Proton Therapy Plans Research Articles

Clinical Flow Improvement by Direct Conversion of Proton Plans across Different Platforms

<h3>Purpose/Objective(s)</h3> For proton therapy plans, switching proton machines without re-optimization can greatly improve the clinical efficiency, when proton machines belong to different platforms. This study focused on machine switching efficiency between Proteus-1 and Proteus-plus platforms by modeling a Proteus-1 proton machine with built-in range shifter (P1RS) for direct recalculation of treatment plans between P1 and universal nozzle of Proteus-plus (P+US) systems. <h3>Materials/Methods</h3> For institutions with multiple platform proton machines (i.e., P+ to P1), re-planning is usually required if a patient needs to be moved from P+ to P1 machines due to their different spot sizes. This usually requires re-planning of the patient and creates significant time delay when one machine is down or overloaded. We are proposing commissioning a P1 machine model use built-in range shifter (P1RS) with snout position fixed at 45cm upstream from isocenter. The in-air spot size and PDD of the P1RS are compared to those of the P+US. The P+ patient plans are recalculated using P1RS machine directly with both pencil beam and Monte Carlo dose engines. <h3>Results</h3> The P1RS machine model has similar in-air spot size as those of P+US (see Table). There are noticeable differences between the PDDs of the two models. For patient plan with field size less than 20cm by 24cm, preliminary investigation of direct conversion of treatment plans between the two machine models indicates that it is feasible. <h3>Conclusion</h3> P1 model with a built-in range shifter can simulate a P+US system. Direct recalculation of treatment plan between the two systems is feasible with acceptable dosimetric differences and could increase machine switching capabilities and improve clinical flow efficiency.

Quantitative and qualitative evaluation of density resolution of pCT images using Cirs062m phantom simulation in Geant4

Accuracy in the treatment planning (TP) of proton therapy (PT) depends on the precision of the information employed to calculate the relative stopping power (RSP) of the tissues in the patient's body. This information is obtained from the x-ray computed tomography (xCT) images and the calibration curve needed to convert the Hounsfield unit to RSP values. Using xCT bears errors in proton range estimation and dose calculation of TP. Proton computed tomography (pCT) can decrease the inherent uncertainty in PT by directly measuring RSP. Though by using pCT in the integral mode of energy loss, this error is removed, and the RSP map of tissues is calculated directly. This study simulated a modern pCT imaging system with particle-by-particle tracking capability using Geant4 Monte Carlo code. This simulation sought to improve the density resolution of tissue images without increasing the dose. The CIRS062M standard phantom was irradiated with 300 MeV protons, and the energy, position, and direction of the particle were recorded before and after the phantom. The matrix of the RSP image was modified using the normalization algorithm of the amount of integral energy loss and the correction of the angles of the projections.

Pre-treatment analysis of non-rigid variations can assist robust intensity-modulated proton therapy plan selection for head and neck patients.

To incorporate small non-rigid variations of head and neck patients into the robust evaluation of intensity-modulated proton therapy (IMPT) for the selection of robust treatmentplans. A cohort of 20 nasopharynx cancer patients with weekly kilovoltage CT (kVCT) and 15 oropharynx cancer patients with weekly cone-beam CT (CBCT) were retrospectively included. Anatomical variations between week 0/week 1 of treatment were acquired using deformable image registration (DIR) for all 35 patients and then applied to the planning CT of four patients who have kVCT scanned each week to simulate potential small non-rigid variations (sNRVs). The robust evaluations were conducted on IMPT plans with: (1) different number of beam fields from 3-field to 5-field; (2) different beam angles. The robust evaluation before treatment, including the sNRVs and setup uncertainty, referred to as sNRV+R evaluation was compared with the conventional evaluation (without sNRVs) in terms of robustness consistency with the gold standard evaluation based on weeklyCT. Among four patients (490 scenarios), we observed a maximum difference in the sNRV+R evaluation to the nominal dose of: 9.37% dose degradation on D95 of clinical target volumes (CTVs), increase in mean dose (D ) of parotid 11.87Gy, increase in max dose (D ) of brainstem 20.82Gy. In contrast, in conventional evaluation, we observed a maximum difference to the nominal dose of: 7.58% dose degradation on D95 of the CTVs, increase in parotid D by 4.88Gy, increase in brainstem D by 13.5 Gy. In the measurement of the robustness ranking consistency with the gold standard evaluation, the sNRV+R evaluation was better or equal to the conventional evaluation in 77% of cases, particularly, better on spinal cord, parotid glands, and low-riskCTV. This study demonstrated the additional dose discrepancy that sNRVs can make. The inclusion of sNRVs can be beneficial to robust evaluation, providing information on clinical uncertainties additional to the conventional rigid isocentershift.

Low-dose CT allows for accurate proton therapy dose calculation and plan optimization

Objective. Protons offer a more conformal dose delivery compared to photons, yet they are sensitive to anatomical changes over the course of treatment. To minimize range uncertainties due to anatomical variations, a new CT acquisition at every treatment session would be paramount to enable daily dose calculation and subsequent plan adaptation. However, the series of CT scans results in an additional accumulated patient dose. Reducing CT radiation dose and thereby decreasing the potential risk of radiation exposure to patients is desirable, however, lowering the CT dose results in a lower signal-to-noise ratio and therefore in a reduced quality image. We hypothesized that the signal-to-noise ratio provided by conventional CT protocols is higher than needed for proton dose distribution estimation. In this study, we aim to investigate the effect of CT imaging dose reduction on proton therapy dose calculations and plan optimization. Approach. To verify our hypothesis, a CT dose reduction simulation tool has been developed and validated to simulate lower-dose CT scans from an existing standard-dose scan. The simulated lower-dose CTs were then used for proton dose calculation and plan optimization and the results were compared with those of the standard-dose scan. The same strategy was adopted to investigate the effect of CT dose reduction on water equivalent thickness (WET) calculation to quantify CT noise accumulation during integration along the beam. Main results. The similarity between the dose distributions acquired from the low-dose and standard-dose CTs was evaluated by the dose-volume histogram and the 3D Gamma analysis. The results on an anthropomorphic head phantom and three patient cases indicate that CT imaging dose reduction up to 90% does not have a significant effect on proton dose calculation and plan optimization. The relative error was employed to evaluate the similarity between WET maps and was found to be less than 1% after reducing the CT imaging dose by 90%. Significance. The results suggest the possibility of using low-dose CT for proton therapy dose estimation, since the dose distributions acquired from the standard-dose and low-dose CTs are clinically equivalent.

Assessment of IMPT versus VMAT plans using different uncertainty scenarios for prostate cancer

BackgroundTo assess the impact of systematic setup and range uncertainties for robustly optimized (RO) intensity modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans in patients with localized prostate cancer.MethodsTwenty-six localized prostate patients previously treated with VMAT (CTV to PTV expansion of 3-5 mm) were re-planned with RO-IMPT with 3 mm and 5 mm geometrical uncertainties coupled with 3% range uncertainties. Robust evaluations (RE) accounting for the geometrical uncertainties of 3 and 5 mm were evaluated for the IMPT and VMAT plans. Clinical target volume (CTV), anorectum, and bladder dose metrics were analyzed between the nominal plans and their uncertainty perturbations.ResultsWith geometric uncertainties of 5 mm and accounting for potential inter-fractional perturbations, RO-IMPT provided statistically significant (p < 0.05) sparing at intermediate doses (V4000cGy) to the anorectum and bladder and high dose sparring (V8000cGy) to the bladder compared to VMAT. Decreasing the RO and RE parameters to 3 mm improved IMPT sparing over VMAT at all OAR dose levels investigated while maintaining equivalent coverage to the CTV.ConclusionsFor localized prostate treatments, if geometric uncertainties can be maintained at or below 3 mm, RO-IMPT provides clear dosimetric advantages in anorectum and bladder sparing compared to VMAT. This advantage remains even under uncertainty scenarios. As geometric uncertainties increase to 5 mm, RO-IMPT still provides dosimetric advantages, but to a smaller magnitude.

Training and validation of a knowledge-based dose-volume histogram predictive model in the optimisation of intensity-modulated proton and volumetric modulated arc photon plans for pleural mesothelioma patients

BackgroundTo investigate the performance of a narrow-scope knowledge-based RapidPlan (RP) model for optimisation of intensity-modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans applied to patients with pleural mesothelioma. Second, estimate the potential benefit of IMPT versus VMAT for this class of patients.MethodsA cohort of 82 patients was retrospectively selected; 60 were used to "train" a dose-volume histogram predictive model; the remaining 22 provided independent validation. The performance of the RP models was benchmarked, comparing predicted versus achieved mean and near-to-maximum dose for all organs at risk (OARs) in the training set and by quantitative assessment of some dose-volume metrics in the comparison of the validation RP-based data versus the manually optimised training datasets. Treatment plans were designed for a prescription dose of 44 Gy in 22 fractions (proton doses account for a fixed relative biological effectiveness RBE = 1.1).ResultsTraining and validation RP-based plans resulted dosimetrically similar for both VMAT and IMPT groups, and the clinical planning aims were met for all structures. The IMPT plans outperformed the VMAT ones for all OARs for the contra-lateral and the mean and low dose regions for the ipsilateral OARs. Concerning the prediction performance of the RP models, the linear regression for the near-to-maximum dose resulted in Dachieved = 1.03Dpredicted + 0.58 and Dachieved = 1.02Dpredicted + 1.46 for VMAT and IMPT, respectively. For the mean dose it resulted: Dachieved = 0.99Dpredicted + 0.34 and Dachieved = 1.05Dpredicted + 0.27 respectively. In both cases, the linear correlation between prediction and achievement is granted with an angular coefficient deviating from unity for less than 5%. Concerning the dosimetric comparison between manual plans in the training cohort and RP-based plans in the validation cohort, no clinical differences were observed for the target volumes in both the VMAT and IMPT groups. Similar consistency was observed for the dose-volume metrics analysed for the OAR. This proves the possibility of achieving the same quality of plans with manual procedures (the training set) or with automated RP-based methods (the validation set).ConclusionTwo models were trained and validated for VMAT and IMPT plans for pleural mesothelioma. The RP model performance resulted satisfactory as measured by the agreement between predicted and achieved (after full optimisation) dose-volume metrics. The IMPT plans outperformed the VMAT plans for all the OARs (with different intensities for contra- or ipsilateral structures). RP-based planning enabled the automation of part of the optimisation and the harmonisation of the dose-volume results between training and validation. The IMPT data showed a systematic significant dosimetric advantage over VMAT. In general, using an RP-based approach can simplify the optimisation workflow in these complex treatment indications without impacting the quality of plans.

Integrating Structure Propagation Uncertainties in the Optimization of Online Adaptive Proton Therapy Plans.

Simple SummaryThe fast and accurate definition of structures is a main limiting factor in online adaptive proton therapy. In this study, different methods to include structure propagation uncertainties in the optimization were compared with adaptation using physician-drawn structures, uncorrected propagated structures, and no adaptation. While adaptation with physician-drawn structures resulted in the best adaptive plan quality and no adaptation in the worst, manual structure correction could be replaced by a fast ‘plausibility check’, and plans could be adapted with correction-free adaptation strategies.Currently, adaptive strategies require time- and resource-intensive manual structure corrections. This study compares different strategies: optimization without manual structure correction, adaptation with physician-drawn structures, and no adaptation. Strategies were compared for 16 patients with pancreas, liver, and head and neck (HN) cancer with 1–5 repeated images during treatment: ‘reference adaptation’, with structures drawn by a physician; ‘single-DIR adaptation’, using a single set of deformably propagated structures; ‘multi-DIR adaptation’, using robust planning with multiple deformed structure sets; ‘conservative adaptation’, using the intersection and union of all deformed structures; ‘probabilistic adaptation’, using the probability of a voxel belonging to the structure in the optimization weight; and ‘no adaptation’. Plans were evaluated using reference structures and compared using a scoring system. The reference adaptation with physician-drawn structures performed best, and no adaptation performed the worst. For pancreas and liver patients, adaptation with a single DIR improved the plan quality over no adaptation. For HN patients, integrating structure uncertainties brought an additional benefit. If resources for manual structure corrections would prevent online adaptation, manual correction could be replaced by a fast ‘plausibility check’, and plans could be adapted with correction-free adaptation strategies. Including structure uncertainties in the optimization has the potential to make online adaptation more automatable.

PO-1507 Dose comparison of clinical robust intensity modulated proton therapy plans for testicular seminoma

PO-1507 Dose comparison of clinical robust intensity modulated proton therapy plans for testicular seminoma

Single-fraction 34 Gy Lung Stereotactic Body Radiation Therapy Using Proton Transmission Beams: FLASH-dose Calculations and the Influence of Different Dose-rate Methods and Dose/Dose-rate Thresholds

PurposeResearch suggests that in addition to the dose-rate, a dose threshold is also important for the reduction in normal tissue toxicity with similar tumor control after ultrahigh dose-rate radiation therapy (UHDR-RT). In this analysis we aimed to identify factors that might limit the ability to achieve this “FLASH”-effect in a scenario attractive for UHDR-RT (high fractional beam dose, small target, few organs-at-risk): single-fraction 34 Gy lung stereotactic body radiation therapy. Methods and MaterialsClinical volumetric-modulated arc therapy (VMAT) plans, intensity modulated proton therapy (IMPT) plans and transmission beam (TB) plans were compared for 6 small and 1 large lung lesion. The TB-plan dose-rate was calculated using 4 methods and the FLASH-percentage (percentage of dose delivered at dose-rates ≥40/100 Gy/s and ≥4/8 Gy) was determined for various variables: a minimum spot time (minST) of 0.5/2 ms, maximum nozzle current (maxN) of 200/40 0nA, and 2 gantry current (GC) techniques (energy-layer based, spot-based [SB]). ResultsBased on absolute doses 5-beam TB and VMAT-plans are similar, but TB-plans have higher rib, skin, and ipsilateral lung dose than IMPT. Dose-rate calculation methods not considering scanning achieve FLASH-percentages between ∼30% to 80%, while methods considering scanning often achieve <30%. FLASH-percentages increase for lower minST/higher maxN and when using SB GC instead of energy-layer based GC, often approaching the percentage of dose exceeding the dose-threshold. For the small lesions average beam irradiation times (including scanning) varied between 0.06 to 0.31 seconds and total irradiation times between 0.28 to 1.57 seconds, for the large lesion beam times were between 0.16 to 1.47 seconds with total irradiation times of 1.09 to 5.89 seconds. ConclusionsIn a theoretically advantageous scenario for FLASH we found that TB-plan dosimetry was similar to that of VMAT, but inferior to that of IMPT, and that decreasing minST or using SB GC increase the estimated amount of FLASH. For the appropriate machine/delivery parameters high enough dose-rates can be achieved regardless of calculation method, meaning that a possible FLASH dose-threshold will likely be the primary limiting factor.

Robust automated radiation therapy treatment planning using scenario-specific dose prediction and robust dose mimicking.

PurposeWe present a framework for robust automated treatment planning using machine learning, comprising scenario‐specific dose prediction and robust dose mimicking.Methods The scenario dose prediction pipeline is divided into the prediction of nominal dose from input image and the prediction of scenario dose from nominal dose, each using a deep learning model with U‐net architecture. By using a specially developed dose–volume histogram–based loss function, the predicted scenario doses are ensured sufficient target coverage despite the possibility of the training data being non‐robust. Deliverable plans may then be created by solving a robust dose mimicking problem with the predictions as scenario‐specific reference doses.ResultsNumerical experiments are performed using a data set of 52 intensity‐modulated proton therapy plans for prostate patients. We show that the predicted scenario doses resemble their respective ground truth well, in particular while having target coverage comparable to that of the nominal scenario. The deliverable plans produced by the subsequent robust dose mimicking were showed to be robust against the same scenario set considered for prediction.ConclusionsWe demonstrate the feasibility and merits of the proposed methodology for incorporating robustness into automated treatment planning algorithms.

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

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

Detection of anatomical changes using two-dimensional x-ray images for head and neck adaptive radiotherapy.

To develop a system for detecting anatomical changes using two-dimensional (2D) x-ray images. Ten patients with head and neck cancer were retrospectively analyzed using 2D x-ray and cone-beam computed tomography (CBCT) images. The 2D x-ray images were acquired daily, whereas the CBCT images were acquired weekly during the treatment period. The developed system imported the 2D x-ray images obtained on the initial treatment day and on another day, and thereafter converted them into the water equivalent thickness (WET) using the conversion table. The difference between the WET images for the first and other treatment days (ΔWET) was calculated as the quantitative value for anatomical changes and visualized to recognize the anatomical change location. We compared ΔWET and the difference in the lateral neck distance (ΔLND) on the corresponding CBCT images. ΔLND was used as the ground truth for anatomical changes. ΔWET and ΔLND were measured at the first cervical vertebra (C1) and the tumor center (TC). C1 and TC were selected to observe the volume changes in the parotid gland and tumor, respectively. Sensitivity and specificity were calculated to evaluate the performance of the 2D-WET system. The cut-off values of WET and LND were set to 2-10mm. Furthermore, intensity-modulated proton therapy (IMPT) plans for six patients with rescan CT images were generated. The IMPT plans on the rescan CT images were compared to the original plans on simulation CT using the dosimetric parameters for the target and the organs at risk. The mean differences between ΔWET and ΔLND for C1 and TC were -0.62 ± 1.66mm and -0.93 ± 1.28mm (mean ± 1 SD), respectively. ΔWET in the proposed system was in good agreement with ΔLND using the CBCT images. In the sensitivity and specificity results for C1 and TC with cut-off values from 2 to 10mm, the sensitivity was>85% for all cut-off values, while the specificity was>90% at 5-10mm and<90% at less than 5mm. The average ΔWET at the time of replanning was 12.8mm which resulted in maximum dose increase in the spinal cord D1cc by 8.4Gy, the parotid gland D50 by 26.6Gy, and the oral cavity D50 by 23.2Gy. We developed a new system for detecting anatomical changes using 2D x-ray images. The developed system with ΔWET showed an agreement with ΔLND at C1 and TC with an average difference of less than 1mm. ΔWET detected anatomical changes with high sensitivity and specificity with a cut-off value of 5-10mm. This system can monitor daily anatomical changes without causing high exposure to patients and requiring any inefficient work, and it can be applied to daily online adaptive proton beam therapy and triggered adaptive radiotherapy.

Proton Radiation Therapy for Nasopharyngeal Cancer Patients: Dosimetric and NTCP Evaluation Supporting Clinical Decision.

Simple SummaryRadiotherapy is the cornerstone of treatment of nasopharyngeal cancer, in different settings with or without chemotherapy. This role has been recently strengthened by the introduction of proton therapy, as a radiation treatment option for head and neck cancer, obtaining improved plans with a reduced dose to organs-at-risk. Definition of strategies to identify patients who would benefit the most from proton therapy in terms of reduced toxicity is highly desirable, due to limited availability and higher costs of this treatment option. Two parallel working pipelines were depicted in this study for nasopharyngeal cancer patients. The introduction of a synthetic index describing the overall expected reduction in toxicities in the head and neck region with proton therapy was supported by the application of the well-established model-based selection methodology, relative to the same patient cohort. Based on this analysis, the fraction of nasopharyngeal cancer patients expected to receive a benefit with proton therapy was in line with the Dutch experience for the head and neck cancer population.(1) Background: we proposed an integrated strategy to support clinical allocation of nasopharyngeal patients between proton and photon radiotherapy. (2) Methods: intensity-modulated proton therapy (IMPT) plans were optimized for 50 consecutive nasopharyngeal carcinoma (NPC) patients treated with volumetric modulated arc therapy (VMAT), and differences in dose and normal tissue complication probability (ΔNTCPx-p) for 16 models were calculated. Patient eligibility for IMPT was assessed using a model-based selection (MBS) strategy following the results for 7/16 models describing the most clinically relevant endpoints, applying a model-specific ΔNTCPx-p threshold (15% to 5% depending on the severity of the complication) and a composite threshold (35%). In addition, a comprehensive toxicity score (CTS) was defined as the weighted sum of all 16 ΔNTCPx-p, where weights follow a clinical rationale. (3) Results: Dose deviations were in favor of IMPT (ΔDmean ≥ 14% for cord, esophagus, brainstem, and glottic larynx). The risk of toxicity significantly decreased for xerostomia (−12.5%), brain necrosis (−2.3%), mucositis (−3.2%), tinnitus (−8.6%), hypothyroidism (−9.3%), and trismus (−5.4%). There were 40% of the patients that resulted as eligible for IMPT, with a greater advantage for T3–T4 staging. Significantly different CTS were observed in patients qualifying for IMPT. (4) Conclusions: The MBS strategy successfully drives the clinical identification of NPC patients, who are most likely to benefit from IMPT. CTS summarizes well the expected global gain.

Proceedings to the 7th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA)

Proceedings to the 7th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA)

Intensity Modulated Proton Therapy for Bilateral Breast or Chest Wall and Comprehensive Nodal Irradiation for Synchronous Bilateral Breast Cancer: Initial Clinical Experience and Dosimetric Comparison

PurposeSynchronous bilateral breast cancer (SBBC) poses distinct challenges for radiation therapy planning. We report our proton therapy experience in treating patients with SBBC. We also provide a dosimetric comparison of intensity modulated proton therapy (IMPT) versus photon therapy. Methods and MaterialsPatients with SBBC who received IMPT at our institution were retrospectively analyzed. The clinical target volume (CTV) included the breast or chest wall and comprehensive regional lymph nodes, including axilla, supraclavicular fossa, and the internal mammary chain. Intensity modulated proton therapy and volumetric modulated arc therapy (VMAT) plans were generated with the goal that 90% of the CTV would recieve at least 90% of the prescription dose (D90>=90%). Comparisons between modalities were made using the Wilcoxon signed rank test. Physician-reported acute toxic effects and photography were collected at baseline, end of treatment, and each follow-up visit. ResultsBetween 2015 and 2018, 11 patients with SBBC were treated with IMPT. The prescription was 50 Gy in 25 fractions. The median CTV D90 was 99.9% for IMPT and 97.6% for VMAT (P = .001). The mean heart dose was 0.7 Gy versus 7.2 Gy (P = .001), the total lung mean dose was 7.8 Gy versus 17.3 Gy (P = .001), and the total lung volume recieving 20 Gy was 13.0% versus 27.4% (P = .001). The most common acute toxic effects were dermatitis (mostly grade 1-2 with 1 case of grade 3) and grade 1 to 2 fatigue. The most common toxic effects at the last-follow up (median, 32 months) were grade 1 skin hyperpigmentation, superficial fibrosis, and extremity lymphedema. No nondermatologic or nonfatigue adverse events of grade >1 were recorded. ConclusionsBilateral breast and/or chest wall and comprehensive nodal IMPT is technically feasible and associated with low rates of severe acute toxic effects. Treatment with IMPT offered improved target coverage and normal-tissue sparing compared with photon therapy. Long-term follow-up is ongoing to assess efficacy and toxic effects.

Integrated MRI‐guided proton therapy planning: Accounting for the full MRI field in a perpendicular system

To present a first study on the treatment planning feasibility in perpendicular field MRI-integrated proton therapy that considers the full transport of protons from the pencil beam scanning (PBS) assembly to the patient inside the MRIscanner. A generic proton PBS gantry was modeled as being integrated with a realistic split-bore MRI system in the perpendicular orientation. MRI field strengths were modeled as 0.5, 1, and 1.5T. The PBS beam delivery and dose calculation was modeled using the TOPAS Monte Carlo toolkit coupled with matRad as the optimizer engine. A water phantom, liver, and prostate plans were evaluated and optimized in the presence of the full MRI field distribution. A simple combination of gantry angle offset and small PBS nozzle skew was used to direct the proton beams along a path that closely follows the reference planning scenario, that is, without magneticfield. All planning metrics could be successfully achieved with the inclusion of gantry angle offsets in the range of 8 -29 when coupled with a PBS nozzle skew of 1.6 -4.4 . These two hardware-based corrections were selected to minimize the average Euclidean distance (AED) in the beam path enabling the proton beams to travel inside the patient in a path that is close to the original path (AED smaller than 3mm at 1.5T). Final dose optimization, performed through further changes in the PBS delivery, was then shown to be feasible for our selection of plans studied yielding comparable plan quality metrics to referenceconditions. For the first time, we have shown a robust method to account for the full proton beam deflection in a perpendicular orientation MRI-integrated proton therapy. These results support the ongoing development of the current prototypesystems.

Intensity Modulated Proton Therapy Better Spares Non-Adjacent Organs and Reduces the Risk of Secondary Malignant Neoplasms in the Treatment of Sinonasal Cancers.

This study compare dosimetric parameters and secondary malignancy risk (SMN) using intensity modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans for the treatment of sinonasal cancer (SC). After IRB-approval, 10 patients previously treated with IMPT for cancers of the ethmoid, sphenoid, maxillary, or frontal sinuses were identified. Dosimetrists blinded to the IMPT plans generated VMAT plans for comparison. Volume coverage and dose to organs at risk (OAR) were recorded and compared. Organ equivalent dose (OED) of tissues outside of the treatment volume was used to define the excess absolute and relative risk of SMNs. In all cases, both VMAT and IMPT provided acceptable target volume coverage and were able to meet OAR constraints. IMPT was superior for brain V10, V30, and mean, brainstem D0.01 ipsilateral cochlea V30, contralateral cochlea mean, contralateral lacrimal gland mean, contralateral parotid mean, spinal cord D0.01 and body outside of the CTV V10, V20, and V30. VMAT was superior for ipsilateral eye mean, ipsilateral lens mean, CTV V100 and maximum hotspot. The relative risk of SMNs with VMAT compared to IMPT is 3.35 (95% CI, 1.92-5.89). For the treatment of SC, IMPT spares OARs that are not immediately adjacent to the treatment volume and reduces the risk of SMNs when compared to VMAT. VMAT spares OARs abutting the target volume better than IMPT and has more homogenous target coverage. Tumors of the ethmoid sinus, benefit more from IMPT, while tumors located elsewhere require application of our findings on a case by case basis.

Clinical Outcomes after International Referral of Uveal Melanoma Patients for Proton Therapy.

Simple SummaryThis study aims to assess cancer control and preservation of the eye and visual acuity after proton therapy abroad for eye melanoma. For this, medical files were reviewed of Dutch uveal melanoma patients who were treated in Switzerland with proton therapy from 1987 to 2019. The tumours of these patients were too large and/or localised too close to the optic nerve to be treated with local plaque irradiation. There were 103 patients, of whom one had a uveal melanoma in both eyes. The tumours were relatively large and often localised around the central part of the retina. At five years after treatment, proton therapy had controlled the uveal melanomas of 94% of the patients and 81% had preserved their eye. Spread of the cancer beyond the eye was observed in 30% of the patients. Most patients (79%) became blind or had severe visual impairment after proton therapy; a small group of patients had mild or no visual impairment (17%). The size of the tumour, its localisation and the dose of proton therapy were important for the risk of decline in visual acuity. This study shows that proton therapy abroad for uveal melanoma is feasible and yields good results.Objective: To assess oncological and ophthalmological outcomes after international referral of uveal melanoma patients for proton therapy. Materials and Methods: This is a retrospective study among Dutch uveal melanoma patients who were treated in Switzerland with 60.0 CGE proton therapy (in 4 fractions) from 1987 to 2019. All patients were ineligible for brachytherapy due to tumour size and/or proximity to the optic nerve. Time-to-event analyses were performed using Kaplan–Meier’s methodology and Cox proportional hazards models. Results: There were 103 patients (104 eyes) with a median largest tumour diameter of 19 mm (range 6–26 mm). Tumours were localised centrally (11%), mid-peripherally (65%) or peripherally (34%). Median follow-up was 7 years. Five-year local control, distant metastasis-free survival and eye preservation rates were 94%, 70% and 81% respectively. At five years, severe, moderate and mild visual impairment was observed in respectively 79%, 4% and 6% of the patients. Larger tumour volumes and more central tumour localisation were associated with severe visual impairment. After correction for these factors, dose to the macula, optic disc and retina, but not optic nerve was significantly associated with severe visual impairment. Conclusion: International referral for proton therapy yielded good tumour control and eye preservation rates, but risk of distant metastasis and severe visual impairment were substantial, possibly due to the selection of advanced tumour stages and/or central localisation. Dose to the macula may be more relevant than dose to the optic nerve for preservation of visual acuity, which is relevant for the treatment planning of proton therapy.

Scripted spot removal in PBS proton therapy planning.

BackgroundIt is well known in proton therapy that the relative biological effectiveness (RBE) is not constant across the entire Bragg peak, with higher RBE at the distal end of the Bragg peak due to higher linear energy transfer (LET). Treatment planning systems are moving toward LET optimization to mitigate this potentially higher biological impact at a track end. However, using a simple script, proton users can begin to simulate this process by deleting spots from critical structures during optimization. In most cases, nominal target coverage and plan robustness remain satisfactory.MethodsIn our clinic, we developed a script that allows the user to delete spots in all organs at risk (OARs) of interest for one or more treatment beams. The purpose of this script is to potentially reduce side effects by eliminating Bragg peaks within OARs. The script was first used for prostate patients where spots in the rectum and sigmoid, outside of the overlap with the target, were deleted. We then began to use the script for head and neck (H&N) and breast/chestwall patients to reduce acute side effects of the skin by removing spots in a 0.5‐cm skin rind.ConclusionsBy utilizing a simple script for deleting spots in critical structures, we have seen excellent clinical results thus far. We have noted reduced skin reactions for nearly all H&N and breast patients.

Radiation-Induced Toxicity Risks in Photon Versus Proton Therapy for Synchronous Bilateral Breast Cancer.

PurposeThis study compares photon and proton therapy plans for patients with synchronous bilateral early breast cancer and estimates risks of early and late radiation-induced toxicities.Materials and MethodsTwenty-four patients with synchronous bilateral early breast cancer receiving adjuvant radiation therapy using photons, 3-dimensional conformal radiation therapy or volumetric modulated arc therapy, were included and competing pencil beam scanning proton therapy plans were created. Risks of dermatitis, pneumonitis, acute esophageal toxicity, lung and breast fibrosis, hypothyroidism, secondary lung and esophageal cancer and coronary artery events were estimated using published dose-response relationships and normal tissue complication probability (NTCP) models.ResultsThe primary clinical target volume V95% and/or nodal clinical target volume V90% were less than 95% in 17 photon therapy plans and none of the proton plans. Median NTCP of radiation dermatitis ≥ grade 2 was 18.3% (range, 5.4-41.7) with photon therapy and 58.4% (range, 31.4-69.7) with proton therapy. Median excess absolute risk (EAR) of secondary lung cancer at age 80 for current and former smokers was 4.8% (range, 0.0-17.0) using photons and 2.7% (range, 0.0-13.6) using protons. Median EAR of coronary event at age 80, assuming all patients have preexisting cardiac risk factors, was 1.0% (range, 0.0-5.6) with photons and 0.2% (range, 0.0-1.3) with protons.ConclusionProton therapy plans improved target coverage and reduced risk of coronary artery event and secondary lung cancer while increasing the risk of radiation dermatitis.