Pencil Beam Scanning Proton Therapy Research Articles

PO-1643 End-2-End testing of PBS proton therapy workflow with the PTW RUBY phantom

PO-1643 End-2-End testing of PBS proton therapy workflow with the PTW RUBY phantom

Clinical Outcome of Sacral Chordoma Patients Treated with Pencil Beam Scanning Proton Therapy

AimsSacral chordomas are locally aggressive, radio-resistant tumours. Proton therapy has the potential to deliver high radiation doses, which may improve the therapeutic ratio when compared with conventional radiotherapy. We assessed tumour control and radiation-induced toxicity in a cohort of sacral chordoma patients treated with definitive or postoperative pencil beam scanning proton therapy. Methods and materialsSixty patients with histologically proven sacral chordoma treated between November 1997 and October 2018 at the Paul Scherrer Institute with postoperative (n = 50) or definitive proton therapy (n = 10) were retrospectively analysed. Only 10 (17%) patients received combined photon radiotherapy and proton therapy. Survival rates were calculated using the Kaplan–Meier actuarial method. The Log-rank test was used to compare different functions for local control, freedom from distant recurrence and overall survival. Acute and late toxicity were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. ResultsThe median follow-up was 48 months (range 4–186). Local recurrence occurred in 20 (33%) patients. The 4-year local control, freedom from distant recurrence and overall survival rates were 77%, 89% and 85%, respectively. On univariate analysis, subtotal resection/biopsy (P = 0.02), tumour extension restricted to bone (P = 0.01) and gross tumour volume >130 ml (P = 0.04) were significant predictors for local recurrence. On multivariate analysis, tumour extension restricted to bone (P = 0.004) and gross total resection (P = 0.02) remained independent favourable prognostic factors for local recurrence. Twenty-four (40%), 28 (47%) and eight (11%) patients experienced acute grade 1, 2 and 3 toxicities, respectively. The 4-year late toxicity-free survival was 91%. Two patients developed secondary malignancies to the bladder 3–7 years after proton therapy. ConclusionsOur data indicate that pencil beam scanning proton therapy for sacral chordomas is both safe and effective. Gross total resection, tumour volume <130 ml and tumour restricted to the bone are favourable prognostic factors for local tumour control.

A Beam-Specific Optimization Target Volume for Stereotactic Proton Pencil Beam Scanning Therapy for Locally Advanced Pancreatic Cancer

PurposeWe investigate two margin-based schemes for optimization target volumes (OTV), both isotropic expansion (2 mm) and beam-specific OTV, to account for uncertainties due to the setup errors and range uncertainties in pancreatic stereotactic pencil beam scanning (PBS) proton therapy. Also, as 2-mm being one of the extreme sizes of margin, we also study whether the plan quality of 2-mm uniform expansion could be comparable to other plan schemes. Methods and MaterialsWe developed 2 schemes for OTV: (1) a uniform expansion of 2 mm (OTV2mm) for setup uncertainty and (2) a water equivalent thickness–based, beam-specific expansion (OTVWET) on beam direction and 2 mm expansion laterally. Six LAPC patients were planned with a prescribed dose of 33 Gy (RBE) in 5 fractions. Robustness optimization (RO) plans on gross tumor volumes, with setup uncertainties of 2 mm and range uncertainties of 3.5%, were implemented as a benchmark. ResultsAll 3 optimization schemes achieved decent target coverage with no significant difference. The OTV2mm plans show superior organ at risk (OAR) sparing, especially for proximal duodenum. However, OTV2mm plans demonstrate severe susceptibility to range and setup uncertainties with a passing rate of 19% of the plans meeting the goal of 95% volume covered by the prescribed dose. The proposed dose spread function analysis shows no significant difference. ConclusionsThe use of OTVWET mimics a union volume for all scenarios in robust optimization but saves optimization time noticeably. The beam-specific margin can be attractive to online adaptive stereotactic body proton therapy owing to the efficiency of the plan optimization.

Proton vs. photon radiotherapy for MR-guided dose escalation of intraprostatic lesions

Background Dose escalation has been associated with improved biochemical control for prostate cancer. Focusing the high dose on the MRI-defined intraprostatic lesions (IL) could spare the surrounding organs at risk and hence allow further escalation. We compare treatment efficacy between state-of-the-art focally-boosted proton and photon-based radiotherapy, and investigate possible predictive guidelines regarding individualized treatment prescriptions. Material and methods Ten prostate cancer patients with well-defined ILs were selected. Multiparametric MRI was used to delineate ILs, which were transferred to the planning CT via image registration. Pencil beam scanning proton therapy and volumetric modulated arc therapy treatment plans, were created for each patient. Each modality featured 6 plans: (1) moderately hypofractionated dose: 70 Gy to the prostate in 28 fractions, (2)–(6) plan 1 plus additional simultaneous-integrated-boost to ILs to 75.6, 81.2, 86.6, 98 and 112 Gy in 28 fractions. Equivalent dose to 2 Gy-per-fraction (EqD2) was used to calculate tumor control (TCP) and normal tissue complication probabilities (NTCP) for ILs and organs-at-risk. Results For both modalities, the maximum necessary dose to achieve TCP > 99% was 98 Gy for very high-risk ILs. For lower risk ILs lower doses were sufficient. NTCP was <25% and 35% for protons and photons at the maximum dose escalation, respectively. For the cases and beam characteristics considered, proton therapy was dosimetrically superior when IL was >4 cc or located <2.5 mm from the rectum. Conclusion This work demonstrated the potential role for proton therapy in the setting of prostate focal dose escalation. We propose that anatomical characteristic could be used as criteria to identify patients who would benefit from proton treatment.

Clinical Outcomes of Pencil Beam Scanning Proton Therapy in Locally Advanced Non-Small Cell Lung Cancer: Propensity Score Analysis.

Simple SummaryWe analyzed the oncologic outcomes and toxicities after intensity-modulated radiation therapy (IMRT) or pencil beam scanning proton therapy (PBSPT) in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiation therapy. Due to an imbalance in baseline characteristics between IMRT and PBSPT, we used propensity score-based statistical analysis. Regarding radiation therapy planning, PBSPT exhibited superior sparing of the lung, heart, and spinal cord compared to intensity-modulated (photon) radiotherapy in patients with advanced NSCLC. However, PBSPT resulted in higher incidence of grade 3 or more dermatitis and esophagitis compared to IMRT. Despite declined baseline lung function, PBSPT demonstrated a comparable rate of symptomatic radiation pneumonitis compared to IMRT. PBSPT could be an effective and safe treatment technique with comparable locoregional control.This study compared the efficacy and safety of pencil beam scanning proton therapy (PBSPT) versus intensity-modulated (photon) radiotherapy (IMRT) in patients with stage III non-small cell lung cancer (NSCLC). We retrospectively reviewed 219 patients with stage III NSCLC who received definitive concurrent chemoradiotherapy between November 2016 and December 2018. Twenty-five patients (11.4%) underwent PBSPT (23 with single-field optimization) and 194 patients (88.6%) underwent IMRT. Rates of locoregional control (LRC), overall survival, and acute/late toxicities were compared between the groups using propensity score-adjusted analyses. Patients treated with PBSPT were older (median: 67 vs. 62 years) and had worse pulmonary function at baseline (both FEV1 and DLCO) compared to those treated with IMRT. With comparable target coverage, PBSPT exhibited superior sparing of the lung, heart, and spinal cord to radiation exposure compared to IMRT. At a median follow-up of 21.7 (interquartile range: 16.8–26.8) months, the 2-year LRC rates were 72.1% and 84.1% in the IMRT and PBSPT groups, respectively (p = 0.287). The rates of grade ≥ 3 esophagitis were 8.2% and 20.0% after IMRT and PBSPT (p = 0.073), respectively, while corresponding rates of grade ≥ 2 radiation pneumonitis were 28.9% and 16.0%, respectively (p = 0.263). PBSPT appears to be an effective and safe treatment technique even for patients with poor lung function, and it does not jeopardize LRC.

Risk of radiation-induced second malignant neoplasms from photon and proton radiotherapy in paediatric abdominal neuroblastoma.

Background and PurposeState-of-the-art radiotherapy modalities have the potential of reducing late effects of treatment in childhood cancer survivors. Our aim was to investigate the carcinogenic risk associated with 3D conformal (photon) radiation (3D-CRT), intensity modulated arc therapy (IMAT) and pencil beam scanning proton therapy (PBS-PT) in the treatment of paediatric abdominal neuroblastoma.Materials and MethodsThe risk of radiation-induced second malignant neoplasm (SMN) was estimated using the concept of organ equivalent dose (OED) for eleven organs (lungs, rectum, colon, stomach, small intestine, liver, bladder, skin, central nervous system (CNS), bone, and soft tissues). The risk ratio (RR) between radiotherapy modalities and lifetime absolute risks (LAR) were reported for twenty abdominal neuroblastoma patients (median, 4y; range, 1-9y) historically treated with 3D-CRT that were also retrospectively replanned for IMAT and PBS-PT.ResultsThe risk of SMN due to primary radiation was reduced in PBS-PT against 3D-CRT and IMAT for most patients and organs. The RR across all organs ranged from 0.38 ± 0.22 (bladder) to 0.98 ± 0.04 (CNS) between PBS-PT and IMAT, and 0.12 ± 0.06 (rectum and bladder) to 1.06 ± 0.43 (bone) between PBS-PT and 3D-CRT. The LAR for most organs was within 0.01–1% (except the colon) with a cumulative risk of 21 ± 13%, 35 ± 14% and 35 ± 16% for PBS-PT, IMAT and 3D-CRT, respectively.ConclusionsPBS-PT was associated with the lowest risk of radiation-induced SMN compared to IMAT and 3D-CRT in abdominal neuroblastoma treatment. Other clinical endpoints and plan robustness should also be considered for optimal plan selection.

Applications of a novel detector for pencil beam scanning proton therapy beam quality assurance

This study utilized a new type of detector, the CROSS II (Liverage Biomedical Inc., Taiwan), to perform a beam quality assurance (QA) procedure on a Sumitomo (Sumitomo Heavy Industries, Inc., Japan) pencil beam linear scanning proton therapy machine. The Cross II can monitor proton Pristine Bragg peak range, beam width, beam size, beam position, and scanning speed. All the data presented here were collected during a time span of over one year. The accuracy of the QA program could be verified if all the QA items were tested stably and within the programmed tolerances. Our results showed that the proton range remained within the [Formula: see text] mm tolerance, with the majority of measurements within [Formula: see text] mm, [Formula: see text] mm for spot size, 1.5 mm for spot position, and [Formula: see text]% for scanning speed. We found that the CROSS II detector is in high precise and steady state with highly efficient. Our proton therapy system was also proven to be in an accurate and reliable condition according to our QA results.

Innovations and the Use of Collimators in the Delivery of Pencil Beam Scanning Proton Therapy.

PurposeThe development of collimating technologies has become a recent focus in pencil beam scanning (PBS) proton therapy to improve the target conformity and healthy tissue sparing through field-specific or energy-layer–specific collimation. Given the growing popularity of collimators for low-energy treatments, the purpose of this work was to summarize the recent literature that has focused on the efficacy of collimators for PBS and highlight the development of clinical and preclinical collimators.Materials and MethodsThe collimators presented in this work were organized into 3 categories: per-field apertures, multileaf collimators (MLCs), and sliding-bar collimators. For each case, the system design and planning methodologies are summarized and intercompared from their existing literature. Energy-specific collimation is still a new paradigm in PBS and the 2 specific collimators tailored toward PBS are presented including the dynamic collimation system (DCS) and the Mevion Adaptive Aperture.ResultsCollimation during PBS can improve the target conformity and associated healthy tissue and critical structure avoidance. Between energy-specific collimators and static apertures, static apertures have the poorest dose conformity owing to collimating only the largest projection of a target in the beam's eye view but still provide an improvement over uncollimated treatments. While an external collimator increases secondary neutron production, the benefit of collimating the primary beam appears to outweigh the risk. The greatest benefit has been observed for low- energy treatment sites.ConclusionThe consensus from current literature supports the use of external collimators in PBS under certain conditions, namely low-energy treatments or where the nominal spot size is large. While many recent studies paint a supportive picture, it is also important to understand the limitations of collimation in PBS that are specific to each collimator type. The emergence and paradigm of energy-specific collimation holds many promises for PBS proton therapy.

Proton Therapy for Skull-Base Chordomas and Chondrosarcomas: Initial Results From the Beaumont Proton Therapy Center.

Background:Skull-base chordomas and chondrosarcomas are rare tumors that arise directly adjacent to important critical structures. Appropriate management consists of maximal safe resection followed by postoperative dose-escalated radiation therapy. Proton beam therapy is often employed in this context to maximize the sparing of organs at risk, such as the brainstem and optic apparatus.Methods: This is a single-institutional experience treating skull-base chordomas and chondrosarcomas with postoperative pencil beam scanning proton therapy. We employed a simultaneous integrated boost to the gross tumor volume (GTV) for increased conformality. Demographic, clinicopathologic, toxicity, and dosimetry information were collected. Toxicity was assessed according to Common Terminology Criteria for Adverse Events (CTCAE), v. 4.0.Results: Between 2017 and 2020, 13 patients were treated with postoperative proton therapy. There were 10 patients with chordoma (77%) and three with chondrosarcoma (23%). A gross total resection was achieved in six (60%) patients with chordoma and one patient with chondrosarcoma (33%). Nine patients (69%) received postoperative therapy, whereas four (31%) received treatment at recurrence/progression following re-excision. The median dose to the GTV was 72.4 cobalt-Gray equivalents (range, 70.0 to 75.8). The mean GTV was 3.4 cc (range, 0.2-38.7). There were no grade 3 or greater toxicities. One patient developed grade 2 temporal lobe necrosis. At 10.7 months' median follow-up (range, 2.1-30.6), the rates of local control and overall survival were 100%.Conclusions: Proton beam therapy with pencil beam scanning and simultaneous integrated boost to the GTV affords excellent early local control with the suggestion of low morbidity. This method deserves consideration as an optimal method for limiting dose to adjacent organs at risk and delivering clinically effective doses to the treatment volume.

Commissioning of a clinical pencil beam scanning proton therapy unit for ultra‐high dose rates (FLASH)

The purpose of this work was to provide a flexible platform for FLASH research with protons by adapting a former clinical pencil beam scanning gantry to irradiations with ultra-high dose rates. PSI Gantry 1 treated patients until December 2018. We optimized the beamline parameters to transport the 250MeV beam extracted from the PSI COMET accelerator to the treatment room, maximizing the transmission of beam intensity to the sample. We characterized a dose monitor on the gantry to ensure good control of the dose, delivered in spot-scanning mode. We characterized the beam for different dose rates and field sizes for transmission irradiations. We explored scanning possibilities in order to enable conformal irradiations or transmission irradiations of large targets (with transverse scanning). We achieved a transmission of 86% from the cyclotron to the treatment room. We reached a peak dose rate of 9000Gy/s at 3mm water equivalent depth, along the central axis of a single pencil beam. Field sizes of up to 5×5mm2 were achieved for single-spot FLASH irradiations. Fast transverse scanning allowed to cover a field of 16×1.2cm2 . With the use of a nozzle-mounted range shifter, we are able to span depths in water ranging from 19.6 to 37.9cm. Various dose levels were delivered with precision within less than 1%. We have realized a proton FLASH irradiation setup able to investigate continuously a wide dose rate spectrum, from 1 to 9000Gy/s in single-spot irradiation as well as in the pencil beam scanning mode. As such, we have developed a versatile test bench for FLASH research.

An approach for estimating dosimetric uncertainties in deformable dose accumulation in pencil beam scanning proton therapy for lung cancer

Deformable image registration (DIR) is an important component for dose accumulation and associated clinical outcome evaluation in radiotherapy. However, the resulting deformation vector field (DVF) is subject to unavoidable discrepancies when different algorithms are applied, leading to dosimetric uncertainties of the accumulated dose. We propose here an approach for proton therapy to estimate dosimetric uncertainties as a consequence of modeled or estimated DVF uncertainties. A patient-specific DVF uncertainty model was built on the first treatment fraction, by correlating the magnitude differences of five DIR results at each voxel to the magnitude of any single reference DIR. In the following fractions, only the reference DIR needs to be applied, and DVF geometric uncertainties were estimated by this model. The associated dosimetric uncertainties were then derived by considering the estimated geometric DVF uncertainty, the dose gradient of fractional recalculated dose distribution and the direction factor from the applied reference DIR of this fraction. This estimated dose uncertainty was respectively compared to the reference dose uncertainty when different DIRs were applied individually for each dose warping. This approach was validated on seven NSCLC patients, each with nine repeated CTs. The proposed model-based method is able to achieve dose uncertainty distribution on a conservative voxel-to-voxel comparison within ±5% of the prescribed dose to the ‘reference’ dosimetric uncertainty, for 77% of the voxels in the body and 66%–98% of voxels in investigated structures. We propose a method to estimate DIR induced uncertainties in dose accumulation for proton therapy of lung tumor treatments.

Development and validation of the Dynamic Collimation Monte Carlo simulation package for pencil beam scanning proton therapy.

The aim of this work was to develop and experimentally validate a Dynamic Collimation Monte Carlo (DCMC) simulation package specifically designed for the simulation of collimators in pencil beam scanning proton therapy (PBS-PT). The DCMC package was developed using the TOPAS Monte Carlo platform and consists of a generalized PBS source model and collimator component extensions. A divergent point-source model of the IBA dedicated nozzle (DN) at the Miami Cancer Institute (MCI) was created and validated against on-axis commissioning measurements taken at MCI. The beamline optics were mathematically incorporated into the source to model beamlet deflections in the X and Y directions at the respective magnet planes. Off-axis measurements taken at multiple planes in air were used to validate both the off-axis spot size and divergence of the source model. The DCS trimmers were modeled and incorporated as TOPAS geometry extensions that linearly translate and rotate about the bending magnets. To validate the collimator model, a series of integral depth dose (IDD) and lateral profile measurements were acquired at MCI and used to benchmark the DCMC performance for modeling both pristine and range shifted beamlets. The water equivalent thickness (WET) of the range shifter was determined by quantifying the shift in the depth of the 80% dose point distal to the Bragg peak between the range shifted and pristine uncollimated beams. A source model of the IBA DN system was successfully commissioned against on- and off-axis IDD and lateral profile measurements performed at MCI. The divergence of the source model was matched through an optimization of the source-to-axis distance and comparison against in-air spot profiles. The DCS model was then benchmarked against collimated IDD and in-air and in-phantom lateral profile measurements. Gamma analysis was used to evaluate the agreement between measured and simulated lateral profiles and IDDs with 1%/1mm criteria and a 1% dose threshold. For the pristine collimated beams, the average 1%/1mm gamma pass rates across all collimator configurations investigated were 99.8% for IDDs and 97.6% and 95.2% for in-air and in-phantom lateral profiles. All range shifted collimated IDDs passed at 100% while in-air and in-phantom lateral profiles had average pass rates of 99.1% and 99.8%, respectively. The measured and simulated WET of the polyethylene range shifter was determined to be 40.9 and 41.0mm, respectively. We have developed a TOPAS-based Monte Carlo package for modeling collimators in PBS-PT. This package was then commissioned to model the IBA DN system and DCS located at MCI using both uncollimated and collimated measurements. Validation results demonstrate that the DCMC package can be used to accurately model other aspects of a DCS implementation via simulation.

Combining rescanning and gating for a time-efficient treatment of mobile tumors using pencil beam scanning proton therapy

Background and purposeRespiratory motion during proton therapy can severely degrade dose distributions, particularly due to interplay effects when using pencil beam scanning. Combined rescanning and gating treatments for moving tumors mitigates dose degradation, but at the cost of increased treatment delivery time. The objective of this study was to identify the time efficiency of these dose degradation-motion mitigation strategies for different range of motions. Materials and methodsSeventeen patients with thoracic or abdominal tumors were studied. Tumor motion amplitudes ranged from 2–30 mm. Deliveries using different combinations of rescanning and gating were simulated with a dense dose spot grid (4 × 4 × 2.5 mm3) for all patients and a sparse dose spot grid (8 × 8 × 5 mm3) for six patients with larger tumor movements (>8 mm). The resulting plans were evaluated in terms of CTV coverage and time efficiency. ResultsBased on the studied patient cohort, it has been shown that for amplitudes up to 5 mm, no motion mitigation is required with a dense spot grid. For amplitudes between 5 and 10 mm, volumetric rescanning should be applied while maintaining a 100% duty cycle when using a dense spot grid. Although gating could be envisaged to reduce the target volume for intermediate motion, it has been shown that the dose to normal tissues would only be reduced marginally. Moreover, the treatment time would increase. Finally, for larger motion amplitudes, both volumetric rescanning and respiratory gating should be applied with both spot grids. In addition, it has been shown that a dense spot grid delivers better CTV dose coverage than a sparse dose grid. ConclusionVolumetric rescanning and/or respiratory gating can be used in order to effectively and efficiently mitigate dose degradation due to tumor movement.

Proton therapy delivery method affects dose-averaged linear energy transfer in patients

The dosimetric advantages of proton therapy have led to its rapid proliferation in recent decades. This has been accompanied by a shift in technology from older units that deliver protons by passive scattering (PS) to newer units that increasingly use pencil-beam scanning (PBS). The biologic effectiveness of proton physical dose purportedly rises with increasing dose-weighted average linear energy transfer (LETD). The objective of this study was to determine the extent to which proton delivery methods affect LETD. We calculated LETD from simple, dosimetrically matched, and clinical treatment plans with TOPAS Monte-Carlo transport code. Simple treatment plans comprised single fields of PS and PBS protons in a water phantom. We performed simulations of matched and clinical treatment plans by using the treatment and anatomic data obtained from a cohort of children with craniopharyngioma who previously received PS or PBS proton therapy. We compared the distributions of LETD from PS and PBS delivery methods in clinically relevant ROIs. Wilcoxon signed-rank tests comparing single fields in water revealed that the LETD values from PBS were significantly greater than those from PS inside and outside the targeted volume (p < 0.01). Statistical tests comparing LETD-volume histograms from matched and clinical treatment plans showed that LETD was generally greater for PBS treatment plans than for PS treatment plans (p < 0.05). In conclusion, the proton delivery method affects LETD both inside and outside of the target volume. These findings suggest that PBS is more biologically effective than PS. Given the rapid expansion of PBS proton therapy, future studies are needed to confirm the applicability of treatment evaluation methods developed for PS proton therapy to those for modern PBS treatments to ensure their safety and effectiveness for the growing population of patients receiving proton therapy. This study uses data from two clinical trials: NCT01419067 and NCT02792582.

Plan quality effects of maximum monitor unit constraints in pencil beam scanning proton therapy for central nervous system and skull base tumors

Purpose/objective(s)With reports of CNS toxicity in patients treated with proton therapy at doses lower than would be expected based on photon data, it has been proposed that heavy monitor unit (MU) weighting of pencil beam scanning (PBS) proton therapy spots may potentially increase the risk of toxicity. We evaluated the impact of maximum MU weighting per spot (maxMU/spot) restrictions on PBS plan quality, prior to implementing clinic-wide maxMU/spot restrictions. Materials/methodsPBS plans of 11 patients, of which 3 plans included boosts, for a total of 14 PBS sample cases were included. Per sample case, a single dosimetrist created 4 test plans, gradually reducing the maxMU/spot in the plan. Test Plan 1, unrestricted in maxMU/spot, was the reference for all restricted plan comparisons (comparison sets 2 vs. 1; 3 vs. 1; and 4 vs. 1). The impact of MU/spot restrictions on plan quality metrics were analyzed with Wilcoxon signed rank test analyses. Treatment delivery time was modeled for a representative case. ResultsA total of 14 PBS sample cases, 7 (50%) single-field optimized, 7 (50%) multi-field optimized, 9 (64%) delivering > 3500 cGy, 9 (64%) with 3 beams, and 7 (50%) without a range shifter were included. There were no differences in plan quality metrics of target coverage (V95% and V100% prescription), conformality and gradient indices, hot spot volume (V105% prescription), and dose to normal brain (V10%/30%/50%/70%/90%/100% prescription) with reductions of allowable maxMU/spot across all comparison sets (p > 0.05). Max MU/spot restrictions did not increase treatment delivery time when analyzed for a representative case. ConclusionMaxMU/spot restrictions within the thresholds evaluated in this study did not degrade overall plan quality metrics. Future studies should evaluate spot weighting with linear energy transfer/relative biologic effectiveness-informed planning to determine if spot weighting manipulation impacts clinical outcomes and mitigates toxicity.

Characterization of penumbra sharpening and scattering by adaptive aperture for a compact pencil beam scanning proton therapy system.

To quantitatively access penumbra sharpening and scattering by adaptive aperture (AA) under various beam conditions and clinical cases for a Mevion S250i compact pencil beam scanning proton therapy system. First, in-air measurements were performed using a scintillation detector for single spot profile and lateral penumbra for five square field sizes (3×3 to 18×18cm2 ), three energies (33.04, 147.36, and 227.16MeV), and three snout positions (5, 15, and 33.6cm) with Open and AA field. Second, treatment plans were generated in RayStation treatment planning system (TPS) for various combination of target size (3- and 10-cm cube), target depth (5, 10, and 15cm) and air gap (5-20cm) for both Open and AA field. These plans were delivered to EDR2 films in the solid water and penumbra reduction by AA was quantified. Third, the effect of the AA scattered protons on the surface dose was studied at 5mm depth by EDR2 film and the RayStation TPS computation. Finally, dosimetric advantage of AA over Open field was studied for five brain and five prostate cases using the TPS simulation. The spot size changed dramatically from 3.8mm at proton beam energy of 227.15MeV to 29.4mm at energy 33.04MeV. In-air measurements showed that AA substantially reduced the lateral penumbra by 30% to 60%. The EDR2 film measurements in solid water presented the maximum penumbra reduction of 10 to 14mm depending on the target size. The maximum increase of 25% in field edge dose at 5mm depth as compared to central axis was observed. The substantial penumbra reduction by AA produced less dose to critical structures for all the prostate and brain cases. Adaptive aperture sharpens the penumbra by factor of two to three depending upon the beam condition. The absolute penumbra reduction with AA was more noticeable for shallower target, smaller target, and larger air gap. The AA-scattered protons contributed to increase in surface dose. Clinically, AA reduced the doses to critical structures.

Dosimetric Effect of Biozorb Markers for Accelerated Partial Breast Irradiation in Proton Therapy.

PurposeTo investigate dosimetric implications of biodegradable Biozorb (BZ) markers for proton accelerated partial breast irradiation (APBI) plans.Materials and MethodsSix different BZs were placed within in-house breast phantoms to acquire computed tomography (CT) images. A contour correction method with proper mass density overriding for BZ titanium clip and surrounding tissue was applied to minimize inaccuracies found in the CT images in the RayStation planning system. Each breast phantom was irradiated by a monoenergetic proton beam (103.23 MeV and 8×8 cm2) using a pencil-beam scanning proton therapy system. For a range perturbation study, doses were measured at 5 depths below the breast phantoms by using an ionization chamber and compared to the RayStation calculations with 3 scenarios for the clip density: the density correction method (S1: 1.6 g/cm3), raw CT (S2), and titanium density (S3: 4.54 g/cm3). For the local dose perturbation study, the radiographic EDR2 film was placed at 0 and 2 cm below the phantoms and compared to the RayStation calculations. Clinical effects of the perturbations were retrospectively examined with 10 APBI plans for the 3 scenarios (approved by our institutional review board).ResultsIn the range perturbation study, the S1 simulation showed a good agreement with the chamber measurements, while excess pullbacks of 1∼2 mm were found in the S2 and S3 simulations. The film study showed local dose shadowing and perturbation by the clips that RayStation could not predict. In the plan study, no significant differences in the plan quality were found among the 3 scenarios. However, substantial range pullbacks were observed for S3.ConclusionThe density correction method could minimize the dose and range difference between measurement and RayStation prediction. It should be avoided to simply override the known physical density of the BZ clips for treatment planning owing to overestimation of the range pullback.

Investigating volumetric repainting to mitigate interplay effect on 4D robustly optimized lung cancer plans in pencil beam scanning proton therapy.

PurposeThe interplay effect between dynamic pencil proton beams and motion of the lung tumor presents a challenge in treating lung cancer patients in pencil beam scanning (PBS) proton therapy. The main purpose of the current study was to investigate the interplay effect on the volumetric repainting lung plans with beam delivery in alternating order (“down” and “up” directions), and explore the number of volumetric repaintings needed to achieve acceptable lung cancer PBS proton plan.MethodThe current retrospective study included ten lung cancer patients. The total dose prescription to the clinical target volume (CTV) was 70 Gy(RBE) with a fractional dose of 2 Gy(RBE). All treatment plans were robustly optimized on all ten phases in the 4DCT data set. The Monte Carlo algorithm was used for the 4D robust optimization, as well as for the final dose calculation. The interplay effect was evaluated for both the nominal (i.e., without repainting) as well as volumetric repainting plans. The interplay evaluation was carried out for each of the ten different phases as the starting phases. Several dosimetric metrics were included to evaluate the worst‐case scenario (WCS) and bandwidth based on the results obtained from treatment delivery starting in ten different breathing phases.ResultsThe number of repaintings needed to meet the criteria 1 (CR1) of target coverage (D95% ≥ 98% and D99% ≥ 97%) ranged from 2 to 10. The number of repaintings needed to meet the CR1 of maximum dose (ΔD1% < 1.5%) ranged from 2 to 7. Similarly, the number of repaintings needed to meet CR1 of homogeneity index (ΔHI < 0.03) ranged from 3 to 10. For the target coverage region, the number of repaintings needed to meet CR1 of bandwidth (<100 cGy) ranged from 3 to 10, whereas for the high‐dose region, the number of repaintings needed to meet CR1 of bandwidth (<100 cGy) ranged from 1 to 7. Based on the overall plan evaluation criteria proposed in the current study, acceptable plans were achieved for nine patients, whereas one patient had acceptable plan with a minor deviation.ConclusionThe number of repaintings required to mitigate the interplay effect in PBS lung cancer (tumor motion < 15 mm) was found to be highly patient dependent. For the volumetric repainting with an alternating order, a patient‐specific interplay evaluation strategy must be adopted. Determining the optimal number of repaintings based on the bandwidth and WCS approach could mitigate the interplay effect in PBS lung cancer treatment.

Technical Note: Investigating interplay effects in pencil beam scanning proton therapy with a 4D XCAT phantom within the RayStation treatment planning system.

Pencil beam scanning (PBS) for moving targets is known to be impacted by interplay effects. Four-dimensional computed tomography (4DCT)-based motion evaluation is crucial for understanding interplay and developing mitigation strategies. Availability of high-quality 4DCTs with variable breathing traces is limited. Purpose of this work is the development of a framework for interplay analysis using 4D-XCAT phantoms in conjunction with time-resolved irradiation patterns in a commercial treatment planning system (TPS). Four-dimensional dynamically accumulated dose distributions (4DDDs) are simulated in an in-silico study for a PBS liver treatment. An XCAT phantom with 50 phases, varying linearly in amplitude each by 1mm, was combined with the RayStation TPS (7.99.10). Deformable registration was used with time-resolved dose calculation, mapping XCAT phases to motion signals. To illustrate the applicability of the method a two-field liver irradiation plan was used. A variety sin4 type motion signals, varying in amplitude (1-20mm), period (1.6-5.2s) and phase (0-2π) were applied. Either single variable variations or random combinations were selected. The interplay effect within a clinical target (5cm diameter) was characterized in terms of homogeneity index (HI5), with and without five paintings. In total 2092 scenarios were analyzed within RayStation. A framework is presented for interplay research, allowing for flexibility in determining motion management techniques, increasing reproducibility, and enabling comparisons of different methods. A case study showed the interplay effect was correlated with amplitude and strongly affected by the starting phase, leading to large variance. The average of all scenarios (single fraction) resulted in HI5 of 0.31 (±0.11), while introduction of five times layered repainting reduced this to 0.11(±0.03). The developed framework, which uses the XCAT phantom and RayStation, allows detailed analysis of motion in context of PBS with comparable results to clinical cases. Flexibility in defining motion patterns for detailed anatomies in combination with time-resolved dose calculation, facilitates investigation of optimal treatment and motion mitigation strategies.

Dosimetric impact of random spot positioning errors in intensity modulated proton therapy plans of small and large volume tumors

To study dosimetric impact of random spot positioning errors on the clinical pencil beam scanning proton therapy plans. IMPT plans of 10 patients who underwent proton therapy for tumors in brain or pelvic regions representing small and large volumes, respectively, were included in the study. Spot positioning errors of 1 mm, -1 mm or ±1 mm were introduced in these clinical plans by modifying the geometrical co-ordinates of proton spots using a script in the MATLAB programming environment. Positioning errors were simulated to certain numbers of (20%, 40%, 60%, 80%) randomly chosen spots in each layer of these treatment plans. Treatment plans with simulated errors were then imported back to the Raystation (Version 7) treatment planning system and the resultant dose distribution was calculated using Monte-Carlo dose calculation algorithm.Dosimetric plan evaluation parameters for target and critical organs of nominal treatment plans delivered for clinical treatments were compared with that of positioning error simulated treatment plans. For targets, D95% and D2% were used for the analysis. Dose received by optic nerve, chiasm, brainstem, rectum, sigmoid, and bowel were analyzed using relevant plan evaluation parameters depending on the critical structure. In case of intracranial lesions, the dose received by 0.03 cm3 volume (D0.03 cm3) was analyzed for optic nerve, chiasm and brainstem. In rectum, the volume of it receiving a dose of 65 Gy(RBE) (V65) and 40 Gy(RBE) (V40) were compared between the nominal and error introduced plans. Similarly, V65 and V63 were analyzed for Sigmoid and V50 and V15 were analyzed for bowel. The maximum dose variation in PTV D95% (1.88 %) was observed in a brain plan in which the target volume was the smallest (2.7 cm3) among all 10 plans included in the study. This variation in D95% drops down to 0.3% for a sacral chordoma plan in which the PTV volume is significantly higher at 672 cm3. The maximum difference in OARs in terms of absolute dose (D0.03 cm3) was found in left optic nerve (9.81%) and the minimum difference was observed in brainstem (2.48%). Overall, the magnitude of dose errors in chordoma plans were less significant in comparison to brain plans. The dosimetric impact of different error scenarios in spot positioning becomes more prominent for treatment plans involving smaller target volume compared to plans involving larger target volumes. Provides information on the dosimetric impact of various possible spot positioning errors and its dependence on the tumor volume in intensity modulated proton therapy.