Biomedical subjects

H Thierens

Publications and source records attributed to H Thierens.

At least 19 recordsLinked to original sources

PubMed2006

Analysis of image quality in digital chest imaging.

An evaluation of the image quality of an amorphous silicon flat-panel detector system and a computed radiology system compared with a screen-film system was performed by means of contrast-detail phantom images. Hard and soft copy images were evaluated. Although patient dose at clinical settings was strongly decreased with the amorphous silicon system, the low-contrast visibility with this system was still significantly better than with the screen-film system. For the computed radiology system, low-contrast visibility was comparable to the screen-film system. Best results were obtained by soft copy reading at full resolution with adaptation of contrast and brightness. Changing tube voltage (102-133 kV), or additional filtration, did not significantly affect image quality. However, low-contrast visibility improved significantly with increasing exposure. It was clearly demonstrated that, in chest imaging, the amorphous silicon system has superior imaging characteristics compared to the screen-film and the computed radiology system.

Calibration↗

PubMed2006

Denoising of Monte Carlo dose calculations: smoothing capabilities versus introduction of systematic bias.

In order to evaluate the performance of denoising algorithms applied to Monte Carlo calculated dose distributions, conventional evaluation methods (rms difference, 1% and 2% difference) can be used. However, it is illustrated that these evaluation methods sometimes underestimate the introduction of bias, since possible bias effects are averaged out over the complete dose distribution. In the present work, a new evaluation method is introduced based on a sliding window superimposed on a difference dose distribution (reference dose-noisy/denoised dose). To illustrate its importance, a new denoising technique (ANRT) is presented based upon a combination of the principles of bilateral filtering and Savitzky-Golay filters. This technique is very conservative in order to limit the introduction of bias in high dose gradient regions. ANRT is compared with IRON for three challenging cases, namely an electron and photon beam impinging on heterogeneous phantoms and two IMRT treatment plans of head-and-neck cancer patients to determine the clinical relevance of the obtained results. For the electron beam case, IRON outperforms ANRT concerning the smoothing capabilities, while no differences in systematic bias are observed. However, for the photon beam case, although ANRT and IRON perform equally well on the conventional evaluation tests (rms difference, 1% and 2% difference), IRON clearly introduces much more bias in the penumbral regions while ANRT seems to introduce no bias at all. When applied to the IMRT patient cases, both denoising methods perform equally well regarding smoothing and bias introduction. This is probably caused by the summation of a large set of different beam segments, decreasing dose gradients compared to a single beam. A reduction in calculation time without introducing large systematic bias can shorten a Monte Carlo treatment planning process considerably and is therefore very useful for the initial trial and error phase of the treatment planning process.

Algorithms↗

PubMed2005

Decoupling initial electron beam parameters for Monte Carlo photon beam modelling by removing beam-modifying filters from the beam path.

A new method is presented to decouple the parameters of the incident e(-) beam hitting the target of the linear accelerator, which consists essentially in optimizing the agreement between measurements and calculations when the difference filter, which is an additional filter inserted in the linac head to obtain uniform lateral dose-profile curves for the high energy photon beam, and flattening filter are removed from the beam path. This leads to lateral dose-profile curves, which depend only on the mean energy of the incident electron beam, since the effect of the radial intensity distribution of the incident e- beam is negligible when both filters are absent. The location of the primary collimator and the thickness and density of the target are not considered as adjustable parameters, since a satisfactory working Monte Carlo model is obtained for the low energy photon beam (6 MV) of the linac using the same target and primary collimator. This method was applied to conclude that the mean energy of the incident e- beam for the high energy photon beam (18 MV) of our Elekta SLi Plus linac is equal to 14.9 MeV. After optimizing the mean energy, the modelling of the filters, in accordance with the information provided by the manufacturer, can be verified by positioning only one filter in the linac head while the other is removed. It is also demonstrated that the parameter setting for Bremsstrahlung angular sampling in BEAMnrc ('Simple' using the leading term of the Koch and Motz equation or 'KM' using the full equation) leads to different dose-profile curves for the same incident electron energy for the studied 18 MV beam. It is therefore important to perform the calculations in 'KM' mode. Note that both filters are not physically removed from the linac head. All filters remain present in the linac head and are only rotated out of the beam. This makes the described method applicable for practical usage since no recommissioning process is required.

Algorithms↗

PubMed2005

Investigation of geometrical and scoring grid resolution for Monte Carlo dose calculations for IMRT.

Monte Carlo based treatment planning of two different patient groups treated with step-and-shoot IMRT (head-and-neck and lung treatments) with different CT resolutions and scoring methods is performed to determine the effect of geometrical and scoring voxel sizes on DVHs and calculation times. Dose scoring is performed in two different ways: directly into geometrical voxels (or in a number of grouped geometrical voxels) or into scoring voxels defined by a separate scoring grid superimposed on the geometrical grid. For the head-and-neck cancer patients, more than 2% difference is noted in the right optical nerve when using voxel dimensions of 4 x 4 x 4 mm3 compared to the reference calculation with 1 x 1 x 2 mm3 voxel dimensions. For the lung cancer patients, 2% difference is noted in the spinal cord when using voxel dimensions of 4 x 4 x 10 mm3 compared to the 1 x 1 x 5 mm3 calculation. An independent scoring grid introduces several advantages. In cases where a relatively high geometrical resolution is required and where the scoring resolution is less important, the number of scoring voxels can be limited while maintaining a high geometrical resolution. This can be achieved either by grouping several geometrical voxels together into scoring voxels or by superimposing a separate scoring grid of spherical voxels with a user-defined radius on the geometrical grid. For the studied lung cancer cases, both methods produce accurate results and introduce a speed increase by a factor of 10-36. In cases where a low geometrical resolution is allowed, but where a high scoring resolution is required, superimposing a separate scoring grid on the geometrical grid allows a reduction in geometrical voxels while maintaining a high scoring resolution. For the studied head-and-neck cancer cases, calculations performed with a geometrical resolution of 2 x 2 x 2 mm3 and a separate scoring grid containing spherical scoring voxels with a radius of 2 mm produce accurate results and introduce a speed increase by a factor of 13. The scoring grid provides an additional degree of freedom for limiting calculation time and memory requirements by selecting optimized scoring and geometrical voxel dimensions in an independent way.

Algorithms↗

PubMed2005

Experimental verification of lung dose with radiochromic film: comparison with Monte Carlo simulations and commercially available treatment planning systems.

The purpose of this study was to assess the absorbed dose in and around lung tissue by performing radiochromic film measurements, Monte Carlo simulations and calculations with superposition convolution algorithms. We considered a layered polystyrene phantom of 12 x 12 x 12 cm3 containing a central cavity of 6 x 6 x 6 cm3 filled with Gammex RMI lung-equivalent material. Two field configurations were investigated, a small 1 x 10 cm2 field and a larger 10 x 10 cm2 field. First, we performed Monte Carlo simulations to investigate the influence of radiochromic film itself on the measured dose distribution when the film intersects a lung-equivalent region and is oriented parallel to the central beam axis. To that end, the film and the lung-equivalent materials were modelled in detail, taking into account their specific composition. Next, measurements were performed with the film oriented both parallel and perpendicular to the central beam axis to verify the results of our Monte Carlo simulations. Finally, we digitized the phantom in two commercially available treatment planning systems, Helax-TMS version 6.1A and Pinnacle version 6.2b, and calculated the absorbed dose in the phantom with their incorporated superposition convolution algorithms to compare with the Monte Carlo simulations. Comparing Monte Carlo simulations with measurements reveals that radiochromic film is a reliable dosimeter in and around lung-equivalent regions when the film is positioned perpendicular to the central beam axis. Radiochromic film is also able to predict the absorbed dose accurately when the film is positioned parallel to the central beam axis through the lung-equivalent region. However, attention must be paid when the film is not positioned along the central beam axis, in which case the film gradually attenuates the beam and decreases the dose measured behind the cavity. This underdosage disappears by offsetting the film a few centimetres. We find deviations of about 3.6% between Monte Carlo and the superposition convolution algorithm of Pinnacle behind the lung region, for both field configurations. Pinnacle is quite accurate in the lung region. Deviations up to 5.6% for the small field are found in the lung region between Monte Carlo and the superposition convolution algorithm of Helax-TMS. Behind the lung region, Helax-TMS is in better agreement with Monte Carlo. Radiochromic film measurements or Monte Carlo simulations are reliable methods to establish the dose in and around lung tissue.

Algorithms↗

PubMed2005

Cytogenetic biodosimetry of an accidental exposure of a radiological worker using multiple assays.

A technician involved in the maintenance of X-ray equipment visited the occupational medicine service with complaints of skin lesions, apparently caused by an accidental exposure three months earlier. To estimate the dose received by the technician in the accident, biodosimetry was performed 6 and 18 months post-exposure with the dicentric and micronucleus assays. Part of the latest blood sample was also used for retrospective dosimetry by fluorescence in situ hybridisation (FISH) analysis for translocations. The data obtained 6 and 18 months post-exposure indicate that both dicentrics and micronuclei disappear with a half-time of 1 y. After correction for delayed blood sampling, dose values of 0.75 Gy (95% confidence limits 0.56-1.05 Gy) from dicentrics and 0.96 Gy (95% confidence limits 0.79-1.18 Gy) from micronuclei were obtained. FISH analysis of translocations resulted in a dose estimate of 0.79 Gy (95% confidence limits 0.61-0.99 Gy). The satisfactory agreement between the three cytogenetic endpoints supports the use of the micronucleus assay for triage purposes in the case of large scale radiological accidents and provides further evidence for the valid use of FISH for translocations as a reliable retrospective biological dosimeter.

Adult↗

PubMed2005

The importance of accurate linear accelerator head modelling for IMRT Monte Carlo calculations.

Two Monte Carlo dose engines for radiotherapy treatment planning, namely a beta release of Peregrine and MCDE (Monte Carlo dose engine), were compared with Helax-TMS (collapsed cone superposition convolution) for a head and neck patient for the Elekta SLi plus linear accelerator. Deviations between the beta release of Peregrine and MCDE up to 10% were obtained in the dose volume histogram of the optical chiasm. It was illustrated that the differences are not caused by the particle transport in the patient, but by the modelling of the Elekta SLi plus accelerator head and more specifically the multileaf collimator (MLC). In MCDE two MLC modules (MLCQ and MLCE) were introduced to study the influence of the tongue-and-groove geometry, leaf bank tilt and leakage on the actual dose volume histograms. Differences in integral dose in the optical chiasm up to 3% between the two modules have been obtained. For single small offset beams though the FWHM of lateral profiles obtained with MLCE can differ by more than 1.5 mm from profiles obtained with MLCQ. Therefore, and because the recent version of MLCE is as fast as MLCQ, we advise to use MLCE for modelling the Elekta MLC. Nevertheless there still remains a large difference (up to 10%) between Peregrine and MCDE. By studying small offset beams we have shown that the profiles obtained with Peregrine are shifted, too wide and too flat compared with MCDE and phantom measurements. The overestimated integral doses for small beam segments explain the deviations observed in the dose volume histograms. The Helax-TMS results are in better agreement with MCDE, although deviations exceeding 5% have been observed in the optical chiasm. Monte Carlo dose deviations of more than 10% as found with Peregrine are unacceptable as an influence on the clinical outcome is possible and as the purpose of Monte Carlo treatment planning is to obtain an accuracy of 2%. We would like to emphasize that only the Elekta MLC has been tested in this work, so it is certainly possible that alpha releases of Peregrine provide more accurate results for other accelerators.

Dose-Response Relationship, Radiation↗

PubMed2005

Osteopontin and bone metabolism: a histology and scintigraphy study in rats.

Osteopontin (OPN) is one of the major non-collagen proteins in extracellular bone matrix. To elucidate the function of OPN in bone metabolism, a cellular defect was created in parietal bone and tibia of 12 rats. In Group 1, the left defects were filled with OPN-coated hydroxyapatite (OPN-H). In Group 2, the right defects were filled with non-coated hydroxyapatite (N-H). In both groups, the contra lateral defects were used as control defects. In Group 3, OPN-H was inserted in the left defects and N-H in the right defects. Bone metabolism was measured by (45)Ca and technetium-99m methylene diphosphonate scintigraphy for 4 weeks. Scintigraphy did not show any significant differences in bone metabolism between the defects filled with OPN-H and N-H. A higher bone metabolism was measured between the parietal defects filled with OPN-H or N-H in comparison with the parietal control defects. This difference, however, was not significant and was less for tibia defects. Histological observation (7th week) shows less inflammatory cells at the tibia defects filled with OPN-H compared to the tibia defects filled with N-H. This study did not show any acceleration or inhibition of bone metabolism in parietal or tibia bone in rats, but there is some evidence that OPN might influence inflammatory cells in bone matrix.

Animals↗

PubMed2005

Microsatellite polymorphisms in DNA repair genes XRCC1, XRCC3 and XRCC5 in patients with gynecological tumors: association with late clinical radiosensitivity and cancer incidence.

This study investigates the association of microsatellite polymorphisms in XRCC1, XRCC3 and XRCC5 with the development of late radiation-induced radiotherapy reactions and examines the correlation between these microsatellites and cancer incidence. Sixty-two women with cervical or endometrial cancer treated with radiotherapy were included in the study. According to the CTCAEv3.0 scale, 22 patients showed late adverse radiotherapy reactions (grade 2 or more). PCR on lymphocyte DNA followed by automated fragment analysis was performed to examine the number of tandem repeat units at each locus. No significant association was found between the repeat length at any of the microsatellites in XRCC1, XRCC3 or XRCC5 and the incidence of late radiotherapy complications. Since higher odds ratios (ORs) were found for the rare XRCC1 [AC]11 and [AC]21 repeats (OR = 2.65, P = 0.325 and OR = 8.67, P = 0.093, respectively), the possible involvement of these small and large repeats in clinical radiosensitivity cannot be completely ruled out. When specific numbers of repeats were examined, no significant correlation was found between the microsatellite repeat length in XRCC1 and XRCC5 and cancer incidence. A weak correlation between XRCC3 [AC]16 homozygotes and cancer incidence was found (OR = 2.56, P = 0.055). A large-scale multicenter study of cancer patients with a high number of radiosensitive individuals is needed to clarify the value of rare polymorphic microsatellite repeats in XRCC1 and XRCC3 as a biomarker of clinical radiosensitivity or increased cancer risk.

Adult↗

PubMed2004

Optimised tracer-dependent dosage cards to obtain weight-independent effective doses.

PURPOSE: The aim of this study was twofold: firstly, to determine whether the European Association of Nuclear Medicine (EANM) dosage card results in weight-independent effective doses or weight-independent count rates; secondly, to determine whether one dosage card is sufficient for 95 different radiopharmaceuticals, and, if not, how many cards we reasonably need to take into account inter-tracer variability. METHODS: Normalisation factors for count rate and effective dose were calculated as a function of body weight, with 70 kg as standard. Calculations were performed, using whole-body absorption fractions and MIRDOSE 3 software, for seven anthropomorphic phantoms and ten radionuclides. An analytic function for both relations was proposed. Normalisation factors for effective dose for 95 radiopharmaceuticals were investigated using cluster analysis. RESULTS: Normalisation factors for count rate and effective dose can be estimated accurately as a function of body weight W by (W/70)a holding only one parameter, called the a value. The a values for 95 radiopharmaceuticals were classified into three clusters (nA=7, nB=76, nC=12). Cluster A contains tracers for renal studies. Cluster B contains all remaining tracers, except iodine-labelled tracers for thyroid studies and 89Sr for therapy, which belong to cluster C. CONCLUSION: Correction factors proposed by the EANM task group mainly correct for effective dose. They are very similar to the factors obtained for cluster A. Using the EANM factors for tracers belonging to clusters B and C results in significantly higher effective doses to children. We suggest using three tracer-dependent dosage cards for which the correction factors have been calculated to obtain weight-independent effective doses.

Adult↗

PubMed2004

DOSSCORE: an accelerated DOSXYZnrc code with an efficient stepping algorithm and scoring grid.

DOSSCORE is an accelerated version of DOSXYZnrc that allows photons to cross voxel boundaries of the same medium and utilizes a separate scoring grid superimposed on the geometrical grid. Two different stepping algorithms, the hownear method and the scaling method are implemented in DOSSCORE. The hownear method allows particles to travel larger distances in homogeneous regions where there is no interest in the dose deposition of these particles, whilst the scaling method utilizes a stepping algorithm in which particles are only slowed down by the boundaries of the geometrical voxels and not by the boundaries of the scoring voxels. For CT-based phantoms, only photon ray tracing is applied, which results in a rather modest speed gain of factor 1.2 compared to DOSXYZnrc. The hownear method and scaling method do not increase the speed for CT-based phantoms, but only for homogeneous phantoms and phantoms with a limited number of small heterogeneities. In cases where a small number of scoring voxels are needed, the hownear method performs better than the scaling method, whilst the opposite is true for cases when many scoring voxels are needed. The photon transport is accelerated by almost a factor of 2 for all phantoms (homogeneous, heterogeneous with much homogeneity and CT-based phantoms) compared to DOSXYZnrc. For a small number of scoring voxels, the hownear method is up to a factor of 2.6 and 1.9 faster than DOSXYZnrc for homogeneous and heterogeneous phantoms in the case of photon beams. For an electron beam, a speed gain of factor 2.4 is obtained. For a full scoring grid like the one used in DOSXYZnrc, the scaling method is up to a factor of 2.2 and 1.7 faster than DOSXYZnrc for homogeneous and heterogeneous phantoms in the case of photon beams. For an electron beam, a speed gain of factor 2 is obtained. A speed increase without biasing the results is very relevant. The use of two separate grids, the more efficient stepping algorithms and the accelerated photon transport can be applied to every EGS-based or other Monte Carlo code.

Algorithms↗

PubMed2004

MCDE: a new Monte Carlo dose engine for IMRT.

A new accurate Monte Carlo code for IMRT dose computations, MCDE (Monte Carlo dose engine), is introduced. MCDE is based on BEAMnrc/DOSXYZnrc and consequently the accurate EGSnrc electron transport. DOSXYZnrc is reprogrammed as a component module for BEAMnrc. In this way both codes are interconnected elegantly, while maintaining the BEAM structure and only minimal changes to BEAMnrc.mortran are necessary. The treatment head of the Elekta SLiplus linear accelerator is modelled in detail. CT grids consisting of up to 200 slices of 512 x 512 voxels can be introduced and up to 100 beams can be handled simultaneously. The beams and CT data are imported from the treatment planning system GRATIS via a DICOM interface. To enable the handling of up to 50 x 10(6) voxels the system was programmed in Fortran95 to enable dynamic memory management. All region-dependent arrays (dose, statistics, transport arrays) were redefined. A scoring grid was introduced and superimposed on the geometry grid, to be able to limit the number of scoring voxels. The whole system uses approximately 200 MB of RAM and runs on a PC cluster consisting of 38 1.0 GHz processors. A set of in-house made scripts handle the parallellization and the centralization of the Monte Carlo calculations on a server. As an illustration of MCDE, a clinical example is discussed and compared with collapsed cone convolution calculations. At present, the system is still rather slow and is intended to be a tool for reliable verification of IMRT treatment planning in the case of the presence of tissue inhomogeneities such as air cavities.

Adenocarcinoma↗

PubMed2004

Chromosomal aberrations and in vitro radiosensitivity: intra-individual versus inter-individual variability.

In order to assess the applicability of the micronucleus (MN) and G2 assays as biomarkers of in vitro radiosensitivity and cancer susceptibility, we investigated the inter- and intra-individual variation of these endpoints. For the MN assay unstimulated blood cultures from 57 healthy donors were exposed in vitro to 3.5 Gy Co gamma-rays and for the G2 assay PHA stimulated cultures were irradiated with a dose of 0.4 Gy Co gamma-rays in the G2 phase of the cell cycle. For 14 donors, 2-15 repeat samples were tested over a period of 3 years. The repeat experiments revealed that the intra-individual variability was not significantly different from the inter-individual variability for both G2 and MN assays. As the intra-individual variability determines the reproducibility of the assay, our results highlight the limitations of these endpoints in detecting reproducible differences in radiation sensitivity between individuals within a normal population. Due to the high intra-individual variability and no significant difference with the inter-individual variability found in our study we conclude that care has to be taken when results obtained with chromosomal aberration assays based on one blood sample are used to assess the individual radiosensitivity. Multiple blood sampling may be necessary to draw reliable conclusions. Although more validation studies on the reliability of the G2 and MN assay will be required before they can be used in a confident way as biomarkers of individual radiosensitivity or cancer susceptibility the assays are very valuable to examine population radiosensitivity and the relationship between radiosensitivity, cancer predisposition and genotype.

Adult↗

PubMed2004

Chromosomal radiosensitivity in BRCA1 and BRCA2 mutation carriers.

PURPOSE: The chromosomal radiosensitivity of a selected group of familial breast cancer patients carrying a mutation in BRCA1 (n=11) or BRCA2 (n=9) and a group of healthy mutation carriers (n=12) was investigated and compared to a reference group of breast cancer patients without a BRCA1/2 mutation (n=78) and a group of healthy women carrying no mutation (n=58). MATERIALS AND METHODS: The chromosomal radiosensitivity was assessed with the G2 and the G0-micronucleus (MN)-assay on fresh blood samples and on Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines. For the MN-assay, lymphocytes were exposed in vitro to 3.5 Gy and 2 Gy 60Co gamma-rays at a high dose rate (HDR) or low dose rate (LDR). 70-h post-irradiation cultures were arrested and micronuclei were scored in 1000 binucleate cells. For the G2-assay lymphocytes were irradiated in vitro with a dose of 0.4 Gy 60Co gamma-rays after 71h incubation. Cultures were arrested 90 min after irradiation and chromatid breaks were scored in 50 metaphases. RESULTS: The group of breast cancer patients with a BRCA1 or 2 mutation was on average more radiosensitive than the control group, but not different from breast cancer patients without a BRCA mutation. The radiation response of healthy BRCA1/2 carriers was not significantly different from the control group and also not different from relatives without a BRCA mutation. Comparing the radiation response in EBV cell lines derived from breast cancer patients with or without a BRCA1 mutation revealed no significant difference. CONCLUSIONS: Our results reveal that chromosomal radiosensitivity observed in breast cancer patients heterozygous for BRCA1 or 2 mutations, could not be demonstrated in healthy BRCA1/2 mutation carriers. This suggests that mutations in BRCA1 or 2 genes are not playing a main role in chromosomal radiosensitivity, this although BRCA1 and 2 are both involved in DNA repair/signalling processes.

BRCA1 Protein↗

PubMed2004

The use of EBV-transformed cell lines of breast cancer patients to measure chromosomal radiosensitivity.

To investigate the chromosomal radiosensitivity of lymphocytes in cancer patients the micronucleus (MN) assay is often used and performed on freshly drawn peripheral blood lymphocytes. The use of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines may have a lot of advantages (e.g. large pool of cells) compared with fresh blood samples. In this study we have investigated whether the response of EBV-transformed lymphoblastoid cell lines to irradiation in the G1/S/G2 phases of the cell cycle is the same as in concordant whole blood cultures where primary lymphocytes were irradiated in the G0 phase of the cell cycle. For this study the MN assay (2 Gy) was performed on EBV-transformed cell lines of breast cancer patients and a group of healthy women. Those breast cancer patients were selected who showed an elevated chromosomal radiosensitivity in fresh blood samples in a previous study. The results demonstrated that the enhanced chromosomal radiosensitivity observed in fresh blood cultures of breast cancer patients is not present in EBV-transformed cell lines derived from the same blood samples. Therefore, care must be taken when EBV cell lines are used to assess chromosomal radiosensitivity in breast cancer patients.

Breast Neoplasms↗

PubMed2004

The use of IL-2 cultures to measure chromosomal radiosensitivity in breast cancer patients.

Enhanced chromosomal radiosensitivity in breast cancer patients has been demonstrated in several studies. To investigate the chromosomal radiosensitivity of lymphocytes in breast cancer patients the G2 and micronucleus (MN) assays are often used. In these assays blood samples are exposed to ionizing radiation and the number of radiation-induced micronuclei or chromatid breaks are scored. In most studies investigating the in vitro chromosomal radiosensitivity of breast cancer patients the G2 and MN assays were performed on freshly drawn blood. The disadvantage of working with fresh blood samples is that in most cases only one blood sample can be obtained and that the assay cannot be easily repeated without further blood sampling. To allow repeated testing we propose the use of long-term cultures of T lymphocytes (IL-2 cultures). In this study we therefore investigated whether the radiation-induced MN response in IL-2 cultures was the same as in concordant whole blood cultures. For this study the MN assay (2 Gy) was performed on IL-2 cultures of 11 sensitive breast cancer patients and 20 healthy women. The results demonstrate that the enhanced chromosomal radiosensitivity observed in whole blood cultures of breast cancer patients is not present in IL-2 cultures derived from the same blood samples. Therefore, care has to be taken when IL-2 cultures are used to assess chromosomal radiosensitivity in breast cancer patients.

Blood Cells↗

PubMed2004

Screening for supra-additive effects of cytotoxic drugs and gamma irradiation in an in vitro model for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. A wide variety of treatment modalities is available for palliative therapy of HCC, although there is no strong evidence that these treatments can have a significant impact on survival. The aim of this work was to screen cytotoxic drugs relevant in the treatment of HCC for enhancement of the effect of irradiation in an in vitro model. As the majority of patients presenting with HCC suffer reduced liver function, attention was paid to low-dose effects of the cytotoxic drugs tested. To reflect this situation in vivo, multicellular tumor aggregates or "spheroids" of HepG2 cells were cultured and exposed to gamma irradiation alone or in combination with cisplatin for 4 h, gemcitabin for 4 or 24 h, or 5-fluorouracil for 4 h. In one experiment, the spheroids were cultured for 4 weeks in multiwell plates that allowed adhesion. Measurement of two-dimensional spheroid outgrowth was made every week for each spheroid. This kind of growth depends on the proliferation and motility of the cells that form the spheroid. In a second experiment, toxicity was evaluated by comparative growth curves by means of a three-dimensional growth assay and by histology. Supra-additive effects lasting for 4 weeks were observed for all drugs tested in combination with a gamma irradiation of 10 Gy.

Antineoplastic Agents↗

PubMed2003

The value of radiochromic film dosimetry around air cavities: experimental results and Monte Carlo simulations.

In this study we investigate radiochromic film dosimetry around air cavities with particular focus on the perturbation of the dose distribution by the film when the film is parallel to the beam axis. We considered a layered polystyrene phantom containing an air cavity as a model for the air-soft tissue geometry that may occur after surgical resection of a paranasal sinus tumour. A radiochromic film type MD-55 was positioned within the phantom so that it intersected the cavity. Two phantom set-ups were examined. In the first case, the air cavity is at the centre of the phantom, thus the film is lying along the central beam axis. In the second case, the cavity and film are located 2 cm offset from the phantom centre and the central beam axis. In order to examine the influence of the film on the dose distribution and to interpret the film-measured results, Monte Carlo simulations were performed. The film was modelled rigorously to incorporate the composition and structure of the film. Two field configurations, a 1 x 10 cm2 field and a 10 x 10 cm2 field, were examined. The dose behind the air cavity is reduced by 6 to 7% for both field configurations when a film that intersects the cavity contains the central beam axis. This is due to the attenuation exerted by the film when photons cross the cavity. Offsetting the beam to the cavity and the film by 2 cm removes the dose reduction behind the air cavity completely. Another result was that the rebuild-up behind the cavity for the 10 x 10 cm2 field, albeit less significant than for the 1 x 10 cm2 field, could only be measured by the film that was placed offset with respect to the central beam axis. Although radiochromic film is approximately soft-tissue equivalent and energy independent as compared to radiographic films, care should be taken in the case of inhomogeneous phantoms when the film intersects air cavities and contains the beam central axis. Errors in dose measurement can be expected distal to the air cavity due to attenuation in the film itself. This attenuation would not occur in the absence of the film. Both experiments and Monte Carlo computations support this conclusion.

Air↗