quantitative, descriptive survey was conducted between February and March 2023. The online survey included the Hungarian versions of the internationally validated Athens Insomnia Scale (AIS) and Perceived Stress Scale (PSS). Statistical analysis involved descriptive statistics, independent t-tests, analysis of variance (ANOVA), and Mann-Whitney and Kruskal-Wallis tests (p < 0.05). We analyzed 304 responses, and females dominated (n = 270; 88.8%). Students in a relationship had significantly higher AIS scores (t = -2.470; p = 0.014). Medium average (2.50-3.49) students and those who rarely/never exercise showed significantly higher AIS and PSS (p ≤ 0.05). Students on the phone/watching a series during online education, daily laptop/TV use for more than 2 h, and pre-sleep use of smart devices for more than 60 min also negatively affected AIS and PSS scores (p ≤ 0.05). Nursing, physiotherapy, and radiography students were the most affected regarding insomnia and perceived stress (p ≤ 0.05). Our survey shows that excessive smart device use and lack of exercise are associated with higher stress levels and poorer sleep quality.