H Thierens

Estimation of risk based on biological dosimetry for patients treated with radioiodine.

A multicentre study was undertaken to assess the cytogenetic damage to peripheral blood lymphocytes in 31 patients treated with 131I for thyrotoxicosis using the cytokinesis-blocked micronucleus assay. The results were compared to those for eight thyroid carcinoma patients using the same method. For each patient, blood samples were taken immediately before and 1 week after iodine administration. The first blood sample was divided into three fractions and each fraction was subsequently irradiated in vitro with 0, 0.5 and 1 Gy 60Co gamma rays, respectively. After blood culture for 70 h, cells were harvested, stained with Romanowsky-Giemsa and the micronuclei scored in 1000 binucleated cells. For both patient groups, a linear-quadratic dose-response curve was fitted through the data set of the first blood sample by a least squares analysis. The mean increase in micronuclei after 131I therapy (second blood sample) was fitted to this curve and the mean equivalent total body dose (ETBD) calculated. Surprisingly, in view of the large difference in administered activity between thyroid carcinoma patients and thyrotoxicosis patients, the increase in micronuclei after therapy (mean +/- S.D.: 32 +/- 30 and 32 +/- 23, respectively) and the equivalent total body dose (0.34 and 0.32 Gy, respectively) were not significantly different (P > 0.1). The small number of micronuclei induced by 131I therapy (32 +/- 29), compared with external beam radiotherapy for Hodgkins disease (640 +/- 381) or cervix carcinoma (298 +/- 76) [1], gave a cancer mortality estimate of less than 1%. This also explains why late detrimental effects in patients after 131I treatment have not been reported in the literature.

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.

Patient dosimetry for 131I-lipiodol therapy

Patient dosimetry data for intra-arterialiodine-131 lipiodol therapy for hepatocellular carcinoma (HCC) are scarce. The aim of this study was to determine the absorbed dose (D) to the tumour and healthy tissues, as well as the effective dose (E), by different methods for 17 therapies in 15 patients who received a mean activity of 1.9xa0GBq (SD 0.2) 131I-lipiodol. Eight patients received thyroid blocking by potassium iodide (KI). Patient dosimetry was performed based on bi-planar total body scans using the Monte Carlo simulation program MCNP-4B and the MIRDOSE-3 standard software program. CT images of each patient were used to determine liver and tumour volume and position. The total body dose to the patient was also determined by biological dosimetry with the in vitro micronucleus (MN) assay. From the increase in micronucleus yield after therapy, the equivalent total body dose (ETBD) was calculated. Results for D and E were comparable between MCNP and MIRDOSE (liver: mean 7.8xa0Gy, SD 1.8, lungs: 6.8xa0Gy, SD 2.9, E: 2.01xa0Gy, SD 0.58). MIRDOSE gave a systematic overestimation for the tumour dose, especially for tumours <3xa0cm (15%). The MCNP method is more accurate since the dose contributions from tumour to organs and vice versa can be accounted for. The absorbed dose to the thyroid was significantly lower for patients who received KI (7.2xa0Gy, SD 2.2) than for the other patients (13.8xa0Gy, SD 5.0). MN yields could be obtained for only 12 of the 17 therapies due to hypersplenism. A mean ETBD of 1.66xa0Gy (SD 0.73) was obtained, but the MN results showed no correlation between the ETBD and the total body dose values of the physical dosimetry. Also, in all except one of the patients, no further reduction in the number of thrombocytes was observed after therapy, probably due to the existing hypersplenism. It is concluded that in view of the high E values, patient dosimetry is necessary for patients receiving 131I-lipiodol therapy. Except in the case of the smaller tumours, comparable results were obtained with MCNP and MIRDOSE. Due to hypersplenism, biological dosimetry results based on the MN assay are not reliable.

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.

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.

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.

Patient dosimetry after 131I-MIBG therapy for neuroblastoma and carcinoid tumours

Aim The aim of the study was to determine the equivalent total body dose (ETBD) using the cytokinesis-blocked micronucleus assay in 22 131I-meta-iodobenzylguanidine (131I-MIBG) therapies (18 neuroblastoma, mean 5097 MBq, SD 1591; and four carcinoid tumours, mean 7681 MBq, SD 487). The results are correlated with the total body radiation dose according to the Medical Internal Radiation Dosimetry (MIRD) formalism. Methods For each patient, blood samples were taken immediately before and 1 week after 131I-MIBG therapy. The first blood sample was irradiated in vitro with 60Co γ-rays to determine the dose-response curve. Micronuclei were scored in 1000 binucleated cells. By using the dose-response curve the ETBD was derived from the increase in micronuclei after 131I-MIBG therapy (second blood sample). Based on three consecutive biplanar scans taken at 3, 6 and 9 days post-administration respectively, the total body dose following the MIRD formalism was calculated. Results The micronucleus assay was evaluable in only 14 out of 22 131I-MIBG therapies due to cell division inhibition caused by previous chemotherapy treatments and lymphocyte dilution due to blood transfusions given shortly after 131I-MIBG therapy. For these 14 therapies, the mean micronucleus yield after 131I-MIBG therapy was significantly increased (P<0.01) with a mean of 92 (SD 77) for neuroblastoma patients and with a mean of 35 (SD 8) for carcinoid patients. The increase observed in the present study is greater than previously observed after 131I therapy and 89Sr therapy but much lower than after external beam radiotherapy. For all patients treated with multiple therapies, the initial increase in micronucleus yield had at least partially recovered by the time of the next therapy. This might be explained by an increased turnover of lymphocytes. A mean ETBD of 0.95 Gy (SD 0.55) for neuroblastoma patients and a mean of 0.46 Gy (SD 0.09) for carcinoid patients was calculated. A reasonable correlation (R = 0.87) between the ETBD and the MIRD dose was obtained. The slope value of 0.75 can be explained by the low dose rate effect. Conclusions The observation in the present study of important inter-individual variability in the total body dose, with the possibility of high dose values, suggests the necessity of individual dosimetry when administering 131I-MIBG therapy, especially considering that generally more than one therapy is given to each patient.

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.