Jaselskė, Evelina

Introduction Radiotherapy is a vital therapeutic option in the treatment of breast cancer nowadays. However, a major obstacle to the full effectiveness of radiation therapy is still the radioresistance of cancer cells. Various studies have proven sulforaphane's (SFN) beneficial effects against cancer and its possible utilization as a radiosensitizer in radiotherapy. This study aimed to investigate whether SFN has a radiosensitizing effect on breast cancer cells.

Material and methods The anticancer efficiency of SFN and radiosensitizing effect in MCF-7 and MDA-MB-231 cell lines were assessed by the MTT assay. Using a flow cytometric assay, the apoptosis level and changes in the cell cycle were measured. RT-qPCR and Western blot analysis were used to determine BCL-2 and BCL-XL genes expresion and proteins level.

Results According to our results, SFN reduced the viability of cells, and combining SFN with radiation therapy (IR) caused much greater anticancer effects on cells. SFN+IR was shown to enhance the number of cells in the G2/M phase and the percentage of cells going through apoptosis. SFN reduced the expression of apoptosis-relative genes BCL-2 and BCL-XL. Consistent with this data, Western blot analysis revealed that BCL-2 and BCL-XL protein levels were decreased in tested cells. As a result of the combination treatment, the downregulation of the BCL-2 protein was observed only in MDA-MB-231 cells.

Conclusions These results indicate that SFN acts as a radiosensitizer by enhancing apoptotic cell death and reducing anti-apoptotic genes in breast cancer cells.

Background and Objectives Laryngeal cancer is among the most common malignancies of the upper respiratory tract, with early-stage (T1,T2) cases typically treated by surgery or radiotherapy (RT), achieving comparable overall survival rates. Nowadays intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques are used for laryngeal cancer treatment irradiating a whole larynx volume. New technologies, such as magnetic resonance based linear accelerator (MR-linac), led to reduce the target volume and treatment time. This study aims to explore the clinical and dosimetric feasibility of stereotactic ablative radiotherapy (SABR) guided by MR-linac technology (SMART) as an alternative for early-stage laryngeal cancer. Material (patients) and research method used Two complementary investigations were performed. The first compared standard fractionated RT (63 Gy/28 fr.) to MR-Linac-based SABR (42.5 Gy/5 fr.) in 32 patients, evaluating safety, treatment duration, toxicity, and precision. The second focused on validating dosimetric accuracy using individualized 3D-printed phantoms filled with radiation-sensitive gels and assessed treatment plans through gamma analysis. Findings/results in sufficient details to support conclusions Results demonstrated that SMART enables more precise dose delivery, reduces treatment time and irradiated volume (up to 15%), and preserves laryngeal function. Dosimetric analysis showed high concordance between planned and delivered doses, with gamma passing rates above 95%. Conclusions and recommendations In conclusion, MR-Linac-guided SMART appears to be a safe, efficient, and innovative approach for early-stage laryngeal cancer treatment, with promising implications for clinical implementation and patient quality of life. However, challenges remain in target volume definition and further accuracy enhancement, highlighting the potential role of machine learning in future personalization.

Purpose/Objective: Laryngeal cancer is the one of the most common upper respiratory tract cancer with 40 025 new cases and 19 728 deaths in Europe in 2020 [1]. The overall survival rate for patients undergoing surgery is around 80% and 90% for RT [2]. Laryngeal preservation has been evaluated only in few clinical trials [3]. The aim of this study is to develop an innovative stereotactic ablative magnetic resonance image-guided radiotherapy (SMART) treatment method, clinical parameters and results of individualized phantom dosimetry measurements and apply it for early stage laryngeal cancer treatment in MRI-LINAC modality. Main objectives are to evaluate clinical and dosimetric parameters of early-stage laryngeal cancer patients, to introduce phantom-based dose verification method, including development and fabrication of individualized 3D printed phantom which enables dose mapping functions due to application of specially developed [4] radiationsensitive gels and to evaluate the feasibility of SMART method for the clinical laryngeal cancer treatment. Material/Methods: Diagnostic images of patients were acquired using CT (LightSpeed RT16), MRI (Siemens Magnetom Avanto 1.5T), and PET/CT facility. Six patients were treated using the adaptive radiotherapy modality Electa Unity, 1.5T MRI and patient treatment plans were prepared and analyzed using TPS Monaco. Gafchromic films and volumetric gel dosimetry were used for dose plans verification. Data of patients treated in Trilogy and Truebeam linacs and dose plans prepared by TPS Eclipse 15.5™ (Varian Medical Systems) were analyzed. For 3D printout was used ZORTRAX M300 printer. Special 3D printing materials were used. Dosimetric gels were prepared, irradiated and dosimetric characteristics investigated. Results: All TP were generated with 42.5Gy (8.5Gy/fr) in five fractions. MRI-CT individualized phantom was created based on patient DICOM images [1fig] and filled with dose gels. 3D printed components, dosimetric gel and in target center positioned radiochromic films were irradiated with one fraction dose and compared with planned in TPS. It was estimated phantom components and dose gel densities similarity to patient's tissues in Hounsfield units (HU). All structures met requirements: phantom (plastic/bone) 187HU, target 152HU, gelatin 10-15HU. Gamma passing rate was 95.7% to radiochromic films, 96.8% to dosimetric gels. During TP comparison (Eclipse/Monaco) was found that using SMART treatment method is possible to reduce treatment volume at least 15%. Conclusion: SMART treatment integration into clinical practice could improve access to services for cancer patients, shorten the duration of treatment, preserve laryngeal function, and protect organs at risk.

Ionizing radiation covers a broad spectrum of applications. Since radioactive/radiation pollution is directly related to radiation risk, radiation levels should be strictly controlled. Different detection methods can be applied for radiation registration and monitoring. In this paper, radiation-induced variations in the optical properties of silver-enriched PVA-based hydrogel films with and without azo dye (Toluidine blue O, TBO, and Methyl red, MR) additives were investigated, and the feasibility of these free-standing films to serve as radiation detectors/exposure indicators was assessed. AgNO admixed with PVA gel was used as a source for the radiation-induced synthesis of silver nanoparticles (AgNPs) in irradiated gel films. Three types of sensors were prepared: silver-enriched PVA films containing a small amount of glycerol (AgPVAGly); silver-enriched PVA films with toluidine blue adducts (AgPVAGlyTBO); and silver-enriched PVA films with methyl red additives (AgPVAGlyMR). The selection of TBO and MR was based on their sensitivity to irradiation. The irradiation of the samples was performed in TrueBeam2.1 (VARIAN) using 6 MeV photons. Different doses up to 10 Gy were delivered to the films. The sensitivity of the films was assessed by analyzing the characteristic UV-Vis absorbance peaks on the same day as irradiation and 7, 30, 45, 90, and 180 days after irradiation. It was found that the addition of azo dyes led to an enhanced radiation sensitivity of the AgNPs containing films (0.6 Gy for AgPVAGlyTBO and 0.4 Gy for AgPVAGlyMR) irradiated with <2 Gy doses, indicating their applicability as low-dose exposure indicators. The irradiated films were less sensitive to higher doses. Almost no dose fading was detected between the 7th and 45th day after irradiation. Based on the obtained results, competing AgNP formation and color-bleaching effects in the AgPVAGly films with dye additives are discussed.

Abstract: Accuracy is one of the most important requirements for radiation therapy treatment delivery. Therefore, this work was aimed to evaluate dose planning risk associated with set-up errors arising during patient positioning. To evaluate the risks, the planning organ at the risk margins (PRV) was calculated and implemented. Results have shown that the use of PRV margin, on average, reduces doses delivered to the organs at risk by 1.69 - 3.08 Gy. Additionally, no significant decrease in plan quality was observed.

Galvos ir kaklo navikai yra heterogeniška navikų grupė, kurių lokalizacija gali būti nuo kaukolės pamato iki raktikaulių. Šiose anatominėse srityse daug kritinių organų, svarbių juslėms, išvaizdai, kvėpavimui, bendravimui ir valgymui. Tiek šalutinės reakcijos, tiek gydomosios dozės paskyrimas į naviką ir patologinius limfmazgius priklauso nuo radioterapijos kokybės. Pastaraisiais dešimtmečiais spindulinės terapijos kokybė, atsižvelgiant į naujas vaizdavimo, planavimo ir paskyrimo galimybes, labai pagerėjo. Norint visapusiškai išnaudoti naujų technologijų privalumus vis svarbesnis darosi tikslus taikinių ir kritinių organų apibrėžimas. Siekiant sumažinti skirtumus tarp gydytojų ir radioterapijos skyrių specialistų sampratos apibrėžiant taikinio tūrį ir kritinius organus buvo sudarytos galvos ir kaklo navikų sritinių limfmazgių lygmenų nustatymo gairės ir kritinių organų apibrėžimo gairės. Įvairiose publikacijose autoriai pateikia skirtingus kritinių organų dozės ir tūrio vertinimo kriterijus. Dėl šių skirtumų, naudojant skirtingus apibrėžimo protokolus, neįmanoma palyginti skirtingų studijų rezultatų tarpusavyje, todėl siūloma, kad tiek kasdienėje klinikinėje praktikoje, tiek daugiainstituciniuose klinikiniuose tyrimuose būtų vadovaujamasi bendromis kritinių organų apibrėžimo bei dozės ir tūrio vertinimo gairėmis. Siekiant užtikrinti aukštą radioterapijos kokybę, būtina vadovautis rekomendacijomis, kurias pateikia pasaulinės radioterapijos organizacijos: AIRO (Italijos onkologų ir radioterapeutų asociacija), CACA (Galvos ir kaklo vėžio komitetas, Nosiaryklės vėžio komitetas, Kinijos kovos su vėžiu asociacija), DAHANCA (Danijos galvos ir kaklo vėžio grupė), EORTC (Europos vėžio tyrimų ir gydymo organizacija), GORTEC (Prancūzijos galvos ir kaklo radioterapinės onkologijos grupė), IAG-KHT (Vokietijos multidisciplininė galvos ir kaklo navikų grupė), RTOG (JAV spindulinio gydymo tyrimus koordinuojančioji grupė), TROG (Tran-Tasmanijos radioterapinės onkologijos grupė) ir kitos. Mokomoji knyga skirta gydytojams onkologams-radioterapeutams, gydytojams onkologams-chemoterapeutams, gydytojams otorinolaringologams, gydytojams veido žandikaulių chirurgams bei šių specialybių gydytojams rezidentams ir medicinos studentams.

Background and Objectives: To our knowledge, this is the first study that investigated the prognostic value of radiomics features extracted from not only staging 18F-fluorodeoxyglucose positron emission tomography (FDG PET/CT) images, but also post-induction chemotherapy (ICT) PET/CT images. This study aimed to construct a training model based on radiomics features obtained from PET/CT in a cohort of patients with locally advanced head and neck squamous cell carcinoma treated with ICT, to predict locoregional recurrence, development of distant metastases, and the overall survival, and to extract the most significant radiomics features, which were included in the final model. Materials and Methods: This retrospective study analyzed data of 55 patients. All patients underwent PET/CT at the initial staging and after ICT. Along the classical set of 13 parameters, the original 52 parameters were extracted from each PET/CT study and an additional 52 parameters were generated as a difference between radiomics parameters before and after the ICT. Five machine learning algorithms were tested. Results: The Random Forest algorithm demonstrated the best performance (R2 0.963–0.998) in the majority of datasets. The strongest correlation in the classical dataset was between the time to disease progression and time to death (r = 0.89). Another strong correlation (r ≥ 0.8) was between higher-order texture indices GLRLM_GLNU, GLRLM_SZLGE, and GLRLM_ZLNU and standard PET parameters MTV, TLG, and SUVmax. Patients with a higher numerical expression of GLCM_ContrastVariance, extracted from the delta dataset, had a longer survival and longer time until progression (p = 0.001). Good correlations were observed between Discretized_SUVstd or Discretized_SUVSkewness and time until progression (p = 0.007). Conclusions: Radiomics features extracted from the delta dataset produced the most robust data. Most of the parameters had a positive impact on the prediction of the overall survival and the time until progression. The strongest single parameter was GLCM_ContrastVariance. Discretized_SUVstd or Discretized_SUVSkewness demonstrated a strong correlation with the time until progression.

Objective Main objective of this research is to find out what is the pattern of patient positioning errors when treating with a gamma knife. Methods In this study it was analyzed at the theoretical level the methodology of fractional treatment with a gamma knife. Evaluated and compared with each other the accuracy of several patients positioning without correction in the fractional treatment. Compared the obtained empirical data and estimated the possible errors if no additional positioning correction is applied. Results Study showed errors in the treatment with a gamma knife, when no additional patient positioning corrections are made, and the patterns of the errors. Assessing the positioning accuracy of fractional treatment without correction, it was observed that the errors are variable and different. However, pattern is seen in all investigated cases. The deviation was greatest at the beginning of fractional treatment and the smallest at mid- or late-treatment. Thus, dividing the treatment into more fractions reduces errors. ConclusionsThe Gamma Knife is a very precise treatment in the field of stereotactic radiosurgery. Treatment with a gamma knife uses cobalt-60 isotopes. 192 rays of ionizing radiation concentrated at a single point affect the desired cells and kill them. With the help of computers and many sensors, this is done very accurately. The treatment can be performed once or in fractions - several times. Assessing the positioning accuracy of fractional treatment without correction, it was observed that the errors are variable and different. However, pattern is seen in all five cases. The deviation was greatest at the beginning of fractional treatment and the smallest at mid- or late-treatment. Thus, dividing the treatment into more fractions reduces errors. In the absence of additional correction, treatment would be inaccurate and cause damage to healthy tissues. Although the errors are small, accuracy is the most important indicator when working with ioniz ing radiation.Brief description of the abstractThe Gamma Knife is a very precise treatment in the field of stereotactic radiosurgery. Treatment with a gamma knife uses cobalt-60 isotopes. 192 rays of ionizing radiation concentrated at a single point affect the desired cells and kill them. The treatment can be performed once or in fractions. However there is patient possitioning errors. The research shows those error patterns. Although the errors are small, accuracy is the most important indicator when working with ionizing radiation.

In vivo dosimetry involves the assessment of external irradiation doses to cancer patients with the aim to ensure high precision and accuracy in dose planning and delivery during radiotherapy procedure. In vivo dosimetry can also be used for the estimation of uncertainties that may occur during radiotherapy treatment and for prevention against systematic errorsand undesirable exposure. Implementation of in vivo dosimetry during irradiation can assist in detecting of doses that exceed the limits or are insufficient to treat the cancer according to the prepared dose plan. However, the availability of the various in vivo dosimetry systems remains is limited. This is partially related to the needs for the new installations of doserecording and dose verification systems and the general belief in the usefulness of these systems in detecting patient set-up errors, as well as beam energy, treatment accessory and geometry errors. Despite of this, implementation of in vivo dosimetry systems is ongoing and is seen as a crucial part of a radiation safety system in radiotherapy department […].

Highly precise dose delivery to the target (tumor or cancerous tissue) is a key point whenbrain diseases are treated applying recent stereotactic techniques: intensity-modulated, image-guidedradiotherapy, volumetric modulated arc therapy, Gamma knife radiosurgery. The doses in onesingle shot may vary between tens and hundreds of Gy and cause significant cell/tissue/organdamages. This indicates the need for implementation of quality assurance (QA) measures whichare realized performing treatment dose verification with more than one calibrated quality assurancemethod or tool, especially when functional radiosurgery with a high dose (up to 40 Gy in ourcase) shall be delivered to the target using small 4 mm collimator. Application of two dosimetrymethods: radiochromic film dosimetry using RTQA2 and EBT3 films and dose gel dosimetry usingmodified nPAG polymer gels for quality assurance purposes in stereotactic radiosurgery treatmentsusing Leksell Gamma Knife© Icon™ facility is discussed in this paper. It is shown that due to theirpolymerization ability upon irradiation nPAG gels might be potentially used as a quality assurancetool in Gamma knife radiosurgery: they indicate well pronounced linear dose response in hypofractionated(up to 10 Gy) dose range and are sensitive enough to irradiation dose changes with ahigh (at least 0.2 mm) spatial resolution. Dose assessment sensitivity of gels depends on parametersof a dose evaluation method (optical or magnetic resonance imaging), however, is similar to thisestimated using film dosimetry, which is set as a standard dosimetry method for dose verificationin radiotherapy.