Intensity Modulated Proton Therapy Plans Research Articles

Robust optimization incorporating weekly predicted anatomical CTs in IMPT of nasopharyngeal cancer.

Objective.This study proposes a robust optimization (RO) strategy utilizing virtual CTs (vCTs) predicted by an anatomical model in intensity-modulated proton therapy (IMPT) for nasopharyngeal cancer (NPC).Methods and Materials.For ten NPC patients, vCTs capturing anatomical changes at different treatment weeks were generated using a population average anatomy model. Two RO strategies of a 6 beams IMPT with 3 mm setup uncertainty (SU) and 3% range uncertainty (RU) were compared: conventional robust optimization (cRO) based on a single planning CT (pCT), and anatomical RO incorporating 2 and 3 predicted anatomies (aRO2 and aRO3). The robustness of these plans was assessed by recalculating them on weekly CTs (week 2-7) and extracting the voxel wise-minimum and maximum doses with 1 mm SU and 3% RU (voxmin\voxmax1mm3%).Results.The aRO plans demonstrated improved robustness in high-risk CTV1 and low-risk CTV 2 coverage compared to cRO plans. The weekly evaluation showed a lower plan adaptation rate for aRO3 (40%) vs. cRO (70%). The weekly nominal and voxmax1mm3%doses to OARs, especially spinal cord, are better controlled relative to their baseline doses at week 1 with aRO plans. The accumulated dose analysis showed that CTV1&2 had adequate coverage and serial organs (spinal cord and brainstem) were within their dose tolerances in the voxmin\voxmax1mm3%, respectively.Conclusion.Incorporating predicted weekly CTs from a population based average anatomy model in RO improves week-to-week target dose coverage and reduces false plan adaptations without increasing normal tissue doses. This approach enhances IMPT plan robustness, potentially facilitating reduced SU and further lowering OAR doses.

Dosimetric Comparison and Selection Criteria of Intensity-Modulated Proton Therapy and Intensity-Modulated Radiation Therapy for Adaptive Re-Plan in T3-4 Nasopharynx Cancer Patients.

Proton therapy requires caution when treating patients with targets near neural structures. Intuitive and quantitative guidelines are needed to support decision-making concerning the treatment modality. This study compared dosimetric profiles of intensity-modulated proton therapy (IMPT) and intensity-modulated radiation therapy (IMRT) using helical tomotherapy (HT) for adaptive re-planning in cT3-4 nasopharyngeal cancer (NPCa) patients, aiming to establish criteria for selecting appropriate treatment modalities. HT and IMPT plans were generated for 28 cT3-4 NPCa patients undergoing definitive radiotherapy. Dosimetric comparisons were performed for target coverage and high-priority organs at risk (OARs). The correlation between dosimetric parameters and RT modality selection was analyzed with the target OAR distances. Target coverages were similar, while IMPT achieved better dose spillage. HT was more favorable for brainstem D1, optic chiasm Dmax, optic nerves Dmax, and p-cord D1. IMPT showed advantages for oral cavity Dmean. Actually, 14 IMPT and 14 HT plans were selected as adaptive plans, with IMPT allocated to most cT3 patients (92.9% vs. 42.9%, p = 0.013). The shortest distances from the target to neural structures were negatively correlated with OAR doses. Receiver operating characteristic curve analyses were carried out to discover the optimal cut-off values of the shortest distances between the target and the OARs (temporal lobes and brainstem), which were 0.75 cm (AUC = 0.908, specificity = 1.00) and 0.85 cm (AUC = 0.857, specificity = 0.929), respectively. NPCa patients with cT4 tumor or with the shortest distance between the target and critical neural structures < 0.8 cm were suboptimal candidates for IMPT adaptive re-planning. These criteria may improve resource utilization and clinical outcomes.

Intensity-modulated proton radiotherapy spares musculoskeletal structures in regional nodal irradiation for breast cancer: a dosimetric comparison.

Regional nodal irradiation (RNI) for breast cancer delivers radiation in proximity to the shoulder and torso, and radiation exposure may contribute to long-term upper extremity and postural morbidity. To date, no studies have assessed the differential dosimetric impact of proton versus photon radiation on shoulder and torso anatomy. This study examined clinically relevant musculoskeletal (MSK) structures and assessed the dose delivered with each modality. Ten MSK structures were contoured on IMPT (intensity-modulated proton therapy) and VMAT (volumetric modulated arc therapy) plans for 30 patients receiving RNI. Relevant dose metrics were compared for each of the structures. Intensity-modulated proton therapy dose was calculated using the relative biological effective value of 1.1. Hypo-fractionated plans were scaled to the equivalent dose in 2 Gy fractions (EQD2) using an alpha/beta ratio of four. Wilcoxon signed rank sum tests compared doses. Select three-dimensional and optimised VMAT plans were also informally compared. Each of the 10 structures received a statistically significantly lower dose with the use of IMPT compared with VMAT. Differences were greatest for posterior structures, including the trapezius, latissimus dorsi and glenohumeral joint. Mean absolute differences were as great as 23 Gy (supraspinatus D5cc) and up to 30-fold dose reductions were observed (deltoid D50cc). An average 3.7-fold relative dose reduction existed across all structures. Measures of low/intermediate dose (V15Gy and D50cc) showed the largest differences. Intensity-modulated proton therapy results in statistically lower radiation exposure to relevant shoulder and torso anatomy compared to photon radiation for patients requiring RNI. Prospective study is needed to correlate functional outcomes with radiation dose.

Emulating the Delivery of Sawtooth Proton Arc Therapy Plans on a Cyclotron-Based Proton Beam Therapy System

Purpose: To evaluate and compare the deliverability of ‘sawtooth’ proton arc therapy (PAT) plans relative to static intensity modulated proton therapy (IMPT) at a cyclotron-based clinical facility. Methods: The delivery of single and dual arc Sawtooth PAT plans for an abdominal CT phantom and multiple clinical cases of brain, head and neck (H&amp;N) and base of skull (BoS) targets was emulated under the step-and-shoot and continuous PAT delivery regimes and compared to that of a corresponding static IMPT plan. Results: Continuous PAT delivery increased the time associated with beam delivery and gantry movement in single/dual PAT plans by 4.86/7.34 min (brain), 7.51/12.40 min (BoS) and 6.59/10.57 min (H&amp;N) on average relative to static IMPT. Step-and-shoot PAT increased this delivery time further by 4.79 min on average as the delivery was limited by gantry motion. Conclusions: The emulator can approximately model clinical sawtooth PAT delivery but requires experimental validation. No clear benefit was observed regarding beam-on time for sawtooth PAT relative to static IMPT.

Investigate potential clinical benefits and linear energy transfer sparing utilizing proton arc therapy for hepatocellular carcinoma

PurposeTo investigate the potential clinical benefits and dose-averaged Linear Energy Transfer (LETd) sparing, utilizing proton arc plan for hepatocellular carcinoma (HCC) patients in comparison with Intensity Modulated Proton Therapy (IMPT). MethodsTen HCC patients have been retrospectively selected. Two planning groups were created: Proton Arc plans using Monaco ver. 6 and the clinical IMPT plan. Both planning groups used the same robustness parameters. The prescription dose is 67.5 Gy (RBE) in 15 fractions of the Clinical Target Volume (CTV). Robustness evaluations were performed to ensure dose coverage. Normal Tissue Complicated Probability (NTCP) model was utilized to predict the possibility of Radiation-Induced Liver Disease (RILD) and evaluate the potential benefit of proton arc therapy. LETd calculation and evaluation were performed as well. ResultsProton arc plan has shown better dosimetric improvements of most Organ-At-Risks (OARs). More specifically, the liver mean dose has been significantly reduced from 14.7 GyE to 10.62 GyE compared to the IMPT plan. The predicted possibility of RILD has also been significantly reduced for cases with a large and deep liver target where healthy liver tissue sparing is a challenge. Additionally, proton arc therapy could increase the average LETd in the target and reduce LETd in adjacent OARs. ConclusionsThe potential clinical benefit of utilizing proton arc therapy HCC varies depending on the patient-specific geometry. With more freedom, proton arc therapy can offer a better dosimetric plan quality in the challenge cases, which might not be feasible using the current IMPT technique.

Explore the feasibility of using spot-scanning proton arc therapy for a synchrotron accelerator-based proton therapy system - A simulation study.

The aim of this study was to evaluate the feasibility and plan quality of spot-scanning proton arc therapy (SPArc) using a synchrotron-accelerator-based proton therapy system compared to intensity-modulated proton therapy (IMPT). Five representative disease sites, including head and neck, lung, liver, brain chordoma, and prostate cancers, were retrospectively selected. Both IMPT and SPArc plans are generated with the HITACHI ProBEAT PBS system's minimum MU constraints and physics beam model. The SPArc plans are generated with 2.5° sampling frequency. The static delivery time was simulated based on the previously published synchrotron delivery sequence model, and the dynamic delivery time was simulated using a proton arc gantry mechanical model integrated with the synchrotron delivery sequence. Both dosimetric plan quality and delivery efficiency are evaluated. A superior plan quality is reached compared with the IMPT plans generated for the same disease site. However, a relatively prolonged static and dynamic delivery time post new challenge, as static time increased by 49.22% and dynamic time 59.10% on average. This study presents the first simulation results of delivering the SPArc plans using a synchrotron-accelerated proton therapy system. The result shows its feasibility and limitations, which could guide future development.

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.

In Silico Comparison of Three Different Beam Arrangements for Intensity-Modulated Proton Therapy for Postoperative Whole Pelvic Irradiation of Prostate Cancer.

Background and purpose: Proton therapy has been shown to provide dosimetric benefits in comparison with IMRT when treating prostate cancer with whole pelvis radiation; however, the optimal proton beam arrangement has yet to be established. The aim of this study was to evaluate three different intensity-modulated proton therapy (IMPT) beam arrangements when treating the prostate bed and pelvis in the postoperative setting. Materials and Methods: Twenty-three post-prostatectomy patients were planned using three different beam arrangements: two-field (IMPT2B) (opposed laterals), three-field (IMPT3B) (opposed laterals inferiorly matched to a posterior-anterior beam superiorly), and four-field (IMPT4B) (opposed laterals inferiorly matched to two posterior oblique beams superiorly) arrangements. The prescription was 50 Gy radiobiological equivalent (GyE) to the pelvis and 70 GyE to the prostate bed. Comparisons were made using paired two-sided Wilcoxon signed-rank tests. Results: CTV coverages were met for all IMPT plans, with 99% of CTVs receiving ≥ 100% of prescription doses. All organ at risk (OAR) objectives were met with IMPT3B and IMPT4B plans, while several rectum objectives were exceeded by IMPT2B plans. IMPT4B provided the lowest doses to OARs for the majority of analyzed outcomes, with significantly lower doses than IMPT2B +/- IMPT3B for bladder V30-V50 and mean dose; bowel V15-V45 and mean dose; sigmoid maximum dose; rectum V40-V72.1, maximum dose, and mean dose; femoral head V37-40 and maximum dose; bone V40 and mean dose; penile bulb mean dose; and skin maximum dose. Conclusion: This study is the first to compare proton beam arrangements when treating the prostate bed and pelvis. four-field plans provided better sparing of the bladder, bowel, and rectum than 2- and three-field plans. The data presented herein may help inform the future delivery of whole pelvis IMPT for prostate cancer.

Proton therapy reduces the effective dose to immune cells in breast cancer patients.

The effective dose to circulating immune cells (EDIC) is associated with survival in lung and esophageal cancer patients. This study aimed to evaluate the benefit of intensity-modulated proton therapy (IMPT) for EDIC reduction as compared to volumetric modulated arc therapy (VMAT) in patients with locally advanced breast cancer (BC). Ten BC patients treated with locoregional VMAT after breast-conserving surgery were included. Mean dose to the heart (MHD), lungs (MLD), and liver (MlD), as well as the integral dose to the body (ITD), were retrieved, and we calculated EDIC as 0.12 × MLD + 0.08 × MHD + 0.15 × 0.85 × √(n/45) × MlD + (0.45 + 0.35 × 0.85 × √(n/45)) × ITD/(62 × 103), where n is the number of fractions. EDIC was compared between VMAT and IMPT plans. Median EDIC was reduced from 3.37 Gy (range: 2.53-5.99) with VMAT to 2.13 Gy (1.31-3.77) with IMPT (p < 0.01). For left-sided BC patients, EDIC was reduced from 3.15 Gy (2.53-3.78) with VMAT to 1.65 Gy (1.31-3.77) with IMPT (p < 0.01). For right-sided BC patients, EDIC was reduced from 5.60 Gy (5.06-5.99) with VMAT to 3.38 Gy (3.10-3.77) with IMPT (p < 0.01). Right-sided BC patients had ahigher EDIC irrespective of the technique. Integral dose reduction was the main driver of EDIC reduction with IMPT and was associated with lung sparing for left-sided BC patients or liver sparing for right-sided BC patients. IMPT significantly reduced EDIC in BC patients undergoing locoregional adjuvant radiotherapy. Integral total dose reduction, associated with improved lung sparing in left-sided BC patients or liver sparing in right-sided BC patients, mainly drove EDIC reduction with IMPT. The emergence of dynamic models taking into account the circulatory kinetics of immune cells may improve the accuracy of the estimate of the dose received by the immune system compared to calculation of the EDIC, which is based solely on static dosimetric data.

Proton dose deposition matrix prediction using multi-source feature driven deep learning approach

Proton dose deposition results are influenced by various factors, such as irradiation angle, beamlet energy and other parameters. The calculation of the proton dose deposition matrix (DDM) can be highly complex but is crucial in intensity-modulated proton therapy (IMPT). In this work, we present a novel deep learning (DL) approach using multi-source features for proton DDM prediction. The DL5 proton DDM prediction method involves five input features containing beamlet geometry, dosimetry and treatment machine information like patient CT data, beamlet energy, distance from voxel to beamlet axis, distance from voxel to body surface, and pencil beam (PB) dose. The dose calculated by Monte Carlo (MC) method was used as the ground truth dose label. A total of 40 000 features, corresponding to 8000 beamlets, were obtained from head patient datasets and used for the training data. Additionally, seventeen head patients not included in the training process were utilized as testing cases. The DL5 method demonstrates high proton beamlet dose prediction accuracy, with an average determination coefficient R 2 of 0.93 when compared to the MC dose. Accurate beamlet dose estimation can be achieved in as little as 1.5 milliseconds for an individual proton beamlet. For IMPT plan dose comparisons to the dose calculated by the MC method, the DL5 method exhibited gamma pass rates of γ(2 mm, 2%) and γ(3 mm, 3%) ranging from 98.15% to 99.89% and 98.80% to 99.98%, respectively, across all 17 testing cases. On average, the DL5 method increased the gamma pass rates to γ(2 mm, 2%) from 82.97% to 99.23% and to γ(3 mm, 3%) from 85.27% to 99.75% when compared with the PB method. The proposed DL5 model enables rapid and precise dose calculation in IMPT plan, which has the potential to significantly enhance the efficiency and quality of proton radiation therapy.

Evaluation of magnetic resonance imaging derived synthetic computed tomography for proton therapy planning in prostate cancer

Background and purposeMagnetic resonance imaging (MRI)-only workflow is used in photon radiotherapy (RT) today, but not yet for protons. To bring MRI-only proton RT into clinical use, proton dose calculation on MRI-derived synthetic CT (sCT) must be validated. We evaluated proton dose calculation accuracy of prostate cancer proton plans using a commercially available sCT generator already validated for photon planning. Materials and methodsThe retrospective planning study included 10 prostate cancer patients who underwent MRI and planning CT (pCT) before RT. sCT were generated from the MRI with MRI Planner v2.3, and compared to pCT using structural mean absolute error (MAE). The pCT was used to create one-arc volumetric modulated arc therapy (VMAT) photon plan and two-field intensity modulated proton therapy (IMPT) proton plan. Each plan was recalculated on the sCT and compared to pCT doses. Dose volume histogram parameters, gamma analyses and range differences were evaluated. ResultsMedian MAE for the body contour was 71 HU. Dose differences between pCT and sCT were small and similar for VMAT and IMPT plans. Median (range) gamma pass rates were lower for IMPT plans with 95.8 (89.3–98.7) % compared to VMAT plans with 99.4 (91.2–99.6) %. The proton range difference was 1.0 (interquartile range –0.1 – 0.2) mm deeper for sCT compared to the reference. ConclusionMRI-only IMPT planning for prostate cancer seems feasible in a clinical setting for the evaluated beam arrangement and sCT generator. More patients and evaluation of other beam arrangements are needed for a more general conclusion.

Dosimetric comparison of IMPT vs VMAT for multiple lung lesions: an NTCP model-based decision-making strategy

To compare the dosimetric differences in volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) in stereotactic body radiation therapy (SBRT) of multiple lung lesions and determine a normal tissue complication probability (NTCP) model-based decision strategy that determines which treatment modality the patient will use. A total of 41 patients were retrospectively selected for this study. The number of patients with 1-6 lesions was 5, 16, 7, 6, 3, and 4, respectively. A prescription dose of 70 GyRBE in 10 fractions was given to each lesion. SBRT plans were generated using VMAT and IMPT. All the IMPT plans used robustness optimization with ± 3.5% range uncertainties and 5 mm setup uncertainties. Dosimetric metrics and the predicted NTCP value of radiation pneumonitis (RP), esophagitis, and pericarditis were analyzed to evaluate the potential clinical benefits between different planning groups. In addition, a threshold for the ratio of PTV to lungs (%) to determine whether a patient would benefit highly from IMPT was determined using receiver operating characteristic curves. All plans reached target coverage (V70GyRBE ≥ 95%). Compared with VMAT, IMPT resulted in a significantly lower dose of most thoracic normal tissues. For the 1-2, 3-4 and 5-6 lesion groups, the lung V5 was 29.90 ± 9.44%, 58.33 ± 13.35%, and 81.02 ± 5.91% for VMAT and 11.34 ± 3.11% (p < 0.001), 21.45 ± 3.80% (p < 0.001), and 32.48 ± 4.90% (p < 0.001) for IMPT, respectively. The lung V20 was 12.07 ± 4.94%, 25.57 ± 6.54%, and 43.99 ± 11.83% for VMAT and 6.76 ± 1.80% (p < 0.001), 13.14 ± 2.27% (p < 0.01), and 19.62 ± 3.48% (p < 0.01) for IMPT. The Dmean of the total lung was 7.65 ± 2.47 GyRBE, 14.78 ± 2.75 GyRBE, and 21.64 ± 4.07 GyRBE for VMAT and 3.69 ± 1.04 GyRBE (p < 0.001), 7.13 ± 1.41 GyRBE (p < 0.001), and 10.69 ± 1.81 GyRBE (p < 0.001) for IMPT. Additionally, in the VMAT group, the maximum NTCP value of radiation pneumonitis was 73.91%, whereas it was significantly lower in the IMPT group at 10.73%. The accuracy of our NTCP model-based decision model, which combines the number of lesions and PTV/Lungs (%), was 97.6%. The study demonstrated that the IMPT SBRT for multiple lung lesions had satisfactory dosimetry results, even when the number of lesions reached 6. The NTCP model-based decision strategy presented in our study could serve as an effective tool in clinical practice, aiding in the selection of the optimal treatment modality between VMAT and IMPT.

A planning study of proton therapy dose escalation for non-small cell lung cancer

In non-small-cell lung cancer (NSCLC), improving local control through radiotherapy dose escalation might improve survival. However, a photon-based RCT showed increased organ at risk dose exposure and worse overall survival in the dose escalation arm. In this study, intensity-modulated proton therapy plans with dose escalation to the primary tumour were created for 20 NSCLC patients. The mediastinal envelope was delineated to spare structures around the heart. It was possible to increase primary tumour dose up to 74.0 Gy without a significant increase in organ at risk doses and predicted toxicity.

Quantifying the Dosimetric Impact of Proton Range Uncertainties on RBE-Weighted Dose Distributions in Intensity-Modulated Proton Therapy for Bilateral Head and Neck Cancer.

In current clinical practice, intensity-modulated proton therapy (IMPT) head and neck cancer (HNC) plans are generated using a constant relative biological effectiveness (cRBE) of 1.1. The primary goal of this study was to explore the dosimetric impact of proton range uncertainties on RBE-weighted dose (RWD) distributions using a variable RBE (vRBE) model in the context of bilateral HNC IMPT plans. The current study included the computed tomography (CT) datasets of ten bilateral HNC patients who had undergone photon therapy. Each patient's plan was generated using three IMPT beams to deliver doses to the CTV_High and CTV_Low for doses of 70 Gy(RBE) and 54 Gy(RBE), respectively, in 35 fractions through a simultaneous integrated boost (SIB) technique. Each nominal plan calculated with a cRBE of 1.1 was subjected to the range uncertainties of ±3%. The McNamara vRBE model was used for RWD calculations. For each patient, the differences in dosimetric metrices between the RWD and nominal dose distributions were compared. The constrictor muscles, oral cavity, parotids, larynx, thyroid, and esophagus showed average differences in mean dose (Dmean) values up to 6.91 Gy(RBE), indicating the impact of proton range uncertainties on RWD distributions. Similarly, the brachial plexus, brain, brainstem, spinal cord, and mandible showed varying degrees of the average differences in maximum dose (Dmax) values (2.78-10.75 Gy(RBE)). The Dmean and Dmax to the CTV from RWD distributions were within ±2% of the dosimetric results in nominal plans. The consistent trend of higher mean and maximum doses to the OARs with the McNamara vRBE model compared to cRBE model highlighted the need for consideration of proton range uncertainties while evaluating OAR doses in bilateral HNC IMPT plans.

The first investigation of the dosimetric perturbations from the spot position errors in spot-scanning arc therapy (SPArc)

Objective. To quantitatively investigate the impact of spot position error (PE) on the dose distribution in (Spot-scanning arc therapy) SPArc plans compared to Intensity-Modulated Proton Therapy (IMPT). Approach. Twelve representative cases, including brain, lung, liver, and prostate cancers, were retrospectively selected. Spot PEs were simulated during dynamic SPArc treatment delivery. Two types of errors were generated, including random error and systematic error. Two different probability distributions of random errors were used (1) Gaussian distribution (PEran-GS) (2) uniform distribution (PEran-UN). In PEran-UN, four sub-scenarios were considered: 25%, 50%, 75%, and 100% spots were randomly selected in various directions on the scale of 0–1 mm or 0–2 mm of PE. Additionally, systematic error was simulated by shifting all the spot uniformly by 1 or 2 mm in various directions (PEsys). Gamma-index Passing Rate (GPR) is applied to assess the dosimetric perturbation quantitatively. Main results. For PEran-GS in the 1 mm scenario, both SPArc and IMPT are comparable with a GPR exceeding 99%. However, for PEran-GS in 2 mm scenario, SPArc could provide better GPR. As PEsys of 2 mm, SPArc plans have a much better GPR compared to IMPT plans: SPArc’s GPR is 99.59 ± 0.47%, 93.82 ± 4.07% and 64.58 ± 15.83% for 3 mm/3%, 2 mm/2% and 1 mm/1% criteria compared to IMPT with 97.49 ± 2.44%, 84.59 ± 4.99% and 42.02 ± 6.31%. Significance. Compared to IMPT, SPArc shows better dosimetric robustness in spot PEs. This study presents the first simulation results and the methodology that serves as a reference to guide future investigations into the accuracy and quality assurance of SPArc treatment delivery.

Reducing the lateral dose penumbra in IMPT by incorporating transmission pencil beams

ObjectiveIn intensity-modulated proton therapy (IMPT), Bragg peaks result in steep distal dose fall-offs, while the lateral IMPT dose fall-off is often less steep than in photon therapy. High-energy pristine transmission (‘shoot through’) pencil beams have no Bragg peak in the patient, but show a sharp lateral penumbra at the target level. We investigated whether combining Bragg peaks with Transmission pencil beams (‘IMPT&TPB’) could improve head-and-neck plans by exploiting the steep lateral dose fall-off of transmission pencil beams. ApproachOur system for automated multi-criteria IMPT plan optimisation was extended for combined optimisation of BPs and TPBs. The system generates for each patient a Pareto-optimal plan using a generic ‘wish-list’ with prioritised planning objectives and hard constraints. For eight nasopharynx cancer patients (NPC) and eight oropharynx cancer (OPC) patients, the IMPT&TPB plan was compared to the competing conventional IMPT plan with only Bragg peaks, which was generated with the same optimiser, but without transmission pencil beams. Main resultsClinical OAR and target constraints were met in all plans. By allowing transmission pencil beams in the optimisation, on average 14 of the 25 investigated OAR plan parameters significantly improved for NPC, and 9 of the 17 for OPC, while only one OPC parameter showed small but significant deterioration. Non-significant differences were found in the remaining parameters. In NPC, cochlea Dmean reduced by up to 17.5 Gy and optic nerve D2% by up to 11.1 Gy. ConclusionCompared to IMPT, IMPT&TPB resulted in comparable target coverage with overall superior OAR sparing, the latter originating from steeper dose fall-offs close to OARs.

The partial adaptation strategy for online-adaptive proton therapy: A proof of concept study in head and neck cancer patients.

The accuracy of intensity-modulated proton therapy (IMPT) is greatly affected by anatomy variations that might occur during the treatment course. Online plan adaptations have been proposed as a solution to intervene promptly during a treatment session once the anatomy changes are detected. The implementation of online-adaptive proton therapy (OAPT) is still hindered by time-consuming tasks in the workflow. The study introduces the novel concept of partial adaptation and aims at investigating its feasibility as a potential solution to parallelize tasks during an OAPT workflow for saving valuable in-room time. The proof-of-principle simulation study includes datasets from six head and neck cancer (HNC) patients, each consisting of one planning CT (pCT) and three contoured control CTs (cCTs). Robust 3-field normo-fractionated initial IMPT plans were generated on the pCTs with a standardized field configuration, delivering 66 Gy and 54Gy to the high-risk and low-risk clinical target volume (CTVHigh and CTVLow), respectively.For each cCT, a dose-mimicking-based partial adaptation was applied: two fields were adapted on the current anatomy taking into account the background dose of the first non-adapted field supposedly delivered in the meantime. Fraction doses on the cCTs resulting from partially adapted plans with different first (non-adapted) field assignments were compared against those from non-adapted and fully adapted plans regarding target coverage and organs at risk (OARs) sparing. The robustness of partially adapted plans was also evaluated. Partially adapted plans showed comparable results to fully adapted plans and were superior to non-adapted plans for both target coverage and OAR sparing. Target coverage degradation in the non-adapted plans (median D98%: 95.9% and 97.5% for CTVLow and CTVHigh, respectively) was recovered by both partial (98.0% and 98.5%) and full adaptation (98.2% and 98.7%) in comparison to the initial plans (98.7% and 98.8%). The initial hotspot dose for the CTVHigh (median D2%: 101.8%) increased in the non-adapted plans (102.9%) and was recovered by the adaptive strategies (partial: 102.5%, full: 101.9%). The near-maximum dose (D0.01cc) to brainstem and spinal cord was within clinical constraints for all investigated dose distributions, but clearly increased for no adaptation and improved in the (both partially and fully) adapted plans with respect to the non-adapted ones. The parotids' median doses (D50) were mainly patient-specific depending on the proximity to the target region, but anyway lower for the partially and fully adapted plans compared to the non-adapted ones. OAR sparing was furthermore improved for the partially adapted plans in comparison to full adaptation. Robustness of the target dose metrics was preserved in all evaluated scenarios. For OAPT of HNC patients, partial adaptation is able to generate plans of superior conformity to non-adapted plans and of comparable conformity as fully adapted plans, while having the potential to speed up the online-adaptive workflows. Thus, partial adaptation represents an intermediate approach until fast online adaptation workflows become available. Furthermore, it can be applied in workflows where online treatment verification stops the delivery and triggers an online adaptation for the remaining fraction.

Radiotherapy Plan Quality Assurance in NRG Oncology Trials for Brain and Head/Neck Cancers: An AI-Enhanced Knowledge-Based Approach.

The quality of radiation therapy (RT) treatment plans directly affects the outcomes of clinical trials. KBP solutions have been utilized in RT plan quality assurance (QA). In this study, we evaluated the quality of RT plans for brain and head/neck cancers enrolled in multi-institutional clinical trials utilizing a KBP approach. The evaluation was conducted on 203 glioblastoma (GBM) patients enrolled in NRG-BN001 and 70 nasopharyngeal carcinoma (NPC) patients enrolled in NRG-HN001. For each trial, fifty high-quality photon plans were utilized to build a KBP photon model. A KBP proton model was generated using intensity-modulated proton therapy (IMPT) plans generated on 50 patients originally treated with photon RT. These models were then applied to generate KBP plans for the remaining patients, which were compared against the submitted plans for quality evaluation, including in terms of protocol compliance, target coverage, and organ-at-risk (OAR) doses. RT plans generated by the KBP models were demonstrated to have superior quality compared to the submitted plans. KBP IMPT plans can decrease the variation of proton plan quality and could possibly be used as a tool for developing improved plans in the future. Additionally, the KBP tool proved to be an effective instrument for RT plan QA in multi-center clinical trials.

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.

Immune System Dose With Proton Versus Photon Radiotherapy for Treatment of Locally Advanced NSCLC

PurposeEmerging data have illuminated the impact of effective radiation dose to immune cells (EDIC) on outcomes in patients with locally advanced, unresectable non‐small cell lung cancer (NSCLC) treated with intensity-modulated radiotherapy (IMRT). Hypothesizing that intensity-modulated proton therapy (IMPT) may reduce EDIC versus IMRT, we conducted a dosimetric analysis of patients treated at our institution. Materials and MethodsData were retrospectively collected for 12 patients with locally advanced, unresectable NSCLC diagnosed between 2019 and 2021 who had physician-approved IMRT and IMPT plans. Data to calculate EDIC from both Jin et al (PMID: 34944813) and Ladbury et al’s (PMID: 31175902) models were abstracted. Paired t tests were utilized to compare the difference in mean EDIC between IMPT and IMRT plans. ResultsIMPT decreased EDIC for 11 of 12 patients (91.7%). The mean EDIC per the Jin model was significantly lower with IMPT than IMRT (3.04 GyE vs 4.99 Gy, P < .001). Similarly, the mean EDIC per the Ladbury model was significantly lower with IMPT than IMRT (4.50 GyE vs 7.60 Gy, P < .002). Modeled 2-year overall survival was significantly longer with IMPT than IMRT (median 71% vs 63%; P = .03). ConclusionIMPT offers a statistically significant reduction in EDIC compared to IMRT. Given the emergence of EDIC as a modifiable prognostic factor in treatment planning, our dosimetric study highlights a potential role for IMPT to address an unmet need in improving oncologic outcomes in patients with locoregionally advanced NSCLC.