Accumulation of sublethal radiation damage and its effect on cell survival.

Objective.Determine the extent of sublethal radiation damage (SRD) in a cell population that received a given dose of radiation and the impact of this damage on cell survival.Approach.We developed a novel formalism to account for accumulation of SRD with increasing dose. It is based on a very general formula for cell survival that correctly predicts the basic properties of cell survival curves, such as the transition from the linear-quadratic to a linear dependence at high doses. Using this formalism we analyzed extensive experimental data for photons, protons and heavy ions to evaluate model parameters, quantify the extent of SRD and its impact on cell survival.Main results.Significant accumulation of SRD begins at doses below 1 Gy. As dose increases, so does the number of damaged cells and the amount of SRD in individual cells. SRD buildup in a cell increases the likelihood of complex irrepairable damage. For this reason, during a dose fraction delivery, each dose increment makes cells more radiosensitive. This gradual radosensitization is evidenced by the increasing slope of survival curves observed experimentally. It continues until the fraction is delivered, unless radiosensitivity reaches its maximum first. The maximum radiosensitivity is achieved when SRD accumulated in most cells is the maximum damage they can repair. After this maximum is reached, the slope of a survival curve, logarithm of survival versus dose, becomes constant, dose independent. The survival curve becomes a straight line, as experimental data at high doses show. These processes are random. They cause large cell-to-cell variability in the extent of damage and radiosensitivity of individual cells.Significance.SRD is in effect a radiosensitizer and its accumulation is a significant factor affecting cell survival, especially at high doses. We developed a novel formalism to study this phenomena and reported pertinent data for several particle types.

Monte Carlo evaluation of target dose coverage in lung stereotactic body radiation therapy with flattening filter-free beams.

Aim: Previous studies showed that replacing conventional flattened beams (FF) with flattening filter-free (FFF) beams improves the therapeutic ratio in lung stereotactic body radiation therapy (SBRT), but these findings could have been impacted by dose calculation uncertainties caused by the heterogeneity of the thoracic anatomy and by respiratory motion, which were particularly high for target coverage. In this study, we minimized such uncertainties by calculating doses using high-spatial-resolution Monte Carlo and four-dimensional computed tomography (4DCT) images. We aimed to evaluate more reliably the benefits of using FFF beams for lung SBRT. Materials and methods: For a cohort of 15 patients with early stage lung cancer that we investigated in a previous treatment planning study, we recalculated dose distributions with Monte Carlo using 4DCT images. This included fifteen FF and fifteen FFF treatment plans. Results: Compared to Monte Carlo, the treatment planning system (TPS) over-predicted doses in low-dose regions of the planning target volume. For most patients, replacing FF beams with FFF beams improved target coverage, tumor control, and uncomplicated tumor control probabilities. Conclusions: Monte Carlo tends to reveal deficiencies in target coverage compared to coverage predicted by the TPS. Our data support previously reported benefits of using FFF beams for lung SBRT.

Impact of Intra-Fractional Motion on Dose Distributions in Lung IMRT.

AIM: To investigate the impact of intra-fractional motion on dose distribution in patients treated with intensity-modulated radiation therapy (IMRT) for lung cancer. MATERIALS AND METHODS: Twenty patients who had undergone IMRT for non-small cell lung cancer were selected for this retrospective study. For each patient, a four-dimensional computed tomography (CT) image set was acquired and clinical treatment plans were developed using the average CT. Dose distributions were then re-calculated for each of the 10 phases of respiratory cycle and combined using deformable image registration to produce cumulative dose distributions that were compared with the clinical treatment plans. RESULTS: Intra-fractional motion reduced planning target volume (PTV) coverage in all patients. The median reduction of PTV volume covered by the prescription isodose was 3.4%; D98 was reduced by 3.1 Gy. Changes in the mean lung dose were within ±0.7 Gy. V20 for the lung increased in most patients; the median increase was 1.6%. The dose to the spinal cord was unaffected by intra-fractional motion. The dose to the heart was slightly reduced in most patients. The median reduction in the mean heart dose was 0.22 Gy, and V30 was reduced by 2.5%.The maximum dose to the esophagus was also reduced in most patients, by 0.74 Gy, whereas V50 did not change significantly. The median number of points in which dose differences exceeded 3%/3 mm was 6.2%. FINDINGS: Intra-fractional anatomical changes reduce PTV coverage compared to the coverage predicted by clinical treatment planning systems that use the average CT for dose calculation. Doses to organs at risk were mostly over-predicted.

On calculation of the average linear energy transfer for radiobiological modelling.

Applying the concept of linear energy transfer (LET) to modeling of biological effects of charged particles usually involves calculation of the average LET. To calculate this, the energy distribution of particles is characterized by either the source spectrum or fluence spectrum. Also, the average can be frequency-or dose-weighted. This makes four methods of calculating the average LET, each producing a different number. The purpose of this note is to describe which of these four methods is best suited for radiobiological modelling. We focused on data for photons (x-rays and gamma radiation) because in this case differences in the four averaging methods are most pronounced. However, our conclusions are equally applicable to photons and hadrons. We based our arguments on recently emerged Monte Carlo data that fully account for transport of electrons down to very low energies comparable to the ionization potential of water. We concluded that the frequency average LET calculated using the fluence spectrum has better predictive power than does that calculated using any of the other three options. This optimal method is not new but is different from those currently dominating research in this area.

Using FFF Beams to Improve the Therapeutic Ratio of Lung SBRT.

Aim: To investigate the extent to which lung stereotactic body radiotherapy (SBRT) treatment plans can be improved by replacing conventional flattening filter (FF) beams with flattening filter-free (FFF) beams. Material and Methods: We selected 15 patients who had received SBRT with conventional 6-MV photon beams for early-stage lung cancer. We imported the patients' treatment plans into the Eclipse 13.6 treatment planning system, in which we configured the AAA dose calculation model using representative beam data for a TrueBeam accelerator operated in 6-MV FFF mode. We then created new treatment plans by replacing the conventional FF beams in the original plans with FFF beams. Results: The FFF plans had better target coverage than the original FF plans did. For the planning target volume, FFF plans significantly improved the D98, D95, D90, homogeneity index, and uncomplicated tumor control probability. In most cases, the doses to organs at risk were lower in FFF plans. FFF plans significantly reduced the mean lung dose, V10, V20, V30, and normal tissue complication probability for the total lung and improved the dosimetric indices for the ipsilateral lung. For most patients, FFF beams achieved lower maximum doses to the esophagus, heart, and the spinal cord; and a lower chest wall V30. Findings: Compared with FF beams, FFF beams achieved lower doses to organs at risk, especially the lung, without compromising tumor coverage; in fact, FFF beams improved coverage in most cases. Thus, replacing FF beams with FFF beams can achieve a better therapeutic ratio.

A simple model for calculating relative biological effectiveness of X-rays and gamma radiation in cell survival.

OBJECTIVES: The relative biological effectiveness (RBE) of X-rays and γ radiation increases substantially with decreasing beam energy. This trend affects the efficacy of medical applications of this type of radiation. This study was designed to develop a model based on a survey of experimental data that can reliably predict this trend. METHODS: In our model, parameters α and ß of a cell survival curve are simple functions of the frequency-average linear energy transfer (LF) of delta electrons. The choice of these functions was guided by a microdosimetry-based model. We calculated LF by using an innovative algorithm in which LF is associated with only those electrons that reach a sensitive-to-radiation volume (SV) within the cell. We determined model parameters by fitting the model to 139 measured (α,ß) pairs. RESULTS: We tested nine versions of the model. The best agreement was achieved with [Formula: see text] and ß being linear functions of [Formula: see text] .The estimated SV diameter was 0.1-1 µm. We also found that α, ß, and the α/ß ratio increased with increasing [Formula: see text] . CONCLUSIONS: By combining an innovative method for calculating [Formula: see text] with a microdosimetric model, we developed a model that is consistent with extensive experimental data involving photon energies from 0.27 keV to 1.25 MeV. ADVANCES IN KNOWLEDGE: We have developed a photon RBE model applicable to an energy range from ultra-soft X-rays to megaelectron volt γ radiation, including high-dose levels where the RBE cannot be calculated as the ratio of α values. In this model, the ionization density represented by [Formula: see text] determines the RBE for a given photon spectrum.

AAPM Task Group 329: Reference dose specification for dose calculations: Dose-to-water or dose-to-muscle?

Linac calibration is done in water, but patients are comprised primarily of soft tissue. Conceptually, and specified in NRG/RTOG trials, dose should be reported as dose-to-muscle to describe the dose to the patient. Historically, the dose-to-water of the linac calibration was often converted to dose-to-muscle for patient calculations through manual application of a 0.99 dose-to-water to dose-to-muscle correction factor, applied during the linac clinical reference calibration. However, many current treatment planning system (TPS) dose calculation algorithms approximately provide dose-to-muscle (tissue), making application of a manual scaling unnecessary. There is little guidance on when application of a scaling factor is appropriate, resulting in highly inconsistent application of this scaling by the community. In this report we provide guidance on the steps necessary to go from the linac absorbed dose-to-water calibration to dose-to-muscle in patient, for various commercial TPS algorithms. If the TPS does not account for the difference between dose-to-water and dose-to-muscle, then TPS reference dose scaling is warranted. We have tabulated the major vendors' TPS in terms of whether they approximate dose-to-muscle or calculate dose-to-water and recommend the correction factor required to report dose-to-muscle directly from the TPS algorithm. Physicists should use this report to determine the applicable correction required for specifying the reference dose in their TPS to achieve this goal and should remain attentive to possible changes to their dose calculation algorithm in the future.

Systematic microdosimetric data for protons of therapeutic energies calculated with Geant4-DNA.

The purpose of this study was to generate physical data needed for microdosimetry-based models of proton RBE. Our focus was on the frequency and dose average lineal energies, y  F and y  D . We report data for proton energies from 0.1 to 100 MeV, for spherical volumes 2-103 nm in diameter. These data were calculated using Geant4-DNA Monte Carlo software. The physics implemented in Geant4-DNA has been extensively tested for this type of calculations but data on y  F and y  D for protons generated with this code have been very limited. An innovative aspect of our study is that we introduced a straightforward procedure for calculation of y  F and y  D for polyenergetic beams and presented the data in a format that simplifies these calculations. We compared our data with previous studies that used different Monte Carlo codes and with experimental data.

Analysis of histone ubiquitylation by MSL1/MSL2 proteins in vitro.

Histone posttranslational modifications (PTM) control gene activity by targeting chromatin-regulatory proteins. By altering histone charges PTMs could also modulate inter- and intra-nucleosomal interactions, and thus affect chromatin high-order compaction and nucleosome stochastic folding, respectively. However, recently it has been shown that histone H2BK34- ubiquitylation (which is deposited in vivo by MOF-MSL) can destabilize one of the nucleosomal H2A-H2B dimers in symmetrically and (albeit to a lesser extend) asymmetrically modified nucleosomes, and thus promote formation of a hexasome particle. Here we have studied ubiquitylation patterns by purified MSL1/MSL2 using nucleosomes and different histone substrates. We have shown that H2B-ubiquitylation by MSL1/2 depends on substrate configuration. In addition, MSL1/2 efficiently ubiquitylate histone substrates but very poorly modify nucleosomes, which implies a requirement for nucleosome structural alteration for efficient ubiquitylation of H2BK34. Nucleosome modification by MSL1/MSL2 in vitro was analyzed directly using nucleosome gel-mobility shift assay, which suggested that MSL1/2 can deposit two ubiquitin moieties in one nucleosome.

Radiotherapy of lung cancers: FFF beams improve dose coverage at tumor periphery compromised by electronic disequilibrium.

The purpose of this work was to investigate radiotherapy underdosing at the periphery of lung tumors, and differences in dose for treatments delivered with flattening filter-free (FFF) beams and with conventional flattened (FF) beams. The true differences between these delivery approaches, as assessed with Monte Carlo simulations, were compared to the apparent differences seen with clinical treatment planning algorithms AAA and Acuros XB. Dose was calculated in a phantom comprised of a chest wall, lung parenchyma, and a spherical tumor (tested diameters: 1, 3, and 5 cm). Three lung densities were considered: 0.26, 0.2, and 0.1 g cm-3, representing normal lung, lung at full inspiration, and emphysematous lung, respectively. The dose was normalized to 50 Gy to the tumor center and delivered with 7 coplanar, unmodulated 6 MV FFF or FF beams. Monte Carlo calculations used EGSnrc and phase space files for the TrueBeam accelerator provided by Varian Medical Systems. Voxel sizes were 0.5 mm for the 1 cm tumor and 1 mm for the larger tumors. AAA and Acuros XB dose calculations were performed in Eclipse™ with a 2.5 mm dose grid, the resolution normally used clinically. Monte Carlo dose distributions showed that traditional FF beams underdosed the periphery of the tumor by up to ~2 Gy as compared to FFF beams; the latter provided a more uniform dose throughout the tumor. In all cases, the underdosed region was a spherical shell about 5 mm thick around the tumor and extending into the tumor by 2-3 mm. The effect was most pronounced for smaller tumors and lower lung densities. The underdosing observed with conventional FF beams was not captured by the clinical treatment planning systems. We concluded that FFF beams mitigate dose loss at tumor periphery and current clinical practice fails to capture tumor periphery underdosing and possible ways to mitigate it.

Average stopping powers for electron and photon sources for radiobiological modeling and microdosimetric applications.

This study concerns calculation of the average electronic stopping power for photon and electron sources. It addresses two problems that have not yet been fully resolved. The first is defining the electron spectrum used for averaging in a way that is most suitable for radiobiological modeling. We define it as the spectrum of electrons entering the sensitive to radiation volume (SV) within the cell nucleus, at the moment they enter the SV. For this spectrum we derive a formula that combines linearly the fluence spectrum and the source spectrum. The latter is the distribution of initial energies of electrons produced by a source. Previous studies used either the fluence or source spectra, but not both, thereby neglecting a part of the complete spectrum. Our derived formula reduces to these two prior methods in the case of high and low energy sources, respectively. The second problem is extending electron spectra to low energies. Previous studies used an energy cut-off on the order of 1 keV. However, as we show, even for high energy sources, such as 60Co, electrons with energies below 1 keV contribute about 30% to the dose. In this study all the spectra were calculated with Geant4-DNA code and a cut-off energy of only 11 eV. We present formulas for calculating frequency- and dose-average stopping powers, numerical results for several important electron and photon sources, and tables with all the data needed to use our formulas for arbitrary electron and photon sources producing electrons with initial energies up to ∼1 MeV.

A new formalism for modelling parameters α and ß of the linear-quadratic model of cell survival for hadron therapy.

We propose a new formalism for calculating parameters α and ß of the linear-quadratic model of cell survival. This formalism, primarily intended for calculating relative biological effectiveness (RBE) for treatment planning in hadron therapy, is based on a recently proposed microdosimetric revision of the single-target multi-hit model. The main advantage of our formalism is that it reliably produces α and ß that have correct general properties with respect to their dependence on physical properties of the beam, including the asymptotic behavior for very low and high linear energy transfer (LET) beams. For example, in the case of monoenergetic beams, our formalism predicts that, as a function of LET, (a) α has a maximum and (b) the α/ß ratio increases monotonically with increasing LET. No prior models reviewed in this study predict both properties (a) and (b) correctly, and therefore, these prior models are valid only within a limited LET range. We first present our formalism in a general form, for polyenergetic beams. A significant new result in this general case is that parameter ß is represented as an average over the joint distribution of energies E 1 and E 2 of two particles in the beam. This result is consistent with the role of the quadratic term in the linear-quadratic model. It accounts for the two-track mechanism of cell kill, in which two particles, one after another, damage the same site in the cell nucleus. We then present simplified versions of the formalism, and discuss predicted properties of α and ß. Finally, to demonstrate consistency of our formalism with experimental data, we apply it to fit two sets of experimental data: (1) α for heavy ions, covering a broad range of LETs, and (2) ß for protons. In both cases, good agreement is achieved.

Radial dose distributions from carbon ions of therapeutic energies calculated with Geant4-DNA.

We report on radial dose distributions [Formula: see text] for carbon ions calculated with Geant4-DNA code. These distributions characterize ion tracks on a nanoscale and are important for understanding the biological effects of ion beams. We present data for carbon ion beams in the energy range from 20 to 400 MeV u-1. To approximate the Monte Carlo results, we developed a simple formula that combines the well-known inverse square distance dependence with a factor correcting [Formula: see text] for small [Formula: see text]. The proposed formula can be used to calculate [Formula: see text] for any energy within the above range and for distances [Formula: see text] from 1 nm to 2 µm with a maximum error not exceeding 14%. This range of distances corresponds to a dose range of over seven orders of magnitude. Differences between our results and those of previously published analytical models are discussed.

Reducing the cost of proton radiation therapy: the feasibility of a streamlined treatment technique for prostate cancer.

Proton radiation therapy is an effective modality for cancer treatments, but the cost of proton therapy is much higher compared to conventional radiotherapy and this presents a formidable barrier to most clinical practices that wish to offer proton therapy. Little attention in literature has been paid to the costs associated with collimators, range compensators and hypofractionation. The objective of this study was to evaluate the feasibility of cost-saving modifications to the present standard of care for proton treatments for prostate cancer. In particular, we quantified the dosimetric impact of a treatment technique in which custom fabricated collimators were replaced with a multileaf collimator (MLC) and the custom range compensators (RC) were eliminated. The dosimetric impacts of these modifications were assessed for 10 patients with a commercial treatment planning system (TPS) and confirmed with corresponding Monte Carlo simulations. We assessed the impact on lifetime risks of radiogenic second cancers using detailed dose reconstructions and predictive dose-risk models based on epidemiologic data. We also performed illustrative calculations, using an isoeffect model, to examine the potential for hypofractionation. Specifically, we bracketed plausible intervals of proton fraction size and total treatment dose that were equivalent to a conventional photon treatment of 79.2 Gy in 44 fractions. Our results revealed that eliminating the RC and using an MLC had negligible effect on predicted dose distributions and second cancer risks. Even modest hypofractionation strategies can yield substantial cost savings. Together, our results suggest that it is feasible to modify the standard of care to increase treatment efficiency, reduce treatment costs to patients and insurers, while preserving high treatment quality.

Radial dose distributions from protons of therapeutic energies calculated with Geant4-DNA.

Models based on the amorphous track structure approximation have been successful in predicting the biological effects of heavy charged particles. Development of such models remains an active area of research that includes applications to hadrontherapy. In such models, the radial distribution of the dose deposited by delta electrons and directly by the particle is the main characteristic of track structure. We calculated these distributions with Geant4-DNA Monte Carlo code for protons in the energy range from 10 to 100 MeV. These results were approximated by a simple formula that combines the well-known inverse square distance dependence with two factors that eliminate the divergence of the radial dose integral at both small and large distances. A clear physical interpretation is given to the asymptotic behaviour of the radial dose distribution resulting from these two factors. The proposed formula agrees with the Monte Carlo data within 10% for radial distances of up to 10 µm, which corresponds to a dose range covering over eight orders of magnitude. Differences between our results and those of previously published analytical models are discussed.

Remodeling of nucleosome-dimer particles with yIsw2 promotes their association with ALL-1 SET domain in vitro.

Functioning of histone lysine methyltransferases (HKMTs) involves interactions of their catalytic domain "SET" with the N-termini of histone H3. However, these interactions are restricted in canonical nucleosomes due to the limited accessibility of H3 termini. Here we investigated whether nucleosome remodeling with the yeast Isw2 affects nucleosome affinity to the SET domain of ALL-1 HKMT. Reconstitution of mononucleosomes by salt dilutions also produces some nucleosome-dimer particles (self-associated mononucleosomes, described by: Tatchell and van Holde (1977) Biochemistry, 16, 5295-5303). The GST-tagged SET-domain polypeptide of ALL-1 was assayed for binding to assembled mononucleosomes and nucleosome-dimer particles, either intact or remodeled with purified yeast Isw2. Remodeling of mononucleosomes does not noticeably affect their affinity to SET domain; however, yIsw2 remodeling of nucleosome-dimer particles facilitated their association with GST-SET polypeptide. Therefore, it is conceivable that nucleosome interactions in trans could be implicated in the maintenance of chromatin methylation patterns in vivo.

Electron slowing-down spectra in water for electron and photon sources calculated with the Geant4-DNA code.

Recently, a very low energy extension was added to the Monte Carlo simulation toolkit Geant4. It is intended for radiobiological modeling and is referred to as Geant4-DNA. Its performance, however, has not been systematically benchmarked in terms of transport characteristics. This study reports on the electron slowing-down spectra and mean energy per ion pair, the W-value, in water for monoenergetic electron and photon sources calculated with Geant4-DNA. These quantities depend on electron energy, but not on spatial or angular variables which makes them a good choice for testing the model of energy transfer processes. The spectra also have a scientific value for radiobiological modeling as they describe the energy distribution of electrons entering small volumes, such as the cell nucleus. Comparisons of Geant4-DNA results with previous studies showed overall good agreement. Some differences in slowing-down spectra between Geant4-DNA and previous studies were found at 100 eV and at approximately 500 eV that were attributed to approximations in models of vibrational excitations and atomic de-excitation after ionization by electron impact. We also found that the high-energy part of the Geant4-DNA spectrum for a 1 keV electron source was higher, and the asymptotic high-energy W-value was lower than previous studies reported.

Formulation of the multi-hit model with a non-Poisson distribution of hits.

PURPOSE: We proposed a formulation of the multi-hit single-target model in which the Poisson distribution of hits was replaced by a combination of two distributions: one for the number of particles entering the target and one for the number of hits a particle entering the target produces. Such an approach reflects the fact that radiation damage is a result of two different random processes: particle emission by a radiation source and interaction of particles with matter inside the target. METHODS AND MATERIALS: Poisson distribution is well justified for the first of the two processes. The second distribution depends on how a hit is defined. To test our approach, we assumed that the second distribution was also a Poisson distribution. The two distributions combined resulted in a non-Poisson distribution. We tested the proposed model by comparing it with previously reported data for DNA single- and double-strand breaks induced by protons and electrons, for survival of a range of cell lines, and variation of the initial slopes of survival curves with radiation quality for heavy-ion beams. RESULTS: Analysis of cell survival equations for this new model showed that they had realistic properties overall, such as the initial and high-dose slopes of survival curves, the shoulder, and relative biological effectiveness (RBE) In most cases tested, a better fit of survival curves was achieved with the new model than with the linear-quadratic model. The results also suggested that the proposed approach may extend the multi-hit model beyond its traditional role in analysis of survival curves to predicting effects of radiation quality and analysis of DNA strand breaks. CONCLUSIONS: Our model, although conceptually simple, performed well in all tests. The model was able to consistently fit data for both cell survival and DNA single- and double-strand breaks. It correctly predicted the dependence of radiation effects on parameters of radiation quality.

Dosimetric impact of fiducial markers in patients undergoing photon beam radiation therapy.

Fiducial markers are widely used in image-guided radiation therapy to correct for setup error and organ motion. These markers, however, can cause dose perturbations in the target volume for patients undergoing external-beam radiation therapy. The goal of this study was to determine the dosimetric impact of various types of fiducial markers commonly used in patients receiving photon radiation therapy. Monte Carlo simulations based on a newly developed EGSnrcMP user code were used to investigate three types of gold fiducial markers and a carbon marker. A single photon field with each fiducial in various orientations and two parallel-opposed beams were simulated at 6-MV and 18-MV energies. The results indicated that dose perturbations depended on marker size, material, and orientation, as well as on incident beam energy. Maximum dose perturbations were found for a single 6-MV beam. The increase in dose reached a factor of 1.58 near the upstream surface of the gold marker because of electron backscatter. At the downstream surface, the dose was reduced to a factor of 0.53 at the same point without the marker. For the 18-MV beam, the maximum dose factor was 1.48 and the minimum dose factor was 0.66. For the two parallel-opposed beams, the maximum dose reduction was within 5% at 6 MV and 2% at 18 MV. Dose enhancement, however, remained significant, reaching factors of 1.20 and 1.33 for the two energies near the fiducial surface. Carbon fiducials caused dose perturbations of only ~1%.

Displacement of periurethral stranded seeds and its dosimetric consequences in prostate brachytherapy.

PURPOSE: The use of stranded seeds for prostate brachytherapy has raised concern that displacement of strands, particularly in the periurethral region, may result in inadequate coverage of the prostate. We sought here to evaluate the displacement of periurethral stranded seeds after a prostate brachytherapy implant (Day 0) and its dosimetric consequences 1 month later (Day 30). METHODS AND MATERIALS: Subjects were 10 consecutive patients who underwent implantation with (125)I stranded seeds via a peripheral-loading technique. Computed tomography scanning was done on Days 0 and 30. Seeds were located and dose distributions calculated with a Variseed 7.2 treatment planning system (Varian Medical Systems). Images were registered by two methods, one using the penile bulb as reference and the other using the pubic bones for verification. Only seeds within the periurethral strands were analyzed. RESULTS: The mean displacement of periurethral stranded seeds relative to the prostate did not exceed 1mm in any direction. Calculated displacements were not affected by the registration method used. The mean dose covering 90% of the prostate volume (D(90)) and prostate volume receiving 100% of the prescribed dose (V(100)) were 169Gy and 97% on Day 0 and 186.5Gy and 98.7% on Day 30 (p<0.001 for D(90)). CONCLUSIONS: Displacement of periurethral stranded seeds 30 days after implantation was minimal and did not compromise dosimetric coverage of the prostate.