Intensity Modulated Radiation Fields Research Articles

Oxygen enhancement ratios of cancer cells after exposure to intensity modulated x-ray fields: DNA damage and cell survival

Hypoxic cancer cells within solid tumours show radio-resistance, leading to malignant progression in fractionated radiotherapy. When prescribing dose to tumours under heterogeneous oxygen pressure with intensity-modulated radiation fields, intercellular signalling could have an impact on radiosensitivity between in-field and out-of-field (OF) cells. However, the impact of hypoxia on radio-sensitivity under modulated radiation intensity remains to be fully clarified. Here, we investigate the impact of hypoxia on in-field and OF radio-sensitivities using two types of cancer cells, DU145 and H1299. Using a nBIONIX hypoxic culture kit and a shielding technique to irradiate 50% of a cell culture flask, oxygen enhancement ratios for double-strand breaks (DSB) and cell death endpoints were determined. These in vitro measurements indicate that hypoxia impacts OF cells, although the hypoxic impacts on OF cells for cell survival were dose-dependent and smaller compared to those for in-field and uniformly irradiated cells. These decreased radio-sensitivities of OF cells were shown as a consistent tendency for both DSB and cell death endpoints, suggesting that radiation-induced intercellular communication is of importance in advanced radiotherapy dose-distributions such as with intensity-modulated radiotherapy.

Intensity Modulated Radiation Fields Induce Protective Effects and Reduce Importance of Dose-Rate Effects

In advanced radiotherapy, intensity modulated radiation fields and complex dose-delivery are utilized to prescribe higher doses to tumours. Here, we investigated the impact of modulated radiation fields on radio-sensitivity and cell recovery during dose delivery. We generated experimental survival data after single-dose, split-dose and fractionated irradiation in normal human skin fibroblast cells (AGO1522) and human prostate cancer cells (DU145). The dose was delivered to either 50% of the area of a T25 flask containing the cells (half-field) or 100% of the flask (uniform-field). We also modelled the impact of dose-rate effects and intercellular signalling on cell-killing. Applying the model to the survival data, it is found that (i) in-field cell survival under half-field exposure is higher than uniform-field exposure for the same delivered dose; (ii) the importance of sub-lethal damage repair (SLDR) in AGO1522 cells is reduced under half-field exposure; (iii) the yield of initial DNA lesions measured with half-field exposure is smaller than that with uniform-field exposure. These results suggest that increased cell survival under half-field exposure is predominantly attributed not to rescue effects (increased SLDR) but protective effects (reduced induction of initial DNA lesions). In support of these protective effects, the reduced DNA damage leads to modulation of cell-cycle dynamics, i.e., less G1 arrest 6 h after irradiation. These findings provide a new understanding of the impact of dose-rate effects and protective effects measured after modulated field irradiation.

Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields

To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions.

Scanning Properties of Dipole Bending Magnets used in Ion-Therapy Gantries

In modern ion-therapy facilities, there is a trend to develop and use scanning beam delivery systems. One of the most important advantages of scanning systems is that the field-shaping material devices in the beam path are minimized or removed entirely. Scanning systems inherently provide the intensity modulated radiation fields of ion beams that allow for a much greater flexibility in tailoring the dose distribution than in the case of passive delivery systems. A study of scanning properties of dipole bending magnets is published in order to provide engineers the theoretical tool for the early stage of a scanning-system design. This study is focused on scanning properties of dipole bending magnets with pure dipole fields without any gradient. The 90°, 60°, 45° and 30° bending magnets are studied. A two-directional magnetic scanning system with two scanners, one in the horizontal and another one in the vertical plane, is considered. This 2D magnetic scanning system ensures a parallel scanning mode in both transverse planes. The ion-optical properties of 2D magnetic scanning system and the study results for dipole bending magnets mentioned above are discussed.

Differential Mechanisms of Cellular Radiobiological Response Following Exposure to Intensity Modulated Radiation Fields

Cell survival was determined by clonogenic assay in human prostate cancer (DU145) and transformed fibroblast (AG0-1522) cells following exposure to modulated radiation fields created delivered using a X-Rad 225 kV X-ray generator. Uniform survival responses were compared to inand out-of-field responses in which 50% of the cell population was placed outside of the radiation field. Cell survival responses were determined under oxic and hypoxic conditions (0.1 % N2) and differential mechanisms of DNA damage response investigated use specific inhibitors of the DNA damage response pathway including ataxia telangiectasia mutated kinase (ATM, KU55933, Kudos Pharmaceuticals) and ataxia telangiectasia and Rad3-related protein kinase (ATR, Compound 45, Dr Chris Bakkenist, University of Pittsburgh). Temporal dependency of survival responses was determined by reseeding cells from the inand outof-field regions at different time post after irradiation. Differential mechanisms of cellular radiobiological response following exposure to intensity-modulated radiation fields

Skin dose assessment in unmodulated and intensity-modulated radiation fields with film dosimetry

Abstract Superficial dose from 6- and 18-MV photon beams has been studied by measuring surface dose and shallow build-up dose using radiographic film EDR2, radiochromic film EBT2 and plane-parallel chamber. Measurements have been made for intensity- and non-intensity-modulated beams. The results show that the surface dose was found to be 19.8% and 10% of maximum dose in unmodulated fields for 6 and 18 MV photon beams, respectively. The study further showed that intensity modulation decreased surface dose by 1.1% and 0.7% for the same field size at 6 and 18 MV, respectively, and surface dose was dropped by magnetically sweeping contaminating electrons. EDR2 and EBT2 films show in good agreement in shallow build-up region. This study demonstrated the capability of EDR2 film, in addition to radiochromic film, to measure surface and build-up dose in case of treatment planning system uncertainties with regard to skin toxicity or shallow target coverage.

Out-of-field Cell Survival and Radiation Induced Bystander Responses following Exposure to Intensity Modulated Radiation Fields

Out-of-field Cell Survival and Radiation Induced Bystander Responses following Exposure to Intensity Modulated Radiation Fields

Realization of intensity modulated radiation fields using multileaf collimator

Realization of intensity modulated radiation fields using multileaf collimator

A quality assurance method for analyzing and verifying intensity modulated fields

A quality assurance method is developed for measuring, verifying and analyzing intensity modulated radiation fields. It is applicable for rotational and fixed-beam intensity modulated radiation therapy (IMRT) treatments. A gantry-mount device was constructed to measure the transmission dose of an IMRT field using radiographic films. A double-exposure technique with optimal kernel estimate method was developed to minimize the errors from measurements. A chi2 confidence level test method was developed to detect the discrepancies between measured and prescribed IMRT fluence distributions. Our method was tested for rotational and fixed-beam IMRT treatment verifications. The method was found insensitive to the hardware-related parameters for rotational and fixed-beam IMRT deliveries. The chi2 confidence level test was found to be more sensitive than linear correlation method in detecting relative small errors for cases with a few segments or narrow regions of interest. In conclusion, we demonstrated a quantitative method for verifying and analyzing IMRT treatment deliveries.

VERIDOS: a new tool for quality assurance for intensity modulated radiotherapy.

The use of intensity modulated radiation fields needs an extended quality assurance concept. This consists of a linac related part and a case related part. Case related means the verification of an individual treatment plan, optimized on a CT data set of an individual patient and prepared for the treatment of this patient. This part of the quality assurance work is usually time consuming, delivers only partially quantitative results and is uncomfortable without additional help. It will be shown in this paper how the software VERIDOS will improve the optimization of the case related part of the quality assurance work. The main function of the software is the quantitative comparison of the calculated dose distribution from the treatment planning software with the measured dose distribution of an irradiated phantom. Several additional functions will be explained. Two self-developed phantoms made of RW3 (solid water) and GAFCHROMIC films or Kodak EDR2 films for the measurement of the dose distributions were used. VERIDOS was tested with the treatment planning systems Helay-TMS and Brainscan. VERIDOS is a suitable tool for the import of calculated dose matrices from the treatment planning systems Helax-TMS and Brainscan and of measured dose matrices exported from the dosimetry software Mephysto (PTW). The import from other treatment planning systems and scanning software applications for film dosimetry is generally possible. In such case the import function has to be adapted to the special header of the import matrix. All other functions of this software tool like normalization (automatically, manually), working with corrections (ground substraction, factors), overlay/comparison of dose distributions, difference matrix, cutting function (profiles) and export functions work reliable. VERIDOS improves the optimization of the case related part of the quality assurance work for intensity modulated radiation therapy (IMRT). The diverse functions of the software offer the radiation physicist a wide base to verify the IMRT plan independent from the mode of its delivery (compensator technology or MLC technology).

Optimization of intensity modulated radiotherapy under constraints for static and dynamic MLC delivery

Multi-leaf collimators (MLCs) are emerging as the prevalent modality to apply intensity modulated radiotherapy (IMRT). Both the principle and the particular design of MLCs stipulate complex constraints on the practically applicable intensity modulated radiation fields. Most consequentially, the distribution of exposure times across the maximum field outline is either a piecewise constant function in the static mode or a piecewise linear function in the dynamic mode of driving an MLC. In view of clinical utility, the total leaf movement should be minimized, which requires that MLC-related constraints be considered in the dose optimization process. A method is proposed to achieve this for both static MLC fields and dynamic leaf close-in application. The method is an amendment to a generic gradient-based IMRT dose optimization algorithm and solves numerical problems related to the non-convexity of the MLC constraints, which can cause erratic behaviour of a gradient-based algorithm. It employs bistable penalty functions to select preferrable leaf configurations from the configuration space of the MLC, which is limited by specific design features. Together with an ‘annealing’ escape mechanism from local minima, the algorithm is capable of finding the optimum of an IMRT problem as leaf sequences with minimized leaf travel. In particular, the efficiency of static IMRT can be raised to the levels of unmodulated fields with very few field segments, thereby increasing the utility of IMRT in clinical practice.