Small field output factor measurement and verification for CyberKnife robotic radiotherapy and radiosurgery system using 3D polymer gel, ionization chamber, diode, diamond and scintillator detectors, Gafchromic film and Monte Carlo simulation.

The dosimetry of small fields has become tremendously important with the advent of intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery, where small field segments or very small fields are used to treat tumors. With high dose gradients in the stereotactic radiosurgery or radiotherapy treatment, small field dosimetry becomes challenging due to the lack of lateral electronic equilibrium in the field, x-ray source occlusion, and detector volume averaging. Small volume and tissue-equivalent detectors are recommended to overcome the challenges. With the lack of a perfect radiation detector, studies on available detectors are ongoing with reasonable disagreement and uncertainties. The joint IAEA and AAPM international code of practice (CoP) for small field dosimetry, TRS 483 (Alfonso et al., 2017) provides guidelines and recommendations for the dosimetry of small static fields in external beam radiotherapy. The CoP provides a methodology for field output factor (FOF) measurements and use of field output correction factors for a series of small field detectors and strongly recommends additional measurements, data collection and verification for CyberKnife (CK) robotic stereotactic radiotherapy/radiosurgery system using the listed detectors and more new detectors so that the FOFs can be implemented clinically. The present investigation is focused on using 3D gel along with some other commercially available detectors for the measurement and verification of field output factors (FOFs) for the small fields available in the CK system. The FOF verification was performed through a comparison with published data and Monte Carlo simulation. The results of this study have proved the suitability of an in-house developed 3D polymer gel dosimeter, several commercially available detectors, and Gafchromic films as a part of small field dosimetric measurements for the CK system.

The Use of Intraoperative Radiation Therapy (IORT) in Multimodality Management of Cancer Patients: a Single Institution Experience.

BACKGROUND: Intraoperative radiation therapy (IORT) is a highly conformal type of radiation therapy given at time of surgery aiming for better tumor local control. It increases the tumor radiation dose without exceeding normal tissues tolerance doses. PURPOSE: To assess the feasibility of IORT and short-term toxicities in patients with different cancer sites treated with multidisciplinary protocol including IORT. PATIENTS AND METHODS: Medical records of cancer patients who received IORT as a part of their multidisciplinary treatment at King Faisal Specialized Hospital and Research center (KFSH&RC), Riyadh, Saudi Arabia, from January 2013 until December 2017 were retrospectively reviewed. RESULTS: A total of 188 patients with 210 IORT applications were analyzed. Twenty-two patients had two applications at the same time. One hundred sixteen patients were males. Median age at time of diagnosis was 49.5 years (19-77). One hundred thirty-four patients had primary, while 54 cases had recurrent disease. Gastroesophageal cancer and soft tissue sarcoma were the most frequent diagnosis in 49 patients followed by colorectal cancer in 35 patients. Major surgeries with curative intent done in 183 patients (97.3%). Hyperthermic intraperitoneal chemotherapy (HIPEC) was performed in 118 (62.8%) patients. The 30-day postoperative mortality rate was 3.2%. Fifty-four (28.7%) patients develop grades III-IV complications according to Clavien-Dindo grading system. CONCLUSION: The data presented discusses using of IORT treatment for different malignant tumors as a part of multimodality treatment. IORT seems safe and feasible; however, a longer follow-up period is needed for proper evaluation and to define the role of IORT in a tailored multimodality approach.

Image-Guided Brachytherapy for Rectal Cancer: Reviewing the Past Two Decades of Clinical Investigation.

(1) Background: The introduction of total mesorectal excision (TME) for rectal cancer has led to improvement in local recurrence (LR) outcomes. Furthermore, the addition of preoperative external beam radiotherapy to TME reduces LR to less than 6%. As a trade-off to these gradual improvements in local therapies, the oncology community's work is now focusing on mitigating treatment-related toxicities. In other words, if a small proportion of 4-6% of rectal cancer patients benefit from additional local therapy beyond TME, the burden of acute and long-term side effects must be considered with care. (2) Methods: With the introduction of better-quality imaging for tumor visualization and treatment planning, a new conformed radiation treatment was introduced with high-dose-rate endorectal brachytherapy. The treatment concept was tested in phase I and II studies: first in the pre-operative setting, and then as a boost after external beam radiation therapy, as a dose-escalation study, to achieve higher local tumor control. (3) Results: HDREBT is safe and effective in achieving a high tumor regression rate and was well tolerated in a phase II multicenter and two matched-pair studies. (4) Conclusions: HDREBT is a conformed radiation therapy that is safe and effective, and is presently explored in a phase III dose-escalation study in the NOM of patients with operable rectal cancer.

Effect of gamma irradiation on filtering facepiece respirators and SARS-CoV-2 detection.

To cope with the shortage of filtering facepiece respirators (FFRs) during the coronavirus (COVID-19) pandemic, healthcare institutions were forced to reuse FFRs after applying different decontamination methods including gamma-irradiation (GIR). The aim of this study was to evaluate the effect of GIR on the filtration efficiency (FE) of FFRs and on SARS-CoV-2 detection. The FE of 2 FFRs types (KN95 and N95-3 M masks) was assessed at different particle sizes (0.3-5 µm) following GIR (0-15 kGy) delivered at either typical (1.65 kGy/h) or low (0.5088 kGy/h) dose rates. The detection of two SARS-CoV-2 RNA genes (E and RdRp4) following GIR (0-50 kGy) was carried out using RT-qPCR assay. Both masks showed an overall significant (P < 0.001) reduction in FE with increased GIR doses. No significant differences were observed between GIR dose rates on FE. The GIR exhibited significant increases (P ≤ 0.001) in the cycle threshold values (ΔCt) of both genes, with no detection following high doses. In conclusion, complete degradation of SARS-CoV-2 RNA can be achieved by high GIR (≥ 30 kGy), suggesting its potential use in FFRs decontamination. However, GIR exhibited adverse effects on FE in dose- and particle size-dependent manners, rendering its use to decontaminate FFRs debatable.

In-House Filtration Efficiency Assessment of Vapor Hydrogen Peroxide Decontaminated Filtering Facepiece Respirators (FFRs).

To cope with the shortage of filtering facepiece respirators (FFRs) caused by the coronavirus disease (COVID-19), healthcare institutions have been forced to reuse FFRs using different decontamination methods, including vapor hydrogen peroxide (VHP). However, most healthcare institutions still struggle with evaluating the effect of VHP on filtration efficiency (FE) of the decontaminated FFRs. We developed a low-cost in-house FE assessment using a novel 3D-printed air duct. Furthermore, we assessed the FE of seven types of FFRs. Following 10 VHP cycles, we evaluated the FE of KN95 and 3M-N95 masks. The 3M-N95 and Benehal-N95 masks showed significant lower FE (80.4-91.8%) at fine particle sizes (0.3-1 µm) compared to other FFRs (FE ≥ 98.1%, p < 0.05). Following 10 VHP cycles, the FE of KN95 masks was almost stable (FE stability > 99.1%) for all particle sizes, while 3M-N95 masks were stable only at 2 and 5 µm (FE stability > 98.0%). Statistically, FE stability of 3M-N95 masks at 0.3, 0.5, and 0.7 µm was significantly lower (p ≤ 0.006) than 2 and 5 µm. The in-house FE assessment may be used as an emergency procedure to validate the decontaminated FFRs, as well as a screening option for production control of FFRs. Following VHP cycles, both masks showed high stability at 5 µm, the size of the most suspected droplets implicated in COVID-19 transmission.

Investigation of the survival viability of cervical cancer cells (HeLa) under visible light induced photo-catalysis with facile synthesized WO3/ZnO nanocomposite.

The photo catalytic degradation, a proven chemical process used for the decontamination of organic/inorganic pollutants and microorganisms in water was implemented. In this work for the selective killing of cervical cancer cells (HeLa cells) by using nano-composite of ZnO (Zinc Oxcide), WO3 (tungsten oxide) and (n-WO3/ZnO) as a photo-catalyst under the irradiation of visible light. All the three nanostructured semiconducting materials (WO3, ZnO and n-WO3/ZnO) were synthesized by facile chemical precipitation method and their morphological and optical characterization studies were carried out to elucidate the observed enhancement in the photo-catalytic killing of HeLa cancer cells with n-WO3/ZnO as a photo-catalyst. After 60 min of photo-catalytic reaction with n-WO3/ZnO as a photo-catalyst, a survival viability of HeLa cancer cells as low as 15% was achieved (nearly 85% of killing), as compared to 65% of HeLa cancer cell survival viability (nearly 35% of killing) with individual use of WO3 and ZnO as photo-catalysts under the same irradiation and experimental conditions. This improved photo-catalytic killing of HeLa cancer cells using n-WO3/ZnO in the visible spectral region is attributed to the enhanced visible light absorption and reduced electron hole recombination, characteristically brought about in the n-WO3/ZnO composite material. As photo-catalytic killing of the cancer cells can be selective, localized and reasonably efficient, in principle, this method can be considered as a non-invasive targeted treatment option for killing any type of cancer cells. HeLa cells, in particular are the cervical cancer cell and the tumors in and around cervix, containing HeLa cells can be non-surgically accessed and photo-catalytically treated with appropriate photo-catalyst and light source.

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.

Quality assurance of Cyberknife robotic stereotactic radiosurgery using an angularly independent silicon detector.

PURPOSE: The aim of this work was to evaluate the use of an angularly independent silicon detector (edgeless diodes) developed for dosimetry in megavoltage radiotherapy for Cyberknife in a phantom and for patient quality assurance (QA). METHOD: The characterization of the edgeless diodes has been performed on Cyberknife with fixed and IRIS collimators. The edgeless diode probes were tested in terms of basic QA parameters such as measurements of tissue-phantom ratio (TPR), output factor and off-axis ratio. The measurements were performed in both water and water-equivalent phantoms. In addition, three patient-specific plans have been delivered to a lung phantom with and without motion and dose measurements have been performed to verify the ability of the diodes to work as patient-specific QA devices. The data obtained by the edgeless diodes have been compared to PTW 60016, SN edge, PinPoint ionization chamber, Gafchromic EBT3 film, and treatment planning system (TPS). RESULTS: The TPR measurement performed by the edgeless diodes show agreement within 2.2% with data obtained with PTW 60016 diode for all the field sizes. Output factor agrees within 2.6% with that measured by SN EDGE diodes corrected for their field size dependence. The beam profiles' measurements of edgeless diodes match SN EDGE diodes with a measured full width half maximum (FWHM) within 2.3% and penumbra widths within 0.148 mm. Patient-specific QA measurements demonstrate an agreement within 4.72% in comparison with TPS. CONCLUSION: The edgeless diodes have been proved to be an excellent candidate for machine and patient QA for Cyberknife reproducing commercial dosimetry device measurements without need of angular dependence corrections. However, further investigation is required to evaluate the effect of their dose rate dependence on complex brain cancer dose verification.

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.

Commissioning of applicator-guided stereotactic body radiation therapy boost with high-dose-rate brachytherapy for advanced cervical cancer using radiochromic film dosimetry.

PURPOSE: To describe an EBT3 GAFCHROMIC film-based dosimetry method to be used in commissioning of a combined HDR brachytherapy (HDRB) and stereotactic body radiation therapy (SBRT) boost for treatment of advanced cervical cancer involving extensive residual disease after external beam treatment. METHODS AND MATERIALS: A cube phantom was designed to firmly fit an intrauterine tandem applicator and EBT3 radiochromic film pieces. A high-risk clinical target volume (CTVHR, Total) was contoured with an extended arm at one side. The HDRB treatment was planned to cover the proximal CTVHR, Total with 7 Gy and the distal volume, referred to as CTVHR, Distal, was planned by SBRT for dose augmentation. After HDRB treatment delivery, SBRT treatment was delivered within 1 hour by image guidance using the applicator geometry. Intentional 1D and 2D misalignments were introduced to evaluate the effect on target volumes. In addition, effect of film reirradiation at different time gaps and dose levels was evaluated. RESULTS: Film dosimetric accuracy, with up to 2 hours gap between irradiations, was shown to be unaffected. A 2%/2 mm gamma analysis between measured and planned doses showed agreement of >99%. Misalignments of more than 2 mm between applicator and SBRT isocenter resulted in suboptimal dose-volume histogram affecting mostly D98% and D90% of CTVHR, Distal. CONCLUSIONS: Visualizing how target dose-volume metrics are affected by minor misalignments between SBRT and HDRB dose gradients, in light of achievable phantom-based experimental quality assurance level, encourages the clinical applicability of this technique. Radiochromic film was shown to be a valuable tool to commission procedures combining two different treatment planning systems and modalities with varying dose rates and energy ranges.

New normoxic N-(Hydroxymethyl)acrylamide based polymer gel for 3D dosimetry in radiation therapy.

A novel composition of normoxic polymer gel dosimeters based on radiation-induced polymerization of N-(Hydroxymethyl)acrylamide (NHMA) is introduced in this study for 3D dosimetry for Quality Assurance (QA) in radiation therapy. Dosimeters were irradiated by 6, 10 and 18MV photon beams of a medical linear accelerator at various dose rates to doses of up to 20Gy. The dose response of polymer gel dosimeters was studied using nuclear magnetic resonance (NMR) spin-spin relaxation rate (R2) of hydrogen protons within the water molecule. Also, we measured gel response using absorption spectroscopy and found that this novel gel can be successfully utilized for both MRI- and OCT- (Optical Computed Tomography) based 3D dosimetry. We investigated dosimetric properties of six different compositions of the new NHMA-based gel in terms of dose rate, radiation beam quality and stability of dose-dependent polymerization after irradiation. We found no significant effects of these parameters on the novel gel dosimeter performance in both relaxation rate and absorbance measurements.

Failure modes and effects analysis in image-guided high-dose-rate brachytherapy: Quality control optimization to reduce errors in treatment volume.

PURPOSE: Analyze the inputs which cause treatment to the wrong volume in high-dose-rate brachytherapy (HDRB), with emphasis on imaging role during implant, planning, and treatment verification. The end purpose is to compare our current practice to the findings of the study and apply changes where necessary. METHODS AND MATERIALS: Failure mode and effects analysis was used to study the failure pathways for treating the wrong volume in HDRB. The role of imaging and personnel was emphasized, and subcategories were formed. A quality assurance procedure is proposed for each high-scoring failure mode (FM). RESULTS: Forty FMs were found that lead to treating the wrong volume. Of these, 73% were human failures, 20% were machine failures, and 7% were procedural/guideline failures. The use of imaging was found to resolve 85% of the FMs. We also noted that imaging processes were under used in current practice of HDRB especially in pretreatment verification. Twelve FMs (30%) scored the highest, and for each one of them, we propose clinical/practical solutions that could be applied to reduce the risk by increasing detectability. CONCLUSIONS: This work resulted in two conclusions: the role of imaging in improving failure detection and the emphasized role of human-based failures. The majority of FMs are human failures, and imaging increased the ability to detect 85% of all FMs. We proposed quality assurance practices for each high-scoring FM and have implemented some of them in our own practice.

Gender bias in individual radiosensitivity and the association with genetic polymorphic variations.

PURPOSE: To assess the extent of variation in radiosensitivity between individuals, gender-related dissimilarity and impact on the association with single nucleotide polymorphisms (SNPs). MATERIALS AND METHODS: Survival curves of 152 fibroblast cell strains derived from both gender were generated. Individual radiosensitivity was characterized by the surviving fraction at 2Gy (SF2). SNPs in 10 radiation responsive genes were genotyped by direct sequencing. RESULTS: The wide variation in SF2 (0.12-0.50; mean=0.33) was significantly associated with 3 SNPs: TP53 G72C (P=0.007), XRCC1 G399A (P=0.002) and ATM G1853A (P=0.01). Females and males differed significantly in radiosensitivity (P=0.004) that impacted genetic association where only XRCC1 remained significant in both gender (P<0.05). Meanwhile, discordant association was observed for TP53 that was significant in females (P=0.012) and ATM that was significant in males (P=0.0006). When gender-specific SF2-mean (0.31 and 0.35 for females and males; respectively) was considered, further discordance was observed where XRCC1 turned out not to be associated with radiosensitivity in males (P>0.05). CONCLUSIONS: Although the variation in individual radiosensitivity was associated with certain SNPs, gender bias for both endpoints was evident. Therefore, assessing the risk of radiation exposure in females and males should be considered separately in order to achieve the ultimate goal of personalized radiation medicine.

Use of a control film piece in radiochromic film dosimetry.

PURPOSE: Radiochromic films change their color upon irradiation due to polymerization of the sensitive component embedded within the sensitive layer. However, agents, other than monitored radiation, can lead to a change in the color of the sensitive layer (temperature, humidity, UV light) that can be considered as a background signal and can be removed from the actual measurement by using a control film piece. In this work, we investigate the impact of the use of control film pieces on both accuracy and uncertainty of dose measured using radiochromic film based reference dosimetry protocol. METHODS: We irradiated "control" film pieces (EBT3 GafChromic(TM) film model) to known doses in a range of 0.05-1 Gy, and five film pieces of the same size to 2, 5, 10, 15 and 20 Gy, considered to be "unknown" doses. Depending on a dose range, two approaches to incorporating control film piece were investigated: signal and dose corrected method. RESULTS: For dose values greater than 10 Gy, the increase in accuracy of 3% led to uncertainty loss of 5% by using dose corrected approach. At lower doses and signals of the order of 5%, we observed an increase in accuracy of 10% with a loss of uncertainty lower than 1% by using the corrected signal approach. CONCLUSIONS: Incorporation of the signal registered by the control film piece into dose measurement analysis should be a judgment call of the user based on a tradeoff between deemed accuracy and acceptable uncertainty for a given dose measurement.

Continuous versus step-by-step scanning mode of a novel 3D scanner for CyberKnife measurements.

The purpose of the study is to investigate the continuous versus step-by-step scanning mode of a commercial circular 3D scanner for commissioning measurements of a robotic stereotactic radiosurgery system. The 3D scanner was used for profile measurements in step-by-step and continuous modes with the intent of comparing the two scanning modes for consistency. The profile measurements of in-plane, cross-plane, 15 degree, and 105 degree were performed for both fixed cones and Iris collimators at depth of maximum dose and at 10cm depth. For CyberKnife field size, penumbra, flatness and symmetry analysis, it was observed that the measurements with continuous mode, which can be up to 6 times faster than step-by-step mode, are comparable and produce scans nearly identical to step-by-step mode. When compared with centered step-by-step mode data, a fully processed continuous mode data gives rise to maximum of 0.50% and 0.60% symmetry and flatness difference respectfully for all the fixed cones and Iris collimators studied.

A practical method of modeling a treatment couch using cone-beam computed tomography for intensity-modulated radiation therapy and RapidArc treatment delivery.

The effect of a treatment couch on dose perturbation is not always fully considered in intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). In the course of inverse planning radiotherapy techniques, beam parameter optimization may change in the absence of the couch, causing errors in the calculated dose distributions. Although modern treatment planning systems (TPS) include data for the treatment couch components, they are not manufactured identically. Thus, variations in their Hounsfield unit (HU) values may exist. Moreover, a radiotherapy facility may wish to have a third-party custom tabletop installed that is not included by the TPS vendor. This study demonstrates a practical and simple method of acquiring reliable computed tomography (CT) data for the treatment couch and shows how the absorbed dose calculated with the modeled treatment couch can differ from that with the default treatment couch found in the TPS. We also experimentally verified that neglecting to incorporate the treatment couch completely in the treatment planning process might result in dose differences of up to 9.5% and 7.3% for 4-MV and 10-MV photon beams, respectively. Furthermore, 20 RapidArc and IMRT cases were used to quantify the change in calculated dose distributions caused by using either the default or modeled couch. From 2-dimensional (2D) ionization chamber array measurements, we observed large dose distribution differences between the measurements and calculations when the couch was omitted that varied according to the planning technique and anatomic site. Thus, incorporating the treatment couch in the dose calculation phase of treatment planning significantly decreases dose calculation errors.

Radiochromic film based dosimetry of image-guidance procedures on different radiotherapy modalities.

In this work we compare doses from imaging procedures performed on today's state-of-the-art integrated imaging systems using a reference radiochromic film dosimetry system. Skin dose and dose profile measurements from different imaging systems were performed using radiochromic films at different anatomical sites on a humanoid RANDO phantom. EBT3 film was used to measure imaging doses from a TomoTherapy MVCT system, while XRQA2 film was used for dose measurements from kilovoltage imaging systems (CBCT on 21eX and TrueBeam Varian linear accelerators and CyberKnife stereoscopic orthogonal imagers). Maximum measured imaging doses in cGy at head, thorax, and pelvis regions were respectively 0.50, 1.01, and 4.91 for CBCT on 21eX, 0.38, 0.84, and 3.15 for CBCT on TrueBeam, 4.33, 3.86, and 6.50 for CyberKnife imagers, and 3.84, 1.90, and 2.09 for TomoTherapy MVCT. In addition, we have shown how an improved calibration system of XRQA2 film can achieve dose uncertainty level of better than 2% for doses above 0.25 cGy. In addition to simulation-based studies in literature, this study provides the radiation oncology team with data necessary to aid in their decision about imaging frequency for image-guided radiation therapy protocols.

Establishing cytogenetic biodosimetry laboratory in Saudi Arabia and producing preliminary calibration curve of dicentric chromosomes as biomarker for medical dose estimation in response to radiation emergencies.

In cases of public or occupational radiation overexposure and eventual radiological accidents, it is important to provide dose assessment, medical triage, diagnoses and treatment to victims. Cytogenetic bio-dosimetry based on scoring of dicentric chromosomal aberrations assay (DCA) is the "gold standard" biotechnology technique for estimating medically relevant radiation doses. Under the auspices of the National Science, Technology and Innovation Plan in Saudi Arabia, we have set up a biodosimetry laboratory and produced a national standard dose-response calibration curve for DCA, pre-required to estimate the doses received. For this, the basic cytogenetic DCA technique needed to be established. Peripheral blood lymphocytes were collected from four healthy volunteers and irradiated with radiation doses between 0 and 5 Gy of 320 keV X-rays. Then, lymphocytes were PHA stimulated, Colcemid division arrested and stained cytogenetic slides were prepared. The Metafer4 system (MetaSystem) was used for automatic and manually assisted metaphase finding and scoring of dicentric chromosomes. Results were fit to the linear-quadratic dose-effect model according to the IAEA EPR-Biodosimetry-2011 report. The resulting manually assisted dose-response calibration curve (Y = 0.0017 + 0.026 × D + 0.081 × D2) was in the range of those described in other populations. Although the automated scoring over-and-under estimates DCA at low (<1 Gy) and high (>2 Gy) doses, respectively, it showed potential for use in triage mode to segregate between victims with potential risk to develop acute radiotoxicity syndromes. In conclusion, we have successfully established the first biodosimetry laboratory in the region and have produced a preliminary national dose-response calibration curve. The laboratory can now contribute to the national preparedness plan in response to eventual radiation emergencies in addition to providing information for decision makers and public health officials who assess the magnitude of public, medical, occupational and accidental radiation exposures.

Among 45 variants in 11 genes, HDM2 promoter polymorphisms emerge as new candidate biomarker associated with radiation toxicity.

Due to individual variations in radiosensitivity, biomarkers are needed to tailor radiation treatment to cancer patients. Since single nucleotide polymorphisms (SNPs) are frequent in human, we hypothesized that SNPs in genes that mitigate the radiation response are associated with radiotoxicity, in particular late complications to radiotherapy and could be used as genetic biomarkers for radiation sensitivity. A total of 155 patients with nasopharyngeal cancer were included in the study. Normal tissue fibrosis was scored using RTOG/EORTC grading system. Eleven candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were selected for their presumed influence on radiosensitivity. Forty-five SNPs (12 primary and 33 neighboring) were genotyped by direct sequencing of genomic DNA. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107). Results showed statistically significant (P < 0.05) association with radiation complications for six SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). We conclude that these six SNPs are candidate genetic biomarkers for radiosensitivity in our patients that have cumulative effects as patients with severe fibrosis harbored significantly higher number of risk alleles than the controls (P < 0.001). Larger cohort, independent replication of these findings and genome-wide association studies are required to confirm these results in order for SNPs to be used as biomarkers to individualize radiotherapy on genetic basis.

Influence of electron density spatial distribution and X-ray beam quality during CT simulation on dose calculation accuracy.

Impact of the various kVp settings used during computed tomography (CT) simulation that provides data for heterogeneity corrected dose distribution calculations in patients undergoing external beam radiotherapy with either high-energy photon or electron beams have been investigated. The change of the Hounsfield Unit (HU) values due to the influence of kVp settings and geometrical distribution of various tissue substitute materials has also been studied. The impact of various kVp settings and electron density (ED) distribution on the accuracy of dose calculation in high-energy photon beams was found to be well within 2%. In the case of dose distributions obtained with a commercially available Monte Carlo dose calculation algorithm for electron beams, differences of more than 10% were observed for different geometrical setups and kVp settings. Dose differences for the electron beams are relatively small at shallow depths but increase with depth around lower isodose values.