Spatiotemporal optimisation of prostate intensity modulated proton therapy (IMPT) treatments.

Objective.In intensity modulated particle therapy (IMPT), the adoption of spatially and temporally heterogeneous dose distributions allows to decouple the fractionation scheme from the patient anatomy, so that an hypofractionated schedule can be selectively created inside the tumour, while simultaneously exploiting the fractionation effect in the healthy tissues. In this paper, the authors show the reproducibility of the method on a set of prostate patients, quantifying the dependencies of the achievable benefit with respect to conventional and hypofractionated schemes and the sensitivity of the method to setup errors and range uncertainty.Approach.On a cohort of 9 patients, non-uniform IMPT plans were optimised and compared to conventional and hypofractionated schedules. For each patient, the comparison of the three strategies has been based on the output of the cost function used to optimise the treatments. The analysis has been repeated considering differentα/ßratios for the tumour, namely 1.5, 3 and 4.5 Gy. For a single patient, setup errors and beam range uncertainty have been analysed: the plans, for each optimisation strategy, have been iteratively forward planned 500 times with randomly varying the patient position in each fraction, and 200 times for systematic range shift.Main results.An average 10% benefit has been shown for the lowestα/ßratio considered for the tumour, where the non-uniform schedule generally converges to hypofractionation; the benefit decreases to 5%-7% for higherα/ßratios, for which the non-uniform schedule always showed better outcomes with respect to the other fractionation schedules. An increased sensitivity to uncertainty, especially for setup errors, has been shown, which can be associated to the spatial non-uniformity of the dose distributions peculiar of the spatiotemporal plans.Significance.This work represents the first investigation of spatiotemporal fractionation for prostate cancer and the beginning of further investigations before clinical implementation can be considered.

Conic formulation of fluence map optimization problems.

The convexity of objectives and constraints in fluence map optimization (FMO) for radiation therapy has been extensively studied. Next to convexity, there is another important characteristic of optimization functions and problems, which has thus far not been considered in FMO literature: conic representation. Optimization problems that are conically representable using quadratic, exponential and power cones are solvable with advanced primal-dual interior-point algorithms. These algorithms guarantee an optimal solution in polynomial time and have good performance in practice. In this paper, we construct conic representations for most FMO objectives and constraints. This paper is the first that shows that FMO problems containing multiple biological evaluation criteria can be solved in polynomial time. For fractionation-corrected functions for which no exact conic reformulation is found, we provide an accurate approximation that is conically representable. We present numerical results on the TROTS data set, which demonstrate very stable numerical performance for solving FMO problems in conic form. With ongoing research in the optimization community, improvements in speed can be expected, which makes conic optimization a promising alternative for solving FMO problems.

Compact Method for Proton Range Verification Based on Coaxial Prompt Gamma-Ray Monitoring: a Theoretical Study.

Range uncertainties in proton therapy hamper treatment precision. Prompt gamma-rays were suggested 16 years ago for real-time range verification, and have already shown promising results in clinical studies with collimated cameras. Simultaneously, alternative imaging concepts without collimation are investigated to reduce the footprint and price of current prototypes. In this manuscript, a compact range verification method is presented. It monitors prompt gamma-rays with a single scintillation detector positioned coaxially to the beam and behind the patient. Thanks to the solid angle effect, proton range deviations can be derived from changes in the number of gamma-rays detected per proton, provided that the number of incident protons is well known. A theoretical background is formulated and the requirements for a future proof-of-principle experiment are identified. The potential benefits and disadvantages of the method are discussed, and the prospects and potential obstacles for its use during patient treatments are assessed. The final milestone is to monitor proton range differences in clinical cases with a statistical precision of 1 mm, a material cost of 25000 USD and a weight below 10 kg. This technique could facilitate the widespread application of in vivo range verification in proton therapy and eventually the improvement of treatment quality.

Optimal treatment plan adaptation using mid-treatment imaging biomarkers.

Previous studies on personalized radiotherapy (RT) have mostly focused on baseline patient stratification, adapting the treatment plan according to mid-treatment anatomical changes, or dose boosting to selected tumor subregions using mid-treatment radiological findings. However, the question of how to find the optimal adapted plan has not been properly tackled. Moreover, the effect of information uncertainty on the resulting adaptation has not been explored. In this paper, we present a framework to optimally adapt radiation therapy treatments to early radiation treatment response estimates derived from pre- and mid-treatment imaging data while considering the information uncertainty. The framework is based on the optimal stopping in radiation therapy (OSRT) framework. Biological response is quantified using tumor control probability (TCP) and normal tissue complication probability (NTCP) models, and these are directly optimized for in the adaptation step. Two adaptation strategies are discussed: (1) uniform dose adaptation and (2) continuous dose adaptation. In the first strategy, the original fluence-map is simply scaled upwards or downwards, depending on whether dose escalation or de-escalation is deemed appropriate based on the mid-treatment response observed from the radiological images. In the second strategy, a full NTCP-TCP-based fluence map re-optimization is performed to achieve the optimal adapted plans. We retrospectively tested the performance of these strategies on 14 canine head and neck cases treated with tomotherapy, using as response biomarker the change in the 3'-deoxy-3'[(18)F]-fluorothymidine (FLT)-PET signals between the pre- and mid-treatment images, and accounting for information uncertainty. Using a 10% uncertainty level, the two adaptation strategies both yield a noteworthy average improvement in guaranteed (worst-case) TCP.

Systematic analysis of biological and physical limitations of proton beam range verification with offline PET/CT scans.

The clinical use of offline positron emission tomography/computed tomography (PET/CT) scans for proton range verification is currently under investigation at the Massachusetts General Hospital (MGH). Validation is achieved by comparing measured activity distributions, acquired in patients after receiving one fraction of proton irradiation, with corresponding Monte Carlo (MC) simulated distributions. Deviations between measured and simulated activity distributions can either reflect errors during the treatment chain from planning to delivery or they can be caused by various inherent challenges of the offline PET/CT verification method. We performed a systematic analysis to assess the impact of the following aspects on the feasibility and accuracy of the offline PET/CT method: (1) biological washout processes, (2) patient motion, (3) Hounsfield unit (HU) based tissue classification for the simulation of the activity distributions and (4) tumor site specific aspects. It was found that the spatial reproducibility of the measured activity distributions is within 1 mm. However, the feasibility of range verification is restricted to a limited amount of positions and tumor sites. Washout effects introduce discrepancies between the measured and simulated ranges of about 4 mm at positions where the proton beam stops in soft tissue. Motion causes spatial deviations of up to 3 cm between measured and simulated activity distributions in abdominopelvic tumor cases. In these later cases, the MC simulated activity distributions were found to be limited to about 35% accuracy in absolute values and about 2 mm in spatial accuracy depending on the correlativity of HU into the physical and biological parameters of the irradiated tissue. Besides, for further specific tumor locations, the beam arrangement, the limited accuracy of rigid co-registration and organ movements can prevent the success of PET/CT range verification. All the addressed factors explain why the proton beam range can only be verified within an accuracy of 1-2 mm in low-perfused bony structures of head and neck patients for which an accurate co-registration of predominant bony anatomy is possible, as shown previously. However, most of the limitations of the current approach are conquerable. By implementing technological and methodological improvements like the use of in-room PET scanners, PET measurements could soon be used to provide proton range verification in clinical routine.

Optimal combined proton-photon therapy schemes based on the standard BED model.

This paper investigates the potential of combined proton-photon therapy schemes in radiation oncology, with a special emphasis on fractionation. Several combined modality models, with and without fractionation, are discussed, and conditions under which combined modality treatments are of added value are demonstrated analytically and numerically. The combined modality optimal fractionation problem with multiple normal tissues is formulated based on the biologically effective dose (BED) model and tested on real patient data. Results indicate that for several patients a combined modality treatment gives better results in terms of biological dose (up to [Formula: see text] improvement) than single modality proton treatments. For several other patients, a combined modality treatment is found that offers an alternative to the optimal single modality proton treatment, being only marginally worse but using significantly fewer proton fractions, putting less pressure on the limited availability of proton slots. Overall, these results indicate that combined modality treatments can be a viable option, which is expected to become more important as proton therapy centers are spreading but the proton therapy price tag remains high.

A new way of adapting IMRT delivery fraction-by-fraction to cater for variable intrafraction motion.

In this paper a technique is presented for adaptive therapy to compensate for variable intrafraction tissue motion. So long as the motion can be measured or deduced for each fraction the technique modifies the fluence profile for the subsequent fractions in a repeatable cyclic way. The fluence modification is based on projecting the dose discrepancies between the cumulative delivered dose after each fraction and the expected planned dose at the same stage. It was shown that, in general, it is best to adapt the fluence profile to moving leaves that also have been modified to 'breathe' according to some regular default motion. However, it is important to point out that, if this regular default motion were to differ too much from the variable motion at each fraction, then the result can be worse than adapting to non-breathing leaves in a dynamic MLC technique. Furthermore, in general it should always be possible to improve results by starting the adaptation process with a constrained deconvolution of the regular default motion.

Quantitative assessment of the physical potential of proton beam range verification with PET/CT.

A recent clinical pilot study demonstrated the feasibility of offline PET/CT range verification for proton therapy treatments. In vivo PET measurements are challenged by blood perfusion, variations of tissue compositions, patient motion and image co-registration uncertainties. Besides these biological and treatment specific factors, the accuracy of the method is constrained by the underlying physical processes. This phantom study distinguishes physical factors from other factors, assessing the reproducibility, consistency and sensitivity of the PET/CT range verification method. A spread-out Bragg-peak (SOBP) proton field was delivered to a phantom consisting of poly-methyl methacrylate (PMMA), lung and bone equivalent material slabs. PET data were acquired in listmode at a commercial PET/CT scanner available within 10 min walking distance from the proton therapy unit. The measured PET activity distributions were compared to simulations of the PET signal based on Geant4 and FLUKA Monte Carlo (MC) codes. To test the reproducibility of the measured PET signal, data from two independent measurements at the same geometrical position in the phantom were compared. Furthermore, activation depth profiles within identical material arrangements but at different positions within the irradiation field were compared to test the consistency of the measured PET signal. Finally, activation depth profiles through air/lung, air/bone and lung/bone interfaces parallel as well as at 6 degrees to the beam direction were studied to investigate the sensitivity of the PET/CT range verification method. The reproducibility and the consistency of the measured PET signal were found to be of the same order of magnitude. They determine the physical accuracy of the PET measurement to be about 1 mm. However, range discrepancies up to 2.6 mm between two measurements and range variations up to 2.6 mm within one measurement were found at the beam edge and at the edge of the field of view (FOV) of the PET scanner. PET/CT range verification was found to be able to detect small range modifications in the presence of complex tissue inhomogeneities. This study indicates the physical potential of the PET/CT verification method to detect the full-range characteristic of the delivered dose in the patient.

Pareto navigation: algorithmic foundation of interactive multi-criteria IMRT planning.

Inherently, IMRT treatment planning involves compromising between different planning goals. Multi-criteria IMRT planning directly addresses this compromising and thus makes it more systematic. Usually, several plans are computed from which the planner selects the most promising following a certain procedure. Applying Pareto navigation for this selection step simultaneously increases the variety of planning options and eases the identification of the most promising plan. Pareto navigation is an interactive multi-criteria optimization method that consists of the two navigation mechanisms 'selection' and 'restriction'. The former allows the formulation of wishes whereas the latter allows the exclusion of unwanted plans. They are realized as optimization problems on the so-called plan bundle -- a set constructed from pre-computed plans. They can be approximately reformulated so that their solution time is a small fraction of a second. Thus, the user can be provided with immediate feedback regarding his or her decisions. Pareto navigation was implemented in the MIRA navigator software and allows real-time manipulation of the current plan and the set of considered plans. The changes are triggered by simple mouse operations on the so-called navigation star and lead to real-time updates of the navigation star and the dose visualizations. Since any Pareto-optimal plan in the plan bundle can be found with just a few navigation operations the MIRA navigator allows a fast and directed plan determination. Besides, the concept allows for a refinement of the plan bundle, thus offering a middle course between single plan computation and multi-criteria optimization. Pareto navigation offers so far unmatched real-time interactions, ease of use and plan variety, setting it apart from the multi-criteria IMRT planning methods proposed so far.

Effects of organ motion on IMRT treatments with segments of few monitor units.

Interplay between organ (breathing) motion and leaf motion has been shown in the literature to have a small dosimetric impact for clinical conditions (over a 30 fraction treatment). However, previous studies did not consider the case of treatment beams made up of many few-monitor-unit (MU) segments, where the segment delivery time (1-2 s) is of the order of the breathing period (3-5 s). In this study we assess if breathing compromises the radiotherapy treatment with IMRT segments of low number of MUs. We assess (i) how delivered dose varies, from patient to patient, with the number of MU per segment, (ii) if this delivered dose is identical to the average dose calculated without motion over the path of the motion, and (iii) the impact of the daily variation of the delivered dose as a function of MU per segment. The organ motion was studied along two orthogonal directions, representing the left-right and cranial-caudal directions of organ movement for a patient setup in the supine position. Breathing motion was modeled as sin(x), sin4(x), and sin6(x), based on functions used in the literature to represent organ motion. Measurements were performed with an ionization chamber and films. For a systematic study of motion effects, a MATLAB simulation was written to model organ movement and dose delivery. In the case of a single beam made up of one single segment, the dose delivered to point in a moving target over 30 fractions can vary up to 20% and 10% for segments of 10 MU and 20 MU, respectively. This dose error occurs because the tumor spends most of the time near the edges of the radiation beam. In the case of a single beam made of multiple segments with low MU, we observed 2.4%, 3.3%, and 4.3% differences, respectively, for sin(x), sin4(x), and sin6(x) motion, between delivered dose and motion-averaged dose for points in the penumbra region of the beam and over 30 fractions. In approximately 5-10% of the cases, differences between the motion-averaged dose and the delivered 30-fraction dose could reach 6%, 8% and 10-12%, respectively for sin(x), sin4(x), and sin6(x) motion. To analyze a clinical IMRT beam, two patient plans were randomly selected. For one of the patients, the beams showed a likelihood of up to 25.6% that the delivered dose would deviate from the motion-averaged dose by more than 1%. For the second patient, there was a likelihood of up to 62.8% of delivering a dose that differs by more than 1% from the motion-averaged dose and a likelihood of up to approximately 30% for a 2% dose error. For the entire five-beam IMRT plan, statistical averaging over the beams reduces the overall dose error between the delivered dose and the motion-averaged dose. For both patients there was a likelihood of up to 7.0% and 33.9% that the dose error was greater than 1%, respectively. For one of the patients, there was a 12.6% likelihood of a 2% dose error. Daily intrafraction variation of the delivered dose of more than 10% is non-negligible and can potentially lead to biological effects. We observed [for sin(x), sin4(x), and sin6(x)] that below 10-15 MU leads to large daily variations of the order of 15-35%. Therefore, for small MU segments, non-negligible biological effects can be incurred. We conclude that for most clinical cases the effects may be small because of the use of many beams, it is desirable to avoid low-MU segments when treating moving targets. In addition, dose averaging may not work well for hypo-fractionation, where fewer fractions are used. For hypo-fractionation, PDF modeling of the tumor motion in IMRT optimization may not be adequate.

How much margin reduction is possible through gating or breath hold?

We determined the relationship between intra-fractional breathing motion and safety margins, using daily real-time tumour tracking data of 40 patients (43 tumour locations), treated with radiosurgery at Hokkaido University. We limited our study to the dose-blurring effect of intra-fractional breathing motion, and did not consider differences in positioning accuracy or systematic errors. The additional shift in the prescribed isodose level (e.g. 95 %) was determined by convolving a one-dimensional dose profile, having a dose gradient representing an 8 MV beam through either lung or water, with the probability density function (PDF) of breathing. This additional shift is a measure for the additional margin that should be applied in order to maintain the same probability of tumour control as without intra-fractional breathing. We show that the required safety margin is a nonlinear function of the peak-to-peak breathing motion. Only a small reduction in the shift of isodose curves was observed for breathing motion up to 10 mm. For larger motion, 20 or 30 mm, control of patient breathing during irradiation, using either gating or breath hold, can allow a substantial reduction in safety margins of about 7 or 12 mm depending on the dose gradient prior to blurring. Clinically relevant random setup uncertainties, which also have a blurring effect on the dose distribution, have only a small effect on the margin needed for intra-fractional breathing motion. Because of the one-dimensional nature of our analysis, the resulting margins are mainly applicable in the superior-inferior direction. Most measured breathing PDFs were not consistent with the PDF of a simple parametric curve such as cos4, either because of irregular breathing or base-line shifts. Instead, our analysis shows that breathing motion can be modelled as Gaussian with a standard deviation of about 0.4 times the peak-to-peak breathing motion.

Optimized planning using physical objectives and constraints.

Intensity-modulated radiation therapy (IMRT) allows one to achieve a better conformation of the high-dose region to the prescribed tumor target volume than uniform beam therapy, especially in complex treatment situations. Still, perfect conformation is impossible. Hence the goal of optimized IMRT planning or inverse planning is to find the beam profiles that yield the optimum among the physically achievable treatment plans. The principal physical advantage of IMRT is best exploited if the optimization is driven by physical criteria. This article presents an overview of such physical, yet clinically relevant, criteria along with optimization algorithms that take these criteria into account. Practical computer implementations are described, which allow one to perform the optimization in an interactive manner within a few minutes. The application of these methods to some complex clinical example cases is presented, and the results are compared with uniform beam treatment plans and with biologically optimized plans.

Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuroectodermal tumors: reduction of the supratentorial target volume.

PURPOSE: One of the components of radiotherapy (RT) in medulloblastoma/primitive neuroectodermal tumors is the prophylactic irradiation of the whole brain (WBI). With the aim of reducing late neuropsychologic morbidity a CT-scan-based dosimetric study was undertaken in which treatment was confined mainly or exclusively to supratentorial sites considered at high risk for disease recurrence. METHODS AND MATERIALS: A comparative dosimetric study is presented in which a three field (two laterals and one posterior) proton plan (spot scanning method) is compared with a two-field conventional WBI 6 MV x-ray plan, to a 6-field "hand-made" 6 MV x-ray plan, and to a computer-optimized 9-field "inverse" 15 MV x-ray plan. For favorable patients, 30 Gy were delivered to the ventricles and main cisterns, the subfrontal and subtemporal regions, and the posterior fossa. For the unfavorable patients, 10 Gy WBI preceeded a boost to 30 Gy to the same treatment volume chosen for favorable patients. The dose distribution was evaluated with dose-volume histograms to examine the coverage of the targets as well as the dose to the nontarget brain and optical structures. In addition, the risks of radiation-related late neuropsychologic effects after WBI were collected from the literature and used to predict normal tissue complication probabilities (NTCPs) for an intelligence quotient deficit after treatment with photon or proton beams. RESULTS: Proton beams succeeded better in reducing the dose to the brain hemispheres and eye than any of the photon plans. A 25.1% risk of an IQ score <90 was predicted after 30 Gy WBI. Almost a 10% drop in the predicted risk was observed when using proton beams in both favorable and unfavorable patients. However, predicted NTCPs for both optimized photon plans ("hand made" and "inverse") were only slightly higher (0.3-2.5%) than those of proton beams. An age-modifying factor was introduced in the predictive NTCP model to assess for IQ differences in relation with age at irradiation. Children with ages between age 4 to 8 benefitted most from the dose reduction in this exercise (similar NTCP predictions for both proton and "inverse" plans). CONCLUSION: Modulated proton beams may help to significantly reduce the irradiation of normal brain while optimally treating the supratentorial subsites at higher risk for relapse. A decrease in morbidity can be expected from protons and both optimized proton plans compared to WBI.

Computer systems and mechanical tools for stereotactically guided conformation therapy with linear accelerators.

An integrated system for fractionated, stereotactically guided conformation radiotherapy has been developed. The system components are a stereotactic fixation system that can be used each treatment day, a localization, and positioning unit that can be used during x-ray computer tomography, magnetic resonance imaging, positron emission tomography, and radiographical examinations as well as for treatment. Conformal precision radiotherapy is planned with a new three-dimensional treatment planning system (Voxel-Plan-Heidelberg) which comprises, among others options, a three-dimensional image correlation procedure as well as routines for the calculation of coplanar and non-coplanar irradiations with irregularly shaped fields. Two different multi-leaf collimators have been designed for precision radiotherapy in the head and neck region. A manual multi-leaf collimator is used for irradiations with stationary beams or for moving beam treatments with invariable irregularly shaped fields. This collimator system is now being used for patient treatments. The design of a computer controlled multi-leaf collimator unit for multiple fixed field irradiation techniques is discussed. All system components are aimed at conforming dose distributions for fractionated radiotherapy treatments to the target to improve sparing of adjacent normal tissues, and at achieving a sufficient geometrical accuracy in the dose application.

X-ray field compensation with multileaf collimators.

PURPOSE: It has been proposed that conformal therapy can be carried out with static ports that are each individually compensated to deliver an optimal total dose distribution. If this proposal is to be implemented, one must have a means of compensating or modulating the fluence distributions within the boundaries of individual treatment fields. A theory was developed and implemented to achieve this goal. METHODS AND MATERIALS: The theory allowed creation of a leaf-setting sequence for a desired level of field-modulation precision. This method of beam modulation was experimentally verified using radiographic film to integrate the dose delivered by the sequence of discrete static multileaf collimator-defined subfields. RESULTS: Beam profiles were generated that matched the planned beam profiles to within the specified degree of precision. CONCLUSION: This methodology is a candidate for implementation of inverse planning for conformal therapy.

Realization and verification of three-dimensional conformal radiotherapy with modulated fields.

PURPOSE: We describe the experimental demonstration of the delivery of a three-dimensional conformal radiotherapy dose distribution using in-field modulation of nine fixed-gantry fields. METHODS AND MATERIALS: Two-dimensional in-field modulation profiles, varying from field to field, were realized by quasi-dynamic multileaf collimation using the prototype of a commercially available multileaf collimator installed on a medical linear accelerator. The profiles were calculated to deliver an optimal dose distribution for a patient with a prostate carcinoma. The target volume surface was invaginated and bifurcated. The calculated dose distribution was delivered to a homogeneous polystyrene phantom consisting of 1 cm thick slices that were cut to match the patient's outer contour. Seven therapy verification films were placed between the phantom slices. RESULTS: Analysis of the films revealed a degree of conformation of the high-dose region to the target shape that would not be possible with unmodulated conformal therapy. However, small observed spatial displacements of the dose distribution confirm the need for very accurate positioning. CONCLUSIONS: It is feasible to deliver clinically relevant, three-dimensional dose distributions that conform to invaginated and bifurcated target volumes using fields modulated by multileaf collimators.

Intensity modulation with the "step and shoot" technique using a commercial MLC: a planning study. Multileaf collimator.

PURPOSE/OBJECTIVE: For complex planning situations where organs at risk (OAR) surrounding the target volume place stringent constraints, intensity-modulated treatments with photons provide a promising solution to improve tumor control and/or reduce side effects. One approach for the clinical implementation of intensity-modulated treatments is the use of a multileaf collimator (MLC) in the "step and shoot" mode, in which multiple subfields are superimposed for each beam direction to generate stratified intensity distributions with a discrete number of intensity levels. In this paper, we examine the interrelation between the number of intensity levels per beam for various numbers of beams, the conformity of the resulting dose distribution, and the treatment time on a commercial accelerator (Siemens Mevatron KD2) with built-in MLC. METHODS AND MATERIALS: Two typical, clinically relevant cases of patients with head and neck tumors were selected for this study. Using the inverse planning technique, optimized treatment plans are generated for 3-25 evenly distributed coplanar beams as well as noncoplanar beams. An iterative gradient method is used to optimize a physical treatment objective that is based on the specified target dose and individual dose constraints assigned to each organ at risk (brain stem, eyes, optic nerves) by the radiation oncologist. The intensity distribution of each beam is discretized within the inverse planning program into three to infinitely many intensity levels or strata. These stratified intensity distributions are converted into MLC leaf position sequences, which can be subsequently transferred via computer link to the linac console, and can be delivered without user intervention. The quality of the plan is determined by comparing the values of the objective function, dose-volume histograms (DVHs), and isodose distributions. RESULTS: Highly conformal dose distributions can be achieved with five intensity levels in each of seven beams. The merit of using more intensity levels or more beams is relatively small. Acceptable results are achievable even with three levels only. On average, the number of subfields per beam is about 2-2.5 times the number of intensity levels. The average treatment time per subfield is about 20 s. The total treatment time for the three-level and seven-beam case with a total of 39 subfields is 13 min. CONCLUSION: Optimizing stratified intensity distributions in the inverse planning process allows us to achieve close to optimum results with a surprisingly small number of intensity levels. This finding may help to facilitate and accelerate the delivery of intensity-modulated treatments with the "step and shoot" technique.

The role of proton therapy in the treatment of large irradiation volumes: a comparative planning study of pancreatic and biliary tumors.

PURPOSE: The purpose of this study was to examine the potential benefit of proton therapy for abdominal tumors. Extensive comparative planning was conducted investigating the most up-to-date photon and proton irradiation technologies. METHODS AND MATERIALS: A number of rival plans were generated for four patients: two inoperable pancreatic tumors, one inoperable and one postoperative biliary duct tumor. The dose prescription goal for these large targets was 50 Gy, followed by a boost dose up to 20 Gy to a smaller planning target volume (PTV). Photon plans were developed using "forward" planning of coplanar and noncoplanar conformal fields and "inverse" planning of intensity-modulated (IM) fields. Proton planning was simulated as administered using the so called spot-scanning technique. Plans were evaluated on the basis of normal tissues' dose-volume constraints (Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1990;21:109-122) and coverage of treatment volumes with prescribed doses. RESULTS: For all cases, none of the forward calculated photon plans was able to deliver 50 Gy to large PTVs at the same time respecting the dose-volume constraints on all critical organs. Nine evenly spaced IM fields achieved or nearly achieved all maximum dose constraints to critical structures for two out of three inoperable patients. IM plans also obtained good results for the postoperative patient, even though the dose to the liver was very close to the maximum allowed. In all cases, photon irradiation of large PTV1s to 50 Gy followed by a 20 Gy boost entailed a risk very close to or higher than 5% for serious complications to the kidneys, liver, or bowel. Simple arrangements of 2, 3, and 4 proton fields obtained better dose conformation to the target, allowing the delivery of planned doses including the boost to all patients, without excessive risk of morbidity. Dose homogeneity inside the targets was also superior with protons. CONCLUSION: For the irradiation of large PTVs located in the abdominal cavity, where multiple, parallel structured organs surround the target volumes, proton therapy, delivered with a sophisticated isocentric technique, has the potential to achieve superior dose distributions compared with state-of-the-art photon irradiation techniques. IM photon plans obtain better results in the postoperative case, because the reduced volume lessens the effect of the unavoidable increase of integral dose to surrounding tissues.

Conformal radiation treatment of prostate cancer using inversely-planned intensity-modulated photon beams produced with dynamic multileaf collimation.

PURPOSE: To implement radiotherapy with intensity-modulated beams, based on the inverse method of treatment design and using a multileaf collimation system operating in the dynamic mode. METHODS AND MATERIALS: An algorithm, based on the inverse technique, has been integrated into the radiotherapy treatment-planning computer system in our Center. This method of computer-assisted treatment design was used to derive intensity-modulated beams to optimize the boost portion of the treatment plan for a patient with a T1c cancer of the prostate. A dose of 72 Gy (in 40 fractions) was given with a six-field plan, and an additional 9 Gy (in five fractions) with six intensity-modulated beams. The intensity-modulated fields were delivered using dynamic multileaf collimation, that is, individual leaves were in motion during radiation delivery, with the treatment machine operating in the clinical mode. Exhaustive quality assurance measurement and monitoring were carried out to ensure safe and accurate implementation. RESULTS: Dose distribution and dose-volume histogram of the "inverse method" boost plan and of the composite (72 Gy primary + 9 Gy boost) plan were judged clinically acceptable. Compared to a manually designed boost plan, the inverse treatment design gave improved conformality and increased dose homogeneity in the planning target volume. Film and ion chamber dosimetry, performed prior to the first treatment, indicated that each of the six intensity-modulated fields was accurately produced. Thermoluminescent dosimeter (TLD) measurements performed on the patient confirmed that the intended dose was delivered in the treatment. In addition, computer-aided treatment-monitoring programs assured that the multileaf collimator (MLC) position file was executed to the specified precision. In terms of the overall radiation treatment process, there will likely be labor savings in the planning and the treatment phases. CONCLUSIONS: We have placed into clinical use an integrated system of conformal radiation treatment that incorporated the inverse method of treatment design and the use of dynamic multileaf collimation to deliver intensity-modulated beams. The system can provide better treatment design, which can be implemented reliably and safely. We are hopeful that improved treatment efficacy will result.

Dynamic X-ray compensation for conformal radiotherapy by means of multi-leaf collimation.

The application of a multiple fixed field technique employing individually shaped and intensity-modulated beams makes it possible to produce dose distributions of high conformity even in the case of concave target volumes. With the technique presented here arbitrary intensity-modulated beams for the practical solution of the inverse problem can be generated. It is also possible to omit wedges, blocks and compensators in conventional radiotherapy. A continuous unidirectional sweep of independently computer-controlled leaves of a multi-leaf collimator is used to modulate the primary uniform beam. A new algorithm is introduced that computes the leaf trajectories. Also, a method is presented that accounts for leaf penumbra and transmission, which causes the generated fluence distribution to deviate from the desired fluence distribution. An optimization algorithm minimizing this deviation is described. The algorithm calculating the leaf trajectories, as well as the method considering penumbra and transmission and the successive optimization technique are used to calculate examples. Treatment times are calculated and compared to those needed when using compensators. A relationship between the treatment time and the maximum leaf speed is also deduced. To achieve good performance the maximum leaf speed should be no less than 20 mm/s.