Non-Homogeneous Tumor Growth and Its Implications for Radiotherapy: A Phenomenological Approach

Tumor regrowth and heterogeneity are important clinical parameters during radiotherapy, and the probability of treatment benefit critically depends on the tumor progression pattern in the interval between the fractional irradiation treatments. We propose an analytic, easy-to-use method to take into account clonal subpopulations with different specific growth rates and radiation resistances. The different strain regrowth effects, as described by Gompertz law, require a dose-boost to reproduce the survival probability of the corresponding homogeneous system and for uniform irradiation. However, the estimate of the survival fraction for a tumor with a hypoxic subpopulation is more reliable when there is a slow specific regrowth rate and when the dependence on the oxygen enhancement ratio of radiotherapy is consistently taken into account. The approach is discussed for non-linear two-population dynamics for breast cancer and can be easily generalized to a larger number of components and different tumor phenotypes.

Experimental therapy for rabbits with radiation cystitis

Using a new model of the induction of radiation cystitis (RC) in rabbits, the treatment effectiveness of animals with intravesical administration of a biodegradable drug - a gel containing salts of alginic and hyaluronic acids, as well as dioxidine and lidocaine (AHDL) was assessed. The work was performed on female rabbits of the “Chinchilla” breed. Fractional irradiation of the rabbit urinary bladder was carried out by a linear photon accelerator: a single dose per fraction was 6 Gy administered daily for 5 days to a total focal dose of 30 Gy. As a result of irradiation of the bladder, the animals developed RC. AHDL-gel was injected intravesically using a catheter at a dose of 2500 mg / kg of body weight 3 times a day weekly for 2 months, starting from 1 month after irradiation. The drug had a pronounced therapeutic effect on the rabbits with RC: the values ​​of clinical and laboratory indicators of cystitis in urea and blood were reduced, it was observed regression of morphological manifestations of inflammation in the bladder mucosa.

Correction of genetic instability of the genome by fractional irradiation of MDBK cells

With respect to given contradictory data in radiobiology, that according to some authors, irradiation of cells of plant and animal origin initiates DNA changes and according to others, repeated irradiation of cells in small doses has a stimulating effect on metabolism without increasing the purity of mutations, we conducted the present study, with the aim to study the stability of the genome of MDBK cell line against a background of single and double (fractional) irradiation. The object of the study was a continuous MDBK cell line (Madin-Darby Bovire Kidney Cell, cattle, kidney), which was grown in medium 199, manufactured by Federal State Budget Institution FCTRB-ARRVI (Kazan) with 10% bovine serum and the addition of antibiotics (benzylpenicillin sodium salt, kanamycin at 100 units/ml) (streptomycin sulfate at 100 μg/ml) according to standard procedure. A monolayer culture of MDBK cells in the logarithmic growth phase (3-4 days after culture) served as contacting cells. As a result, a radio-modified cell line, called MDBK-2, was obtained. Moreover, in an unirradiated MDBK cell culture, the level of chromosomal breakdowns was in the range of 1.03-3.1% with respect to the total number of studied anaphases. Based on the obtained data, it can be concluded, that during prolonged cultivation of MDBK cells, irradiated in a small (adaptive) dose and re-irradiated in 3-minute higher dose (5.95 Gy), there is a significant decrease in the yield of aberrant cells, induced by a test dose of γ-rays.

Diffusion kurtosis imaging and tumour microstructure for monitoring response to radiotherapy in human nasopharyngeal carcinoma xenografts

Objective To investigate the correlations and feasibility of diffusion kurtosis imaging (DKI) parameters and tumour histopathology after radiotherapy in human nasopharyngeal carcinoma (NPC) xenografts on nude mice. Materials and Methods Seventy-two nude mice were used for the construction of CNE-1 (radio-insensitive) and CNE-2 (radio-sensitive) NPC xenograft models, followed by fraction irradiation at different doses of X-ray. The nude mice were randomly divided into six groups in each cell line models according to the dose of X-ray they have received and with six mice in each group. DKI scan was performed after radiation. DKI parameters, tumour histopathology and AQP-1 biomarkers were detected. One-way ANOVA and Pearson’s correlation analysis were used in statistical analysis. Results In CNE-1 and CNE-2 NPC xenografts, D values were increased (P < 0.01 and P < 0.001), while K values (P < 0.01 and P < 0.001) and tumour size (P < 0.001 and P < 0.001) were reduced during fraction irradiation. Additionally, cell density (CD) and AQP-1 expressions were decreased, and necrosis ratio (NR) was increased in CNE-2 xenografts after fraction irradiation (P < 0.001). The changes in D values were negatively correlated with tumour size (r = −0.856, P < 0.001), CD (r = −0.918, P < 0.001), AQP-1 mRNA (r = −0.856, P < 0.001) and protein (r = −0.381, P = 0.022) expressions while positively correlated with NR (r = 0.908, P < 0.001) in CNE-2 xenografts. The changes in K values were positively correlated with tumour size (r = 0.964, P < 0.001), CD (r = 0.888, P < 0.001), AQP-1 mRNA (r = 0.955, P < 0.001) and protein (r = 0.330, P = 0.049) expression levels while negatively correlated with NR (r = −0.930, P < 0.001). However, in CNE-1 xenografts, there were no correlation between DKI parameters and the expression of AQP-1. Conclusion Changes in D and K parameters after fractional irradiation are closely related with NPC cellular and pathological characteristics, especially size reduction and necrosis induction. These parameters exhibit potential abilities of monitoring the response to fractional irradiation in radio-sensitive NPC xenografts.

Study on Integrated Setup System with Computer Vision for Breast Cancer Radiotherapy

Purpose: To discuss a setup verification method based on computer stereo vision for the repeat setup in breast cancer fractional irradiation. Methods and Materials: A photogrammetric system is composed of two cameras and one computer. First, multiple characteristic markers’ coordinates are gotten by the two cameras, then the three-dimensional coordinates of the markers are calculated according to the basic principle of binocular calculated, which can construct breast and chest surface stereo features shape, thus the setup error can judge and correct before radiation therapy. At the tracking process, we use SITF (Scale Invariant Feature Transform) as the registration algorithm, which has strong robustness and accurate matching performance, meanwhile, dynamic choice matching image and local searching strategy are used in the process of calculation and mergence in order to make the target image matching more precisely. Results: Experimental results show that in breast cancer fractional irradiation, the system can accurately display setup error and can achieve real-time calculation. Conclusion: The proposed method can reduce setup error in breast cancer fractional irradiation, and has good stability and high precision.

Bone fragility induced by x-ray irradiation in relation to cortical bone-mineral content

Purpose: A large single dose of irradiation to bone tissue causes bone fragility, and such bone will be susceptible to fracture even without trauma. the purpose of this study was to investigate the effects of fractional irradiation on the biomechanical properties of bone in the rat in relation to the cortical bone-mineral content (BMC), and to compare these effects with those brought about by single-dose irradiation Material and Methods: Seventy-five veteran female Wistar rats were divided into 4 groups. Group 1 was the control group. the left tibiae of the remaining rats were exposed to irradiation. Group 2 received one single dose of X-rays at 10–60 Gy. Groups 3 and 4 received fractional irradiation up to different cumulative doses (10–60 Gy): group 3 received 2.5 Gy once a day; group 4 received 1.25 Gy twice a day. Twenty-four weeks after irradiation, the rats were killed and the BMC in each tibial diaphysis was determined by dual-energy X-ray absorptiometry (DXA). the bones were then loaded to failure in a three-point bending test Results: the control group showed no difference (p<0.05) between left and right tibiae, neither in BMC nor in the maximum load at fracture. Single-dose irradiation caused a 16% ( p = 0.0366) decrease in the maximum load at 40 Gy, and a 19% ( p = 0.008) decrease at 60 Gy. the once-daily fractional dose of irradiation caused a 10% ( p = 0.0022) decrease in the maximum load of the irradiated tibiae at 60 Gy when compared to the intact contralateral tibiae. the twice-daily fractional dose of irradiation had no observable effect on the maximum load of the irradiated tibiae. Neither fractional irradiation modality had an effect on BMC Conclusion: the study suggested that bone fragility induced by single fractional irradiation doses (given once daily up to high cumulative doses) was not associated with change in the cortical BMC. It also confirmed the preference for twice-daily fractional irradiation as compared to once-daily fractional irradiation and the total single dose