Intensity Modulated Particle Therapy Research Articles

Intensity-modulated radiation therapy - you can have your cake and eat it too!

Arguably, intensity-modulated radiotherapy (IMRT) is one of the most important contributions by physicists in medicine to the treatment of cancer. It enabled the achievement of dose distributions that allowed treatment of targets to high doses and yet spared normal tissues to degrees previously considered virtually impossible. The concept underlying IMRT for photons, originally called "inverse planning," was introduced by Anders Brahme in the early 1980s. Since then, many physicists have been conducting research to advance the state of the art, to overcome obstacles discovered and to develop tools and techniques to translate it clinically. IMRT was first implemented clinically the early 1990's. Soon thereafter, it was also incorporated into intensity modulated particle therapy (IMPT), initially for protons and eventually for ions heavier than protons. In IMRT, intensities of small segments or beamlets of multiple incident beams are optimized to produce the best approximation of desired dose distributions that deliver the requisite tumor dose and maximally spare normal tissues. Such dose distributions are delivered using dynamic multi-leaf collimators whose leaves move continuously while the radiation is on or in a step-and-shoot fashion. For IMPT, there is an extra degree of freedom, that of energies of particle beamlets, which are part of the optimization process. IMPT dose distributions allow substantial additional sparing of normal tissues. They are delivered using scanning beams. IMRT and IMPT represents a true paradigm shift in the way cancer patients are treated. Their evolution, especially that of IMPT, is still ongoing, with new advancements being added continually. With the improving understanding of the immunomodulatory effects of radiotherapy, it is quite plausible that a combination of IMPT and immunotherapy will mature into one of the most effective ways of treating not just localized cancers but also systemic disease.

Biological Dose Optimization for Particle Arc Therapy Using Helium and Carbon Ions

To present biological dose optimization for particle arc therapy using helium and carbon ions. Treatment planning and optimization procedures were developed for spot-scanning hadron arc (SHArc) delivery using the RayStation treatment planning system and FRoG dose engine. The SHArc optimization algorithm is applicable for charged particle beams and determines angle dependencies for spot and energy selection with three main initiatives: (i) achieve standard clinical optimization goals and constraints for target and organs at risk (OARs), (ii) target dose robustness, and (iii) increase linear energy transfer (LET) in the target volume. Three patient cases previously treated at the Heidelberg Ion-beam Therapy Center (HIT) were selected for evaluation of conventional versus arc delivery for the two clinical particle beams (helium [4He] and carbon [12C] ions): glioblastoma, prostate adenocarcinoma, and skull-base chordoma. Biological dose and dose-averaged LET (LETd) distributions for SHArc were evaluated against conventional planning techniques (volumetric modulated arc therapy [VMAT] and 2-field intensity modulated particle therapy) applying the modified microdosimetric kinetic model with (α/β)x = 2 Gy. Clinical viability and deliverability were assessed via evaluation of plan quality, robustness, and irradiation time. For all investigated patient cases, SHArc treatment optimizations met planning goals and constraints for target coverage and OARs, exhibiting acceptable target coverage and reduced normal tissue volumes, with effective dose >10-GyRBE compared with conventional 2F planning. For carbon ions, LETd was increased in the target volume from ∼40-60 to ∼80-140 keV/µm for SHArc compared with conventional treatments. Favorable LETd distributions were possible with the SHArc approach, with maximum LETd in clinical target volume/gross tumor volume and potential reductions of high-LET regions in normal tissues and OARs. Compared with VMAT, SHArc affords substantial reductions in normal tissue dose (40%-70%). SHArc therapy offers potential treatment benefits such as increased normal tissue sparing from higher doses >10-GyRBE, enhanced target LETd, and potential reduction in high-LET components in OARs. Findings justify further development of robust SHArc treatment planning toward potential clinical translation.

Developments in Mathematical Algorithms and Computational Tools for Proton CT and Particle Therapy Treatment Planning

We summarize recent results and ongoing activities in mathematical algorithms and computer science methods related to proton computed tomography (pCT) and intensity-modulated particle therapy (IMPT) treatment planning. Proton therapy necessitates a high level of delivery accuracy to exploit the selective targeting imparted by the Bragg peak. For this purpose, pCT utilizes the proton beam itself to create images. The technique works by sending a low-intensity beam of protons through the patient and measuring the position, direction, and energy loss of each exiting proton. The pCT technique allows reconstruction of the volumetric distribution of the relative stopping power (RSP) of the patient tissues for use in treatment planning and pretreatment range verification. We have investigated new ways to make the reconstruction both efficient and accurate. Better accuracy of RSP also enables more robust inverse approaches to IMPT. For IMPT, we developed a framework for performing intensity modulation of the proton pencil beams. We expect that these developments will lead to additional project work in the years to come, which requires a regular exchange between experts in the fields of mathematics, computer science, and medical physics. We have initiated such an exchange by organizing annual workshops on the pCT and IMPT algorithm and technology developments. This report is, admittedly, tilted toward our interdisciplinary work and methods. We offer a comprehensive overview of results, problems, and challenges in pCT and IMPT with the aim of making other scientists wanting to tackle such issues and to strengthen their interdisciplinary collaboration by bringing together cutting-edge know-how from medicine, computer science, physics, and mathematics to bear on medical physics problems at hand.

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

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

When Everything Revolves Around Internal Carotid Artery: Analysis of Different Management Strategies in Patients With Very Advanced Cancer Involving the Skull Base.

Internal or common carotid artery encasement (CAE) is observed in almost 2-7% of head and neck cancers (HNC) and designates the tumor with the T4b category. This clinical scenario is associated with a dismal prognosis, owing to the risk for thrombosis and bleeding that usually characterizes such an advanced cancer. Standardized radiological criteria to infer invasion of the carotid artery are lacking. Complete surgical resection in the context of a multimodality treatment is supposed to offer the greatest chances of cure. Surgery can either be carotid-sparing or include carotidectomy. Data on probability of cerebrovascular and non-cerebrovascular complications, risk of carotid blowout, poor oncologic outcomes, and less-than-certain efficacy of diagnostic and interventional preventive procedures against cerebral infarction make it difficult to define surgery as the recommended option among other therapeutic strategies. Non-surgical therapies based on radiation therapy possibly combined with chemotherapy are more frequently employed in HNC with CAE. In this context, carotid blowout is the most feared complication, and its probability increases with tumor stage and cumulative radiation dose received by the vessel. The use of highly conformal radiotherapies such as intensity-modulated particle therapy might substantially improve the manageability of HNC with CAE by possibly reducing the risk of late sequalae. Despite evidence is frail, it appears logical that a case-by-case evaluation through multidisciplinary decision making between head and neck surgeons, radiation oncologists, medical oncologists, diagnostic and interventional radiologists, and vascular surgeons are of paramount value to offer the best therapeutic solution to patients affected by HNC with CAE.

Efficient uncertainty quantification for Monte Carlo dose calculations using importance (re-)weighting

Objective. To present an efficient uncertainty quantification method for range and set-up errors in Monte Carlo (MC) dose calculations. Further, we show that uncertainty induced by interplay and other dynamic influences may be approximated using suitable error correlation models. Approach. We introduce an importance (re-)weighting method in MC history scoring to concurrently construct estimates for error scenarios, the expected dose and its variance from a single set of MC simulated particle histories. The approach relies on a multivariate Gaussian input and uncertainty model, which assigns probabilities to the initial phase space sample, enabling the use of different correlation models. Through modification of the phase space parameterization, accuracy can be traded between that of the uncertainty or the nominal dose estimate. Main results. The method was implemented using the MC code TOPAS and validated for proton intensity-modulated particle therapy (IMPT) with reference scenario estimates. We achieve accurate results for set-up uncertainties (γ 2 mm/2% ≥ 99.01% (E[ d ]), γ 2 mm/2% ≥ 98.04% (σ( d ))) and expectedly lower but still sufficient agreement for range uncertainties, which are approximated with uncertainty over the energy distribution. Here pass rates of 99.39% (E[ d ])/ 93.70% (σ( d )) (range errors) and 99.86% (E[ d ])/ 96.64% (σ( d )) (range and set-up errors) can be achieved. Initial evaluations on a water phantom, a prostate and a liver case from the public CORT dataset show that the CPU time decreases by more than an order of magnitude. Significance. The high precision and conformity of IMPT comes at the cost of susceptibility to treatment uncertainties in particle range and patient set-up. Yet, dose uncertainty quantification and mitigation, which is usually based on sampled error scenarios, becomes challenging when computing the dose with computationally expensive but accurate MC simulations. As the results indicate, the proposed method could reduce computational effort while also facilitating the use of high-dimensional uncertainty models.

Technological Advances in Charged-Particle Therapy.

Charted-particle therapy (CPT) benefits cancer patients by localizing doses in the tumor volume while minimizing the doses delivered to normal tissue through its unique physical and biological characteristics. The world’s first CPT applied on humans was proton beam therapy (PBT), which was performed in the mid-1950s. Among heavy ions, carbon ions showed the most favorable biological characteristics for the treatment of cancer patients. Carbon ions show coincidence between the Bragg peak and maximum value of relative biological effectiveness. In addition, they show low oxygen enhancement ratios. Therefore, carbon-ion radiotherapy (CIRT) has become mainstream in the treatment of cancer patients using heavy ions. CIRT was first performed in 1977 at the Lawrence Berkeley Laboratory. The CPT technology has advanced in the intervening decades, enabling the use of rotating gantry, beam delivery with fast pencil-beam scanning, image-guided particle therapy, and intensity-modulated particle therapy. As a result, as of 2019, a total of 222,425 and 34,138 patients with cancer had been treated globally with PBT and CIRT, respectively. For more effective and efficient CPT, many groups are currently conducting further studies worldwide. This review summarizes recent technological advances that facilitate clinical use of CPT.

Robust treatment planning with 4D intensity modulated carbon ion therapy for multiple targets in stage IV non-small cell lung cancer

Intensity modulated particle therapy (IMPT) with carbon ions can generate highly conformal treatment plans; however, IMPT is limited in robustness against range and positioning uncertainty. This is particularly true for moving targets, even though all motion states of a 4DCT are considered in 4D-IMPT. Here, we expand 4D-IMPT to include robust non-linear RBE-weighted optimization to explore its potential in improving plan robustness and sparing critical organs. In this study, robust 4D-optimization—based on worst-case optimization on 9 scenarios—was compared to conventional 4D-optimization with PTV margins using 4D dose calculation and robustness analysis for 21 uncertainty scenarios. Slice-by-slice rescanning was used for motion mitigation. Both 4D-optimization strategies were tested on a cohort of 8 multi-lesion lung cancer patients with the goal of prioritizing OAR sparing in a hypofractionated treatment plan. Planning objectives were to keep the OAR volume doses below corresponding limits while simultaneously achieve CTV coverage with D95% ≥ 95 %. For the conventional plans, average D95% was at 98.7% which fulfilled the target objective in 83.2% of scenarios. For the robust plans, average D95% was reduced to 97.6% which still fulfilled the target objective in 80.7% of cases, but led to significantly improved overall OAR sparing: Volume doses were below the limits in 96.2% of cases for the conventional and 99.5% for the robust plans. When considering the particularly critical smaller airways only, fulfillment rates could be increased from 76.2% to 96% for the robust plans. This study has shown that plan robustness of 4D-IMPT could be improved by using robust 4D-optimization, offering greater control over uncertainties in the actual delivered dose. In some cases, this required sacrificing target coverage for the benefit of better OAR sparing.

Automatic phase space generation for Monte Carlo calculations of intensity modulated particle therapy

Monte Carlo (MC) is generally considered as the most accurate dose calculation tool for particle therapy. However, a proper description of the beam particle kinematics is a necessary input for a realistic simulation. Such a description can be stored in phase space (PS) files for different beam energies. A PS file contains kinetic information such as energies, positions and travelling directions for particles traversing a plane perpendicular to the beam direction. The accuracy of PS files plays a critical role in the performance of the MC method for dose calculations. A PS file can be generated with a set of parameters describing analytically the beam kinematics. However, determining such parameters can be tedious and time consuming. Thus, we have developed an algorithm to obtain those parameters automatically and efficiently. In this paper, we presented such an algorithm and compared dose calculations using PS automatically generated for the Shanghai Proton and Heavy Ion Center (SPHIC) with measurements. The gamma-index for comparing calculated depth dose distributions (DDD) with measurements are above 96.0% with criterion 0.6%/0.6 mm. For each single energy, the mean difference percentage between calculated lateral spot sizes at 5 different locations along beam direction and measurements are below 3.5%.

Simultaneous optimization of RBE-weighted dose and nanometric ionization distributions in treatment planning with carbon ions

Inverse treatment planning in intensity modulated particle therapy (IMPT) with scanned carbon–ion beams is currently based on the optimization of RBE-weighted dose to satisfy requirements of target coverage and limited toxicity to organs-at-risk (OARs) and healthy tissues. There are many feasible IMPT plans that meet these requirements, which allows the introduction of further criteria to narrow the selection of a biologically optimal treatment plan. We propose a novel treatment planning strategy based on the simultaneous optimization of RBE-weighted dose and nanometric ionization details (ID) as a new physical characteristic of the delivered plan beyond LET. In particular, we focus on the distribution of large ionization clusters (more than 3 ionizations) to enhance the biological effect across the target volume while minimizing biological effect in normal tissues. Carbon–ion treatment plans for different patient geometries and beam configurations generated with the simultaneous optimization strategy were compared against reference plans obtained with RBE-weighted dose optimization alone. Quality indicators, inhomogeneity index and planning volume histograms of RBE-weighted dose and large ionization clusters were used to evaluate the treatment plans. We show that with simultaneous optimization, ID distributions can be optimized in carbon–ion radiotherapy without compromising the RBE-weighted dose distributions. This strategy can potentially be used to account for optimization of endpoints closely related to radiation quality to achieve better tumor control and reduce risks of complications.

P203] WEPL-corrected margins for moving targets in carbon-ion gated treatments: Preliminary results

Purpose To evaluate intra- and inter-fractional robustness of carbon-ion treatment plans based on water-equivalent path length (WEPL) corrected ITV margins for moving targets irradiated with gated pencil-beam scanning. Methods As a preliminary study, three patients with thoraco-abdominal targets were considered. Clinical plans were optimized with an Intensity Modulated Particle Therapy (IMPT) algorithm and the use of case-specific avoidance structures to prevent radiation pathways on regions subject to intra- and inter-fractional variations. Plans were optimized on the end-exhale CT of a 4DCT dataset using 2 fields and tested for consistency within the gating window by recalculation on the 30%-exhale and 30%-inhale CTs. Single Field Uniform Dose (SFUD) plans were optimized on beam-specific WEPL-corrected ITV ( ITV WEPL ), which comprised the envelope of water-equivalent target positions within the ideal gating window. Differently from clinical plans, avoidance structures were not used in this approach. Clinical plans were taken as reference for comparison. Dose recalculations on the planning 4DCT and on synthetic 4DCT simulating irregular breathing allowed to evaluate intra-fractional robustness of the two approaches, whereas inter-fractional robustness was estimated on re-evaluation CTs (one per patient). Differences in the conformity index CI = V 95 % / V target , target coverage D 95 % and homogeneity index HI = ( D 2 % − D 98 % )/ D 50 % between the end-exhale plan and the recalculated dose distributions were computed. Doses to the involved organs at risk (OARs) were evaluated as well. Results The CI presented slightly higher median intra-/inter-fractional variations and absolute values in the ITV WEPL approach (13%–1.47) with respect to reference plans (6%–1.36). D 95 % and HI showed lower median intra-fractional variations for the ITV WEPL approach (0.1% and 35%) compared to reference plans (3.4% and 46%). In case of inter-fractional changes, the use of ITV WEPL led to higher median variations but comparable absolute values for D 95 % (3.8% vs 2.2%) and for HI (144% vs 20%, absolute median values: 0.11 vs 0.14). The two methods performed similarly in OARs. Conclusions The use of WEPL-corrected ITV permits adequate tumor coverage even in presence of irregular breathing motion, for the small analyzed sample. Although uncertainties due only to intra-fractional organ motion were considered in the ITV WEPL approach, comparable inter-fractional robustness was found among the two strategies.

Significance of intra-fractional motion for pancreatic patients treated with charged particles

BackgroundUncertainties associated with the delivery of treatment to moving organs might compromise the accuracy of treatment. This study explores the impact of intra-fractional anatomical changes in pancreatic patients treated with charged particles delivered using a scanning beam. The aim of this paper is to define the potential source of uncertainties, quantify their effect, and to define clinically feasible strategies to reduce them.MethodsThe study included 14 patients treated at our facility with charged particles (protons or 12C) using intensity modulated particle therapy (IMPT). Treatment plans were optimized using the Treatment Planning System (TPS) Syngo® RT Planning. The pre-treatment dose distribution under motion (4D) was simulated using the TPS TRiP4D and the dose delivered for some of the treatment fractions was reconstructed. The volume receiving at least 95% of the prescribed dose (V95CTV) and the target dose homogeneity were evaluated. The results from the 4D dose calculations were compared with dose distributions in the static case and its variation correlated with the internal motion amplitude and plan modulation, through the Pearson correlation coefficient, as well the significant p-value. The concept of the modulation index (MI) was introduced to assess the degree of modulation of IMPT plans, through the quantification of intensity gradients between neighboring pencil beams.ResultsThe induced breathing motion together with dynamic beam delivery results in an interplay effect, which affects the homogeneity and target coverage of the dose distribution. This effect is stronger (∆V95CTV > 10%) for patients with tumor motion amplitude above 5 mm and a highly modulated dose distribution between and within fields. The MI combined with the internal motion amplitude is shown to correlate with the target dose degradation and a lack of plan robustness against range and positioning uncertainties.ConclusionsUnder internal motion the use of inhomogeneous plans results in a decrease in the dose homogeneity and target coverage of dose distributions in comparison to the static case. Plan robustness can be improved by using multiple beams and avoiding beam entrance directions susceptible to density changes. 4D dose calculations support the selection of the most suitable plan for the specific patient’s anatomy.

Treatment planning with intensity modulated particle therapy for multiple targets in stage IV non-small cell lung cancer

Intensity modulated particle therapy (IMPT) can produce highly conformal plans, but is limited in advanced lung cancer patients with multiple lesions due to motion and planning complexity. A 4D IMPT optimization including all motion states was expanded to include multiple targets, where each target (isocenter) is designated to specific field(s). Furthermore, to achieve stereotactic treatment planning objectives, target and OAR weights plus objective doses were automatically iteratively adapted. Finally, 4D doses were calculated for different motion scenarios. The results from our algorithm were compared to clinical stereotactic body radiation treatment (SBRT) plans. The study included eight patients with 24 lesions in total. Intended dose regimen for SBRT was 24 Gy in one fraction, but lower fractionated doses had to be delivered in three cases due to OAR constraints or failed plan quality assurance. The resulting IMPT treatment plans had no significant difference in target coverage compared to SBRT treatment plans. Average maximum point dose and dose to specific volume in OARs were on average 65% and 22% smaller with IMPT. IMPT could also deliver 24 Gy in one fraction in a patient where SBRT was limited due to the OAR vicinity. The developed algorithm shows the potential of IMPT in treatment of multiple moving targets in a complex geometry.

Optimization of Carbon Ion Treatment Plans by Integrating Tissue Specific α/β-Values for Patients with Non-Resectable Pancreatic Cancer.

BackgroundThe aim of the thesis is to improve treatment plans of carbon ion irradiation by integrating the tissues’ specific -values for patients with locally advanced pancreatic cancer (LAPC).Material and MethodsFive patients with LAPC were included in this study. By the use of the treatment planning system Syngo RT Planning (Siemens, Erlangen, Germany) treatment plans with carbon ion beams have been created. Dose calculation was based on -values for both organs at risk (OAR) and the tumor. Twenty-five treatment plans and thirty-five forward calculations were created. With reference to the anatomy five field configurations were included. Single Beam Optimization (SBO) and Intensity Modulated Particle Therapy (IMPT) were used for optimization. The plans were analyzed with respect to both dose distributions and individual anatomy. The plans were evaluated using a customized index.ResultsWith regard to the target, a field setup with one single posterior field achieves the highest score in our index. Field setups made up of three fields achieve good results in OAR sparing. Nevertheless, the field setup with one field is superior in complex topographic conditions. But, allocating an -value of 2 Gy to the spinal cord leads to critical high maximum doses in the spinal cord. The evaluation of dose profiles showed significant dose peaks at borders of the -gradient, especially in case of a single posterior field.ConclusionOptimization with specific -values allows a more accurate view on dose distribution than previously. A field setup with one single posterior field achieves good results in case of difficult topographic conditions, but leads to high maximum doses to the spinal cord. So, field setups with multiple fields seem to be more adequate in case of LAPC, being surrounded by highly radiosensitive normal tissues.

Motion mitigation in intensity modulated particle therapy by internal target volumes covering range changes

Particle therapy offers benefits over conventional photon therapy but also introduces sensitivity to changes in the water-equivalent path length (WEPL) in case of target motion, e.g., breathing. Target motion can be addressed by the internal target volume (ITV) approach, defined as the CTV plus target movement. In photon therapy, the ITV can be constructed as the geometric union of CTVs in all motion states (GEO-ITV) of a 4D-CT, but this does not account for WEPL-changes. An ITV including WEPL-changes can be defined as the union of all CTVs transformed to a WEPL-equivalent axis along beam's eye view. The resulting WEPL-ITV is field-specific and thus unsuitable for intensity modulated particle therapy (IMPT). The purpose of this study was an IMPT-compatible ITV by splitting geometrical motion and field-specific WEPL changes, following ICRU 78 recommendations. For all fields, the GEO-ITV was used as a common target. This identical geometry for all fields was mapped to an enlarged WEPL extent with a field-specific transformation. As the dose distribution is determined by the WEPL, this is sufficient to achieve equivalent dose coverage as for a geometrically enlarged target volume. The WEPL enlargement is only visible to the specific field and therefore does not increase the target volume of other fields. This avoids unnecessary lateral field extensions, reducing the dose to normal tissue. Homogeneous dose coverage in IMPT is achieved only if the inhomogeneous doses from the individual fields match up during delivery. As the course of the WEPL within each motion phase differs, this cannot be guaranteed by optimizing the fields only in the reference phase. The WEPL-ITV for the reference phase can be amended by CTVs from a subset of motion phases (4D-WEPL-ITV). Here, end-exhale as the reference phase was combined with end-inhale to cover the whole motion range. The GEO-ITV, WEPL-ITV, and 4D-WEPL-ITV were applied in an IMPT simulation of a lung cancer patient case using a four-field geometry and the heart as an OAR. A static plan of the CTV in end-exhale was computed for reference. The CTV was moving approximately 20 mm in SI and was partly overlapping the heart. For a single fraction a target dose of 17.7 GyE was prescribed, with a 50% maximum dose for the heart. With 21 rescans to counter interplay, the homogeneity (D5-D95) was 17.0%, 9.0%, 6.0%, and 3.5% for the GEO-ITV, WEPL-ITV, 4D-WEPL-ITV, and a 3D CTV plan computed for reference, respectively. Due to the overlap, the 50% maximum dose was violated by all plans, with V50 of 3.8%, 3.5%, 3.7%, and 2.0% for the four plans. A 4D-WEPL-ITV method was developed that is suitable for IMPT, covers range changes, and drastically improves dose homogeneity in the target without increasing the OAR dose.

Comparison of intensity modulated radiotherapy (IMRT) with intensity modulated particle therapy (IMPT) using fixed beams or an ion gantry for the treatment of patients with skull base meningiomas

BackgroundTo examine the potential improvement in treatment planning for patients with skull base meningioma using IMRT compared to carbon ion or proton beams with and without a gantry.MethodsFive patients originally treated with photon IMRT were selected for the study. Ion beams were chosen using a horizontal beam or an ion gantry. Intensity controlled raster scanning and the intensity modulated particle therapy mode were used for plan optimization. The evaluation included analysis of dose-volume histograms of the target volumes and organs at risk.ResultsIn comparison with carbon and proton beams only with horizontal beams, carbon ion treatment plans could spare the OARs more and concentrated on the target volumes more than proton and photon IMRT treatment plans. Using only a horizontal fixed beam, satisfactory plans could be achieved for skull base tumors.ConclusionThe results of the case studies showed that using IMPT has the potential to overcome the lack of a gantry for skull base tumors. Carbon ion plans offered slightly better dose distributions than proton plans, but the differences were not clinically significant with established dose prescription concepts.

TU‐G‐BRA‐04: Biological Optimization in Carbon Therapy

The application of high linear energy transfer (LET) radiation in modern radiation oncology, like carbon‐ion therapy, requires different concepts of treatment plan optimization when compared RT‐planning for photon beams. Although, by far not perfect, the standard strategy employs the concept of relative biological effectiveness (RBE), which converts the delivered physical particle dose into a radio‐biologically equivalent dose of low LET beams. In order to introduce the respective RBE models into the inverse planning process of particle therapy one directly aims to optimize the biological effect, mostly expressed in terms of a linear quadratic model (LQM) for a dose‐effect relationship.We will first introduce the general framework of biological optimization for inverse planning of intensity modulated particle therapy (IMPT). The effects of the intrinsic radiation quality on the design of treatment plans will be demonstrated for various forms of dose delivery methods, like spread‐out Bragg peaks (SOBP), distal edge‐tracking (DET) or 3D‐spot scanning and different clinical treatment sites. So far, the employed models only account for the most important radiobiological factor, the anticipated local LET distribution, while other additional factors like the oxygen enhancement ratio or the influence of different fractionation schemes are not considered explicitly.Finally, another important issue will be briefly mentioned, the robustness of biologically optimized treatment plans versus uncertainties in the dose delivery process or even the limited knowledge of the biological input parameters of the employed models that are predicting the biological effect. Some results in the framework of the worst‐case optimization will be discussed.Learning Objectives:1. To review the framework of biological inverse planning of carbon therapy2. To understand the potential and inherent limitations of the optimization approach

Advanced treatment planning methods for efficient radiation therapy with laser accelerated proton and ion beams

Laser plasma acceleration can potentially replace large and expensive cyclotrons or synchrotrons for radiotherapy with protons and ions. On the way toward a clinical implementation, various challenges such as the maximum obtainable energy still remain to be solved. In any case, laser accelerated particles exhibit differences compared to particles from conventional accelerators. They typically have a wide energy spread and the beam is extremely pulsed (i.e., quantized) due to the pulsed nature of the employed lasers. The energy spread leads to depth dose curves that do not show a pristine Bragg peak but a wide high dose area, making precise radiotherapy impossible without an additional energy selection system. Problems with the beam quantization include the limited repetition rate and the number of accelerated particles per laser shot. This number might be too low, which requires a high repetition rate, or it might be too high, which requires an additional fluence selection system to reduce the number of particles. Trying to use laser accelerated particles in a conventional way such as spot scanning leads to long treatment times and a high amount of secondary radiation produced when blocking unwanted particles. The authors present methods of beam delivery and treatment planning that are specifically adapted to laser accelerated particles. In general, it is not necessary to fully utilize the energy selection system to create monoenergetic beams for the whole treatment plan. Instead, within wide parts of the target volume, beams with broader energy spectra can be used to simultaneously cover multiple axially adjacent spots of a conventional dose delivery grid as applied in intensity modulated particle therapy. If one laser shot produces too many particles, they can be distributed over a wider area with the help of a scattering foil and a multileaf collimator to cover multiple lateral spot positions at the same time. These methods are called axial and lateral clustering and reduce the number of particles that have to be blocked in the beam delivery system. Furthermore, the optimization routine can be adjusted to reduce the number of dose spots and laser shots. The authors implemented these methods into a research treatment planning system for laser accelerated particles. The authors' proposed methods can decrease the amount of secondary radiation produced when blocking particles with wrong energies or when reducing the total number of particles from one laser shot. Additionally, caused by the efficient use of the beam, the treatment time is reduced considerably. Both improvements can be achieved without extensively changing the quality of the treatment plan since conventional intensity modulated particle therapy usually includes a certain amount of unused degrees of freedom which can be used to adapt to laser specific properties. The advanced beam delivery and treatment planning methods reduce the need to have a perfect laser-based accelerator reproducing the properties of conventional accelerators that might not be possible without increasing treatment time and secondary radiation to the patient. The authors show how some of the differences to conventional beams can be overcome and efficiently used for radiation treatment.

The future of heavy ion radiotherapy

Currently, there is an increasing interest in heavy ion radiotherapy (RT) and a number of new facilities are being installed in Europe and Japan. This development is accompanied by intensive technical, physical, and clinical research. The authors identify six research fields where progress is likely and propose a thesis on the expected achievements for each of the fields: (1) Synchrotrons with active energy variation and three-dimensional beam scanning will be the standard in ion beam RT. (2) Common standards for precise measurement, prescription, and reporting of dose will be available. (3) Intensity-modulated particle therapy will be state-of-the-art. (4) Time-adaptive treatments of moving targets will be feasible. (5) Therapeutic effectiveness of heavy ions will be known for the most important indications while cost effectiveness will remain to be shown. (6) The potential of high-linear energy transfer radiation will be known. The rationale for each of these theses is described.

SU-FF-T-28: A Monte Carlo Study On Carbon RBE for Carbon Therapy

Purpose: To estimate carbon RBE for radiotherapy planning based on a RBE‐LET model using Monte Carlo(MC) simulations. Method and Materials: The MC method has been implemented for carbon (C6+) dose calculations for radiation therapytreatment planning. The FLUKA code is used to generate carbon ion tracks in medium and incorporate them into MCDOSE for patient dose calculation. A two‐step optimization scheme is used to yield 3‐D conformal and homogeneous dose distributions. First, we select the small carbon beams (beamlets) with proper energy spectra to generate SOBPs based on Boltzmann transport equation. Those beamlets with SOBPs can be used for conventional particle therapy (CPT) and can be further used for intensity‐modulated particle therapy (IMPT). We have either used a constant RBE (=5) or a variable RBE in the beamlet dose calculation. RBE is calculated based on the RBE‐LET model: RDE ( D , L , α 0 , λ, α, β) = α 2 + 4β D (α 0 + λ L + β D ) − α 2β D where α0, λ, α, β are determined by experiments. L is energy linear transfer (LET) that can be calculated by the Bethe‐Bloch formula: L = − dE dx = 2π N a r e 2 m e c 2 ρ Z A z 2 β 2 [ ln ( 2 m e γ 2 β 2 W max I 2 ) − 2β 2 ] . Results: Ten prostate treatment plans were generated using carbon beams for this study. The target dose was prescribed to 76 Gy (Co‐equivalent), and 7–9 beams were used for all the plans. Comparisons were made between carbon CPT and carbon IMPT with a constant RBE and variable RBE. The ratio of mean doses with a constant RBE and with variable RBE varied depending on the plan and the organ. Generally, for CPT plans, the ratio was 1.06 for the target dose, 1.26 for the bladder, and 1.3 for the rectum. Through optimization, these differences were reduced for IMPT plans; the ratio for the target was about 1.0, 1.11 for the bladder and 1.03 for the rectum after RBE‐corrected optimization. Conclusion: The RBE‐based optimization is needed to correct the RBE effect for optimal target coverage and critical structure sparing in IMPT treatment planning.