Optimization of 3D conformal electron beam therapy in inhomogeneous media by concomitant fluence and energy modulation

The possibilities of using simultaneous fluence and energy modulation techniques in electron beam therapy to shape the dose distribution and almost eliminate the influences of tissue inhomogeneities have been investigated. By using a radiobiologically based optimization algorithm the radiobiological properties of the tissues can be taken into account when trying to find the best possible dose delivery. First water phantoms with differently shaped surfaces were used to study the effect of surface irregularities. We also studied water phantoms with internal inhomogeneities consisting of air or cortical bone. It was possible to improve substantially the dose distribution by fluence modulation in these cases. In addition to the fluence modulation the most suitable single electron energy in each case was also determined. Finally, the simultaneous use of several preselected electron beam energies was also tested, each with an individually optimized fluence profile. One to six electron energies were used, resulting in a slow improvement in complication-free cure with increasing number of beam energies. To apply these techniques to a more clinically relevant situation a post-operative breast cancer patient was studied. For simplicity this patient was treated with only one anterior beam portal to clearly illustrate the effect of inhomogeneities like bone and lung on the dose distribution. It is shown that by using fluence modulation the influence of dose inhomogeneities can be significantly reduced. When two or more electron beam energies with individually optimized fluence profiles are used the dose conformality to the internal target volume is further increased, particularly for targets with complex shapes.     

Monte Carlo method to study the proton fluence for treatment planning

The proton beam at the Hahn Meitner Institute (HMI) in Berlin will be used for proton therapy of eye melanoma in the near future. As part of the pre-therapeutic studies, Monte Carlo calculations have been performed to investigate the primary fluence distribution of the proton beam including the influence of scattering foils, range shifters, modulator wheels, and collimators. Any material in the beam path will modify the therapeutic beam because of energy loss, multiple scattering, range straggling, and nuclear reactions. The primary fluence information is a pre-requisite for most pencil-beam treatment planning algorithms. The measured beam penumbra has been used as one of the parameters to characterize a proton beam for further calculations in a treatment planning algorithm. However, this phenomenological quantity represents only indirect information about the properties of the proton beam. In this work, an alternative parameterization of the beam exiting the vacuum window of the accelerator, as well as the beam right in front of the patient collimator, is introduced. A beam is fully characterized if one knows (for instance from Monte Carlo simulations) the particle distribution in energy, position, and angle, i.e., the phase space distribution. Therefore, parameters derived from this distribution can provide an alternative input in treatment planning algorithms. In addition, the method of calculation is introduced as a tool to investigate the influence of modifications in the beam delivery system on the behavior of the therapeutic proton beam.     

Tomotherapeutic portal imaging for radiation treatment verification

In their tomotherapy concept Mackie and co-workers proposed not only a new technique for IMRT but also an appropriate and satisfactory method of treatment verification. This method allows both monitoring of the portal dose distribution and imaging of the patient anatomy during treatment by means of online CT. This would enable the detection of inaccuracies in dose delivery and patient set-up errors. In this paper results are presented showing that a single electronic portal imaging device (EPID) could deliver all data necessary to establish such a complete verification system for tomotherapy and even other IMRT techniques. Consequently it has to be shown that it is able to record both the low-intensity photon fluences encountered in tomographic imaging and the intense photon transmission of each treatment field. The detector under investigation is a video-based EPID, the BIS 710 (manufactured by Wellh?fer Dosimetrie, Schwarzenbruck, Germany). To examine the suitability of the BIS for CT at 6 MV beam quality, different phantoms were scanned and reconstructed. The agreement between a diamond detector and BIS responses is quantitative. Tomographic reconstruction of a complete set of these transmission profiles resulted in images which resolve 3 cm large objects having a (theoretical) contrast to water of less than 9%. Three millimetre objects with a 100% contrast are clearly visible. The BIS signal was shown to measure photon fluence distributions. The reconstructed images possess a spatial and contrast resolution sufficient for accurate imaging of the patient anatomy, needed for treatment verification in many clinical cases.     

Intensity modulation with electrons: calculations, measurements and clinical applications

Intensity modulation of electron beams is one step towards truly conformal therapy. This can be realized with the MM50 racetrack microtron that utilizes a scanning beam technique. By adjusting the scan pattern it is possible to obtain arbitrary fluence distributions. Since the monitor chambers in the treatment head are segmented in both x- and y-directions it is possible to verify the fluence distribution to the patient at any time during the treatment. Intensity modulated electron beams have been measured with film and a plane parallel chamber and compared with calculations. The calculations were based on a pencil beam method. An intensity distribution at the multileaf collimator (MLC) level was calculated by superposition of measured pencil beams over scan patterns. By convolving this distribution with a Gaussian pencil beam, which has propagated from the MLC to the isocentre, a fluence distribution at isocentre level was obtained. The agreement between calculations and measurements was within 2% in dose or 1 mm in distance in the penumbra zones. A standard set of intensity modulated electron beams has been developed. These beams have been implemented in a treatment planning system and are used for manual optimization. A clinical example (prostate) of such an application is presented and compared with a standard irradiation technique.     

Monte Carlo calculation of dose enhancement by neutron capture of 10B in fast neutron therapy

Since 1978 the Essen Medical Cyclotron Facility has been used for fast neutron therapy. The treatment of deep-seated tumours by d(14) + Be neutron beam therapy (mean energy = 5.8 MeV) is still limited because of the steep decrease in depth-dose distribution. The interactions of fast neutrons in tissue leads to a thermal neutron distribution. These partially thermalized neutrons can be used to produce neutron capture reactions with 10B. Thus incorporation of 10B in tumours treated with fast neutrons will increase the relative local tumour dose due to the reaction 10B (n, alpha) 7Li. The magnitude of dose enhancement by 10B depends on the distribution of the thermal neutron fluence, 10B concentration, field size of the neutron beam, beam energy and the specific phantom geometry. The slowing down of the fast neutrons, resulting in a thermal neutron distribution in a phantom, has been computed using a Monte Carlo model. This model, which includes a deep-seated tumour, was experimentally verified by measurements of the thermal neutron fluence rate in a phantom using neutron activation of gold foil. When non-boronated water phantoms were irradiated with a total dose of 1 Gy at a depth of 6 cm, the thermal fluencies at this depth were found to be 2 x 10(10) cm-2. The absorbed dose in a tumour with 100 ppm 10B, at the same depth, was enhanced by 15%.     

On compensator design for photon beam intensity-modulated conformal therapy

Recently the compensator has been shown to be an in expensive and reliable dose delivery device for photon beam intensity-modulated radiation therapy (IMRT). The goal of IMRT compensator design is to produce an optimized primary fluence profile at the patient's surface obtained from the optimization procedure. In this paper some of the problems associated with IMRT compensator design, specifically the beam perturbations caused by the compensator, are discussed. A simple formula is derived to calculate the optimal compensator thickness profile from an optimized primary fluence profile. The change of characteristics of a 6 MV beam caused by the introduction of cerrobend compensators in the beam is investigated using OMEGA Monte Carlo codes. It is found that the compensator significantly changes the energy spectrum and the mean energy of the primary photons at the patient's surface. However, beam hardening does not have as significant an effect on the percent depth dose as it does on the energy spectrum. We conclude that in most situations the beam hardening effect can be ignored during compensator design and dose calculation. The influence of the compensator on the contaminant electron buildup dose is found to be small and independent of the compensator thickness of interest. Therefore, it can be ignored in the compensator design and included as a correction into the final dose distribution. The scattered photons from the compensator are found to have no effect on the surface dose. These photons produce a uniform low fluence distribution at the patient's surface, which is independent of compensator shape. This is also true for very large fields and extremely asymmetric and nonuniform compensator thickness profiles. Compared to the primary photons, the scattered photons have much larger angular spread and similar energy spectrum at the patient's surface. These characteristics allow the compensator thickness profile and the dose distribution to be calculated from the optimized fluence profile of primary photons, without considering the scattered photons.     

A three-dimensional algorithm for optimizing beam weights and wedge filters

An essential step towards optimizing and automating radiation therapy treatment planning is to develop an effective algorithm to find the optimal beam weights and wedge filters for a given set of beam directions and modalities. This problem is solved by introducing a variable transformation based on the universal and omni wedge principles. Instead of directly optimizing an objective function with respect to wedge angles and orientations, each field is first decomposed into a superposition of an open field and two orthogonal wedged fields. This transforms the problem of finding J beam weights, wedge angles, and orientations to that of optimizing a system with 3J beam weights (J open beams and 2J nominal wedged beams), where J is the total number of incident beam directions. An iterative algorithm based on a method originally developed for image reconstruction is used to find the 3J beam weights. The technique is applied to a few clinical cases. Treatment plans are improved compared to those obtained through the conventional manual trial and error planning process. In addition, planning time and effort are greatly reduced.     

A totally integrated simulation technique for three-field breast treatment using a CT simulator

A method was devised to simulate patients with breast cancer in the actual treatment position utilizing a diagnostic CT spiral scanner, 3-D Image Workstation for virtual simulation, and a laser coordinate system to transfer planning parameters to the patient's skin. It was desired to produce non-divergent tangential beams through the lung as well as a matched line for tangential and supraclavicular fields. The patients were immobilized in an Alpha CradleTM cast. Radio-opaque markers were placed on the superior, inferior, medial, and lateral margins of the field so as to afford appropriate initial field set-up approximations. The patient was scanned. The data set was then transferred to the workstation where an isocenter was chosen. The patient was marked. Virtual simulation was then performed. This method employed a half beam technique for the posterior edge of the tangential fields. Table rotation and blocking of the superior margin of the tangential fields were used to produce a vertical edge to match a supraclavicular field. Using a beam's eye view the lateral tangent was matched to the medial exit. A digitally reconstructed radiograph was created to define the tangent fields and place the supraclavicular block. Our initial experience with 50 patients verifies that this is a reproducible and accurate technique. Time required for immobilization and tangential field simulation is approximately 30 minutes. Data is available for 3-D treatment planning or 2-D treatment planning on a reconstructed transverse slice angled to match the collimator angle through the patient. Using a CT simulator for simulation of breast cancer affords accuracy of at least equal magnitude to conventional simulators as determined by beam films and ease of set-up. This technique also affords greater ease in changing treatment parameters without having to resimulate the patient.     

Combined experimental and Monte Carlo verification of 137Cs brachytherapy plans for vaginal applicators

Dose rates in a phantom around a shielded and an unshielded vaginal applicator containing Selectron low-dose-rate 137Cs sources were determined by experiment and Monte Carlo simulation. Measurements were performed with thermoluminescent dosimeters in a white polystyrene phantom using an experimental protocol geared for precision. Calculations for the same set-up were done using a version of the EGS4 Monte Carlo code system modified for brachytherapy applications into which a new combinatorial geometry package developed by Bielajew was recently incorporated. Measured dose rates agree with Monte Carlo estimates to within 5% (1 SD) for the unshielded applicator, while highlighting some experimental uncertainties for the shielded applicator. Monte Carlo calculations were also done to determine a value for the effective transmission of the shield required for clinical treatment planning, and to estimate the dose rate in water at points in axial and sagittal planes transecting the shielded applicator. Comparison with dose rates generated by the planning system indicates that agreement is better than 5% (1 SD) at most positions. The precision thermoluminescent dosimetry protocol and modified Monte Carlo code are effective complementary tools for brachytherapy applicator dosimetry.     

Negative regulation of the anti-human immunodeficiency virus and chemotactic activity of human stromal cell-derived factor 1alpha by CD26/dipeptidyl peptidase IV

A method to characterize the energy distribution in the whole photon field is valuable when designing an accelerator for choosing target and flattening filter or scan pattern. Another field of application is beam characterization for treatment planning systems or other dosimetric purposes. This work is focused on the energy distribution in different 50 MV bremsstrahlung beams with different scanning of electrons on three different targets. Fluence differential in energy and angle at the exit of each target has been determined by Monte Carlo calculations for a narrow beam. Data for broad beams were obtained by convolution of the narrow beams with different scan patterns. Photon energy fluence differential in energy at SSD 100 were thus found to be rather different for the targets studied. The results are presented as mean energy profiles and narrow beam half-value layer (HVL) in water. Two different experimental setups were used to measure HVL at the central axis and at off-axis positions. The two methods gave results which differ by 5%-6% and the calculated data where within these experimental results. In conclusion, the presented method for characterization of the photon field energy distribution is well within the experimental results and can thus be used to improve accelerator design or dosimetric calculations, e.g., for treatment planning.     

An optimized leaf-setting algorithm for beam intensity modulation using dynamic multileaf collimators

A leaf-setting algorithm is developed for generating arbitrary beam intensity profiles in discrete levels using dynamic multileaf collimators (DMLCs). The algorithm starts with the algebraic expression for the area under the beam profile. It is shown that the coefficients in this expression can be transformed into the specifications for the leaf-setting sequence. It is proven that the algorithm optimizes beam delivery time and total monitor units for the DMLC leaf setting for intensity modulated radiotherapy (IMRT). The algorithm is demonstrated to be applicable to both the 'step-and-shoot' and 'dynamic' type of beam delivery. The graphical interpretation and numerical implementation scheme of the algorithm is illustrated using a simplified example.     

A new genetic algorithm technique in optimization of permanent 125I prostate implants

Real time optimized treatment planning at the time of the implant is desirable for ultrasound-guided transperineal 125I permanent prostate implants. Currently available optimization algorithms are too slow to be used in the operating room. The goal of this work is to develop a robust optimization algorithm, which is suitable for such application. Three different genetic algorithms (sGA, sureGA and securGA) were developed and compared in terms of the number of function evaluations and the corresponding fitness. The optimized dose distribution was achieved by searching the best seed distribution through the minimization of a cost function. The cost function included constraints on the periphery dose of the planned target volume, the dose uniformity within the target volume, and the dose to the critical structure. Adjustment between the peripheral dose, the dose uniformity and critical structure dose can be achieved by varying the weighting factors in the cost function. All plans were evaluated in terms of the dose nonuniformity ratio, the conformation number and the dose volume histograms. Among these three GA algorithms, the securGA provided the best performance. Within 2500 function evaluations, the near optimum results were obtained. For a large target volume (5 cm x 4 cm x 4.5 cm) including urethra with 20 needles, the computer time needed for the optimization was less than 5 min on a HP735 workstation. The results showed that once the best set of parameters was found, they were applicable for all sizes of prostate volume. For a fixed needle geometry, the optimized plan showed much better dose distribution than that of nonoptimized plan. If the critical structure was considered in the optimization, the dose to the critical structure could be minimized. In the cases of irregular and skewed needle geometry, the optimized treatment plans were almost as good as ideal needle geometry. It is concluded that this new genetic algorithm (securGA) allows for an efficient and rapid optimization of dose distribution, which is suitable for real time treatment planning optimization for ultrasound-guided prostate implant.     

Optimizer convergence and local minima errors and their clinical importance

Two of the errors common in the inverse treatment planning optimization have been investigated. The first error is the optimizer convergence error, which appears because of non-perfect convergence to the global or local solution, usually caused by a non-zero stopping criterion. The second error is the local minima error, which occurs when the objective function is not convex and/or the feasible solution space is not convex. The magnitude of the errors, their relative importance in comparison to other errors as well as their clinical significance in terms of tumour control probability (TCP) and normal tissue complication probability (NTCP) were investigated. Two inherently different optimizers, a stochastic simulated annealing and deterministic gradient method were compared on a clinical example. It was found that for typical optimization the optimizer convergence errors are rather small, especially compared to other convergence errors, e.g., convergence errors due to inaccuracy of the current dose calculation algorithms. This indicates that stopping criteria could often be relaxed leading into optimization speed-ups. The local minima errors were also found to be relatively small and typically in the range of the dose calculation convergence errors. Even for the cases where significantly higher objective function scores were obtained the local minima errors were not significantly higher. Clinical evaluation of the optimizer convergence error showed good correlation between the convergence of the clinical TCP or NTCP measures and convergence of the physical dose distribution. On the other hand, the local minima errors resulted in significantly different TCP or NTCP values (up to a factor of 2) indicating clinical importance of the local minima produced by physical optimization.     

Economic Transmission Planning Model Suitable for a Regulated Network Service Provider

Conventional transmission planning models are subject to constant debate in the context of competitive markets, due to the functional unbundling of transmission sector from generation and distribution sectors and due to the new environment regulations. A value-based transmission planning model is proposed, suitable for an unbundled transmission network service provider having no assets in the generation sector. The model minimizes the long-term transmission investment costs and the expected social costs incurred to its clients, energy producers, and consumers, in the power auctions due to transmission bottlenecks. The uncertainties involved when incorporating short-term market models into long-term planning models are modeled with probabilistic representations for the bid prices, the component availabilities, and the hourly load variations. These features make this model suitable in the new environment paradigm. Generalized Benders decomposition technique with nonsequential Monte Carlo technique is employed to solve the final stochastic mixed-integer optimization model. Case studies are given to illustrate the performance of this model by implementing it in the modified Garver’s six-bus test system and the IEEE 24-bus reliability test system for a single planning year.     

Significance of three-dimensional radiation treatment planning

A tumour and its environment constitute a three-dimensional (3D) phenomenon. Consequently, adequate management of the target volume (tumour + safety zone) is feasible only with a 30 treatment planning and irradiating system. The more precise planning and dose delivery involved in such a 30 treatment lead to an improved therapeutic effectiveness.     

Effect of set-up error on the dose across the junction of matching cranial-spinal fields in the treatment of medulloblastoma

PURPOSE: The effect of systematic and stochastic setup error on the dose delivered to the gap region for the three field radiation treatment of medulloblastoma is studied. The consequences of such setup error is discussed. METHODS AND MATERIALS: The treatment of medulloblastoma is typically a 3 field technique, in which two lateral cranial fields are matched with a spine field. The x-ray dose delivered to the region between the matched fields depends upon the gap size. The choice of the gap width between the cranial and spinal fields is controversial. It is currently a compromise between minimizing the risk of dose hot spots to the spine, and the associated clinical complications, as well as the magnitude of cold spots (underdosing) across the gap, with the associated risk of disease recurrence. In this paper, we examine the effect of gap width with a moving junction, referred to as "field feathering", on the dose across the field junction for a 6MV photon beam. In addition, we have studied 129 portal films and 40 simulation films to assess the accuracy and precision of patient setup during treatment with a plan involving feathered fields. Selected landmarks observable on both portal and simulation films were identified and the variation in the distances to the field edges measured. The distribution of patient setup error was convoluted with the beam profiles for a 6MV linac. These convoluted field edges were used obtain dose profiles across the gap region as a function of gap separation. The consequences for therapy are discussed. In addition, analysis of patient setup error on an alternative treatment involving beam modifiers to broaden the beam penumbra is discussed. RESULTS: The magnitude of the spatial stochastic and systematic setup error was determined to be approximately three and two millimeters respectively. The dosimetric consequences of patient setup error lead to over and under dosing in the spinal gap region for the three field technique. The degree of under or over dose depends on the nature and magnitude of the patient setup error. CONCLUSIONS: The effect of patient setup error can lead to significant dosimetric errors in the dose to the gap region depending on the magnitude of the setup errors. The effective over and under dose can be compensated by the use beams modifiers such as a beam spoiler or vibrating jaws.     

Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate

It has been proposed that the generation of O2 during photodynamic therapy (PDT) may lead to photochemical depletion of ambient tumour oxygen, thus causing acute hypoxia and limiting treatment effectiveness. We have studied the effects of fluence rate on pO2, in the murine RIF tumour during and after PDT using 5 mg kg(-1) Photofrin and fluence rates of 30, 75 or 150 mW cm(-2). Median pO2 before PDT ranged from 2.9 to 5.2 mmHg in three treatment groups. Within the first minute of illumination, median tumour pO2 decreased with all fluence rates to values between 0.7 and 1.1 mmHg. These effects were rapidly and completely reversible if illumination was interrupted. During prolonged illumination (20-50 J cm(-2)) pO2 recovered at the 30 mW cm(-2) fluence rate to a median value of 7.4 mmHg, but remained low at the 150 mW cm(-2) fluence rate (median pO2 1.7 mmHg). Fluence rate effects were not found after PDT, and at both 30 and 150 mW cm(-2) median tumour pO2 fell from control levels to 1.0-1.8 mmHg within 1-3 h after treatment conclusion. PDT with 100 J cm(-2) at 30 mW cm(-2) caused significantly (P = 0.0004) longer median tumour regrowth times than PDT at 150 mW cm(-2), indicating that lower fluence rate can improve PDT response. Vascular perfusion studies uncovered significant fluence rate-dependent differences in the responses of the normal and tumour vasculature. These data establish a direct relationship between tumour pO2, the fluence rate applied during PDT and treatment outcome. The findings are of immediate clinical relevance.     

Test procedures for verification of an electron pencil beam algorithm implemented for treatment planning

The calculation of an electron dose distribution in a patient is a difficult problem because of the presence of tissue and surface inhomogeneities. Verification of the dose planning system is therefore essential. In this investigation, a novel method is used to evaluate a commercially available system (Helax-TMS), at electron energies between 10 and 50 MeV, both for a conventional treatment unit and an MLC-collimated scanned beam unit with a helium-filled treatment head. First, the experiments were designed to verify the local beam database and some fundamental characteristics of the electron beam calculations. Secondly, a number of generalised situations that would be encountered in the clinical treatment planning were evaluated oblique incidence, field shaping with multi-leaf collimator, bolus edges, and air cavities. Dose distributions in two generalised anatomical phantoms simulating a neck and a nose were also analysed. The results have, when so possible, been presented as the dose ratio within the 'flattened area' for dose profiles and down to the 'treatment depth' (80% dose level) for depth doses. In the penumbra region and in the dose fall-off region, the comparison has been represented by the distance deviation between calculated and measured dose profiles or depth doses. A new tool, 'volume integration', was used to evaluate the deviations from a more clinical point of view. Most results were within +/- 2% in dose for volumes larger than a sphere with a diameter of 15 mm, or +/- 2 mm in position. Dose deviations were generally found for oblique incidences and below heterogeneities such as small air cavities and bolus edges in limited volumes.     

Abutment region dosimetry for sequential arc IMRT delivery

Arc-based intensity modulated radiation therapy (IMRT) planning and delivery is available as a commercial product (Nomos Corp.). The dose distribution is delivered to 1.68 cm thick regions, and the patient moved in a precise manner between treatments. Assuming accurate patient positioning, the abutment region dose distribution near the gantry isocentre is delivered with no undesired dose heterogeneities. However, for regions far from the isocentre, the dose distribution may exhibit high- or low-dose regions due to uncompensated beam divergence for arc treatments of less than 360 degrees gantry angle length. A study has been initiated to characterize abutment region dose distribution heterogeneities for sequential arc IMRT delivery. Five dose distributions were optimized, each using 8 cm diameter target volumes at different distances from the isocentre, and the arc delivery limited to 290 degrees symmetric about the vertical axis. The target lengths were sufficient to require a treatment consisting of five couch positions, yielding four abutment regions. The dose within the abutment regions was measured using film and analysed as a function of off-axis position along both the vertical and horizontal directions. Little dependence on the dose heterogeneity was seen along the horizontal axis passing through the isocentre. However, the abutment regions along the vertical axis contained 15% low and 7% high doses at 7 cm above and below the isocentre respectively. This dose heterogeneity is not predicted by the current clinical release of the treatment planning software due to limitations of the dose calculation algorithm. The intensity of dose heterogeneity is considered sufficient to warrant further study.