Establishing a Reference Dose-Response Calibration Curve for Dicentric Chromosome Aberrations to Assess Accidental Radiation Exposure in Saudi Arabia.

In cases of nuclear and radiological accidents, public health and emergency response need to assess the magnitude of radiation exposure regardless of whether they arise from disaster, negligence, or deliberate act. Here we report the establishment of a national reference dose-response calibration curve (DRCC) for dicentric chromosome (DC), prerequisite to assess radiation doses received in accidental exposures. Peripheral blood samples were collected from 10 volunteers (aged 20-40 years, median = 29 years) of both sexes (three females and seven males). Blood samples, cytogenetic preparation, and analysis followed the International Atomic Energy Agency EPR-Biodosimetry 2011 report. Irradiations were performed using 320 kVp X-rays. Metafer system was used for automated and assisted (elimination of false-positives and inclusion of true-positives) metaphases findings and DC scoring. DC yields were fit to a linear-quadratic model. Results of the assisted DRCC showed some variations among individuals that were not statistically significant (homogeneity test, P = 0.66). There was no effect of age or sex (P > 0.05). To obtain representative national DRCC, data of all volunteers were pooled together and analyzed. The fitted parameters of the radiation-induced DC curve were as follows: Y = 0.0020 (±0.0002) + 0.0369 (±0.0019) *D + 0.0689 (±0.0009) *D2. The high significance of the fitted coefficients (z-test, P < 0.0001), along with the close to 1.0 p-value of the Poisson-based goodness of fit (χ2 = 3.51, degrees of freedom = 7, P = 0.83), indicated excellent fitting with no trend toward lack of fit. The curve was in the middle range of DRCCs published in other populations. The automated DRCC over and under estimated DCs at low (<1 Gy) and high (>2 Gy) doses, respectively, with a significant lack of goodness of fit (P < 0.0001). In conclusion, we have established the reference DRCC for DCs induced by 320 kVp X-rays. There was no effect of age or sex in this cohort of 10 young adults. Although the calibration curve obtained by the automated (unsupervised) scoring misrepresented dicentric yields at low and high doses, it can potentially be useful for triage mode to segregate between false-positive and near 2-Gy exposures from seriously irradiated individuals who require hospitalization.

Appraisal of mechanisms of radioprotection and therapeutic approaches of radiation countermeasures.

Radiation countermeasures are radioprotective agents that reduce the harmful effects of ionizing radiation. They have wide range of applications extending from protection of normal tissues of cancer patients during radiotherapy to safeguard people aftermath of radiologic or nuclear accidents. Despite the screening of thousands of natural and synthetic compounds, only few found place in clinic with limited tolerance. Therefore, mechanistic understanding is essential in the development of more suitable and customized radiation countermeasure agents. This review focuses on the mechanisms of radioprotection imparted by these agents. Radioprotectors are diverse and act through widely varying mechanisms that can be classified in 10 categories: 1) scavenging of free radicals; 2) enhancing DNA repair; 3) synchronizing of cells; 4) modulating redox sensitive genes; 5) modulating growth factors and cytokines; 6) inhibiting apoptosis; 7) repurposing of drug; 8) interacting and chelating of radionuclides; and therapeutic methods of tissue regeneration such as 9) gene therapy; and 10) stem cell therapy. The most common mechanism of radioprotection is the scavenging of free radicals whereas, modulation of growth factors, cytokines and redox genes emerge as effective strategies. Gene and stem cell therapies as therapeutic radiation countermeasures are being developed and can be applied in the near future to minimize the side effects of radiation exposure through tissues regenerations. Thus, the management of radiation exposure may require a holistic multi-mechanistic approaches to achieve optimal radiation protection during radiotherapy of cancer patients and in cases of nuclear eventualities.

Comparative study on skin dose measurement using MOSFET and TLD for pediatric patients with acute lymphatic leukemia.

BACKGROUND: The object of this study was to compare the difference of skin dose measured in patients with acute lymphatic leukemia (ALL) treated with total body irradiation (TBI) using metal oxide semiconductor field-effect transistors (mobile MOSFET dose verification system (TN-RD-70-W) and thermoluminescent dosimeters (TLD-100 chips, Harshaw/ Bicron, OH, USA). Because TLD has been the most-commonly used technique in the skin dose measurement of TBI, the aim of the present study is to prove the benefit of using the mobile MOSFET (metal oxide semiconductor field effect transistor) dosimeter, for entrance dose measurements during the total body irradiation (TBI) over thermoluminescent dosimeters (TLD). MATERIAL/METHODS: The measurements involved 10 pediatric patients ages between 3 and 14 years. Thermoluminescent dosimeters and MOSFET dosimetry were performed at 9 different anatomic sites on each patient. RESULTS: The present results show there is a variation between skin dose measured with MOSFET and TLD in all patients, and for every anatomic site selected, there is no significant difference in the dose delivered using MOSFET as compared to the prescribed dose. However, there is a significant difference for every anatomic site using TLD compared with either the prescribed dose or MOSFET. The results indicate that the dosimeter measurements using the MOSFET gave precise measurements of prescribed dose. However, TLD measurement showed significant increased skin dose of cGy as compared to either prescribed dose or MOSFET group. CONCLUSIONS: MOSFET dosimeters provide superior dose accuracy for skin dose measurement in TBI as compared with TLD.

Using the computed tomography in comparison to the orthogonal radiography based treatment planning in high dose rate (HDR) brachytherapy in cervical uteri cancer patients; a single institution feasibility study.

INTRODUCTION: Brachytherapy is an integral part in the treatment of cervical uteri cancer patients. Orthogonal treatment planning is the standard mode of calculation based on reference points. Introduction of the innovative 3-D computer based treatment planning allows accurate calculation based on volumetric information as regards the target volume and organs at risk (OAR). Also provide dose volume histogram (DVH) for proper estimation of the dose in relation to the volume. AIM: To correlate and compare the information obtained from the two approaches for high dose rate brachytherapy of cervical uteri cancer; the orthogonal conventional method and the computerized tomography (CT) three dimensions (3D) based calculation method in relation to the target and organ at risk (OAR). METHODS: From 6 patients of cervical uteri cancer, 21 applications with orthogonal planning using the Brachy Vision treatment planning system version 7.3.10 were performed. In 10 applications; comparison between orthogonal and CT based planning was done. In orthogonal planning; the dose to point A, rectum and bladder were defined according to the American Brachytherapy Society (ABS) recommendation. From the CT based planning the target volume and dose volume histogram lpar;DVH) were calculated for the clinical target volume (CTV), rectum and bladder. From these two sets, information was obtained and compared and mean values were derived. RESULTS: For dose prescription at point A, an average of 63.5% of CTV received the prescribed dose. The mean ICRU dose to the bladder point is 2.9 Gy+/-1.2 SD (Standard Deviation) and 17% of the bladder volume derived from CT was encompassed by 2.9 Gy isodose line. The mean ICRU dose at the rectum point is 3.4 Gy+/-1.2 SD and 21% of the rectum volume from CT was encompassed by 3.4 Gy isodose line. The maximum dose to the rectum and the bladder derived from the CT and compared to the maximal dose at ICRU is 1.7 and 2.8 times higher than the orthogonal reference points; with the corresponding p value of (p=0.53 and p=0.005) for the rectum and the bladder respectively. CONCLUSIONS: CT based treatment planning for HDR brachytherapy of cervical uteri cancer is reliable and more accurate in definition and calculation of the dose to the target as well as the critical organs. It allows dose calculation based on the actual volume rather than points or bony landmarks.

Conformal preoperative endorectal brachytherapy treatment for locally advanced rectal cancer: early results of a phase I/II study.

PURPOSE: Downstaging rectal carcinoma by preoperative radiotherapy decreases local recurrence, and recent phase II studies suggest that, in the lower one-third lesions, sphincter-preserving surgery can be considered. The purpose of the current study was to assess the efficacy and the toxicity of endorectal high dose-rate brachytherapy as a preoperative downstaging treatment modality. METHODS: Patients with newly diagnosed invasive rectal adenocarcinoma, T2 to very early T4, operable tumors were eligible. A dose of 26 Gy was given over four consecutive daily treatments of 6.5 Gy prescribed at the tumor radial margin using endorectal brachytherapy with high dose-rate delivery system. Surgery as planned initially was done four to eight weeks later to allow for tumor downstaging. Patients found to have pathologic positive nodes received postoperative external beam (45 Gy/25 fractions) to the pelvis and systemic 5-fluorouracil-leucovorin chemotherapy. RESULTS: Forty-nine patients entered the study. Tumors were in the lower one-third in 24 patients, middle one-third in 22, and upper one-third in 3. With preoperative endorectal ultrasound and magnetic resonance imaging, the clinical staging of the tumors was: 3 T2, 42 T3, 4 T4, and 16 N1-2. Acute toxicity related to brachytherapy was limited to a moderate proctitis (Radiation Therapy Oncology Group acute toxicity scoring system, Grade 2) in all patients, with two patients with tumors extending into the anal canal having Grade 3 dermatitis. Forty-seven patients underwent surgery. Two patients refused their operation based on a normal endoscopic rectal ultrasound after treatment. A complete clinical response was obtained in 32 of 47 (68 percent) patients with 32 percent pathologically pT0N0-1, and 36 percent had only residual microfoci of carcinoma. The surgical approaches did not yield more complications than expected. CONCLUSION: Preoperative high dose-rate endorectal brachytherapy seems to be safe, because acute toxicity was mainly local, with moderate proctitis (Grade 2) and occasional dermatitis (Grade 3) for very low tumors. Finally, this modality, by providing high rate of tumor downstaging and downsizing especially for patients with lesions in the lower one-third of the rectum, represents a definite potential for sphincter-preserving surgery for investigation in future studies.

On the selection of optimization parameters for an inverse treatment planning replacement of a forward planning technique for prostate cancer.

The influence of organ volume sampling, lateral scatter inclusion, and the selection of objectives and constraints on the inverse treatment planning process with a commercial treatment planning system is investigated and suitable parameters are identified for an inverse treatment planning replacement of a clinical forward planning technique for prostate cancer. For the beam geometries of the forward technique, a variable set of parameters is used for the calculation of dose from pencil beams. An optimal set is identified after the evaluation of optimized plans that correspond to different sets of pencil-beam parameters. This set along with a single, optimized set of objectives and constraints is used to perform inverse planning on ten randomly selected patients. The acceptability of the resulting plans is verified by comparisons to the clinical ones calculated with the forward techniques. For the particular commercial treatment planning system, the default values of the pencil beam parameters are found adequate for inverse treatment planning. For all ten patients, the optimized, single set of objectives and constraints results in plans with target coverage comparable to that of the forward plans. Furthermore inverse treatment planning reduces the overall mean rectal and bladder doses by 4.8% and 5.8% of the prescription dose respectively. The study indicates that (i) inverse treatment planning results depend implicitly on the sampling of the dose distribution, (ii) inverse treatment planning results depend on the method used by the dose calculation model to account for scatter, and (iii) for certain sites, a single set of optimization parameters can be used for all patient plans.