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This study examines differences in tumour cellular response using clonogenic cell survival between uniform and non-uniform irradiation. Cells were irradiated with a 6 MV x-ray intensity-modulated beam, in a single large flask (i.e. intercellular communication is possible) or in three small flasks (i.e. intercellular communication is inhibited across the dose gradient). For non-small-cell lung cancer and melanoma cell lines, the dose response over the entire cell culture was significantly different between freely communicating cell cultures and those with inhibited communication across the dose non-uniformity. Communicating cells exhibited poorer survival in the low dose region of the field but improved survival in the high dose region. In general, the response to non-uniform irradiation appeared to 'average out' over the entire cell culture. This was not seen when intercellular communication was inhibited. The results add strength to the body of evidence regarding bystander effects and the inter-dependence of cellular response.

A spatially variable response of the bladder surface to the dose was found for symptoms of urinary dysfunction. Limiting the dose extending anteriorly might help reduce the risk of urinary dysfunction.

Cell survival following exposure to spatially modulated beams, as created by intensity-modulated radiotherapy (IMRT), is investigated. In vitro experiments were performed using malignant melanoma cells (MM576) exposed to a therapeutic megavoltage photon beam. We compared cell survival in modulated fields with cell survival in uniform control fields. Three different spatial modulations of the field were used: a control 'uniform' field in which all cells in a flask were uniformly exposed; a 'quarter' field in which 25% of cells at one end of the flask were exposed and a 'striped' field in which 25% of cells were exposed in three parallel stripes. The cell survival in both the shielded and unshielded regions of the modulated fields, as determined by a clonogenic assay, were compared to the cell survival in the uniform field. We have distinguished three ways in which cell survival is influenced by the fate of neighbouring cells. The first of these (type I effect) is the previously reported classical Bystander effect, where cell survival is reduced when communicating with irradiated cells. We find two new types of Bystander effect. The type II effect is an observed increase in cell survival when nearby cells receive a lethal dose. The type III effect is an increase in the survival of cells receiving a high dose of radiation, when nearby cells receive a low dose. These observations of the Bystander effects emphasize the need for improved radiobiological models, which include communicated effects and account for the effects of modulated dose distribution.

This study examined the variation of dose-volume histogram (DVH) data sourced from multiple radiotherapy treatment planning systems (TPSs). Treatment plan exports were obtained from 33 Australian and New Zealand centres during a dosimetry study. Plan information, including DVH data, was exported from the TPS at each centre and reviewed in a digital review system (SWAN). The review system was then used to produce an independent calculation of DVH information for each delineated structure. The relationships between DVHs extracted from each TPS and independently calculated were examined, particularly in terms of the influence of CT scan slice and pixel widths, the resolution of dose calculation grids and the TPS manufacturer. Calculation of total volume and DVH data was consistent between SWAN and each TPS, with the small discrepancies found tending to increase with decreasing structure size. This was significantly influenced by the TPS model used to derive the data. For target structures covered with relatively uniform dose distributions, there was a significant difference between the minimum dose in each TPS-exported DVH and that calculated independently.

Introduction: Aging skeletal muscle is associated with not only a reduction in muscle size and strength but also in muscle quality which reflects an increase in fatty infiltration of muscle. In men with prostate cancer, androgen deprivation therapy (ADT) accelerates this loss of muscle size and strength, but it is unknown if muscle quality is also adversely affected. Therefore, we examined the effects of ADT on muscle attenuation, an indirect measure of intramuscular lipid content, as well as the muscle cross-sectional area (CSA) in men with prostate cancer. Methods: Pre-and post-CT scans of the pelvis in 39 men aged 49-78 years receiving leuprorelin were examined. The time between baseline and follow-up scans was 14.6-20 weeks after the commencement of ADT. Changes in skeletal muscle attenuation in Hounsfield units of the rectus femoris and the CSA of the rectus femoris, sartorius and quadricep muscles were assessed. Results: Muscle attenuation of the rectus femoris muscle was significantly reduced following the initiation of ADT by 18.9% (P < 0.001). In addition, there was a significant decrease (P < 0.001) in the CSA for the sartorius, quadriceps and rectus femoris muscles. There was no effect of Zometa on muscle attenuation or muscle CSA. Conclusions: Our results indicate that not only muscle size but also muscle quality may be adversely affected by the undertaking of ADT in men with prostate cancer. Consequently, interventions to counteract deteriorations to both muscle mass and possibly muscle quality should be considered in men receiving ADT.

The dosimetric characteristics of a low-kV x-ray device for performing intra-operative irradiations, the Intrabeam (Photoelectron Corporation, Lexington, MA), are examined. Two dosimetric models are considered--an analytical model considering only the primary x-ray beam, and a Monte Carlo model utilizing the EGSnrc code and a spherical simulation geometry. Both models prove reliable for verifying measured dose distributions for the device. The Monte Carlo model is necessary for examining spectral variations and the influence of inhomogeneities. The predictions of the Monte Carlo model are utilized to examine points of consideration for a multi-center clinical trial using the Intrabeam in the intra-operative, single fraction post-resection treatment of low-risk breast cancer. Predicted differences in radiological equivalence of breast tissue and water suggest a 3-5% under-dose of breast tissue (in a 50 kV beam) when dose fall-off data in water is used. A substantial dose enhancement in bone (i.e., ribs) adjacent to the treatment site is predicted though, based on published clinical data for radiation-induced rib fracture, it is concluded that induction of radiation-induced rib fracture would not pose a significant risk. Dose-volume changes with size of the treatment area (defined by the size of the resection volume) are examined indicating large variations in dose-volume characteristics across the range of possible "target" volumes.

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