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Beam position uncertainties along the beam trajectory arise from the accelerator, beamline, and scanning magnets (SMs). They can be monitored in real time, e.g., through strip ionization chambers (ICs), and treatments can be paused if needed. Delivery is more reliable and accurate if the beam position is projected from monitored nozzle parameters to the isocenter, allowing for accurate online corrections to be performed. Beam position projection algorithms are also used in post-delivery log file analyses. In this paper, we investigate the four potential algorithms that can be applied to all pencil beam scanning (PBS) nozzles. For some combinations of nozzle configurations and algorithms, however, the projection uses beam properties determined offline (e.g., through beam tuning or technical commissioning). The best algorithm minimizes either the total uncertainty (i.e., offline and online) or the total offline uncertainty in the projection. Four beam position algorithms are analyzed (A1-A4). Two nozzle lengths are used as examples: a large nozzle (1.5 m length) and a small nozzle (0.4 m length). Three nozzle configurations are considered: IC after SM, IC before SM, and ICs on both sides. Default uncertainties are selected for ion chamber measurements, nozzle entrance beam position and angle, and scanning magnet angle. The results for other uncertainties can be determined by scaling these results or repeating the error propagation. We show the propagation of errors from two locations and the SM angle to the isocenter for all the algorithms. The best choice of algorithm depends on the nozzle length and is A1 and A3 for the large and small nozzles, respectively. If the total offline uncertainty is to be minimized (a better choice if the offline uncertainty is not stable), the best choice of algorithm changes to A1 for the small nozzle for some hardware configurations. Reducing the nozzle length can help to reduce the gantry size and make proton therapy more accessible. This work is important for designing smaller nozzles and, consequently, smaller gantries. This work is also important for log file analyses.

The use of field-specific apertures, routine in scattered or uniform-scanned proton fields, are still a necessity in pencil-beam scanned (PBS) fields to sharpen the penumbral edge at low energies and in high fraction dose application beyond that achievable with small spot size. We describe a model implemented in our clinical pencil-beam algorithm that models the insertion of a shaped aperture, including shapes adapted per energy layer such as may be achieved with a multi-leaf collimator. The model decomposes the spot transport into discrete steps. The first step transport a uniform intensity field of high-resolution sub-pencil-beams at the layer energy through the medium. This transport only considers primary scattering in both the patient and an optional range-shifter. The second step models the aperture areas and edge penumbral transition as a modulation of the uniform intensity. The third step convolves individual steps over the uniform-transported field including the aperture-modified intensities. We also introduce an efficient model based on a Clarkson sector integration for nuclear scattered halo protons. This avoids the explicit modeling of long range halo protons to the detriment of computational efficiency in calculation and optimization. We demonstrate that the aperture effect is primarily due to in-patient and shifter scattering with a small contribution from the apparent beam source position. The model provides insight into the primary physics contributions to the penumbra and the nuclear halo. The model allowed us to fully deploy our PBS capacity at our two-gantry center without which PBS treatments would have been inferior compared to scattered fields with apertures. Finally, Monte Carlo calculations have (nearly) replaced phenomenological pencil-beam models for collimated fields. Phenomenological models do, however, allow exposition of underlying clinical phenomena and closer connection to representative clinical observables., (© 2022 IOP Publishing Ltd.)

To adopt Monte Carlo (MC) simulations as an independent dose calculation method for proton pencil beam radiotherapy, an interface that converts the plan information in DICOM format into MC components such as geometries and beam source is a crucial element. For this purpose, a DICOM-RT Ion interface (https://github.com/topasmc/dicom-interface) has been developed and integrated into the TOPAS MC code to perform such conversions on-the-fly. DICOM-RT objects utilized in this interface include Ion Plan (RTIP), Ion Beams Treatment Record (RTIBTR), CT image, and Dose. Beamline geometries, gantry and patient coordinate systems, and fluence maps are determined from RTIP and/or RTIBTR. In this interface, DICOM information is processed and delivered to a MC engine in two steps. A MC model, which consists of beamline geometries and beam source, to represent a treatment machine is created by a DICOM parser of the interface. The complexities from different DICOM types, various beamline configurations and source models are handled in this step. Next, geometry information and beam source are transferred to TOPAS on-the-fly via the developed TOPAS extensions. This interface with two treatment machines was successfully deployed into our automated MC workflow which provides simulated dose and LET distributions in a patient or a water phantom automatically when a new plan is identified. The developed interface provides novel features such as handling multiple treatment systems based on different DICOM types, DICOM conversions on-the-fly, and flexible sampling methods that significantly reduce the burden of handling DICOM based plan or treatment record information for MC simulations., (Copyright © 2020 Associazione Italiana di Fisica Medica. All rights reserved.)

Setup and range uncertainties compromise radiotherapy plan robustness. We introduce a method to evaluate the clinical effect of these uncertainties on the population using tumor control probability (TCP) and normal tissue complication probability (NTCP) models. Eighteen oropharyngeal cancer patients treated with curative intent were retrospectively included. Both photon (VMAT) and proton (IMPT) plans were created using a planning target volume as planning objective. Plans were recalculated for uncertainty scenarios: two for range over/undershoot (IMPT) or CT-density scaling (VMAT), six for shifts. An average shift scenario ([Formula: see text]) was calculated to assess random errors. Dose differences between nominal and scenarios were translated to TCP (2 models) and NTCP (15 models). A weighted average (W_Avg) of the TCP\NTCP based on Gaussian distribution over the variance scenarios was calculated to assess the clinical effect of systematic errors on the population. TCP/NTCP uncertainties were larger in IMPT compared to VMAT. Although individual perturbations showed risks of plan deterioration, the [Formula: see text] scenario did not show a substantial decrease in any of the TCP endpoints suggesting evaluated plans in this cohort were robust for random errors. Evaluation of the W_Avg scenario to assess systematic errors showed in VMAT no substantial decrease in TCP endpoints and in IMPT a limited decrease. In IMPT, the W_Avg scenario had a mean TCP loss of 0%-2% depending on plan type and primary or nodal control. The W_Avg for NTCP endpoints was around 0%, except for mandible necrosis in IMPT (W_Avg: 3%). The estimated population impact of setup and range uncertainties on TCP/NTCP following VMAT or IMPT of oropharyngeal cancer patients was small for both treatment modalities. The use of TCP/NTCP models allows for clinical interpretation of the population effect and could be considered for incorporation in robust evaluation methods. Highlights: - TCP/NTCP models allow for a clinical evaluation of uncertainty scenarios. - For this cohort, in silico-PTV based IMPT plans and VMAT plans were robust for random setup errors. - Effect of systematic errors on the population was limited: mean TCP loss was 0%-2%.

Background: In scanned proton beam therapy systematic deviations in spot size at iso-center can occur as a result of changes in the beam-line optics. There is currently no general guideline of the spot size accuracy required clinically. In this work we quantify treatment plan robustness to systematic spot size variations as a function of spot size and spot spacing, and we suggest guidelines for tolerance levels for spot size variations., Methods: Through perturbation of spot size in treatment plans for 7 patients and a phantom, we evaluated the dose impact of systematic spot size variations of 5% up to 50%. We investigated the dependence on nominal spot size by studying scenarios with small, medium and large spot sizes for various inter-spot spacings. To come to tolerance levels, we used the Γ passing rate and dose-volume-histograms., Results: Limits on spot size accuracy were extracted for 8 sites, 3 different spot sizes and 3 different inter-spot spacings. While the allowable spot size variation strongly depends on the spot size, the inter-spot spacing turned out to be only of limited influence., Conclusions: Plan robustness to spot size variations strongly depend on spot size, with small spot plans being much more robust than larger spots plans. Inter-spot spacing did not influence plan robustness. Combining our results with existing literature, we propose limits of ±25%, ±20% and ±10% of the spot width σ, for spots with σ of 2.5, 5.0 and 10 mm in proton therapy spot scanning facilities, respectively., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Spot size σ (in air at isocenter), interspot spacing d, and spot charge q influence dose delivery efficiency and plan quality in Intensity Modulated Proton Therapy (IMPT) treatment planning. The choice and range of parameters varies among different manufacturers. The goal of this work is to demonstrate the influence of the spot parameters on dose quality and delivery in IMPT treatment plans, to show their interdependence, and to make practitioners aware of the spot parameter values for a certain facility. Our study could help as a guideline to make the trade-off between treatment quality and time in existing PBS centers and in future systems., Methods: We created plans for seven patients and a phantom, with different tumor sites and volumes, and compared the effect of small-, medium-, and large-spot widths (σ = 2.5, 5, and 10 mm) and interspot distances (1σ, 1.5σ, and 1.75σ) on dose, spot charge, and treatment time. Moreover, we quantified how postplanning charge threshold cuts affect plan quality and the total number of spots to deliver, for different spot widths and interspot distances. We show the effect of a minimum charge (or MU) cutoff value for a given proton delivery system., Results: Spot size had a strong influence on dose: larger spots resulted in more protons delivered outside the target region. We observed dose differences of 2-13 Gy (RBE) between 2.5 mm and 10 mm spots, where the amount of extra dose was due to dose penumbra around the target region. Interspot distance had little influence on dose quality for our patient group. Both parameters strongly influence spot charge in the plans and thus the possible impact of postplanning charge threshold cuts. If such charge thresholds are not included in the treatment planning system (TPS), it is important that the practitioner validates that a given combination of lower charge threshold, interspot spacing, and spot size does not result in a plan degradation. Low average spot charge occurs for small spots, small interspot distances, many beam directions, and low fractional dose values., Conclusions: The choice of spot parameters values is a trade-off between accelerator and beam line design, plan quality, and treatment efficiency. We recommend the use of small spot sizes for better organ-at-risk sparing and lateral interspot distances of 1.5σ to avoid long treatment times. We note that plan quality is influenced by the charge cutoff. Our results show that the charge cutoff can be sufficiently large (i.e., 10 6 protons) to accommodate limitations on beam delivery systems. It is, therefore, not necessary per se to include the charge cutoff in the treatment planning optimization such that Pareto navigation (e.g., as practiced at our institution) is not excluded and optimal plans can be obtained without, perhaps, a bias from the charge cutoff. We recommend that the impact of a minimum charge cut impact is carefully verified for the spot sizes and spot distances applied or that it is accommodated in the TPS., (© 2017 American Association of Physicists in Medicine.)

Background: Spot charge is one parameter of pencil-beam scanning dose delivery system whose accuracy is typically high but whose required value has not been investigated. In this work we quantify the dose impact of spot charge inaccuracies on the dose distribution in patients. Knowing the effect of charge errors is relevant for conventional proton machines, as well as for new generation proton machines, where ensuring accurate charge may be challenging., Methods: Through perturbation of spot charge in treatment plans for seven patients and a phantom, we evaluated the dose impact of absolute (up to 5× 10 6 protons) and relative (up to 30%) charge errors. We investigated the dependence on beam width by studying scenarios with small, medium and large beam sizes. Treatment plan statistics included the Γ passing rate, dose-volume-histograms and dose differences., Results: The allowable absolute charge error for small spot plans was about 2× 10 6 protons. Larger limits would be allowed if larger spots were used. For relative errors, the maximum allowable error size for small, medium and large spots was about 13%, 8% and 6% for small, medium and large spots, respectively., Conclusions: Dose distributions turned out to be surprisingly robust against random spot charge perturbation. Our study suggests that ensuring spot charge errors as small as 1-2% as is commonly aimed at in conventional proton therapy machines, is clinically not strictly needed., (© 2017 American Association of Physicists in Medicine.)

Purpose: This study aimed to assess the clinical impact of spot size and the addition of apertures and range compensators on the treatment quality of pencil beam scanning (PBS) proton therapy and to define when PBS could improve on passive scattering proton therapy (PSPT)., Methods and Materials: The patient cohort included 14 pediatric patients treated with PSPT. Six PBS plans were created and optimized for each patient using 3 spot sizes (∼12-, 5.4-, and 2.5-mm median sigma at isocenter for 90- to 230-MeV range) and adding apertures and compensators to plans with the 2 larger spots. Conformity and homogeneity indices, dose-volume histogram parameters, equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and integral dose were quantified and compared with the respective PSPT plans., Results: The results clearly indicated that PBS with the largest spots does not necessarily offer a dosimetric or clinical advantage over PSPT. With comparable target coverage, the mean dose (Dmean) to healthy organs was on average 6.3% larger than PSPT when using this spot size. However, adding apertures to plans with large spots improved the treatment quality by decreasing the average Dmean and EUD by up to 8.6% and 3.2% of the prescribed dose, respectively. Decreasing the spot size further improved all plans, lowering the average Dmean and EUD by up to 11.6% and 10.9% compared with PSPT, respectively, and eliminated the need for beam-shaping devices. The NTCP decreased with spot size and addition of apertures, with maximum reduction of 5.4% relative to PSPT., Conclusions: The added benefit of using PBS strongly depends on the delivery configurations. Facilities limited to large spot sizes (>∼8 mm median sigma at isocenter) are recommended to use apertures to reduce treatment-related toxicities, at least for complex and/or small tumors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Delivery of pencil beam scanning (PBS) requires the on-line measurement of several beam parameters. If the measurement is outside of specified tolerances and a binary threshold algorithm is used, the beam will be paused. Given instrumentation and statistical noise such a system can lead to many pauses which could increase the treatment time. Statistical quality control methods are typically used on manufacturing lines to monitor a process and give early detection of a gradual problem and stop the process if a deviation is statistically significant. These methods can be used to develop a more intuitive algorithm for (PBS) delivery systems that is robust and safe and leads to decreased treatment times. The Exponentially Weighted Moving Average (EWMA) control scheme monitors deviations in beam properties which are averaged over a specified number of measurements with greater weight applied to the more recent ones. Simulation of an EWMA-style algorithm safely detected shifts in random and systematic delivery errors without false alarms. Binary and EWMA methods can be combined for improved reliability without sacrificing patient safety. In the EWMA method, the mean of a beam property can be related to systematic uncertainties and the standard deviation can be related to random uncertainties. This method allows one to have separate interlock levels for each type of uncertainty and to detect systematic trends.

Intensity modulated proton therapy (IMPT) implies the electromagnetic spatial control of well-circumscribed "pencil beams" of protons of variable energy and intensity. Proton pencil beams take advantage of the charged-particle Bragg peak-the characteristic peak of dose at the end of range-combined with the modulation of pencil beam variables to create target-local modulations in dose that achieves the dose objectives. IMPT improves on X-ray intensity modulated beams (intensity modulated radiotherapy or volumetric modulated arc therapy) with dose modulation along the beam axis as well as lateral, in-field, dose modulation. The clinical practice of IMPT further improves the healthy tissue vs target dose differential in comparison with X-rays and thus allows increased target dose with dose reduction elsewhere. In addition, heavy-charged-particle beams allow for the modulation of biological effects, which is of active interest in combination with dose "painting" within a target. The clinical utilization of IMPT is actively pursued but technical, physical and clinical questions remain. Technical questions pertain to control processes for manipulating pencil beams from the creation of the proton beam to delivery within the patient within the accuracy requirement. Physical questions pertain to the interplay between the proton penetration and variations between planned and actual patient anatomical representation and the intrinsic uncertainty in tissue stopping powers (the measure of energy loss per unit distance). Clinical questions remain concerning the impact and management of the technical and physical questions within the context of the daily treatment delivery, the clinical benefit of IMPT and the biological response differential compared with X-rays against which clinical benefit will be judged. It is expected that IMPT will replace other modes of proton field delivery. Proton radiotherapy, since its first practice 50 years ago, always required the highest level of accuracy and pioneered volumetric treatment planning and imaging at a level of quality now standard in X-ray therapy. IMPT requires not only the highest precision tools but also the highest level of system integration of the services required to deliver high-precision radiotherapy.

Purpose: To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan., Methods and Materials: We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system "Erasmus-iCycle." The method consisted of 2 components: (1) minimizing the logarithm of the total spot weight per energy layer; and (2) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust "time-efficient plan" (with energy layer reduction) with a robust "standard clinical plan" (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases. Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds., Results: The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases., Conclusions: Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Setup, range, and anatomical uncertainties influence the dose delivered with intensity modulated proton therapy (IMPT), but clinical quantification of these errors for oropharyngeal cancer is lacking. We quantified these factors and investigated treatment fidelity, that is, robustness, as influenced by adaptive planning and by applying more beam directions., Methods and Materials: We used an in-house treatment planning system with multicriteria optimization of pencil beam energies, directions, and weights to create treatment plans for 3-, 5-, and 7-beam directions for 10 oropharyngeal cancer patients. The dose prescription was a simultaneously integrated boost scheme, prescribing 66 Gy to primary tumor and positive neck levels (clinical target volume-66 Gy; CTV-66 Gy) and 54 Gy to elective neck levels (CTV-54 Gy). Doses were recalculated in 3700 simulations of setup, range, and anatomical uncertainties. Repeat computed tomography (CT) scans were used to evaluate an adaptive planning strategy using nonrigid registration for dose accumulation., Results: For the recalculated 3-beam plans including all treatment uncertainty sources, only 69% (CTV-66 Gy) and 88% (CTV-54 Gy) of the simulations had a dose received by 98% of the target volume (D98%) >95% of the prescription dose. Doses to organs at risk (OARs) showed considerable spread around planned values. Causes for major deviations were mixed. Adaptive planning based on repeat imaging positively affected dose delivery accuracy: in the presence of the other errors, percentages of treatments with D98% >95% increased to 96% (CTV-66 Gy) and 100% (CTV-54 Gy). Plans with more beam directions were not more robust., Conclusions: For oropharyngeal cancer patients, treatment uncertainties can result in significant differences between planned and delivered IMPT doses. Given the mixed causes for major deviations, we advise repeat diagnostic CT scans during treatment, recalculation of the dose, and if required, adaptive planning to improve adequate IMPT dose delivery., (Copyright © 2013 Elsevier Inc. All rights reserved.)

This study investigates whether 'pencil beam resampling', i.e. iterative selection and weight optimization of randomly placed pencil beams (PBs), reduces optimization time and improves plan quality for multi-criteria optimization in intensity-modulated proton therapy, compared with traditional modes in which PBs are distributed over a regular grid. Resampling consisted of repeatedly performing: (1) random selection of candidate PBs from a very fine grid, (2) inverse multi-criteria optimization, and (3) exclusion of low-weight PBs. The newly selected candidate PBs were added to the PBs in the existing solution, causing the solution to improve with each iteration. Resampling and traditional regular grid planning were implemented into our in-house developed multi-criteria treatment planning system 'Erasmus iCycle'. The system optimizes objectives successively according to their priorities as defined in the so-called 'wish-list'. For five head-and-neck cancer patients and two PB widths (3 and 6 mm sigma at 230 MeV), treatment plans were generated using: (1) resampling, (2) anisotropic regular grids and (3) isotropic regular grids, while using varying sample sizes (resampling) or grid spacings (regular grid). We assessed differences in optimization time (for comparable plan quality) and in plan quality parameters (for comparable optimization time). Resampling reduced optimization time by a factor of 2.8 and 5.6 on average (7.8 and 17.0 at maximum) compared with the use of anisotropic and isotropic grids, respectively. Doses to organs-at-risk were generally reduced when using resampling, with median dose reductions ranging from 0.0 to 3.0 Gy (maximum: 14.3 Gy, relative: 0%-42%) compared with anisotropic grids and from -0.3 to 2.6 Gy (maximum: 11.4 Gy, relative: -4%-19%) compared with isotropic grids. Resampling was especially effective when using thin PBs (3 mm sigma). Resampling plans contained on average fewer PBs, energy layers and protons than anisotropic grid plans and more energy layers and protons than isotropic grid plans. In conclusion, resampling resulted in improved plan quality and in considerable optimization time reduction compared with traditional regular grid planning.

Background and Purpose: Delivery of post-mastectomy radiation (PMRT) in women with bilateral implants represents a technical challenge, particularly when attempting to cover regional lymph nodes. Intensity modulated proton therapy (IMPT) holds the potential to improve dose delivery and spare non-target tissues. The purpose of this study was to compare IMPT to three-dimensional (3D) conformal radiation following bilateral mastectomy and reconstruction., Materials and Methods: Ten IMPT, 3D conformal photon/electron (P/E), and 3D photon (wide tangent) plans were created for 5 patients with breast cancer, all of whom had bilateral breast implants. Using RTOG guidelines, a physician delineated contours for both target volumes and organs-at-risk. Plans were designed to achieve 95% coverage of all targets (chest wall, IMN, SCV, axilla) to a dose of 50.4 Gy or Gy (RBE) while maximally sparing organs-at-risk., Results: IMPT plans conferred similar target volume coverage with enhanced homogeneity. Both mean heart and lung doses using IMPT were significantly decreased compared to both P/E and wide tangent planning., Conclusions: IMPT provides improved homogeneity to the chest wall and regional lymphatics in the post-mastectomy setting with improved sparing of surrounding normal structures for woman with reconstructed breasts. IMPT may enable women with mastectomy to undergo radiation therapy without the need for delay in breast reconstruction., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Treatment planning databases for pencil beam scanning can be large, difficult to manage and problematic for quality assurance when they contain tabulated Bragg peaks at small range resolution. Smaller range resolution, in the absence of an accurate interpolation method, improves the accuracy in dose calculations. In this work, we derive an approximate scaling function to interpolate between tabulated Bragg peaks, and determine the accuracy of this interpolation technique and the minimum number of tabulated peaks in a treatment planning database. With the new interpolation technique, three tabulated mono-energetic Bragg peaks (N = 3) are a suitable lower limit for N to achieve interpolation accuracy better than ±1% of the maximum dose in pristine and spread out Bragg peaks for ranges between 6.8 and 32.1 cm of water.

The γ-index is used routinely to establish correspondence between two dose distributions. The definition of the γ-index can be written with a single equation but solving this equation at millions of points is computationally expensive, especially in three dimensions. Our goal is to extend the vector-equation method in Bakai et al (2003 Phys. Med. Biol.48 3543-53) to higher order for better accuracy and, as important, to determine the magnitude of accuracy in a higher order solution. We construct a numerical framework for calculating the γ-index in two and three dimensions and present an efficient method for calculating the γ-index with zeroth-, first- and second-order methods using tricubic spline interpolation. For an intensity-modulated radiation therapy example with 1.78 × 10⁶ voxels, the zeroth-order, first-order, first-order iterations and semi-second-order methods calculate the three-dimensional γ-index in 1.5, 4.7, 34.7 and 35.6 s with 36.7%, 1.1%, 0.2% and 0.8% accuracy, respectively. The accuracy of linear interpolation with this example is 1.0%. We present efficient numerical methods for calculating the three-dimensional γ-index with tricubic spline interpolation. The first-order method with iterations is the most accurate and fastest choice of the numerical methods if the dose distributions may have large second-order gradients. Furthermore, the difference between iterations can be used to determine the accuracy of the method.

This study is aimed at identifying the potential benefits of using a patient-specific aperture in proton beam scanning. For this purpose, an accurate Monte Carlo model of the pencil beam scanning (PBS) proton therapy (PT) treatment head at Massachusetts General Hospital (MGH) was developed based on an existing model of the passive double-scattering (DS) system. The Monte Carlo code specifies the treatment head at MGH with sub-millimeter accuracy. The code was configured based on the results of experimental measurements performed at MGH. This model was then used to compare out-of-field doses in simulated DS treatments and PBS treatments. For the conditions explored, the penumbra in PBS is wider than in DS, leading to higher absorbed doses and equivalent doses adjacent to the primary field edge. For lateral distances greater than 10 cm from the field edge, the doses in PBS appear to be lower than those observed for DS. We found that placing a patient-specific aperture at nozzle exit during PBS treatments can potentially reduce doses lateral to the primary radiation field by over an order of magnitude. In conclusion, using a patient-specific aperture has the potential to further improve the normal tissue sparing capabilities of PBS.

Proton, as well as other ion, beams applied by electro-magnetic deflection in pencil-beam scanning (PBS) are minimally perturbed and thus can be quantified a priori by their fundamental interactions in a medium. This a priori quantification permits an optimal reduction of characterizing measurements on a particular PBS delivery system. The combination of a priori quantification and measurements will then suffice to fully describe the physical interactions necessary for treatment planning purposes. We consider, for proton beams, these interactions and derive a 'Golden' beam data set. The Golden beam data set quantifies the pristine Bragg peak depth-dose distribution in terms of primary, multiple Coulomb scatter, and secondary, nuclear scatter, components. The set reduces the required measurements on a PBS delivery system to the measurement of energy spread and initial phase space as a function of energy. The depth doses are described in absolute units of Gy(RBE) mm² Gp⁻¹, where Gp equals 10⁹ (giga) protons, thus providing a direct mapping from treatment planning parameters to integrated beam current. We used these Golden beam data on our PBS delivery systems and demonstrated that they yield absolute dosimetry well within clinical tolerance.

Purpose: To describe a fast projection algorithm for optimizing intensity modulated proton therapy (IMPT) plans and to describe and demonstrate the use of this algorithm in multicriteria IMPT planning., Methods: The authors develop a projection-based solver for a class of convex optimization problems and apply it to IMPT treatment planning. The speed of the solver permits its use in multicriteria optimization, where several optimizations are performed which span the space of possible treatment plans. The authors describe a plan database generation procedure which is customized to the requirements of the solver. The optimality precision of the solver can be specified by the user., Results: The authors apply the algorithm to three clinical cases: A pancreas case, an esophagus case, and a tumor along the rib cage case. Detailed analysis of the pancreas case shows that the algorithm is orders of magnitude faster than industry-standard general purpose algorithms (MOSEK'S interior point optimizer, primal simplex optimizer, and dual simplex optimizer). Additionally, the projection solver has almost no memory overhead., Conclusions: The speed and guaranteed accuracy of the algorithm make it suitable for use in multicriteria treatment planning, which requires the computation of several diverse treatment plans. Additionally, given the low memory overhead of the algorithm, the method can be extended to include multiple geometric instances and proton range possibilities, for robust optimization.

Purpose: We completed an implementation of pencil-beam scanning (PBS), a technology whereby a focused beam of protons, of variable intensity and energy, is scanned over a plane perpendicular to the beam axis and in depth. The aim of radiotherapy is to improve the target to healthy tissue dose differential. We illustrate how PBS achieves this aim in a patient with a bulky tumor., Methods and Materials: Our first deployment of PBS uses "broad" pencil-beams ranging from 20 to 35 mm (full-width-half-maximum) over the range interval from 32 to 7 g/cm(2). Such beam-brushes offer a unique opportunity for treating bulky tumors. We present a case study of a large (4,295 cc clinical target volume) retroperitoneal sarcoma treated to 50.4 Gy relative biological effectiveness (RBE) (presurgery) using a course of photons and protons to the clinical target volume and a course of protons to the gross target volume., Results: We describe our system and present the dosimetry for all courses and provide an interdosimetric comparison., Discussion: The use of PBS for bulky targets reduces the complexity of treatment planning and delivery compared with collimated proton fields. In addition, PBS obviates, especially for cases as presented here, the significant cost incurred in the construction of field-specific hardware. PBS offers improved dose distributions, reduced treatment time, and reduced cost of treatment., (Copyright 2010 Elsevier Inc. All rights reserved.)

Proton radiotherapy centers that currently use passively scattered proton beams do field specific calibrations for a non-negligible fraction of treatment fields, which is time and resource consuming. Our improved understanding of the passive scattering mode of the IBA universal nozzle, especially of the current modulation function, allowed us to re-commission our treatment control system for accurate delivery of SOBPs of any range and modulation, and to predict the output for each of these fields. We moved away from individual field calibrations to a state where continued quality assurance of SOBP field delivery is ensured by limited system-wide measurements that only require one hour per week. This manuscript reports on a protocol for generation of desired SOBPs and prediction of dose output.

A mini-multileaf collimator (MMLC) was mounted as a field shaping collimator in a proton beamline at the Massachusetts General Hospital. The purpose is to evaluate the device's dosimetric and mechanical properties for the use in a proton beamline. For this evaluation, the authors compared MMLC and brass aperture shaped dose distributions with regard to lateral and depth dose properties. The lateral fall off is generally broader with the MMLC, with difference varying with proton range from 0.2 to 1.2 mm. Central axis depth dose curves did not show a difference in peak-to-entrance ratio, peak width, distal fall off, or range. Two-dimensional dose distributions to investigate the conformity of MMLC shaped doses show that the physical leaf width of approximately 2.5 mm does not have a significant impact. All differences seen in dose distribution shaped by the MMLC versus brass apertures were shown to be clinically insignificant. Measured neutron doses of 0.03-0.13 mSv/Gy for a closed brass beam block (depending on range) are very low compared to the previously published data. Irradiation of the tungsten MMLC, however, produced 1.5-1.8 times more neutrons than brass apertures. Exposure of the staff resulting from activation of the device is below regulatory limits. The measurements established an equivalency between aperture and MMLC shaped dose distributions.

Field-specific apertures, of sufficient range-absorbing thickness, are used in the majority of proton-therapy treatments today. In current practice, these apertures are modelled as objects of infinitesimal thickness. Such an approximation, however, is not accurate if the aperture edge is close to, or extends over, the beam axis. Practical situations in which this occurs include off-axis patch fields, small apertures, and fields shaped with a multileaf collimator. We develop an extension of the pencil-beam dose model to incorporate the aperture thickness. We derive an exact solution as well as a computationally simpler approximate implementation. The model is validated using measurements of the lateral penumbra. For a set-up with a source size of 2.76 cm, a source-to-axis distance of 227 cm, and a aperture-to-axis distance of 35 cm, the maximum increase in penumbra for a 6 cm thick aperture compared to the thin-aperture model is about 2 mm. The maximum shift in the 95% isodose contour line is larger. The overall effect depends on the aperture thickness, the position of the aperture edge and the intrinsic source size and SAD, but is fairly insensitive to aperture-to-skin distance and depth in patient.

Purpose: In proton radiotherapy, respiration-induced variations in density lead to changes in radiologic path lengths and will possibly result in geometric misses. We compared different treatment planning strategies for lung tumors that compensate for respiratory motion., Methods and Materials: Particle-specific treatment planning margins were applied to standard helical computed tomography (CT) scans as well as to "representative" CT scans. Margins were incorporated beam specific laterally by aperture widening and longitudinally by compensator smearing. Furthermore, treatment plans using full time-resolved 4D-computed tomography data were generated., Results: Four-dimensional treatment planning guaranteed target coverage throughout a respiratory cycle. Use of a standard helical CT data set resulted in underdosing the target volume to 36% of the prescribed dose. For CT data representing average target positions, coverage can be expected but not guaranteed. In comparison to this strategy, 4D planning decreased the mean lung dose by up to 16% and the lung volume receiving 20 Gy (prescribed target dose 72 Gy) by up to 15%., Conclusion: When the three planning strategies are compared, only 4D proton treatment planning guarantees delivery of the prescribed dose throughout a respiratory cycle. Furthermore, the 4D planning approach results in equal or reduced dose to critical structures; even the ipsilateral lung is spared.

The reliable prediction of output factors for spread-out proton Bragg peak (SOBP) fields in clinical practice remained unrealized due to a lack of a consistent theoretical framework and the great number of variables introduced by the mechanical devices necessary for the production of such fields. These limitations necessitated an almost exclusive reliance on manual calibration for individual fields and empirical, ad hoc, models. We recently reported on a theoretical framework for the prediction of output factors for such fields. In this work, we describe the implementation of this framework in our clinical practice. In our practice, we use a treatment delivery nozzle that uses a limited, and constant, set of mechanical devices to produce SOBP fields over the full extent of clinical penetration depths, or ranges, and modulation widths. This use of a limited set of mechanical devices allows us to unfold the physical effects that affect the output factor. We describe these effects and their incorporation into the theoretical framework. We describe the calibration and protocol for SOBP fields, the effects of apertures and range-compensators and the use of output factors in the treatment planning process.

We performed a treatment planning study in order to gather basic insight in the effect of setup errors and breathing motion on the cumulative proton dose to a lung tumor. We used a simplified geometry that simulates a 50 mm diameter gross tumor volume (GTV) located centrally inside lung tissue. The GTV was expanded with a uniform 5 mm margin into a clinical target volume (CTV) and into a variety of planning target volume (PTV's). Proton beam apertures were designed to conform the prescribed dose laterally to the PTV while the range compensator was designed to provide distal coverage of the CTV. Different smearing distances were applied to the range compensators, and the cumulative dose in the CTV was evaluated for different combinations of breathing motion and systematic setup errors. Evaluation parameters were the dose to 99% of the CTV (D99) and the equivalent uniform dose (EUD), with a surviving fraction at 2 Gy of SF2 = 0.5. For a single proton field designed to a 15 mm expansion of the CTV and without smearing applied to the range compensator, D99 of the CTV reduced from 96% for no tumor displacement to 41% and 13% for systematic setup errors of 5 and 10 mm, respectively. For a representative clinical combination, of 5 mm systematic error and 10 mm breathing amplitude, the EUD of the CTV was about 40 Gy (prescribed dose 70 Gy) regardless the CTV to PTV margin, and without smearing. Smearing the range compensator increases the dose to the CTV substantially with a lateral margin and smearing distance of 7.5 mm providing ample tumor coverage. In this latter case, D99 of the target volume increased to 87% for a single field treatment plan. Smearing does, however, lead to an increase in dose to normal tissues distal to the clinical target volume. Next to countering geometric mismatches due to patient setup, smearing can also be used to counter the detrimental effects of breathing motion on the dose to the clinical target volume. We show that the lateral margin and smearing distance can be substantially smaller than the maximum tumor displacement due to setup errors and patient breathing, as measured by the D99 and the EUD.

The magnitude of inter- and intrafractional patient motion has been assessed for a broad set of immobilization devices. Data was analyzed for the three ordinal directions--left-right (x), sup-inf (y), and ant-post (z)--and the combined spatial displacement. We have defined "rigid" and "non-rigid" immobilization devices depending on whether they could be rigidly and reproducibly connected to the treatment couch or not. The mean spatial displacement for intrafractional motion for rigid devices is 1.3 mm compared to 1.9 mm for nonrigid devices. The modified Gill-Thomas-Cosman frame performed best at controlling intrafractional patient motion, with a 95% probability of observing a three-dimensional (3D) vector length of motion (v95) of less than 1.8 mm, but could not be evaluated for interfractional motion. All other rigid and nonrigid immobilization devices had a v95 of more than 3 mm for intrafractional patient motion. Interfractional patient motion was only evaluated for the rigid devices. The mean total interfractional displacement was at least 3.0 mm for these devices while v95 was at least 6.0 mm.

Objective: To determine the outcome and toxicity in patients with vestibular schwannomas treated with conventionally fractionated stereotactic radiotherapy (SRT) and to identify prognostic factors that are predictive of outcome., Methods: Between 1992 and 2001, 70 patients with vestibular schwannomas were treated with linear accelerator-based SRT in our institutions. Eleven patients had neurofibromatosis Type II (NF2). The median age was 53 years (range, 17-82 yrs). The median tumor volume was 2.4 cm3 (range, 0.05-21.1 cm3). The indications for SRT were distributed as follows: 47% newly diagnosed, 31% progressive tumors after watchful waiting, 3% adjuvant postoperative radiation, and 19% recurrent tumors after surgical resection. The median dose was 54 Gy in 1.8 Gy per fraction, prescribed to 95% of the isodose line. Relocatable stereotactic frames were used for daily treatments. The median follow-up was 45.3 months., Results: Tumor recurrence was defined as progressive enlargement of tumor on follow-up magnetic resonance imaging studies. One patient had a tumor recurrence at 38 months after SRT. The actuarial tumor control rates were 100 and 98% at 3 and 5 years, respectively. Three patients with a median tumor volume of 16.2 cm3 required surgical resection for persistent or increasing symptoms at a median of 37 months. The actuarial freedom from resection rates were 98 and 92% at 3 and 5 years, respectively. In multivariate analysis, tumor volume at time of treatment was predictive for neurosurgical intervention (surgical resection or shunt placement) after SRT (P = 0.001). The 3- and 5-year actuarial rates of freedom from any neurosurgical intervention were 100 and 97% for patients with tumor volume less than 8 cm3 and 74 and 47% respectively for patients with tumor of at least 8 cm3 (P < 0.0001). The 3-year actuarial rates of facial and trigeminal nerve preservation were 99 and 96%, respectively. Surgery before SRT was predictive of posttreatment trigeminal neuropathy. The 3-year actuarial rates of freedom from trigeminal neuropathy were 86 and 98% for patients with and without previous resection, respectively (P = 0.04). There was no difference in tumor control and cranial nerve function preservation rates seen in NF2 patients compared with non-NF2 patients. No second primary cancer or malignant transformation was observed., Conclusion: SRT in the conventionally fractionated approach results in a very favorable outcome with minimal toxicity, with results comparable to those of the best of the radiosurgery series. Patients with large tumors are more likely to undergo neurosurgical interventions after SRT. Patients who have undergone previous surgery are at increased risk of developing trigeminal neuropathy.

Monte Carlo dosimetry calculations are essential methods in radiation therapy. To take full advantage of this tool, the beam delivery system has to be simulated in detail and the initial beam parameters have to be known accurately. The modeling of the beam delivery system itself opens various areas where Monte Carlo calculations prove extremely helpful, such as for design and commissioning of a therapy facility as well as for quality assurance verification. The gantry treatment nozzles at the Northeast Proton Therapy Center (NPTC) at Massachusetts General Hospital (MGH) were modeled in detail using the GEANT4.5.2 Monte Carlo code. For this purpose, various novel solutions for simulating irregular shaped objects in the beam path, like contoured scatterers, patient apertures or patient compensators, were found. The four-dimensional, in time and space, simulation of moving parts, such as the modulator wheel, was implemented. Further, the appropriate physics models and cross sections for proton therapy applications were defined. We present comparisons between measured data and simulations. These show that by modeling the treatment nozzle with millimeter accuracy, it is possible to reproduce measured dose distributions with an accuracy in range and modulation width, in the case of a spread-out Bragg peak (SOBP), of better than 1 mm. The excellent agreement demonstrates that the simulations can even be used to generate beam data for commissioning treatment planning systems. The Monte Carlo nozzle model was used to study mechanical optimization in terms of scattered radiation and secondary radiation in the design of the nozzles. We present simulations on the neutron background. Further, the Monte Carlo calculations supported commissioning efforts in understanding the sensitivity of beam characteristics and how these influence the dose delivered. We present the sensitivity of dose distributions in water with respect to various beam parameters and geometrical misalignments. This allows the definition of tolerances for quality assurance and the design of quality assurance procedures.

Purpose: To compare treatment plans from standard photon therapy to intensity modulated X-rays (IMRT) and protons for craniospinal axis irradiation and posterior fossa boost in a patient with medulloblastoma., Methods: Proton planning was accomplished using an in-house 3D planning system. IMRT plans were developed using the KonRad treatment planning system with 6-MV photons., Results: Substantial normal-tissue dose sparing was realized with IMRT and proton treatment of the posterior fossa and spinal column. For example, the dose to 90% of the cochlea was reduced from 101.2% of the prescribed posterior fossa boost dose from conventional X-rays to 33.4% and 2.4% from IMRT and protons, respectively. Dose to 50% of the heart volume was reduced from 72.2% for conventional X-rays to 29.5% for IMRT and 0.5% for protons. Long-term toxicity with emphasis on hearing and endocrine and cardiac function should be substantially improved secondary to nontarget tissue sparing achieved with protons., Conclusion: The present study clearly demonstrates the advantage of conformal radiation methods for the treatment of posterior fossa and spinal column in children with medulloblastoma, when compared to conventional X-rays. Of the two conformal treatment methods evaluated, protons were found to be superior to IMRT.

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%.

Using multiple computed tomography (CT) scans, 50 patients undergoing prostate radiotherapy were tested for clinically significant time trends in the target and surrounding critical structures. Significant trends were observed toward increasing bladder volume and increasing bowel-to-planning target volume separation; however, no trends were observed in the prostate, seminal vesicles, or rectum. The subset of patients undergoing hormone therapy was also tested and did not independently exhibit any significant time trends.

Purpose: Intracranial germ cell tumors are rare, radiosensitive tumors seen most commonly in the second and third decades of life. Radiotherapy alone has been the primary treatment modality for germinomas, and is used with chemotherapy for nongerminomatous tumors. Stereotactic radiotherapy techniques minimize the volume of surrounding normal tissue irradiated and, hence, the late radiation morbidity. This study reports our experience with stereotactic radiotherapy in this group of tumors., Methods and Materials: Between December 1992 and December 1998, 18 patients with intracranial germ cell tumors were treated with stereotactic radiotherapy. A total of 23 histologically proven tumors were treated. Thirteen patients had a histologic diagnosis of germinoma, and 5 patients had germinoma with nongerminomatous elements. Of those patients with a histologic diagnosis of germinoma, 5 had multiple midline tumors. The median age of the patients was 12.9 years (range, 5.6-17.5 years)., Results: A boost using stereotactic radiotherapy was delivered to 19 tumors following whole-brain radiation in 8 cases and craniospinal radiation in 11 cases. Three tumors were treated with stereotactic radiotherapy to the tumor volume alone following chemotherapy, and 1 tumor received a boost using stereotactic radiosurgery following craniospinal radiation. A median dose of 2520 cGy (range, 1500-3600) cGy was given to the whole brain, and a median dose of 2160 (range, 2100-2600) cGy was given to the spinal field. The median boost dose to the tumor was 2600 (range, 2160-3600) cGy, given by stereotactic radiotherapy delivered to the 95% isodose line. At a median follow-up time of 40 (range, 12-73) months, no local or marginal recurrences were reported in patients with germinoma. Two patients with nongerminomatous tumors have relapsed. One had elevation of tumor markers only at 37 months following treatment, and the other had persistent disease following chemotherapy and radiation therapy. Eight patients documented pituitary-hypothalamic dysfunction; in 7 (87.5%) of these patients, the dysfunction was present before commencing radiotherapy. Four patients (22%) developed newly diagnosed diabetes insipidus following surgery. Three patients (17%) received antidepressant medication at follow-up., Conclusion: Our series shows that stereotactic radiotherapy is achievable and well tolerated in this group of patients. Longer follow-up is required to fully assess the impact on long-term toxicity. Psychologic assessment of mood and affect should be performed as part of routine follow-up in this group of adolescent children.

Objective: Current prostatic brachytherapy implant procedures use ultrasound imaging for geometric guidance during surgery, with pre-surgical planning based on ultrasound images and post-surgical dosimetry based on computed tomography (CT). This procedure suffers from the poor soft-tissue contrast of ultrasound and CT and problems inherent in the repositioning of the patient at surgery. We have designed and implemented an integrated real-time imaging and treatment-planning software system that combines the superior soft-tissue contrast of magnetic resonance (MR) images with the real-time acquisition of those images for localization, verification, and dosimetric purposes. The system permits the surgeon and patient to complete all phases of treatment in one setting., Materials and Methods: We utilize an intra-operative MR unit that permits real-time imaging and stereotactic localization during a surgical procedure. Our software system integrates with the unit and features (i) a calibration schema to calibrate the prostatic surgical implant template within the unit, (ii) full volumetric data acquisition of the prostate, (iii) interactive three-dimensional (3D) treatment planning with volumetric dose evaluation, and (iv) geometric and dosimetric feedback during the surgical procedure. We utilize a software architecture that uses mediators between the abstract data types, or objects. These mediators communicate state changes in individual objects (e.g., a change in a catheter position) to other objects (e.g., a dose-volume histogram) that depend on these changes. A consistent 3D representation of the treatment volumes allows interactive reconstruction of the volumes on arbitrary MR image sections and real-time dose computations., Results: We have successfully implemented the system clinically and have treated 143 patients (as of August 2000). The system supports four clinical phases. The first consists of calibrating the implant template with respect to the patient's anatomy and the MR unit. The second consists of acquiring a complete volumetric MR data set of the prostatic volume. The third consists of delineating the treatment volume (often a sub-volume of the prostate) and the dose-limiting critical volumes. These volumes are used in determining the surgical treatment plan based on catheter and seed placement in the prostate and a dosimetric evaluation of all volumes. The final phase consists of implanting the catheters with the radioactive seeds, where each catheter is imaged and compared to the planned position of the catheter, thus allowing a direct comparison, and possible adjustment, of the implanted versus planned catheter position., Conclusions: The system is highly interactive, and has great flexibility in its design, maintainability, and clinical practice. The system provides an efficient model to support the surgical procedure. The system significantly improves the diagnostic information provided to the clinician and the treatment planner and the geometric accuracy of the surgical procedure compared to ultrasound procedures. The system allows excellent critical structure sparing, both through interactive placement of the catheters with high geometric accuracy and through the definition of the actual sub-prostatic volumes possible with MR., (Copyright 2001 Wiley-Liss, Inc.)

Purpose: To determine the extent and predictors for prostatic motion in a large number of patients evaluated with multiple CT scans during radiotherapy, and evaluate the implications of these data on the design of appropriate treatment margins for patients receiving high-dose three-dimensional conformal radiotherapy., Materials and Methods: Fifty patients underwent four serial computerized tomography (CT) scans, consisting of an initial planning scan and subsequent scans at the beginning, middle, and end of the treatment course. Each scan was performed with the patient in the prone treatment position within an immobilization device used during therapy. Contours of the prostate and seminal vesicles were drawn on the axial CT slices of each scan, and the scans were matched by alignment of the pelvic bones with a chamfer matching algorithm. Using the contour information, distributions of the displacement of the organ center of mass and organ border from the planning position were determined separately for the prostate and seminal vesicles in each of the three principle directions: anterior-posterior (AP), superior-inferior (SI) and left-right (LR). Each distribution was fitted to a normal (Gaussian) distribution to determine confidence limits in the center of mass and border displacements and thereby evaluate for the optimal margins needed to contain target motion., Results: The most common directions of displacement of the prostate center of mass (COM) were in the AP and SI directions and were significantly larger than any LR movement. The mean prostate COM displacement (+/- 1 standard deviation, SD) for the entire population was -1.2 +/- 2.9 mm, -0.5 +/- 3.3 mm and -0.6 +/- 0.8 mm in the, AP and SI and LR directions respectively (negative values indicate posterior, inferior or left displacement). The mean (+/- 1 SD) seminal vesicle COM displacement for the entire population was - 1.4 +/- 4.9 mm, 1.3 +/- 5.5 mm and -0.8 +/- 3.1 mm in the AP and SI and LR directions, respectively. The data indicate a tendency for the population towards posterior displacements of the prostate from the planning position and both posterior and superior displacements of the seminal vesicles. AP movement of both the prostate and seminal vesicles were correlated with changes in rectal volume (P = 0.0014 and < 0.0001, respectively) more than with changes in bladder volume (P = 0.030 for seminal vesicles and 0.19 for prostate). A logistic regression analysis identified the combination of rectal volume > 60 cm3 and bladder volumes > 40 cm3 as the only predictor of large ( > 3 mm) systematic deviations for the prostate and seminal vesicles (P = 0.05) defined for each patient as the difference between organ position in the planning scan and mean position as calculated from the three subsequent scans., Conclusions: Prostatic displacement during a course of radiotherapy is more pronounced among patients with initial planning scans with large rectal and bladder volumes. Such patients may require more generous margins around the CTV to assure its enclosure within the prescription dose region. Identification and correction of patients with large systematic errors will minimize the extent of the margin required and decrease the volume of normal tissue exposed to higher radiation doses.

Purpose: We describe a computerized method of determining target margins for beam aperture design in conformal radiotherapy plans., Materials and Methods: The method uses previously measured data from a population of patients to simulate setup error and organ motion in the patient currently being planned. Starting with a clinical target volume (CTV) and nontarget organs from the patient's planning CT scan, the simulation is repeated many times to produce a spatial probability distribution for each organ in the treatment machine coordinate system. This is used to determine a prescribed dose volume (PDV), defined as the volume to receive the prescribed dose, which encompasses the CTV while restricting the volume of nontarget organs within it, according to planner-specified values. The PDV is used to design beam apertures using a conventional margin for beam penumbra., Results: The method is applied to 6-field prostate conformal treatment plans, in which the PDV encloses the prostate and seminal vesicles while limiting the enclosed rectal wall volume. The effect of organ motion is assessed by applying the plans on subsequent CT scans of the same patients, calculating probabilities for tumor control (TCP) and normal tissue complication (NTCP), and comparing with plans designed from a physician-drawn planning target volume (PTV). Although prostate TCP and rectal wall NTCP are found to be similar in the two sets of plans, TCP for the seminal vesicles is significantly higher in the PDV-based plans., Conclusions: The method can improve the dose conformality of treatment plans by incorporating population-based measurements of treatment uncertainties and consideration of nontarget tissues in the design of nonuniform target margins.

Object: To assess the value of stereotactic radiosurgery (SRS) as adjunct therapy in patients suffering from glioblastoma multiforme (GBM), the authors analyzed their experience with 78 patients., Methods: Between June 1988 and January 1995, 78 patients underwent SRS as part of their initial treatment for GBM. All patients had undergone initial surgery or biopsy confirming the diagnosis of GBM and received conventional external beam radiotherapy. Stereotactic radiosurgery was performed using a dedicated 6-MV stereotactic linear accelerator. Thirteen patients were alive at the time of analysis with a median follow-up period of 40.8 months. The median length of actuarial survival for all patients was 19.9 months. Twelve- and 24-month survival rates were 88.5% and 35.9%, respectively. Patient age and Radiation Therapy Oncology Group (RTOG) class were significant prognostic indicators according to univariate analysis (p < 0.05). Twenty-three patients aged younger than 40 years had a median survival time of 48.6 months compared with 55 older patients who had 18.2 months (p < 0.001). Patients in this series fell into RTOG Classes III (27 patients), IV (29 patients), or V (22 patients). Class III patients had a median survival time of 29.5 months following diagnosis; this was significantly longer than median survival times for Classes IV and V, which were 19.2 and 18.2 months, respectively (p = 0.001). Only patient age (< 40 years) was a significant prognostic factor according to multivariate analysis. Acute complications were unusual and limited to exacerbation of existing symptoms. There were no new neuropathies secondary to SRS. Thirty-nine patients (50%) underwent reoperation for symptomatic necrosis or recurrent tumor. The rate of reoperation at 24 months following SRS was 54.8%., Conclusions: The addition of a radiosurgery boost appears to confer a survival advantage to selected patients.

Purpose: This study was performed to establish the dose-localization capability and acute toxicity of a real-time intraoperative magnetic resonance (MR) image-guided approach to prostate brachytherapy in select patients with clinically localized prostate cancer., Methods and Materials: Nine patients with 1997 American Joint Commission on Cancer (AJCC) clinical stage T1cNxM0 prostate cancer, prostate-specific antigen (PSA) < 10 ng/ml, biopsy Gleason score not exceeding 3 + 4, and endorectal coil MR stage T2 disease were enrolled into this study. The prescribed minimum peripheral dose was 160 Gy to the clinical target volume (CTV), which was the MR-defined peripheral zone (PZ) of the prostate gland. Using a real-time 0.5 Tesla intraoperative MR imaging unit, 5-mm image planes were obtained throughout the prostate gland. The PZ of the prostate gland, anterior rectal wall, and prostatic urethra were identified on the T2 weighted axial images by an MR radiologist. An optimized treatment plan for catheter insertion was generated intraoperatively. Each catheter containing the 125Iodine sources was placed under real-time MR guidance to ensure that its position in the coronal, sagittal, and axial planes was in agreement with the planned trajectory. Real-time dose- volume histogram analyses were used intraoperatively to optimize the dosimetry., Results: For the 9 study patients, 89-99% (median 94%) of the CTV received a minimum peripheral dose of 160 Gy and > or = 95% of the volume of the prostatic urethra and 42-89% (median 70%) of the volume of the anterior rectal wall received doses that were below the reported tolerance. All patients voided spontaneously within 3 h after discontinuation of the Foley catheter and no patient required more than a limited course (< or = 3 weeks) of oral alpha-1 blockers for postimplant urethritis., Conclusions: Real-time MR-guided interstitial radiation therapy provided the ability to achieve the planned optimized dose-volume histogram profiles to the CTV and healthy juxtaposed structures intraoperatively, with minimal acute morbidity.

The Joint Center for Radiation Therapy (JCRT) has treated intra-cranial lesions with high-dose single fraction stereotactic radiosurgery (SRS) since 1986 and with multi-fraction stereotactic radiotherapy (SRT) since 1992. This paper describes the JCRT techniques for treatment planning and delivery for SRS, and to a limited extent for SRT. LINAC quality assurance, treatment delivery, and patient management for stereotactic radiosurgery and stereotactic radiotherapy technique are closely related at the JCRT, although differences exist. An historical retrospective of our experience with stereotactic techniques including imaging modalities, treatment planning techniques, optimization methods, and treatment delivery is presented. Three treatment planning approaches, single isocenter, multiple isocenter, and micro-jaw field shaping are used to demonstrate the capabilities and technical dosimetric features of each approach. The major planning differences and clinical of each technique are described. From our experience, lesions less than 3.0 cm in maximum extent are well treated with circular fields using either a single or multiple isocenter configuration. Lesions greater than 3.0 cm in maximum extent usually benefit from field shaping using the micro-jaws. For these large lesions, the shaped field approach typically improves the dose homogeneity as well as reduces the amount of healthy brain irradiated. Our physicians choose between the three techniques to meet the desired clinical outcome the patient's situation requires.

The proximity of the lens to the retina makes the treatment of retinoblastoma a challenge for external beam radiation therapy. The approximately 1 mm separation between the posterior edge of the lens and the anterior region of the retina causes a trade-off between coverage of the entire retina and excessive dose to the lens. A stereotactic, LINAC based, lens sparing technique for treating retinoblastoma is presented. The technique uses noncoplanar arcs with the lens at isocenter. A special noncircular collimator blocks the lens but it also causes the dose distribution to vary across the retina. A fluence modulation filter is used to reduce the dose inhomogeneity across the target. The resulting dose distribution is roughly hemispheric, providing both anterior coverage of the retina and lens blocking unlike conventional techniques. The method used to develop the collimator and filter assembly is presented. Dosimetry of the assembly was carried out using radiochromic film, and the results were entered in a treatment planning system. The dose distribution as measured in a phantom is provided and compared to calculations.

Purpose: Current treatment planning for linear accelerator-based stereotactic radiosurgery and radiotherapy is a lengthy and iterative procedure. The planner has to manually select the beam arcs and carefully consider many different selections to ensure target volume coverage while sparing dose to critical organs. In this article we report an optimization procedure that can automatically select the beam arcs based on geometric and dosimetric analysis of the treatment parameters., Methods and Materials: The optimization problem is introduced by using a Beam's Eye View (BEV) map where a pattern of lines represents a beam arc combination for a treatment plan. The collection of all possible treatment plans is described by using the concept of phase space where each point corresponds to a particular configuration of the system under consideration, and in this case, a particular beam arc combination. A geometric reduction of the phase space is performed by excluding static beam ports that irradiate too much critical organs and too little target volume. The phase space is further reduced by excluding beam arc combinations that do not comply with treatment convenience considerations and established planning experiences. These reductions significantly reduces the number of beam arc combinations to be considered and thus dramatically simplifies the computational complexity. The method of simulated annealing is then used to the reduced phase space to select the set of beam arcs that provides the best surface dose distribution for the target volume. The optimization procedure is applied to a radiosurgery case to compare the optimized beam arcs with the previously manually planned beam arcs. The procedure is also applied to 10 randomly selected cases for a comparison in terms of tissue-volume ratio calculations., Results: The system is a highly automated beam arc planning tool for stereotactic radiosurgery and stereotactic radiotherapy. Its interactive nature allows the planner to rapidly consider many treatment plans to search for the best option. For the case presented, it is shown that the optimized beams substantially reduce the dose to the postrema. The tissue-volume ratio calculations demonstrate that the optimization often produces clinically superior treatment plans than the manual beam planning method., Conclusions: Our method of phase space reduction proves to be very useful in approaching the complex problem of treatment planning optimization. Not only does it substantially reduce the number of beam arcs that need to be considered, but it also simplifies the evaluation of the beam arc options. Both of these greatly reduce the computational complexity of the optimization and make the procedure fast and efficient. Moreover, the reduction of phase space adds another layer of interaction between the user and the beam selection procedure, so that the optimization process is well controlled and thus very effective.

Purpose: The patient population treated with fractionated stereotactic radiotherapy (SRT) is significantly different than that treated with stereotactic radiosurgery (SRS). Generally, lesions treated with SRT are larger, less spherical, and located within critical regions of the central nervous system; hence, they offer new challenges to the treatment planner. Here a simple, cost effective, beam shaping system has been evaluated relative to both circular collimators and an ideal dynamically conforming system for effectiveness in providing conformal therapy for these lesions., Methods and Materials: We have modeled a simple system for conformal arc therapy using four independent jaws. The jaw positions and collimator angle are changed between arcs but held fixed for the duration of each arc. Eleven previously treated SRT cases have been replanned using this system. The rectangular jaw plans were then compared to the original treatment plans which used circular collimators. The plans were evaluated with respect to tissue sparing at 100%, 80%, 50%, and 20% of the prescription dose. A plan was also done for each tumor in which the beam aperture was continuously conformed to the beams eye view projection of the tumor. This was used as an ideal standard for conformal therapy in the absence of fluence modulation., Results: For tumors with a maximum extent of over 3.5 cm the rectangular jaw plans reduced the mean volume of healthy tissue involved at the prescription dose by 57% relative to the circular collimator plans. The ideal conformal plans offered no significant further improvement at the prescription dose. The relative advantage of the rectangular jaw plans decreased at lower isodoses so that at 20% of the prescription dose tissue involvement for the rectangular jaw plans was equivalent to that for the circular collimator plans. At these isodoses the ideal conformal plans gave substantially better tissue sparing., Conclusion: A simple and economical field shaping device has been shown to provide all of the beam shaping advantage of a hypothetical ideal dynamically conforming system at the prescription level. This system may be immediately implemented in the clinic. It offers a substantial advantage over the currently used circular collimators in the high dose region with equivalent performance in the low dose region.

Purpose: A prototype Miniature Multi-Leaf Collimator (MMLC) designed specifically for radiosurgery and small field radiotherapy has been fabricated and evaluated at the University of Texas M. D. Anderson Cancer Center (UTMDACC). This work demonstrates the advantages of a computer-controlled MMLC vs. conventional circular collimation for the treatment of an irregularly shaped target volume in the brain., Methods and Materials: Two patient treatments were selected for this comparison from 38 intracranial tumors treated with radiosurgery at UTMDACC from 8/6/91 to 5/10/94. Target contours and critical structures defined for one of the patients was used to create a simulated target volume and critical structures in a spherical head phantom. Computer simulations were performed using traditional single isocenter treatment with a circular collimator for a set of six arcs. The same arc paths were used to compute the dose distribution for the MMLC and conformed beam geometries were defined using a three-dimensional (3D) treatment planning system with beam's eye view capabilities. Then, the calculated dose distribution for a single isocenter, conformal treatment was delivered to the spherical head phantom under static conditions by shaping the MMLC to conform the target volume shape projected as a function of couch rotation and gantry angle. Planar dose distributions through the target volume were measured using therapy verification film located in the phantom. The measurements were used to verify that the 3D treatment planning system was capable of simulating the MMLC technique. For the second patient with a peanut-shaped tumor, the 3D treatment planning calculations were used to compare dose distributions for the MMLC and for traditional single and multiple isocenter treatments using circular collimators. The resulting integral dose-volume histograms (DVHs) for the target volume, normal brain, and critical structures for the three treatment techniques were compared., Results: (a) Analysis of the film dosimetry data exemplified the degree of conformation of the high-dose region to the target shape that is possible with a computer-controlled MMLC. (b) Comparison of measured and calculated dose distributions indicates that the 3D treatment planning system can simulate the MMLC treatment. (c) Comparison of DVHs from the single isocenter MMLC and circular collimator treatments shows similar coverage of the target volume with increased dose to the brain for circular collimation (4). Comparison of DVHs from the single isocenter MMLC with the multiple isocenter circular collimator treatment approach shows a more inhomogeneous dose distribution through the target volume and increased dose to the brain for the latter., Conclusion: Dosimetry data for single isocenter treatments using computer-controlled field shaping with a MMLC demonstrate the ability to conform the dose distribution to an irregularly shaped target volume. DVHs validated that the single isocenter MMLC treatment is preferable to both single and multiple isocenter, circular collimator treatment because it provides a more uniform dose distribution to an irregularly shaped target volume and reduces the dose to surrounding brain tissue for the example cases.

Purpose: In radiotherapy planning, the clinical target volume (CTV) is typically enlarged to create a planning target volume (PTV) that accounts for uncertainties due to internal organ and patient motion as well as setup error. Margin size clearly determines the volume of normal tissue irradiated, yet in practice it is often given a set value in accordance with a clinical precedent from which variations are rare. The (CTV/PTV) formalism does not account for critical structure dose. We present a numerical simulation to assess (CTV) coverage and critical organ dose as a function of treatment margins in the presence of organ motion and physical setup errors. An application of the model to the treatment of prostate cancer is presented, but the method is applicable to any site where normal tissue tolerance is a dose-limiting factor., Methods and Materials: A Monte Carlo approach was used to simulate the cumulative effect of variation in overall tumor position, for individual treatment fractions, relative to a fixed distribution of dose. Distributions of potential dose-volume histograms (DVHs), for both tumor and normal tissues, are determined that fully quantify the stochastic nature of radiotherapy delivery. We introduce the concept of Probability of Prescription Dose (PoPD) isosurfaces as a tool for treatment plan optimization. Outcomes resulting from current treatment planning methods are compared with proposed techniques for treatment optimization. The standard planning technique of relatively large uniform margins applied to the CTV, in the beam's eye view (BEV), was compared with three other treatment strategies: (a) reduced uniform margins, (b) nonuniform margins adjusted to maximize normal tissue sparing, and (c) a reduced margin plan in which nonuniform fluence profiles were introduced to compensate for potential areas of reduced dose., Results: Results based on 100 simulated full course treatments indicate that a 10 mm CTV to PTV margin, combined with an additional 5 mm dosimetric margin, provides adequate CTV coverage in the presence of known treatment uncertainties. Nonuniform margins can be employed to reduce dose delivered to normal tissues while preserving CTV coverage. Nonuniform fluence profiles can also be used to further reduce dose delivered to normal tissues, though this strategy does result in higher dose levels delivered to a small volume of the CTV and normal tissues., Conclusions: Monte Carlo-based treatment simulation is an effective means of assessing the impact of organ motion and daily setup error on dose delivery via external beam radiation therapy. Probability of Prescription Dose (PoPD) isosurfaces are a useful tool for the determination of nonuniform beam margins that reduce dose delivered to critical organs while preserving CTV dose coverage. Nonuniform fluence profiles can further alter critical organ dose with potential therapeutic benefits. Clinical consequences of this latter approach can only be assessed via clinical trials.

Purpose: To evaluate the efficacy and toxicity of fractionated, stereotactic radiotherapy (SRT) for acoustic neuromas., Methods and Materials: Twelve patients with acoustic neuroma were treated with SRT between June 1992 and October 1994. Follow-up ranged from 16-44 months. Patient age ranged from 27-70 (median: 45). Eight patients were treated with primary SRT and four patients were treated after primary surgical intervention for recurrent [3] or persistent [1] disease. Tumor volumes were 1.2-18.4 cm3 (median: 10.1 cm3). Collimator sizes ranged from 30-50 mm (median: 37.5). Tumors received 1.8 Gy/day normalized to the 95% isodose line. Patients received a minimum prescribed dose of 54 Gy in 27-30 fractions over a 6-week period., Results: After a median follow-up of 26.5 months, local control was obtained in 12 out of 12 lesions. Tumor regression was noted in three patients, and tumor stabilization was found in the remaining nine patients. No patient developed a new cranial nerve deficit. One patients developed worsening of preexisting Vth cranial neuropathy and another experienced a decrease in hearing. However, all nine patients with useful hearing prior to SRT maintained useful hearing at last follow-up., Conclusions: Stereotactic radiotherapy provided excellent local control without new cranial nerve deficits. These results must be viewed as tentative in nature because of the small number of patients and the short median follow-up period.

Distortions of the magnetic field, such as those caused by susceptibility artifacts and peripheral magnetic field warping, can limit geometric precision in the use of magnetic resonance (MR) imaging in stereotactic procedures. The authors have routinely found systematic error in MR stereotactic coordinates with a median of 4 mm compared to computerized tomography (CT) coordinates. This error may place critical neural structures in jeopardy in sme procedures. A description is given of an image fusion technique that uses a chamfer matching algorithm; the advantages of MR imaging in anatomical definition are combined with the geometric precision of CT, while eliminating most of the anatomical spatial distortion of stereotactic MR imaging. A stereotactic radiosurgical case is presented in which the use of MR localization alone would have led to both irradiation of vital neural structures outside the desired target volume and underdose of the intended target volume. The image fusion approach allows for the use of MR imaging, combined with stereotactic CT, as a reliable localizing technique for stereotactic neurosurgery and radiosurgery.

Radiosurgery was historically designed as a technology to be used for the treatment of functional disorders, benign tumors, and vascular malformations. In the last 5 years, malignant lesions have become an increasingly common target for the radiosurgeon. In fact, by 1994 the most common disease treated with radiosurgery in the United States was metastatic disease. Published data suggest that radiosurgery offers excellent local control for intracranial metastatic lesions regardless of location or histology with the majority of patients demonstrating an improved quality of life. Recent information from the Joint Center for Radiation Therapy suggests that radiosurgery compares favorably with interstitial brachytherapy for both recurrent as well as in newly diagnosed patients with malignant gliomas in terms of improved survival and the need of surgery and steroid support for symptomatic radiation changes. Prospective studies (Phase I through III) are ongoing to determine the ultimate role of radiosurgery in the management of patients with newly diagnosed and recurrent malignant gliomas, recurrent pediatric brain tumors disease, and patients with single or multiple intracranial metastases.