Dose-averaged Linear Energy Transfer Research Articles

Assessment of fluence- and dose-averaged linear energy transfer with passive luminescence detectors in clinical proton beams.

This work investigates the use of passive luminescence detectors to determine different types of averaged linear energy transfer (\overline{LET}) for the energies relevant to proton therapy. The experimental results are compared to reference values obtained from Monte Carlo simulations. Optically stimulated luminescence detectors (OSLDs), fluorescent nuclear track detectors (FNTDs), and two different groups of thermoluminescence detectors (TLDs) were irradiated at four different radiation qualities. For each irradiation, the fluence- (\overline{LET}f) and dose-averaged LET (\overline{LET}d) were determined. For both quantities, two sub-types of averages were calculated, either considering contributions from primary and secondary protons or from all protons and heavier charged particles. Both simulated and experimental data were used in combination with a phenomenological model to estimate the relative biological effectiveness (RBE). All types of \overline{LET} could be assessed with the detectors. The experimental determination of \overline{LET}fis in agreement with reference data obtained from simulations across all measurement techniques and types of averaging. On the other hand, \overline{LET}dcan present challenges as a radiation quality metric to describe the detector response in mixed particle fields. However, excluding secondaries heavier than protons from the \overline{LET}dcalculation, as their contribution to the luminescence is suppressed by ionization quenching, leads to equal accuracy between \overline{LET}fand \overline{LET}d. Assessment of RBE through the experimentally determined \overline{LET}dvalues agrees with independently acquired reference values, indicating that the investigated detectors can determine \overline{LET} with sufficient accuracy for proton therapy. OSLDs, TLDs, and FNTDs can be used to determine \overline{LET} and RBE in proton therapy. With the capability to determine dose through ionization quenching corrections derived from \overline{LET}, OSLDs and TLDs can simultaneously ascertain dose, \overline{LET}, and RBE. This makes passive detectors appealing for measurements in phantoms, facilitating the validation of clinical treatment plans or experiments related to proton therapy.

OSLD nanoDot characterization for carbon radiotherapy dosimetry

Objective. This study characterized optically-stimulated luminescent dosimeter (OSLD) nanoDots for use in a therapeutic carbon beam using the Imaging and Radiation Oncology Core (IROC) framework for remote output verification. Approach. The absorbed dose correction factors for OSLD (fading, linearity, beam quality, angularity, and depletion), as defined by AAPM TG 191, were characterized for carbon beams. For the various correction factors, the effect of linear energy transfer (LET) was examined by characterizing in both a low and high LET setting. Main results. Fading was not statistically different between reference photons and carbon, nor between low and high LET beams; thus, the standard IROC-defined exponential function could be used to characterize fading. Dose linearity was characterized with a linear fit; while low and high LET carbon linearity was different, these differences were small and could be rolled into the uncertainty budget if using a single linearity correction. A linear fit between beam quality and dose-averaged LET was determined. The OSLD response at various angles of incidence was not statistically different, thus a correction factor need not be applied. There was a difference in depletion between low and high LET irradiations in a primary carbon beam, but this difference was small over the standard five readings. The largest uncertainty associated with the use of OSLDs in carbon was because of the k Q correction factor, with an uncertainty of 6.0%. The overall uncertainty budget was 6.3% for standard irradiation conditions. Significance. OSLD nanoDot response was characterized in a therapeutic carbon beam. The uncertainty was larger than for traditional photon applications. These findings enable the use of OSLDs for carbon absorbed dose measurements, but with less accuracy than conventional OSLD audit programs.

Deep learning based linear energy transfer calculation for proton therapy.

This study aims to address the limitations of traditional methods for calculating linear energy transfer (LET), a critical component in assessing relative biological effectiveness (RBE). Currently, Monte Carlo (MC) simulation, the gold-standard for accuracy, is resource-intensive and slow for dose optimization, while the speedier analytical approximation has compromised accuracy. Our objective was to prototype a deep-learning-based model for calculating dose-averaged LET (LETd) using patient anatomy and dose-to-water (DW) data, facilitating real-time biological dose evaluation and LET optimization within proton treatment planning systems.
Approach: 275 4-field prostate proton Stereotactic Body Radiotherapy (SBRT) plans were analyzed, rendering a total of 1100 fields. Those were randomly split into 880, 110, and 110 fields for training, validation, and testing. A 3D Cascaded UNet model, along with data processing and inference pipelines, was developed to generate patient-specific LETd distributions from CT images and DW. The accuracy of the LETd of the test dataset was evaluated against MC-generated ground truth through voxel-based mean absolute error (MAE) and gamma analysis.
Main Results: The proposed model accurately inferred LETd distributions for each proton field in the test dataset. A single-field LETd calculation took around 100 ms with trained models running on a NVidia A100 GPU. The selected model yielded an average MAE of 0.94±0.14 MeV/cm and a gamma passing rate of 97.4% ± 1.3% when applied to the test dataset, with the largest discrepancy at the edge of fields where the dose gradient was the largest and counting statistics was the lowest.
Significance: This study demonstrates that deep-learning-based models can efficiently calculate LETd with high accuracy as a fast-forward approach. The model shows great potential to be utilized for optimizing the RBE of proton treatment plans. Future efforts will focus on enhancing the model's performance and evaluating its adaptability to different clinical scenarios.

Dose averaged linear energy transfer optimization for large sacral chordomas in carbon ion therapy.

Carbon ion beams are well accepted as densely ionizing radiation with a high linear energy transfer (LET). However, the current clinical practice does not fully exploit the highest possible dose-averaged LET (LETd) and, consequently, the biological potential in the target. This aspect becomes worse in larger tumors for which inferior clinical outcomes and corresponding lower LETd wasreported. The vicinity to critical organs in general and the inferior overall survival reported for larger sacral chordomas treated with carbon ion radiotherapy (CIRT), makes the treatment of such tumors challenging. In this work it was aimed to increase the LETd in large volume tumors while maintaining the relative biological effectiveness (RBE)-weighted dose, utilizing the LETd optimization functions of a commercial treatment planning system (TPS). Ten reference sequential boost carbon ion treatment plans, designed to mimic clinical plans for large sacral chordoma tumors, were generated. High dose clinical target volumes (CTV-HD) larger than were considered as large targets. The total RBE-weighted median dose prescription with the local effect model (LEM) was in 16 fractions (nine to low dose and seven to high dose planning target volume). No LETd optimization was performed in the reference plans, while LETd optimized plans used the minimum LETd (Lmin) optimization function in RayStation2023B. Three different Lmin values were investigated and specified for the seven boost fractions: , and . To compare the LETd optimized against reference plans, LETd and RBE-weighted dose based goals similar to and less strict than clinical ones were specified for the target. The goals for the organs at risk (OAR) remained unchanged. Robustness evaluation was studied for eight scenarios ( range uncertainty and setup uncertainty along the main three axes). The optimization method with resulted in an optimal LETd distribution with an average increase of (and ) in the CTV-HD by ( ) (and ( )), without significant difference in the RBE-weighted dose. By allowing over- and under-dosage in the target, the (and ) can be increased by ( ) (and ( )), using the optimization parameters . The pass rate for the OAR goals in the LETd optimized plans was in the same level as the reference plans. LETd optimization lead to less robust plans compared to referenceplans. Compared to conventionally optimized treatment plans, the LETd in the target was increased while maintaining the RBE-weighted dose using TPS LETd optimization functionalities. Regularly assessing RBE-weighted dose robustness and acquiring more in-room images remain crucial and inevitable aspects duringtreatment.

The sensitivity of radiobiological models in carbon ion radiotherapy (CIRT) and its consequences on the clinical treatment plan: Differences between LEM and MKM models.

Carbon ion radiotherapy (CIRT) relies on relative biological effectiveness (RBE)-weighted dose calculations. Japanese clinics predominantly use the microdosimetric kinetic model (MKM), while European centers utilize the local effect model (LEM). Despite both models estimating RBE-distributions in tissue, their physical and mathematical assumptions differ, leading to significant disparities in RBE-weighted doses. Several European clinics adopted Japanese treatment schedules, necessitating adjustments in dose prescriptions and organ at risk (OAR) constraints. In the context of these two clinically used standards for RBE-weighted dose estimation, the objective of this study was to highlight specific scenarios for which the translations between models diverge, as shortcomings between them can influence clinical decisions. Our aim was to discuss planning strategies minimizing those discrepancies, ultimately striving for more accurate and robust treatments. Evaluations were conducted in a virtual water phantom and patient CT-geometry, optimizing LEM RBE-weighted dose first and recomputing MKM thereafter. Dose-averaged linear energy transfer (LETd) distributions were also assessed. Results demonstrate how various parameters influence LEM/MKM translation. Similar LEM-dose distributions lead to markedly different MKM-dose distributions and variations in LETd. Generally, a homogeneous LEM RBE-weighted dose aligns with lower MKM values in most of the target volume. Nevertheless, paradoxical MKM hotspots may emerge (at the end of the range), potentially influencing clinical outcomes. Therefore, translation between models requires great caution. Understanding the relationship between these two clinical standards enables combining European and Japanese based experiences. The implementation of optimal planning strategies ensures the safety and acceptability of the clinical plan for both models and therefore enhances plan robustness from the RBE-weighted dose and LETd distribution point of view. This study emphasizes the importance of optimal planning strategies and the need for comprehensive CIRT plan quality assessment tools. In situations where simultaneous LEM and MKM computation capabilities are lacking, it can provide guidance in plan design, ultimately contributing to enhanced CIRT outcomes.

Linear Energy Transfer Measurements and Estimation of Relative Biological Effectiveness in Proton and Helium Ion Beams Using Fluorescent Nuclear Track Detectors

PurposeTo develop a methodology for assessing the linear energy transfer (LET) and relative biological effectiveness (RBE) in clinical proton and helium-ion beams using fluorescent nuclear track detectors (FNTDs). Methods and materialsFNTDs were exposed behind solid water to proton and helium- (4He-) ion spread-out Bragg peaks (SOBPs). Detectors were imaged with a confocal microscope, and the LET spectra were derived from the fluorescence intensity. The track- and dose-averaged LET (LETF and LETD, respectively) were calculated from the LET spectra. LET measurements were used as input on RBE-models to estimate the RBE. Human alveolar adenocarcinoma cells (A549) were exposed at the same positions as the FNTDs. The RBE was calculated from the resulting survival curves. All measurements were compared with Monte Carlo simulations. ResultsFor protons, average relative differences between measurements and simulations were 6% and 19% for LETF and LETD, respectively. For helium ions the same differences were 11% for both quantities. The position of the experimental LET spectra primary peaks agreed with the simulations within 9% and 14% for protons and helium-ions, respectively. For the RBE-models using LETD as input, FNTD-based RBE values ranged from 1.02 ± 0.01 to 1.25 ± 0.04 and from 1.08 ± 0.09 to 2.68 ± 1.26 for protons and helium-ions, respectively. The average relative differences between these values and simulations were 2% and 4%. For A549 cells, the RBE ranged from 1.05 ± 0.07 to 1.47 ± 0.09 and from 0.89 ± 0.06 to 3.28 ± 0.20 for protons and helium-ions, respectively. Regarding the RBE-weighted dose (2.0 Gy at the SOBP), the differences between simulations and measurements were below 0.10 Gy. ConclusionThis study demonstrates for the first time that FNTDs can be used to perform direct LET measurements and to estimate the RBE in clinical proton and helium-ion beams.

Dose-averaged LET optimized carbon-ion radiotherapy for head and neck cancers

This feasibility study confirmed the initial safety and efficacy of a novel carbon-ion radiotherapy (CIRT) using linear energy transfer (LET) painting for head and neck cancer. This study is the first step toward establishing CIRT with LET painting in clinical practice and making it a standard practice in the future.

Single high-energy arc proton therapy with Bragg peak boost (SHARP).

Because of the co-location of critical organs at risk, base of skull tumours require steep dose gradients to achieve the prescribed dosimetric criteria. When available, proton beam therapy (PBT) is often considered a desirable modality for these cases, but in many instances, compromises in target coverage are still required to achieve critical organ at risk (OAR) tolerance doses. A number of techniques have been proposed to further improve the penumbra of PBT. In the current study, we propose a novel, collimator-free treatment planning technique that combines high-energy shoot-through proton beams with conventional Bragg peak spot placement. The small spot size of the high-energy pencil beams provides a sharp penumbra at the target boundary, and the Bragg peak spots provide a higher linear energy transfer (LET) boost to the target centre. Three base of skull chordoma patients were retrospectively planned with three different PBT treatment planning techniques: (1) conventional intensity-modulated proton therapy (IMPT); (2) high-energy proton arc therapy (HE-PAT); and (3) the novel technique combining HE-PAT and IMPT, referred to as single high-energy arc with Bragg peak boost (SHARP). The Monaco 6 treatment planning system was used. SHARP was found to improve the PBT penumbra in the plane perpendicular to the HE-PAT beams. Minimal penumbra differences were observed in the plane of the HE-PAT beams. SHARP reduced dose-averaged LET to surrounding organs at risk. A novel PBT treatment planning technique was successfully implemented. Initial results indicate the potential for SHARP to improve the penumbra of PBT treatments for base of skull tumours.

Up modulation of dose-averaged linear energy transfer by simultaneousintegratedboost in carbon-ion radiotherapy for pancreatic carcinoma.

Local recurrence in locally advanced pancreatic cancer (LAPC) after carbon-ion radiotherapy (CIRT) may partly attribute to low dose-averaged linear energy transfer (LETd ), despite high CIRT dose. This study aimed to investigate the approaches to up-modulate the CIRT LETd and to evaluate the corresponding oxygen enhancement ratio (OER) reduction. 10 LAPCs that had been irradiated by CIRT with 67.5Gy (RBE) in 15 fractions were selected. Their original plans were taken as the control plan for the LETd and OER investigations. Our considerations for up-modulating LETd were: (1) to deliver high doses to gross tumor volume core (GTVcore), while keeping dose constraints of the gastrointestinal (GI) tract in tolerance; (2) to put more Bragg-peak (BP) within the modulated targets; (3) to increase the BP density, high doses were necessary; (4) CIRT LETd could be effectively increased to small volumes; and (5) simultaneous integrated boost technique (SIB) could achieve the aforementioned tasks.The LETd and the corresponding OER distributions of each type of SIB plan were evaluated. We delivered up to 100Gy (RBE) to GTVcore using SIB. The mean LETd of GTV increased significantly by 21.3% from 47.8 to 58.0keV/μm (p<0.05). Meanwhile, the mean OER of GTVcore decreased by 6.6%, from 1.51 to 1.41 (p<0.05). The GI LETd S in all modulated plans were not more than those in the original plans. SIB could effectively increase CIRT LETd to LAPC, thus producing reduced OER, which may effectively overcome the radioresistance of LAPCs.

Deep learning-based synthetic dose-weighted LET map generation for intensity modulated proton therapy

The advantage of proton therapy as compared to photon therapy stems from the Bragg peak effect, which allows protons to deposit most of their energy directly at the tumor while sparing healthy tissue. However, even with such benefits, proton therapy does present certain challenges. The biological effectiveness differences between protons and photons are not fully incorporated into clinical treatment planning processes. In current clinical practice, the relative biological effectiveness (RBE) between protons and photons is set as constant 1.1. Numerous studies have suggested that the RBE of protons can exhibit significant variability. Given these findings, there is a substantial interest in refining proton therapy treatment planning to better account for the variable RBE. Dose-average linear energy transfer (LETd) is a key physical parameter for evaluating the RBE of proton therapy and aids in optimizing proton treatment plans. Calculating precise LETd distributions necessitates the use of intricate physical models and the execution of specialized Monte-Carlo simulation software, which is a computationally intensive and time-consuming progress. In response to these challenges, we propose a deep learning based framework designed to predict the LETd distribution map using the dose distribution map. This approach aims to simplify the process and increase the speed of LETd map generation in clinical settings. The proposed CycleGAN model has demonstrated superior performance over other GAN-based models. The mean absolute error (MAE), peak signal-to-noise ratio and normalized cross correlation of the LETd maps generated by the proposed method are 0.096 ± 0.019 keV μm−1, 24.203 ± 2.683 dB, and 0.997 ± 0.002, respectively. The MAE of the proposed method in the clinical target volume, bladder, and rectum are 0.193 ± 0.103, 0.277 ± 0.112, and 0.211 ± 0.086 keV μm−1, respectively. The proposed framework has demonstrated the feasibility of generating synthetic LETd maps from dose maps and has the potential to improve proton therapy planning by providing accurate LETd information.

Effects of nuclear interaction corrections and trichrome fragment spectra modelling on dose and linear energy transfer distributions in carbon ion radiotherapy

Background and PurposeNuclear interaction correction (NIC) and trichrome fragment spectra modelling improve relative biological effectiveness-weighted dose (DRBE) and dose-averaged linear energy transfer (LETd) calculation for carbon ions. The effect of those novel approaches on the clinical dose and LET distributions was investigated. Materials and MethodsThe effect of the NIC and trichrome algorithm was assessed, creating single beam plans for a virtual water phantom with standard settings and NIC + trichrome corrections. Reference DRBE and LETd distributions were simulated using FLUKA version 2021.2.9. Thirty clinically applied scanned carbon ion treatment plans were recalculated applying NIC, trichrome and NIC + trichrome corrections, using the LEM low dose approximation and compared to clinical plans (base RS). Four treatment sites were analysed: six prostate adenocarcinoma, ten head and neck, nine locally advanced pancreatic adenocarcinoma and five sacral chordoma. The FLUKA and clinical plans were compared in terms of DRBE deviations for D98%, D50%, D2% for the clinical target volume (CTV) and D50% in ring-like dose regions retrieved from isodose curves in base RS plans. Additionally, region-based median LETd deviations and global gamma parameters were evaluated. ResultsDose deviations comparing baseRS and evaluation plans were within ± 1% supported by γ-pass rates over 97% for all cases. No significant LETd deviations were reported in the CTV, but significant median LETd deviations were up to 80% for very low dose regions. ConclusionOur results showed improved accuracy of the predicted DRBE and LETd. Considering clinically relevant constraints, no significant modifications of clinical protocols are expected with the introduction of NIC + trichrome.

LETd Optimization Verification With an SOI Microdosimeter

A first of its kind experimental verification of dose-averaged linear energy transfer (LETd) optimized treatment plans for proton therapy has been carried out using a silicon-on-insulator microdosimeter at the Massachusetts General Hospital (MGH), Boston, USA. Three clinical treatment plans of a typical ependymoma structure set were designed using the standard clinical approach, the proposed protocol approach, and a one-field approach. The plans were then reoptimized to reduce the LETd-weighted dose in the brain stem. All six plans were delivered in a solid water phantom and the experimental yD‾ measured. After LETd optimization, a reduction in yD‾ was found within the brain stem by an average of 12%, 19%, and 4% for the clinical, protocol, and one-field plans, respectively, while maintaining adequate coverage of the tumor structure. The experimental LETd-weighted doses were in agreement with the treatment planning system calculations and Monte Carlo simulations and reinforced the improvement of the optimization. This work demonstrates the first experimental verification of the clinical implementation of LETd optimization for patient treatment with proton therapy.

Linear energy transfer (LET) distribution outside small radiotherapy field edges produced by 6 MV X-rays

In modern radiotherapy with photons, the absorbed dose outside the radiation field is generally investigated. But it is well known that the biological damage depends not only on the absorbed dose but also on LET. This work investigated the dose-average LET (LΔ,D) outside several small radiotherapy fields to provide information that can help for better evaluating the biological effect in organs at risk close to the tumour volume. The electron fluences produced in liquid water by a 6 MV X-rays Varian iX linac were calculated using the EGSnrc Monte Carlo code. With the electron spectra, LΔ,D calculations were made for eight open small square fields and the reference field at water depths of 0.15 cm, 1.35 cm, 9.85 cm and 19.85 cm and several off-axis distances. The variation of LΔ,D from the centre of the beam to 2 cm outside the field’s edge depends on the field size and water depth. Using radiobiological data reported in the literature for chromosomal aberrations as an endpoint for the induction of dicentrics determined in Human Lymphocytes, we estimated the maximum low-dose relative biological effectiveness, (RBEM) finding an increase of up to 100% from the centre of the beam to 2 cm from the field's edge.

Incorporating variable RBE in IMPT optimization for ependymoma.

To study the dosimetric impact of incorporating variable relative biological effectiveness (RBE) of protons in optimizing intensity-modulated proton therapy (IMPT) treatment plans and to compare it with conventional constant RBE optimization and linear energy transfer (LET)-based optimization. This study included 10 pediatric ependymoma patients with challenging anatomical features for treatment planning. Four plans were generated for each patient according to different optimization strategies: (1) constant RBE optimization (ConstRBEopt) considering standard-of-care dose requirements; (2) LET optimization (LETopt) using a composite cost function simultaneously optimizing dose-averaged LET (LETd ) and dose; (3) variable RBE optimization (VarRBEopt) using a recent phenomenological RBE model developed by McNamara etal.; and (4) hybrid RBE optimization (hRBEopt) assuming constant RBE for the target and variable RBE for organs at risk. By normalizing each plan to obtain the same target coverage in either constant or variable RBE, we compared dose, LETd , LET-weighted dose, and equivalent uniform dose between the different optimization approaches. We found that the LETopt plans consistently achieved increased LET in tumor targets and similar or decreased LET in critical organs compared to other plans. On average, the VarRBEopt plans achieved lower mean and maximum doses with both constant and variable RBE in the brainstem and spinal cord for all 10 patients. To compensate for the underdosing of targets with 1.1 RBE for the VarRBEopt plans, the hRBEopt plans achieved higher physical dose in targets and reduced mean and especially maximum variable RBE doses compared to the ConstRBEopt and LETopt plans. We demonstrated the feasibility of directly incorporating variable RBE models in IMPT optimization. A hybrid RBE optimization strategy showed potential for clinical implementation by maintaining all current dose limits and reducing the incidence of high RBE in critical normal tissues in ependymoma patients.

A linear energy transfer distributions computation method for inhomogeneous medium by using the water equivalent ratio approximation.

Dose-averaged linear energy transfer (LET), LETd is widely used in proton therapy. Compared with analytical models, Monte Carlo (MC) simulations are more accurate in obtaining LETd distributions, but they are time-consuming. This study used the 3D LETd distributions of proton beam spots in water by MC simulations as a benchmark data set. Subsequently, by combining the water equivalent ratio of various human tissues, the 3D LETd distributions of clinical cases could be quickly obtained. Our method was applied to a single spot of 160MeV proton beam in a water-bone phantom and a pelvic case. We also computed the 3D LETd distributions for multiple proton beam spots in the pelvic case and a lung case. The results of our method were compared with the results of MC simulations, demonstrating that our method can rapidly provide 3D LETd distributions of clinical cases with acceptable differences from MC simulations.

The LET trilemma: Conflicts between robust target coverage, uniform dose, and dose-averaged LET in carbon therapy.

Linear energy transfer (LET) is closely related to the biological effect of ionizing radiation. Increasing the dose-averaged LET (LETd ) within the target volume has been proposed as a means to improve clinical outcome for hypoxic tumors. However, doing so can lead to reduced robustness to range uncertainty. To quantify the relationship between robust target coverage, target dose uniformity, and LETd , we employ robust optimization using dose-based and LETd -based functions and allow varying amounts of target non-uniformity. Robust carbon therapy optimization is used to create plans for phantom cases with increasing target sizes (radii 1, 3, and 5cm). First, the influence of respectively range and setup uncertainty on the LETd in the target is studied. Second, we employ strategies allowing overdosage in the clinical target volume (CTV) or gross tumor volume (GTV), which enable increased LETd in the target. The relationship between robust target coverage and LETd in the target is illustrated by tradeoff curves generated by optimization using varying weights for the LETd -based functions. As the range uncertainty used in the robust optimization increased from 0% to 5%, the near-minimum nominal LETd decreased by 17%-29% (9-21keV/µm) for the different target sizes. The effect of increasing setup uncertainty was marginal. Allowing 10% overdosage in the CTV enabled 9%-29% (6-12keV/µm) increased near-minimum worst case LETd for the different target sizes, compared to uniform dose plans. When 10% overdosage was allowed in the GTV only, the increase was 1%-20% (1-8keV/µm). There is an inherent conflict between range uncertainty robustness and high LETd in the target, which is aggravated with increasing target size. For large tumors, it is possible to simultaneously achieve two of the three qualities range robustness, uniform dose, and high LETd in the target.

Carbon-ion radiotherapy (CIRT) as treatment of pancreatic cancer at HIT: initial radiation plan analysis of the prospective phase II PACK-study

PurposeTo analyze the dose objectives and constraints applied at the prospective phase II PACK-study at Heidelberg ion therapy center (HIT) for different radiobiological models. MethodsTreatment plans of 14 patients from the PACK-study were analyzed and recomputed in terms of physical, biological dose and dose-averaged linear energy transfer (LETd). Both LEM-I (local effect model 1) and the adapted NIRS-MKM (microdosimetric kinetic model), were used for relative biological effectiveness (RBE)-weighted dose calculations (DBio|HIT and DBio|NIRS). A new constraint to the gastrointestinal (GI) tract was derived from the National Institute of Radiological Science (NIRS) clinical experience and considered for plan reoptimization (DBio|NIRS-const_48Gy and DBio|NIRS-const_50.4Gy). The Lyman-Kutcher-Burman (LKB) model of Normal Tissue Complication Probability (NTCP) for GI toxicity endpoints was computed. Furthermore, the computed LETd distribution was evaluated and correlated with Local Control (LC). ResultsOnly two patients showed a LETd98% in the GTV greater than 44 keV/μm. A HIT-dose constraint to the GI of D2cm3=48.6GyRBEHIT was derived from the NIRS experience, in alternative to the standard at HIT Dmax = 45.6 GyRBEHIT. In comparison with the original DBio|HIT,DBio|NIRS-const_48GyandDBio|NIRS-const_50.4Gy resulted in an increase in the ITV’s D98% of 8.7% and 11.3%. The NTCP calculation resulted in a probability for gastrointestinal bleeding of 4.5%, 12.3% and 13.0%, for DBio|NIRS, DBio|NIRS-const_48Gy and DBio|NIRS-const_50.4Gy, respectively. ConclusionThe results indicate that the current standards applied at HIT for CIRT closely align with the Japanese experience. However, to enhance tumor coverage, a more relaxed constraint on the GI tract may be considered. As the PACK-trial progresses, further analyses of various clinical endpoints are anticipated.

GPU-accelerated calculation of proton microdosimetric spectra as a function of target size, proton energy, and bounding volume size

Objective. Shortcomings of dose-averaged linear energy transfer (LETD), the quantity which is most commonly used to quantify proton relative biological effectiveness, have long been recognized. Microdosimetric spectra may overcome the limitations of LETD but are extremely computationally demanding to calculate. A systematic library of lineal energy spectra for monoenergetic protons could enable rapid determination of microdosimetric spectra in a clinical environment. The objective of this work was to calculate and validate such a library of lineal energy spectra. Approach. SuperTrack, a GPU-accelerated CUDA/C++ based application, was developed to superimpose tracks calculated using Geant4 onto targets of interest and to compute microdosimetric spectra. Lineal energy spectra of protons with energies from 0.1 to 100 MeV were determined in spherical targets of diameters from 1 nm to 10 μm and in bounding voxels with side lengths of 5 μm and 3 mm. Main results. Compared to an analogous Geant4-based application, SuperTrack is up to 3500 times more computationally efficient if each track is resampled 1000 times. Dose spectra of lineal energy and dose-mean lineal energy calculated with SuperTrack were consistent with values published in the literature and with comparison to a Geant4 simulation. Using SuperTrack, we developed the largest known library of proton microdosimetric spectra as a function of primary proton energy, target size, and bounding volume size. Significance. SuperTrack greatly increases the computational efficiency of the calculation of microdosimetric spectra. The elevated lineal energy observed in a 3 mm side length bounding volume suggests that lineal energy spectra determined experimentally or computed in small bounding volumes may not be representative of the lineal energy spectra in voxels of a dose calculation grid. The library of lineal energy spectra calculated in this work could be integrated with a treatment planning system for rapid determination of lineal energy spectra in patient geometries.

High–Linear Energy Transfer Irradiation in Clinical Carbon-Ion Beam With the Linear Energy Transfer Painting Technique for Patients With Head and Neck Cancer

Dose-averaged linear energy transfer (LETd) is one of the important factors in determining clinical outcomes for carbon-ion radiation therapy. Innovative LET painting (LP) has been developed as an advanced form of conventional intensity modulated carbon-ion radiation therapy (IMIT) at the QST Hospital. The study had 2 motivations: to increase the minimum LETd (LETdmin) and to improve uniformity of the LETd distribution within the gross tumor volume (GTV) by using LP treatment plans for patients with head and neck cancer while maintaining the relative biologic effectiveness (RBE)-weighted dose coverage within the planning tumor volume (PTV) the same as in the conventional IMIT plan. The LP treatment plans were designed with the in-house treatment planning system. For the plans, LETd constraints and LETdmin, goal-LETd, and maximum-LETd (LETdmax) constraints for the GTV were added to the conventional dose constraints in the IMIT prescription. For 13 patients with head and neck cancer, the RBE-weighted dose to 90% (D90) and 50% (D50) of the PTV and the LETdmin, mean (LETdmean), and LETdmax values within the GTV in the LP plans were evaluated by comparing them with those in the conventional IMIT plans. The LP for 13 patients with head and neck cancer could keep D90s and D50s for the PTV within 1.0% of those by the conventional IMIT. Among the 13 patients, the mean LETdmin of the LP plans for the GTV was 59.2 ± 7.9 keV/μm, whereas that of the IMIT plans was 45.9 ± 6.0 keV/μm. The LP increased the LETdmin to 8 to 24 keV/μm for the GTV compared with IMIT. While maintaining the dose coverage to the PTV as comparable to that for IMIT, the LP increased the mean LETdmin to 13.2 keV/μm for the GTV. For a GTV up to 170 cm3, LETd > 44 keV/μm could be achieved using LP, which according to previous studies was associated with lower recurrence. In addition, the LP method delivered more uniform LETd distributions compared with IMIT.

Optically stimulated luminescence detectors for dosimetry and LET measurements in light ion beams

Objective. This work investigates the use of Al2O3:C and Al2O3:C,Mg optically stimulated luminescence (OSL) detectors to determine both the dose and the radiation quality in light ion beams. The radiation quality is here expressed through either the linear energy transfer (LET) or the closely related metric Q eff, which depends on the particle’s speed and effective charge. The derived LET and Q eff values are applied to improve the dosimetry in light ion beams. Approach. OSL detectors were irradiated in mono-energetic 1H-, 4He-, 12C-, and 16O-ion beams. The OSL signal is associated with two emission bands that were separated using a pulsed stimulation technique and subjected to automatic corrections based on reference irradiations. Each emission band was investigated independently for dosimetry, and the ratio of the two emission intensities was parameterized as a function of fluence- and dose-averaged LET, as well as Q eff. The determined radiation quality was subsequently applied to correct the dose for ionization quenching. Main results. For both materials, the Q eff determinations in 1H- and 4He-ion beams are within 5 % of the Monte Carlo simulated values. Using the determined radiation quality metrics to correct the nonlinear (ionization quenched) detector response leads to doses within 2 % of the reference doses. Significance. Al2O3:C and Al2O3:C,Mg OSL detectors are applicable for dosimetry and radiation quality estimations in 1H- and 4He-ions. Only Al2O3:C,Mg shows promising results for dosimetry in 12C-ions. Across both materials and the investigated ions, the estimated Q eff values were less sensitive to the ion types than the estimated LET values were. The reduced uncertainties suggest new possibilities for simultaneously estimating the physical and biological dose in particle therapy with OSL detectors.