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.

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.

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.

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 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.

The effect of knockout and overexpression of the ADAMTS1 on the radiation-induced response in HeLa cell line was analyzed. The cell line with the ADAMTS1 gene knockout was created using the CRISPR/Cas9 genome editing technology. The ADAMTS1 gene overexpression was ensured by transient transfection of the plasmid containing the gene of interest. Clonogenic survival, micronuclei frequency, and the γH2AX and 53BP1 foci level after irradiation with 2–8 Gy of γ rays were assessed. It was shown that the HeLa cell line with the ADAMTS1 gene knockout was characterized by a 1.9-fold decrease in clonogenic survival after an irradiation dose of 2 Gy ( p < 0.05) and an increase in micronuclei frequency (55.3 ± 8.3‰) in comparison with intact HeLa (36.0 ± 7.2‰, p < 0.05), but did not differ in the DNA repair foci level. Transfection of the plasmid carrying the ADAMTS1 gene into HeLa cell line with the ADAMTS1 gene knockout led to a decrease in the radiation-induced micronuclei frequency from 55.3 ± 8.3 to 28.7 ± 10.3‰ ( p < 0.05), which was comparable with the micronuclei frequency in the original HeLa cell line after irradiation (36.0 ± 7.2‰). Our results indicate that the ADAMTS1 gene is involved in radiation-induced cellular response in the HeLa cell line.

Introduction Some patients with locally advanced cervical cancer (LACC) cannot undergo brachytherapy (BT). Possible treatment includes two-stage external beam radiotherapy (sequential boost - SEQ) or single-stage external beam radiotherapy (simultaneous integrated boost - SIB). The goal of this paper was to carry out dosimetric and radiobiological comparison of these techniques with respect to tumour and organs-at-risk (OARs) irradiation. Methods The anatomic data of six patients with LACC were used for this study. The single-stage SIB-VMAT (25, 27 or 30 fractions) and double-stage SEQ-VMAT (25 + 6 fractions) plans were developed to deliver EQD(2) = 50 Gy to the pelvic region and EQD(2) = 90 Gy to the tumour. The developed plans were compared with respect to an EQD(2) dose delivered to a tumour and to the OARs, expected tumour control probability and normal tissue complications probability. Results The developed SIB-VMAT and SEQ-VMAT plans had physical coverage of the CTV tumours with more than 95% of the prescribed dose delivered to more than 95% of the volume. The irradiation of the tumour for both SIB-VMAT and SEQ-VMAT has comparable EQD(2) values close to 87-88 Gy. SIB-VMAT treatment plans provided lower levels of irradiation of OARs than SEQ-VMAT plans. The optimal number of fractions for SIB-VMAT was 27. Conclusion SIB-VMAT is a better treatment option for patients with LACC that are not eligible for BT. Results show that both SIB-VMAT and SEQ-VMAT allowed good coverage of the tumour and high-quality dose delivery. SIB-VMAT allowed minimising irradiation of OARs and shortening the overall treatment time by a week.

The development of linac–based narrow–band THz sources with sub–picosecond, μ J -level radiation pulses is in demand from the scientific community. Intrinsically monochromatic emitters such as coherent Smith–Purcell radiation sources appear as natural candidates. However, the lack of broad spectral tunability continues to stimulate active research in this field. We hereby present the first experimental investigation of coherent grating diffraction radiation (GDR), for which comparable radiation intensity with central frequency fine–tuning in a much wider spectral range has been confirmed. Additionally, the approach allows for bandwidth selection at the same central frequency. The experimental validation of performance included the basic spectral, spatial and polarization properties. The discussion of the comparison between GDR intensity and other coherent radiation sources is also presented. These results further strengthen the foundation for the design of a tabletop wide–range tunable quasi–monochromatic or multi–colour radiation source in the GHz–THz frequency range.

In this study, the effect of the THBS1 gene knockout on the survival of human tumor cells, the frequency of spontaneous and radiation-induced micronuclei, and the expression profile of genes in the HeLa cell line was investigated. It was shown that the THBS1 gene knockout led to a decrease in the plating efficiency before and after irradiation (1.4-fold, p = 0.0002 and 1.7-fold, p = 0.00009, respectively) and an increase in the frequency of spontaneous and radiation-induced micronuclei (1.9-fold, p = 0.02 and 2.5-fold, p = 0.01, respectively). In addition, expression of genes involved in the DNA repair processes, apoptosis, and G2/M cell cycle checkpoint was changed after THBS1 knockout in comparison with the intact HeLa cell line. Thus, the THBS1 gene knockout leads to an increase in the radiosensitivity of the HeLa cell line. This indicates the possible role of the THBS1 gene in the regulation of a radiation-induced cellular response.

This research considers potential dose increase in a target due to cisplatin (Pt) concentration and radiation type. Dose changes were calculated with cisplatin concentrations from 0.003 to 120 mM. Monte-Carlo simulation of Linear accelerator (Elekta Synergy) and X-ray tube (Xstrahl300) was carried out using Geant4 and PClab. At the first stage of this research, we performed a simulation of energy spectrum from radiotherapy units (spectrum model). The next stage was the modeling of a linear accelerator head and an X-ray tube, and the dose distribution in the water phantom (PDD model). At the second stage, dose changes were investigated in the presence of cisplatin in the target (CIS model). The simulation results showed that the dose escalation can be caused by photon-capture therapy (PCT). There is a dose enhancement in the volume where cisplatin is accumulated. However, the photon energy increase from 60 to 250 kV and the increase of the target depth reduces the effect of PCT due to the decrease of the photoelectric effect cross-section. It should be noticed, that the orthovoltage X-rays energy, listed in the table with results, shows higher dose enhancement, than the megavoltage photon beam generated from linear acceleration sources. In addition, the dose enhancement factors (DEF) are higher in a linac without a flattening filter, than in a linac with a flattening filter.

Objective. To determine the most effective irradiation regimen (total dose and dose per fraction) for hypofractionated treatment for prostate carcinomas according the TCP/NTCP radiobiological criteria.Material and methods. Using the tomographic information of five patients with low-risk prostate adenocarcinoma as an example, the authors devised dosimetric radiation therapy plans using the volumetric modulated arc therapy (VMAT) procedure. They considered the range of total doses of 33.5 to 38 Gy administered in 4 and 5 fractions. Based on the equivalent uniform dose concept proposed by A. Niemierko and on the computed differential dose volume histograms, the investigators modeled local tumor control probability (TCP) values, by taking into account the uncertainties of main radiobiological parameters, and estimated normal tissue complication probabilities (NTCP) for the anterior rectal wall as the organ most at risk of irradiation. An effective dosimetric plan was selected according to the UTCP criterion and the probability of complication-free tumor control, i.e. TCP (1 – NTCP).Results. The results of modeling the UTCP criterion show that with a higher total dose, the TCP value increases and so does the NTCP value, therefore the optimal radiation therapy plans are to irradiate with a total dose of 34 Gy over 4 fractions or with a dose of 36–37 Gy over 5 fractions. The difference between the fractionation regimens is that the UTCP value is achieved with a higher TCP value over 4 fractions and with a lower load on the rectal wall over 5 fractions.Conclusion. The choice of a specific fractionation regimen should be determined from the calculated values of differential dose volume histograms for each patient, as well as from radiobiological criteria, such as TCP, NTCP and UTCP.

Introduction: Stereotactic body radiation therapy is widely used for the hypofractionated treatment of prostate cancer. The range of total doses used in different clinical trials varies from 33.5 to 50 Gy delivered in 4 or 5 fractions. The choice of an optimal total dose value and fractionation regimen for a particular patient can be carried out using the integral radiobiological criteria, namely tumour control probability (TCP) and normal tissue complication probability (NTCP). In this study, we have investigated the dependence of simulated TCP/NTCP values on total dose in the range of 30-40 Gy delivered in 4 or 5 fractions for patients with low-risk prostate cancer in order to find the optimal total dose value and fractionation regimen. Methods: The anatomic data (DICOM CT images) of 12 patients with low-risk prostate cancer, who were treated at Tomsk Regional Oncology Centre, were used for the calculation. Dosimetric treatment plans for all patients were simulated using VMAT with 2 arcs in the Monaco treatment planning system v5.10 (Elekta Instrument AB, Stockholm) with a total dose equal to 36.25 Gy. The dosimetric plans were rescaled in the dose range of 30-40 Gy. The TCP and NTCP values were calculated based on differential dose volume histograms using the Niemierko model for both TCP and NTCP, and the Kallman-s model for NTCP calculations. The TCP calculation was carried out using the uncertainty of well-known tumour radiobiological parameters values, including alpha/beta value. NTCP was calculated for an anterior rectal wall, which was the most irradiated organ at risk due to its close contact with the planning target volume. Results: The TCP and NTCP calculations for VMAT of the prostate cancer have shown that the optimal total dose ranges were equal to 32-34 Gy delivered in 4 fractions or 35-38 Gy delivered in 5 fractions. At doses lower than the optimal ones, the TCP values were lower than 95%, while TCP uncertainties were significant (as low as 80%). This fact might bring unexpectedly poor treatment results. At doses higher than optimal ones, the probability of toxicity to the anterior rectal wall became significant. Conclusion: The optimization of radiation therapy regimen based on TCP/NTCP criteria could help to determine an optimal total dose and a number of fractions for a particular patient depending on patient-specific anatomic features and planned dose distribution.