Pencil Beam Scanning Research Articles

Fast MCsquare-Based Independent Dose Verification Platform for Pencil Beam Scanning Proton Therapy.

Purpose:To commission MCsquare (a multi-cores CPU-based dose calculation engine) for pencil beam scanning (PBS) proton therapy, integrate it into RayStation treatment plan system (TPS) to create a dedicated platform for fast independent dose verification.Method:A MCsquare-based independent dose verification platform (MC2InRS) was developed to realize automatic dose re-calculation for clinical use, including data preparation, dose calculation, 2D/3D gamma analysis. MCsquare was commissioned based on in-air lateral dose profiles, integrated depth dose, and the absolute dose of different beam energies for Proteus®ONE. MC2InRS was validated with measurement data using various targets and depths in a water phantom. This study also investigated 15 clinical cases to demonstrate the feasibility and effectiveness of MC2InRS platform in clinic practice.Results:Between simulation and measurement, the distal range differences at 80% (R80) and 20% (R20) dose levels for each energy were below 0.05 mm, and 0.1 mm, respectively, and the absolute dose differences were below 0.5%. 29 out of 36 QA planes reached a 100% gamma passing rate (GPR) for 2%/2mm criteria, and a minimum of 98.3% gamma was obtained in water phantom between simulation and measurement. For the 15 clinical cases investigated, the average 2D GPR (2%/2mm) was 95.4%, 99.3% for MCsquare vs. measurement, MCsquare vs. TPS, respectively. The average 3D GPR (2%/2mm) was 98.9%, 95.3% for MCsquare vs. TPS in water, and computed tomography (CT), respectively.Conclusion:MC2InRS, a fast, independent dose verification platform, has been developed to perform dose verification with high accuracy and efficiency for Pencil Bream Scanning (PBS). Its potential to be applied in routine clinical practice has also been discussed.

A Phase IV Trial of Proton Therapy in Children: The First Report from SJPROTON1

Background: Early reports suggest adverse events following proton therapy (PT) for childhood cancer are more prevalent. We evaluated treatment-failure and toxicity following Pencil Beam Scanning (PBS)-PT in children. Methods: The single-institution Phase IV trial screened 856 children, of which 528 were eligible for PBS-PT, and 500 enrolled in SJPROTON1 from 2017–2020. The median follow-up was 2.1 years (range 1.1-4.4). The primary objective was the cumulative incidence (CI) of ≥grade 3 non-hematologic, PBS-PT attributable toxicity by CTCAE v4.0. Additional outcomes included PBS-PT toxicity attributable hospitalization, procedures, and treatment-related mortality. Toxicities including necrosis, vasculopathy, neurologic deficits, and fracture/osteoradionecrosis were further characterized (any grade). Competing risk regression was used to evaluate predictors of ≥grade 3 PBS-PT attributable toxicity. Findings: At two years, the event-free survival was 73.2% (95% CI, 68.9%-77.8%). Distant and local failure predominated with a 2-year CI of 16.5% (95% CI 13.1-20.4) and 6.8% (95% CI 4.6-9.5) respectively. The 4 year CI of ≥grade 3 toxicity was 24.5%; including necrosis (3.7%), neurologic deficit (2.9%), and fracture/osteoradionecrosis (0.79%). The rates of PBS-PT-toxicity attributable hospitalization and procedures were 3.9% and 7.6%. Predictors of any ≥grade 3 toxicity included baseline total toxicity burden (TTB) (HR 1.043, 95% CI 1.012-1.07, p=0.007), and mixed photon/PBS-PT (HR 2.62, 95% CI 1.51-4.54, p=0.006) in CNS patients, and pelvic radiotherapy (HR 4.25, 95% CI 1.08-16.72, p=0.038), and TTB (HR 1.1, 95% CI 1.04-1.16, p=0.002) in non-CNS patients. Interpretation: PBS-PT yields a low incidence of toxicity, but subsets are at increased risk, and may require additional procedures or hospitalization. Funding: This work was supported by ALSAC and Cancer Center Core Grant CA21765. Declaration of Interest: None to declare. Ethical Approval: The SJPROTON1 trial was reviewed and approved by the Institutional Review Board at St. Jude. Informed consent was obtained from the parent, caregiver, or patient, with assent from the patient, as appropriate.

Dosimetric comparison of intensity-modulated proton radiotherapy versus intensity-modulated photon-based radiotherapy for breast cancer

Purpose: This study aims to compare the dosimetric differences in intensity-modulated proton therapy (IMPT) using pencil beam scanning technology and intensity-modulated photon-based radiotherapy (IMRT) in hypofractionated whole-breast irradiation (HF-WBI) and find out the more beneficial technique. Methods and Materials: Eight breast cancer (BC) patients with pathological stage T1 ~ 2N0M0 were immobilized and underwent 4D-CT scanning used deep inspiration breath-hold (DIBH) technology. The IMPT and IMRT plans were designed for each patient. The IMPT plans used two en-face beam angles. IMRT plans were designed using the field in field technique. The optimization constraints of the two types of plans were identical. Prescription dose and regimen was 40.05 Gy (relative biological effect [RBE])/15 fx with a 10 Gy (RBE)/5 fx boost, five fractions a week. A dose of 95% of the target volume should not be less than the prescribed dose. The target coverage was evaluated using D1, D2, D50, D95, D98, and D99. The target dose distribution and conformity were evaluated using the Conformity index (CI) and the homogeneity index (HI). The Organs at risk (OARs) were evaluated using mean dose (Dmean) and maximum dose (Dmax). Ipsilateral Lung and Contralateral Lung were evaluated additionally using V5, V10, V20, V30. Results: The mean dose (Dmean) of the Heart (P = 0.012), Ipsilateral Lung (P = 0.036), Contralateral Lung (P = 0.012), and Spinal Cord (P = 0.012) were significantly reduced in IMPT plans. The IMPT also showed a tendency to reduce the V20 (P = 0.05) and V30 (P = 0.05) of the Ipsilateral Lung. But there was no significant difference in target coverage, homogeneity, and conformity between the IMRT and IMPT plans. Conclusion: Compared to IMRT, the IMPT using pencil beam scanning technology can spare OARs without compromising target coverage in BC patients undergoing HF-WBI, which potentially reduce the incidence of radiation-related adverse effects and thus may positively impact long-term survival.

PROTON THERAPY – MEDICAL PROCEDURE IN ONCOLOGICAL THERAPY S

The paper presents proton therapy as a method of treating cancer, the action of proton therapy, the proton as a subatomic particle that can controlled to obtain and deliver radiation directed to tumors and radioactivity. A comparison is made between proton therapy and X-ray radiation, pencil beam scanning technology is presented, treatment with proton therapy, advantages and disadvantages of proton therapy and it finishes with a conclusion and a bibliography.

A Probability-Based Investigation on the Setup Robustness of Pencil-beam Proton Radiation Therapy for Skull-Base Meningioma.

IntroductionThe intracranial skull-base meningioma is in proximity to multiple critical organs and heterogeneous tissues. Steep dose gradients often result from avoiding critical organs in proton treatment plans. Dose uncertainties arising from setup errors under image-guided radiation therapy are worthy of evaluation.Patients and MethodsFourteen patients with skull-base meningioma were retrospectively identified and planned with proton pencil beam scanning (PBS) single-field uniform dose (SFUD) and multifield optimization (MFO) techniques. The setup uncertainties were assigned a probability model on the basis of prior published data. The impact on the dose distribution from nominal 1-mm and large, less probable setup errors, as well as the cumulative effect, was analyzed. The robustness of SFUD and MFO planning techniques in these scenarios was discussed.ResultsThe target coverage was reduced and the plan dose hot spot increased by all setup uncertainty scenarios regardless of the planning techniques. For 1 mm nominal shifts, the deviations in clinical target volume (CTV) coverage D99% was −11 ± 52 cGy and −45 ± 147 cGy for SFUD and MFO plans. The setup uncertainties affected the organ at risk (OAR) dose both positively and negatively. The statistical average of the setup uncertainties had <100 cGy impact on the plan qualities for all patients. The cumulative deviations in CTV D95% were 1 ± 34 cGy and −7 ± 18 cGy for SFUD and MFO plans.ConclusionIt is important to understand the impact of setup uncertainties on skull-base meningioma, as the tumor target has complex shape and is in proximity to multiple critical organs. Our work evaluated the setup uncertainty based on its probability distribution and evaluated the dosimetric consequences. In general, the SFUD plans demonstrated more robustness than the MFO plans in target coverages and brainstem dose. The probability-weighted overall effect on the dose distribution is small compared to the dosimetric shift during single fraction.

Using patient-specific bolus for pencil beam scanning proton treatment of periorbital disease.

PurposeA unique mantle cell lymphoma case with bilateral periorbital disease unresponsive to chemotherapy and with dosimetry not conducive to electron therapy was treated with pencil beam scanning (PBS) proton therapy. This patient presented treatment planning challenges due to the thin target, immediately adjacent organs at risk (OAR), and nonconformal orbital surface anatomy. Therefore, we developed a patient‐specific bolus and hypothesized that it would provide superior setup robustness, dose uniformity and dose conformity.Materials/MethodsA blue‐wax patient‐specific bolus was generated from the patient's face contour to conform to his face and eliminate air gaps. A relative stopping power ratio (RSP) of 0.972 was measured for the blue‐wax, and the HUs were overridden accordingly in the treatment planning system (TPS). Orthogonal kV images were used for bony alignment and then to ensure positioning of the bolus through fiducial markers attached to the bolus and their contours in TPS. Daily CBCT was used to confirm the position of the bolus in relation to the patient's surface. Dosimetric characteristics were compared between (a) nonbolus, (b) conventional gel bolus and (c) patient‐specific bolus plans. An in‐house developed workflow for assessment of daily treatment dose based on CBCT images was used to evaluate inter‐fraction dose accumulation.ResultsThe patient was treated to 24 cobalt gray equivalent (CGE) in 2 CGE daily fractions to the bilateral periorbital skin, constraining at least 50% of each lacrimal gland to under 20 Gy. The bolus increased proton beam range by adding 2–3 energy layers of different fields to help achieve better dose uniformity and adequate dose coverage. In contrast to the plan with conventional gel bolus, dose uniformity was significantly improved with patient‐specific bolus. The global maximum dose was reduced by 7% (from 116% to 109%). The max and mean doses were reduced by 6.0% and 7.7%, respectively, for bilateral retinas, and 3.0% and 13.9% for bilateral lacrimal glands. The max dose of the lens was reduced by 2.1%. The rigid shape, along with lightweight, and smooth fit to the patient face was well tolerated and reported as “very comfortable” by the patient. The daily position accuracy of the bolus was within 1 mm based on IGRT marker alignment. The daily dose accumulation indicates that the target coverage and OAR doses were highly consistent with the planning intention.ConclusionOur patient‐specific blue‐wax bolus significantly increased dose uniformity, reduced OAR doses, and maintained consistent setup accuracy compared to conventional bolus. Quality PBS proton treatment for periorbital tumors and similar challenging thin and shallow targets can be achieved using such patient‐specific bolus with robustness on both setup and dosimetry.

Proton beam therapy reduces the risk of severe radiation-induced lymphopenia during chemoradiotherapy for locally advanced non-small cell lung cancer: A comparative analysis of proton versus photon therapy

HypothesisWe investigated differences in severe radiation-induced lymphopenia (SRL) after pencil beam scanning proton therapy (PBSPT) or intensity-modulated (photon) radiotherapy (IMRT) for patients with locally advanced non-small cell lung cancer. MethodsWe retrospectively reviewed 223 patients who received definitive concurrent chemoradiotherapy with PBSPT (n = 29) or IMRT (n = 194). SRL was defined when ≥2 events of absolute lymphocyte counts (ALCs) of <200 cells/μL were observed in weekly laboratory tests conducted during treatment. Stepwise multivariate logistic regression with 10-fold cross-validation was performed to identify predictive values of SRL. Furthermore, 1:2 propensity score matching (PSM) analysis was performed between the PBSPT and IMRT groups. ResultsBaseline ALC was comparable between the PBSPT and IMRT groups (median, 2130 vs. 2040 cells/μL; p = 0.983). Lung volumes receiving ≥ 5–20 GyE and the mean dose were significantly lower in patients receiving PBSPT than those receiving IMRT (p < 0.001). Among 72 (32.3%) patients with SRL; 69 (95.8%) and 3 (4.2%) patients were treated with IMRT and PBSPT, respectively. After multivariable analysis, PBSPT reduced SRL compared to IMRT (odds ratio [OR] 0.13, p = 0.003). Specifically, lung V5Gy were identified as the strongest predictor of SRL before (OR 1.11) and after PSM (OR, 1.07) (p < 0.05). With a median follow-up of 23.0 months, the 2-year overall survival in patients with SRL was worse than that those without SRL (63.4% vs. 79.9%; p = 0.003). ConclusionsReduced irradiated lung volumes of PBSPT consequently reduced SRL. In addition, lung V5Gy contributed to the SRL. Reduction of SRL through the optimized RT might be essential to improve the outcomes.

Impact of air gap, range shifter, and delivery technique on skin dose in proton therapy.

Side effects of radiation therapy may include skin damage. The surface dose is of great interest and contains the buildup effect. In particular, the proton therapy community requires further experimental data to quantify doses in the surface region. This specification includes the skin dose, which is defined according to ICRU Report No. 39 at 70μm water equivalent depth. The aim of this study is to gather more knowledge of the skin dose by varying key parameters defined by the patient treatment plan. This consists of clinical aspects such as the influence of the air gap, the application of a range shifter (RS), or the proton delivery technique. Skin doses were determined with a PTW 23391 extrapolation chamber with three thin Kapton® entrance windows operated as a conventional ionization chamber. The impact on the skin dose for quasi-monoenergetic pencil beam scanning (PBS) proton beams was evaluated for clinical air gaps between 3.5 and 51.1cm. The differences in skin dose were assessed by irradiating equivalent fields with an RS of 51mm water equivalent thickness (RS51) and without. Furthermore, the delivery techniques PBS, uniform scanning (US), and double scattering (DS) were compared by defining a spread-out Bragg peak (SOBP). TOPAS (V.3.1.2) was used to model an IBA nozzle with PBS and to score dose to water at the surface of a water phantom. For the monoenergetic fields without the application of the RS the skin dose was constant down to an air gap of 6.2cm. A lower air gap of 3.5cm showed a variation in skin dose by up to 2.4% compared to the results obtained with larger air gaps. With the inserted RS51 an increase in the skin dose was found for air gaps smaller than 11.3cm. Experimentally, a dose difference of 1.4% was recorded for an air gap of 6.2cm by inserting an RS and none. With the Monte Carlo calculations the largest dose increase was observed at the air gap of 3.5cm with 1.7% and 4.0% relative to the skin dose results without the RS and to the largest evaluated air gap of 51.1cm, respectively. The SOBP comparison of the beam modalities at the measuring plane at the isocenter revealed higher skin doses without RS (including RS) by up to +1.9% (+1.5%) for DS and +1.3% (+1.1%) for US compared to PBS. For all three techniques an approx. 2% rise in skin dose was observed for the largest evaluated air gap of 37.7cm to an air gap of 6.2cm when using an RS51. The study investigated aspects of skin dose of a water equivalent phantom by varying key parameters of a proton treatment plan. Parameters like the RS, the air gap, and the delivery modality have an impact on the order of 4.0% for the skin dose at the depth of 70μm. The increases in skin dose are the effects of the contribution of the increased electron fluence at small air gaps and the emitted hadronic particles produced by the RS.

Auto-Trending daily quality assurance program for a pencil beam scanning proton system aligned with TG 224.

The Daily Quality Assurance (DQA) for a proton modality is not standardized. The modern pencil beam scanning proton system is becoming a trend and an increasing number of proton centers with PBS are either under construction or in planning. The American Association of Physicists in Medicine has a Task Group 224 report published in 2019 for proton modality routine QA. Therefore, there is a clinical need to explore a DQA procedure to meet the TG 224 guideline. The MatriXX PT and a customized phantom were used for the dosimetry constancy checking. An OBI box was used for imaging QA. The MyQA(TM) software was used for logging the dosimetry results. An in‐house developed application was applied to log and auto analyze the DQA results. Another in‐house developed program "DailyQATrend" was used to create DQA databases for further analysis. All the functional and easy determined tasks passed. For dosimetry constancy checking, the outputs for four gantry rooms were within ±3% with room to room baseline differences within ±1%. The energy checking was within ±1%. The spot location checking from the baseline was within 0.63 mm and the spot size checking from the baseline was within −1.41 ± 1.27 mm (left–right) and −0.24 ± 1.27 mm (in–out) by averaging all the energies. We have found that there was also a trend for the beam energies of two treatment rooms slowly going down (0.76% per month and 0.48 per month) after analyzing the whole data trend with linear regression. A DQA program for a PBS proton system has been developed and fully implemented into the clinic. The DQA program meets the TG 224 guideline and has web‐based logging and auto treading functions. The clinical data show the DQA program is efficient and has the potential to identify the PBS proton system potential issue.

Proton Therapy for Intracranial Meningioma for the Treatment of Primary/Recurrent Disease Including Re-Irradiation

Meningeal tumors represent approximately 10–25% of primary brain tumors and occur usually in elderly female patients. Most meningiomas are benign (80–85%) and for symptomatic and/or large tumors, surgery, with or without radiation therapy (RT), has been long established as an effective means of local tumor control. RT can be delivered to inoperable lesions or to those with non-benign histology and for Simpson I–III and IV–V resection. RT can be delivered with photons or particles (protons or carbon ions) in stereotactic or non-stereotactic conditions. Particle therapy delivered for these tumors uses the physical properties of charged carbon ions or protons to spare normal brain tissue (i.e. Bragg peak), with or without or a dose-escalation paradigm for non-benign lesions. PT can substantially decrease the dose delivered to the non-target brain tissues, including but not limited to the hippocampi, optic apparatus or cochlea. Only a limited number of meningioma patients have been treated with PT in the adjuvant or recurrent setting, as well as for inoperable lesions with pencil beam scanning and with protons only. Approximately 500 patients with image-defined or WHO grade I meningioma have been treated with protons. The reported outcome, usually 5-year local tumor control, ranges from 85 to 99% (median, 96%). For WHO grade II or III patients, the outcome of only 97 patients has been published, reporting a median tumor local control rate of 52% (range, 38–71.1). Only 24 recurring patients treated previously with photon radiotherapy and re-treated with PT were reported. The clinical outcome of these challenging patients seems interesting, provided that they presented initially with benign tumors, are not in the elderly category and have been treated previously with conventional radiation dose of photons. Overall, the number of meningioma patients treated or-re-irradiated with this treatment modality is small and the clinical evidence level is somewhat low (i.e. 3b–5). In this review, we detail the results of upfront PT delivered to patients with meningioma in the adjuvant setting and for inoperable tumors. The outcome of meningioma patients treated with this radiation modality for recurrent tumors, with or without previous RT, will also be reviewed.

Single pencil beam benchmark of a module for Monte Carlo simulation of proton transport in the PENELOPE code.

PENH is a recently coded module for simulation of proton transport in conjunction with the Monte Carlo code PENELOPE. PENELOPE applies class II simulation to all type of interactions, in particular, to elastic collisions. PENH uses calculated differential cross sections for proton elastic collisions that include electron screening effects as well as nuclear structure effects. Proton-induced nuclear reactions are simulated from information in the ENDF-6 database or from alternative nuclear databases in ENDF format. The purpose of this work is to benchmark this module by simulating absorbed dose distributions from a single finite spot size proton pencil beam in water. Monte Carlo simulations with PENH are compared with simulation results from TOPAS Monte Carlo (v3.1p2) and RayStation Monte Carlo (v6). Different beam models are examined in terms of mean energy and energy spread to match the measured profiles. The phase-space file is derived from experimental measurements. Simulated absorbed dose distributions are compared to experimental data obtained with the ionization chamber array MatriXX 2D detector (IBA Dosimetry) in a water tank. The experiments were conducted with a clinical IBA pencil beam scanning dedicated nozzle. In all simulations a Fermi-Eyges phase-space representation of a single finite spot size proton pencil beam is used. In general, there is a good agreement between simulated results and experimental data up to a distance of 3cm from the central axis. In the core region (region where the dose is more than 10% of the maximum dose) PENH shows, overall, the smallest deviations from experimental data, with the largest radial rms (root mean square) smaller than 0.2. The results achieved by TOPAS and RayStation in that region are very close to those of PENH. For the halo region, that is the area of the dose distribution outside the core region reaching down to 0.01% of the maximum intensity, the largest rms achieved by TOPAS is always smaller than 0.5, yielding better results than the rest of the codes. The physics modeling of the PENELOPE/PENH code yields results consistent with measurements in the dose range relevant for proton therapy. The discrepancies between PENH appearing at distances larger than 3cm from the central-beam axis are accountable to the lack of neutron simulation in this code. In contradistinction, TOPAS has a better agreement with experimental data at large distances from the central-beam axis because of the simulation of neutrons.

Patient-specific CT calibration based on ion radiography for different detector configurations in 1H, 4He and 12C ion pencil beam scanning

The empirical conversion of the treatment planning x-ray computed tomography (CT) image to ion stopping power relative to water causes dose calculation inaccuracies in ion beam therapy. A patient-specific calibration of the CT image is enabled by the combination of an ion radiography (iRad) with the forward-projection of the empirically converted CT image along the estimated ion trajectories. This work investigated the patient-specific CT calibration for list-mode and integration-mode detector configurations, with reference to a ground truth ion CT (iCT) image. Analytical simulations of idealized carbon ion and proton trajectories in a numerical anthropomorphic phantom and realistic Monte Carlo simulations of proton, helium and carbon ion pencil beam scanning in a clinical CT image of a head-and-neck patient were considered. Controlled inaccuracy and noise levels were applied to the calibration curve and to the iRad, respectively. The impact of the selection of slices and angles of the iRads, as well as the choice of the optimization algorithm, were investigated. Accurate and robust CT calibration was obtained in analytical simulations of straight carbon ion trajectories. Analytical simulations of non-straight proton trajectories due to scattering suggested limitations for integration-mode but not for list-mode. To make the most of integration-mode, a dedicated objective function was proposed, demonstrating the desired accuracy for sufficiently high proton statistics in analytical simulations. In clinical data the inconsistencies between the iRad and the forward-projection of the ground truth iCT image were in the same order of magnitude as the applied inaccuracies (up to 5%). The accuracy of the CT calibration were within 2%–5% for integration-mode and 1%–3% for list-mode. The feasibility of successful patient-specific CT calibration depends on detector technologies and is primarily limited by these above mentioned inconsistencies that slightly penalize protons over helium and carbon ions due to larger scattering and beam spot size.

Feasibility of quasi-prompt PET-based range verification in proton therapy

Compared to photon therapy, proton therapy allows a better conformation of the dose to the tumor volume with reduced radiation dose to co-irradiated tissues. In vivo verification techniques including positron emission tomography (PET) have been proposed as quality assurance tools to mitigate proton range uncertainties. Detection of differences between planned and actual dose delivery on a short timescale provides a fast trigger for corrective actions. Conventional PET-based imaging of 15O (T1/2 = 2 min) and 11C (T1/2 = 20 min) distributions precludes such immediate feedback. We here present a demonstration of near real-time range verification by means of PET imaging of 12N (T1/2 = 11 ms). PMMA and graphite targets were irradiated with a 150 MeV proton pencil beam consisting of a series of pulses of 10 ms beam-on and 90 ms beam-off. Two modules of a modified Siemens Biograph mCT PET scanner (21 × 21 cm2 each), installed 25 cm apart, were used to image the beam-induced PET activity during the beam-off periods. The modifications enable the detectors to be switched off during the beam-on periods. 12N images were reconstructed using planar tomography. Using a 1D projection of the 2D reconstructed 12N image, the activity range was obtained from a fit of the activity profile with a sigmoid function. Range shifts due to modified target configurations were assessed for multiples of the clinically relevant 108 protons per pulse (approximately equal to the highest intensity spots in the pencil beam scanning delivery of a dose of 1 Gy over a cubic 1 l volume). The standard deviation of the activity range, determined from 30 datasets obtained from three irradiations on PMMA and graphite targets, was found to be 2.5 and 2.6 mm (1σ) with 108 protons per pulse and 0.9 and 0.8 mm (1σ) with 109 protons per pulse. Analytical extrapolation of the results from this study shows that using a scanner with a solid angle coverage of 57%, with optimized detector switching and spot delivery times much smaller than the 12N half-life, an activity range measurement precision of 2.0 mm (1σ) and 1.3 mm (1σ) within 50 ms into an irradiation with 4 × 107 and 108 protons per pencil beam spot can be potentially realized. Aggregated imaging of neighboring spots or, if possible, increasing the number of protons for a few probe beam spots will enable the realization of higher precision range measurement.

Performance evaluation of adaptive aperture's static and dynamic collimation in a compact pencil beam scanning proton therapy system: A dosimetric comparison study for multiple disease sites

A compact pencil beam scanning (PBS) proton therapy system, Mevion S250i with Hyperscan, is equipped with adaptive aperture (AA) to collimate the beam with 2 different techniques: Static aperture (SA) and dynamic aperture (DA). SA (single aperture) collimates the outermost contour of the target and DA (multi-layer aperture) collimates each energy layer of the proton beam. This study evaluates dosimetric performance of SA and DA for different disease sites. This study includes 5 disease sites (brain, head and neck (HN), partial breast, lung, and prostate), and 8 patients for each. A total of 80 patient treatment plans (5 sites × 8 patients per site × 2 collimation techniques) were created using 2 to 4 proton beams. Both SA and DA plans were made using the same plan and optimization parameters calculated by a Monte Carlo dose algorithm. Multi-field optimization (MFO) was used for HN treatment plans, whereas treatment plans for the other sites were made with single-field optimization (SFO). All plans were robustly optimized with 3 mm (brain and HN) or 5 mm (breast, lung, and prostate) position uncertainty along with 3.5% range uncertainty. Treatment plans were normalized such that 99% of the clinical target volume (CTV) received 100% of the prescribed dose. Dose volume histogram (DVH) parameters were evaluated for CTV and organs at risk (OARs). The CTV was also evaluated for dose homogeneity, dose conformity, and dose gradient. In general, the DA plan made CTV hotter, while it saved OARs better. DA produced better conformity with sharper dose falloff around CTV, while SA generated better homogenous target coverage. DA decreased Dmax to brainstem (1.2% = [(SA-DA)/DA × 100%]) for brain, Dmax to the spinal cord (137.3%) for HN, D1% of the ipsilateral lung (50.5%) for breast, and Dmax to the spinal cord (74.0%) for lung. The dose reduction in bladder and rectum for prostate plans with DA was less than 2.5%. The DA plans reduced the dose to OARs for all disease sites but escalated the target maximum dose for the same target coverage than the SA plans. The OAR saving and dose escalation depended on CTV size, proximity of the OARs to CTV, and the plan complexity.

Deep learning prediction of proton and photon dose distributions for paediatric abdominal tumours

ObjectiveDose prediction using deep learning networks prior to radiotherapy might lead tomore efficient modality selections. The study goal was to predict proton and photon dose distributions based on the patient-specific anatomy and to assess their clinical usage for paediatric abdominal tumours. Material and methodsData from 80 patients with neuroblastoma or Wilms’ tumour was included. Pencil beam scanning (PBS) (5 mm/ 3%) and volumetric-modulated arc therapy (VMAT) plans (5 mm) were robustly optimized on the internal target volume (ITV). Separate 3-dimensional patch-based U-net networks were trained to predict PBS and VMAT dose distributions. Doses, planning-computed tomography images and relevant optimization masks (ITV, vertebra and organs-at-risk) of 60 patients were used for training with a 5-fold cross validation.The networks’ performance was evaluated by computing the relative error between planned and predicted dose-volume histogram (DVH) parameters for 20 inference patients. In addition, the organs-at-risk mean dose difference between modalities was calculated using planned and predicted dose distributions (ΔDmean = DVMAT-DPBS). Two radiation oncologists performed a blind PBS/VMAT modality selection based on either planned or predicted ΔDmean. ResultsAverage DVH differences between planned and predicted dose distributions were ≤ |6%| for both modalities. The networks classified the organs-at-risk Dmean difference as a gain (ΔDmean > 0) with 98% precision. An identical modality selection based on planned compared to predicted ΔDmean was made for 18/20 patients. ConclusionDeep learning networks for accurate prediction of proton and photon dose distributions for abdominal paediatric tumours were established. These networks allowing fast dose visualisation might aid in identifying the optimal radiotherapy technique when experience and/or resources are unavailable.

Biological Effects of Scattered Versus Scanned Proton Beams on Normal Tissues in Total Body Irradiated Mice: Survival, Genotoxicity, Oxidative Stress and Inflammation.

Side effects of proton therapy are poorly studied. Moreover, the differences in the method of dose delivery on normal tissues are not taken into account when proton beams are scanned instead of being scattered. We proposed here to study the effects of both modalities of proton beam delivery on blood; skin; lung and heart in a murine model. In that purpose; C57BL/6 mice were total body irradiated by 190.6 MeV proton beams either by Double Scattering (DS) or by Pencil Beam Scanning (PBS) in the plateau phase before the Bragg Peak. Mouse survival was evaluated. Blood and organs were removed three months after irradiation. Biomarkers of genotoxicity; oxidative stress and inflammation were measured. Proton irradiation was shown to increase lymphocyte micronucleus frequency; lung superoxide dismutase activity; erythrocyte and skin glutathione peroxidase activity; erythrocyte catalase activity; lung; heart and skin oxidized glutathione level; erythrocyte and lung lipid peroxidation and erythrocyte protein carbonylation even 3 months post-irradiation. When comparing both methods of proton beam delivery; mouse survival was not different. However, PBS significantly increased lymphocyte micronucleus frequency; erythrocyte glutathione peroxidase activity and heart oxidized glutathione level compared to DS. These results point out the necessity to take into account the way of delivering dose in PT as it could influence late side effects.

Four-dimensional carbon-ion pencil beam treatment planning comparison between robust optimization and range-adapted internal target volume for respiratory-gated liver and lung treatment.

We investigated the dose differences between robust optimization-based treatment planning (4DRO) and range-adapted internal target volume (rITV). We used 4DCT dataset of 20 lung cancer and 20 liver cancer patients, respectively, who had been treated with respiratory-gated carbon-ion pencil beam scanning therapy. 4DRO and rITV plans were created with the same clinical target volume (CTV) and organs at risk (OAR) contours. Four-dimensional dose distribution was calculated using deformable image registration. Dose metrics (e.g. D95, V20) were analyzed. Statistical significance was assessed by the Wilcoxon signed-rank test. For the lung cases, the mean CTV-D95 value for the rITV plan (=98.5%) was same as that for the 4DRO plan (=98.5%, P=0.106), while the mean D95 value for the CTV+setup margin contour for the rITV plan (=98.2%) was higher than that for the 4DRO plan (95.2%, P<0.001). For the liver cases, the mean CTV-D95 value for the rITV plan (=98.1%) was slightly lower than that for the 4DRO plan (=98.5%, P<0.01), while the mean D95 value for the CTV+setup margin contour for the rITV plan (=98.0%) was higher than that for the 4DRO plan (94.1%, P<0.001). For the doses to the organs at risk (OARs), the ipsilateral lung-V20/liver-V20 values for the rITV plan (=10.1%/19.7%) was significantly higher than that for the 4DRO plan (=8.6%/17.6, P<0.001). Although the target coverage for 4DRO plan may be worse than that for rITV plan in the presence of the setup error, the 4DRO plan can improve OAR dose while preserving acceptable target dose coverage.

Dosimetric analysis of local failures in skull-base chordoma and chondrosarcoma following pencil beam scanning proton therapy

BackgroundDespite combined modality treatment involving surgery and radiotherapy, a relevant proportion of skull-base chordoma and chondrosarcoma patients develop a local recurrence (LR). This study aims to analyze patterns of recurrence and correlate LR with a detailed dosimetric analysis.Methods222 patients were treated with proton radiotherapy for chordoma (n = 151) and chondrosarcoma (n = 71) at the PSI between 1998 and 2012. All patients underwent surgery, followed by pencil-beam scanning proton therapy to a mean dose of 72.5 ± 2.2GyRBE. A retrospective patterns of recurrence analysis was performed: LR were contoured on follow-up MRI, registered with planning-imaging and the overlap with initial target structures (GTV, PTVhigh-dose, PTVlow-dose) was calculated. DVH parameters of planning structures and recurrences were calculated and correlated with LR using univariate and multivariate cox regression.ResultsAfter a median follow-up of 50 months, 35 (16%) LR were observed. Follow-up MRI imaging was available for 27 (77%) of these recurring patients. Only one (3.7%) recurrence was located completely outside the initial PTV (surgical pathway recurrence). The mean proportions of LR covered by the initial target structures were 48% (range 0–86%) for the GTV, 70% (range 0–100%) for PTVhigh and 83% (range 0–100%) for PTVlow. In the univariate analysis, the following DVH parameters were significantly associated with LR: GTV(V < 66GyRBE, p = 0.01), GTV(volume, p = 0.02), PTVhigh(max, p = 0.02), PTVhigh(V < 66GyRBE, p = 0.03), PTVhigh(V < 59GyRBE, p = 0.02), PTVhigh(volume, p = 0.01) and GTV(D95, p = 0.05). In the multivariate analysis, only histology (chordoma vs. chondrosarcoma, p = 0.01), PTVhigh(volume, p = 0.05) and GTV(V < 66GyRBE, p = 0.02) were independent prognostic factors for LR.ConclusionThis study identified DVH parameters, which are associated with the risk of local recurrence after proton therapy using pencil-beam scanning for patients with skull-base chordoma and chondrosarcoma.

A framework for defining FLASH dose rate for pencil beam scanning.

PurposeTo develop a method of (a) calculating the dose rate of voxels within a proton field delivered using pencil beam scanning (PBS), and (b) reporting a representative dose rate for the PBS treatment field that enables correspondence between multiple treatment modalities. This method takes into account the unique spatiotemporal delivery patterns of PBS FLASH radiotherapy.MethodsThe dose rate at each voxel of a PBS radiation field is approximately the quotient of the voxel’s dose and “effective” irradiation time. Each voxel’s “effective” irradiation time starts when the cumulative dose rises above a chosen threshold value, and stops when its cumulative dose reaches its total dose minus the same threshold value. The above calculation yields a distribution of dose rates for the voxels within a PBS treatment field. To report a representative dose rate for the PBS field, we propose a user‐selectable parameter of pth percentile of the dose rate distribution, such that (100 − p) % of the field is above the corresponding dose rate. To demonstrate the method described above, we design FLASH transmission fields using 250 MeV protons and calculate the PBS dose rate distributions in both two‐dimensional (2D) and three‐dimensional (3D) models. To further evaluate the formalism, we provide an example of a clinical PBS treatment field.ResultsWith the 2D PBS transmission field, it is demonstrated that the time to accumulate the total dose at a voxel is limited to a fraction of the delivery time of the entire field. In addition, the spatial distributions of dose and dose rate are quite different within the field. For the 10 × 10 cm2 PBS field irradiating a 3D water phantom, the prescribed dose of 10 Gy at 10 cm depth is delivered in 1.0 s. The dose rate decreases in the irradiated volume with increasing depth (until the Bragg peak) due to increase of beam spot size by Coulomb scattering. For example, 95% of the irradiated volume between 0 and 10 cm depth receive >40 Gy/s, whereas between 0–20 cm and 0–30 cm depth, 95% of the irradiated volume received >36 Gy/s and >24 Gy/s, respectively. For the clinical PBS treatment field, the scanning pattern conforms to the PTV. PBS dose rate data are presented for the PTV and adjacent normal organs.ConclusionWe have developed a method of calculating the dose rate distribution of a PBS proton field and have recommended nomenclature for reporting PBS treatment dose rate. We believe that standardizing the method for calculating and reporting PBS treatment dose rates, in a manner that corresponds with other treatment modalities, will advance the research and potential application of PBS FLASH radiotherapy.

Evaluations of a flat-panel based compact daily quality assurance device for proton pencil beam scanning (PBS) system.

To evaluate the flat-panel detector quenching effect and clinical usability of a flat-panel based compact QA device for PBS daily constancy measurements. The QA device, named Sphinx Compact, is composed of a 20x20 cm2 flat-panel imager mounted on a portable frame with removable plastic modules for constancy checks of proton energy (100MeV, 150MeV, 200MeV), Spread-Out-Bragg-Peak (SOBP) profile, and machine output. The potential quenching effect of the flat-panel detector was evaluated. Daily PBS QA tests of X-ray/proton isocenter coincidence, the constancy of proton spot position and sigma as well as the energy of pristine proton beam, and the flatness of SOBP proton beam through the 'transformed' profile were performed and analyzed. Furthermore, the sensitivity of detecting energy changes of pristine proton beam was also evaluated. The quenching effect was observed at depths near the pristine peak regions. The flat-panel measured range of the distal 80% is within 0.9mm to the defined ranges of the delivered proton beams. X-ray/proton isocenter coincidence tests demonstrated maximum mismatch of 0.3mm between the two isocenters. The device can detect 0.1mm change of spot position and 0.1MeV energy changes of pristine proton beams. The measured transformed SOBP beam profile through the wedge module rendered as flat. Even though the flat-panel detector exhibited quenching effect at the Bragg peak region, the proton range can still be accurately measured. The device can fulfill the requirements of the daily QA tests recommended by the AAPM TG224 Report.