The molecular profile in patients with polycythemia vera and essential thrombocythemia is dynamic and correlates with disease’s phenotype

IntroductionPolycythemia vera (PV) and essential thrombocythemia (ET) are diseases driven by canonical mutations in JAK2, CALR, or MPL gene. Previous studies revealed that in addition to driver mutations, patients with PV and ET can harbor other mutations in various genes, with no established impact on disease phenotype. We hypothesized that the molecular profile of patients with PV and ET is dynamic throughout the disease.MethodsIn this study, we performed a 37-gene targeted next-generation sequencing panel on the DNA samples collected from 49 study participants in two-time points, separated by 78-141 months. We identified 78 variants across 37 analyzed genes in the study population.ResultsBy analyzing the change in variant allele frequencies and revealing the acquisition of new mutations during the disease, we confirmed the dynamic nature of the molecular profile of patients with PV and ET. We found connections between specific variants with the development of secondary myelofibrosis, thrombotic events, and response to treatment. We confronted our results with existing conventional and mutation-enhanced prognostic systems, showing the limited utility of available prognostic tools.DiscussionThe results of this study underline the significance of repeated molecular testing in patients with PV and ET and indicate the need for further research within this field to better understand the disease and improve available prognostic tools

Diagnosis and treatment of patients with breast cancer and mutation in the BRCA1/2 genes

Breast cancer is the most common cancer among women in Poland and worldwide, second only to lung cancer in terms of mortality. Germline mutations account for approximately 5–10% of all breast cancer cases, with mutations in the BRCA1/2 genes being the most frequently identified. The presence of pathogenic variants in the BRCA1/2 genes is associated with a more than 60% risk of developing breast cancer, a 40–60% risk of ovarian cancer in women with a BRCA1 mutation, and a 13–30% risk in women with a BRCA2 variant. Breast cancer is often diagnosed at a younger age in BRCA1/2 mutation carriers. The prevalence and increased accessibility of genetic testing, especially next-generation sequencing, lead to a higher number of diagnosed individuals and healthy family members. Identifying a pathogenic variant in the BRCA1/2 genes, analyzing a family history, and genetic counseling enables the development of individual recommendations for further management. This article aims to present the diagnostic and therapeutic approach in breast cancer patients with a pathogenic variant in the BRCA1/2 genes

Methodological recommendations for the diagnostics of EGFR gene mutations and ALK gene rearrangement in the selection of non-small-cell lung cancer patients to molecularly targeted therapies

Testing for EGFR gene mutations and ALK gene rearrangement is routinely used in advanced non-small-cell lung cancer for adequate patient selection to molecularly targeted therapies. We present Polish methodological recommendations for molecular analysis of EGFR and ALK genetic abnormalities. Recommendations specify clinical indications for testing, sample types and handling, as well as requirements for laboratories performing molecular diagnostics.Badania molekularne mające na celu wykrycie mutacji genu EGFR i rearanżacji genu ALK wykonuje się rutynowo w zaawansowanym niedrobnokomórkowym raku płuca (NDRP) w celu właściwej kwalifikacji chorych do terapii ukierunkowanych molekularnie. Przedstawiamy polskie zalecenia metodyczne prowadzenia diagnostyki molekularnej nieprawidłowości w genach EGFR i ALK. Zalecenia te opisują szczegółowo wskazania kliniczne do wykonania testów, rodzaj materiału oraz sposób postępowania z nim, a także wymagania stawiane laboratoriom wykonującym diagnostykę molekularną

Carotid intima–media thickness (IMT) in patients with severe familial and non-familial hypercholesterolemia: The effect of measurement site on the IMT correlation with traditional cardiovascular risk factors and calcium scores

Background: The carotid intima–media thickness (IMT) measurement may be carried out proximally (pIMT) or distally (dIMT) in relation to the bulb of the common carotid artery which has significant implications on the results and correlation with risk factors. The aim of the study was to compare the pIMT and dIMT in patients with familial hypercholesterolemia confirmed by genetic testing (FH group) and patients with severe non-familial hypercholesterolemia, with negative results of genetic testing (NFH group) and to determine the correlation of results with traditional atherosclerotic risk factors and calcium scores.Methods: A total of 86 FH and 50 NFH patients underwent pIMT and dIMT measurements of both carotid arteries as well as computed tomography (CT) with coronary and thoracic aorta calcium scoring.Results: The meanpIMT of both right and left common carotid artery were significantly higher in patients with FH compared to the NFH group (meanpRIMT 0.721 ± 0.152 vs. 0.644 ± 0.156, p < 0.01, meanpLIMT 0.758 ± 0.173 vs. 0.670 ± 0.110, p < 0.01). Patient age, pre-treatment lowdensity lipoprotein (LDL) cholesterol levels (LDLmax) at baseline and systolic blood pressure were independent predictors of pIMT increases in both carotid arteries. Smoking history, age and LDLmax were independent predictors of dIMT increase. There was a significant correlation between the calcium scores of the ascending aorta, coronary artery and aortic valve and all IMT parameters.Conclusions: The IMT measured proximally better between patients with familial and non-familial hypercholesterolemia. The association between IMT and traditional cardiovascular risk factors varies between measurement sites. IMT values correlate CT calcium scores in all patients with hypercholesterolaemia regardless of genetic etiology

Clinical and economic benefits of using next-generation sequencing (NGS) in the diagnostics of patients with non-small cell lung cancer with rare mutations

Molecular diagnostics are necessary to make therapeutic decisions in patients with non-small cell lung cancer (NSCLC), especially regarding targeted therapies. They include the analysis of PD-L1 expression and mutations or rearrangements in the EGFR, KRAS, BRAF, ALK, ROS1, NTRK1/2/3, and RET genes. In Poland, it is recommended to perform analyses for point mutations in exons 18, 19, 20, and 21 of the EGFR gene and rearrangements of the ALK and ROS1 genes. Due to the turnaround time, costs, and availability of biological material, the benefits of routine use of NGS in NSCLC patients are increasingly highlighted compared to performing multiple tests of individual genes. Pharmacoeconomic analyzes were conducted to assess the impact of the use of next-generation sequencing (NGS) in clinical practice on the budget of the public payer in Poland in comparison with the current practice. They demonstrated a decrease in incremental expenses of the public payer related to molecular diagnostics with NGS in all eligible patients by approx. 3.4 million PLN in 2023 and 2024 and a reduction in diagnostic costs per patient by 1 695 (21%) PLN. This article presents the efficacy and safety of amivantamab in NSCLC patients with an insertion in exon 20 of the EGFR gene. In conclusion, NGS should be the preferred diagnostic method in patients with advanced NSCLC

Long-term lipoprotein apheresis in the treatment of severe familial hypercholesterolemia refractory to high intensity statin therapy: Three year experience at a lipoprotein apheresis centre

Background: Severe familial hypercholesterolemia (FH) individuals, refractory to conventional lipidloweringmedications are at exceptionally high risk of cardiovascular events. The established therapeuticoption of last choice is lipoprotein apheresis (LA). Herein, it was sought to investigate the clinical usefulnessof LA in a highly selected group of severe heterozygous FH (HeFH), as recently described by theInternational Atherosclerosis Society (IAS), for their efficacy in lipid reduction and safety.Methods: Efficacy and safety of LA were investigated in 318 sessions of 7 severe HeFH females withcardiovascular disease, over a mean period of 26.9 ± 6.5 months. Relative reduction of low density lipoproteincholesterol (LDL-C) ≥ 60%, clinical complications and vascular access problems were evaluatedand compared between the direct adsorption of lipoproteins (DALI) and lipoprotein filtration (MembraneFiltration Optimized Novel Extracorporeal Treatment [MONET]). Additionally, lipoprotein (a)[Lp(a)], total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) andfibrinogen concentrations were investigated.Results: The relative reduction of LDL-C, TC, TG and Lp(a) were 69.4 ± 12.9%, 59.7 ± 9.1, 51.5 ±± 14.2% and 71.3 ± 14.4%, respectively. A similar efficacy was found in both systems in LDL-C removal.DALI system led to larger depletions of Lp(a) (80.0 [76–83]% vs. 73.0 [64.7–78.8]%; p < 0.001).The frequency of clinical side effects and vascular access problems were low (8.5%).Conclusions: Long-term LA in severe HeFH individuals is safe and efficiently reduces LDL-C andLp(a). Higher efficacy of the DALI system than MONET in Lp(a) removal may indicate the need for individualizedapplication of the LA system in severe HeFH individuals

Methodological recommendations for the diagnostics of EGFR gene mutations and ALK gene rearrangement in the selection of non-small-cell lung cancer patients to molecularly targeted therapies

Badania molekularne mające na celu wykrycie mutacji genu EGFR i rearanżacji genu ALK wykonuje się rutynowo w zaawansowanym niedrobnokomórkowym raku płuca (NDRP) w celu właściwej kwalifikacji chorych do terapii ukierunkowanych molekularnie. Przedstawiamy polskie zalecenia metodyczne w prowadzeniu diagnostyki molekularnych nieprawidłowości w genach EGFR i ALK. Zalecenia te opisują szczegółowo wskazania kliniczne do wykonania testów, rodzaj materiału oraz sposób postępowania z nim, a także wymagania stawiane laboratoriom wykonującym diagnostykę molekularną.Testing for EGFR gene mutations and ALK gene rearrangement is routinely used in advanced non-small-cell lung cancer for adequate patient selection to molecularly targeted therapies. We present Polish methodological recommendations for molecular analysis of EGFR and ALK genetic abnormalities. Recommendations specify clinical indications for testing, sample types and handling, as well as requirements for laboratories performing molecular diagnostics