Pencil Beam Scanning Research Articles

Investigating aperture-based approximations to model a focused dynamic collimation system for pencil beam scanning proton therapy

Purpose. The Dynamic Collimation System (DCS) is an energy layer-specific collimation device designed to reduce the lateral penumbra in pencil beam scanning proton therapy. The DCS consists of two pairs of nickel trimmers that rapidly and independently move and rotate to intercept the scanning proton beam and an integrated range shifter to treat targets less than 4 cm deep. This work examines the validity of a single aperture approximation to model the DCS, a commonly used approximation in commercial treatment planning systems, as well as higher-order aperture-based approximations for modeling DCS-collimated dose distributions. Methods. An experimentally validated TOPAS/Geant4-based Monte Carlo model of the DCS integrated with a beam model of the IBA pencil beam scanning dedicated nozzle was used to simulate DCS- and aperture-collimated 100 MeV beamlets and composite treatment plans. The DCS was represented by three different aperture approximations: a single aperture placed halfway between the upper and lower trimmer planes, two apertures located at the upper and lower trimmer planes, and four apertures, located at both the upstream and downstream faces of each pair of trimmers. Line profiles and three-dimensional regions of interest were used to evaluate the validity and limitations of the aperture approximations investigated. Results. For pencil beams without a range shifter, minimal differences were observed between the DCS and single aperture approximation. For range shifted beamlets, the single aperture approximation yielded wider penumbra widths (up to 18%) in the X-direction and sharper widths (up to 9.4%) in the Y-direction. For the example treatment plan, the root-mean-square errors (RMSEs) in an overall three-dimensional region of interest were 1.7%, 1.3%, and 1.7% for the single aperture, two aperture, and four aperture models, respectively. If the region of interest only encompasses the lateral edges outside of the target, the resulting RMSEs were 1.7%, 1.1%, and 0.5% single aperture, two aperture, and four aperture models, respectively. Conclusions. Monte Carlo simulations of the DCS demonstrated that a single aperture approximation is sufficient for modeling pristine fields at the Bragg depth while range shifted fields require a higher-order aperture approximation. For the treatment plan considered, the double aperture model performed the best overall, however, the four-aperture model most accurately modeled the lateral field edges at the expense of increased dose differences proximal to and within the target.

Technical challenges in the treatment of mediastinal lymphomas by proton pencil beam scanning and deep inspiration breath-hold

PurposeTo comprehensively describe the treatment of mediastinal lymphoma by pencil beam scanning (PBS) proton therapy. MethodsFourteen patients underwent PBS proton treatment in a supine position in deep inspiration breath-hold (DIBH). Three DIBH computed tomography (CT) scans were acquired for each patient to delineate the Internal Target Volume (ITV). Intensity-modulated proton therapy (IMPT) was planned by min–max robust optimization on the ITV, with a 6 mm setup and 3.5% range uncertainties. Robustness analysis was performed and dose coverage was visually inspected on the corresponding voxel-wise minimum map. Layer repainting was set equal to 5 to compensate for cardiac motion. Intra-fraction reproducibility during treatment was assessed by repeated daily DIBH X-ray imaging. Finally, an additional CT was acquired at half treatment to estimate the impact of inter-fraction dosimetric reproducibility. ResultsIMPT guaranteed robust mediastinal target coverage and organs-at-risk sparing. However, visual voxel-wise robustness evaluation showed that in five patients a second optimization with focused objectives in the cost-function was necessary to achieve a robust coverage of the target regions at the interface between lungs and soft tissue. In six patients, repainting was not used due to excessive treatment time length and poor patient compliance. Intra-fraction average reproducibility was within 1 mm/1degree. On repeated CT scans, inter-fraction setup errors and/or anatomical changes showed minimal dosimetric differences in CTV coverage. ConclusionIMPT in DIBH is effective and reproducible to treat mediastinal lymphomas. Caution is recommended to guarantee robust dose delivery to high-risk regions at the interface between lungs and soft tissue.

Out-of-field doses in pediatric craniospinal irradiations with 3D-CRT, VMAT, and scanning proton radiotherapy: A phantom study.

Craniospinal irradiation (CSI) has greatly increased survival rates for patients with a diagnosis of medulloblastoma and other primitive neuroectodermal tumors. However, as it includes exposure of a large volume of healthy tissue to unwanted doses, there is a strong concern about the complications of the treatment, especially for the children. To estimate the risk of second cancers and other unwanted effects, out-of-field dose assessment is necessary. The purpose of this study is to evaluate and compare out-of-field doses in pediatric CSI treatment using conventional and advanced photon radiotherapy (RT) and advanced proton therapy. To our knowledge, it is the first such comparison based on in-phantom measurements. Additionally, for out-of-field doses during photon RT in this and other studies, comparisons were made using analytical modeling. In order to describe the out-of-field doses absorbed in a pediatric patient during actual clinical treatment, an anthropomorphic phantom, which mimics the 10-year-old child, was used. Photon 3D-conformal RT (3D-CRT) and two advanced, highly conformal techniques: photon volumetric-modulated arc therapy (VMAT) and active pencil beam scanning (PBS) proton RT were used for CSI treatment. Radiophotoluminescent and poly-allyl-diglycol-carbonate nuclear track detectors were used for photon and neutron dosimetry in the phantom, respectively. Out-of-field doses from neutrons were expressed in terms of dose equivalent. A two-Gaussian model was implemented for out-of-field doses during photon RT. The mean VMAT photon doses per target dose to all organs in this study were under 50% of the target dose (i.e.,<500mGy/Gy), while the mean 3D-CRT photon dose to oesophagus, gall bladder, and thyroid, exceeded that value. However, for 3D-CRT, better sparing was achieved for eyes and lungs. The mean PBS photon doses for all organs were up to three orders of magnitude lower compared to VMAT and 3D-CRT and exceeded 10mGy/Gy only for the oesophagus, intestine, and lungs. The mean neutron dose equivalent during PBS for eight organs of interest (thyroid, breasts, lungs, liver, stomach, gall bladder, bladder, prostate) ranged from 1.2mSv/Gy for bladder to 23.1 mSv/Gy for breasts. Comparison of out-of-field doses in this and other phantom studies found in the literature showed that a simple and fast two-Gaussian model for out-of-field doses as a function of distance from the field edge can be applied in a CSI using photon RT techniques. PBS is the most promising technique for out-of-field dose reduction in comparison to photon techniques. Among photon techniques, VMAT is a preferred choice for most of out-of-field organs and especially for the thyroid, while doses for eyes, breasts, and lungs are lower for 3D-CRT. For organs outside the field edge, a simple analytical model can be helpful for clinicians involved in treatment planning using photon RT but also for retrospective data analysis for cancer risk estimates and epidemiology in general.

Time structure of pencil beam scanning proton FLASH beams measured with scintillator detectors and compared with log files.

Key factors in FLASH treatments are the ultra-high dose rate (UHDR) and the time structure of the beam delivery. Measurement of the time structure in pencil beam scanning (PBS) proton FLASH treatments is challenging for many types of detectors since high temporal resolution is needed. In this study, a fast scintillator detector system was developed and used to measure the individual spot durations as well as the time when the beam moves between two positions (transition duration) during PBS proton FLASH and UHDR treatments. The spot durations were compared with machine log-file recordings. A detector system based on inorganic scintillating crystals was developed. The system consisted of four detector probes made of a sub-millimeter ZnSe:O crystal that was coupled via an optical fiber to an optical reader with 50kHz sampling rate. The detector system was used in two experiments, both performed with a PBS proton beam with 250MeV beam energy and 215nA requested nozzle beam current. The sampling rate enabled multiple measurements during each spot delivery and during the beam transition between spots. First, the detector was tested in a phantom experiment, where a total of 305 scan sequences were delivered to the four detectors. The number of spots delivered without beam interruption in a single scan sequence ranged from one to 35. The spot duration and transition duration were measured for each individual spot. Secondly, the detector system was used in vivo in preclinical experiments with FLASH irradiation of mouse legs placed in the entrance plateau of the beam. A single detector was placed 1cm downstream of the irradiated mouse leg. The mouse dose ranged from 30.5 to 44.2Gy and the field consisted of 35 spots. The spot durations as well as the mean dose rate (field dose divided by the measured field duration) for each mouse were determined using the detector and then compared with the corresponding log files. The phantom experiment showed that the logged total duration of an uninterrupted spot sequence was consistently shorter than the measured duration with a difference of -0.252ms (95% confidence interval: [-0.255, -0.249ms]). This corresponded to 0.05%-0.07% of the spot sequence duration in the mice experiments. For individual spots, the mean±1SD difference between logged and measured spot duration was -0.39±0.05ms for the first spot in a sequence, 0.13±0.04ms for the last spot in a sequence, and -0.0017±0.09ms for the intermediate spots in a sequence. The measured spot transition durations were 0.20±0.04ms (5.1mm horizontal steps) and 0.50±0.04ms (5.0mm vertical steps). For the mouse experiments, the mean dose rate calculated from the measured field duration was 84.1-92.5Gy/s. It agreed with log files with a root mean square difference of 0.02Gy/s. Fiber-coupled scintillator detectors were designed with sufficient temporal resolution to measure the spot and transition duration during PBS proton UHDR deliveries. Their small volume makes them feasible for in vivo use in preclinical FLASH studies. The logged spot durations were in excellent agreement with measurements but showed small systematic errors in the logged duration for the first and last spot in a sequence.

Evaluation of beamline subsystem performance during technical commissioning of an superconducting proton therapy facility

ABSTRACT The new superconducting proton therapy facility consists of a dedicated 200 MeV superconducting cyclotron, new beamlines, a 360° gantry and a fixed beam room for eye treatment. A degrader and laminated magnets in the beamline enable rapid energy changes to modulate the range of the scanning pencil beam applied to patients. In the design of the systems, much emphasis was placed on reliability, easy maintenance, and clear separation of responsibilities. To evaluate the performance of the beamline’s subsystems, technical commissioning began as soon as a proton beam of sufficient intensity could be obtained from the cyclotron. According to the new beam’s parameters, the beamline optics were designed. A mathematical model relating magnetic field (B) and current (I) was established to determine the magnet coil currents required for the different types of magnets, whose magnetic field error was totally controlled to within 5 Gs. A 200 MeV proton beam was extracted from the cyclotron and transported to the fixed treatment room via the beam transport system within 10 days. The terminal equipment of the fixed beamline successfully detected proton beam, indicating that the physical design, engineering, manufacturing and integration of the beamline’s subsystems are highly reliable.

NTCP Modeling for High-Grade Temporal Radionecroses in a Large Cohort of Patients Receiving Pencil Beam Scanning Proton Therapy for Skull Base and Head and Neck Tumors

To develop a normal tissue complication probability model including clinical and dosimetric parameters for high-grade temporal lobe radionecroses (TRN) after pencil beam scanning proton therapy. We included data on 299 patients with skull base and head and neck tumors treated with pencil-beam scan proton therapy, with a total dose of ≥60 GyRBE (relative biological effectiveness) from May 2004 to November 2018. We considered 9 clinical and 27 dosimetric parameters for the structure-wise modeling of high-grade (grade ≥2) TRN. After eliminating strongly cross-correlated variables, we generated logistic regression models using least absolute shrinkage and selection operator regression. We performed bootstrapping to assess parameter selection robustness and evaluated model performance via cross-correlation by assessing the area under the curve of receiver operating characteristic curves and calibration with a Hosmer-Lemeshow test statistic. After a median radiologic follow-up of 51.5 months (range, 4-190), 27 patients (9%) developed grade ≥2 TRN. Eleven patients had bitemporal necrosis, resulting in 38 events in 598 temporal lobes for structure-wise analysis. During our bootstrapping analysis, we found that the highest selection frequency was for prescription dose, followed by age, V40Gy (%), hypertension, and dose to at least 1 cc (D1cc) (Gy) in the temporal lobe. During our cross-validation, we found that age*prescription-dose*D1cc (Gy)*hypertension was superior in all described test statistics. We built full cohort structure-wise and patient-wise models with maximum area under the curve of receiver operating characteristic curves of 0.79 (structure-wise) and 0.76 (patient-wise). While developing a logistic regression normal tissue complication probability model to predict grade ≥2 TRN, the best fit was found for the model containing age, prescription dose, D1cc (Gy), and hypertensive blood pressure as risk factors. External validation will be the next step to improve generalizability and potential introduction into clinical routine.

Beam properties within the momentum acceptance of a clinical gantry beamline for proton therapy.

Energy changes in pencil beam scanning proton therapy can be a limiting factor in delivery time, hence, limiting patient throughput and the effectiveness of motion mitigation techniques requiring fast irradiation. In this study, we investigate the feasibility of performing fast and continuous energy modulation within the momentum acceptance of a clinical beamline for proton therapy. The alternative use of a local beam degrader at the gantry coupling point has been compared with a more common upstream regulation. Focusing on clinically relevant parameters, a complete beam properties characterization has been carried out. In particular, the acquired empirical data allowed to model and parametrize the errors in range and beam current to deliver clinical treatment plans. For both options, the local and upstream degrader, depth-dose curves measured in water for off-momentum beams were only marginally distorted (γ(1%, 1mm)>90%) and the errors in the spot position were within the clinical tolerance, even though increasing at the boundaries of the investigated scan range. The impact on the beam size was limited for the upstream degrader, while dedicated strategies could be required to tackle the beam broadening through the local degrader. Range correction models were investigated for the upstream regulation. The impaired beam transport required a dedicated strategy for fine range control and compensation of beam intensity losses. Our current parameterization based on empirical data allowed energy modulation within acceptance with range errors (median 0.05mm) and transmission (median -14%) compatible with clinical operation and remarkably low average 27ms dead time for small energy changes. The technique, tested for the delivery of a skull glioma treatment, resulted in high gamma pass rates at 1%, 1mm compared to conventional deliveries in experimental measurements with about 45% reduction of the energy switching time when regulation could be performed within acceptance. Fast energy modulation within beamline acceptance has potential for clinical applications and, when realized with an upstream degrader, does not require modification in the beamline hardware, therefore, being potentially applicable in any running facility. Centers with slow energy switching time can particularly profit from such a technique for reducing dead time during treatment delivery.

The Effects of Pencil Beam Scanning Proton Beam Therapy on a HeartMate 3 Left Ventricular Assist Device: Implications for Patient Safety.

The Effects of Pencil Beam Scanning Proton Beam Therapy on a HeartMate 3 Left Ventricular Assist Device: Implications for Patient Safety.

AAPM Task Group Report 290: Respiratory motion management for particle therapy.

Dose uncertainty induced by respiratory motion remains a major concern for treating thoracic and abdominal lesions using particle beams. This Task Group report reviews the impact of tumor motion and dosimetric considerations in particle radiotherapy, current motion‐management techniques, and limitations for different particle‐beam delivery modes (i.e., passive scattering, uniform scanning, and pencil‐beam scanning). Furthermore, the report provides guidance and risk analysis for quality assurance of the motion‐management procedures to ensure consistency and accuracy, and discusses future development and emerging motion‐management strategies. This report supplements previously published AAPM report TG76, and considers aspects of motion management that are crucial to the accurate and safe delivery of particle‐beam therapy. To that end, this report produces general recommendations for commissioning and facility‐specific dosimetric characterization, motion assessment, treatment planning, active and passive motion‐management techniques, image guidance and related decision‐making, monitoring throughout therapy, and recommendations for vendors. Key among these recommendations are that: (1) facilities should perform thorough planning studies (using retrospective data) and develop standard operating procedures that address all aspects of therapy for any treatment site involving respiratory motion; (2) a risk‐based methodology should be adopted for quality management and ongoing process improvement.

A Universal Range Shifter and Range Compensator Can Enable Proton Pencil Beam Scanning Single-Energy Bragg Peak FLASH-RT Treatment Using Current Commercially Available Proton Systems

Transmission beams have been proposed for ultra-high dose (or FLASH) proton planning, limiting the organ sparing potentials of proton therapy. By pulling back the ranges of the highest energy proton beams and compensating proton ranges to adapt to the target distally, the exit dose of proton beams can be eliminated to better protect organs at risk while still preserving FLASH dose rate delivery. An inverse planning tool was developed to optimize intensity modulated proton therapy using a single-energy layer for FLASH radiation therapy planning. The range pull-backs were calculated to stop single-energy proton beams at the distal edge of the target. The spot map and weights of each field were optimized to achieve a sufficient dose rate using proton beam Bragg peaks. A C-shape target in phantom, along with 6 consecutive lung cancer patients previously treated using proton stereotactic body radiation therapy were planned using this novel Bragg Peak method and also transmission technique. Dosimetry characteristics and 3-dimensional dose rate were investigated. The minimum monitor units (MU) for transmission and Bragg peak plans were 400 MU/spot and 1200 MU/spot, respectively, corresponding to spot peak dose rates of 670 GyRBE (relative biological effectiveness) per second and 1950 GyRBE per second. Bragg peak plans yield a generally comparable target uniformity while significantly reducing dose spillage volume from the low to medium dose level. For all the 6 lung cases delivery of 34 GyRBE in 1 fraction, assessing Radiation Therapy Oncology Group 0915 constraints, the lung V7GyRBE volume was reduced by up to 32% (P=.001) for Bragg peak plans. The transmission plans tended to generate 2.4% higher FLASH dose rate coverage (V40GyRBE/s) versus Bragg peak plans over the major organs at risk. However, Bragg peak plans could also reach the FLASH radiation therapy threshold of V40GyRBE/s using a higher MU/spot and sophisticated dose-rate optimization algorithm. This first proof-of-concept study has demonstrated this novel method of combining range pull-back and powerful inverse optimization capable of achieving FLASH dose rate based on currently available machine parameters using a single-energy Bragg peak. Similar target coverage and uniformity can be maintained by Bragg peak FLASH plans while substantially improving the sparing of organs at risk compared with transmission plans.

Fetal dose from proton pencil beam scanning craniospinal irradiation during pregnancy: a Monte Carlo study

Objective. We conducted a Monte Carlo study to comprehensively investigate the fetal dose resulting from proton pencil beam scanning (PBS) craniospinal irradiation (CSI) during pregnancy. Approach. The gestational-age dependent pregnant phantom series developed at the University of Florida (UF) were converted into DICOM-RT format (CT images and structures) and imported into a treatment planning system (TPS) (Eclipse v15.6) commissioned to a IBA PBS nozzle. A proton PBS CSI plan (prescribed dose: 36 Gy) was created on the phantoms. The TOPAS MC code was used to simulate the proton PBS CSI on the phantoms, for which MC beam properties at the nozzle exit (spot size, spot divergence, mean energy, and energy spread) were matched to IBA PBS nozzle beam measurement data. We calculated mean absorbed doses for 28 organs and tissues and whole body of the fetus at eight gestational ages (8, 10, 15, 20, 25, 30, 35, and 38 weeks). For contextual purposes, the fetal organ/tissue doses from the treatment planning CT scan of the mother’s head and torso were estimated using the National Cancer Institute dosimetry system for CT (NCICT, Version 3) considering a low-dose CT protocol (CTDIvol: 8.97 mGy). Main results. The majority of the fetal organ/tissue doses from the proton PBS CSI treatment fell within a range of 3–6 mGy. The fetal organ/tissue doses for the 38 week phantom showed the largest variation with the doses ranging from 2.9 mGy (adrenals) to 8.2 mGy (eye lenses) while the smallest variation ranging from 3.2 mGy (oesophagus) to 4.4 mGy (brain) was observed for the doses for the 20 week phantom. The fetal whole-body dose ranged from 3.7 mGy (25 weeks) to 5.8 mGy (8 weeks). Most of the fetal doses from the planning CT scan fell within a range of 7–13 mGy, approximately 2-to-9 times lower than the fetal dose equivalents of the proton PBS CSI treatment (assuming a quality factor of 7). Significance. The fetal organ/tissue doses observed in the present work will be useful for one of the first clinically informative predictions on the magnitude of fetal dose during proton PBS CSI during pregnancy.

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.

FLASH Radiotherapy Using Single-Energy Proton PBS Transmission Beams for Hypofractionation Liver Cancer: Dose and Dose Rate Quantification.

PurposeThis work aims to study the dose and ultra-high-dose rate characteristics of transmission proton pencil beam scanning (PBS) FLASH radiotherapy (RT) for hypofractionation liver cancer based on the parameters of a commercially available proton system operating under FLASH mode.Methods and MaterialsAn in-house treatment planning software (TPS) was developed to perform intensity-modulated proton therapy (IMPT) FLASH-RT planning. Single-energy transmission proton PBS plans of 4.5 Gy × 15 fractions were optimized for seven consecutive hepatocellular carcinoma patients, using 2 and 5 fields combined with 1) the minimum MU/spot chosen between 100 and 400, and minimum spot time (MST) of 2 ms, and 2) the minimum MU/spot of 100, and MST of 0.5 ms, based upon considerations in target uniformities, OAR dose constraints, and OAR FLASH dose rate coverage. Then, the 3D average dose rate distribution was calculated. The dose metrics for the mean dose of Liver-GTV and other major OARs were characterized to evaluate the dose quality for the different combinations of field numbers and minimum spot times compared to that of conventional IMPT plans. Dose rate quality was evaluated using 40 Gy/s volume coverage (V40Gy/s).ResultsAll plans achieved favorable and comparable target uniformities, and target uniformity improved as the number of fields increased. For OARs, no significant dose differences were observed between plans of different field numbers and the same MST. For plans using shorter MST and the same field numbers, better sparing was generally observed in most OARs and was statistically significant for the chest wall. However, the FLASH dose rate coverage V40Gy/s was increased by 20% for 2-field plans compared to 5-field plans in most OARs with 2-ms MST, which was less evident in the 0.5-ms cases. For 2-field plans, dose metrics and V40Gy/s of select OARs have large variations due to the beam angle selection and variable distances to the targets. The transmission plans generally yielded inferior dosimetric quality to the conventional IMPT plans.ConclusionThis is the first attempt to assess liver FLASH treatment planning and demonstrates that it is challenging for hypofractionation with smaller fractional doses (4.5 Gy/fraction). Using fewer fields can allow higher minimum MU/spot, resulting in higher OAR FLASH dose rate coverages while achieving similar plan quality compared to plans with more fields. Shorter MST can result in better plan quality and comparable or even better FLASH dose rate coverage.

Technical note: Does the greater power of pencil beam scanning reduce the need for a proton gantry? A study of head‐and‐neck and brain tumors

Proton therapy systems without a gantry can be more compact and less expensive in terms of capital cost and therefore more available to a larger patient population. Would the advances in pencil beam scanning (PBS) and robotics make gantry-less treatment possible? In this study, we explore if the high-quality treatment plans can be obtained without a gantry. We recently showed that proton treatments with the patient in an upright position may be feasible with a new soft robotic immobilization device and imaging which enables multiple possible patient orientations during a treatment. In this study, we evaluate if this new treatment geometry could enable high quality treatment plans without a gantry. We created PBS treatment plans for seven patients with head-and-neck or brain tumors. Each patient was planned with two scenarios: one with a gantry with the patient in supine position and the other with a gantry-less fixed horizontal beam-line with the patient sitting upright. For the treatment plans, dose-volume-histograms (DVHs), target homogeneity index (HI), mean dose, , and are reported. A robustness analysis of one plan was performed with 2.5-mm setup errors and 3.5% range uncertainties with nine scenarios. Most of the PBS-gantry-less plans had similar target HI and organs-at-risk mean dose as compared to PBS-gantry plans and similar robustness with respect to range uncertainties and setup errors. PBS provides sufficient power to deliver high quality treatment plans without requiring a gantry for head-and-neck or brain tumors. In combination with the development of the new positioning and immobilization methods required to support this treatment geometry, this work suggests the feasibility of further development of a compact proton therapy system with a fixed horizontal beam-line to treat patients in sitting and reclined positions.

Small spot size versus large spot size: Effect on plan quality for lung cancer in pencil beam scanning proton therapy.

PurposeThe purpose of the current study was to evaluate the impact of spot size on the interplay effect, plan robustness, and dose to the organs at risk for lung cancer plans in pencil beam scanning (PBS) proton therapyMethodsThe current retrospective study included 13 lung cancer patients. For each patient, small spot (∼3 mm) plans and large spot (∼8 mm) plans were generated. The Monte Carlo algorithm was used for both robust plan optimization and final dose calculations. Each plan was normalized, such that 99% of the clinical target volume (CTV) received 99% of the prescription dose. Interplay effect was evaluated for treatment delivery starting in two different breathing phases (T0 and T50). Plan robustness was investigated for 12 perturbed scenarios, which combined the isocenter shift and range uncertainty. The nominal and worst‐case scenario (WCS) results were recorded for each treatment plan. Equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) were evaluated for the total lung, heart, and esophagus.ResultsIn comparison to large spot plans, the WCS values of small spot plans at CTV D95%, D96%, D97%, D98%, and D99% were higher with the average differences of 2.2% (range, 0.3%–3.7%), 2.3% (range, 0.5%–4.0%), 2.6% (range, 0.6%–4.4%), 2.7% (range, 0.9%–5.2%), and 2.7% (range, 0.3%–6.0%), respectively. The nominal and WCS mean dose and EUD for the esophagus, heart, and total lung were higher in large spot plans. The difference in NTCP between large spot and small spot plans was up to 1.9% for the total lung, up to 0.3% for the heart, and up to 32.8% for the esophagus. For robustness acceptance criteria of CTV D95% ≥ 98% of the prescription dose, seven small spot plans had all 12 perturbed scenarios meeting the criteria, whereas, for 13 large spot plans, there were ≥2 scenarios failing to meet the criteria. Interplay results showed that, on average, the target coverage in large spot plans was higher by 1.5% and 0.4% in non‐volumetric and volumetric repainting plans, respectively.ConclusionFor robustly optimized PBS lung cancer plans in our study, a small spot machine resulted in a more robust CTV against the setup and range errors when compared to a large spot machine. In the absence of volumetric repainting, large spot PBS lung plans were more robust against the interplay effect. The use of a volumetric repainting technique in both small and large spot PBS lung plans led to comparable interplay target coverage.

A Planning Comparison of IMRT vs. Pencil Beam Scanning for Deep Inspiration Breath Hold Lung Cancers.

Deep inspiration breath hold (DIBH) has dosimetric advantages for lung cancer patients treated with external beam therapy, but is difficult for many patients to perform. Proton therapy permits sparing of the downstream organs at risk (OAR). We compared conventionally fractionated proton (p) and photon(x) plans on both free breathing (FB) and DIBH planning CTs to determine the effect of DIBH with proton therapy. We evaluated 24 plans from 6 lung cancer patients treated with photon DIBH on a prospective protocol. All patients were re-planned using pencil beam scanning (PBS) proton therapy. New plans were generated for FB datasets with both modalities. All plans were renormalized to 60 Gy. We evaluated dosimetric parameters for heart, lung and esophagus. We also compared FBp to DIBHx parameters to quantify how FBp plans compare to DIBHx plans. Significant differences were found for lung metrics V20 and mean lung dose between FB and DIBH plans regardless of treatment modality. Furthermore, lung metrics for FBp were comparable or superior to DIBHx, suggesting that FB protons may be a viable alternative for those patients that cannot perform DIBH with IMRT. The heart dose metrics were significantly different for the 5 out of 6 patients where the PTV overlapped the heart as DIBH moved heart out of the high dose volume. Heart dose metrics were further reduced by proton therapy. DIBH offers similar relative advantages for lung sparing for PBS as it does for IMRT but the magnitude of the DIBH related gains in OAR sparing were smaller for PBS than IMRT. FBp plans offer similar or better lung and heart sparing compared to DIBHx plans. For IMRT patients who have difficulty performing DIBH, FB protons may offer an alternative.

Normal tissue exposure and second malignancy risk in vertebral-body-sparing craniospinal irradiation.

The purpose of this study was to compare dose to anterior organs at risk (OARs) and quantify the risk of developing secondary malignancy (SMN) in pediatric patients treated with vertebral-body-sparing (VBS) vs vertebral body (VB) pencil beam scanning proton craniospinal irradiation (CSI). Comparative plans of VBS and VB CSI were created for 10 previously treated patients. Dose-volume histograms were used to evaluate dose to OARs. Absolute excess risk of SMN was calculated according to the organ-specific, radiation-induced cancer incidence based on the organ equivalent dose. OAR dosimetric parameters and absolute excess risk of SMN were compared for VBS and VB plans using the Kruskal-Wallis H test (α = 0.05). VBS CSI leads to significantly lower radiation dose to the heart, esophagus, kidney, liver and bowel. Excluding the vertebral body also significantly decreases the absolute excess risk of SMN for liver, esophagus and bowel. For these reasons, implementation of VBS pencil beam scanning proton CSI should be considered.

Utilizing Pencil Beam Scan Dynamics and a Scintillation Screen to produce 3D Dose Distribution of Proton Beams

This study describes a method for producing volumetric dose profiles of proton beams from 2D slices of optical scintillation images. The method relies on a high frame rate camera acquisition (100 frames per second), the spot scanning capabilities of current proton pencil beam scanning systems, and a water equivalent scintillation screen. The acquired slices are corrected for optical blurring and ionization quenching and stacked to produce volumetric dose distribution. The volumetric optical dose profile had a pass rate of 98.3% for 2%/2mm local gamma analysis, suggesting the method can accurately measure dose profiles. The method can potentially image all clinical proton beams for pencil beam scanning systems and can extend to imaging patient plans, with further verification.

Pencil-beam scanning catheter for intracoronary optical coherence tomography

Current gradient-index (GRIN) lens based proximal-driven intracoronary optical coherence tomography (ICOCT) probes consist of a spacer and a GRIN lens with large gradient constant. This design provides great flexibility to control beam profiles, but the spacer length should be well controlled to obtain desired beam profiles and thus it sets an obstacle in mass catheter fabrication. Besides, although GRIN lens with large gradient constant can provide tight focus spot, it has short depth of focus and fast-expanded beam which leads to poor lateral resolution for deep tissue. In this paper, a type of spacer-removed probe is demonstrated with a small gradient constant GRIN lens. This design simplifies the fabrication process and is suitable for mass production. The output beam of the catheter is a narrow nearly collimated light beam, referred to as pencil beam here. The full width at half maximum beam size varies from 35.1 µm to 75.3 µm in air over 3-mm range. Probe design principles are elaborated with probe/catheter fabrication and performance test. The <em>in vivo</em> imaging of the catheter was verified by a clinical ICOCT system. Those results prove that this novel pencil-beam scanning catheter is potentially a good choice for ICOCT systems.

Pencil Beam Scanning (PBS) Intensity-Modulated Proton Therapy (IMPT) Chemoradiotherapy for Anal Canal Cancer-Single Institution Experience.

Background: A favourable dose distribution has been described for proton beam therapy (PBT) of anal cancer in dosimetric studies. The relationship between dosimetric parameters in bone marrow and haematologic toxicity, treatment interruptions, and treatment efficacy has also been documented. There are only few references on clinical results of PBT for anal cancer. The primary objective of the retrospective study was to assess the efficacy of pencil beam scanning intensity-modulated proton therapy (PBS IMPT) in the definitive chemoradiotherapy of anal cancer. Secondary objectives were established to identify the risks of acute chronic toxicity risks and to assess colostomy rates. Materials and methods: Patients were treated for biopsy-proven squamous cell cancer (SCC) of the anus at initial or advanced stages. Eligible patients received PBS IMPT at a single institution. Treatment was administered in two volumes: 1-tumour with margins plus involved lymph nodes; 2-regional lymph node groups: perirectal (mesorectal), obturatory, inguinal, internal, external, and common iliac. The total doses of 57.5 GyE and 45 GyE, respectively, were administered in volumes 1 and 2 in 25 fractions, 5 fractions per week, respectively (a simultaneous integrated boost). Concomitant chemotherapy cisplatinum (CDDP) plus 5-FU or CDDP plus capecitabine was administered as per protocol. The treatment effect was assessed using DRE (digital rectal examination) and MRI (magnetic resonance imaging) within the follow-up period. Toxicity was scaled using CTCAE version 4.0 criteria. Results: 39 of 41 patients treated during the period of February 2014-August 2021 were eligible for analysis. All patients completed treatment, 76.9% without interruption. The median treatment time was 35 days (32-35). The median follow-up period was 30 months, 34 patients are alive to-date, 5 patients died prior to the date of analysis, and 2 deaths were unrelated to the primary disease. The 2-year overall survival, relapse-free survival, and colostomy-free survival were 94.2%, 93.8%, and 91.0%, respectively. Complete regression was achieved in 36 patients (92.3%), partial regression was achieved in 2 (5.1%), and immediate progression at end of treatment occurred in 1 patient (2.6%). Salvage resection was indicated for two patients in partial regression and due to severe chronic dermatologic toxicity. The grade 3 and 4 haematological toxicity rates were 7.7% and 5.1%, respectively. The most frequent non-haematological acute toxicities of grade 3-4 observed were dermatitis (23.1%), diarrhoea (7.7%), and dehydration (7.7%). Chronic toxicity emerged predominantly as skin atrophy/ulceration grade 2 (26.5%) and grade 3-4 (5.8%), and radiation proctitis grade 2 (38.2%) and grade 3 (2.9%). Discussion, conclusions: This single-institution study showed the high efficacy of PBS IMPT, achieving a high rate of complete regression. The haematological acute toxicity of grade 3-4 remained low; however, the impact of altered chemotherapy (CDDP instead of mitomycin C) remains unclear. The incidence of other acute toxicities shares similarity with photon therapy investigated in large studies. The acute toxicity completely resolved in all patients, had no lethal outcomes, and never resulted in the necessity for colostomy. By contrast, it was chronic toxicity, skin ulceration, perirectal fistulation, and fibrosis that resulted in salvage surgery and/or the need for a colostomy. A challenging question remains: to what extent can PBT prevent chronic toxicity? Longer follow-up remains necessary.