PURPOSE: For unbiased comparison of different radiation modalities and techniques, consensus on delineation of radiation sensitive organs at risk (OARs) and on their dose constraints is warranted. Following the publication of a digital, online atlas for OAR delineation in neuro-oncology by the same group, we assessed the brain OAR-dose constraints in a follow-up study. METHODS: We performed a comprehensive search to identify the current papers on OAR dose constraints for normofractionated photon and particle therapy in PubMed, Ovid Medline, Cochrane Library, Embase and Web of Science. Moreover, the included articles' reference lists were cross-checked for potential studies that met the inclusion criteria. Consensus was reached among 20 radiation oncology experts in the field of neuro-oncology. RESULTS: For the OARs published in the neuro-oncology literature, we summarized the available literature and recommended dose constraints associated with certain levels of normal tissue complication probability (NTCP) according to the recent ICRU recommendations. For those OARs with lacking or insufficient NTCP data, a proposal for effective and efficient data collection is given. CONCLUSION: The use of the European Particle Therapy Network-consensus OAR dose constraints summarized in this article is recommended for the model-based approach comparing photon and proton beam irradiation as well as for prospective clinical trials including novel radiation techniques and/or modalities.

• Klíčová slova
• Dose constraints, European Particle Therapy Network, Organs at risk, Particle therapy,
• MeSH
• celková dávka radioterapie * MeSH
• konsensus MeSH
• kritické orgány * účinky záření   MeSH
• lidé MeSH
• nádory mozku radioterapie   MeSH
• plánování radioterapie pomocí počítače metody   MeSH
• protonová terapie škodlivé účinky   MeSH
• radioterapie těžkými ionty škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

AIMS: Curative sphincter sparing radiotherapy is a treatment option for early rectal cancer. There are many methods developed for fertility preservation in young patients treated with pelvic radiotherapy. Pregnancy rates after radiotherapy are dependent on the radiation dose to ovaries and uterus. Data on outcomes of total body irradiation suggest a pregnancy is possible following 12-14 Gy TBI, despite elevated rates of preterm deliveries and other complications. METHODS: We report a case of full-term delivery of twins after curative chemoradiotherapy for anorectal adenocarcinoma T2 N0 M0 with the total dose 58.6 Gy. The patient underwent laparoscopic laterocranial ovarian transposition before radiotherapy. RESULTS: Long term complete remission was achieved after treatment. Although a spontaneous conception was not successful, the patient underwent an in vitro fertilisation procedure with donor eggs and conceived twins 10 years after the radiotherapy treatment. The mean dose to the uterus was 16 Gy and to the uterine cervix 35 Gy. She reached a full-term pregnancy and delivered two healthy babies by caesarean section at a gestational age of 38 weeks, weighing 2420 g and 2220 g. CONCLUSION: This is the first case report of the successful pregnancy following sphincter sparing curative pelvic radiotherapy for rectal cancer. Furthermore it allows us to propose an increased limit dose to the uterus enabling fertility sparing beyond the limits achieved from total body irradiation series with 12-14 Gy and accept 16 Gy as uterine body (35 Gy for uterine cervix) limit for IMRT treatment planning in young patients asking for maintaining fertility potential.

• Klíčová slova
• dose constraints, fertility sparing, radiotherapy, rectal adenocarcinoma, uterus dose,
• MeSH
• adenokarcinom terapie   MeSH
• celková dávka radioterapie MeSH
• chemoradioterapie * MeSH
• dospělí MeSH
• fertilizace in vitro MeSH
• léčba šetřící orgány metody   MeSH
• lidé MeSH
• nádory rekta terapie   MeSH
• těhotenství MeSH
• uterus MeSH
• výsledek těhotenství MeSH
• zachování plodnosti metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Radical radiotherapy of lung cancer with dose escalation has been associated with increased tumor control. However, these attempts to continually improve local control through dose escalation, have met mixed results culminating in the findings of the RTOG trial 0617, where the heart dose was associated with a worse overall survival, indicating a significant contribution to radiation-induced cardiac morbidity. It is, therefore, very likely that poorly understood cardiac toxicity may have offset any potential improvement in overall survival derived from dose escalation and may be an obstacle that limits disease control and survival of patients. The manifestations of cardiac toxicity are relatively common after high dose radiotherapy of advanced lung cancers and are independently associated with both heart dose and baseline cardiac risk. Toxicity following the treatment may occur earlier than previously thought and, therefore, heart doses should be minimized. In patients with lung cancer, who not only receive substantial heart dose, but are also older with more comorbidities, all cardiac events have the potential to be clinically significant and life-threatening. Sophisticated radiation treatment planning techniques, charged particle therapy, and modern imaging methods in radiotherapy planning, may lead to reduction of the heart dose, which could potentially improve the clinical outcomes in patients with lung cancer. Efforts should be made to minimize heart radiation exposure whenever possible even at doses lower than those generally recommended. Heart doses should be limited as much as possible. A heart dosimetry as a whole is important for patient outcomes, rather than emphasizing just one parameter.

• Klíčová slova
• Cardiac toxicity, Heart dose constraints, Lung cancer, Thoracic radiotherapy,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVE: Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure. METHODS: This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value. RESULTS: The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness. CONCLUSIONS: BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

• Klíčová slova
• Gamma Knife radiosurgery, biologically effective dose, facial numbness, facial pain, stereotactic radiosurgery, trigeminal neuralgia,
• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• měření bolesti MeSH
• následné studie MeSH
• neuralgie trigeminu * radioterapie   chirurgie   MeSH
• radiochirurgie * škodlivé účinky   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Betaine-homocysteine S-methyltransferase (BHMT) is an important zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. In the liver, BHMT performs to half of the homocysteine remethylation. In this study, we systematically investigated the tolerance of the enzyme for modifications at the "homocysteine" part of the previously reported potent inhibitor (R,S)-5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid (1). In the new compounds, which are S-alkylated homocysteine derivatives, we replaced the carboxylic group in the "homocysteine" part of inhibitor 1 with different isosteric moieties (tetrazole and oxadiazolone); we suppressed the carboxylic negative charge by amidations; we enhanced acidity by replacing the carboxylate with phosphonic or phosphinic acids; and we introduced pyrrolidine steric constraints. Some of these compounds display high affinity toward human BHMT and may be useful for further pharmacological studies of this enzyme. Although none of the new compounds were more potent inhibitors than the reference inhibitor 1, this study helped to completely define the structural requirements of the active site of BHMT and revealed the remarkable selectivity of the enzyme for homocysteine.

• Klíčová slova
• 1,1′-carbonyldiimidazole, 1,8-diazabicyclo[5.4.0]undec-7-ene, Amino acid derivative, BHMT, Bioisostere, Boc, Boc(2)O, CDI, DBU, DCM, DMF, DMS, Homocysteine, IPA, Inhibitor, MsCl, N,N′-dimethylformamide, Phosphinate, Phosphonate, S-Alkylated homocysteine, TEA, TFA, TFAA, THF, betaine-homocysteine S-methyltransferase, di-tert butyl dicarbonate, dichloromethane, dimethyl sulfide, isopropyl alcohol, methanesulfonyl chloride, tert-butoxycarbonyl, tetrahydrofuran, triethylamine, trifluoroacetic acid, trifluoroacetic anhydride,
• MeSH
• betain-homocystein-S-methyltransferasa antagonisté a inhibitory   metabolismus   MeSH
• inhibitory enzymů chemická syntéza   chemie   farmakologie   MeSH
• kyseliny pentanové chemická syntéza   chemie   farmakologie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• sulfidy chemická syntéza   chemie   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 5-(3-amino-3-carboxypropylsulfanyl)pentanoic acid MeSH Prohlížeč
• betain-homocystein-S-methyltransferasa MeSH
• inhibitory enzymů MeSH
• kyseliny pentanové MeSH
• sulfidy MeSH

PURPOSE: Despite advancements in radiation techniques, concerns persist regarding the adverse effects of radiation therapy, particularly cardiotoxicity or radiation-induced heart disease. Recently, arrhythmogenic toxicity has come to the forefront-the impact of radiation therapy on the cardiac conduction system. Our objective was to conduct a dosimetric study and subsequently investigate the feasibility of optimizing the sinoatrial (SA) and atrioventricular (AV) nodes as organs at risk (OARs) in proton radiation therapy for non-small cell lung cancer with N3 disease. PATIENTS AND METHODS: Thirty-two non-small cell lung cancer patients with N3 disease undergoing proton radiation therapy were included. Sinoatrial and AV nodes, along with standard OARs, were delineated. Dosimetric analysis and optimization were performed using intensity-modulated proton therapy. RESULTS: Patients surpassing a predefined SA node dose threshold underwent dose optimization. Proton radiation therapy with pencil beam scanning demonstrated a significant reduction in SA and AV node doses without compromising target volume coverage or significant shift in the dose to other monitored OARs. CONCLUSION: Dose reduction to the SA and AV nodes for pencil beam scanning is a relatively simple task, and the reduction can be very substantial. Larger cohort studies and diverse radiotherapeutic modalities are needed for further validation and refinement of dose constraints.

• Klíčová slova
• Cardiac substructure, Cardiotoxicity, Conduction nodes, Non–small cell lung cancer, Proton therapy,
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Seasonal influenza vaccination rates among the elderly in the Czech Republic are alarmingly low, making it one of the least vaccinated countries in Europe. This study explored the role of vaccine literacy and insurance coverage on vaccination status. METHODS: An analytical cross-sectional study was conducted in Summer 2023 using a self-administered questionnaire covering vaccine literacy (functional, interactive, and critical skills), negative perceptions towards influenza vaccination, and the 5C model (confidence, complacency, constraints, calculation, and collective responsibility). Individuals aged 55 and older were included in the study. Mediation analyses assessed the indirect effects of insurance coverage on vaccination status. RESULTS: Significant differences were noted in vaccination rates based on insurance coverage, chronic diseases, regular medication use, and previous COVID-19 and pneumococcal vaccinations. Vaccine literacy, especially interactive and critical skills, was higher among vaccinated individuals. Confidence and collective responsibility were significant promoters, while complacency and constraints were barriers to vaccination. Mediation analyses indicated that negative perceptions, confidence, and collective responsibility significantly mediated the relationship between insurance coverage and vaccination status. CONCLUSION: Enhancing vaccine literacy and addressing psychological antecedents are crucial for improving influenza vaccination rates among the elderly. Policy measures should include improving vaccine literacy, building public confidence, and addressing negative perceptions.

• Klíčová slova
• Czech Republic, aged, health literacy, influenza, vaccination hesitancy,
• MeSH
• chřipka lidská * prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• odkládání očkování * psychologie   MeSH
• pojistné krytí MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• roční období MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vakcinace psychologie   statistika a číselné údaje   MeSH
• vakcíny proti chřipce * MeSH
• Východoevropané MeSH
• zdraví - znalosti, postoje, praxe MeSH
• zdravotní gramotnost * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• vakcíny proti chřipce * MeSH

Eukaryotic genome surveillance is dependent on the multiple, highly coordinated network functions of the DNA damage response (DDR). Highlighted conserved features of DDR in plants and animals represent a challenging opportunity to develop novel interdisciplinary investigations aimed at expanding the sets of DNA damage biomarkers currently available for radiation exposure monitoring (REM) in environmental and biomedical applications. In this review, common and divergent features of the most relevant DDR players in animals and plants are described, including the intriguing example of the plant and animal kingdom-specific master regulators SOG1 (suppressor of gamma response) and p53. The potential of chromatin remodelers as novel predictive biomarkers of DNA damage is considered since these highly evolutionarily conserved proteins provide a docking platform for the DNA repair machinery. The constraints of conventional REM biomarkers can be overcome using biomarkers identified with the help of the pool provided by high-throughput techniques. The complexity of radiation-responsive animal and plant transcriptomes and their usefulness as sources of novel REM biomarkers are discussed, focusing on ionizing (IR) and UV-radiation. The possible advantages resulting from the exploitation of plants as sources of novel DNA damage biomarkers for monitoring the response to radiation-mediated genotoxic stress are listed. Plants could represent an ideal system for the functional characterization of knockout mutations in DDR genes which compromise cell survival in animals. However, the pronounced differences between plant and animal cells need to be carefully considered in order to avoid any misleading interpretations. Radioresistant plant-based systems might be useful to explore the molecular bases of LD (low dose)/LDR (low dose rate) responses since nowadays it is extremely difficult to perform an accurate assessment of LD/LDR risk to human health. To overcome these constraints, researchers have started exploring radiotolerant non-human species as potential sources of information on the mechanisms involved in LD/LDR and general radiation responses.

• Klíčová slova
• DNA damage response, Ionizing radiation, Radiation exposure monitoring, Radiotolerance, Ultraviolet radiation,
• MeSH
• biologické markery metabolismus   MeSH
• ionizující záření MeSH
• lidé MeSH
• nádorový supresorový protein p53 * genetika   metabolismus   MeSH
• poškození DNA * MeSH
• rostlinné proteiny * genetika   metabolismus   MeSH
• rostliny * genetika   metabolismus   MeSH
• transkripční faktory * genetika   metabolismus   MeSH
• ultrafialové záření škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• nádorový supresorový protein p53 * MeSH
• rostlinné proteiny * MeSH
• TP53 protein, human MeSH Prohlížeč
• transkripční faktory * MeSH

BACKGROUND AND PURPOSE: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing. MATERIALS AND METHODS: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared. RESULTS: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2). CONCLUSION: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines.

• MeSH
• celková dávka radioterapie * MeSH
• dítě MeSH
• infratentoriální nádory * radioterapie   MeSH
• kritické orgány účinky záření   MeSH
• lidé MeSH
• mozkový kmen účinky záření   MeSH
• plánování radioterapie pomocí počítače * metody   MeSH
• předškolní dítě MeSH
• protonová terapie * metody   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Stereotactic body radiotherapy (SBRT) is used to treat localized tumor lesions and consists of applying high doses of radiation to a small number of fractions using specially equipped linear accelerators, modern immobilization devices, and imaging methods, which are considered special, advanced techniques in modern day radiotherapy. SBRT is a very well tolerated, non-invasive, short-term treatment that does not require hospitalization or any complicated preparation. Compared to standard radiotherapy techniques, SBRT allows, due to its precision, significantly higher doses to be applied to the target with less damage to surrounding healthy tissues. If dose constraints are not exceeded, the risk of damage to tissues and organs around the irradiated volume is reduced to minimum. The principle of SBRT is the application of ablative doses of radiation that cause necrosis of the irradiated tissue. PURPOSE: The aim of this review is to provide a basic overview of SBRT indications, radiation doses used, and potential side effects. It is not intended to be a detailed description of treatment itself (such as discussion of patient fixation systems, management of respiratory movements, or image guided strategies of treatment). This review also discusses rarer indications for SBRT, such as pancreatic carcinoma or hepatocellular carcinoma. CONCLUSION: Advances in image navigation, radiation planning, and dose application have enabled successful introduction of SBRT as a treatment regimen for many primary tumors and oligometastatic disease. If surgery is not possible or the patient refuses surgery, it is always reasonable to consider SBRT. SBRT has curative potential for the treatment of primary lung or prostate tumors. High-dose irradiation of oligometastases of various primary tumors can lead to long-term survival without disease symptoms, delay administration of toxic systemic therapies, and improve the quality of life of oncological patients. Key words radiotherapy - stereotactic body radiotherapy - review - ablative radiotherapy - lung cancer - prostate cancer - oligometastatic disease This work was supported in part by the Ministry of Health, Czech Republic - Conceptual Development of Research Organization (MMCI 00209805). The results of this research have been acquired within CEITEC 2020 (LQ1601) project with the financial contribution made by the Minis-try of Education, Youths and Sports of the Czech Republic within special support paid from the National Programme for Sustainability II funds. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 30. 10. 2018 Accepted: 4. 11. 2018.

• Klíčová slova
• Czech Republic - Conceptual Development of Research Organization (MMCI 00209805). The results of this research have been acquired within CEITEC 2020 (LQ1601) project with the financial contribution made by the Minis­try of Education, Youths and Sports of the Czech Republic within special support paid from the National Programme for Sustainability II funds. The authors declare they have no potential conflicts of interest concerning drugs, or&#8239;services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 30. 10. 2018 Accepted: 4. 11. 2018, products, radiotherapy - stereotactic body radiotherapy - review - ablative radiotherapy - lung cancer - prostate cancer - oligometastatic disease This work was supported in part by the Ministry of Health,
• MeSH
• lidé MeSH
• nádory radioterapie   MeSH
• radiochirurgie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH