Purpose-To determine the in-field and out-of-field cell survival of cells irradiated with either primary field or scattered radiation in the presence and absence of intercellular communication.Methods and Materials-Cell survival was determined by clonogenic assay in human prostate cancer (DU145) and primary fibroblast (AGO1552) cells following exposure to different field configurations delivered using a 6-MV photon beam produced with a Varian linear accelerator.Results-Nonuniform dose distributions were delivered using a multileaf collimator (MLC) in which half of the cell population was shielded. Clonogenic survival in the shielded region was significantly lower than that predicted from the linear quadratic model. In both cell lines, the outof-field responses appeared to saturate at 40%-50% survival at a scattered dose of 0.70 Gy in DU-145 cells and 0.24 Gy in AGO1522 cells. There was an approximately eightfold difference in the initial slopes of the out-of-field response compared with the α-component of the uniform field response. In contrast, cells in the exposed part of the field showed increased survival. These observations were abrogated by direct physical inhibition of cellular communication and by the addition of the inducible nitric oxide synthase inhibitor aminoguanidine known to inhibit intercellular bystander effects. Additional studies showed the proportion of cells irradiated and dose delivered to the shielded and exposed regions of the field to impact on response.Conclusions-These data demonstrate out-of-field effects as important determinants of cell survival following exposure to modulated irradiation fields with cellular communication between differentially irradiated cell populations playing an important role. Validation of these observations in additional cell models may facilitate the refinement of existing radiobiological models and the observations considered important determinants of cell survival.

This work investigated the differences between multileaf collimator (MLC) positioning accuracy determined using either log files or electronic portal imaging devices (EPID) and then assessed the possibility of reducing patient specific quality control (QC) via phantom-less methodologies. In-house software was developed, and validated, to track MLC positional accuracy with the rotational and static gantry picket fence tests using an integrated electronic portal image. This software was used to monitor MLC daily performance over a 1 year period for two Varian TrueBeam linear accelerators, with the results directly compared with MLC positions determined using leaf trajectory log files. This software was validated by introducing known shifts and collimator errors. Skewness of the MLCs was found to be 0.03 ± 0.06° (mean ±1 standard deviation (SD)) and was dependent on whether the collimator was rotated manually or automatically. Trajectory log files, analysed using in-house software, showed average MLC positioning errors with a magnitude of 0.004 ± 0.003 mm (rotational) and 0.004 ± 0.011 mm (static) across two TrueBeam units over 1 year (mean ±1 SD). These ranges, as indicated by the SD, were lower than the related average MLC positioning errors of 0.000 ± 0.025 mm (rotational) and 0.000 ± 0.039 mm (static) that were obtained using the in-house EPID based software. The range of EPID measured MLC positional errors was larger due to the inherent uncertainties of the procedure. Over the duration of the study, multiple MLC positional errors were detected using the EPID based software but these same errors were not detected using the trajectory log files. This work shows the importance of increasing linac specific QC when phantom-less methodologies, such as the use of log files, are used to reduce patient specific QC. Tolerances of 0.25 mm have been created for the MLC positional errors using the EPID-based automated picket fence test. The software allows diagnosis of any specific leaf that needs repair and gives an indication as to the course of action that is required.

Tissue mimicking materials (TMMs), typically contained within phantoms, have been used for many decades in both imaging and therapeutic applications. This review investigates the specifications that are typically being used in development of the latest TMMs. The imaging modalities that have been investigated focus around CT, mammography, SPECT, PET, MRI and ultrasound. Therapeutic applications discussed within the review include radiotherapy, thermal therapy and surgical applications. A number of modalities were not reviewed including optical spectroscopy, optical imaging and planar x-rays. The emergence of image guided interventions and multimodality imaging have placed an increasing demand on the number of specifications on the latest TMMs. Material specification standards are available in some imaging areas such as ultrasound. It is recommended that this should be replicated for other imaging and therapeutic modalities. Materials used within phantoms have been reviewed for a series of imaging and therapeutic applications with the potential to become a testbed for cross-fertilization of materials across modalities. Deformation, texture, multimodality imaging and perfusion are common themes that are currently under development.

The motivation for this study was to reduce physics workload relating to patient‐specific quality assurance (QA). VMAT plan delivery accuracy was determined from analysis of pre‐ and on‐treatment trajectory log files and phantom‐based ionization chamber array measurements. The correlation in this combination of measurements for patient‐specific QA was investigated. The relationship between delivery errors and plan complexity was investigated as a potential method to further reduce patient‐specific QA workload. Thirty VMAT plans from three treatment sites — prostate only, prostate and pelvic node (PPN), and head and neck (H&N) — were retrospectively analyzed in this work. The 2D fluence delivery reconstructed from pretreatment and on‐treatment trajectory log files was compared with the planned fluence using gamma analysis. Pretreatment dose delivery verification was also carried out using gamma analysis of ionization chamber array measurements compared with calculated doses. Pearson correlations were used to explore any relationship between trajectory log file (pretreatment and on‐treatment) and ionization chamber array gamma results (pretreatment). Plan complexity was assessed using the MU/ arc and the modulation complexity score (MCS), with Pearson correlations used to examine any relationships between complexity metrics and plan delivery accuracy. Trajectory log files were also used to further explore the accuracy of MLC and gantry positions. Pretreatment 1%/1 mm gamma passing rates for trajectory log file analysis were 99.1% (98.7%–99.2%), 99.3% (99.1%–99.5%), and 98.4% (97.3%–98.8%) (median (IQR)) for prostate, PPN, and H&N, respectively, and were significantly correlated to on‐treatment trajectory log file gamma results (normalR=0.989,p<0.001). Pretreatment ionization chamber array (2%/2 mm) gamma results were also significantly correlated with on‐treatment trajectory log file gamma results (normalR=0.623,p<0.001). Furthermore, all gamma results displayed a significant correlation with MCS (normalR>0.57,p<0.001), but not with MU/arc. Average MLC position and gantry angle errors were 0.001±0.002.15emmm and 0.025°±0.008° over all treatment sites and were not found to affect delivery accuracy. However, variability in MLC speed was found to be directly related to MLC position accuracy. The accuracy of VMAT plan delivery assessed using pretreatment trajectory log file fluence delivery and ionization chamber array measurements were strongly correlated with on‐treatment trajectory log file fluence delivery. The strong correlation between trajectory log file and phantom‐based gamma results demonstrates potential to reduce our current patient‐specific QA. Additionally, insight into MLC and gantry position accuracy through trajectory log file analysis and the strong correlation between gamma analysis results and the MCS could also provide further methodologies to both optimize the VMAT planning and QA process.PACS number: 87.53.Bn, 87.55.Kh, 87.55.Qr

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Objective: To assess the accuracy and efficiency of four different techniques, thus determining the optimum method for recalculating dose on cone beam CT (CBCT) images acquired during radiotherapy treatments. Methods: Four established techniques were investigated and their accuracy assessed via dose calculations: (1) applying a standard planning CT (pCT) calibration curve, (2) applying a CBCT site-specific calibration curve, (3) performing a density override and (4) using deformable registration. Each technique was applied to 15 patients receiving volumetric modulated arc therapy to one of three treatment sites, head and neck, lung and prostate. Differences between pCT and CBCT recalculations were determined with dose volume histogram metrics and 2.0%/0.1 mm gamma analysis using the pCT dose distribution as a reference. Results: Dose volume histogram analysis indicated that all techniques yielded differences from expected results between 0.0 and 2.3% for both target volumes and organs at risk. With volumetric gamma analysis, the dose recalculation on deformed images yielded the highest pass-rates. The median pass-rate ranges at 50% threshold were 99.6–99.9%, 94.6–96.0%, and 94.8.0-96.0% for prostate, head and neck and lung patients, respectively. Conclusion: Deformable registration, HU override and site-specific calibration curves were all identified as dosimetrically accurate and efficient methods for dose calculation on CBCT images. Advances in knowledge: With the increasing adoption of CBCT, this study provides clinical radiotherapy departments with invaluable information regarding the comparison of dose reconstruction methods, enabling a more accurate representation of a patient’s treatment. It can also integrate studies in which CBCT is used in image-guided radiation therapy and for adaptive radiotherapy planning processes.

It is now widely accepted that intercellular communication can cause significant variations in cellular responses to genotoxic stress. The radiation-induced bystander effect is a prime example of this effect, where cells shielded from radiation exposure see a significant reduction in survival when cultured with irradiated cells. However, there is a lack of robust, quantitative models of this effect which are widely applicable. In this work, we present a novel mathematical model of radiation-induced intercellular signalling which incorporates signal production and response kinetics together with the effects of direct irradiation, and test it against published data sets, including modulated field exposures. This model suggests that these so-called “bystander” effects play a significant role in determining cellular survival, even in directly irradiated populations, meaning that the inclusion of intercellular communication may be essential to produce robust models of radio-biological outcomes in clinically relevant in vivo situations.

Objective: Consistency in target organ and organ at risk position from planning to treatment is an important basic principle of radiotherapy. This study evaluates the effectiveness of bladder-filling instructions in achieving a consistent and reproducible bladder volume at the time of planning CT and daily during the course of radical radiotherapy for prostate cancer. It also assessed the rate of bladder filling before and at the end of radiotherapy. Methods: 30 men attending for radiation therapy planning for prostate cancer received written and verbal bladder-filling instructions. They had their bladder volume assessed using a bladder ultrasound scanner post-void, immediately prior to planning CT scan and then daily immediately prior to treatment while in the therapy position. The inflow was calculated using the void and full bladder volumes and the time for the bladder to fill. Results: The mean bladder volume at the time of planning was 282 ml (range 89-608 ml, standard deviation (SD)5144.5 ml). This fell during treatment, with a mean value for all treatments of 189 ml (range 11-781 ml, SD5134 ml). During radiotherapy, 76% (828/1090), 53% (579/1090) and 36% (393/1090) of bladder volumes had .50 ml, .100 ml and .150 ml difference, respectively when compared with their volume at the time of planning. Inflow reduced from 4.6 ml min -1 , SD52.9 min -1 at planning to 2.5 min -1 , SD51.8 min -1 after radiotherapy. Conclusion: The Bladderscan device (BVI 6400 Bladderscan, Verathon Medical UK, Sandford, UK) provides an effective means of assessing bladder volume prior to radiotherapy for prostate cancer. The evaluated bladder-filling protocol does not produce consistent, reproducible bladder volumes for radiotherapy. Reproducibility of target volume position is a fundamental component of external beam radiotherapy at any site, but is of particular importance where a doseescalated regimen is being employed and where the surrounding organs are both dose and volume sensitive. For men receiving dose-escalated radical prostate radiotherapy, a consistent bladder volume between planning and treatment is vital. Although there are differing opinions on the influence of bladder volume on interfraction prostate position [1][2][3][4][5][6][7], the influence of the irradiated bladder volume on acute and late urinary [8] and bowel toxicity [2,9] has been well documented.Despite the apparent importance of controlling bladder volume for prostate radiotherapy, there is surprisingly limited research into the provision of bladder-filling instructions that produce acceptable dose-volume histograms (DVHs) and provide a reproducible bladder volume from planning through to treatment [1-2, 10, 11] rather than an unreliable and misleading snapshot at the time of planning.This study was designed to first validate bladder volume measurements using a non-invasive transabdominal bladder ultrasound device (BVI 6400 Bladderscan, Verathon Medical UK, Sandford, UK) before using it to evaluate the effectiveness of standardised bladder-filling instru...