Characteristics of Myeloid Differentiation and Maturation Pathway Derived from Human Hematopoietic Stem Cells Exposed to Different Linear Energy Transfer Radiation Types

Exposure of hematopoietic stem/progenitor cells (HSPCs) to ionizing radiation causes a marked suppression of mature functional blood cell production in a linear energy transfer (LET)- and/or dose-dependent manner. However, little information about LET effects on the proliferation and differentiation of HSPCs has been reported. With the aim of characterizing the effects of different types of LET radiations on human myeloid hematopoiesis, in vitro hematopoiesis in Human CD34⁺ cells exposed to carbon-ion beams or X-rays was compared. Highly purified CD34⁺ cells exposed to each form of radiation were plated onto semi-solid culture for a myeloid progenitor assay. The surviving fractions of total myeloid progenitors, colony-forming cells (CFC), exposed to carbon-ion beams were significantly lower than of those exposed to X-rays, indicating that CFCs are more sensitive to carbon-ion beams (D ₀ = 0.65) than to X-rays (D ₀ = 1.07). Similar sensitivities were observed in granulocyte-macrophage and erythroid progenitors, respectively. However, the sensitivities of mixed-type progenitors to both radiation types were similar.In liquid culture for 14 days, no significant difference in total numbers of mononuclear cells was observed between non-irradiated control culture and cells exposed to 0.5 Gy X-rays, whereas 0.5 Gy carbon-ion beams suppressed cell proliferation to 4.9% of the control, a level similar to that for cells exposed to 1.5 Gy X-rays. Cell surface antigens associated with terminal maturation, such as CD13, CD14, and CD15, on harvest from the culture of X-ray-exposed cells were almost the same as those from the non-irradiated control culture. X-rays increased the CD235a⁺ erythroid-related fraction, whereas carbon-ion beams increased the CD34⁺CD38⁻ primitive cell fraction and the CD13⁺CD14^+/−CD15⁻ fraction. These results suggest that carbon-ion beams inflict severe damage on the clonal growth of myeloid HSPCs, although the intensity of cell surface antigen expression by mature myeloid cells derived from HSPCs exposed to each type of radiation was similar to that by controls.     

Effects of X-irradiation and adriamycin on quiescent and proliferating cells of the seminal vesicle in the castrated mouse

The sensitivity of resting and proliferating cells of the seminal vesicle to X-irradiation and adriamycin has been investigated. Stimulation with testosterone propionate (250 μg/day) was started 11 days after castration in BALB/c mice. X-rays (2.5–7.5 Gy total body irradiation) and intraperitoneal injections of adriamycin (4–16 mg/kg body weight) were administered at various times before or after induction of proliferation by testosterone injection. The DNA contents and the weights of the seminal vesicles were determined at 4 days after the start of stimulation. A D₀ for X-rays of about 10 Gy was found for the seminal vesicle epithelium. For both X-irradiation and adriamycin no significant differences in sensitivity were observed between quiescent (G₀) and proliferating (G₁; S) seminal vesicle cells.     

Clinical Trial of Prophylactic Extended-Field Carbon-Ion Radiotherapy for Locally Advanced Uterine Cervical Cancer (Protocol 0508)

To evaluate the efficacy and the toxicity of prophylactic extended-field carbon-ion radiotherapy (C-ion RT, Protocol 0508) for locally advanced squamous cell carcinoma of the uterine cervix in phase I / II clinical trial. Between May 2006 and January 2012, 26 patients of Protocol 0508 were treated with C-ion RT. The numbers of patients with stage IIB, IIIB, and IVA disease were 13, 11, and 2, respectively. Twenty patients had pelvic lymph node metastases. Median tumor size was 6.1 cm (range, 4.0–10.0 cm). The treatment consisted of extended-field irradiation of 39.0 gray equivalents (GyE) in 13 fractions, and additional 15.0 GyE in 5 fractions was given to the gross tumor volume (GTV) and surrounding tissues. With regard to local boost, 18.0 GyE in 2 fractions was given to GTV only. Total dose to the cervical tumor was 72.0 GyE over 20 fractions. The median follow-up period was 37 months. Twenty-one patients had grade 1 or 2 acute gastrointestinal toxicity, but all patients completed the treatment on schedule. There were no grade 3 or higher late complications, with 8 patients having grade 1 or 2 toxicities, 1 had grade 2 gastrointestinal toxicity and 2 had grade 2 genitourinary toxicity. Four patients (15.4%) developed local recurrence, and 8 patients (30.8%) had distant metastases. The 2-year local control rate, progression-free survival rate and overall survival rate were 83.6%, 61.5% and 73.1%, respectively. There were no severe acute or late complications in this trial. Prophylactic extended-field C-ion RT for locally advanced squamous cell carcinoma of the uterine cervix was a safe treatment. Although the number of patients in this study was small, the results support further investigations to confirm the therapeutic efficacy and to avoid or reduce toxicity.

Trial Registration

UMIN-CTR UMIN000016169     

Suppression of E. multilocularis Hydatid Cysts after Ionizing Radiation Exposure

Background

Heavy-ion therapy has an advantage over conventional radiotherapy due to its superb biological effectiveness and dose conformity in cancer therapy. It could be a potential alternate approach for hydatid cyst treatment. However, there is no information currently available on the cellular and molecular basis for heavy-ion irradiation induced cell death in cystic echinococcosis.

Methododology/Principal Findings

LD50 was scored by protoscolex death. Cellular and ultrastructural changes within the parasite were studied by light and electron microscopy, mitochondrial DNA (mtDNA) damage and copy number were measured by QPCR, and apoptosis was determined by caspase 3 expression and caspase 3 activity. Ionizing radiation induced sparse cytoplasm, disorganized and clumped organelles, large vacuoles and devoid of villi. The initial mtDNA damage caused by ionizing radiation increased in a dose-dependent manner. The kinetic of DNA repair was slower after carbon-ion radiation than that after X-rays radiation. High dose carbon-ion radiation caused irreversible mtDNA degradation. Cysts apoptosis was pronounced after radiation. Carbon-ion radiation was more effective to suppress hydatid cysts than X-rays.

Conclusions

These studies provide a framework to the evaluation of attenuation effect of heavy-ion radiation on cystic echinococcosis in vitro. Carbon-ion radiation is more effective to suppress E. multilocularis than X-rays.     

Proliferation kinetics and PCNA expression of HL-60 cells following ionizing irradiation and granulocytic differentiation

The human promyelocytic leukaemia cell line, HL-60, was investigated with regard to proliferation and terminal differentiation following irradiation. The cells were X-irradiated and induced with 1.25% dimethyl sulfoxide (DMSO) towards the granulocytic lineage. Proliferation was measured via cell growth, clonogenicity and the bromodeoxyuridine/DNA incorporation assay. Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) expression was used to discriminate cycling from non-cycling cells. The differentiation obtained was proved by testing for the immune function of the respiratory burst (NBT reduction test). The HL-60 cells studied revealed a high radiosensitivity (D₀= 0.63 Gy). After induction with DMSO, declines in cell growth, clonogenicity and PCNA positivity of the cells indicated a decrease in proliferation and an increase in differentiation. Starting on day 2 in culture, irradiation after seeding with 1 Gy accelerated the loss of the PCNA expression in induced cells (46%v. 3% PCNA-negative control cells on day 3). Induced cells gained the capability of exerting the respiratory burst, which was found to be dose-dependent radiosensitive (42% and 12% NBT-positive cells after 1 and 2 Gy, respectively, v. 53% NBT-positive control cells on day 8). Subpopulations in the cell line were evident in all parameters investigated. We discuss the HL-60 cell, not only as a model comparable to human progenitor cells, but also as a suitable tool in radiobiological research with regard to proliferation and differentiation following ionizing irradiation.     

The response of mouse skin to hyperthermia combined with fast neutrons or X-rays

The effects of hyperthermia combined with fast neutrons (mean energy approximately 7.5 MeV) or X-rays (250 kVp) were studied in the skin of the mouse ear and foot. Hyperthermia was achieved by immersion in water at temperatures of 41.5-43.0 degrees C for 1 hour. The heat treatments used caused no observable tissue injury other than transient erythema but they enhanced the response to both neutrons and X-rays. The enhancement of neutron damage increased as the heating temperature was increased, as is well known for X-rays. When heat was given after irradiation the thermal enhancement ratio (t.e.r.) for neutrons was similar to that for X-rays. When heat was given before irradiation the neutron t.e.r. was less than that for X-rays. Consequently, the relative biological effectiveness of fast neutrons compared with X-rays was not altered by giving heat after irradiation but it was reduced by giving heat before irradiation.     

Host cell cytotoxicity, cellular repopulation dynamics, and phase-specific cell survival in X-irradiated rat rhabdomyosarcoma tumors

Postirradiation tumor volume response, cellular repopulation dynamics, cell-cycle perturbations, and phase-specific cell survival were characterized in rat rhabdomyosarcoma R-1 tumors (the R2C5 subline) following an in situ 10-Gy dose of 225-kVp X rays. This X-ray dose produced a 7.5-day delay in tumor growth to twice the volume measured at the time of irradiation, and reduced the initial surviving fraction of R2C5 cells to 0.17 as measured by the excision assay procedure. The surviving fraction of R2C5 cells returned to unity by the 16th day after tumor irradiation. On the basis of flow cytometry measurements of DNA content in tumor cells stained with a noncytotoxic concentration of Hoechst 33342 (5 microM, 2 h, 37 degrees C), a transient G2 block was observed 1 day after irradiation. Flow cytometry measurements also demonstrated that the tetraploid R2C5 cells constituted only 30% of the total tumor cell population, with the remainder being diploid host cells comprised of macrophages, monocytes, lymphocytes, and granulocytes. Large numbers of host cells infiltrated the irradiated tumors, leading to an increase in the percentage of diploid cells by Day 2 and reaching a level of more than 80% of the total tumor cell population by 4 to 8 days after irradiation. The influx of host cells into irradiated tumors was correlated temporally with a significant 12-fold decrease in the surviving fraction of R2C5 cells that occurred between Days 2 and 4 postirradiation. When the diploid host cell population was removed by cell sorting procedures, the surviving fraction of R2C5 cells at Day 4 was substantially greater than that in the presence of the host cells. Experiments involving the mixing of 4/1 and 12/1 ratios of diploid host cells and tetraploid tumor cells isolated from irradiated and unirradiated tumors demonstrated that the cytotoxic effect of the host cells was specific for the irradiated tumor cells. The significant toxic effect of host cells on irradiated tumor cells was observed only at 2 to 4 days after irradiation, and not at earlier or later times. The data obtained in these experiments indicate that the immunogenicity of R2C5 cells is increased significantly by irradiation, and a resultant cell-mediated host immune response produced a delayed decrease in tumor cell survival that is most pronounced 4 days after irradiation. The cell survival characteristics of R2C5 cells in different cell-cycle phases were found to be similar through the 16-day postirradiation interval that was studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lipid peroxidation of rat spleen and thymus lymphocytes treated with x-rays (0-5-1.0 Gy)

It is established, that low doses of X-ray irradiation have affected activation of lipid peroxidation (LPO) in immunocompetent cells of the spleen and thymus. The amount of malonic dialdehyde (MDA) in lymphocytes of spleen and thymocytes increases 2 times twenty-four hours after animals' irradiation by X-rays in a dose of 0.5 Gy; when a dose grows to 1.0 Gy, the MDA content in the spleen lymphocytes increases from the 1st to the 6th days and in thymocytes from the 1st to the 3d days reaching its maximum at the 3d day. MDA accumulation in the immunocompetent cells of irradiated animals varies depending on the method of lipid peroxidation initiation.     

Glutathione metabolism in Urtica dioica in response to cadmium based oxidative stress

To investigate the antioxidative response of glutathione metabolism in Urtica dioica L. to a cadmium induced oxidative stress, activities of glutathione reductase (GR), glutathione-S-transferase (GST), and glutathione peroxidase (GSH-Px), content of reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation (LPO), and also accumulation of Fe, Zn, Mn, Cu besides Cd were determined in the roots, stems, and leaves of plants exposed to 0 (control), 0.045, and 0.09 mM CdCl₂ for 58 h. Whereas the Cd content continuously increased in all organs, the Fe, Zn, Mn, and Cu content decreased in dependence on the applied Cd concentration and incubation time. The Cd treatment resulted in increased GR and GST activities in all organs, however, GSH-Px activity was dependent on Cd concentration and plant organ. The GSH/GSSG ratio maintained above the control level in the stems at both Cd concentrations. The LPO was generally close to the control values in the roots and stems but it increased in the leaves especially at 0.09 mM Cd.     

Multiparameter analysis of CHO AL mutant populations sorted on CD59 expression after gamma irradiation

The flow cytometry mutation assay is based on detecting mutations in the CD59 gene on human chromosome 11 in CHO A(L) cells with flow cytometry, but the kinetics of mutant expression and the histogram region for mutant selection have not been studied in detail. CHO A(L) cells were analyzed by flow cytometry for CD59 expression at various times after irradiation. The mutant fraction increased to a maximum at day 6 but decreased to near background levels by day 20. Cells were sorted from six different regions on the CD59 histograms after irradiation. The growth rate was similar for cells from all regions, and the surviving fraction was 50% of that for control cells. By 14 days the CD59 expression of cells from regions 2-5 was reduced to that of region 1. Cells were also analyzed for simultaneous expression of CD59, CD44 and CD90 (all on chromosome 11) to roughly characterize the size of the mutations. Triple mutants from the sorted populations were reduced from 41% on day 6 to 8% on day 24. We conclude that the mutant region should be increased to include cells with intermediate CD59 expression; also, the loss of CD59 mutant expression over time could be explained in part by the loss of triple mutants from the population.     

HZE radiation effects for hereditary renal carcinomas.

Eker rat known as a model of hereditary renal carcinoma (RC) is an example of Mendelian dominantly inherited predisposition to a specific cancer in experimental animals. We investigate the effects of simulated space radiation on carcinogenesis using HIMAC. We estimated RBE from the Eker rats exposed to the heavy-ions, C (290 MeV/u) and Fe (500 MeV/u) ions, comparing to the effects of X-ray irradiation. Pregnant rats were exposed to C and Fe ions and X-rays with a single dose of 1 Gy, 2 Gy, 3 Gy on day 19 of gestation. The offspring were sacrificed at 8 weeks of age. We evaluated organ weights and tumor genesis. The weights of thymus, lung, liver, spleen were found to be no difference from the control at 1 Gy irradiation but 50% decrease at 3 Gy irradiation. We found in the irradiated animal that kidney, brain and testis were very sensitive organs of which the weight decreased to approximately 80% at 1 Gy and to 40% at 3 Gy irradiations. Based on the dose-response relationship of the radiation-induced carcinoma, averaged RBE ware calculated to be 1.1 for C-ion, 1.6 for Fe-ion.     

Blood Glutathione as an Index of Radiation-Induced Oxidative Stress in Mice and Humans

The effect of x-rays on GSH and GSSG levels in blood was studied in mice and humans. An HPLC method that we recently developed was applied to accurately determine GSSG levels in blood. The glutathione redox status (GSH/GSSG) decreases after irradiation. This effect is mainly due to an increase in GSSG levels. Mice received single fraction radiotherapy, at total doses of 1.0 to 7.0 Gy. Changes in GSSG in mouse blood can be detected 10 min after irradiation and last for 6 h within a range of 2.0–7.0 Gy. The highest levels of GSSG (20.1 ± 2.9 ), a 4.7-fold increase as compared with controls) in mouse blood are found 2 h after radiation exposure (5 Gy). Breast and lung cancer patients received fractionated radiotherapy at total doses of 50.0 or 60.0 Gy, respectively. GSH/GSSG also decreases in humans in a dose–response fashion. Two reasons may explain the radiation-induced increase in blood GSSG: (a) the reaction of GSH with radiation-induced free radicals resulting in the formation of thyl radicals that react to produce GSSG; and (b) an increase of GSSG release from different organs (e.g., the liver) into the blood. Our results indicate that the glutathione redox ratio in blood can be used as an index of radiation-induced oxidative stress. © 1997 Elsevier Science Inc.     

Sensitivity of the conidia of plant pathogenic fungi to Gamma-rays,electron particles and X-ray (Bremsstrahlung) irradiation

Twelve species of plant pathogenic fungi were exposed to high-energy irradiation and their sensitivities compared by the irradiation (termed D ₁₀) required to decrease the viability of conidia by 10%. The D ₁₀ of conidia in 0.06 Mxxx phosphate buffer and irradiated with gamma-rays at 32 to 35°C ranged from 0.16 to 0.71 kGy. When conidia were mixed with trehalose and vacuum dried, their sensitivity towards gamma-rays doubled. There was no identifiable trend in the response of dry conidia towards irradiation by gamma-rays, electron particles or X-rays.M. LebaiJuri and N. Yusof are with the Nuclear Energy Unit, PUSPATI Complex, Bangi, 43000 Kajang, Malaysia; M. Omar is with the Department of Microbiology, Universiti Kebangsaan Malaysia 43600 Ukm Bangi, Malaysia.     

Retrospective review of locally set tolerances for VMAT prostate patient specific QA using the COMPASS® system

PurposeThis study retrospectively reviewed locally set pass rates/tolerances for COMPASS^® pre-treatment quality assurance results for RapidArc prostate plans to determine if these are appropriate. This was performed via quantifying the agreement between treatment planning system calculations and measurements based on absolute dose comparisons (3% tolerance for all dose points) and global gamma index assessment (3%/3 mm criterion for 97% of points).MethodSeventy-three prostate one-arc RapidArc plans, delivered by four dosimetrically matched linacs, were measured using the MatriXX Evolution two-dimensional array and analysed using COMPASS^® (v.3, IBA Dosimetry). For the planning target volumes (PTV) considered, the D_99%, D_50%, D_1% and D_Mean differences were analysed. The percentage volume with gamma greater than 1, average gamma and D_Mean difference were investigated for all structures. Nine plans were also assessed across the linac fleet to investigate potential linac dependence of results.Results and ConclusionsRegarding PTV D_Mean differences, all plans fell within the 3% tolerance and mostly within 2%, although there was a relatively small systematic difference. The absolute percentage differences of average and median doses suggested a weak linac dependence of the results which was found to be clinically insignificant. New stricter tolerances were established both for dose comparisons and gamma evaluation. Correlation between the gamma pass rates and the differences in the D_99%, D_50% and D_1% was found to be moderate suggesting that gamma analysis in isolation has questionable clinical meaning and should only be used to indicate outliers for further analysis.     

Dosimetric impact of Acuros XB on cervix radiotherapy using RapidArc technique: a dosimetric study

BackgroundAcuros XB (AXB) may predict better rectal toxicities and treatment outcomes in cervix carcinoma. The aim of the study was to quantify the potential impact of AXB computations on the cervix radiotherapy using the RapidArc (RA ) technique as compared to anisotropic analytical algorithm (AA) computations.Materials and methodsA cohort of 30 patients previously cared for cervix carcinoma (stages II–IIIB) was selected for the present analysis. The RA plans were computed using AA and AXB dose computation engines under identical beam setup and MLC pattern.ResultsThere was no significant (p > 0.05) difference in D_95% and D_98% to the planning target volume (PTV); moreover, a significant (p < 0.05) rise was noticed for mean dose to the PTV (0.26%), D_50% (0.26%), D_2% (0.80%) and V_110% (44.24%) for AXB computation as compared to AA computations. Further, AXB estimated a significantly (p < 0.05) lower value for maximum and minimum dose to the PTV. Additionally, there was a significant (p < 0.05) reduction observed in mean dose to organs at risk (OARs) for AXB computation as compared to AA, though the reduction in mean dose was non-significant (p > 0.05) for the rectum. The maximum difference observed was 4.78% for the rectum V_50Gy, 1.72%, 1.15% in mean dose and 2.22%, 1.48% in D_2% of the left femur and right femur, respectively, between AA and AXB dose estimations.ConclusionFor similar target coverage, there were significant differences observed between the AAA and AXB computations. AA underestimates the V_50Gy of the rectum and overestimates the mean dose and D_2% for femoral heads as compared to AXB. Therefore, the use of AXB in the case of cervix carcinoma may predict better rectal toxicities and treatment outcomes in cervix carcinoma using the RA technique.     

Glutathione redox system,GSH-Px activity and lipid peroxidation (LPO) levels in tadpoles of R.r.ridibunda and B.viridis

Total glutathione (t-GSH), reduced glutathione (GSH), glutathione disulphide (GSSG) levels, t-GSH/GSSG ratio, glutathione peroxidase (GSH-Px) activity and lipid peroxidation (LPO) levels were investigated during the development period of a predominantly aquatic amphibian R.r.ridibunda and a predominantly terrestrial amphibian B. viridis. While t-GSH and GSH showed a similar trend, GSSG concentration increased significantly (p<0.05) during the larval stages in R.r.ridibunda larvae. In contrast to R.r.ridibunda larvae, there was no significant (p>0.05) change between 1 and 5 weeks in the t-GSH and GSH concentrations of B. viridis. t-GSH and GSH concentrations of B. viridis larvae became sharply elevated after the fifth week, GSSG levels increased 3.25-fold during the metamorphosis. The t-GSH/GSSG ratio fluctuated and the lowest t-GSH/GSSG ratios were observed at the third week for both species. GSH-Px activities for both species increased significantly (p<0.05) during the growing period. The highest GSH-Px activities in R.r.ridibunda and B.viridis were observed at the eighth week and they were 3.45 +/- 0.17 and 4.1 +/- 0.21 IU mg(-1), respectively. The membrane LPO levels in the R.r.ridibunda and B. viridis tadpoles significantly (p<0.001) decreased from 206 +/- 10.3 to 146 +/- 7.3 and from 198 +/- 9.9 to 23 +/- 1.15 nmol MDA g(-1) w.w., respectively.     

Reduction of patient dose in medical radiography by utilizing scattered X-rays: Relation between permissible limit of scatter fraction,viewer brightness,and perceptibility of vision

This paper proposes a new technique for reducing the patient dose when employing medical radiographs prepared by using screen-film systems. In this technique the patient dose can be reduced by employing scattered X-rays in order to obtain the same film density as that realized without the use of scattered X-rays. The minimum perceptible thickness difference ΔX_min, which can be recognized by liminal vision, was psychophysically calculated by considering the energy spectrum of incident X-ray, sensitivity spectrum of the screen layer, and the perception capability of human vision. From the calculated ΔX_mins in various conditions, the permissible upper limit of scatter fraction for obtaining the same ΔX_min for three kinds of luminances, and the fraction of reduction in the primary X-rays were determined.As an example of the results, when the object size required for perception is 1.3 mm, a scatter fraction up to 42% can be permitted at a density D of 1.0 for a luminance of 2548 cd m^?2. When we increase the luminance of the viewer from 478 cd m^?2 to 2548 cd m^?2, the upper limit of the permitted scatter fraction varies from 30% to 42% at a D of 1.0, i.e., the patient dose can be reduced by 17% under the same perceptibility of ΔX_min by utilizing scattered X-rays. This reduction can be successfully achieved by changing the lead content of the grid from 0.45 to 0.38 g cm^?2.     

Ultraviolet Light-Induced Division Delay in Synchronized Chinese Hamster Cells

The age-dependent, ultraviolet light (UVL) (254 nm)-induced division delay of surviving and nonsurviving Chinese hamster cells was studied. The response was examined after UVL exposures adjusted to yield approximately the same survival levels at different stages of the cell cycle, 60% or 30% survival. Cells irradiated in the middle of S suffered the longest division delay, and cells exposed in mitosis or in G₁ had about the same smaller delay in division. Cells irradiated in G₂, however, were not delayed at either survival level. It was further established, after exposures that yielded about 30% survivors at various stages of the cycle, that surviving cells had shorter delays than nonsurvivors. This difference was not observed for cells in G₂ at the time of exposure; i.e., neither surviving nor nonsurviving G₂ cells were delayed in division. The examination of mitotic index vs. time revealed that most cells reach mitosis, but all of the increase in the number of cells in the population can be accounted for by the increase of the viable cell fraction. These observations suggest strongly that nonsurviving cells, although present during most of the experiment, are stopped at mitosis and do not divide. Cells in mitosis at the time of irradiation complete their division, and in the same length of time as unirradiated controls. Division and mitotic delays after UVL are relatively much larger than after X-ray doses that reduce survival to about the same level.     

Modifying properties of 2,5-diphenyloxazole during low-dose X-ray exposure of mice

The ability of 2,5-diphenyloxazole (DPO) to modify biological consequences of the X-rays irradiation of mice was studied with a dose of 16 cGy at the administration of the agent in a wide range of concentrations before or after irradiation was studied. It was shown that the administration of the agent in doses 9.9 x 10(-3)-9.8 mg/kg 35-60 min before irradiation causes a reliable decrease in the spleen mass within 1 month after the action; for the dose 1 mg/kg, it causes the tendency to decrease of the content of lipid peroxidation (LPO) products; the dose 9.8 mg/kg causes a decrease in the cell-free DNA amount in blood plasma of mice. The administration of DPO before irradiation causes changes in the scale and direction of the correlation between the DNA and LPO products contents in blood plasma of irradiated mice compared with the control. The administration of DPO 15-60 min after irradiation do not cause any reliable changes in the investigated parameters. The aviability of the study of the radioprotective properties of the DPO derivatives as agents with a nontraditional character of action is supposed.     

Finding safe dose-volume constraints for re-irradiation with SBRT of patients with prostate cancer relapse: The IEO experience

AimThe primary aim of this study is to provide preliminary indications for safe constraints of rectum and bladder in patients re-irradiated with stereotactic body RT (SBRT).MethodsData from patients treated for prostate cancer (PCa) and intraprostatic relapse, from 1998 to 2016, were retrospectively collected. First RT course was delivered with 3D conformal RT techniques, SBRT or volumetric modulated arc therapy (VMAT). All patients underwent re-irradiation with SBRT with heavy hypofractionated schedules. Cumulative dose-volume values to organs at risk (OARs) were computed and possible correlation with developed toxicities was investigated.ResultsTwenty-six patients were included. Median age at re-irradiation was 75 years, mean interval between the two RT courses was 5.6 years and the median follow-up was 47.7 months (13.4–114.3 months). After re-irradiation, acute and late G ≥ 2 GU toxicity events were reported in 3 (12%) and 10 (38%) patients, respectively, while late G ≥ 2 GI events were reported in 4 (15%) patients. No acute G ≥ 2 GI side effects were registered. Patients receiving an equivalent uniform dose of the two RT treatments < 131 Gy appeared to be at higher risk of progression (4-yr b-PFS: 19% vs 33%, p = 0.145). Cumulative re-irradiation constraints that appear to be safe are D_30% < 57.9 Gy for bladder and D_30% < 66.0 Gy, D_60% < 38.0 Gy and V_{122.1 Gy} < 5% for rectum.ConclusionPreliminary re-irradiation constraints for bladder and rectum have been reported. Our preliminary investigation may serve to clear some grey areas of PCa re-irradiation.