Radioterapie patří k nejúčinnějším modalitám onkologické léčby, ale její využití je zatíženo rizikem rozvoje nežádoucích účinků. Při plánování léčby zářením je nezbytné maximálně šetřit okolní zdravé tkáně k zajištění přijatelného rizika toxicity a k zachování dobré kvality života pacientů. Nežádoucí účinky ozařování vznikají na podkladě různorodých patofyziologických mechanismů a jejich závažnost je ovlivněna množstvím biologických a klinických faktorů, dále aplikovanou dávkou, velikostí ozařovaného objemu, radiomickými charakteristikami nebo individuální radiosenzitivitou. Na podkladě těchto parametrů je možné různými způsoby predikovat riziko rozvoje nežádoucích účinků radioterapie. Předkládané sdělení nabízí základní přehled mechanismů rozvoje poradiační toxicity a možností predikce těchto projevů radiobiologickými nástroji - projekt QUANTEC, modelování na podkladě EUD, NTCP a s využitím metod umělé inteligence. Prediktivní modely mohou prohloubit pochopení toxicity radioterapie a do budoucna mohou přispět k individualizaci léčebného přístupu za účelem dosažení maximálního přínosu a minimalizace toxicity léčby.

Radiotherapy is one of the most effective modalities of cancer treatment, however its application is associated with the risk of adverse effects. When planning radiation treatment, it is essential to spare the surrounding healthy tissues as much as possible to ensure an acceptable risk of toxicity and to maintain a good quality of life for patients. Radiation side effects result from diverse pathophysiological mechanisms and their severity is modulated by a variety of biological and clinical factors, as well as the applied dose, the size of the irradiated volume, radiomic characteristics or individual radiosensitivity. Based on these parameters, the risk of developing adverse effects of radiotherapy can be predicted by different methods. This paper offers a basic overview of the development mechanisms of radiation toxicity and the possibilities of predicting these effects by radiobiological tools - QUANTEC project, modelling based on EUD, NTCP and using artificial intelligence methods. Predictive models can strengthen the understanding of radiotherapy toxicity and in the future may contribute to individualize the treatment approach to maximize benefit and minimize toxicity.

• MeSH
• Models, Biological MeSH
• Humans MeSH
• Neoplasms * complications   therapy   MeSH
• Radiation Injuries physiopathology   MeSH
• Radiobiology methods   MeSH
• Radiotherapy * adverse effects   MeSH
• Risk Factors MeSH
• Artificial Intelligence MeSH
• Dose-Response Relationship, Radiation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Introduction: Metastatic cutaneous squamous cell carcinoma (cSCC) is a very rare condition. The lack of definition of an oligometastatic subgroup means that there is no consensus for its treatment, unlike the mucosal head and neck counterpart. Like the latter, the cutaneous form is able to develop bulky tumor masses. When this happens, the classic care approach is just for palliative intent due to a likely unfavorable benefit-risk balance typical of aggressive treatments. Here we proposed a novel radiotherapy (RT) technique to treat bulky metastases from cSCC in the context of an overall limited tumor burden and tried to explain its clinical outcome by the currently available mathematical radiobiological and ad hoc developed models. Methods: We treated a case of facial cSCC with three metastases: two of them by classic stereotactic RT and the other by lattice RT supported by metabolic imaging (18F-FDG PET) due to its excessively large dimensions. For the latter lesion, we compared four treatment plans with different RT techniques in order to define the best approach in terms of normal tissue complication probability (NTCP) and tumor control probability (TCP). Moreover, we developed an ad hoc mathematical radiobiological model that could fit better with the characteristics of heterogeneity of this bulky metastasis for which, indeed, a segmentation of normoxic, hypoxic, and necrotic subvolumes might have been assumed. Results: We observed a clinical complete response in all three disease sites; the bulky metastasis actually regressed more rapidly than the other two treated by stereotactic RT. For the large lesion, NTCP predictions were good for all four different plans but even significantly better for the lattice RT plan. Neither the classic TCP nor the ad hoc developed radiobiological models could be totally adequate to explain the reported outcome. This finding might support a key role of the host immune system. Conclusions: PET-guided lattice RT might be safe and effective for the treatment of bulky lesions from cSCC. There might be some need for complex mathematical radiobiological models that are able to take into account any immune system's role in order to explain the possible mechanisms of the tumor response to radiation and the relevant key points to enhance it.

• Publication type
• Journal Article MeSH

The chemical stage of the Monte Carlo track-structure (MCTS) code Geant4-DNA was extended for its use in DNA strand break (SB) simulations and compared against published experimental data. Geant4-DNA simulations were performed using pUC19 plasmids (2686 base pairs) in a buffered solution of DMSO irradiated by60Co or137Csγ-rays. A comprehensive evaluation of SSB yields was performed considering DMSO, DNA concentration, dose and plasmid supercoiling. The latter was measured using the super helix density value used in a Brownian dynamics plasmid generation algorithm. The Geant4-DNA implementation of the independent reaction times method (IRT), developed to simulate the reaction kinetics of radiochemical species, allowed to score the fraction of supercoiled, relaxed and linearized plasmid fractions as a function of the absorbed dose. The percentage of the number of SB after •OH + DNA and H• + DNA reactions, referred as SSB efficiency, obtained using MCTS were 13.77% and 0.74% respectively. This is in reasonable agreement with published values of 12% and 0.8%. The SSB yields as a function of DMSO concentration, DNA concentration and super helix density recreated the expected published experimental behaviors within 5%, one standard deviation. The dose response of SSB and DSB yields agreed with published measurements within 5%, one standard deviation. We demonstrated that the developed extension of IRT in Geant4-DNA, facilitated the reproduction of experimental conditions. Furthermore, its calculations were strongly in agreement with experimental data. These two facts will facilitate the use of this extension in future radiobiological applications, aiding the study of DNA damage mechanisms with a high level of detail.

• MeSH
• Dimethyl Sulfoxide * MeSH
• DNA chemistry   MeSH
• Nucleic Acid Conformation MeSH
• Monte Carlo Method MeSH
• Plasmids MeSH
• Computer Simulation MeSH
• DNA Damage * MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Východiská: Reožarovanie, v kombinácii so systémovou a biologickou liečbou, sa v súčasnosti stáva významnou opciou pre recidivujúce tumory a "in-field" sekundárne malignity, pokiaľ je chirurgia kontraindikovaná. Rozvoj zobrazovacích metód a nových ožarovacích techník v rádioterapii vytvorili priestor pre vývoj a aplikáciu presnejších postupov reožarovania s využitím rádiobio­logického modelovania účinkov v režimoch hypofrakcionácie a jej extrémneho módu – stereotaxie. Normálne tkanivá a orgány po rádioterapii dokážu regenerovať a opraviť svoje poškodenie. Zvyšková tolerančná dávka orgánov v riziku (OaR) je však značne rozdielna. Pri tkanivách so skorou odpoveďou dochádza temer ku kompletnej obnove v priebehu niekoľkých mesiacov, takže druhá séria ožiarenia by mohla byť aplikovaná skoro v rovnakej výške dávky. Pre tkanivá a orgány s neskorou odpoveďou rozsah poškodenia závisí na výške celkovej dávky z ožiarenia, štruktúre funkčných subjednotiek a na intervale medzi sériami. Výrazná obnova prebieha do 3–6 mesiacov u kože, sliznice, miechy a pľúc. Iné tkanivá, napr. obličky, srdce, mechúr, disponujú len malou regeneračnou kapacitou. Cieľ: Príspevok, fokusovaný na reožarovanie, poskytuje prehľad o hodnotách kumulatívnej biologickej efektívnej dávky (BEDcum) jednotlivých orgánov v riziku (OaR) extirpovaných z retrospektívnych štúdii, metodike stanovenia reziduálnych dávok s popisom pôvodného modelu autorov príspevku zapracovaného do výpočtu pravdepodobnosti komplikácií normálnych tkanív (normal tissue complication probability – NTCP) pri individuálnych ožarovacích plánoch reožarovania pomocou programu "BioGray" vyvinutom na pracovisku autorov.

Background: Re-irradiation, in combination with systemic and bio­logical therapy in recent years, has become a meaningful option for locally recurrent cancers and for in-field second malignancies in cases where surgical salvage is not feasible. The development of imaging techniques and their applications in radiotherapy have created a space for the development of procedures and, by means of radiobio­logical modelling, for the estimation of the residual/additional tolerance doses for organs at risk (OaR) during re-irradiation. Normal tissues and organs can regenerate and repair their damage after initial radiotherapy. However, residual tolerance doses of OaR are considerably different. In the tissues with early response, a complete restoration occurs almost within a couple of months so that the second series of the exposure could be applied in almost the same amount. In the tissues and organs with the late response, the extent of the damage depends on several parameters: a total dose from the initial therapy, a structure of the sub-functional units of the tissue and an interval between the series. Strong recovery takes place in 3–6 months in case of the skin, mucosa, spinal cord and lung. Other tissue, e. g. kidneys, heart or bladder, dispose with a small regenerative capacity only. Purpose: The article provides an overview about the cumulative values of the biological effective dose (BEDcum) on organs-at-risk (OaR) obtained from retrospective studies and description of the original model for the determination of the residual tolerance dose implemented to calculating normal tissue complication probability (NTCP) from the individual treatment plans by means of the own-made program "BioGray".

• MeSH
• Humans MeSH
• Neoplasms radiotherapy   MeSH
• Re-Irradiation * methods   MeSH
• Radiation Tolerance MeSH
• Dose-Response Relationship, Radiation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Publikace propojuje informace z obecné biologie, jež jsou nutné pro pochopení účinků ionizujícího záření na lidský organizmus, a konkrétních účinků záření. Zabývá se problematikou ozářených, respektive kontaminovaných osob, diagnostikou a specializovanou léčbou v centrech k tomu určených.

• Keywords
• Ostatní lékařské obory,
• MeSH
• Cells radiation effects   MeSH
• Radiologic Health MeSH
• Disaster Medicine MeSH
• Radiation Injuries nursing   MeSH
• Radiation Effects MeSH
• Radiobiology MeSH
• Radioactive Hazard Release MeSH
• Radiation MeSH

• NML Fields
• biologie
• radiologie, nukleární medicína a zobrazovací metody

• MeSH
• Models, Biological MeSH
• Brachytherapy MeSH
• Chemoradiotherapy methods   MeSH
• Dose Fractionation, Radiation MeSH
• Humans MeSH
• Radiation Injuries MeSH
• Radiobiology * MeSH
• Radiotherapy * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Publikace je zaměřená na klinickou radiobiologii. Seznamuje s nejnovějšími poznatky vlivu ionizujícího záření na subcelulární úrovni, důsledky poškození na tkáňové úrovni, klinickými následky, léčbou ozářením kontaminovaných osob nebo s prací záchranného systému. Učebnicě využívá i odborné zkušenosti autorů.; Publikace propojuje informace z obecné biologie, jež jsou nutné pro pochopení účinků ionizujícího záření na lidský organizmus, a konkrétních účinků záření. Zabývá se problematikou ozářených, respektive kontaminovaných osob, diagnostikou a specializovanou léčbou v centrech k tomu určených.

• MeSH
• Cells radiation effects   MeSH
• Radiologic Health MeSH
• Disaster Medicine MeSH
• Radiation Injuries nursing   MeSH
• Radiation Effects MeSH
• Radiobiology MeSH
• Radioactive Hazard Release MeSH
• Radiation MeSH
• Publication type
• Textbook MeSH

• Conspectus
• Patologie. Klinická medicína
• Učební osnovy. Vyučovací předměty. Učebnice
• NML Fields
• biologie
• radiologie, nukleární medicína a zobrazovací metody
• NML Publication type
• kolektivní monografie

• Publication type
• Meeting Abstract MeSH

The European Space Agency (ESA) is currently expanding its efforts in identifying requirements and promoting research towards optimizing radiation protection of astronauts. Space agencies use common limits for tissue (deterministic) effects on the International Space Station. However, the agencies have in place different career radiation exposure limits (for stochastic effects) for astronauts in low-Earth orbit missions. Moreover, no specific limits for interplanetary missions are issued. Harmonization of risk models and dose limits for exploratory-class missions are now operational priorities, in view of the short-term plans for international exploratory-class human missions. The purpose of this paper is to report on the activity of the ESA Topical Team on space radiation research, whose task was to identify the most pertinent research requirements for improved space radiation protection and to develop a European space radiation risk model, to contribute to the efforts to reach international consensus on dose limits for deep space. The Topical Team recommended ESA to promote the development of a space radiation risk model based on European-specific expertise in: transport codes, radiobiological modelling, risk assessment, and uncertainty analysis. The model should provide cancer and non-cancer radiation risks for crews implementing exploratory missions. ESA should then support the International Commission on Radiological Protection to harmonize international models and dose limits in deep space, and guarantee continuous support in Europe for accelerator-based research configured to improve the models and develop risk mitigation strategies.

• MeSH
• Radiation Dosage MeSH
• Risk Assessment methods   MeSH
• Incidence MeSH
• Cosmic Radiation adverse effects   MeSH
• Space Flight MeSH
• Astronauts MeSH
• Humans MeSH
• Neoplasms, Radiation-Induced epidemiology   MeSH
• Radiation Protection standards   MeSH
• Radiation Injuries epidemiology   MeSH
• Radiobiology MeSH
• Research Design * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH

PURPOSE: The Geant4 Monte Carlo simulation toolkit was used to reproduce radiobiological parameters measured by irradiating three different cancerous cell lines with monochromatic and clinical proton beams. METHODS: The experimental set-up adopted for irradiations was fully simulated with a dedicated open-source Geant4 application. Cells survival fractions was calculated coupling the Geant4 simulations with two analytical radiobiological models: one based on the LEM (Local Effect Model) approach and the other on a semi-empirical parameterisation. Results was evaluated and compared with experimental data. RESULTS AND CONCLUSIONS: The results demonstrated the Geant4 ability to reproduce radiobiological quantities for different cell lines.

• MeSH
• Radiotherapy Dosage MeSH
• Humans MeSH
• Monte Carlo Method * MeSH
• Cell Line, Tumor MeSH
• Proton Therapy * MeSH
• Radiobiology MeSH
• Reproducibility of Results MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH