Energy optimization procedure for treatment planning with laser-accelerated protons

A simple analytical model is found that predicts the exact proton spectrum needed to obtain a spread-out-Bragg peak (SOBP) distribution for laser-accelerated proton beams. The theory is based on the solution to the Boltzmann kinetic equation for the proton distribution function. The resulting analytical expression allows one to calculate the SOBP proton energy spectra for the different beamlet sizes and modulation depths that can be readily implemented in the calculation of energy and intensity modulated proton dose distributions. Since the practical implementation of energy modulation for proton beams is realized through the discrete superposition of individual Bragg peaks, it is shown that there exists an optimal relationship between the energy sampling size and the width of the initial proton energy distribution.     

A dosimetric system for quantitative cell irradiation experiments with laser-accelerated protons

An integrated dosimetry and cell irradiation system (IDOCIS) with laser-accelerated proton beams was developed, characterized, calibrated and successfully used for systematic in vitro experiments. Due to the broad exponentially shaped energy spectrum, the low-energy range of the protons (<20 MeV) and the high pulse dose, the absolute dosimetry for this beam quality is challenging. Therefore, a dedicated Faraday cup is used as an energy and dose rate independent absolute dosimeter that has been calibrated consistently with three independent methods. A transmission ionization chamber providing online relative dose information is cross-calibrated against the Faraday cup. Providing both online and absolute dose information, the IDOCIS allows for quantitative dosimetric and radiobiological studies at current low-energy laser-accelerated proton beams. Finally, first dosimetric characterizations of a laser-accelerated proton beam with the IDOCIS are presented.     

Particle selection and beam collimation system for laser-accelerated proton beam therapy

In a laser-accelerated proton therapy system, the initial protons have broad energy and angular distributions, which are not suitable for direct therapeutic applications. A compact particle selection and collimation device is needed to deliver small pencil beams of protons with desired energy spectra. In this work, we characterize a superconducting magnet system that produces a desired magnetic field configuration to spread the protons with different energies and emitting angles for particle selection. Four magnets are set side by side along the beam axis; each is made of NbTi wires which carry a current density of approximately 10(5) A/cm2 at 4.2 K, and produces a magnetic field of approximately 4.4 T in the corresponding region. Collimation is applied to both the entrance and the exit of the particle selection system to generate a desired proton pencil beam. In the middle of the magnet system, where the magnetic field is close to zero, a particle selection collimator allows only the protons with desired energies to pass through for therapy. Simulations of proton transport in the presence of the magnetic field show that the selected protons have successfully refocused on the beam axis after passing through the magnetic field with the optimal magnet system. The energy spread for any given characteristic proton energy has been obtained. It is shown that the energy spread is a function of the magnetic field strength and collimator size and reaches the full width at half maximum of 25 MeV for 230 MeV protons. Dose distributions have also been calculated with the GEANT3 Monte Carlo code to study the dosimetric properties of the laser-accelerated proton beams for radiation therapy applications.     

Optimization of intensity-modulated very high energy (50-250 MeV) electron therapy

This work evaluates the potential of very high energy (50-250 MeV) electron beams for dose conformation and identifies those variables that influence optimized dose distributions for this modality. Intensity-modulated plans for a prostate cancer model were optimized as a function of the importance factors, beam energy and number of energy bins, number of beams, and the beam orientations. A trial-and-error-derived constellation of importance factors for target and sensitive structures to achieve good conformal dose distributions was 500, 50, 10 and I for the target, rectum, bladder and normal tissues respectively. Electron energies greater than 100 MeV were found to be desirable for intensity-modulated very high energy electron therapy (VHEET) of prostate cancer. Plans generated for lower energy beams had relatively poor conformal dose distributions about the target region and delivered high doses to sensitive structures. Fixed angle beam treatments utilizing a large number of fields in the range 9-21 provided acceptable plans. Using more than 21 beams at fixed gantry angles had an insignificant effect on target coverage, but resulted in an increased dose to sensitive structures and an increased normal tissue integral dose. Minor improvements in VHEET plans utilizing a 'small' number (< or =9) of beams may be achieved if, in addition to intensity modulation, energy modulation is implemented using a small number (< or =3) of beam energies separated by 50 to 100 MeV. Rotation therapy provided better target dose homogeneity but unfortunately resulted in increased rectal dose, bladder dose and normal tissue integral dose relative to the 21-field fixed angle treatment plan. Modulation of the beam energy for rotation therapy had no beneficial consequences on the optimized dose distributions. Lastly, selection of beam orientations influenced the optimized treatment plan even when a large number of beams (approximately 15) were employed.     

Particle in cell simulation of laser-accelerated proton beams for radiation therapy

In this article we present the results of particle in cell (PIC) simulations of laser plasma interaction for proton acceleration for radiation therapy treatments. We show that under optimal interaction conditions protons can be accelerated up to relativistic energies of 300 MeV by a petawatt laser field. The proton acceleration is due to the dragging Coulomb force arising from charge separation induced by the ponderomotive pressure (light pressure) of high-intensity laser. The proton energy and phase space distribution functions obtained from the PIC simulations are used in the calculations of dose distributions using the GEANT Monte Carlo simulation code. Because of the broad energy and angular spectra of the protons, a compact particle selection and beam collimation system will be needed to generate small beams of polyenergetic protons for intensity modulated proton therapy.     

Intensity modulation methods for proton radiotherapy

The characteristic Bragg peak of protons or heavy ions provides a good localization of dose in three dimensions. Through their ability to deliver laterally and distally shaped homogenous fields, protons have been shown to be a precise and practical method for delivering highly conformal radiotherapy. However, in an analogous manner to intensity modulation for photons, protons can be used to construct dose distributions through the application of many individually inhomogeneous fields, but with the localization of dose in the Bragg peak providing the possibility of modulating intensity within each field in two or three dimensions. We describe four different methods of intensity modulation for protons and describe how these have been implemented in an existing proton planning system. As a preliminary evaluation of the efficacy of these methods, each has been applied to an example case using a variety of field combinations. Dose-volume histogram analysis of the resulting dose distributions shows that when large numbers of fields are used, all techniques exhibit both good target homogeneity and sparing of neighbouring critical structures, with little difference between the four techniques being discerned. As the number of fields is decreased, however, only a full 3D modulation of individual Bragg peaks can preserve both target coverage and sparing of normal tissues. We conclude that the 3D method provides the greatest flexibility for constructing conformal doses in challenging situations, but that when large numbers of beam ports are available, little advantage may be gained from the additional modulation of intensity in depth.     

Comparative analysis of 60Co intensity-modulated radiation therapy

In this study, we perform a scientific comparative analysis of using (60)Co beams in intensity-modulated radiation therapy (IMRT). In particular, we evaluate the treatment plan quality obtained with (i) 6 MV, 18 MV and (60)Co IMRT; (ii) different numbers of static multileaf collimator (MLC) delivered (60)Co beams and (iii) a helical tomotherapy (60)Co beam geometry. We employ a convex fluence map optimization (FMO) model, which allows for the comparison of plan quality between different beam energies and configurations for a given case. A total of 25 clinical patient cases that each contain volumetric CT studies, primary and secondary delineated targets, and contoured structures were studied: 5 head-and-neck (H&N), 5 prostate, 5 central nervous system (CNS), 5 breast and 5 lung cases. The DICOM plan data were anonymized and exported to the University of Florida optimized radiation therapy (UFORT) treatment planning system. The FMO problem was solved for each case for 5-71 equidistant beams as well as a helical geometry for H&N, prostate, CNS and lung cases, and for 3-7 equidistant beams in the upper hemisphere for breast cases, all with 6 MV, 18 MV and (60)Co dose models. In all cases, 95% of the target volumes received at least the prescribed dose with clinical sparing criteria for critical organs being met for all structures that were not wholly or partially contained within the target volume. Improvements in critical organ sparing were found with an increasing number of equidistant (60)Co beams, yet were marginal above 9 beams for H&N, prostate, CNS and lung. Breast cases produced similar plans for 3-7 beams. A helical (60)Co beam geometry achieved similar plan quality as static plans with 11 equidistant (60)Co beams. Furthermore, 18 MV plans were initially found not to provide the same target coverage as 6 MV and (60)Co plans; however, adjusting the trade-offs in the optimization model allowed equivalent target coverage for 18 MV. For plans with comparable target coverage, critical structure sparing was best achieved with 6 MV beams followed closely by (60)Co beams, with 18 MV beams requiring significantly increased dose to critical structures. In this paper, we report in detail on a representative set of results from these experiments. The results of the investigation demonstrate the potential for IMRT radiotherapy employing commercially available (60)Co sources and a double-focused MLC. Increasing the number of equidistant beams beyond 9 was not observed to significantly improve target coverage or critical organ sparing and static plans were found to produce comparable plans to those obtained using a helical tomotherapy treatment delivery when optimized using the same well-tuned convex FMO model. While previous studies have shown that 18 MV plans are equivalent to 6 MV for prostate IMRT, we found that the 18 MV beams actually required more fluence to provide similar quality target coverage.     

Particle selection for laser-accelerated proton therapy feasibility study

In this paper we present calculations for the design of a particle selection system for laser-accelerated proton therapy. Laser-accelerated protons coming from a thin high-density foil have broad energy and angular spectra leading to dose distributions that cannot be directly used for therapeutic applications. Our solution to this problem is a compact particle selection and collimation device that delivers small pencil beams of protons with desired energy spectra. We propose a spectrometer-like particle selection and beam modulation system in which the magnetic field will be used to spread the protons spatially according to their energies and emitting angles. Subsequently, an aperture will be used to select the protons within a therapeutic window of energy (energy modulation). It will be shown that for the effective proton spatial differentiation, the primary collimation device should be used, which will collimate protons to the desired angular distribution and limit the spatial mixing of different energy protons once they have traveled through the magnetic system. Due to the angular proton distribution, the spatial mixing of protons of different energies will always be present and it will result in a proton energy spread with the width depending on the energy. For 250 MeV protons, the width (from the maximum to the minimum energy) is found to be 50 MeV for the magnetic field configuration used in our calculations. As the proton energy decreases, its energy width decreases as well, and for 80 MeV protons it equals 9 MeV. The presence of the energy width in the proton energy distribution will modify the depth dose curves needed for the energy modulation calculation. The matching magnetic field setup will ensure the refocusing of the selected protons and the final beam will be collimated by the secondary collimator. The calculations presented in this article show that the dose rate that the selection system can yield is on the order of D=260 Gy/min for a field size of 1 x 1 cm2.     

Energy- and intensity-modulated electron beams for radiotherapy

This work investigates the feasibility of optimizing energy- and intensity-modulated electron beams for radiation therapy. A multileaf collimator (MLC) specially designed for modulated electron radiotherapy (MERT) was investigated both experimentally and by Monte Carlo simulations. An inverse-planning system based on Monte Carlo dose calculations was developed to optimize electron beam energy and intensity to achieve dose conformity for target volumes near the surface. The results showed that an MLC with 5 mm leaf widths could produce complex field shapes for MERT. Electron intra- and inter-leaf leakage had negligible effects on the dose distributions delivered with the MLC, even at shallow depths. Focused leaf ends reduced the electron scattering contributions to the dose compared with straight leaf ends. As anticipated, moving the MLC position toward the patient surface reduced the penumbra significantly. There were significant differences in the beamlet distributions calculated by an analytic 3-D pencil beam algorithm and the Monte Carlo method. The Monte Carlo calculated beamlet distributions were essential to the accuracy of the MERT dose distribution in cases involving large air gaps, oblique incidence and heterogeneous treatment targets (at the tissue-bone and bone-lung interfaces). To demonstrate the potential of MERT for target dose coverage and normal tissue sparing for treatment of superficial targets, treatment plans for a hypothetical treatment were compared using photon beams and MERT.     

Shielding design for a laser-accelerated proton therapy system

In this paper, we present the shielding analysis to determine the necessary neutron and photon shielding for a laser-accelerated proton therapy system. Laser-accelerated protons coming out of a solid high-density target have broad energy and angular spectra leading to dose distributions that cannot be directly used for therapeutic applications. A special particle selection and collimation device is needed to generate desired proton beams for energy- and intensity-modulated proton therapy. A great number of unwanted protons and even more electrons as a side-product of laser acceleration have to be stopped by collimation devices and shielding walls, posing a challenge in radiation shielding. Parameters of primary particles resulting from the laser-target interaction have been investigated by particle-in-cell simulations, which predicted energy spectra with 300 MeV maximum energy for protons and 270 MeV for electrons at a laser intensity of 2 x 10(21) W cm(-2). Monte Carlo simulations using FLUKA have been performed to design the collimators and shielding walls inside the treatment gantry, which consist of stainless steel, tungsten, polyethylene and lead. A composite primary collimator was designed to effectively reduce high-energy neutron production since their highly penetrating nature makes shielding very difficult. The necessary shielding for the treatment gantry was carefully studied to meet the criteria of head leakage <0.1% of therapeutic absorbed dose. A layer of polyethylene enclosing the whole particle selection and collimation device was used to shield neutrons and an outer layer of lead was used to reduce photon dose from neutron capture and electron bremsstrahlung. It is shown that the two-layer shielding design with 10-12 cm thick polyethylene and 4 cm thick lead can effectively absorb the unwanted particles to meet the shielding requirements.     

Determining optimal two-beam axial orientations for heart sparing in left-sided breast cancer patients

BACKGROUND AND PURPOSE: The optimal intensity fluence profile of a beam depends on the profiles of other beams but most optimizations assume fixed beam orientations, a priori. Breast cancer radiotherapy attempts to cover the target and to spare critical structures such as the heart and lungs. The study aims are (1) to determine and document the optimal two-beam orientation that best spares the heart for left-sided breast cancer patients and (2) to investigate the influence of the treatment technique (i.e., conformal versus intensity modulation) on the optimal objective cost function. MATERIAL AND METHODS: Ten left-sided breast cancer patients were planned using a conformal (3DCRT) and a simplified intensity modulated (sIMRT) technique using predefined segments and different two-beam orientations. Optimal segment weights were determined exhaustively for all axial two-beam combinations, in 5 degree increments, by minimizing a quadratic objective cost function. The resulting objective cost function was analyzed with respect to target geometry and treatment technique. RESULTS: The sIMRT plans are generally less sensitive to beam orientation compared to 3DCRT plans. Optimal two-beam orientations for 3DCRT and sIMRT plans exist and they correspond to a hinge angle of approximately 188 degrees and 160 degrees or 210 degrees (the latter is bimodal), respectively. CONCLUSIONS: The optimization software is a useful tool that can test many different beam combinations and estimate their associated objective cost values. Afterwards, the most promising beam orientations could be re-optimized under the TPS to fine-tune and verify the dose distributions. Optimal uniform two-beam orientations for the breast consist of opposing tangential medial and lateral beams. Optimal nonuniform two-beam orientations for left-sided breast cancers are bimodal, containing hinge angles around 160 degrees and 210 degrees. Nonuniform beam techniques are less sensitive to beam orientation compared to uniform beam techniques and result in significantly improved heart sparing but at a cost of slightly compromised planning target volume coverage.     

Isotropic beam bouquets for shaped beam linear accelerator radiosurgery.

In stereotactic radiosurgery and radiotherapy treatment planning, the steepest dose gradient is obtained by using beam arrangements with maximal beam separation. We propose a treatment plan optimization method that optimizes beam directions from the starting point of a set of isotropically convergent beams, as suggested by Webb. The optimization process then individually steers each beam to the best position, based on beam's-eye-view (BEV) critical structure overlaps with the target projection and the target's projected cross sectional area at each beam position. This final optimized beam arrangement maintains a large angular separation between adjacent beams while conformally avoiding critical structures. As shown by a radiosurgery plan, this optimization method improves the critical structure sparing properties of an unoptimized isotropic beam bouquet, while maintaining the same degree of dose conformity and dose gradient. This method provides a simple means of designing static beam radiosurgery plans with conformality indices that are within established guidelines for radiosurgery planning, and with dose gradients that approach those achieved in conventional radiosurgery planning.     

A prototype beam delivery system for the proton medical accelerator at Loma Linda.

A variable energy proton accelerator was commissioned at Fermi National Accelerator Laboratory for use in cancer treatment at the Loma Linda University Medical Center. The advantages of precise dose localization by proton therapy, while sparing nearby healthy tissue, are well documented [R. R. Wilson, Radiology 47, 487 (1946); M. Wagner, Med. Phys. 9, 749 (1982); M. Goitein and F. Chen, Med. Phys. 10, 831 (1983)]. One of the components of the proton therapy facility is a beam delivery system capable of delivering precise dose distributions to the target volume in the patient. To this end, a prototype beam delivery system was tested during the accelerator's commissioning period. The beam delivery system consisted of a beam spreading device to produce a large, uniform field, a range modulator to generate a spread out Bragg peak (SOBP), and various beam detectors to measure intensity, beam centering, and dose distributions. The beam delivery system provided a uniform proton dose distribution in a cylindrical volume of 20-cm-diam area and 9-cm depth. The dose variations throughout the target volume were found to be less than +/- 5%. Modifications in the range modulator should reduce this considerably. The central axis dose rate in the region of the SOBP was found to be 0.4 cGy/spill with an incident beam intensity of 6.7 x 10(9) protons/spill. With an accelerator repetition rate of 30 spills/min and expected intensity of 2.5 x 10(10) protons/spill for patient treatment, this system can provide 50 cGy/min for a 20-cm-diam field and 9-cm range modulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment planning for heavy ion radiotherapy: clinical implementation and application

The clinical implementation and application of a novel treatment planning system (TPS) for scanned ion beams is described, which is in clinical use for carbon ion treatments at the German heavy ion facility (GSI). All treatment plans are evaluated on the basis of biologically effective dose distributions. For therapy control, in-beam positron emission tomography (PET) and an online monitoring system for the beam intensity and position are used. The absence of a gantry restricts the treatment plans to horizontal beams. Most of the treatment plans consist of two nearly opposing lateral fields or sometimes orthogonal fields. In only a very few cases a single beam was used. For patients with very complex target volumes lateral and even distal field patching techniques were applied. Additional improvements can be achieved when the patient's head is fixed in a tilted position, in order to achieve sparing of the organs at risk. In order to test the stability of dose distributions in the case of patient misalignments we routinely simulate the effects of misalignments for patients with critical structures next to the target volume. The uncertainties in the range calculation are taken into account by a margin around the target volume of typically 2-3 mm, which can, however, be extended if the simulation demonstrates larger deviations. The novel TPS developed for scanned ion beams was introduced into clinical routine in December 1997 and was used for the treatment planning of 63 patients with head and neck tumours until July 2000. Planning strategies and methods were developed for this tumour location that facilitate the treatment of a larger number of patients with the scanned heavy ion beam in a clinical setting. Further developments aim towards a simultaneous optimization of the treatment field intensities and more effective procedures for the patient set-up. The results demonstrate that ion beams can be integrated into a clinical environment for treatment planning and delivery.     

Intensity and energy modulated radiotherapy with proton beams: variables affecting optimal prostate plan

Inverse planning for intensity- and energy-modulated radiotherapy (IEMRT) with proton beams involves the selection of (i) the relative importance factors to control the relative importance of the target and sensitive structures, (ii) an appropriate energy resolution to achieve an acceptable depth modulation, (iii) an appropriate beamlet width to modulate the beam laterally, and (iv) a sufficient number of beams and their orientations. In this article we investigate the influence of these variables on the optimized dose distribution of a simulated prostate cancer IEMRT treatment. Good dose conformation for this prostate case was achieved using a constellation of I factors for the target, rectum, bladder, and normal tissues of 500, 50, 15, and 1, respectively. It was found that for an active beam delivery system, the energy resolution should be selected on the basis of the incident beams' energy spread (sigmaE) and the appropriate energy resolution varied from 1 MeV at sigmaE = 0.0 to 5 MeV at sigmaE= 2.0 MeV. For a passive beam delivery system the value of the appropriate depth resolution for inverse planning may not be critical as long as the value chosen is at least equal to one-half the FWHM of the primary beam Bragg peak. Results indicate that the dose grid element dimension should be equal to or no less than 70% of the beamlet width. For this prostate case, we found that a maximum of three to four beam ports is required since there was no significant advantage to using a larger number of beams. However for a small number (< or = 4) of beams the selection of beam orientations, while having only a minor effect on target coverage, strongly influenced the sensitive structure sparing and normal tissue integral dose.     

A robust algorithm of intensity modulated proton therapy for critical tissue sparing and target coverage

Intensity modulated proton therapy (IMPT) offers the possibility of generating excellent target coverage while sparing the neighbouring organs at risk. However, treatment plans optimized for IMPT may be very sensitive to range and setup uncertainties. We developed a method to deal with these uncertainties in the dose optimization. This method aims at two objectives: one for maintaining the dose coverage within the target, and the other for preventing undesired exposure to organs at risk. The former objective was achieved by the algorithm described in our previous paper to suppress the in-field dose gradient within the target. In this study, the latter objective was achieved by a novel algorithm in which we suppressed pencil beams with high risk to deliver undesired doses to organs at risk under conditions where range and setup uncertainties occur. We defined the risk index that quantifies the likelihood of each pencil beam delivering high doses to organs at risk, and introduced it into the objective function of dose optimizations. In order to test the algorithm's performance, this method was applied to an RTOG benchmark phantom geometry and to a cervical chordoma case. These simulations demonstrated that our method provides IMPT plans that are more robust against range and setup errors compared to conventional IMPT plans. Compared to the conventional IMPT plan, the optimization time for the robust plan increased by a factor of only 3, from 4 to 11 min.     

A computational implementation and comparison of several intensity modulated proton therapy treatment planning algorithms

The authors present a comparative study of intensity modulated proton therapy (IMPT) treatment planning employing algorithms of three-dimensional (3D) modulation, and 2.5-dimensional (2.5D) modulation, and intensity modulated distal edge tracking (DET) [A. Lomax, Phys. Med. Biol. 44, 185-205 (1999)] applied to the treatment of head-and-neck cancer radiotherapy. These three approaches were also compared with 6 MV photon intensity modulated radiation therapy (IMRT). All algorithms were implemented in the University of Florida Optimized Radiation Therapy system using a finite sized pencil beam dose model and a convex fluence map optimization model. The 3D IMPT and the DET algorithms showed considerable advantages over the photon IMRT in terms of dose conformity and sparing of organs at risk when the beam number was not constrained. The 2.5D algorithm did not show an advantage over the photon IMRT except in the dose reduction to the distant healthy tissues, which is inherent in proton beam delivery. The influences of proton beam number and pencil beam size on the IMPT plan quality were also studied. Out of 24 cases studied, three cases could be adequately planned with one beam and 12 cases could be adequately planned with two beams, but the dose uniformity was often marginally acceptable. Adding one or two more beams in each case dramatically improved the dose uniformity. The finite pencil beam size had more influence on the plan quality of the 2.5D and DET algorithms than that of the 3D IMPT. To obtain a satisfactory plan quality, a 0.5 cm pencil beam size was required for the 3D IMPT and a 0.3 cm size was required for the 2.5D and the DET algorithms. Delivery of the IMPT plans produced in this study would require a proton beam spot scanning technique that has yet to be developed clinically.     

Variable versus fixed modulation of proton beams for treatments in the cranium

Dose distributions in the cranium with fixed and with variably modulated proton beams were compared. The variable modulation was designed to tailor the proximal high-dose region of each field to the target volume surface whereas the fixed modulation beams had a constant modulation determined by the greatest extent of the target. Dose-volume histograms of normal tissues were compared, as were the estimated complication probabilities. Twelve patients with chordomas or chondrosarcomas of the base of skull who had been treated to approximately 70 cobalt Gray equivalent (CGE) were evaluated. Dose distributions of the actual treatments were compared to those which would have been delivered had the proton beams been variably modulated; two patients for whom x-ray plans were available were also evaluated. The greatest difference in dose between the variable and fixed modulation proton beams, averaged over all the patients, was 13.8 CGE (8.0-18.0 CGE range). Much of this reduction occurred in the brain, particularly the temporal lobes. In those temporal lobes receiving significant doses, variable modulation reduced the volume receiving more than 54 CGE by 3.0 cc; all temporal lobes had at least a 5 CGE difference to some portion, half had more than 10 CGE and three more than 15 CGE difference to some portion. The optic structures, brainstem and spinal cord received from 1 to 3 CGE less dose with the variability modulated beams. Eight of the parotid glands received more than 20 CGE to more than half their volume with the fixed modulation beams; in these, variable modulation reduced the mean dose by 5.3 CGE. The reduction in integral dose with variable as compared to fixed modulation was in the range 3 to 12%; this gain was considerably less than the gain for uniformly modulated proton beams over x-rays in the two patients for whom x-ray plans were available.