Neutron dose in proton radiation therapy: in regard to Eric J. Hall (Int J Radiat Oncol Biol Phys 2006;65:1-7).
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Biomedical subjects
Publications and source records attributed to Thomas Bortfeld.
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Unlike conventional optimization with dose-volume (DV) constraints, multi-criteria optimization (MCO) with DV objectives provides tradeoff information which we believe is necessary for choosing better treatment plans. We show that the MCO formulation with DV objectives is better suited to convex approximation than conventional formulations with DV constraints. We provide a relaxation of the integer programming formulation which reduces the computation time for a single plan from over 5 h to about 2 min, without significantly compromising the results. We also derive a heuristic to improve on the relaxed solutions, adding only a few additional minutes of computation time. We apply these techniques to a skull based tumour case and a paraspinal tumour case. Based on a careful examination of the driving terms in the relaxed formulation and the heuristic, we argue that our techniques should apply more generally for DV objectives in multi-objective IMRT treatment planning.
PURPOSE: To explore the biologic relevance of deviations from the intended uniform fractionation scheme. METHODS AND MATERIALS: We study the effect of the variance of the dose per fraction on the normalized total dose (NTD), which incorporates the linear-quadratic model of radiation effects. In regions of steep dose gradients, we determine the shift between NTD isodose lines and physical isodose lines. We also look at ways to compensate for dose-variation effects through dose adjustments, without changing the number of fractions. RESULTS: Simple equations quantify effects of dose variation on the NTD. If the standard deviation of the dose is 10% of the daily dose fraction, the effects on the NTD for a given point in the irradiated area are always less than 1%, independent of the biologic parameters. In adaptive dose-correction schemes, the dose correction should be applied uniformly over the remaining fractions, to minimize the variance. Incomplete repair leads to a coupling of doses delivered on different days, which complicates the issue. Repopulation appears to be insignificant in the context of this study (constant overall treatment time). CONCLUSIONS: A variation of the dose between fractions always leads to a larger biologic effect than does the same total dose delivered with standard uniform fractionation. The increase in NTD is negligible if the standard deviation of the dose is less than 10% of the dose per fraction.
The very first cornerstone paper on intensity-modulated radiation therapy (IMRT) was published in Physics in Medicine and Biology, and many seminal IMRT works have since appeared in this journal. Today IMRT is a widely used clinical treatment modality in many countries. This contribution to the 50th anniversary issue reviews the physical, mathematical, and technological milestones that have facilitated the clinical implementation and success of IMRT. In particular, the basic concepts and developments of both IMRT treatment planning ('inverse planning') and the delivery of cone-beam IMRT with a multileaf collimator from a fixed number of static beam directions are discussed. An outlook into the future of IMRT concludes the paper.
Managing uncertainty is a major challenge in radiation therapy treatment planning, including uncertainty induced by intrafraction motion, which is particularly important for tumours in the thorax and abdomen. Common methods to account for motion are to introduce a margin or to convolve the static dose distribution with a motion probability density function. Unlike previous work in this area, our development does not assume that the patient breathes according to a fixed distribution, nor is the patient required to breathe the same way throughout the treatment. Despite this generality, we create a robust optimization framework starting from the convolution method that is robust to fluctuations in breathing motion, yet spares healthy tissue better than a margin solution. We describe how to generate the data for our model using breathing motion data and we test our model on a computer phantom using data from real patients. In our numerical results, the robust solution delivers approximately 38% less dose to the healthy tissue than the margin solution, while providing the same level of protection against breathing uncertainty.
We propose and study a unified model for handling dose constraints (physical dose, equivalent uniform dose (EUD), etc) and radiation source constraints in a single mathematical framework based on the split feasibility problem. The model does not impose on the constraints an exogenous objective (merit) function. The optimization algorithm minimizes a weighted proximity function that measures the sum of the squares of the distances to the constraint sets. This guarantees convergence to a feasible solution point if the split feasibility problem is consistent (i.e., has a solution), or, otherwise, convergence to a solution that minimally violates the physical dose constraints and EUD constraints. We present computational results that demonstrate the validity of the model and the power of the proposed algorithmic scheme.
Because proton beams activate positron emitters in patients, positron emission tomography (PET) has the potential to play a unique role in the in vivo verification of proton radiotherapy. Unfortunately, the PET image is not directly proportional to the delivered radiation dose distribution. Current treatment verification strategies using PET therefore compare the actual PET image with full-blown Monte Carlo simulations of the PET signal. In this paper, we describe a simpler and more direct way to reconstruct the expected PET signal from the local radiation dose distribution near the distal fall-off region, which is calculated by the treatment planning programme. Under reasonable assumptions, the PET image can be described as a convolution of the dose distribution with a filter function. We develop a formalism to derive the filter function analytically. The main concept is the introduction of 'Q' functions defined as the convolution of a Gaussian with a powerlaw function. Special Q functions are the Gaussian itself and the error function. The convolution of two Q functions is another Q function. By fitting elementary dose distributions and their corresponding PET signals with Q functions, we derive the Q function approximation of the filter. The new filtering method has been validated through comparisons with Monte Carlo calculations and, in one case, with measured data. While the basic concept is developed under idealized conditions assuming that the absorbing medium is homogeneous near the distal fall-off region, a generalization to inhomogeneous situations is also described. As a result, the method can determine the distal fall-off region of the PET signal, and consequently the range of the proton beam, with millimetre accuracy. Quantification of the produced activity is possible. In conclusion, the PET activity resulting from a proton beam treatment can be determined by locally filtering the dose distribution as obtained from the treatment planning system. The filter function can be calculated analytically using convolutions of Gaussians and powerlaw functions.
In radiotherapy practice, one often needs to compare two dose distributions. Especially with the wide clinical implementation of intensity-modulated radiation therapy, software tools for quantitative dose (or fluence) distribution comparison are required for patient-specific quality assurance. Dose distribution comparison is not a trivial task since it has to be performed in both dose and spatial domains in order to be clinically relevant. Each of the existing comparison methods has its own strengths and weaknesses and there is room for improvement. In this work, we developed a general framework for comparing dose distributions. Using a new concept called maximum allowed dose difference (MADD), the comparison in both dose and spatial domains can be performed entirely in the dose domain. Formulae for calculating MADD values for various comparison methods, such as composite analysis and gamma index, have been derived. For convenience in clinical practice, a new measure called normalized dose difference (NDD) has also been proposed, which is the dose difference at a point scaled by the ratio of MADD to the predetermined dose acceptance tolerance. Unlike the simple dose difference test, NDD works in both low and high dose gradient regions because it considers both dose and spatial acceptance tolerances through MADD. The new method has been applied to a test case and a clinical example. It was found that the new method combines the merits of the existing methods (accurate, simple, clinically intuitive and insensitive to dose grid size) and can easily be implemented into any dose/intensity comparison tool.
The purpose of this study is to calculate Pareto surfaces in multi-criteria radiation treatment planning and to analyse the dependency of the Pareto surfaces on the objective functions used for the volumes of interest. We develop a linear approach that allows us to calculate truly Pareto optimal treatment plans, and we apply it to explore the tradeoff between tumour dose homogeneity and critical structure sparing. We show that for two phantom and two clinical cases, a smooth (as opposed to kinked) Pareto tradeoff curve exists. We find that in the paraspinal cases the Pareto surface is invariant to the response function used on the spinal cord: whether the mean cord dose or the maximum cord dose is used, the Pareto plan database is similar. This is not true for the lung studies, where the choice of objective function on the healthy lung tissue influences the resulting Pareto surface greatly. We conclude that in the special case when the tumour wraps around the organ at risk, e.g. prostate cases and paraspinal cases, the Pareto surface will be largely invariant to the objective function used to model the organ at risk.
With the recent availability of 4D-CT, the accuracy of information on internal organ motion during respiration has improved significantly. We investigate the utility of organ motion information in IMRT treatment planning, using an in-house prototype optimization system. Four approaches are compared: (1) planning with optimized margins, based on motion information; (2) the 'motion kernel' approach, in which a more accurate description of the dose deposit from a pencil beam to a moving target is achieved either through time-weighted averaging of influence matrices, calculated for different instances of anatomy (subsets of 4D-CT data, corresponding to various phases of motion) or through convolution of the pencil beam kernel with the probability density function describing the target motion; (3) optimal gating, or tracking with beam intensity maps optimized independently for each instance of anatomy; and (4) optimal tracking with beam intensity maps optimized simultaneously for all instances of anatomy. The optimization is based on a gradient technique and can handle both physical (dose-volume) and equivalent uniform dose constraints. Optimization requires voxel mapping from phase to phase in order to score the dose in individual voxels as they move. The results show that, compared to the other approaches, margin expansion has a significant disadvantage by substantially increasing the integral dose to patient. While gating or tracking result in the best dose conformation to the target, the former elongates treatment time, and the latter significantly complicates the delivery procedure. The 'motion kernel' approach does not provide a dosimetric advantage, compared to optimal tracking or gating, but might lead to more efficient delivery. A combination of gating with the 'motion kernel' or margin expansion approach will increase the duty cycle and may provide one with the most efficient solution, in terms of complexity of the delivery procedure and dose conformality to the target.
The objective of radiotherapy planning is to find a compromise between the contradictive goals of delivering a sufficiently high dose to the target volume while widely sparing critical structures. The search for such a compromise requires the computation of several plans, which mathematically means solving several optimization problems. In the case of intensity modulated radiotherapy (IMRT) these problems are large-scale, hence the accumulated computational expense is very high. The adaptive clustering method presented in this paper overcomes this difficulty. The main idea is to use a preprocessed hierarchy of aggregated dose-volume information as a basis for individually adapted approximations of the original optimization problems. This leads to a decisively reduced computational expense: numerical experiments on several sets of real clinical data typically show computation times decreased by a factor of about 10. In contrast to earlier work in this field, this reduction in computational complexity will not lead to a loss in accuracy: the adaptive clustering method produces the optimum of the original optimization problem.
A geometric model is presented which allows calculation of the dosimetric consequences of rectal motion in prostate radiotherapy. Variations in the position of the rectum are measured by repeat CT scanning during the courses of treatment of five patients. Dose distributions are calculated by applying the same conformal treatment plan to each imaged fraction and rectal dose-surface histograms produced. The 2D model allows isotropic expansion and contraction in the plane of each CT slice. By summing the dose to specific volume elements tracked by the model, composite dose distributions are produced that explicitly include measured inter-fraction motion for each patient. These are then used to estimate effective dose-surface histograms (DSHs) for the entire treatment. Results are presented showing the magnitudes of the measured target and rectal motion and showing the effects of this motion on the integral dose to the rectum. The possibility of using such information to calculate normal tissue complication probabilities (NTCP) is demonstrated and discussed.
PURPOSE: A comparative treatment planning study has been undertaken between intensity modulated (IM) photon therapy and IM proton therapy (IMPT) in paraspinal sarcomas, so as to assess the potential benefits and limitations of these treatment modalities. In the case of IM proton therapy, plans were compared also for two different sizes of the pencil beam. Finally, a 10% and 20% dose escalation with IM protons was planned, and the consequential organ at risk (OAR) irradiation was evaluated. METHODS AND MATERIALS: Plans for 5 patients were computed for IM photons (7 coplanar fields) and protons (3 coplanar beams), using the KonRad inverse treatment planning system (developed at the German Cancer Research Center). IMPT planning was performed assuming 2 different sizes of the pencil beam: IMPT with a beam of full width at half-maximum of 20 mm, and IMPT with a "mini-beam" (IMPT(M), full width at half-maximum = 12 mm). Prescribed dose was 77.4 Gy or cobalt Gray equivalent (CGE) for protons to the gross tumor volume (GTV). Surface and center spinal cord dose constraint for all techniques was 64 and 53 Gy/CGE, respectively. Tumor and OAR dose-volume histograms were calculated. Results were analyzed using dose-volume histogram parameters, inhomogeneity coefficient, and conformity index. RESULTS: Gross tumor volume coverage was optimal and equally homogeneous with both IM photon and IM proton plans. Compared to the IM photon plans, the use of IM proton beam therapy leads to a substantial reduction of the OAR total integral dose in the low-level to mid-dose level. Median heart, lung, kidney, stomach, and liver mean dose and dose at the 50% volume level were consistently reduced by a factor of 1.3 to 25. Tumor dose homogeneity in IMPT(M) plans was always better than with IMPT planning (median inhomogeneity coefficient, 0.19 vs. 0.25). IMPT dose escalation (to 92.9 CGE to the GTV) was possible in all patients without exceeding the normal-tissue dose limits. CONCLUSIONS: These results suggest that the use of IM photon therapy, when compared to IM protons, can result in similar levels of tumor conformation. IM proton therapy, however, reduces the OAR integral dose substantially, compared to IM photon radiation therapy. As a result, tumor dose escalation was always possible with IM proton planning, within the maximal OAR dose constraints. In IM proton planning, reducing the size of the proton pencil beam (using the "mini-beam") improved the dose homogeneity, but it did not have a significant effect on the dose conformity.
The success of highly target-conformal treatments such as intensity-modulated radiotherapy (IMRT) can be compromised by motion of the inner organs and random patient setup errors. This article gives an overview of different studies that looked at the effect of organ motion and setup errors on radiation therapy dose distributions, both from a qualitative and quantitative point of view. The qualitative findings are generally applicable (ie, case independent). It is found that motion always leads to a blurring of the dose distribution. In addition, there are so-called interplay effects if the treatment delivery involves moving parts, such as multileaf collimators. After a large number of fractions, the interplay effects lead to a normal distribution of the dose value around the average blurred value. Thirdly, organ motion can also cause a spatial deformation of the dose distribution. Quantitatively it has been found that both deformation and interplay effects appear to be small (in the order of 1%-2%) in many typical clinical cases. The dominant effect is the blurring of the dose distribution, which is, in essence, independent of the treatment technique, and is not more pronounced in IMRT than in more conventional treatment techniques. However, because in IMRT there is a tendency to reduce or compromise target margins, the blurring has potentially a bigger effect on the outcome of IMRT, unless precision dose delivery techniques (such as gated or motion-synchronized beams) are used. An alternative to the use of margins is to do the planning based on blurred dose distributions.
A common requirement of radiation therapy is that treatment planning for different radiation modalities is devised on the basis of the same treatment planning system (TPS). The present study presents a novel multi-modal TPS with separate modules for the dose calculation, the optimization engine and the graphical user interface, which allows to integrate different treatment modalities. For heavy-charged particles, both most promising techniques, the distal edge tracking (DET) and the 3-dimensional scanning (3D) technique can be optimized. As a first application, the quality of optimized intensity-modulated treatment plans for photons (IMXT) and protons (IMPT) was analyzed in one clinical case on the basis of the achieved physical dose distributions. A comparison of the proton plans with the photon plans showed no significant improvement in terms of target volume dose, however there was an improvement in terms of organs at risk as well as a clear reduction of the total integral dose. For the DET technique, it is possible to create a treatment plan with almost the same quality of the 3D technique, however with a clearly reduced number (factor of 5) of beam spots as well as a reduced optimization time. Due to its modular design, the system can be easily expanded to more sophisticated dose-calculation algorithms or to modeling of biological effects.
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We derive, from first principles, a model to predict the output factors for spread-out Bragg peak proton fields (SOBP). The model is based on the simple observation that the output factor is the ratio of SOBP plateau dose to the dose measured in the ionization reference chamber. The latter, in turn, equates to the entrance dose of the SOBP corrected for inverse square. We use a theoretical derivation of this ratio to establish the relationship between the output factor and the distal range and modulation width of the SOBP. In addition, the theoretical derivation reduces the dependence on the distal range and modulation width into a single factor r = (R - M)/M. We compare the theoretical derivation against measurements obtained at the Northeast Proton Therapy Facility for output factors for clinical fields. The agreement between measurements and prediction is 2.9%.
Respiration-induced tumour motion can potentially compromise the use of intensity-modulated radiotherapy (IMRT) as a dose escalation tool for lung tumour treatment. We have experimentally investigated the intra-fractional organ motion effects in lung IMRT treatments delivered by multi-leaf collimator (MLC). An in-house made motor-driven platform, which moves sinusoidally with an amplitude of 1 cm and a period of 4 s, was used to mimic tumour motion. Tumour motion was simulated along cranial-caudal direction while MLC leaves moved across the patient from left to right, as in most clinical cases. The dose to a point near the centre of the tumour mass was measured according to geometric and dosimetric parameters from two five-field lung IMRT plans. For each field, measurement was done for two dose rates (300 and 500 MU min(-1)), three MLC delivery modes (sliding window, step-and-shoot with 10 and 20 intensity levels) and eight equally spaced starting phases of tumour motion. The dose to the measurement point delivered from all five fields was derived for both a single fraction and 30 fractions by randomly sampling from measured dose values of each field at different initial phases. It was found that the mean dose to a moving tumour differs slightly (<2-3%) from that to a static tumour. The variation in breathing phase at the start of dose delivery results in a maximum variation around the mean dose of greater than 30% for one field. The full width at half maximum for the probability distribution of the point dose is up to 8% for all five fields in a single fraction, but less than 1-2% after 30 fractions. In general, lower dose rate can reduce the motion-caused dose variation and therefore might be preferable for lung IMRT when no motion mitigation techniques are used. From the two IMRT cases we studied where tumour motion is perpendicular to MLC leaf motion, the dose variation was found to be insensitive to the MLC delivery mode.