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Background and Purpose: Hypo-fractionated lung Stereotactic Ablative Body Radiotherapy (SABR) has often been avoided when tumours are close to the chest wall. Our strategic objective was the reduction of fraction number, while maintaining target biological effective dose coverage without increasing chest wall toxicity (CWT) predictors., Materials and Methods: Twenty previously treated lung SABR patients were stratified into four cohorts according to distance from PTV to the chest wall, <1 cm, <0.5 cm, overlapping up to 0.5 cm and 1.0 cm. For each patient, four plans were created; a chest wall optimised plan for 54 Gy in 3 fractions, the clinical plan re-prescribed for 55 Gy in 5, 48 Gy in 3 and 45 Gy in 3 fractions., Results: For a PTV distance of 0.5-0.0 cm, a reduction of the median (range) D max from 55.7 (57.5-54.1) Gy to 40.0 (37.1-42.0 Gy) Gy was observed for the chest wall optimised plans. The median V 30Gy decreased from 18.9 (9.7-25.6) cm 3 to 3.1 (1.8-4.5) cm 3 . For a PTV overlap of up to 0.5 cm, the D max reduced from 66.5 (64.1-70) Gy to 53.2 (50.6-55.1) Gy. The V 30Gy decreased from 21.5 (16.5-29.5) cm 3 to 14.9 (11.3-20.2) cm 3 . For the cohort with up to 1.0 cm overlap, there was a reduction in D max values of 9.9 Gy. The V 30Gy for clinical plans, at 66.8 (18.7-188.8) cm 3 , decreased to 55.3 (15.5-149) cm 3 ., Conclusion: When PTVs are within 0.5 cm of chest wall, lung SABR dose heterogeneity can be used to reduce fraction number without increasing CWT predictors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Kilovoltage radiotherapy dose calculations are generally performed with manual point dose calculations based on water dosimetry. Tissue heterogeneities, irregular surfaces, and introduction of lead cutouts for treatment are either not taken into account or crudely approximated in manual calculations. Full Monte Carlo (MC) simulations can account for these limitations but require a validated treatment unit model, accurately segmented patient tissues and a treatment planning interface (TPI) to facilitate the simulation setup and result analysis. EGSnrc was used in this work to create a model of Xstrahl kilovoltage unit extending the range of energies, applicators, and validation parameters previously published. The novel functionality of the Python-based framework developed in this work allowed beam modification using custom lead cutouts and shields, commonly present in kilovoltage treatments, as well as absolute dose normalization using the output of the unit. 3D user-friendly planning interface of the developed framework facilitated non-co-planar beam setups for CT phantom MC simulations in DOSXYZnrc. The MC models of 49 clinical beams showed good agreement with measured and reference data, to within 2% for percentage depth dose curves, 4% for beam profiles at various depths, 2% for backscatter factors, 0.5 mm of absorber material for half-value layers, and 3% for output factors. End-to-end testing of the framework using custom lead cutouts resulted in good agreement to within 3% of absolute dose distribution between simulations and EBT3 GafChromic film measurements. Gamma analysis demonstrated poor agreement at the field edges which was attributed to the limitations of simulating smooth cutout shapes. Dose simulated in a heterogeneous phantom agreed to within 7% with measured values converted using the ratio of mass energy absorption coefficients of appropriate tissues and air., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Irradiation of the tumour site during treatment for cancer with external-beam ionising radiation results in a complex and dynamic series of effects in both the tumour itself and the normal tissue which surrounds it. The development of a spectral model of the effect of each exposure and interaction mode between these tissues would enable label free assessment of the effect of radiotherapeutic treatment in practice. In this study Fourier transform Infrared microspectroscopic imaging was employed to analyse an in-vitro model of radiotherapeutic treatment for prostate cancer, in which a normal cell line (PNT1A) was exposed to low-dose X-ray radiation from the scattered treatment beam, and also to irradiated cell culture medium (ICCM) from a cancer cell line exposed to a treatment relevant dose (2 Gy). Various exposure modes were studied and reference was made to previously acquired data on cellular survival and DNA double strand break damage. Spectral analysis with manifold methods, linear spectral fitting, non-linear classification and non-linear regression approaches were found to accurately segregate spectra on irradiation type and provide a comprehensive set of spectral markers which differentiate on irradiation mode and cell fate. The study demonstrates that high dose irradiation, low-dose scatter irradiation and radiation-induced bystander exposure (RIBE) signalling each produce differential effects on the cell which are observable through spectroscopic analysis., Competing Interests: The authors declare no conflict of interest.

On May 14, 2021, the Health Service Executive (HSE) of Ireland experienced a major ransomware cyberattack. The HSE initially took down all of its information technology systems to protect its core systems. All Internet connections within the HSE were unavailable from 7 am for approximetely three weeks which had a major effect on the radiation oncology service nationally within the public service. St. Luke's Radiation Oncology Network (SLRON) is a complex, 3-center radiation oncology service, and it is the largest in the country; with 14 linear accelerators, it is one of the largest radiation centers in Europe. This article details the response of SLRON to the outage resultant from the cyberattack. Although the outage affected all patient services, including laboratory, diagnostic imaging, and inpatient care, the article primarily focuses on our response to get the radiation oncology service restarted as quickly as possible and details the steps we took to reinstate our systems safely, how we prioritized patient treatments, and how we communicated with patients, staff, and the public without having access to standard communication pathways. All decisions were risk assessed and were made with the best resources available to us at the time to maximize the outcome for our patients and mitigate significant delays. The risk remains ongoing, and the onerous task of uploading backlogs and reconciling patient records is a continuing risk., (© 2022 The Authors.)

On Friday, May 14, 2021, the Health Service Executive, the organization providing public health services in the Republic of Ireland, was the victim of a significant cyberattack on its information technology systems. All systems were subsequently shut down to prevent further damage and to allow cybersecurity experts to investigate the attack. As a result, oncology services were severely disrupted, with the cessation of radiation therapy treatments in all public radiation therapy departments. Ireland has 5 large public and 6 smaller private radiation therapy centers in total. Because of the widespread adoption of electronic medical records in radiation therapy departments, it wasn't possible to retrieve patient details of those who were undergoing radiation therapy at the time of the cyberattack. In total, 513 patients nationally had their radiation therapy interrupted. A national radiation therapy cyberattack response team was formed immediately to oversee the response to the attack. The immediate concerns were radiation therapy emergencies and category 1 patients where gaps in treatment would have an adverse effect on outcome. Communication with patients and the public was also established as a priority and agreements were reached with the private sector for the treatment of patients affected by the cyberattack. The national media was used to alert patients of the need to communicate with their radiation therapy department. Dedicated phone lines were established. Locally, radiation therapy departments held daily crisis meetings with key staff members, including information technology personnel. Individual centers employed different technologies for treatment planning and data storage, so local solutions to the cyberattack to reestablish radiation therapy for patients were developed. In addition, national documentation on prioritization of patients to resume treatment was produced and a national approach was made to compensate for gaps in treatment caused by the attack. All 5 centers had reestablished radiation therapy by May 30, although there has been a long aftermath to the cyberattack. In this article, we provide an overview of the effects of the cyberattack on our national radiation therapy service and our strategy to resume patient treatment in a timely fashion., (© 2022 The Authors.)

Purpose: The purpose of this study was to evaluate the interobserver variability in the contouring of the gross tumor volume (GTV) on magnetic resonance (MR) imaging and computed tomography (CT) for colorectal liver metastases in the setting of SABR., Methods and Materials: Three expert radiation oncologists contoured 10 GTV volumes on 3 MR imaging sequences and on the CT image data set. Three metrics were chosen to evaluate the interobserver variability: the conformity index, the DICE coefficient, and the maximum Hausdorff distance (HDmax). Statistical analysis of the results was performed using a 1-sided permutation test., Results: For all 3 metrics, the MR liver acquisition volume acquisition (MR LAVA) showed the lowest interobserver variability. Analysis showed a significant difference ( P < .01) in the mean DICE, an overlap metric, for MR LAVA (0.82) and CT (0.74). The HDmax that highlights boundary errors also showed a significant difference ( P  = .04) with MR LAVA having a lower mean HDmax (7.2 mm) compared with CT (5.7 mm). The mean HDmax for both MR single shot fast spin echo (SSFSE) (19.3 mm) and diffusion weighted image (9.5 mm) showed large interobserver variability with MR SSFSE having a mean HDmax of 19.3 mm. A volume comparison between MR LAVA and CT showed a significantly higher volume for small GTVs (<5 cm 3 ) when using MR LAVA for contouring in comparison to CT., Conclusions: This study reported the lowest interobserver variability for the MR LAVA, thus indicating the benefit of using MR to complement CT when contouring GTV for colorectal liver metastases., (© 2022 Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.)

Aims: To retrospectively evaluate the quality of fit of 3D printed bolus over four different treatment sites to determine whether certain sites favor a 3D printed approach and if the quality of fit changes over the course of treatment., Materials and Methods: A retrospective analysis of the first 60 cases treated using 3D printed bolus in our radiotherapy center was undertaken. All boluses were printed using flexible thermoplastic polyurethane (TPU) material. We developed a system of rating the quality of fit using four quality categories. The analysis of 60 patients consisted of a review of a total 627 treatment fractions for head and neck (H&N), scalp, pelvis, and extremity treatment sites., Results: Out of 627 fractions evaluated, 75.1% were rated either "good" or "excellent", 20.6% were rated as "acceptable" and 4.3% were rated "poor". H&N, scalp, and extremity treatment regions were found to favor a 3D printed approach. However, pelvis cases had a higher proportion of "acceptable" and "poor" ratings. Trend analysis showed no notable change in the quality of 3D printed bolus fit over the course of treatment, except for pelvis cases which tended to change categories more than other treatment sites., Conclusion: This evaluation demonstrates that 3D printed bolus, created using semi-flexible materials such as TPU, is an effective and practical bolus choice for radiotherapy. In particular, using a 3D printed approach for H&N, scalp, and extremities was found to have a highly conformal fit., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4-gene signature panel of CDKN1, FDXR, SESN1 and PCNA previously reported to be radiation-responsive genes, using the conventional G2 chromosomal radiosensitivity assay. Radiation-induced G2 chromosomal radiosensitivity at 0.05 Gy and 0.5 Gy IR is presented for a healthy control ( n = 45) and a prostate cancer ( n = 14) donor cohort. For the prostate cancer cohort, data from two sampling time points (baseline and Androgen Deprivation Therapy (ADT)) is provided, and a significant difference ( p > 0.001) between 0.05 Gy and 0.5 Gy was evident for all donor cohorts. Selected donor samples from each cohort also exposed to 0.05 Gy and 0.5 Gy IR were analysed for relative gene expression of the 4-gene signature. In the healthy donor cohort, there was a significant difference in gene expression between IR dose for CDKN1, FXDR and SESN1 but not PCNA and no significant difference found between all prostate cancer donors, unless they were classified as radiation-induced G2 chromosomal radiosensitive. Interestingly, ADT had an effect on radiation response for some donors highlighting intra-individual heterogeneity of prostate cancer donors.

Positive behavioral support (PBS) employs applied behavioral analysis to enhance the quality of life of people who behave in challenging ways. PBS builds on the straightforward and intuitively appealing notion that if people know how to control their environments, they will have less need to behave in challenging ways. Accordingly, PBS focuses on the perspective of those who have behavioral issues, and assesses success via reduction in incidences of challenging behaviors. The qualitative research presented in this report approaches PBS from a different viewpoint and, using thematic analysis, considers the impact of PBS training on the lived experience of staff who deliver services. Thirteen support staff who work for a company supplying social care and supported living services for people with learning disabilities and complex needs in the northwest of England took part. Analysis of interviews identified five major themes. These were: (1) training: enjoyable and useful; (2) widening of perspective: different ways of thinking; (3) increased competence: better outcomes; (4) spill over into private lives: increased tolerance in relationships; and (5) reflecting on practice and moving to a holistic view: "I am aware that people…are not just being naughty." These themes evidenced personal growth on the part of service providers receiving training. Explicitly, they demonstrated that greater awareness of PBS equipped recipients with an appropriate set of values, and the technical knowledge required to realize them., (Copyright © 2019 Walsh, McClean, Doyle, Ryan, Scarborough-Lang, Rishton and Dagnall.)

It is now well accepted that radiation induced bystander effects can occur in cells exposed to media from irradiated cells. The aim of this study was to follow the bystander cells in real time following addition of media from irradiated cells and to determine the effect of inhibiting these signals. A human keratinocyte cell line, HaCaT cells, was irradiated (0.005, 0.05 and 0.5 Gy) with γ irradiation, conditioned medium was harvested after one hour and added to recipient bystander cells. Reactive oxygen species, nitric oxide, Glutathione levels, caspase activation, cytotoxicity and cell viability was measured after the addition of irradiated cell conditioned media to bystander cells. Reactive oxygen species and nitric oxide levels in bystander cells treated with 0.5Gy ICCM were analysed in real time using time lapse fluorescence microscopy. The levels of reactive oxygen species were also measured in real time after the addition of extracellular signal-regulated kinase and c-Jun amino-terminal kinase pathway inhibitors. ROS and glutathione levels were observed to increase after the addition of irradiated cell conditioned media (0.005, 0.05 and 0.5 Gy ICCM). Caspase activation was found to increase 4 hours after irradiated cell conditioned media treatment (0.005, 0.05 and 0.5 Gy ICCM) and this increase was observed up to 8 hours and there after a reduction in caspase activation was observed. A decrease in cell viability was observed but no major change in cytotoxicity was found in HaCaT cells after treatment with irradiated cell conditioned media (0.005, 0.05 and 0.5 Gy ICCM). This study involved the identification of key signaling molecules such as reactive oxygen species, nitric oxide, glutathione and caspases generated in bystander cells. These results suggest a clear connection between reactive oxygen species and cell survival pathways with persistent production of reactive oxygen species and nitric oxide in bystander cells following exposure to irradiated cell conditioned media.

Multileaf collimators (MLCs) need to be characterized accurately in treatment planning systems to facilitate accurate intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT). The aim of this study was to examine the use of MapCHECK 2 and ArcCHECK diode arrays for optimizing MLC parameters in Monaco X-ray voxel Monte Carlo (XVMC) dose calculation algorithm. A series of radiation test beams designed to evaluate MLC model parameters were delivered to MapCHECK 2, ArcCHECK, and EBT3 Gafchromic film for comparison. Initial comparison of the calculated and ArcCHECK-measured dose distributions revealed it was unclear how to change the MLC parameters to gain agreement. This ambiguity arose due to an insufficient sampling of the test field dose distributions and unexpected discrepancies in the open parts of some test fields. Consequently, the XVMC MLC parameters were optimized based on MapCHECK 2 measurements. Gafchromic EBT3 film was used to verify the accuracy of MapCHECK 2 measured dose distributions. It was found that adjustment of the MLC parameters from their default values resulted in improved global gamma analysis pass rates for MapCHECK 2 measurements versus calculated dose. The lowest pass rate of any MLC-modulated test beam improved from 68.5% to 93.5% with 3% and 2 mm gamma criteria. Given the close agreement of the optimized model to both MapCHECK 2 and film, the optimized model was used as a benchmark to highlight the relatively large discrepancies in some of the test field dose distributions found with ArcCHECK. Comparison between the optimized model-calculated dose and ArcCHECK-measured dose resulted in global gamma pass rates which ranged from 70.0%-97.9% for gamma criteria of 3% and 2 mm. The simple square fields yielded high pass rates. The lower gamma pass rates were attributed to the ArcCHECK overestimating the dose in-field for the rectangular test fields whose long axis was parallel to the long axis of the ArcCHECK. Considering ArcCHECK measurement issues and the lower gamma pass rates for the MLC-modulated test beams, it was concluded that MapCHECK 2 was a more suitable detector than ArcCHECK for the optimization process., (© 2016 The Authors)

Post-acute community-based rehabilitation is effective in reducing disability. However, while social participation and quality of life are valued as distal outcomes of neurorehabilitation, it is often not possible to observe improvements on these outcomes within the limited time-frames used in most investigations of rehabilitation. The aim of the current study was to examine differences in the sequence of attainments for people with acquired brain injury (ABI) undergoing longer term post-acute neurorehabilitation. Participants with ABI who were referred to comprehensive home and community-based neurorehabilitation were assessed at induction to service, at 6 months and again at 1.5 years while still in service on the Mayo-Portland Adaptability Index (MPAI-4), Community Integration Questionnaire, Hospital Anxiety and Depression Scale, and World Health Organisation Quality of Life measure. At 6 months post-induction to service, significant differences were evident in MPAI abilities, adjustment, and total neurodisability; and in anxiety and depression. By contrast, there was no significant effect at 6 months on more socially oriented features of experience namely quality of life (QoL), Community Integration and Participation. Eighteen month follow-up showed continuation of the significant positive effects with the addition of QoL-related to physical health, Psychological health, Social aspects of QoL and Participation at this later time point. Regression analyses demonstrated that change in QoL and Participation were dependent upon prior changes in aspects of neurodisability. Age, severity or type of brain injury did not significantly affect outcome. Results suggest that different constructs may respond to neurorehabilitation at different time points in a dose effect manner, and that change in social aspects of experience may be dependent upon the specific nature of prior neurorehabilitation attainments.

It is well known that patients can vary in their normal tissue response to radiotherapy, and this can be problematic. As a result, radiobiologists have been using in vitro models to assess variation in response and elucidate the genetic determinants of this variation. However, the clinical relevance of these models is currently unknown. In this study, blood samples from healthy controls (n = 20) and colorectal carcinoma patients (n = 60) were cultured in vitro to assess two radiobiological end points in parallel: intrinsic radiosensitivity assayed by chromosomal aberrations (G(2) scores) and radiation-induced bystander effects assayed by viability testing. Increased intrinsic radiosensitivity was observed in colorectal carcinoma donors (55%) compared to the healthy donors (5%) (P < 0.005). Similarly, more pronounced radiation-induced bystander effects were observed in the colorectal carcinoma donors compared to the healthy donors after 24 h exposure but not after 96 h exposure to donor irradiated cell conditioned medium (ICCM) (P < 0.05). All scores were tested for correlation with the age, sex and clinical stage of the colorectal carcinoma patients. The only statistically significant correlation was found in samples from severe Dukes D patients (P < 0.005), which had low/radioresistant G(2) scores. No correlation was found between radiation-induced intrinsic sensitivity and bystander effects, which suggests that they may have separate underlying molecular mechanisms, but they both show clinical relevance in individual patient samples.

In recent years ethical, legislative and economic pressures have created a renewed interest in the development of alternatives to in vivo animal experiments. In vitro studies, particularly those using cell cultures, have been used increasingly as tools to assess the degree of toxicity associated with or present in particular environments. While cell cultures are useful to give relative toxicity values, genotypic and phenotypic integrity may be compromised in the continuous artificial environment they experience. In addition, cell cultures lack the complexity of functional organs and thus do not truly represent the effects that toxins exert on organ and organism functionality. In this study, ex vivo tissue cultures of rainbow trout gill, skin and spleen samples were analyzed for variation of expression in genes associated with oxidative phosphorylation after exposure to ionizing radiation. Significant radiation-induced changes in gene expression and enzyme activity associated with the mitochondrial oxidative phosphorylation process were identified. The tissues examined in this study demonstrated an exposure threshold at which radiation dose stimulates an alteration in the regulatory activity of mitochondrial-associated genes. Spleen tissues exposed to low levels of radiation (0.1 Gy) appeared most sensitive whereas skin tissues proved least sensitive, reacting only to higher doses (>1 Gy). We propose this investigative approach as an innovative alternative to in vivo studies because it identifies toxic exposure in vitro and could significantly reduce the number of live-animal toxicity tests required.

The bystander effect describes radiation-like damage in unirradiated cells either in the vicinity of irradiated cells or exposed to medium from irradiated cells. This study aimed to further characterize the poorly understood mitochondrial response to both direct irradiation and bystander factor(s) in human keratinocytes (HPV-G) and Chinese hamster ovarian cells (CHO-K1). Oxygen consumption rates were determined during periods of state 4, state 3 and uncoupled respiration. Mitochondrial mass was determined using MitoTracker FM. CHO-K1 cells showed significantly reduced oxygen consumption rates 4 h after exposure to 5 Gy direct radiation and irradiated cell conditioned medium (ICCM) and an apparent recovery 12-24 h later. The apparent recovery was likely due to the substantial increase in mitochondrial mass observed in these cells as soon as 4 h after exposure. HPV-G cells, on the other hand, showed a sustained increase in oxygen consumption rates after ICCM exposure and a transient increase 4 h after exposure to 5 Gy direct radiation. A significant increase in mitochondrial mass per HPV-G cell was observed after exposure to both direct radiation and ICCM. These findings are indicative of a stress response to mitochondrial dysfunction that increases the number of mitochondria per cell.

The aim of this study was to investigate whether exposure of HPV-G cells to irradiated cell conditioned medium (ICCM) could induce an adaptive response if the cells were subsequently challenged with a higher ICCM dose. Clonogenic survival and major steps in the cascade leading to apoptosis, such as calcium influx and loss of mitochondrial membrane potential, were examined to determine whether these events could be modified by giving a priming dose of ICCM before the challenge dose. Clonogenic survival data indicated an ICCM-induced adaptive response in HPV-G cells "primed" with 5 mGy or 0.5 Gy ICCM for 24 h and then exposed to 0.5 Gy or 5 Gy ICCM. Reactive oxygen species (ROS) were found to be involved in the bystander-induced cell death. Calcium fluxes varied in magnitude across the exposed cell population, and a significant number of the primed HPV-G cells did not respond to the challenge ICCM dose. No significant loss of mitochondrial membrane potential was observed when HPV-G cells were exposed to 0.5 Gy ICCM for 24 h followed by exposure to 5 Gy ICCM for 6 h. Exposure of HPV-G cells to 5 mGy ICCM for 24 h followed by exposure to 0.5 Gy ICCM for 18 h caused a significant increase in mitochondrial mass and a change in mitochondrial location, events associated with the perpetuation of genomic instability. This study has shown that a priming dose of ICCM has the ability to induce an adaptive response in HPV-G cells subsequently exposed to a challenge dose of ICCM.

The bystander response has been documented in cell lines and cell cultures derived from aquatic species over the past several years. However, little work has been undertaken to identify a similar bystander response in tissue explant cultures from fish. In this study, indirect effects of ionizing gamma radiation on tissue explant cultures of fish were investigated. Tissue explants in culture were exposed to 0.5 Gy and 5 Gy gamma radiation from a 60Co teletherapy unit. A bystander response in Epithelioma papulosum cyprini (EPC) cells exposed to gamma-irradiated tissue conditioned medium from rainbow trout explants was investigated, and the effects on cell survival were quantified by the clonogenic survival assay. Dichlorofluorescein and rhodamine 123 fluorescent dyes were used to identify alterations in reactive oxygen species (ROS) and mitochondrial membrane potential (MMP), respectively. Results indicate a different response for the three tissue types investigated. Clonogenic assay results vary from a decrease in cell survival (gill) to no effect (skin) to a stimulatory effect (spleen). Results from fluorescence assays of ROS and MMP show similarities to clonogenic assay results. This study identifies a useful model for further studies relating to the bystander effect in aquatic organisms in vivo and ex vivo.