Brendan Mcclean

• Saint Luke's Hospital (Ireland)

Background The Relative Biological Effectiveness (RBE) of kilovoltage photon beams has been previously investigated in vitro and in silico using analytical methods. The estimated values range from 1.03 to 1.82 depending on the methodology and beam energies examined. Purpose The focus of this work was to independently estimate RBE values for a rang...

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...

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 fo...

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...

Purpose: The purpose of this study was to evaluate the interobserver variability in the contouring of the gross tumour volume (GTV) on magnetic resonance imaging (MRI) and computed tomography (CT) for colorectal liver metastases in the setting of stereotactic ablative radiotherapy (SABR). Methods and Materials:Three expert radiation oncologists con...

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-respo...

Purpose: Radiation therapy plans are assessed using dose volume metrics derived from clinical toxicity and outcome data. In this study, plans for patients with locally advanced non-small cell lung cancer (LA-NSCLC) are examined in the context of the implementation of the Acuros XB (AXB) dose calculation algorithm focussing on the impact on common...

Aim This work compares dose-volume constraints (DVCs) and tumour control predictions based on the average intensity projection (AVIP) to those on each phase of the four-dimensional computed tomography. Materials and methods In this prospective study plans generated on an AVIP for nine patients with locally advanced non-small-cell lung cancer were...

The success of radiotherapy in tumour control depends on the total dose given. However, the tolerance of the normal tissues surrounding the tumour limits this dose. It is not known why some patients develop radiation toxicity and, currently, it is not possible to predict before treatment which patients will experience adverse effects. Thus, there i...

Genetic and epigenetic profile changes associated with individual radiation sensitivity are well documented and have led to enhanced understanding of the mechanisms of the radiation-induced DNA damage response. However, the search continues to identify reliable biomarkers of individual radiation sensitivity. Herein, we report on a multi-biomarker a...

In advanced radiotherapy, treatment of the tumor with high-intensity modulated fields is balanced with normal tissue sparing. However, the non-target dose delivered to surrounding healthy tissue within the irradiated volume is a potential cause for concern. Whether the effects observed are caused after exposure to out-of-field radiation or bystande...

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 i...

NO Signaling in bystander cells. It contains the data of Fig 2. (XLSX)

Intracellular measurements of ROS and GSH levels. The file contains the data sets for Fig 3A and 3B as S3A and S3B. (XLSX)

Apo-Tox triplex assay. It contains the data sets of viability assay, caspase activation and cytotoxicity assay data sets. (XLSX)

ROS signaling in bystander cells. It contains the data sets of Fig 1A–1C as S1A-C. (XLSX)

Purpose: Liquid biopsies are a potentially rich store of biochemical information that can be linked to an individual’s response to therapeutic treatments, including radiotherapy, and which may ultimately play a role in the individualization of treatment regimens. Peripheral blood mononuclear cells (PBMCs) can be used for the biochemical profiling o...

A means of reducing Patient Specific QA (PSQA) measurements for VMAT is currently a popular topic due to the resource burden it generates. The reluctance to reduce PSQA may be due to the difficulty in identifying the cause/s of plans that fail. Plans may fail due to a number of potential factors caused by the TPS, linac or measurement device. The g...

The feasibility of a technique using analysis of on-board CBCT images to adapt the dose to the target on a fraction by fraction basis was investigated. A 3D phase-correlation registration algorithm was used to retrospectively register CBCT images to the planning CT for 11 patients receiving VMAT prostate treatments of 74 Gy. The original plan was r...

Purpose: In this study, a 3D phase correlation algorithm was investigated to test feasibility for use in determining the anatomical changes that occur throughout a patient's radiotherapy treatment. The algorithm determines the transformations between two image volumes through analysis in the Fourier domain and has not previously been used in radio...

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...

Patients undergoing prostate intensity modulated arc therapy were retrospectively investigated using the CBCT images acquired for setup purposes to determine the volumetric variability of the target and organs at risk. This was achieved using a novel CT deformable registration algorithm based on analysis of phase correlation in the Fourier domain....

Purpose: The use of radiotherapy fields smaller than 3 cm in diameter has resulted in the need for accurate detector correction factors for small field dosimetry. However, published factors do not always agree and errors introduced by biased reference detectors, inaccurate Monte Carlo models, or experimental errors can be difficult to distinguish....

The use of Raman spectroscopy to measure the biochemical profile of healthy and diseased cells and tissues may be a potential solution to many diagnostic problems in the clinic. Although extensively used to identify changes in the biochemical profiles of cancerous cells and tissue, Raman spectroscopy has been used less often for analyzing changes t...

Purpose/Objective: The literature has reported that some TPSs underestimate the dose outside the radiation field edge (out-of-field). Sources of out-of-field dose are phantom scatter, head scatter and head and MLC leakage and transmission. The issues associated with inaccurate out-of- field dose reporting is with secondary cancer risk estimation, i...

Interest in out-of-field radiation dose has been increasing with the introduction of new techniques, such as volumetric modulated arc therapy (VMAT). These new techniques offer superior conformity of high-dose regions to the target compared to conventional techniques, however more normal tissue is exposed to low-dose radiation with VMAT. There is a...

There is much evidence supporting the existence of bystander effects in cells that were never exposed to radiation. Directly irradiated cells and bystander cells can communicate with each other using gap junctional intercellular communication or by releasing soluble factors into the surrounding medium. Exosomes and microvesicles are also known to m...

Purpose: The aim of this study was to compare levels of apoptosis, necrosis, mitotic cell death and senescence after treatment with both direct radiation and irradiated cell conditioned medium. Materials and methods: Human keratinocytes (HaCaT cell line) were irradiated (0.005, 0.05 and 0.5 Gy) using a cobalt 60 teletherapy unit. For bystander e...

The quantification of accurate output factors for small fields has been an area of active research over the last few years. Recently papers [1,2] have started to report output factors for certain field sizes along with correction factors for a variety of dosimeters based on the new formalism [3] proposed by the joint IAEA/AAPM task force. These cor...

The gamma function is a mathematical technique for the comparison of two dose distributions that is widely used in clinical situations such as IMRT verification and implemented by various commercial software packages. It is a composite distribution that compares both the percentage difference and distance to agreement of two dose distributions rela...

Purpose: The aim of this study was to investigate the importance of serum serotonin levels in the measurement of bystander cell death. The study was undertaken as part of an intercomparison exercise involving seven European laboratories funded under the European Union Sixth Framework Programme (FP6) Non-Targeted Effects (NOTE) integrated project....

Purpose St. Lukes Hospital, Rathgar, Dublin 6, Ireland has recently implemented an Ocular Brachytherapy Service using both Ruthenium‐106 and Iodine‐125 plaques. This work will summarize the initial experience of the hospital in these treatment modalities and provide information on some of the challenges experienced by a new centre performing this t...

Flattening filters (FFs) have been considered as an integral part of the treatment head of a medical accelerator for more than 50 years. The reasons for the longstanding use are, however, historical ones. Advanced treatment techniques, such as stereotactic radiotherapy or intensity modulated radiotherapy have stimulated the interest in operating li...

The aim of this study was to elucidate the sequence of very early bystander signalling events and to determine the role of the different signalling molecules in both the production of the bystander signal and the response to this signal. Human keratinocytes (HaCaT cell line) were irradiated (0.005, 0.05 and 0.5 Gy) using a cobalt 60 teletherapy uni...

A Monte Carlo model of an Elekta Precise linear accelerator has been built and verified by measured data for a 6 and 10 MV photon beam running with and without a flattening filter in the beam line. In this study the flattening filter was replaced with a 6 mm thick copper plate, provided by the linac vendor, in order to stabilize the beam. Several s...

To further evaluate irregular mitochondrial function and mitochondrial genome damage induced by direct γ-irradiation and bystander factors in human keratinocyte (HPV-G) epithelial cells and hamster ovarian fibroblast (CHO-K1) cells. This is as a follow-up to our recent reports of γ-irradiation-induced loss of mitochondrial function and mitochondria...

Recently, there has been an increasing interest in operating conventional linear accelerators without a flattening filter. The aim of this study was to determine beam quality variations as a function of off-axis ray angle for unflattened beams. In addition, a comparison was made with the off-axis energy variation in flattened beams. Two Elekta Prec...

To determine dosimetric properties of unflattened megavoltage photon beams. Dosimetric data including depth dose, profiles, output factors and phantom scatter factors from three different beam qualities provided by Elekta Precise linacs, operated with and without flattening filter were examined. Additional measurements of leaf transmission, leakage...

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 stu...

The characteristics of an Elekta amorphous silicon (a-Si) electronic portal imaging device (EPID) in response to a 6 MV photon beam generated without a flattening filter, an unflattened beam, have been determined. The characteristics were then compared to those for a conventional photon beam generated with a flattening filter in the beam, a flatten...

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 cel...

Radiation-induced bystander effects are now an established phenomenon seen in numerous cell and tissue culture models. The aim of this investigation was to examine the bystander signal and response in a multicellular primary tissue culture system in vitro. Murine bladder samples were explanted and directly exposed to gamma radiation, or treated wit...

The majority of photon dose calculation approaches today are model based dose calculation algorithms, in which the dose distribution is predicted from first principles. At the basic level there are the pencil beam convolution models, with further sophistication introduced by the collapsed cone convolution models. While the basic element of both is...

Radiation-induced bystander effects are now an established phenomenon seen in numerous models; however it is not known whether the magnitude of the bystander effect is determined by the signal produced by the irradiated cells or the response of the exposed cells. The aim of this investigation is to determine the importance of the bystander signal v...

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...

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...

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 we...

This note outlines an improved method of calculating dose per monitor unit values for small electron fields using Khan's lateral build-up ratio (LBR). This modified method obtains the LBR directly from the ratio of measured, surface normalized, electron beam percentage depth dose curves. The LBR calculated using this modified method more accurately...

Much evidence now exists regarding radiation-induced bystander effects, but the mechanisms involved in the transduction of the signal are still unclear. The mitogen-activated protein kinase (MAPK) pathways have been linked to growth factor-mediated regulation of cellular events such as proliferation, senescence, differentiation and apoptosis. Activ...

A dosimetric intercomparison of brachytherapy remote afterloading units in Ireland, Scotland and the North of England has been carried out involving 9 radiotherapy centres, and sampling 5 HDR and 6 LDR units. Absolute calibrations have been performed in air on both HDR and LDR sources. The results are expressed in terms of a ratio of local to calib...

When assessing the impact on workload from an expanding number of new patients and increasing treatment complexity, radiotherapy clinics find that oversimplified workload parameters, such as number of patients or number of fields, are not suitable for managing and predicting workload and organisational dimension. Although the basic treatment equiva...

Background and purpose: Appropriate planning target volume (PTV) definition is critical for local disease eradication in the treatment of non-small cell lung cancer (NSCLC). When margins are added to the gross tumour volume (GTV) in the standard way, the PTV formed may be too large to facilitate dose escalation due to normal tissue tolerance. To i...

When preparing radiation treatment, the prescribed dose and irradiation geometry must be translated into physical machine parameters. An error in the calculations or machine settings can negatively affect the intended treatment outcome. Analysing incidents originating in the treatment preparation chain makes it possible to find weak links and preve...

To evaluate, preclinically, the potential for dose escalation of continuous, hyperfractionated, accelerated radiation therapy (CHART) for non small-cell lung cancer (NSCLC), we examined the strategy of omission of elective nodal irradiation with and without the application of three-dimensional conformal radiation technology (3DCRT). 2D, conventiona...

Scitation is the online home of leading journals and conference proceedings from AIP Publishing and AIP Member Societies

This paper describes the errors in rebinning photon dose point spread functions and pencil beam kernels (PBKs) from cylindrical to Cartesian coordinates. An area overlap method, which assumes that the fractional energy deposited per unit volume remains constant within cylindrical voxels, provides large deviations (up to 20%) in rebinned Cartesian v...

Backscatter from the asymmetric collimators of a linac into the beam monitor chamber (BMC) has been investigated for two accelerators having different BMC configurations. The effect has been quantified as a function of field size and collimator jaw position for 6 and 18 MV beams. The results indicate a maximum 2.5% (6 MV) and 4% (18 MV) decrease in...

A special purpose x-ray CT scanner with the capability of scanning objects 75-220 mm in diameter with constant relative geometrical resolution has been developed. The data collection scheme for the scanner uses multiple rotations of a linearly shifted, asymmetric fan beam permitting user-defined variable resolution. Details of hardware and the cali...