[en] Full text: While repopulation is a clinically observed phe nomenon after radiotherapy, repopulation of tumour cells between cycles of chemotherapy is usually a neglected factor in cancer treatment. As the effect of both radiotherapy and chemotherapy on tumour cells is the same (attack on cancer cells), the response of the tumour to injury and cell loss from the two treatment methods should be similar, including repopulation. Cell recruitment is known to be a possible mechanism responsible for tumour regrowth after radio therapy. The literature data regarding mechanisms of repopulation after chemotherapy is very limited. The current paper employs a Monte Carlo modelling approach to implement the pharmacokinetics of a widely used drug (cisplatin) into a previously developed vit1ual head and neck tumour and to study the effect of cisplatin on tumour regres sion and regrowth during treatment. The mechanism of cell recruitment was modelled by releasing various percentages (5-50%) of quiescent cells into the mitotic cycle after each chemotherapy cell kill. The onset of repopulation was also simulated, with both immediate onset and late onset of cell recruitment. Repopulation during chemotherapy, if occu ring, is a highly potent phenomenon, similar to drug resis tance, therefore it should not be neglected during treatment.

[en] Background. The MammoSite radiotherapy system is an alternative treatment option for patients with early-stage breast cancer to overcome the longer schedules associated with external beam radiation therapy. The device is placed inside the breast surgical cavity and inflated with a combination of saline and radiographic contrast to completely fill the cavity. The treatment schedule for the MammoSite monotherapy is 34 Gy delivered in 10 fractions at 1.0 cm from the balloon surface with a minimum of 6 hours between fractions on the same day. Material and methods. This review article presents the advantages, disadvantages, uncertainties and clinical outcomes associated with the MammoSite brachytherapy (MSB). Results. Potential advantages of MSB are: high localised dose with rapid falloff for normal tissue sparing, minimum delay between surgery and RT, catheter moves with breast, improved local control, no exposure to staff, likely side-effects reduction and potential cost/time saving (e.g. for country patients). The optimal cosmetic results depend on the balloon-to-skin distance. Good-to-excellent cosmetic results are achieved for patients with balloon-skin spacing of =7 mm. There have been very few published data regarding the long term tumour control and cosmesis associated with the MSB. The available data on the local control achieved with the MSB were comparable with other accelerated partial breast irradiation techniques. The contrast medium inside the balloon causes dose reduction at the prescription point. Current brachytherapy treatment planning systems (BTPS) do not take into account the increased photon attenuation due to high Z of contrast. Some BTPS predicted up to 10% higher dose near the balloon surface compared with Monte Carlo calculations using various contrast concentrations (5-25%). Conclusion. Initial clinical results have shown that the MammoSite device could be used as a sole radiation treatment for selected patients with early stage breast cancer providing good local control, minimal complication rate and excellent cosmesis

[en] At high radiation doses, breaks in the DNA are considered the critical lesions in initiation of radiation- induced cancer. However, at the very low radiation doses relevant for the general public, the induction of such breaks will be rare, and other changes to the DNA such as DNA methylation may play a role in radiation responses. DNA methylation is the addition of a methyl group to cytosine in the DNA, usually where a cytosine is adjacent to a guanine (CpG). Methylation affects the way in which genes are read, and is inherited from cell to cell on replication. It is known that high dose radiation can cause changes in methylation in the genome but less is known about the effect of low dose radiation on methylation. We developed a sensitive assay to measure the levels of DNA methylation across the mouse genome by analysing a stretch of DNA sequence within Long Interspersed Nuclear Elements-1(LINE1) that comprise a very large proportion of the mouse and human genomes. Using bisulphite modification followed by quantitative real-time polymerase chain reaction (PCP) and high- resolution melt analysis, a very large pool of DNA sequences from throughout the genome can be studied indicating gain or loss of methylation. We validated the assay in vitro using the chemical demethylating agent 5'-aza-2' -deoxycytidine with changes at as few as 3% of CpG's being reproducibly detected. We have demonstrated a difference in the baseline levels of in vivo DNA methylation between male and female mice and between different tissues. Our initial results suggest no significant short-term or long-term changes in global DNA methylation after low dose whole-body X-radiation of 10 -Gy or 10 mGy, with a significant transient increase in DNA methylation observed 1 day after a high dose of 1 Gy. If the low radiation doses tested are inducing changes in global DNA methylation, these would appear to be smaller than the natural variation observed between the sexes and following the general stress of the sham-irradiation procedure itself.

[en] The dose delivery verification for a head and neck static intensity modulated radiation therapy (IMRT) case using a scanning liquid ionization chamber electronic portal imaging device (SLIC-EPID) was investigated. Acquired electronic portal images were firstly converted into transmitted dose maps using an in-house developed method. The dose distributions were then compared with those calculated in a virtual EPID using the Pinnacle treatment planning system (TPS). Using gamma evaluation with the ΔD_max and DTA criteria of 3%/2.54 mm, an excellent agreement was observed between transmitted dose measured using SLIC-EPID and that calculated by TPS (gamma score approximately 95%) for large MLC fields. In contrast, for several small subfields, due to SLIC-EPID image blurring, significant disagreement was found in the gamma results. Differences between EPID and TPS dose maps were also observed for several parts of the radiation subfields, when the radiation beam passed through air on the outside of tissue. The transmitted dose distributions measured using portal imagers such as SLIC-EPID can be used to verify the dose delivery to a patient. However, several aspects such as accurate calibration procedure and imager response under different conditions should be taken into the consideration. In addition, SLIC-EPID image blurring is another important issue, which should be considered if the SLIC-EPID is used for clinical dosimetry verification. (author)

[en] Head and neck cancer represents a challenge for radiation oncologists due to accelerated repopulation of cancer cells during treatment. This study aims to simulate, using Monte Carlo methods, the response of a virtual head and neck tumor to both conventional and altered fractionation schedules in radiotherapy when accelerated repopulation is considered. Although clinical trials are indispensable for evaluation of novel therapeutic techniques, they are time-consuming processes which involve many complex and variable factors for success. Models can overcome some of the limitations encountered by trials as they are able to simulate in less complex environment tumor cell kinetics and dynamics, interaction processes between cells and ionizing radiation and their outcome. Conventional, hyperfractionated and accelerated treatment schedules have been implemented in a previously developed tumor growth model which also incorporates tumor repopulation during treatment. This study focuses on the influence of three main treatment-related parameters, dose per fraction, inter fraction interval and length of treatment gap and gap timing based on RTOG trial data on head and neck cancer, on tumor control. The model has shown that conventionally fractionated radiotherapy is not able to eradicate the stem population of the tumor. Therefore, new techniques such as hyperfractionated/accelerated radiotherapy schedules should be employed. Furthermore, the correct selection of schedule-related parameters (dose per fraction, time between fractions, treatment gap scheduling) is crucial in overcoming accelerated repopulation. Modeling of treatment regimens and their input parameters can offer better understanding of the radiobiological interactions and also treatment outcome. (author)

[en] Optical CT scanners for a 3D readout of externally irradiated radiosensitive hydrogels currently require the use of a refractive index (RI) matching liquid bath to obtain suitable optical ray paths through the gel sample to the detector. The requirement for a RI matching liquid bath has been negated by the design of a plastic cylindrical gel container that provides parallel beam geometry through the gel sample for the majority of the projection. The design method can be used for various hydrogels. Preliminary test results for the prototype laser beam scanner with ferrous xylenol-orange gel show geometric distortion of 0.2 mm maximum, spatial resolution limited to beam spot size of about 0.4 mm and 0.8% noise (1 SD) for a uniform irradiation. Reconstruction of a star pattern irradiated through the cylinder walls demonstrates the suitability for external beam applications. The extremely simple and cost-effective construction of this optical CT scanner, together with the simplicity of scanning gel samples without RI matching fluid increases the feasibility of using 3D gel dosimetry for clinical external beam dose verifications. (paper)

[en] Full text: Modern radiobiology is undergoing rapid change due to new discoveries contradicting the target concept which is currently used to predict dose-response relationships. Thus relatively recently discovered radiation induced bystander effects (RlBEs), that include additional death, mutation and radio-adaptation in non-irradiated cells, change our understanding of the target concept and broadens its boundaries. This can be significant from a radioprotection point of view and also has the potential to reassess radiation damage models currently used in radiotherapy. This article reviews briefly the general concepts of RlBEs such as the proposed underlying mechanisms of signal induction and propagation, experimental approaches and biological end points used to investigate these phenomena. It also summ rises several mathematical models currently proposed in an attempt to quantify RlBE. The main emphasis of this al1icle is to review and highlight the potential impact of the bystander phenomena in radiotherapy.

[en] The use of a scanning liquid ionization chamber electronic portal imaging device (SLIC-EPID) for two-dimensional transmitted dosimetry was investigated and a calibration method was developed using extended dose range (EDR2) film. In order to convert pixel value to dose, the acquired SLIC-EPID pixel values were calibrated using an ionization chamber on the central axis. The relationship between pixel values, dose rate and absorbed dose was identified for various linac output repetition rates. To correct EPIs for dosimetric purposes, the off-axis ratio of dose profiles measured by EPIDs and EDR2 film was used to derive correction factor matrices (CFMs) for a range of source-to-EPID distances (SEDs). The corrected relative dose maps acquired for different conditions, including open and wedged fields, measured using a SLIC-EPID were compared with EDR2 film images using a gamma function algorithm with distance to agreement (DTA) = 2.5 mm and dose difference (ΔD_max) = 1% criteria. The results showed that (a) for two-dimensional dosimetric purposes, EPIDs must be calibrated using appropriate two-dimensional correction factors and (b) SLIC-EPIDs can be used to measure the transmitted dose with good accuracy

[en] Pinnacle treatment planning system has been successfully commissioned for total body irradiation and will be used for patient treatments in near future. The actual dose delivered to patients will be monitored with TLDs and diode array and the agreement with the prescribed dose will be further investigated

[en] A method was developed to determine the accuracy of multileaf collimator (MLC) positioning using transmitted dose maps measured by a scanning liquid ionization chamber electronic portal imaging device (SLIC-EPID). Several MLC fields were designed, using the Varian C-series standard MLC-80, as reference fields for open fields. The MLC leaves were then shifted from the reference positions along the direction of MLC leaf movement towards the central axis from 0.1 to 1.6 mm. The electronic portal images (EPIs), acquired for each case, were converted to two-dimensional dose maps using an appropriate calibration method and the relative dose difference maps were then calculated. The experiment was then performed at non-zero gantry angles in the presence of an anthropomorphic phantom for typical prostate and head and neck fields. Several standard edge detection algorithms were also used in order to find the shifted MLC leaf position. In addition, the short-term reproducibility of MLC leaf positioning was evaluated using the above-mentioned methods. It was found that the relationship between the relative dose difference and MLC leaf spatial displacement is linear. A variation of 0.2 mm in leaf position leads to approximately 4% change in the relative dose values for open fields. The variation of the relative dose difference for phantom studies depends on the phantom positioning and the EPI normalization. From the standard edge detection algorithms, used in the current study, the 'Canny' algorithm was found to be the optimum method to identify the minimum detectable MLC leaf displacements with a precision of approximately 0.1 mm for all cases. However, the result of edge detection algorithms generally is binary and there is no additional information compared to the relative dose maps. The reproducibility of MLC positions was found to be within 0.3 mm. In conclusion, a SLIC-EPID can be used for regular quality assurance (QA) of MLC leaf positioning. Despite significant difference in the pixel size of the acquired SLIC-EPIs, it can be concluded that the SLIC-EPID can be used for MLC quality assurance protocols with similar accuracy compared to amorphous silicon (a-Si) EPID results. (note)