This paper presents the TCP/NTCP Calculator software, developed in Russia, for determination of optimal dosimetric treatment plans using five patients diagnosed with prostate cancer as an example. The dosimetric planning system was used to create three variants of individual dosimetric plans for each patient using a variety of remote methods of delivering the absorbed dose: three-dimensional conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy with static (IMRT) and rotational (VMAT) irradiation.

Background: Radiosensitivity of tumour cells is a serious problem in the treatment of oncological diseases, which, along with the dama- ging effect of irradiation on healthy tissues, significantly limit the possibilities of radiation therapy; therefore, an important task of modern oncopharmacology is the search and study of new radiosensitizing compounds. The main objective of this study was to investigate the radiosensitising effect of lithium ascorbate in vitro and in vivo under neutron radiation exposure. Material and methods: Evaluation of biological effect in vitro was performed on cell culture of tumour line HCT-116 (human colorectal cancer). To develop a model of tumour growth in vivo, SPF-nude immunodeficient mice (line Nu/j) were used. In vivo xenografts were formed by subcutaneous injection of cell suspension of HCT-116 cell line at a concentration of 2 million cells per 100 µl. The drug was administered to animals before irradiation by intraperitoneal injection in physiological solution at the rate of 2.4 mM/kg of animal weight. Neutron irradiation of cells was performed on cyclotron P-7M, by neutron flux with average energy of 7.5 MeV in the range of absorbed doses of 0.5‒1.5 Gy. Local irradiation of mice tumours was performed once at a dose of 1.5 Gy on a cyclotron with the same flux parameters. Cell viability was assessed by MTT test. Tumour growth parameters were assessed by measuring the sizes of xenografts and calculating the average volume, tumour doubling time and animal life span. Results: Enhancement of cytotoxic effect with combined application of radiation exposure and lithium ascorbate in vitro and in vivo was shown. A dose-dependent decrease in cancer cell viability was found when lithium ascorbate was used at a concentration of 0.1‒0.3 mM in combination with neutron irradiation. It was shown that the average tumour volume decreased by more than 50 % in comparison with the control, the xenografts growth rate slowed down to 72 %, and the median life expectancy of experimental animals increased by 86 % when lithium ascorbate and neutron irradiation were combined. Mechanisms of radiosensitising effect by induction of oxidative stress were proposed. Conclusion: The use of lithium ascorbate results in a more pronounced therapeutic effect of neutron radiation exposure in cellular and animal models of tumour growth.

Purpose: Analysis of potential collisions of elements of the therapeutic complex with the patient on the basis of linear electron accelerator (LEA) using the system of virtual visualization of radiation therapy (VVLT). Material and methods: The research was conducted in the system of virtual visualization of radiation therapy, in which the acceptable positions of the elements of the LEA complex (position of the head part of the LEA at a certain gantry angle and of the therapy table) that do not lead to patient collision were evaluated. The system is a simulation software for radiotherapy procedures. Seven models of therapeutic LEAs (manufacturers Varian, Elekta and Siemens) and 4 patient models of different localizations (prostate tumor, lung tumor, breast tumor, head and neck tumor) with an appropriate set of immobilizing devices were selected for the analysis. Results: The results are presented in the form of graphs of the critical value of the gantry rotation angle at different transverse and vertical displacements of the therapy table for each localization. In the case of lung cancer, it was found that a transverse displacement of the table by 10 cm from the initial position (the position at which the patient model was centered relative to the isocenter of the LEA) resulted in a 15° difference in the gantry rotation angles at which collisions occur. Collisions occur at 90° on Elekta LEA, on Varian CX and iX at 96°, and on Varian TrueBeam at 105°. When the table height is increased by 10 cm, the difference increases to 20° with the same statistics for the transversal bias between linear accelerators. In general, increasing the lateral offset or table elevation results in a reduced range of gantry rotation before collision for all LEA models. Conclusion: Based on experimental simulation using the VVLT system, the values of the critical gantry rotation angle at transverse and vertical displacements of the therapy table were obtained. The obtained results can be used to develop collision prevention algorithms, thus improving the safety of radiation therapy procedures, allowing more accurate prediction and avoidance of possible obstacles during treatment.

The purpose of the study was to evaluate the efficacy of neutron therapy (NT) for salivary gland cancer and recurrent breast cancer. Material and Methods. The study included 130 patients with salivary gland cancer and 125 patients with recurrent breast cancer. Fast neutron therapy using U-120 cyclotron was given to the patients of the study group. Patients of the control group received standard radiotherapy (external beam radiotherapy). Results. Among patients with salivary gland cancer, a recurrence rate was significantly lower in patients who received a postoperative course of NT compared to patients of the control group (21.1 vs 45 %, p<0.05). The five-year overall survival rates were 73.8 ± 9.5 % and 43.2 ± 9.4 % in the study group and the control group, respectively (p<0.05). The five-year disease-free survival rates were 65.6 ± 7.5 % and 34.8 ± 9.1 % in the study and control groups, respectively (p<0.05). In patients with recurrent breast cancer, a significant increase in the frequency of complete regression in the study group compared to the control group was observed (91.8 vs 51.3 %, p<0.05). Ten-year survival rates in patients with no evidence of re-recurrence were 77.4 ± 8.7 % and 44.7 ± 8.8 % in the study group and the control group, respectively (p<0.05). Conclusion. The study demonstrated efficacy of fast neutron therapy in patients with salivary gland cancer and recurrent breast cancer. Neutron therapy did not result in serious complications, improved survival of the patients and decreased the recurrence rate compared with standard radiotherapy.

The concept of biologically effective dose (BED) is widely used to compare the efficacies of different fractionation regimens and to evaluate the responses of normal tissues in radiotherapy, while models describing tumor control probability (TCP) can also be used. The work reported here included comparative analysis of several fractionation regimens using BED and TCP models. The BED model is shown not to take account of uncertainty in the radiobiological parameter α/β, i.e., the level of coverage of tumor volume by the absorbed dose; this prevents appropriate decisions on selection of treatment regimens from being made using only the concept of BED, while the TCP model allows these parameters to be taken into account.

Purpose: The paper is devoted to the comparison of simultaneous (SIB) and sequential (SEQ) radiation therapy of primary-multiple tumors with different absorbed total doses based on the modeling of integral radiobiological criteria. The research is aimed at optimization of treatment of rare primary-multiple tumors, development of optimal approaches based on the analysis of the effectiveness of different irradiation options. Material and methods: This research considers a system of primary-multiple targets, using a gynecologic tumor including vagina (adenosquamous carcinoma), endometrium (moderately differentiated adenocarcinoma with foci of squamous metaplasia), and lymph nodes as an example, to which certain equivalent total doses of irradiation must be delivered (EQD2>=74.8 Gy for vagina, EQD2>=85 Gy for endometrium). Different scenarios of two-stage and one-stage irradiation, including different combinations and doses for each target, are studied in the simulation. Results: Comparison of treatment plans for the triple target system shows that, performing sequential radiotherapy SEQ is characterized by higher levels of equivalent total dose delivered to the target volumes taking into account the total irradiation time and, consequently, to the critical organ volumes, especially in the rectum and sigmoid colon. In case of simultaneous irradiation SIB, the duration of treatment is five weeks instead of seven weeks, which reduces the value of the equivalent total dose to the target by 7-10 Gy. The value of the absorbed single dose delivered to the target volume is up to 3 Gy, which can be attributed to moderate hypofractionation. Levels of radiation exposure for critical organs in this case are much lower than when two-stage irradiation is used. Conclusion: Simultaneous integrated boost radiation therapy allows a significant reduction in radiation exposure to critical organs compared to sequential radiation therapy (reduction to single systems).

Purpose: Analysis of radical radiotherapy efficacy (combination of remote irradiation with simultaneous dose escalation to the tumor focus and subsequent intracavitary component) in a patient diagnosed with stage III endometrial cancer when surgical treatment is impossible. Assessment of the dynamics of the underlying disease and adverse events. The purpose of the study is to analyze the effectiveness of radical radiation therapy in a patient diagnosed with stage III endometrial cancer when surgical treatment is impossible. Material and methods: We present a clinical case of a patient with inoperable stage III endometrial cancer (histologic variant-highly differentiated adenocarcinoma) with metastasis to the lower third of the vagina. The first stage was a course of remote radiotherapy on a linear gas pedal VarianTrueBeamSTx on the uterus, vagina, paravaginal tissues, pelvic lymph nodes up to a total dose of 50 Gy and simultaneous dose intensification on the area of tumor focus in the lower third of the vagina up to a total dose of 62.5 Gy. The method of dose administration was rotational radiotherapy with intensity modulation of photon radiation (Volume-modulated arc therapy ‒ VMAT). The second stage was a course of intracavitary (contact, brachytherapy) radiotherapy on MultiSource HDR device with 60Co ionizing radiation source. A gynecological two-channel applicator was used during treatment. The plan of each treatment session was developed based on CT images on the SagiPlan planning station. Intracavitary radiation therapy mode – single dose of 6 Gy, 4 fractions were performed. The effect of radiation therapy was assessed by MRI of pelvic organs with intravenous contrasting immediately after treatment and further at intervals of every 3 months.We present a clinical case of a 71 year old female patient diagnosed with stage III endometrial cancer (well-differentiated adenocarcinoma), with adenocarcinoma metastasis to the lower 1/3 of the vagina. Planning of radiotherapy and radiation therapy in a patient with inoperable endometrial cancer with simultaneous escalation of the dose of ionizing radiation to the area of ​​metastasis in the vagina during the remote component and subsequent intracavitary boost to the uterine area. Study of the results of radiation therapy. Results: After treatment, MRI data showed complete regression of the tumor nidus in the vagina and reduction of the nidus in the uterine body (more 50 %). Long-term control of the tumor process in the patient, confirmed by clinical and radiological studies (MRI of the pelvic organs), was also achieved.The capabilities of modern radiation therapy make it possible to carry out radical treatment of patients with endometrial cancer in clinical cases when it is necessary to increase the dose of ionizing radiation to a separate tumor focus, without exceeding the tolerable levels of radiation exposure to risk organs. This approach makes it possible to achieve remission in real clinical practice. Conclusion: The capabilities of modern radiation therapy allow radical treatment of patients with inoperable endometrial cancer in clinical cases when it is necessary to increase the dose of ionizing radiation to a separate tumor focus without exceeding tolerance levels of radiation loads on risk organs. This approach makes it possible to achieve remission in real clinical practice.

The aim of the study was to analyze and summarize the available literature data on the modern radiotherapy techniques, indications for radiotherapy (preoperative, radical, postoperative radiation therapy), treatment volumes at different disease stages, and principles of drug and accompanying therapy for patients with vulvar cancer. Material and Methods. The literature review was based on the clinical recommendations of the Ministry of Health of the Russian Federation and National Comprehensive Cancer Network (NCC N), as well as on the search of sources in PubMed and Cochrane Library systems. Literature sources and publications from 2005 to 2023 were included. Results. This contribution outlined the main indications for preoperative, postoperative and radical radiotherapy in patients with vulvar cancer, as well as the basic principles of drug treatment and correction of complications. Potential risk factors for postoperative disease recurrence were identified, the volumes of irradiation at each treatment mode were analyzed, and the feasibility of using brachytherapy in patients with vulvar cancer was discussed. Conclusion. To date, there are recommendations, guidelines for the management of patients with vulvar cancer, as well as clinical trial results. Understanding of the principles of prescribing treatment for vulvar cancer patients can improve local control, overall and recurrence-free survival, and the use of modern radiotherapy techniques will enshure an acceptable quality of life in these patients.

Background . Radiation therapy for high-risk prostate cancer presents a challenge for cancer radiotherapists. The improvement of treatment outcomes is associated with radiation dose escalation and prophylactic irradiation of lymph nodes, therefore, the development of the new treatment schemes is needed. Simultaneous integrated boost technique based on the volumetric modulated arc therapy is the most efficient treatment option. Material and Methods . The anatomical data of 10 patients with high-risk prostate cancer was used for dosimetry-based treatment planning. Both simultaneous integrated boost and sequential boost technique were considered. The treatment planning goal was to deliver the equivalent dose of 96 Gy at 2 Gy per fraction ( EQD 2 =96 Gy) (α/β=1.5 Gy) to the prostate, EQD 2 =62.5 Gy to the seminal vesicles and EQD 2 =50 Gy to lymph nodes avoiding damaging the organs at risk, mainly the bladder and rectum. The irradiation was based on volumetric modulated arc therapy with two partially coplanar arcs and two rotations at each arc. The obtained dose distributions were compared with respect to dose-volume histograms and equivalent uniform doses (EUD). Results . In the case of sequential boost, the minimal dose delivered to the prostate was equal to 95.9 ± 2.1 Gy, EUD=104.9 ± 1.7 Gy. The dose delivered to 2 cm 3 ( D 2cc ) bladder was 97.4 ± 2.0 Gy. Normal tissue complication probability (NTCP) was 1.64 %. The dose delivered to 2 cm3 ( D 2cc ) rectum was 103.4 ± 9.2 Gy and NTCP was 27.4 %. In the case of simultaneous integrated boost, the minimal dose delivered to the prostate was equal to 90.4 ± 2.3 Gy, EUD =103.9 ± 1.3 Gy. The bladder dose was as high as D 2cc =96.1 ± 5.2 Gy, NTCP =0.176 ± 0.132 %, the rectum dose - D 2cc =81.1 ± 6.0 Gy, NTCP =2.34 ± 1.92 %. Conclusion . Volumetric modulated arc therapy along with simultaneous integrated boost have shown the feasibility of simultaneous irradiation of the prostate, seminal vesicles and lymph nodes up to the prescribed dose values without significant over irradiation of the organs at risk (OARs). Dose values in the tumor as high as EUD =103.9 ± 1.3 Gy along with prophylactic irradiation of lymph nodes may result in higher tumor control probability value and should be considered for clinical trials.

The study aimed to assess the radiosensitizing effect of lithium ascorbate on tumor cells. Background: Cancer cells radioresistance is an important factor restraining the success of X-ray therapy. Radiosensitizing drugs make tumor cells more sensitive to ionizing radiation and improve the effectiveness of radiotherapy. Although many chemical substances can potentiate the cytotoxic effects of X-ray radiation, their clinical applications are limited due to possible adverse reactions. Recently, several approaches have been proposed to develop new radiosensitizers that are highly effective and feature low toxicity. Among new enhancers of X-ray therapy, ascorbic acid, and its derivates demonstrate very low toxicity along with a wide therapeutic range. Lithium ascorbate is a promising X-ray therapy enhancer, but its mechanism of action is unknown. This research focuses on the radiosensitizing properties of lithium ascorbate and its effects on both tumor and normal irradiated cells. Methods: The viability of the radiosensitized cells was evaluated by fluorescence flow cytometry using Annexin V-FITC Apoptosis Detection Kit and Cellular ROS Assay Kit (Abcam, UK). The test cell cultures included normal human mononuclear and Jurkat cells. Results: Lithium ascorbate sensitizes normal human mononuclear and Jurkat cells towards ionizing radiation. The combined cytotoxic effect of X-ray irradiation (3 Gy) and lithium ascorbate (1,2 mmol/L) substantially exceeds the effects of the individual factors, i.e. synergetic action appears. The major types of cell death were late apoptosis and necrosis caused by excessive production of reactive oxygen species. Conclusion: Lithium ascorbate in combination with X-ray irradiation exhibited the cytotoxic effect on both normal and cancer lymphoid cells by activating reactive oxygen species (ROS)-induced apoptosis. These findings indicate that lithium ascorbate is a promising substance to develop a new radiosensitizing drug.

Purpose: To investigate the influence of absorbed dose distribution in the tumor volume on the values of integral radiobiological criteria, such as the probability of local tumor control (Tumor Control Probability, TCP) and normal tissue complication probability (NTCP), based on synthetic dose-volume histograms (DVH), which enables to assess the treatment effectiveness and probability of complications from healthy organs and tissues. Material and methods: Synthetic dose-volume histograms were considered theoretically possible to analyze the dependence of equivalent uniform dose (EUD) on values of Nimirko model parameters and absorbed dose distribution for both tumor and critical organs. The calculation was carried out in Wolfram Mathematica program based on the algorithm, where an array of absorbed dose values per fraction of irradiation volume with step by absorbed dose was calculated for the given values of absorbed dose and the parameter determining the width of distribution. The resulting array was differentiated to obtain the differential DVH. The EUD values were obtained from the normalized differential DVHs. Results: During analysis of EUD value dependence on parameter a values determining degree of nonlinearity of absorbed dose summation in sub-volumes of irradiation and on absorbed dose distribution the following was revealed: for critical organs at high values of parameter a the essential role belongs to high and average values of absorbed dose, and for tumors at low values of parameter a the main role belongs to the minimum value of absorbed dose. Thus, the value of parameter a should be negative for a tumor, and positive for critical organs, and should be specifically defined for specific structures. Conclusion: To improve the predictive value (prediction) of the effect of radiotherapy using the TCP/NTCP Nimirko model, an adequate definition of the parameter a, the value of which can only be determined from absorbed dose distributions over the volume of anatomical structures within clinical trials, is necessary.

We present here the results of calculating the probability of complications in patients’ normal tissues using four mathematical models with the aim of assessing damage to critical organs during radiation therapy. The Lyman-Kutcher-Burman and Niemierko models show good agreement and provide equivalent results across the most practical range of probabilities of radiation complications.

Introduction. Radioresistance of cancer cells is a serious problem in radiation therapy of tumor diseases. Radiosensitizers make malignant cells more sensitive to radiation and increase the effectiveness of radiation therapy; however, their widespread clinical use is limited by significant side effects. The development and study of new radiosensitizers seems to be an urgent task of modern pharmacology.Aim. The purpose of this work was to study the effectiveness of lithium ascorbate as a radiosensitizer under the influence of photon and neutron radiation in wide dose range.Materials and methods. Evaluation of the biological effect was carried out using the tumor line of prostate cancer PC-3. We used a cyclotron to produce neutron radiation and a Cobalt-60 source to produce gamma radiation.Results and discussion. We have proved an increase in the cytotoxic effect with the combined use of different types of ionizing radiation and lithium ascorbate. The resistance of the prostate cancer line to gamma radiation at an absorbed dose of 0.5–3.0 Gy was revealed. It was shown that tumor cells of prostate cancer are more sensitive to the effects of the study drug in minimal concentrations in combination with neutron irradiation compared to gamma radiation in the same absorbed dose. The main mechanism of the radiosensitizing action of lithium ascorbate is the local induction of oxidative stress, which synergistically enhances the action of ionizing radiation.Conclusion. The combination of lithium ascorbate with neutron radiation leads to a more pronounced resulting cytotoxic effect. An increase in the concentration of lithium ascorbate led to the pro-oxidative action with an increase in the damaging effect on cells.

Background: The purpose of this study was to evaluate influence of technical parameters on Stereotactic Radiosurgery (SRS) plans on dosimetric evaluation. Materials and methods: There were considered and selected two patients who had brain tumors and had been treating in Tomsk Regional Oncology Center. All treatment plans were simulated using the Monaco treatment planning system v 5.11 (Elekta Instrument AB, Stockholm) on the Elekta Synergy linac with photon beam nominal energy 6 MV. For study there were created several plans with different technical parameters (number of arcs, increment, gantry angle, collimator angle, couch angle, minimum segment width). Each plan was evaluated by metrics such as Conformal, Homogeneity and Gradient indexes. Results: If we use a large increment value it may create few sectors and which can produce low quality plans, and increase treatment time, otherwise if we use a too small increment value it will give us more sectors and they can increase the quality of the plan. The dose which was measured with higher MSW showed to us better agreement with the calculated dose. Conclusion: It is valuable to carefully select technical parameters. The use of rigid increment value, segment width or increasing number of arcs can make plans have lower quality and to rise time of treatment.

The results of inverse dosimetric planning of intensity-modulated photon radiation therapy are presented. Physical and biological weight functions were used to optimize the dose distribution. Irradiation plans based on biological optimization functions were shown to have advantages over plans based on physical optimization for achieving the goal of radiation therapy, as well as reducing radiation exposure and the time required to calculate the dose distribution.

The presented modular educational master's program “Nuclear Medicine” for medical physicists, developed in cooperation between two universities (TPU and Siberian State Medical University) and a medical organization in the field of oncological diseases Tomsk regional Oncology Center, is available for students of the Russian Federation and Countries of the former Soviet Union, as well as for foreign students. The educational program is aimed at training masters who are able to effectively carry out professional activities in such areas as “Nuclear Industry (in the use of nuclear physics and technology)” and “Education and Science (in the field of scientific research in nuclear physics and technology)”.

The level of spontaneous and radiation-induced DNA damage varies depending on genetic and environmental factors in human somatic cells. This variation may be associated with transcriptional changes in cells, allowing the use of gene expression levels as markers of individual sensitivity to mutagenic effects. This study aimed to identify and characterize differentially expressed genes (DEGs) in lymphocytes of individuals with various frequencies of endogenous γH2AX foci and radiation-induced micronuclei (n = 37). The low-focus group was characterized by 0.18 ± 0.02 endogenous γH2AX foci per cell and a 155.78 ± 47.19‰ radiation-induced micronucleus frequency. The high-focus group was characterized by 0.49 ± 0.07 foci/cell and a 78.44 ± 33.21‰ micronucleus frequency. Seven DEGs (ENST00000424415, CRNDE, ADAMTS1, ENST00000424084, EIF2A, PNPLA5, and FRG2C) (FDR < 0.2) were identified by gene expression analysis with microarrays. As the extracellular matrix metalloproteinase, ADAMTS1 is able to activate the latent form of TGFβ, and TGFβ is involved in radiation-induced cellular response; the effects of ADAMTS1 knockout and overexpression on the gene expression profile were further validated in adherent HeLa cells. Twenty-nine of 160 identified DEGs are involved in apoptosis, DNA DSB repair, G2/M cell cycle transition, and the TGFβ signaling pathway. Thus, ADAMTS1 may be useful as a potential target for antitumor therapy.

Purpose: Carrying out the analysis of the physical and radiobiological equivalence of dose distributions obtained during the planning of hypofractionated stereotactic radiation therapy of the prostate cancer and verification using a three-dimensional cylindrical dosimeter. Material and Methods: Based on the anatomical data of twelve patients diagnosed with prostate carcinoma, stage T2N0M0 with low risk, plans were developed for stereotactic radiation therapy with volumetric modulates arc therapy (VMAT). The dose per fraction was 7,25 Gy for 5 fractions (total dose 36,25 Gy) with a normal photon energy of 10 MV. The developed plans were verified using a three-dimensional cylindrical ArcCHECK phantom. During the verification process, the three-dimensional dose distribution in the phantom was measured, based on which the values of the three-dimensional gamma index and the dose–volume histogram within each contoured anatomical structures were calculated with 3DVH software. The gamma index value γ (3 %, 2 mm, GN) at a threshold equal to 20 % of the dose maximum of the plan and the percentage of coincidence of points at least 95 % was chosen as a criterion of physical convergence of the calculated and measured dose distribution according to the recommendations of AAPM TG-218. To analyze the radiobiological equivalence of the calculated and measured dose distribution, the local control probability (TCP) and normal tissue complication probability (NTCP) criteria were used based on the calculated and measured dose–volume histograms. Contours of the target (PTV) and the anterior wall of the rectum were used for the analysis. The approach based on the concept of equivalent uniform dose (EUD) by A. Niemierko was used to calculate the values of TCP/NTCP criteria. Results: The results of physical convergence of plans for all patients on the contour of the whole body were higher than 95 % for the criteria γ (3 %, 2 mm, GN). The convergence along the PTV contour is in the range (75.5–95.2)%. The TCP and NTCP values obtained from the measured dose-volume histograms were higher than the planned values for all patients. It was found that the accelerator delivered a slightly higher dose to the PTV and the anterior wall of the rectum than originally planned. Conclusion: The capabilities of modern dosimetric equipment allow us move to the verification of treatment plans based on the analysis of TCP / NTCP radiobiological equivalence, taking into account the individual characteristics of the patient and the capabilities of radiation therapy equipment.