Technical note: Dosimetry and FLASH potential of UHDR proton PBS for small lung tumors: Bragg-peak-based delivery versus transmission beam and IMPT.

BACKGROUND: High-energy transmission beams (TBs) are currently the main delivery method for proton pencil beam scanning ultrahigh dose-rate (UHDR) FLASH radiotherapy. TBs place the Bragg-peaks behind the target, outside the patient, making delivery practical and achievement of high dose-rates more likely. However, they lead to higher integral dose compared to conventional intensity-modulated proton therapy (IMPT), in which Bragg-peaks are placed within the tumor. It is hypothesized that, when energy changes are not required and high beam currents are possible, Bragg-peak-based beams can not only achieve more conformal dose distributions than TBs, but also have more FLASH-potential. PURPOSE: This works aims to verify this hypothesis by taking three different Bragg-peak-based delivery techniques and comparing them with TB and IMPT-plans in terms of dosimetry and FLASH-potential for single-fraction lung stereotactic body radiotherapy (SBRT). METHODS: For a peripherally located lung target of various sizes, five different proton plans were made using "matRad" and inhouse-developed algorithms for spot/energy-layer/beam reduction and minimum monitor unit maximization: (1) IMPT-plan, reference for dosimetry, (2) TB-plan, reference for FLASH-amount, (3) pristine Bragg-peak plan (non-depth-modulated Bragg-peaks), (4) Bragg-peak plan using generic ridge filter, and (5) Bragg-peak plan using 3D range-modulated ridge filter. RESULTS: Bragg-peak-based plans are able to achieve sufficient plan quality and high dose-rates. IMPT-plans resulted in lowest OAR-dose and integral dose (also after a FLASH sparing-effect of 30%) compared to both TB-plans and Bragg-peak-based plans. Bragg-peak-based plans vary only slightly between themselves and generally achieve lower integral dose than TB-plans. However, TB-plans nearly always resulted in lower mean lung dose than Bragg-peak-based plans and due to a higher amount of FLASH-dose for TB-plans, this difference increased after including a FLASH sparing-effect. CONCLUSION: This work indicates that there is no benefit in using Bragg-peak-based beams instead of TBs for peripherally located, UHDR stereotactic lung radiotherapy, if lung dose is the priority.

Single Ultra-High Dose Rate Proton Transmission Beam for Whole Breast FLASH-Irradiation: Quantification of FLASH-Dose and Relation with Beam Parameters.

Healthy tissue-sparing effects of FLASH (≥40 Gy/s, ≥4-8 Gy/fraction) radiotherapy (RT) make it potentially useful for whole breast irradiation (WBI), since there is often a lot of normal tissue within the planning target volume (PTV). We investigated WBI plan quality and determined FLASH-dose for various machine settings using ultra-high dose rate (UHDR) proton transmission beams (TBs). While five-fraction WBI is commonplace, a potential FLASH-effect might facilitate shorter treatments, so hypothetical 2- and 1-fraction schedules were also analyzed. Using one tangential 250 MeV TB delivering 5 × 5.7 Gy, 2 × 9.74 Gy or 1 × 14.32 Gy, we evaluated: (1) spots with equal monitor units (MUs) in a uniform square grid with variable spacing; (2) spot MUs optimized with a minimum MU-threshold; and (3) splitting the optimized TB into two sub-beams: one delivering spots above an MU-threshold, i.e., at UHDRs; the other delivering the remaining spots necessary to improve plan quality. Scenarios 1-3 were planned for a test case, and scenario 3 was also planned for three other patients. Dose rates were calculated using the pencil beam scanning dose rate and the sliding-window dose rate. Various machine parameters were considered: minimum spot irradiation time (minST): 2 ms/1 ms/0.5 ms; maximum nozzle current (maxN): 200 nA/400 nA/800 nA; two gantry-current (GC) techniques: energy-layer and spot-based. For the test case (PTV = 819 cc) we found: (1) a 7 mm grid achieved the best balance between plan quality and FLASH-dose for equal-MU spots; (2) near the target boundary, lower-MU spots are necessary for homogeneity but decrease FLASH-dose; (3) the non-split beam achieved >95% FLASH for favorable (not clinically available) machine parameters (SB GC, low minST, high maxN), but <5% for clinically available settings (EB GC, minST = 2 ms, maxN = 200 nA); and (4) splitting gave better plan quality and higher FLASH-dose (~50%) for available settings. The clinical cases achieved ~50% (PTV = 1047 cc) or >95% (PTV = 477/677 cc) FLASH after splitting. A single UHDR-TB for WBI can achieve acceptable plan quality. Current machine parameters limit FLASH-dose, which can be partially overcome using beam-splitting. WBI FLASH-RT is technically feasible.

Impact of spot reduction on the effectiveness of rescanning in pencil beam scanned proton therapy for mobile tumours.

Objective. In pencil beam scanning proton therapy, individually calculated and positioned proton pencil beams, also referred to as 'spots', are used to achieve a highly conformal dose distributions to the target. Recent work has shown that this number of spots can be substantially reduced, resulting in shorter delivery times without compromising dosimetric plan quality. However, the sensitivity of spot-reduced plans to tumour motion is unclear. Although previous work has shown that spot-reduced plans are slightly more sensitive to small positioning inaccuracies of the individual pencil beams, the resulting shorter delivery times may allow for more rescanning. The aim of this study was to assess the impact of tumour motion and the effectiveness of 3D volumetric rescanning for spot-reduced treatment plans.Approach.Three liver and two lung cancer patients with non-negligible motion amplitudes were analysed. Conventional and probabilistic internal target volume definitions were used for planning considering single or multiple breathing cycles respectively. For each patient, one clinical and two spot-reduced treatment plans were created using identical field geometries. 4D dynamic dose calculations were then performed and resulting target coverage (V95%), dose homogeneity (D5%-D95%) and hot spots (D2%) evaluated for 1-25 rescans.Main results. Over all patients investigated, spot reduction reduced the number of spots by 91% in comparison to the clinical plan, reducing field delivery times by approximately 50%. This reduction, together with the substantially increased dose per spot resulting from the spot reduction process, allowed for more rescans in the same amount of time as for clinical plans and typically improved dosimetric parameters, in some cases to values better than the reference static (3D calculated) plans. However, spot-reduced plans had an increased possibility of interference with the breathing cycle, especially for simulations of perfectly repeatable breathing.Significance.For the patients analysed in this study, spot-reduced plans were found to be a valuable option to increase the efficiency of 3D volumetric rescanning for motion mitigation, if attention is paid to possible interference patterns.

Ultra-fast pencil beam scanning proton therapy for locally advanced non-small-cell lung cancers: Field delivery within a single breath-hold.

PURPOSE: The use of motion mitigation techniques such as breath-hold can reduce the dosimetric uncertainty of lung cancer proton therapy. We studied the feasibility of pencil beam scanning (PBS) proton therapy field delivery within a single breath-hold at PSI's Gantry 2. METHODS: In PBS proton therapy, the delivery time for a field is determined by the beam-on time and the dead time between proton spots (the time required to change the energy and/or lateral position). We studied ways to reduce beam-on and lateral scanning time, without sacrificing dosimetric plan quality, aiming at a single field delivery time of 15 seconds at maximum. We tested this approach on 10 lung cases with varying target volumes. To reduce the beam-on time, we increased the beam current at the isocenter by developing new beam optics for PSI's PROSCAN beamline and Gantry 2. To reduce the dead time between the spots, we used spot-reduced plan optimization. RESULTS: We found that it is possible to achieve conventional fractionated (2 Gy(RBE)/fraction) and hypofractionated (6 Gy(RBE)/fraction) field delivery times within a single breath-hold (<15 sec) for a variety non-small-cell lung cancer cases. CONCLUSION: In summary, the combination of spot reduction and improved beam line transmission is a promising approach for the treatment of mobile tumours within clinically achievable breath-hold durations.

Treatment planning for Flash radiotherapy: General aspects and applications to proton beams.

The increased radioresistence of healthy tissues when irradiated at very high dose rates (known as the Flash effect) is a radiobiological mechanism that is currently investigated to increase the therapeutic ratio of radiotherapy treatments. To maximize the benefits of the clinical application of Flash, a patient-specific balance between different properties of the dose distribution should be found, that is, Flash needs to be one of the variables considered in treatment planning. We investigated the Flash potential of three proton therapy planning and beam delivery techniques, each on a different anatomical region. Based on a set of beam delivery parameters, on hypotheses on the dose and dose rate thresholds needed for the Flash effect to occur, and on two definitions of Flash dose rate, we generated exemplary illustrations of the capabilities of current proton therapy equipment to generate Flash dose distributions. All techniques investigated could both produce dose distributions comparable with a conventional proton plan and reach the Flash regime, to an extent that was strongly dependent on the dose per fraction and the Flash dose threshold. The beam current, Flash dose rate threshold, and dose rate definition typically had a more moderate effect on the amount of Flash dose in normal tissue. A systematic estimation of the impact of Flash on different patient anatomies and treatment protocols is possible only if Flash-specific treatment planning features become readily available. Planning evaluation tools such as a voxel-based dose delivery time structure, and the inclusion in the optimization cost function of parameters directly associated with Flash (e.g., beam current, spot delivery sequence, and scanning speed), are needed to generate treatment plans that are taking full advantage of the potential benefits of the Flash effect.

A quantitative FLASH effectiveness model to reveal potentials and pitfalls of high dose rate proton therapy.

PURPOSE: In ultrahigh dose rate radiotherapy, the FLASH effect can lead to substantially reduced healthy tissue damage without affecting tumor control. Although many studies show promising results, the underlying biological mechanisms and the relevant delivery parameters are still largely unknown. It is unclear, particularly for scanned proton therapy, how treatment plans could be optimized to maximally exploit this protective FLASH effect. MATERIALS AND METHODS: To investigate the potential of pencil beam scanned proton therapy for FLASH treatments, we present a phenomenological model, which is purely based on experimentally observed phenomena such as potential dose rate and dose thresholds, and which estimates the biologically effective dose during FLASH radiotherapy based on several parameters. We applied this model to a wide variety of patient geometries and proton treatment planning scenarios, including transmission and Bragg peak plans as well as single- and multifield plans. Moreover, we performed a sensitivity analysis to estimate the importance of each model parameter. RESULTS: Our results showed an increased plan-specific FLASH effect for transmission compared with Bragg peak plans (19.7% vs. 4.0%) and for single-field compared with multifield plans (14.7% vs. 3.7%), typically at the cost of increased integral dose compared to the clinical reference plan. Similar FLASH magnitudes were found across the different treatment sites, whereas the clinical benefits with respect to the clinical reference plan varied strongly. The sensitivity analysis revealed that the threshold dose as well as the dose per fraction strongly impacted the FLASH effect, whereas the persistence time only marginally affected FLASH. An intermediate dependence of the FLASH effect on the dose rate threshold was found. CONCLUSIONS: Our model provided a quantitative measure of the FLASH effect for various delivery and patient scenarios, supporting previous assumptions about potentially promising planning approaches for FLASH proton therapy. Positive clinical benefits compared to clinical plans were achieved using hypofractionated, single-field transmission plans. The dose threshold was found to be an important factor, which may require more investigation.

Shortening delivery times for intensity-modulated proton therapy by reducing the number of proton spots: an experimental verification.

Delivery times of intensity-modulated proton therapy (IMPT) can be shortened by reducing the number of spots in the treatment plan, but this may affect clinical plan delivery. Here, we assess the experimental deliverability, accuracy and time reduction of spot-reduced treatment planning for a clinical case, as well as its robustness. For a single head-and-neck cancer patient, a spot-reduced plan was generated and compared with the conventional clinical plan. The number of proton spots was reduced using the iterative 'pencil beam resampling' technique. This involves repeated inverse optimization, while adding in each iteration a small sample of randomly selected spots and subsequently excluding low-weighted spots until plan quality deteriorates. Field setup was identical for both plans and comparable dosimetric quality was a prerequisite. Both IMPT plans were delivered on PSI Gantry 2 and measured in water, while delivery log-files were used to extract delivery times and reconstruct the delivered dose via Monte-Carlo dose calculations. In addition, robustness simulations were performed to assess sensitivity to machine inaccuracies and errors in patient setup and proton range. The number of spots was reduced by 96% (from 33 855 to 1510 in total) without compromising plan quality. The spot-reduced plan was deliverable on our gantry in standard clinical mode and resulted in average delivery times per field being shortened by 46% (from 51.2 to 27.6 s). For both plans, differences between measured and calculated dose were within clinical tolerance for patient-specific verifications and Monte-Carlo dose reconstructions were in accordance with clinical experience. The spot-reduced plan was slightly more sensitive to machine inaccuracies, but more robust against setup and range errors. In conclusion, for an example head-and-neck case, spot-reduced IMPT planning provided a deliverable treatment plan and enabled considerable shortening of the delivery time (∼50%) without compromising plan quality or delivery accuracy, and without substantially affecting robustness.

Towards FLASH proton therapy: the impact of treatment planning and machine characteristics on achievable dose rates.

Background: This study aimed at evaluating spatially varying instantaneous dose rates for different intensity-modulated proton therapy (IMPT) planning strategies and delivery scenarios, and comparing these with FLASH dose rates (>40 Gy/s). Material and methods: In order to quantify dose rates in three-dimensions, we proposed the 'dose-averaged dose rate' (DADR) metric, defined for each voxel as the dose-weighted mean of the instantaneous dose rates of all spots (i.e., pencil beams). This concept was applied to four head-and-neck cases, each planned with clinical (4 fields) and various spot-reduced IMPT techniques: 'standard' (4 fields), 'arc' (120 fields) and 'arc-shoot-through' (120 fields; 229 MeV only). For all plans, different delivery scenarios were simulated: constant beam intensity, variable beam intensity for a clinical Varian ProBeam system, varied per energy layer or per spot, and theoretical spot-wise variable beam intensity (i.e., no monitor/safety limitations). DADR distributions were calculated assuming 2-Gy or 6-Gy fractions. Results: Spot-reduced plans contained 17-52 times fewer spots than clinical plans, with no deterioration of plan quality. For the clinical plans, the mean DADR in normal tissue for 2-Gy fractionation was 1.7 Gy/s (median over all patients) at maximum, whereas in standard spot-reduced plans it was 0.7, 4.4, 7.1, and 12.1 Gy/s, for the constant, energy-layer-wise, spot-wise, and theoretical spot-wise delivery scenarios, respectively. Similar values were observed for arc plans. Arc-shoot-through planning resulted in DADR values of 3.0, 6.0, 14.1, and 24.4 Gy/s, for the abovementioned scenarios. Hypofractionation (3×) generally resulted in higher dose rates, up to 73.2 Gy/s for arc-shoot-through plans. The DADR was inhomogeneously distributed with highest values at beam entrance and at the Bragg peak. Conclusion: FLASH dose rates were not achieved for conventional planning and clinical spot-scanning machines. As such, increased spot-wise beam intensities, spot-reduced planning, hypofractionation and arc-shoot-through plans were required to achieve FLASH compatible dose rates.

Anatomical robust optimization to account for nasal cavity filling variation during intensity-modulated proton therapy: a comparison with conventional and adaptive planning strategies.

The aim of this study is to develop an anatomical robust optimization method for intensity-modulated proton therapy (IMPT) that accounts for interfraction variations in nasal cavity filling, and to compare it with conventional single-field uniform dose (SFUD) optimization and online plan adaptation. We included CT data of five patients with tumors in the sinonasal region. Using the planning CT, we generated for each patient 25 'synthetic' CTs with varying nasal cavity filling. The robust optimization method available in our treatment planning system 'Erasmus-iCycle' was extended to also account for anatomical uncertainties by including (synthetic) CTs with varying patient anatomy as error scenarios in the inverse optimization. For each patient, we generated treatment plans using anatomical robust optimization and, for benchmarking, using SFUD optimization and online plan adaptation. Clinical target volume (CTV) and organ-at-risk (OAR) doses were assessed by recalculating the treatment plans on the synthetic CTs, evaluating dose distributions individually and accumulated over an entire fractionated 50 GyRBE treatment, assuming each synthetic CT to correspond to a 2 GyRBE fraction. Treatment plans were also evaluated using actual repeat CTs. Anatomical robust optimization resulted in adequate CTV doses (V95% ⩾ 98% and V107% ⩽ 2%) if at least three synthetic CTs were included in addition to the planning CT. These CTV requirements were also fulfilled for online plan adaptation, but not for the SFUD approach, even when applying a margin of 5 mm. Compared with anatomical robust optimization, OAR dose parameters for the accumulated dose distributions were on average 5.9 GyRBE (20%) higher when using SFUD optimization and on average 3.6 GyRBE (18%) lower for online plan adaptation. In conclusion, anatomical robust optimization effectively accounted for changes in nasal cavity filling during IMPT, providing substantially improved CTV and OAR doses compared with conventional SFUD optimization. OAR doses can be further reduced by using online plan adaptation.

The impact of treatment accuracy on proton therapy patient selection for oropharyngeal cancer patients.

BACKGROUND AND PURPOSE: The impact of treatment accuracy on NTCP-based patient selection for proton therapy is currently unknown. This study investigates this impact for oropharyngeal cancer patients. MATERIALS AND METHODS: Data of 78 patients was used to automatically generate treatment plans for a simultaneously integrated boost prescribing 70 GyRBE/54.25 GyRBE in 35 fractions. IMRT treatment plans were generated with three different margins; intensity modulated proton therapy (IMPT) plans for five different setup and range robustness settings. Four NTCP models were evaluated. Patients were selected for proton therapy if NTCP reduction was ≥10% or ≥5% for grade II or III complications, respectively. RESULTS: The degree of robustness had little impact on patient selection for tube feeding dependence, while the margin had. For other complications the impact of the robustness setting was noticeably higher. For high-precision IMRT (3 mm margin) and high-precision IMPT (3 mm setup/3% range error), most patients were selected for proton therapy based on problems swallowing solid food (51.3%) followed by tube feeding dependence (37.2%), decreased parotid flow (29.5%), and patient-rated xerostomia (7.7%). CONCLUSIONS: Treatment accuracy has a significant impact on the number of patients selected for proton therapy. Therefore, it cannot be ignored in estimating the number of patients for proton therapy.

Near real-time automated dose restoration in IMPT to compensate for daily tissue density variations in prostate cancer.

Proton therapy is very sensitive to daily density changes along the pencil beam paths. The purpose of this study is to develop and evaluate an automated method for adaptation of IMPT plans to compensate for these daily tissue density variations. A two-step restoration method for 'densities-of-the-day' was created: (1) restoration of spot positions (Bragg peaks) by adapting the energy of each pencil beam to the new water equivalent path length; and (2) re-optimization of pencil beam weights by minimizing the dosimetric difference with the planned dose distribution, using a fast and exact quadratic solver. The method was developed and evaluated using 8-10 repeat CT scans of 10 prostate cancer patients. Experiments demonstrated that giving a high weight to the PTV in the re-optimization resulted in clinically acceptable restorations. For all scans we obtained V 95% ⩾ 98% and V 107% ⩽ 2%. For the bladder, the differences between the restored and the intended treatment plan were below +2 Gy and +2%-point. The rectum differences were below +2 Gy and +2%-point for 90% of the scans. In the remaining scans the rectum was filled with air, which partly overlapped with the PTV. The air cavity distorted the Bragg peak resulting in less favorable rectum doses.

Which cervical and endometrial cancer patients will benefit most from intensity-modulated proton therapy?

In this dosimetric comparison study it was shown that IMPT with robust planning reduces dose to surrounding organs in cervical and endometrial cancer treatment compared with IMRT. Especially for the para-aortic region, clinically relevant dose reductions were obtained for kidneys, spinal cord and bowel, justifying the use of proton therapy for this indication.

The price of robustness; impact of worst-case optimization on organ-at-risk dose and complication probability in intensity-modulated proton therapy for oropharyngeal cancer patients.

PURPOSE: To quantify the impact of the degree of robustness against setup errors and range errors on organ-at-risk (OAR) dose and normal tissue complication probabilities (NTCPs) in intensity-modulated proton therapy for oropharyngeal cancer patients. MATERIAL AND METHODS: For 20 oropharyngeal cases (10 unilateral and 10 bilateral), robust treatment plans were generated using 'minimax' worst-case optimization. We varied the robustness against setup errors ('setup robustness') from 1 to 7mm and the robustness against range errors ('range robustness') from 1% to 7% (+1mm). We evaluated OAR doses and NTCP-values for xerostomia, dysphagia and larynx edema. RESULTS: Varying the degree of setup robustness was found to have a considerably larger impact than varying the range robustness. Increasing setup robustness from 1mm to 3, 5, and 7mm resulted in average NTCP-values to increase by 1.9, 4.4 and 7.5 percentage point, whereas they increased by only 0.4, 0.8 and 1.2 percentage point when increasing range robustness from 1% to 3%, 5% and 7%. The degree of setup robustness was observed to have a clinically significant impact in bilateral cases in particular. CONCLUSIONS: For oropharyngeal cancer patients, minimizing setup errors should be given a higher priority than minimizing range errors.

Fast and accurate sensitivity analysis of IMPT treatment plans using Polynomial Chaos Expansion.

The highly conformal planned dose distribution achievable in intensity modulated proton therapy (IMPT) can severely be compromised by uncertainties in patient setup and proton range. While several robust optimization approaches have been presented to address this issue, appropriate methods to accurately estimate the robustness of treatment plans are still lacking. To fill this gap we present Polynomial Chaos Expansion (PCE) techniques which are easily applicable and create a meta-model of the dose engine by approximating the dose in every voxel with multidimensional polynomials. This Polynomial Chaos (PC) model can be built in an automated fashion relatively cheaply and subsequently it can be used to perform comprehensive robustness analysis. We adapted PC to provide among others the expected dose, the dose variance, accurate probability distribution of dose-volume histogram (DVH) metrics (e.g. minimum tumor or maximum organ dose), exact bandwidths of DVHs, and to separate the effects of random and systematic errors. We present the outcome of our verification experiments based on 6 head-and-neck (HN) patients, and exemplify the usefulness of PCE by comparing a robust and a non-robust treatment plan for a selected HN case. The results suggest that PCE is highly valuable for both research and clinical applications.

Robustness Recipes for Minimax Robust Optimization in Intensity Modulated Proton Therapy for Oropharyngeal Cancer Patients.

PURPOSE: We aimed to derive a "robustness recipe" giving the range robustness (RR) and setup robustness (SR) settings (ie, the error values) that ensure adequate clinical target volume (CTV) coverage in oropharyngeal cancer patients for given gaussian distributions of systematic setup, random setup, and range errors (characterized by standard deviations of Σ, σ, and ρ, respectively) when used in minimax worst-case robust intensity modulated proton therapy (IMPT) optimization. METHODS AND MATERIALS: For the analysis, contoured computed tomography (CT) scans of 9 unilateral and 9 bilateral patients were used. An IMPT plan was considered robust if, for at least 98% of the simulated fractionated treatments, 98% of the CTV received 95% or more of the prescribed dose. For fast assessment of the CTV coverage for given error distributions (ie, different values of Σ, σ, and ρ), polynomial chaos methods were used. Separate recipes were derived for the unilateral and bilateral cases using one patient from each group, and all 18 patients were included in the validation of the recipes. RESULTS: Treatment plans for bilateral cases are intrinsically more robust than those for unilateral cases. The required RR only depends on the ρ, and SR can be fitted by second-order polynomials in Σ and σ. The formulas for the derived robustness recipes are as follows: Unilateral patients need SR = -0.15Σ(2) + 0.27σ(2) + 1.85Σ - 0.06σ + 1.22 and RR=3% for ρ = 1% and ρ = 2%; bilateral patients need SR = -0.07Σ(2) + 0.19σ(2) + 1.34Σ - 0.07σ + 1.17 and RR=3% and 4% for ρ = 1% and 2%, respectively. For the recipe validation, 2 plans were generated for each of the 18 patients corresponding to Σ = σ = 1.5 mm and ρ = 0% and 2%. Thirty-four plans had adequate CTV coverage in 98% or more of the simulated fractionated treatments; the remaining 2 had adequate coverage in 97.8% and 97.9%. CONCLUSIONS: Robustness recipes were derived that can be used in minimax robust optimization of IMPT treatment plans to ensure adequate CTV coverage for oropharyngeal cancer patients.

Shortening delivery times of intensity modulated proton therapy by reducing proton energy layers during treatment plan optimization.

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.

Challenges of radiotherapy: report on the 4D treatment planning workshop 2013.

This report, compiled by experts on the treatment of mobile targets with advanced radiotherapy, summarizes the main conclusions and innovations achieved during the 4D treatment planning workshop 2013. This annual workshop focuses on research aiming to advance 4D radiotherapy treatments, including all critical aspects of time resolved delivery, such as in-room imaging, motion detection, motion managing, beam application, and quality assurance techniques. The report aims to revise achievements in the field and to discuss remaining challenges and potential solutions. As main achievements advances in the development of a standardized 4D phantom and in the area of 4D-treatment plan optimization were identified. Furthermore, it was noticed that MR imaging gains importance and high interest for sequential 4DCT/MR data sets was expressed, which represents a general trend of the field towards data covering a longer time period of motion. A new point of attention was work related to dose reconstructions, which may play a major role in verification of 4D treatment deliveries. The experimental validation of results achieved by 4D treatment planning and the systematic evaluation of different deformable image registration methods especially for inter-modality fusions were identified as major remaining challenges. A challenge that was also suggested as focus for future 4D workshops was the adaptation of image guidance approaches from conventional radiotherapy into particle therapy. Besides summarizing the last workshop, the authors also want to point out new evolving demands and give an outlook on the focus of the next workshop.

Intrafraction prostate translations and rotations during hypofractionated robotic radiation surgery: dosimetric impact of correction strategies and margins.

PURPOSE: To investigate the dosimetric impact of intrafraction prostate motion and the effect of robot correction strategies for hypofractionated CyberKnife treatments with a simultaneously integrated boost. METHODS AND MATERIALS: A total of 548 real-time prostate motion tracks from 17 patients were available for dosimetric simulations of CyberKnife treatments, in which various correction strategies were included. Fixed time intervals between imaging/correction (15, 60, 180, and 360 seconds) were simulated, as well as adaptive timing (ie, the time interval reduced from 60 to 15 seconds in case prostate motion exceeded 3 mm or 2° in consecutive images). The simulated extent of robot corrections was also varied: no corrections, translational corrections only, and translational corrections combined with rotational corrections up to 5°, 10°, and perfect rotational correction. The correction strategies were evaluated for treatment plans with a 0-mm or 3-mm margin around the clinical target volume (CTV). We recorded CTV coverage (V100%) and dose-volume parameters of the peripheral zone (boost), rectum, bladder, and urethra. RESULTS: Planned dose parameters were increasingly preserved with larger extents of robot corrections. A time interval between corrections of 60 to 180 seconds provided optimal preservation of CTV coverage. To achieve 98% CTV coverage in 98% of the treatments, translational and rotational corrections up to 10° were required for the 0-mm margin plans, whereas translational and rotational corrections up to 5° were required for the 3-mm margin plans. Rectum and bladder were spared considerably better in the 0-mm margin plans. Adaptive timing did not improve delivered dose. CONCLUSIONS: Intrafraction prostate motion substantially affected the delivered dose but was compensated for effectively by robot corrections using a time interval of 60 to 180 seconds. A 0-mm margin required larger extents of additional rotational corrections than a 3-mm margin but resulted in lower doses to rectum and bladder.

Dose uncertainties in IMPT for oropharyngeal cancer in the presence of anatomical, range, and setup errors.

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.

Shortening treatment time in robotic radiosurgery using a novel node reduction technique.

PURPOSE: The fraction duration of robotic radiosurgery treatments can be reduced by generating more time-efficient treatment plans with a reduced number of node positions, beams, and monitor units (MUs). Node positions are preprogramed locations where the robot can position the focal spot of the x-ray beam. As the time needed for the robot to travel between node positions takes up a large part of the treatment time, the aim of this study was to develop and evaluate a node reduction technique in order to reduce the treatment time per fraction for robotic radiosurgery. METHODS: Node reduction was integrated into the inverse planning algorithm, developed in-house for the robotic radiosurgery modality. It involved repeated inverse optimization, each iteration excluding low-contribution node positions from the planning and resampling new candidate beams from the remaining node positions. Node reduction was performed until the exclusion of a single node position caused a constraint violation, after which the shortest treatment plan was selected retrospectively. Treatment plans were generated with and without node reduction for two lung cases of different complexity, one oropharyngeal case and one prostate case. Plan quality was assessed using the number of node positions, beams and MUs, and the estimated treatment time per fraction. All treatment plans had to fulfill all clinical dose constraints. Extra constraints were added to maintain the low-dose conformality and restrict skin doses during node reduction. RESULTS: Node reduction resulted in 12 residual node positions, on average (reduction by 77%), at the cost of an increase in the number of beams and total MUs of 28% and 9%, respectively. Overall fraction durations (excluding patient setup) were shortened by 25% (range of 18%-40%), on average. Dose distributions changed only little and dose in low-dose regions was effectively restricted by the additional constraints. CONCLUSIONS: The fraction duration of robotic radiosurgery treatments can be reduced considerably by node reduction with minimal changes in dosimetrical plan quality. Additional constraints are required to guarantee low-dose conformality and to avoid unacceptable skin dose.