Intensity-modulated Proton Therapy Treatment Plans Research Articles

Impact of interplay effects on spot scanning proton therapy with motion mitigation techniques for lung cancer: SFUD versus robustly optimized IMPT plans utilizing a four-dimensional dynamic dose simulation tool

BackgroundThe interaction between breathing motion and scanning beams causes interplay effects in spot-scanning proton therapy for lung cancer, resulting in compromised treatment quality. This study investigated the effects and clinical robustness of two types of spot-scanning proton therapy with motion-mitigation techniques for locally advanced non-small cell lung cancer (NSCLC) using a new simulation tool (4DCT-based dose reconstruction).MethodsThree-field single-field uniform dose (SFUD) and robustly optimized intensity-modulated proton therapy (IMPT) plans combined with gating and re-scanning techniques were created using a VQA treatment planning system for 15 patients with locally advanced NSCLC (70 GyRBE/35 fractions). In addition, gating windows of three or five phases around the end-of-expiration phase and two internal gross tumor volumes (iGTVs) were created, and a re-scanning number of four was used. First, the static dose (SD) was calculated using the end-of-expiration computed tomography (CT) images. The four-dimensional dynamic dose (4DDD) was then calculated using the SD plans, 4D-CT images, and the deformable image registration technique on end-of-expiration CT. The target coverage (V98%, V100%), homogeneity index (HI), and conformation number (CN) for the iGTVs and organ-at-risk (OAR) doses were calculated for the SD and 4DDD groups and statistically compared between the SD, 4DDD, SFUD, and IMPT treatment plans using paired t-test.ResultsIn the 3- and 5-phase SFUD, statistically significant differences between the SD and 4DDD groups were observed for V100%, HI, and CN. In addition, statistically significant differences were observed for V98%, V100%, and HI in phases 3 and 5 of IMPT. The mean V98% and V100% in both 3-phase plans were within clinical limits (> 95%) when interplay effects were considered; however, V100% decreased to 89.3% and 94.0% for the 5-phase SFUD and IMPT, respectively. Regarding the significant differences in the deterioration rates of the dose volume histogram (DVH) indices, the 3-phase SFUD plans had lower V98% and CN values and higher V100% values than the IMPT plans. In the 5-phase plans, SFUD had higher deterioration rates for V100% and HI than IMPT.ConclusionsInterplay effects minimally impacted target coverage and OAR doses in SFUD and robustly optimized IMPT with 3-phase gating and re-scanning for locally advanced NSCLC. However, target coverage significantly declined with an increased gating window. Robustly optimized IMPT showed superior resilience to interplay effects, ensuring better target coverage, prescription dose adherence, and homogeneity than SFUD.Trial registration: None.

Optimizing spot intensity with lower bound constraints for IMPT: Exposing shortcomings and introducing an enhanced strategy.

Intensity Modulated Proton Therapy (IMPT) is a sophisticated radiation treatment allowing for precise dose distributions. However, conventional spot selection strategies in IMPT face challenges, particularly with minimum monitor unit (MU) constraints, affecting planning quality and efficiency. This study introduces an innovative Two-Stage Mixed Integer Linear Programming (MILP) method to optimize spot intensity in IMPT with Lower Bound (LB) constraints. This method seeks to improve treatment planning efficiency and precision, overcoming limitations of existing strategies. Our approach evaluates prevalent IMPT spot selection strategies, identifying their limitations, especially concerning MU constraints. We integrated LB constraints into a MILP framework, using a novel three-phase strategy for spot pool selection, to enhance performance over traditional heuristic methods and L1+L∞ strategies. The method's efficacy was tested in eight study cases, using Dose-Volume Histograms (DVHs), spot selection efficiency, and computation time analysis for benchmarking against established methods. The proposed method showed superior performance in DVH quality, adhering to LB constraints while maintaining high-quality treatment plans. It outperformed existing techniques in spot selection, reducing unnecessary spots and balancing precision with efficiency. Cases studies confirmed the method's effectiveness in producing clinically feasible plans with enhanced dose distributions and reduced hotspots, especially in cases with elevated LB constraints. Our Two-Stage MILP strategy signifies a significant advancement in IMPT treatment planning. By incorporating LB constraints directly into the optimization process, it achieves superior plan quality and deliverability compared to current methods. This approach is particularly advantageous in clinical settings requiring minimum spot number and high MU LB constraints, offering the potential for improved patient outcomes through more precise and efficient radiation therapy plans.

Dosimetric Comparison Between Proton and Photon Radiation Therapies for Pediatric Neuroblastoma

PurposeThe aim of this study is to determine the most beneficial radiation treatment technique for pediatric patients with thoracic and abdominal neuroblastoma (NBL), through a dosimetric comparison between photon Volumetric Modulated Arc Therapy and proton Intensity-Modulated Proton Therapy treatment plans. Materials and MethodsA retrospective analysis was conducted on a multicentre case series of 19 patients with thoracic and/or abdominal NBL who underwent radiation therapy, following the recommendations of the European protocol for high-risk NBL (HR-NBL2/SIOPEN). The prescribed dose was 21.6 Gy in 12 fractions (1.8 Gy/fraction) delivered over the preoperative disease volume. The dose volume histograms were analyzed for each patient, and a Wilcoxon signed-rank test with a significance level of 0.01 was employed to assess statistical differences between the dosimetric parameters investigated. Two homogeneity indices (HI and newHI) were compared to evaluate the uniformity in dose, delivered to the adjacent vertebrae (VBs_Adj). ResultsBoth radiation techniques conform to the protocol regarding CTV/PTV coverage for every location. Proton therapy resulted in statistically significant dose sparing for the heart and lungs in supradiaphragmatic locations and for the contralateral kidney, liver, spleen, and bowel in subdiaphragmatic locations. For both techniques, sparing the non-adjacent vertebrae (VBs_NAdj) results more challenging, although promising results were obtained. Furthermore, the dose delivered to the VBs_Adj was not statistically different, in terms of homogeneity, for the 2 radiation techniques that both met the protocol’s requirements. ConclusionThis dosimetric analysis highlights the potential of protons to reduce radiation dose to healthy tissue. These findings apply to all the investigated patients, regardless of primary tumor location, making proton therapy a valuable option for the treatment of neuroblastoma. However, a multidisciplinary assessment of each case is essential to ensure the selection of the most effective and suitable treatment modality.

Feasibility and constraints of Bragg peak FLASH proton therapy treatment planning.

FLASH proton therapy (FLASH-PT) requires ultra-high dose rate (≥40 Gy/s) protons to be delivered in a short timescale whilst conforming to a patient-specific target. This study investigates the feasibility and constraints of Bragg peak FLASH-PT treatment planning, and compares the in silico results produced to plans for intensity modulated proton therapy (IMPT). Bragg peak FLASH-PT and IMPT treatment plans were generated for bone (n=3), brain (n=3), and lung (n=4) targets using the MIROpt research treatment planning system and the Conformal FLASH library developed by Applications SA from the open-source version of UCLouvain. FLASH-PT beams were simulated using monoenergetic spot-scanned protons traversing through a conformal energy modulator, a range shifter, and an aperture. A dose rate constraint of ≥ 40 Gy/s was included in each FLASH-PT plan optimisation. Space limitations in the FLASH-PT adapted beam nozzle imposed a maximum target width constraint, excluding 4 cases from the study. FLASH-PT plans did not satisfy the imposed target dose constraints (D95% ≥ 95% and D2%≤ 105%) but achieved clinically acceptable doses to organs at risk (OARs). IMPT plans adhered to all target and OAR dose constraints. FLASH-PT plans showed a reduction in both target homogeneity (p < 0.001) and dose conformity (non-significant) compared to IMPT. Without accounting for a sparing effect, IMPT plans were superior in target coverage, dose conformity, target homogeneity, and OAR sparing compared to FLASH-PT. Further research is warranted in treatment planning optimisation and beam delivery for clinical implementation of Bragg peak FLASH-PT.

FLASH radiotherapy sparing effect on the circulating lymphocytes in pencil beam scanning proton therapy: impact of hypofractionation and dose rate

Purpose. The sparing effect of ultra-high dose rate (FLASH) radiotherapy has been reported, but its potential to mitigate depletion of circulating blood and lymphocytes (CL) has not been investigated in pencil-beam scanning-based (PBS) proton therapy, which could potentially reduce the risk of radiation-induced lymphopenia. Material and methods. A time-dependent framework was used to score the dose to the CL during the course of radiotherapy. For brain patients, cerebral vasculatures were semi-automatic segmented from 3T MR-angiography data. A dynamic beam delivery system was developed capable of simulating spatially varying instantaneous dose rates of PBS treatment plans, and which is based on realistic beam delivery parameters that are available clinically. We simulated single and different hypofractionated PBS intensity modulated proton therapy (IMPT) FLASH schemes using 600 nA beam current along with conventionally fractionated IMPT treatment plan at 2 nA beam current. The dosimetric impact of treatment schemes on CL was quantified, and we also evaluated the depletion in subsets of CL based on their radiosensitivity. Results. The proton FLASH sparing effect on CL was observed. In single-fraction PBS FLASH, just 1.5% of peripheral blood was irradiated, whereas hypofractionated FLASH irradiated 7.3% of peripheral blood. In contrast, conventional fractionated IMPT exposed 42.4% of peripheral blood to radiation. PBS FLASH reduced the depletion rate of CL by 69.2% when compared to conventional fractionated IMPT. Conclusion. Our dosimetric blood flow model provides quantitative measures of the PBS FLASH sparing effect on the CL in radiotherapy for brain cancer. FLASH Single treatment fraction offers superior CL sparing when compared to hypofractionated FLASH and conventional IMPT, supporting assumptions about reducing risks of lymphopenia compared to proton therapy at conventional dose rates. The results also indicate that faster conformal FLASH delivery, such as passive patient-specific energy modulation, may further enhance the sparing of the immune system.

Treatment planning comparison for head and neck cancer between photon, proton, and combined proton–photon therapy – From a fixed beam line to an arc

Background and purposeThis study investigates whether combined proton–photon therapy (CPPT) improves treatment plan quality compared to single-modality intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) for head and neck cancer (HNC) patients. Different proton beam arrangements for CPPT and IMPT are compared, which could be of specific interest concerning potential future upright-positioned treatments. Furthermore, it is evaluated if CPPT benefits remain under inter-fractional anatomical changes for HNC treatments. Material and methodsFive HNC patients with a planning CT and multiple (4–7) repeated CTs were studied. CPPT with simultaneously optimized photon and proton fluence, single-modality IMPT, and IMRT treatment plans were optimized on the planning CT and then recalculated and reoptimized on each repeated CT. For CPPT and IMPT, plans with different degrees of freedom for the proton beams were optimized. Fixed horizontal proton beam line (FHB), gantry-like, and arc-like plans were compared. ResultsThe target coverage for CPPT without adaptation is insufficient (average V95%=88.4 %), while adapted plans can recover the initial treatment plan quality for target (average V95%=95.5 %) and organs-at-risk. CPPT with increased proton beam flexibility increases plan quality and reduces normal tissue complication probability of Xerostomia and Dysphagia. On average, Xerostomia NTCP reductions compared to IMRT are −2.7 %/-3.4 %/-5.0 % for CPPT FHB/CPPT Gantry/CPPT Arc. The differences for IMPT FHB/IMPT Gantry/IMPT Arc are + 0.8 %/-0.9 %/-4.3 %. ConclusionCPPT for HNC needs adaptive treatments. Increasing proton beam flexibility in CPPT, either by using a gantry or an upright-positioned patient, improves treatment plan quality. However, the photon component is substantially reduced, therefore, the balance between improved plan quality and costs must be further determined.

Applicator-guided proton therapy versus multichannel brachytherapy for vaginal vault irradiation.

To dosimetrically compare applicator-guided intensity-modulated proton therapy(IMPT) and multichannel brachytherapy (MC-BRT) for vaginal vault irradiation(VVI) with special focus on dose to organs at risk (OARs) and normal tissues. Ten patients with uterine confined endometrial cancer who received adjuvant vaginal cuff brachytherapy were included in this study. For each patient an additional IMPT treatment plan was created using the same computed tomography dataset and contours segmented for MC-BRT plans. Clinical target volume (CTV) was defined as the proximal 3.5 cm of the vagina including the entire thickness of vaginal wall. Planning target volume for IMPT plans was generated from the CTV with an addition isotropic 3 mm margin. OARs included rectum, bladder, sigmoid, small bowel and femoral heads. The prescribed dose was 21 Gy in 3 fractions. For simplicity, all doses were expressed in Gy and a constant relative biological effectiveness of 1.1 was used for IMPT plans. Plan comparison was performed using dose-volume histogram and treatment planning parameters. A significant improvement of the D98% coverage for CTV was reached by the applicator-guided IMPT plans (p < 0.01). IMPT also provided a dose reduction in all OARs except for femoral heads due to the lateral beam direction, especially significant reduction of V5Gy, D2cc, D0.1 cc, Dmean, V95% values for the rectum and Dmean, D0.1 cc to bladder, sigmoid, small bowel. Additionally, IMPT plans showed a significant reduction of integral dose to normal tissue with respect to MC-BRT (221.5 cGy.L vs. 653.6 cGy.L, p < 0.01). Applicator-guided IMPT has the potential for improving plan quality in VVI while maintaining the high conformity afforded by the state-of-the-art intracavitary brachytherapy.

Evaluating the effect of setup uncertainty reduction and adaptation to geometric changes on normal tissue complication probability using online adaptive head and neck intensity modulated proton therapy

Objective. To evaluate the impact of setup uncertainty reduction (SUR) and adaptation to geometrical changes (AGC) on normal tissue complication probability (NTCP) when using online adaptive head and neck intensity modulated proton therapy (IMPT). Approach. A cohort of ten retrospective head and neck cancer patients with daily scatter corrected cone-beam CT (CBCT) was studied. For each patient, two IMPT treatment plans were created: one with a 3 mm setup uncertainty robustness setting and one with no explicit setup robustness. Both plans were recalculated on the daily CBCT considering three scenarios: the robust plan without adaptation, the non-robust plan without adaptation and the non-robust plan with daily online adaptation. Online-adaptation was simulated using an in-house developed workflow based on GPU-accelerated Monte Carlo dose calculation and partial spot-intensity re-optimization. Dose distributions associated with each scenario were accumulated on the planning CT, where NTCP models for six toxicities were applied. NTCP values from each scenario were intercompared to quantify the reduction in toxicity risk induced by SUR alone, AGC alone and SUR and AGC combined. Finally, a decision tree was implemented to assess the clinical significance of the toxicity reduction associated with each mechanism. Main results. For most patients, clinically meaningful NTCP reductions were only achieved when SUR and AGC were performed together. In these conditions, total reductions in NTCP of up to 30.48 pp were obtained, with noticeable NTCP reductions for aspiration, dysphagia and xerostomia (mean reductions of 8.25, 5.42 and 5.12 pp respectively). While SUR had a generally larger impact than AGC on NTCP reductions, SUR alone did not induce clinically meaningful toxicity reductions in any patient, compared to only one for AGC alone. Significance Online adaptive head and neck proton therapy can only yield clinically significant reductions in the risk of long-term side effects when combining the benefits of SUR and AGC.

Dose Planning Evaluation of Intensity-Modulated Proton Therapy (IMPT) Technique Based on In-House Dynamic Thorax Phantom

One of the drawbacks of the Intensity Modulated Radiation Therapy (IMRT) technique is that the absorbed dose in healthy tissue is relatively high. Proton beam has characteristics that can compensate for these drawbacks. The Bragg peak characteristic of a proton beam allows the administration of high radiation doses to the target organ only. Non-Small Cell Lung Cancer (NSCLC) cases are located in the vicinity of many vital organs, so radiation doses that exceed a certain limit will have a significant impact on these organs. Proton is a heavy particle that exhibits interaction patterns with tissue heterogeneity that differ from that of photon. This study aims to determine the distribution of proton beam planning doses in the NSCLC cases with the Intensity Modulated Proton Therapy (IMPT) technique and compare its effectiveness with the IMRT technique. Treatment planning was done by using TPS Eclipse on the water phantom and on the in-house thorax dynamic phantom. The water phantom planning parameters used are one field at 0° and three fields at 45°, 135°, and 225°. In this study, a single, sum, and multiple field techniques on the in-house thorax dynamic phantom were used. The evaluation was performed by calculating Conformity Index (CI), Homogeneity Index (HI), and Gradient Index (GI) parameters for each treatment planning. As a result, a bit of difference in the CI the HI values are shown between IMPT and IMRT planning. The GI values of IMPT planning are in the range between 4.15-4.53, while the GI value of IMRT is 7.89. The histogram results of the planar dose distribution show that the IMPT treatment planning provides fewer off-target organ doses than the IMRT planning. Evaluation was also carried out on the IMPT treatment planning of target organs in five areas of interest and four OAR positions. The evaluation results were then compared with the IMRT measurement data. As a result, the value of the point doses at the target organ did not differ significantly. However, the absorbed dose with the IMPT technique at four OAR positions is nearly zero, which had a large difference compared to the IMRT technique.

Spot delivery error predictions for intensity modulated proton therapy using robustness analysis with machine learning.

The purpose of this work is to assess the robustness of treatment plans when spot delivery errors were predicted with a machine learning (ML) model for intensity modulated proton therapy (IMPT). Over 6000 machine log files from delivered IMPT treatment plans were included in this study. From these log files, over 4.1 106 delivered proton spots were used to train the ML model. The presented model was tested and used to predict the spot position as well as the monitor units (MU) per spot, based on the original planning parameters. Two patient plans (one accelerated partial breast irradiation [APBI] and one ependymoma) were recalculated with the predicted spot position/MUs by the ML model and then were re-analyzed for robustness. Plans with ML predicted spots were less robust than the original clinical plans. In the APBI plan, dosimetric changes to the left lung and heart were not clinically relevant. In the ependymoma plan, the hot spot in the brainstem decreased and the hot spot in the cervical cord increased. Despite these differences, after robustness analysis, both ML spot delivery error plans resulted in >95% of the CTV receiving >95% of the prescription dose. The presented workflow has the potential benefit of including realistic spots information for plan quality checks in IMPT. This work demonstrates that in the two example plans, the plans were still robust when accounting for spot delivery errors as predicted by the ML model.

Advanced pencil beam scanning Bragg peak FLASH-RT delivery technique can enhance lung cancer planning treatment outcomes compared to conventional multiple-energy proton PBS techniques

To investigate the dosimetric characteristics between an advanced proton pencil beam scanning (PBS) Bragg peak FLASH technique and conventional PBS planning technique in lung tumors. To evaluate the "FLASHness" of single-field in a multiple-field delivery scheme for a hypofractionation regimen and move a step forward to clinical application. Single-energy PBS Bragg peak FLASH treatment plans were optimized based on a novel Bragg peak tracking technique to enable Bragg peaks to stop at the distal edge of the target. Inverse treatment planning using multiple-field optimization (MFO) can achieve sufficient FLASH dose rate and intensity-modulated proton therapy (IMPT)-equivalent dosimetric quality. The dose rate of organs-at-risk (OARs) and the target were calculated under FLASH machine parameters. A group of 10 consecutive lung SBRT patients was optimized to 34Gy/fraction using a standard treatment of PBS technique with multiple energy layers as references to the Bragg peak plans. The dosimetric quality was compared between Bragg peak FLASH and conventional plans based on RTOG0915 dose metrics. FLASH dose rate ratios (V40Gy/s) were calculated as a metric of the FLASH-sparing effect. For higher dose thresholds, the Bragg peak plans achieved greater V40Gy/s FLASH coverage for all major OARs. The V40Gy/s was close to 100% for all OARs when the dose thresholds were>5Gy for full plan and single beam evaluations. The less "FLASHness" region was associated with a low dose distribution, mainly occurring in the PBS field penumbra region. The conventional IMPT treatment plans yielded slightly superior target dose uniformity with a D2%(%) of 108.02% versus that of Bragg peak 300 MU plans of 111.81% (p<0.01) and that of Bragg peak 1200 MU plans of 115.95% (p<0.01). No significant difference in dose metrics was found between Bragg peak and IMPT treatment plans for the spinal cord, esophagus, heart, or lung-GTV (all p>0.05). Hypofractionated lung Bragg peak plans can maintain comparable plan quality to conventional PBS while achieving sufficient FLASH dose rate coverage for major OARs for each field under the multiple-field delivery scheme. The novel Bragg peak FLASH technique has the potential to enhance lung cancer planning treatment outcomes compared to standard PBS treatment techniques.

Dosimetric comparison of intensity modulated radiotherapy and intensity modulated proton therapy in the treatment of recurrent nasopharyngeal carcinoma.

To compare the dosimetric performance of Intensity Modulated Proton Therapy (IMPT) and Intensity Modulated Radiotherapy (IMRT) in terms of target volume coverage and sparing of neurological organs-at-risk (OARs) in salvaging recurrent nasopharyngeal carcinoma (rNPC). The maximum dose to the internal carotid artery (ICA) and nasopharyngeal (NP) mucosa, which are associated with potential carotid blowout and massive epistaxis, were also evaluated. IMRT and IMPT treatment plans were created for twenty patients with locally advanced rNPC. Planning Target Volume (PTV) was used to account for the setup and spatial error/uncertainty in the IMRT planning. Robust optimization on Clinical Target Volume (CTV) coverage with consideration of range and setup uncertainty was employed to produce two IMPT plans with 3-field and 4-field arrangements. The planning objective was to deliver 60 Gy to the PTV (IMRT) and CTV (IMPT) without exceeding the maximum lifetime cumulative Biologically Effective Dose (BED) of the neurological OARs (applied to the Planning organs-at-risk volume). The target dose coverage as well as the maximum dose to the neurological OARs, ICA, and NP mucosa were compared. Compared with IMRT, 3-field IMPT achieved better coverage to GTV V100% (83.3% vs. 73.2%, P <0.01) and CTV V100% (80.5% vs. 72.4%, P <0.01), and lower maximum dose to the critical OARs including the spinal cord (19.2 Gy vs. 22.3 Gy, P <0.01), brainstem (30.0 Gy vs. 32.3 Gy, P <0.01) and optic chiasm (6.6 Gy vs. 9.8 Gy, P <0.01). The additional beam with the 4-fields IMPT plans further improved the target coverage from the 3-field IMPT (CTV V98%: 85.3% vs. 82.4%, P <0.01) with similar OAR sparing. However, the target dose was highly non-uniform with both IMPT plans, leading to a significantly higher maximum dose to the ICA (∼68 Gy vs. 62.6 Gy, P <0.01) and NP mucosa (∼72 Gy vs. 62.8 Gy, P <0.01) than IMRT. IMPT demonstrated some dosimetric advantage over IMRT in treating rNPC. However, IMPT could also result in very high dose hot spots in the target volume. Careful consideration of the ICA and NP mucosal complications is recommended when applying IMPT on rNPC patients.

Estimating the second primary cancer risk due to proton therapy compared to hybrid IMRT for left sided breast cancer

Background and purpose Proton therapy has been proposed as a technique to improve the long-term quality of life of breast cancer patients. This is due to its ability to reduce the dose to healthy tissue compared to conventional X-ray therapy. The aim of this study was to investigate the risk of secondary carcinogenesis due to proton therapy compared to hybrid IMRT for breast treatments. Material and methods In this study, the Pinnacle treatment planning system was used to simulate treatment plans for 15 female left-sided whole breast cancer patients with deep inspiration breath hold scans. Two treatment plans were generated for each patient: hybrid intensity modulated radiotherapy (h-IMRT) and intensity modulated proton therapy (IMPT). Using the dose-volume histograms (DVHs) from these plans, the mean lifetime attributed risk (LAR) for both lungs and the contralateral breast were evaluated using the BEIR VII and Schneider full risk models. Results The results from both risk models show lower LAR estimates for the IMPT treatment plan compared to the h-IMRT treatment plan. This result was observed for all organs of interest and was consistent amongst the two separate risk models. For both treatment plans, the organs from most to least at risk were: ipsilateral lung, contralateral breast, and contralateral lung. In all cases, the risk estimated via the BEIR VII model was higher that the Schneider full risk model. Conclusion The use of proton therapy for breast treatments leads to reduced risk estimates for secondary carcinogenesis. Therefore, proton therapy shows promise in improving the long term treatment outcome of breast patients.

Analysis of the applicability of two-dimensional detector arrays in terms of sampling rate and detector size to verify scanned intensity-modulated proton therapy plans.

The introduction of advanced treatment techniques in proton therapy, such as intensity-modulated proton therapy, leads to an increased need for patient-specific quality assurance, especially an accurate treatment plan verification becomes inevitable. In this study, signal theoretical analysis of dose distributions in scanned proton therapy is performed to investigate the feasibility and limits of two-dimensional (2D) detector arrays for treatment plan verification. 2D detector arrays are characterized by two main aspects: the distance between the single detectors on the array or the sampling frequency; and the lateral response functions of a single detector. The analysis is based on single spots, reference fields and on measured and calculated dose distributions of typical intensity-modulated proton therapy treatment plans with and without range shifter. Measurements were performed with Gafchromic EBT3 films (Ashland Speciality Ingredients G.P., Bridgewater, NJ, USA), the MatriXX PT detector array (IBA Dosimetry, Schwarzenbruck, Germany) and the OCTAVIUS detector array 1500XDR (PTW-Freiburg, Germany) at an IBA Proteus PLUS proton therapy system (Ion Beam Applications, Louvain-la-Neuve, Belgium). Dose calculations were performed with the treatment planning system RayStation 6 or 8 (RaySearch Laboratories, Sweden). The Fourier analysis of the data of the treatment planning system and film measurements show maximum frequencies of 0.06/mm for the plan with range shifter and 0.083/mm for the plan without range shifter. According to the Nyquist theorem, this corresponds to minimum required sampling distances of 8.3 and 6mm, respectively. By comparison, the sampling distances of the arrays of 7.6mm (MatriXX PT) and 7.1mm (OD1500XDR) are sufficient to reconstruct the dose distributions adequately from measurements if range shifters are used, whereas some fields of the plans without range shifter violated the Nyquist requirement. The lateral dose response functions of the single detectors within the arrays have clearly higher frequencies than the treatment plans and thus the volume effect only slightly influences the measurements. Consequently, the array measurements show high gamma passing rates with at least 96 % and a good agreement between the investigated line profiles. The results indicate that the detector dimensions and sampling distances of the arrays are in most studied cases adequate not to substantially influence the measurement process when they are used for analyzing typical intensity-modulated proton therapy treatment plans. Nevertheless, clinical conditions have been identified, for instance treatment plans without range shifter, under which the Nyquist theorem is violated such that a full representation of the dose distributions with the measurements is not feasible. In these cases, analysis of measurements is limited to pointwise comparisons.

A Model for Secondary Monitor Unit Calculations of PBS Proton Therapy Treatment Plans.

Purpose:This article summarizes a volume-based method by which secondary monitor unit (MU) calculations may be performed for pencil beam scanning, single field uniform dose (SFUD) proton therapy treatment plans.Materials and Methods:Treatment planning system (TPS) simulations were performed by using the local beam model to define relationships between planning target volume (PTV) characteristics and the MUs required to deliver a uniform dose for a given beam orientation. Relevant target attributes included volume, depth (ie, beam range), range-shifter air gap, and the projected area of the target volume in the beam's eye view (BEV). The proposed model approximates the PTV as a simplified cuboid region of interest as defined by its volume and BEV projected area. Output factors (cGy/MU) were then tabulated for the idealized geometry through TPS simulations using region of interests with a range of dimensions expected to be seen clinically. Correction factors were applied that account for differences between the PTV and the idealized conditions, and MUs for each beam were then scaled according to the measured spread out Bragg peak (SOBP) dose in water.Results:Our model was applied to various treatment sites, including pelvis, brain, lung, and head and neck. Monitor units prescribed by the TPS were compared to those predicted by using the model for 78 treatment beams. The total mean percentage difference for all beams was −0.2% ± 3.8%.Conclusion:This work demonstrates the potential for reasonably accurate secondary verification of MUs in pencil beam scanning proton therapy for SFUD treatment plans with the proposed method. Required inputs are few, and are readily accessible, facilitating automation and clinical application. Further investigation will expand the current model to accommodate a broader range of potential optimization problems, and intensity-modulated proton therapy treatment plans.

Evaluation of an Automated Proton Planning Solution.

PurposeIntensity-modulated proton therapy (IMPT) treatments are increasing, however, treatment planning remains complex and prone to variability. RapidPlanTMPT (Varian Medical Systems, Palo Alto, California, USA) is a pre-clinical, proton-specific, automated knowledge-based planning solution which could reduce variability and increase efficiency. It uses a library of previous IMPT treatment plans to generate a model which can predict organ-at-risk (OAR) dose for new patients, and guide IMPT optimization. This study details and evaluates RapidPlanTMPT.MethodsIMPT treatment plans for 50 head-and-neck cancer patients populated the model-library. The model was then used to create knowledge-based plans (KBPs) for 10 evaluation-patients. Model quality and accuracy were evaluated using model-provided OAR regression plots and examining the difference between predicted and achieved KBP mean dose. KBP quality was assessed through comparison with respective manual IMPT plans on the basis of boost/elective planning target volume (PTVB/PTVE) homogeneity and OAR sparing. The time to create KBPs was recorded.ResultsModel quality was good, with an average R2 of 0.85 between dosimetric and geometric features. The model showed high predictive accuracy with differences of <3 Gy between predicted and achieved OAR mean doses for 88/109 OARs. On average, KBPs were comparable to manual IMPT plans with differences of <0.6% in homogeneity. Only 2 of 109 OARs in KBPs had a mean dose >3 Gy more than the manual plan. On average, dose-volume histogram (DVH) predictions required 0.7 minutes while KBP optimization and dose calculation required 4.1 minutes (a ‘continue optimization’ phase, if required, took an additional 2.8 minutes, on average).ConclusionsRapidPlanTMPT demonstrated efficiency and consistency and IMPT KBPs were comparable to manual plans. Because worse OAR sparing in a KBP was not always associated with geometric-outlier warnings, manual plan checks remain important. Such an automated planning solution could also assist in clinical trial quality assurance and overcome the learning curve associated with IMPT.

A comprehensive dosimetric study of Monte Carlo and pencil-beam algorithms on intensity-modulated proton therapy for breast cancer.

PB algorithms are commonly used for proton therapy. Previously reported limitations of the PB algorithm for proton therapy are mainly focused on high‐density gradients and small‐field dosimetry, the effect of PB algorithms on intensity‐modulated proton therapy (IMPT) for breast cancer has yet to be illuminated. In this study, we examined 20 patients with breast cancer and systematically investigated the dosimetric impact of MC and PB algorithms on IMPT. Four plans were generated for each patient: (a) a PB plan that optimized and computed the final dose using a PB algorithm; (b) a MC‐recomputed plan that recomputed the final dose of the PB plan using a MC algorithm; (c) a MC‐renormalized plan that renormalized the MC‐recomputed plan to restore the target coverage; and (d) a MC‐optimized plan that optimized and computed the final dose using a MC algorithm. The DVH on CTVs and on organ‐at‐risks (OARs) from each plan were studied. The Mann–Whitney U‐test was used for testing the differences between any two types of plans. We found that PB algorithms significantly overestimated the target dose in breast IMPT plans. The median value of the CTV D99%, D95%, and Dmean dropped by 3.7%, 3.4%, and 2.1%, respectively, of the prescription dose in the MC‐recomputed plans compared with the PB plans. The magnitude of the target dose overestimation by the PB algorithm was higher for the breast CTV than for the chest wall CTV. In the MC‐renormalized plans, the target dose coverage was comparable with the original PB plans, but renormalization led to a significant increase in target hot spots as well as skin dose. The MC‐optimized plans led to sufficient target dose coverage, acceptable target hot spots, and good sparing of skin and other OARs. Utilizing the MC algorithm for both plan optimization and final dose computation in breast IMPT treatment planning is therefore desirable.

Advantages of intensity modulated proton therapy during hippocampal avoidance whole brain radiation therapy.

Intensity modulated proton therapy (IMPT) allows for modulation parameterized for individual beamlets by position, intensity, and depth. This modulation capability is ideally suited for sparing organs at risk intermediate of the radiation target, such as hippocampal volumes within the whole brain. This work compared IMPT relative to volumetric modulated arc therapy (VMAT) during hippocampal avoidance whole brain radiation therapy (HA WBRT). Ten adult and ten pediatric patients previously treated for central nervous system malignancies were identified. IMPT and VMAT treatment plans employing HA WBRT were generated for each patient, delivering 30 GyE (Gray Equivalent) in 10 fractions for adults and 36 GyE in 20 fractions for pediatrics. Dose indices, including dose volume histogram metrics and homogeneity index HI = [D5% - D95%]/[Dmean] × 100, were used to assess plan quality and describe target coverage and normal-tissue sparing. IMPT offered significant benefits relative to VMAT for hippocampal sparing. Hippocampal mean dose was reduced from 13.7 ± 0.8 Gy with VMAT to 5.4 ± 0.3 GyE using IMPT for pediatrics, and was reduced from 11.7 ± 0.9 Gy with VMAT to 4.4 ± 0.2 GyE using IMPT for adults. IMPT similarly lowered left hippocampal mean dose. Dose to 95% of the clinical target volume was statistically equivalent for both groups; however IMPT reduced the homogeneity index by roughly half. This manuscript demonstrates that HA IMPT can match or exceed dosimetric benefits offered with modulated X-rays. Inclusion of IMPT in future prospective studies is warranted.

A robust intensity modulated proton therapy optimizer based on Monte Carlo dose calculation.

Accuracy of dose calculation models and robustness under various uncertainties are key factors influencing the quality of intensity modulated proton therapy (IMPT) plans. To mitigate the effects of uncertainties and to improve the dose calculation accuracy, an all-scenario robust IMPT optimization based on accurate Monte Carlo (MC) dose calculation was developed. In the all-scenario robust IMPT optimization, dose volume histograms (DVHs) were computed for the nominal case and for each uncertainty scenario. All scenarios were weighted by DVH values dynamically throughout optimization iterations. In contrast, probabilistic approach weighted scenarios with fixed scenario weights and worst case optimizations picked one single scenario - the worst scenario for each iteration. Uncertainties in patient setup and proton range were considered in all clinical cases studied. Graphics processing unit (GPU) computation was employed to reduce the computational time in both the MC dose calculation and optimization stages. A previously published adaptive quasi-Newton method for proton optimization was extended to include robustness. To validate the all-scenario algorithm extension, it was compared with the single scenario optimization target volume (OTV) based approach in clinical cases of three different disease sites. Additional comparisons with worst case optimization methods were conducted to evaluate the performance of the all-scenario robust optimization against other robust optimizations. The all-scenario robust IMPT optimization spared organs at risk (OARs) better than the OTV-based method while maintaining target coverage and improving the robustness of targets and OARs. Compared with composite and voxel-wise worst case optimization, the all-scenario robust optimization converged faster, and arrived at solutions of tighter DVH robustness spread, better target coverage and lower OAR dose. An all-scenario robust IMPT treatment planning system was developed using an adaptive quasi-Newton optimization method. The optimization system was GPU-accelerated and based on MC dose calculation. Improved performance was observed in clinical cases when compared with worst case optimization methods.

Can differences in linear energy transfer and thus relative biological effectiveness compromise the dosimetric advantage of intensity-modulated proton therapy as compared to passively scattered proton therapy?

Purpose To investigate the effect of differences in linear energy transfer (LET) and thus the relative biological effectiveness (RBE) between passively scattered proton therapy (PS) and pencil-beam scanning intensity-modulated proton therapy (IMPT). Methods IMPT treatment plans were generated for six ependymoma patients, originally treated with PS, using the original plan’s computed tomography image sets and beam directions, and its dose-volume values as optimization constraints. Two beam spot sizes and both single-field optimization (SFO) and multi-field optimization (MFO) techniques were used for each patient. Three-dimensional variable-RBE-weighted dose distributions were computed, using Monte Carlo calculated dose and LET distributions, and a linear dose and LET-based RBE model, and were compared between the two delivery methods. Results Increased target dose coverage and decreased mean and maximum dose to the OARs was achieved with IMPT compared to PS, for constant RBE value of 1.1. Nevertheless, the maximum variable-RBE-weighted dose to the brainstem, was increased up to 6% for the IMPT plans compared to the corresponding PS plans. Conclusions IMPT can be dosimetrically superior to PS for ependymoma patients. However, caution should be exercised so that the increased dose conformity is not counteracted by an increase in radiobiological effect in adjacent critical structures.