Time is NTCP: Should we maximize patient throughput or perform online adaptation on proton therapy systems?

BACKGROUND: Compared to conventional radiotherapy (XT), proton therapy (PT) may improve normal tissue complication probabilities (NTCP). However, PT typically requires higher adaptation rates due to an increased sensitivity to anatomical changes. Systematic online adaptation may address this issue, but it requires additional replanning time, decreasing patient throughput. Therefore, less patients would benefit in such case from PT for a given machine capacity, with results in worse NTCP. AIM: To investigate the trade-off between PT patient throughput and NTCP gain as a function of the time needed for adaptation. METHODS: A retrospective database of 14 lung patients with two repeated 4DCTs was used to compare NTCP values between XT and PT for NTCP2ym (2-year mortality), NTCPdysphagia and NTCPpneumonitis. Four scenarios were considered for PT: no adaptation using clinical robustness parameters (4D robust optimization, 3 % range error and PTV-equivalent setup errors); systematic online adaptation with clinical robustness parameters; setup errors reduced to 4 mm and to 2 mm. Dose was accumulated on the planning CT. The number of patients treated with PT depended on the extra time needed for adaptation, assuming an 8-hours capacity (assuming 14 patients a day; thus minimum 34.2 min per treatment session if there is no or instantaneous adaptation). RESULTS: Baseline NTCP gains (PT against XT without adaptation) equaled 6.9 %, 6.1 %, and 7.7 % for NTCP2ym, NTCPdysphagia and NTCPpneumonitis, respectively. Using instantaneous online adaptation and setup errors of 2 mm, the overall gains were then 10.7 %, 13.6 % and 12.4 %. Taking into account loss of capacity, 13.7 min was the maximum extra-time allowed to complete adaptation and maintain an advantage on all three metrics for the 2-mm setup error scenario. CONCLUSION: This study highlights the critical importance of keeping short online adaptation times when using systems with limited capacity like PT.

Robustness evaluation of pencil beam scanning proton therapy treatment planning: A systematic review.

Compared to conventional radiotherapy using X-rays, proton therapy, in principle, allows better conformity of the dose distribution to target volumes, at the cost of greater sensitivity to physical, anatomical, and positioning uncertainties. Robust planning, both in terms of plan optimization and evaluation, has gained high visibility in publications on the subject and is part of clinical practice in many centers. However, there is currently no consensus on the methods and parameters to be used for robust optimization or robustness evaluation. We propose to overcome this deficiency by following the modified Delphi consensus method. This method first requires a systematic review of the literature. We performed this review using the PubMed and Web Of Science databases, via two different experts. Potential conflicts were resolved by a third expert. We then explored the different methods before focusing on clinical studies that evaluate robustness on a significant number of patients. Many robustness assessment methods are proposed in the literature. Some are more successful than others and their implementation varies between centers. Moreover, they are not all statistically or mathematically equivalent. The most sophisticated and rigorous methods have seen more limited application due to the difficulty of their implementation and their lack of widespread availability.

Dose mimicking based strategies for online adaptive proton therapy of head and neck cancer.

Objective.To compare a not adapted (NA) robust planning strategy with three fully automated online adaptive proton therapy (OAPT) workflows based on the same optimization method: dose mimicking (DM). The added clinical value and limitations of the OAPT methods are investigated for head and neck cancer (HNC) patients.Approach.The three OAPT strategies aimed at compensating for inter-fractional anatomical changes by mimiking different dose distributions on corrected cone beam CT images (corrCBCTs). Order by complexity, the OAPTs were: (1) online adaptive dose restoration (OADR) where the approved clinical dose on the planning-CT (pCT) was mimicked, (2) online adaptation using DM of the deformed clinical dose from the pCT to corrCBCTs (OADEF), and (3) online adaptation applying DM to a predicted dose on corrCBCTs (OAML). Adaptation was only applied in fractions where the target coverage criteria were not met (D98% < 95% of the prescribed dose). For 10 HNC patients, the accumulated dose distributions over the 35 fractions were calculated for NA, OADR, OADEF, and OAML.Main results.Higher target coverage was observed for all OAPT strategies compared to no adaptation. OADEF and OAML outperformed both NA and OADR and were comparable in terms of target coverage to initial clinical plans. However, only OAML provided comparable NTCP values to those from the clinical dose without statistically significant differences. When the NA initial plan was evaluated on corrCBCTs, 51% of fractions needed adaptation. The adaptation rate decreased significantly to 25% when the last adapted plan with OADR was selected for delivery, to 16% with OADEF, and to 21% with OAML. The reduction was even greater when the best plan among previously generated adapted plans (instead of the last one) was selected.Significance. The implemented OAPT strategies provided superior target coverage compared to no adaptation, higher OAR sparing, and fewer required adaptations.

Monte Carlo computed machine-specific correction factors for reference dosimetry of TomoTherapy static beam for several ion chambers.

PURPOSE: To determine k(Q(msr),Q(o) ) (f(msr),f(o) ) correction factors for machine-specific reference (msr) conditions by Monte Carlo (MC) simulations for reference dosimetry of TomoTherapy static beams for ion chambers Exradin A1SL, A12; PTW 30006, 31010 Semiflex, 31014 PinPoint, 31018 microLion; NE 2571. METHODS: For the calibration of TomoTherapy units, reference conditions specified in current codes of practice like IAEA∕TRS-398 and AAPM∕TG-51 cannot be realized. To cope with this issue, Alfonso et al. [Med. Phys. 35, 5179-5186 (2008)] described a new formalism introducing msr factors k(Q(msr),Q(o) ) (f(msr),f(o) ) for reference dosimetry, applicable to static TomoTherapy beams. In this study, those factors were computed directly using MC simulations for Q(0) corresponding to a simplified (60)Co beam in TRS-398 reference conditions (at 10 cm depth). The msr conditions were a 10 × 5 cm(2) TomoTherapy beam, source-surface distance of 85 cm and 10 cm depth. The chambers were modeled according to technical drawings using the egs++ package and the MC simulations were run with the egs_chamber user code. Phase-space files used as the source input were produced using PENELOPE after simulation of a simplified (60)Co beam and the TomoTherapy treatment head modeled according to technical drawings. Correlated sampling, intermediate phase-space storage, and photon cross-section enhancement variance reduction techniques were used. The simulations were stopped when the combined standard uncertainty was below 0.2%. RESULTS: Computed k(Q(msr),Q(o) ) (f(msr),f(o) ) values were all close to one, in a range from 0.991 for the PinPoint chamber to 1.000 for the Exradin A12 with a statistical uncertainty below 0.2%. Considering a beam quality Q defined as the TPR(20,10) for a 6 MV Elekta photon beam (0.661), the additional correction k(Q(msr,)Q) (f(msr,)f(ref) ) to k(Q,Q(o) ) defined in Alfonso et al. [Med. Phys. 35, 5179-5186 (2008)] formalism was in a range from 0.997 to 1.004. CONCLUSION: The MC computed factors in this study are in agreement with measured factors for chamber types already studied in literature. This work provides msr correction factors for additional chambers used in reference dosimetry. All of them were close to one (within 1%).

Impact of the number of discrete angles used during dose computation for TomoTherapy treatments.

PURPOSE: To quantify systematically the effect on accuracy of discretizing gantry rotation during the dose calculation process of TomoTherapy treatments. METHODS: Up to version 4.0.x included, TomoTherapy treatment planning system (TPS) approximates gantry rotation by computing dose from 51 discrete angles corresponding to the center of the projections used to control the binary multileaf collimator. Potential effects on dose computation accuracy for off-axis targets and low modulation factors have been shown previously for a few treatment configurations. In versions 4.1.x and later, TomoTherapy oversamples the projections to better account for gantry rotation, but only during full scatter optimization and final calculation (i.e., not during optimization in "beamlet" mode). The effect on accuracy of changing the number of angles was quantified with the following framework: (1) predict the impact of the discretization of gantry rotation for various modulation factors, target sizes, and off-axis positions using a simplified analytical algorithm; (2) perform regular quality assurance using measurements with EDR2 radiographic films; (3) isolating the effect of changing the number of discretized angles only (51, 153, and 459) using a previously validated Monte Carlo model (TomoPen). The diameters of the targets were 2, 3, and 5 cm; off-axis central positions of target volumes were 5, 10 and 15, and 17 cm (when accepted by the treatment unit); planned modulation factors were 1.3 and 2.0. RESULTS: For extreme configurations (3 cm tumor, 1.3 modulation factor, 15 cm off-axis position), effects on dose distributions were significant with 89.3% and 95.4% of the points passing gamma tests with 2%∕2 mm and 3%∕3 mm criteria, respectively, for TPS software version 4.0.x (51 gantry angles). The passing rate was 100% for both gamma criteria for the 4.1.x version (153 gantry angles). Those differences could be attributed almost completely to gantry motion discretization using TomoPen. Using 51 gantry angles for dose computation, TomoPen reproduced within statistical uncertainties (<1% standard deviation) dose distributions computed with version 4.0.x. Using 153 and 459 gantry angles, TomoPen reproduced within statistical uncertainties measurements and dose distributions computed with version 4.1.x. CONCLUSIONS: When low modulation factors and significant off-axis positions are used, accounting for gantry rotation during dose computation using at least 153 gantry angles is required to ensure optimal accuracy.

Evaluation of the clinical value of automatic online dose restoration for adaptive proton therapy of head and neck cancer.

INTRODUCTION: Intensity modulated proton therapy (IMPT) is highly sensitive to anatomical variations which can cause inadequate target coverage during treatment. This study compares not-adapted (NA) robust plans to two adaptive IMPT methods - a fully-offline adaptive (FOA) and a simplified automatic online adaptive strategy (dose restoration (DR)) to determine the benefit of DR, in head and neck cancer (HNC). MATERIAL/METHODS: Robustly optimized clinical IMPT doses in planning-CTs (pCTs) were available for a cohort of 10 HNC patients. During robust re-optimization, DR used isodose contours, generated from the clinical dose on pCTs, and patient specific objectives to reproduce the clinical dose in every repeated-CT(rCT). For each rCT(n = 50), NA, DR and FOA plans were robustly evaluated. RESULTS: An improvement in DVH-metrics and robustness was seen for DR and FOA plans compared to NA plans. For NA plans, 74%(37/50) of rCTs did not fulfill the CTV coverage criteria (D98%>95%Dprescription). DR improved target coverage, target homogeneity and variability on critical risk organs such as the spinal cord. After DR, 52%(26/50) of rCTs met all clinical goals. Because of large anatomical changes and/or inaccurate patient repositioning, 48%(24/50) of rCTs still needed full offline adaptation to ensure an optimal treatment since dose restoration was not able to re-establish the initial plan quality. CONCLUSION: Robust optimization together with fully-automatized DR avoided offline adaptation in 52% of the cases. Implementation of dose restoration in clinical routine could ensure treatment plan optimality while saving valuable human and material resources to radiotherapy departments.

Development and validation of an automatic commissioning tool for the Monte Carlo dose engine in myQA iON.

Independent dose verification with Monte Carlo (MC) simulations is an important feature of proton therapy quality assurance (QA). However, clinical integration of such tools often generates an additional and complex workload for medical physicists. The preparation of the necessary clinical inputs, such as the machine beam model, should therefore be automated. In this work, a methodology for automatic MC commissioning has been devised, validated, and developed into a MATLAB tool for the users of myQA iON, the recent QA platform of IBA Dosimetry. With this workflow, all necessary parameters can easily be tuned using dedicated optimization methods. For the geometrical beam parameters (phase space), the assumption of a single or double Gaussian is made. To model the energy spectrum, a Gaussian function is assumed and parameters are optimized using either MC simulations or a library of pre-computed Bragg peaks. For the absolute dose calibration, commissioning fields can be reproduced with the dose engine to retrieve the necessary parameters. We discuss in a first time the tool efficiency and show that one can optimize all parameters in less than 4 min per energy with excellent accuracy. We then validate a beam model obtained with the tool by simulating homogeneous spread-out Bragg peaks (SOBPs) and patient QA plans previously measured in water. An average range agreement of 0.29 ± 0.34 mm is achieved for the SOBPs while 3%/3 mm local gamma passing rates reach 99.3% on average over all 62 measured patient QA planes, which is well within clinical tolerances.

On the relationships between electron spot size, focal spot size, and virtual source position in Monte Carlo simulations.

PURPOSE: Every year, new radiotherapy techniques including stereotactic radiosurgery using linear accelerators give rise to new applications of Monte Carlo (MC) modeling. Accurate modeling requires knowing the size of the electron spot, one of the few parameters to tune in MC models. The resolution of integrated megavoltage imaging systems, such as the tomotherapy system, strongly depends on the photon spot size which is closely related to the electron spot. The aim of this article is to clarify the relationship between the electron spot size and the photon spot size (i.e., the focal spot size) for typical incident electron beam energies and target thicknesses. METHODS: Three electron energies (3, 5.5, and 18 MeV), four electron spot sizes (FWHM = 0, 0.5, 1, and 1.5 mm), and two tungsten target thicknesses (0.15 and 1 cm) were considered. The formation of the photon beam within the target was analyzed through electron energy deposition with depth, as well as photon production at several phase-space planes placed perpendicular to the beam axis, where only photons recorded for the first time were accounted for. Photon production was considered for "newborn" photons intersecting a 45 x 45 cm2 plane at the isocenter (85 cm from source). Finally, virtual source position and "effective" focal spot size were computed by back-projecting all the photons from the bottom of the target intersecting a 45 x 45 cm2 plane. The virtual source position and focal spot size were estimated at the plane position where the latter is minimal. RESULTS: In the relevant case of considering only photons intersecting the 45 x 45 cm2 plane, the results unambiguously showed that the effective photon spot is created within the first 0.25 mm of the target and that electron and focal spots may be assumed to be equal within 3-4%. CONCLUSIONS: In a good approximation photon spot size equals electron spot size for high energy X-ray treatments delivered by linear accelerators.

Monte Carlo-based simulation of dynamic jaws tomotherapy.

PURPOSE: Original TomoTherapy systems may involve a trade-off between conformity and treatment speed, the user being limited to three slice widths (1.0, 2.5, and 5.0 cm). This could be overcome by allowing the jaws to define arbitrary fields, including very small slice widths (<1 cm), which are challenging for a beam model. The aim of this work was to incorporate the dynamic jaws feature into a Monte Carlo (MC) model called TomoPen, based on the MC code PENELOPE, previously validated for the original TomoTherapy system. METHODS: To keep the general structure of TomoPen and its efficiency, the simulation strategy introduces several techniques: (1) weight modifiers to account for any jaw settings using only the 5 cm phase-space file; (2) a simplified MC based model called FastStatic to compute the modifiers faster than pure MC; (3) actual simulation of dynamic jaws. Weight modifiers computed with both FastStatic and pure MC were compared. Dynamic jaws simulations were compared with the convolution∕superposition (C∕S) of TomoTherapy in the "cheese" phantom for a plan with two targets longitudinally separated by a gap of 3 cm. Optimization was performed in two modes: asymmetric jaws-constant couch speed ("running start stop," RSS) and symmetric jaws-variable couch speed ("symmetric running start stop," SRSS). Measurements with EDR2 films were also performed for RSS for the formal validation of TomoPen with dynamic jaws. RESULTS: Weight modifiers computed with FastStatic were equivalent to pure MC within statistical uncertainties (0.5% for three standard deviations). Excellent agreement was achieved between TomoPen and C∕S for both asymmetric jaw opening∕constant couch speed and symmetric jaw opening∕variable couch speed, with deviations well within 2%∕2 mm. For RSS procedure, agreement between C∕S and measurements was within 2%∕2 mm for 95% of the points and 3%∕3 mm for 98% of the points, where dose is greater than 30% of the prescription dose (gamma analysis). Dose profiles acquired in transverse and longitudinal directions through the center of the phantom were also compared with excellent agreement (2%∕2 mm) between all modalities. CONCLUSIONS: The combination of weights modifiers and interpolation allowed implementing efficiently dynamic jaws and dynamic couch features into TomoPen at a minimal cost in terms of efficiency (simulation around 8 h on a single CPU).

Reference dosimetry for helical tomotherapy: practical implementation and a multicenter validation.

PURPOSE: The aim of this study was to implement a protocol for reference dosimetry in tomotherapy and to validate the beam output measurements with an independent dosimetry system. METHODS: Beam output was measured at the reference depth of 10 cm in water for the following three cases: (1) a 5 × 10 cm(2) static machine specific reference field (MSR), (2) a rotational 5 × 10 cm(2) field without modulation and no tabletop in the beam, (3) a plan class specific reference (PCSR) field defined as a rotational homogeneous dose delivery to a cylindrical shaped target volume: plan with modulation and table-top movement. The formalism for reference dosimetry of small and nonstandard fields [Med.Phys.35: 5179-5186, 2008] and QA recommendations [Med.Phys.37: 4817-4853, 2010] were adopted in the dose measurement protocol. All ionization chamber measurements were verified independently using alanine∕EPR dosimetry. As a pilot study, the beam output was measured on tomotherapy Hi-art systems at three other centers and directly compared to the centers specifications and to alanine dosimetry. RESULTS: For the four centers, the mean static output at a depth of 10 cm in water and SAD = 85 cm, measured with an A1SL chamber following the TG-148 report was 6.238 Gy∕min ± 0.058 (1 SD); the rotational output was 6.255 Gy∕min ± 0.069 (1 SD). The dose stated by the center was found in good agreement with the measurements of the visiting team: D(center)∕D(visit) = 1.000 ± 0.003 (1 SD). The A1SL chamber measurements were all in good agreement with Alanine∕EPR dosimetry. Going from the static reference field to the rotational ∕ non modulated field the dose rate remains constant within 0.2% except for one center where a deviation of 1.3% was detected. CONCLUSIONS: Following the TG-148 report, beam output measurements in water at the reference depth using a local protocol, as developed at different centers, was verified. The measurements were found in good agreement with alanine∕EPR dosimetry. The presented methodology may provide a good concept for reference dosimetry.

Development of robustness evaluation strategies for enabling statistically consistent reporting.

Robustness evaluation of proton therapy treatment plans is essential for ensuring safe treatment delivery. However, available evaluation procedures feature a limited exploration of the actual robustness of the plan and generally do not provide confidence levels. This study compared established and more sophisticated robustness evaluation procedures, with quantified confidence levels. We have evaluated several robustness evaluation methods for 5 bilateral head-and-neck patients optimized considering spot scanning delivery and with a conventional CTV-to-PTV margin of 4 mm. Method (1) good practice scenario selection (GPSS) (e.g. +/- 4 mm setup error 3% range uncertainty); (2) statistically sound scenario selection (SSSS) either only on or both on and inside isoprobability hypersurface encompassing 90% of the possible errors; (3) statistically sound dosimetric selection (SSDS). In the last method, the 90% best plans were selected according to either target coverage quantified by D 95 (SSDS_D 95) or to an approximation of the final objective function (OF) used during treatment optimization (SSDS_OF). For all methods, we have considered systematic setup and systematic range errors. A mix of systematic and random setup errors were also simulated for SSDS, but keeping the same conventional margin of 4 mm. All robustness evaluations have been performed using the fast Monte Carlo dose engine MCsquare. Both SSSS strategies yielded on average very similar results. SSSS and GPSS yield comparable values for target coverage (within 0.5 Gy). The most noticeable differences were found for the CTV between GPSS, on the one hand, and SSDS_D 95 and SSDS_OF, on the other hand (average worst-case D 98 were 2.8 and 2.0 Gy larger than for GPSS, respectively). Simulating explicitly random errors in SSDS improved almost all DVH metrics. We have observed that the width of DVH-bands and the confidence levels depend on the method chosen to sample the scenarios. Statistically sound estimation of the robustness of the plan in the dosimetric space may provide an improved insight on the actual robustness of the plan for a given confidence level.

Ion recombination for ionization chamber dosimetry in a helical tomotherapy unit.

PURPOSE: Ion recombination for ionization chambers in pulsed high-energy photon beams is a well-studied phenomenon. Despite this, the correction for ion recombination is often determined inaccurately due to the inappropriate combination of using a high polarizing voltage and the simple two-voltage method. An additional complication arises in new treatment modalities such as IMRT and tomotherapy, where the dosimetry of a superposition of many constituting fields becomes more relevant than of single static fields. For these treatment modalities, the irradiation of the ion chamber geometry can be instantaneously inhomogeneous and time dependent. METHODS: This article presents a study of ion recombination in ionization chambers used for dosimetry in a helical tomotherapy beam. Models are presented for studying the recombination correction factors in a continuous beam, in pulsed large and small fields, and in helical fields. Measurements using Exradin A1SL, NE2571, and NE2611 type chambers and Monte Carlo simulations using PENELOPE are performed in support of these models. RESULTS: Initial recombination and charge multiplication are found to be the same in 60Co and in the pulsed high-energy photon beam for the chambers and operating voltages used in this study. Applying the two-voltage technique for the A1SL chamber at its recommended operating voltage of 300 V leads to an overestimation of the recombination. Operating at a voltage of 100 V yields larger but more accurate values for the recombination correction. The recombination correction measured for this chamber in the TomoTherapy HiArt unit is lower than the 1% applied in the routine dosimetry for this treatment unit. For a helical dose delivery with a small slice width, lateral electron scatter in the cavity makes that the recombination is smaller than for an open beam delivering the same total dose. In a Farmer type chamber, a helical delivery with a 1 cm slice field results in a time and spatially integrated volume recombination of 55% of that with a 2.5 cm slice field. The relative recombination corrections for different slice widths and different field offsets with respect to the chamber center obtained from the developed models are in good agreement with experimental data. CONCLUSIONS: Because of the presence of charge multiplication, it is more accurate to determine the recombination correction at lower operating voltages than are often applied using the two-voltage method. Models and experiments for partial irradiation conditions of the ion chamber show that resulting recombination corrections are reduced compared to those for an open field. A model for helical dose deliveries results in recombination corrections that get lower with smaller slice widths. This model could be adapted to any IMRT delivery where the ion chamber is instantaneously partial and/or inhomogeneously irradiated, and could provide a practical procedure to calculate the recombination for complex deliveries for which it is difficult to be measured.

Monte Carlo evaluation of the convolution/superposition algorithm of Hi-Art tomotherapy in heterogeneous phantoms and clinical cases.

The reliability of the convolution/superposition (C/S) algorithm of the Hi-Art tomotherapy system is evaluated by using the Monte Carlo model TomoPen, which has been already validated for homogeneous phantoms. The study was performed in three stages. First, measurements with EBT Gafchromic film for a 1.25 x 2.5 cm2 field in a heterogeneous phantom consisting of two slabs of polystyrene separated with Styrofoam were compared to simulation results from TomoPen. The excellent agreement found in this comparison justifies the use of TomoPen as the reference for the remaining parts of this work. Second, to allow analysis and interpretation of the results in clinical cases, dose distributions calculated with TomoPen and C/S were compared for a similar phantom geometry, with multiple slabs of various densities. Even in conditions of lack of lateral electronic equilibrium, overall good agreement was obtained between C/S and TomoPen results, with deviations within 3%/2 mm, showing that the C/S algorithm accounts for modifications in secondary electron transport due to the presence of a low density medium. Finally, calculations were performed with TomoPen and C/S of dose distributions in various clinical cases, from large bilateral head and neck tumors to small lung tumors with diameter of < 3 cm. To ensure a "fair" comparison, identical dose calculation grid and dose-volume histogram calculator were used. Very good agreement was obtained for most of the cases, with no significant differences between the DVHs obtained from both calculations. However, deviations of up to 4% for the dose received by 95% of the target volume were found for the small lung tumors. Therefore, the approximations in the C/S algorithm slightly influence the accuracy in small lung tumors even though the C/S algorithm of the tomotherapy system shows very good overall behavior.

Impact of machine log-files uncertainties on the quality assurance of proton pencil beam scanning treatment delivery.

Irradiation log-files store useful information about the plan delivery, and together with independent Monte Carlo dose engine calculations can be used to reduce the time needed for patient-specific quality assurance (PSQA). Nonetheless, machine log-files carry an uncertainty associated to the measurement of the spot position and intensity that can influence the correct evaluation of the quality of the treatment delivery. This work addresses the problem of the inclusion of these uncertainties for the final verification of the treatment delivery. Dedicated measurements performed in an IBA Proteus Plus gantry with a pencil beam scanning (PBS) dedicated nozzle have been carried out to build a 'room-dependent' model of the spot position uncertainties. The model has been obtained through interpolation of the look-up tables describing the systematic and random uncertainties, and it has been tested for a clinical case of a brain cancer patient irradiated in a dry-run. The delivered dose has been compared with the planned dose with the inclusion of the errors obtained applying the model. Our results suggest that the accuracy of the treatment delivery is higher than the spot position uncertainties obtained from the log-file records. The comparison in terms of DVHs shows that the log-reconstructed dose is compatible with the planned dose within the 95% confidence interval obtained applying our model. The initial mean dose difference between the calculated dose to the patient based on the plan and recorded data is around 1%. The difference is essentially due to the log-file uncertainties and it can be removed with a correct treatment of these errors. In conclusion our new PSQA protocol allows for a fast verification of the dose delivered after every treatment fraction through the use of machine log-files and an independent Monte Carlo dose engine. Moreover, the inclusion of log-file uncertainties in the dose calculation allows for a correct evaluation of the quality of the treatment plan delivery.

Monte Carlo simulation of helical tomotherapy with PENELOPE.

Helical tomotherapy (HT) delivers intensity-modulated radiation therapy (IMRT) using the simultaneous movement of the couch, the gantry and the binary multileaf collimator (MLC), a procedure that differs from conventional dynamic or step-and-shoot IMRT. A Monte Carlo (MC) simulation of HT in the helical mode therefore requires a new approach. Using validated phase-space files (PSFs) obtained through the MC simulation of the static mode with PENELOPE, an analytical model of the binary MLC, called the 'transfer function' (TF), was first devised to perform the transport of particles through the MLC much faster than time-consuming MC simulation and with no significant loss of accuracy. Second, a new tool, called TomoPen, was designed to simulate the helical mode by rotating and translating the initial coordinates and directions of the particles in the PSF according to the instantaneous position of the machine, transporting the particles through the MLC (in the instantaneous configuration defined by the sinogram), and computing the dose distribution in the CT structure using PENELOPE. Good agreement with measurements and with the treatment planning system of tomotherapy was obtained, with deviations generally well within 2%/1 mm, for the simulation of the helical mode for two commissioning procedures and a clinical plan calculated and measured in homogeneous conditions.

Monte carlo evaluation of the AAA treatment planning algorithm in a heterogeneous multilayer phantom and IMRT clinical treatments for an Elekta SL25 linear accelerator.

The Anisotropic Analytical Algorithm (AAA) is a new pencil beam convolution/superposition algorithm proposed by Varian for photon dose calculations. The configuration of AAA depends on linear accelerator design and specifications. The purpose of this study was to investigate the accuracy of AAA for an Elekta SL25 linear accelerator for small fields and intensity modulated radiation therapy (IMRT) treatments in inhomogeneous media. The accuracy of AAA was evaluated in two studies. First, AAA was compared both with Monte Carlo (MC) and the measurements in an inhomogeneous phantom simulating lung equivalent tissues and bone ribs. The algorithm was tested under lateral electronic disequilibrium conditions, using small fields (2 x 2 cm(2)). Good agreement was generally achieved for depth dose and profiles, with deviations generally below 3% in lung inhomogeneities and below 5% at interfaces. However, the effects of attenuation and scattering close to the bone ribs were not fully taken into account by AAA, and small inhomogeneities may lead to planning errors. Second, AAA and MC were compared for IMRT plans in clinical conditions, i.e., dose calculations in a computed tomography scan of a patient. One ethmoid tumor, one orophaxynx and two lung tumors are presented in this paper. Small differences were found between the dose volume histograms. For instance, a 1.7% difference for the mean planning target volume dose was obtained for the ethmoid case. Since better agreement was achieved for the same plans but in homogeneous conditions, these differences must be attributed to the handling of inhomogeneities by AAA. Therefore, inherent assumptions of the algorithm, principally the assumption of independent depth and lateral directions in the scaling of the kernels, were slightly influencing AAA's validity in inhomogeneities. However, AAA showed a good accuracy overall and a great ability to handle small fields in inhomogeneous media compared to other pencil beam convolution algorithms.

Experimental assessment of proton dose calculation accuracy in inhomogeneous media.

PURPOSE: Proton therapy with Pencil Beam Scanning (PBS) has the potential to improve radiotherapy treatments. Unfortunately, its promises are jeopardized by the sensitivity of the dose distributions to uncertainties, including dose calculation accuracy in inhomogeneous media. Monte Carlo dose engines (MC) are expected to handle heterogeneities better than analytical algorithms like the pencil-beam convolution algorithm (PBA). In this study, an experimental phantom has been devised to maximize the effect of heterogeneities and to quantify the capability of several dose engines (MC and PBA) to handle these. METHODS: An inhomogeneous phantom made of water surrounding a long insert of bone tissue substitute (1×10×10 cm3) was irradiated with a mono-energetic PBS field (10×10 cm2). A 2D ion chamber array (MatriXX, IBA Dosimetry GmbH) lied right behind the bone. The beam energy was such that the expected range of the protons exceeded the detector position in water and did not attain it in bone. The measurement was compared to the following engines: Geant4.9.5, PENH, MCsquare, as well as the MC and PBA algorithms of RayStation (RaySearch Laboratories AB). RESULTS: For a γ-index criteria of 2%/2mm, the passing rates are 93.8% for Geant4.9.5, 97.4% for PENH, 93.4% for MCsquare, 95.9% for RayStation MC, and 44.7% for PBA. The differences in γ-index passing rates between MC and RayStation PBA calculations can exceed 50%. CONCLUSION: The performance of dose calculation algorithms in highly inhomogeneous media was evaluated in a dedicated experiment. MC dose engines performed overall satisfactorily while large deviations were observed with PBA as expected.

Potential pitfalls of the PTV concept in dose-to-medium planning optimization.

In typical treatment planning of 3D IMRT, the incident energy fluence is optimized to achieve a homogeneous dose distribution to the PTV. The PTV includes the tumour but also healthy tissues that may have a different dose response for the same incident energy fluence, like bony structures included in the PTV (mandibles in head and neck tumours or femoral bones in sarcomas). Dose to medium optimization compensates for this heterogeneous response, leading to a non-homogeneous energy fluence in the PTV and a non-homogeneous dose in the CTV in the presence of geometric errors. We illustrate qualitatively this statement in a cylindrical geometry where the PTV includes a CTV (7cm diameter) made of water surrounded by ICRU compact bone (1.2cm thickness); such configuration was chosen to exaggerate the aforementioned effect. Optimization was performed assuming dose equals photon energy fluence times mass energy absorption coefficient. Bone has a 4% lower dose response in a 6 MV flattening filter free spectrum. After optimization either in medium or assuming everything as water composition, the geometry was shifted by 1.2cm and dose recomputed. As expected, compensating for the under-response of the bone material during optimization in medium leads to an overdosage of the CTV when patient geometric errors are taken into account. Optimization in dose assuming everything as water composition leads to a uniform coverage. Robust optimization or forcing a uniform atomic composition in the PTV margin may resolve this incompatibility between the PTV concept and dose to medium optimization.

[Robust treatment planning in proton therapy]. / Planification de traitement robuste en protonthérapie.

The concentration of the dose delivered by protons at the end of their path, the Bragg peak, has the potential to improve external radiotherapy treatments. Unfortunately, the main strength of the protons, their finite range, is also their greatest weakness. Any uncertainty on the range may lead to inadequate target coverage or excessive toxicity. The uncertainties have multiple origins and include, among others, ballistic errors, morphological modifications or inaccurate estimations of the physical quantities necessary to predict the proton range. Uncertainties have been part of daily practice in conventional radiotherapy with X-rays for a long time. However, dose distributions delivered with X-rays are much less sensitive to uncertainties than the ones delivered with protons. This relative insensitivity enabled the management of uncertainties through safety margins using a simple formalism. The conditions of validity of this formalism are much more restrictive for proton therapy, leading to the need of developing new tools and adapted strategies to manage accurately these uncertainties. The objective of this paper is to present a vision for the management of uncertainties in proton therapy in the continuity of formalisms established for X-rays. The latter are first summarized before discussing the necessary developments in order to consistently apply them to protons.

Detection of mixed-range proton pencil beams with a prompt gamma slit camera.

With increasing availability of proton and particle therapy centers for tumor treatment, the need for in vivo range verification methods comes more into the focus. Imaging of prompt gamma rays emitted during the treatment is one of the possibilities currently under investigation. A knife-edge shaped slit camera was recently proposed for this task and measurements proved the feasibility of range deviation detection in homogeneous and inhomogeneous targets. In the present paper, we concentrate on laterally inhomogeneous materials, which lead to range mixing situations when crossed by one pencil beam: different sections of the beam have different ranges. We chose exemplative cases from clinical irradiation and assembled idealized tissue equivalent targets. One-dimensional emission profiles were obtained by measuring the prompt gamma emission with the slit camera. It could be shown that the resulting range deviations can be detected by evaluation of the measured data with a previously developed range deviation detection algorithm. The retrieved value, however, strongly depends on the target composition, and is not necessarily in direct relation to the ranges of both parts of the beam. By combining the range deviation detection with an analysis of the slope of the distal edge of the measured prompt gamma profile, the origin of the detected range deviation, i.e. the mixed range of the beam, is also identified. It could be demonstrated that range mixed prompt gamma profiles exhibit less steep distal slopes than profiles from beams traversing laterally homogeneous material. For future application of the slit camera to patient irradiation with double scattered proton beams, situations similar to the range mixing cases are present and results could possibly apply.