Static superconducting gantry‑based proton CT combined with X‑ray CT as prior image for FLASH proton therapy

Proton FLASH therapy with an ultra-high dose rate is in urgent need of more accurate treatment plan system(TPS)to promote the development of proton computed tomography(CT)without intrinsic error compared with the transformation from X-ray CT.This paper presents an imaging mode of proton CT based on static superconducting gantry different from the conventional rotational gantry.The beam energy for proton CT is fixed at 350 MeV,which is boosted by a compact proton linac from 230 MeV,and then delivered by the gantry to scan the patient’s body for proton imaging.This study demonstrates that the static superconducting gantry-based proton CT is effective in clinical applications.In particular,the imaging mode,which combines the relative stopping power(RSP)map from X-ray CT as prior knowledge,can produce much a higher accuracy RSP map for TPSs and positioning and achieve ultra-fast image for real-time image-guided radiotherapy.This paper presents the conceptual design of a boosting linac,static superconducting gantry and proton CT imaging equipment.The feasibility of energy enhancement is verified by simulation,and results from Geant4 simulations and reconstruction algorithms are presented,including the simulation verification of the advantage of the imaging mode.

SAPT:a synchrotron-based proton therapy facility in Shanghai

Because of its excellent dose distribution,proton therapy is becoming increasingly popular in the medical application of cancer treatment.A synchrotron-based proton therapy facility was designed and constructed in Shanghai.The synchrotron,beam delivery system,and other technical systems were commissioned and reached their expected performances.After a clinical trial of 47 patients was finished,the proton therapy facility obtained a registration certificate from the National Medical Products Administration.The characteristics of the accelerator and treatment systems are described in this article.

Design of a rapid-cycling synchrotron for flash proton therapy

The purpose of this study was to design a rapid-cycling synchrotron, making it capable of proton beam ultrahigh dose rate irradiation, inspired by laser accelerators. The design had to be cheap and simple. We consider our design from six aspects: the lattice, injection, extraction, space charge effects, eddy current effects and energy switching. Efficiency and particle quantity must be addressed when injected. The space charge effects at the injection could affect particles' number. The eddy current effects in the vacuum chambers would affect the magnetic field itself and generate heat, all of which need to be taken into account. Fast extraction can obtain 10^(10) protons/pulse, equal to instantaneous dose rate up to 10~7 Gy/s in a very short time, while changing various extraction energies rapidly and easily to various deposition depths. In the further research, we expect to combine a delivery system with this accelerator to realize the FLASH irradiation.

Intensity Modulated Proton Therapy for Re-Irradiation of Bulky Loco-Regional Recurrent Breast Cancer: A Case Report

Patients with recurrent breast cancer to chest wall, who had previous irradiation, are difficult to manage and have limited options. Several reports described the use of photon therapy, hyperthermia, and brachytherapy. This is a case report of a 72-year-old female with Stage IIIA (pT3N1M0) invasive ductal carcinoma of the right breast status post modified radical mastectomy. The patient developed recurrence to the chest wall and one internal mammary lymph node one year later. She received 3-D conformal photon radiation therapy for this recurrence. Two years later, she had progression of the recurrence at the right chest wall and axillary and internal mammary lymph nodes. She was treated with intensity modulated proton therapy (IMPT) for a total of 6600 cGy in 33 fractions. However, four months later, she was found to have biopsy-proven isolated metastatic disease at her right bicep, which was again treated with IMPT for a dose of 6000 cGy in 20 fractions. Proton beam therapy was used in this case to spare dose to the brachial plexus, heart and lung while optimally irradiating the recurrent tumors. At last follow up, the patient is alive and has been disease free for 39 months. This report describes the technique and dosimetry for this unique case, which also reviewed recent series of re-irradiation using proton beam.

Collection efficiency of a monitor parallel plate ionization chamber for pencil beam scanning proton therapy

The collection efficiency of monitor parallel plate ionization chambers is the main uncertainty in the beam control of pencil beam scanning systems.Existing calculation methods for collection efficiency in photon or passive scattering proton systems have not considered the characteristics of non-uniform charge density in pencil beam scanning systems.In this study,Boag’s theory was applied to a proton pencil beam scanning system.The transverse distribution of charge density in the ionization chamber was considered to be a Gaussian function and an analytical solution was derived to calculate collection efficiency in the beam spot area.This calculation method is called the integral method and it was used to investigate the effects of beam parameters on collection efficiency.It was determined that collection efficiency is positively correlated with applied voltage,beam size,and beam energy,but negatively correlated with beam current intensity.Additionally,it was confirmed that collection efficiency is improved when the air filling the monitor parallel plate ionization chamber is replaced with nitrogen.

Radiation shielding design of a compact single-room proton therapy based on synchrotron

A synchrotron-based proton therapy(PT)facility that conforms with the requirement of future development trend in compact PT can be operated without an energy selection system.This article demonstrates a novel radiation shielding design for this purpose.Various FLUKAbased Monte Carlo simulations have been performed to validate its feasibility.In this design,two different shielding scenarios(3-m-thick concrete and 2-m-thick iron–concrete)are proved able to reduce the public annual dose to the limit of 0.1 mSv/year.The calculation result shows that the non-primary radiation from a PT system without an inner shielding wall complies with the IEC 60601-2-64 international standard,making a single room a reality.Moreover,the H/D value of this design decreases from 2.14 to 0.32 mSv/Gy when the distance ranges from 50 to 150 cm from the isocenter,which is consistent with the previous result from another study.By establishing a typical time schedule and procedures in a treatment day for a single room in the simulation,a non-urgent machine maintenance time of 10 min after treatment is recommended,and the residual radiation level in most areas can be reduced to 2.5 lSv/h.The annual dose for radiation therapists coming from the residual radiation is 1 mSv,which is 20%of the target design.In general,this shielding design ensures a low cost and compact facility compared with the cyclotron-based PT system.

Shortening the delivery time of proton therapy by real-time compensation method with raster scanning

Among the various scanning techniques, spot and raster scanning are the most frequently adopted. Raster scanning turns off the beam only when each isoenergy slice irradiation is completed. This feature intrinsically solves the leakage dose and frequent beam-switching problems encountered during spot scanning. However, to shorten the delivery time of raster scanning, a sophisticated dose control strategy is required to guarantee dose distribution.In this study, a real-time compensation method with raster scanning for synchrotron systems was designed. It is characterized by a small spot-spacing planning strategy and real-time subtraction of the transient number of particles delivered between two planning-spot positions from the planned number of particles of the subsequent raster point.The efficacy of the compensation method was demonstrated by performing accurate raster scanning simulations with an in-house simulation code and accurate final dose evaluations with a commercial treatment planning system.Given the similar dose evaluation criteria under a practical high scanning speed, compared with the spot scanning method, the total delivery time of the compensated raster scanning method was significantly shortened by 53.3% in the case of irradiating a cubical target and by 28.8% in a pelvic case. Therefore, it can be concluded that real-time compensated raster scanning with a fast scanning configuration can significantly shorten the delivery time compared to that of spot scanning. It is important to reduce the pressure on patients caused by prolonged immobilization and to improve patient throughput capacity at particle therapy centers.

Design and development of the beamline for a proton therapy system

A proton therapy(PT)facility with multiple treatment rooms based on the superconducting cyclotron scheme is under development at Huazhong University of Science and Technology(HUST).This paper attempts to describe the design considerations and implementation of the PT beamline from a systematic viewpoint.Design considerations covering beam optics and the influence of high-order aberrations,beam energy/intensity modulation,and beam orbit correction are described.In addition to the technical implementation of the main beamline components and subsystems,including the energy degrader,fast kicker,beamline magnets,beam diagnostic system,and beamline control system are introduced.

Proton linac-based therapy facility for ultra-high dose rate (FLASH) treatment

As an advanced treatment method in the past five years,ultra-high dose rate(FLASH)radiotherapy as a breakthrough and milestone in radiotherapy development has been verified to be much less harmful to healthy tissues in different experiments.FLASH treatments require an instantaneous dose rate as high as hundreds of grays per second to complete the treatment in less than 100 ms.Current proton therapy facilities with the spread-out of the Bragg peak formed by different energy layers,to our knowledge,cannot easily achieve an adequate dose rate for FLASH treatments because the energy layer switch or gantry rotation of current facilities requires a few seconds,which is relatively long.A new design for a therapy facility based on a proton linear accelerator(linac)for FLASH treatment is proposed herein.It is designed under two criteria:no mechanical motion and no magnetic field variation.The new therapy facility can achieve an ultrahigh dose rate of up to 300 Gy/s;however,it delivers an instantaneous dose of 30 Gy within 100 ms to complete a typical FLASH treatment.The design includes a compact proton linac with permanent magnets,a fast beam kicker in both azimuth and elevation angles,a fixed gantry with a static superconducting coil to steer proton bunches with all energy,a fast beam scanner using radio-frequency(RF)deflectors,and a fast low-level RF system.All relevant principles and conceptual proposals are presented herein.

New frontiers in proton therapy:applications in cancers

Proton therapy offers dominant advantages over photon therapy due to the unique depth-dose characteristics of proton,which can cause a dramatic reduction in normal tissue doses both distal and proximal to the tumor target volume.In turn,this feature may allow dose escalation to the tumor target volume while sparing the tumor-neighboring susceptible organs at risk,which has the potential to reduce treatment toxicity and improve local control rate,quality of life and survival.Some dosimetric studies in various cancers have demonstrated the advantages over photon therapy in dose distributions.Further,it has been observed that proton therapy confers to substantial clinical advantage over photon therapy in head and neck,breast,hepatocellular,and non-small cell lung cancers.As such,proton therapy is regarded as the standard modality of radiotherapy in many pediatric cancers from the technical point of view.However,due to the limited clinical evidence,there have been concerns about the high cost of proton therapy from an economic point of view.Considering the treatment expenses for late radiation-induced toxicities,cost-effective analysis in many studies have shown that proton therapy is the most cost-effective option for brain,head and neck and selected breast cancers.Additional studies are warranted to better unveil the cost-effective values of proton therapy and to develop newer ways for better protection of normal tissues.This review aims at reviewing the recent studies on proton therapy to explore its benefits and cost-effectiveness in cancers.We strongly believe that proton therapy will be a common radiotherapy modality for most types of solid cancers in the future.

GPU-based cross-platform Monte Carlo proton dose calculation engine in the framework of Taichi

In recent years,graphics processing units(GPUs)have been applied to accelerate Monte Carlo(MC)simulations for proton dose calculation in radiotherapy.Nonetheless,current GPU platforms,such as Compute Unified Device Architecture(CUDA)and Open Computing Language(OpenCL),suffer from cross-platform limitation or relatively high programming barrier.However,the Taichi toolkit,which was developed to overcome these difficulties,has been successfully applied to high-performance numerical computations.Based on the class II condensed history simulation scheme with various proton-nucleus interactions,we developed a GPU-accelerated MC engine for proton transport using the Taichi toolkit.Dose distributions in homogeneous and heterogeneous geometries were calculated for 110,160,and 200 MeV protons and were compared with those obtained by full MC simulations using TOPAS.The gamma passing rates were greater than 0.99 and 0.95 with criteria of 2 mm,2%and 1 mm,1%,respectively,in all the benchmark tests.Moreover,the calculation speed was at least 5800 times faster than that of TOPAS,and the number of lines of code was approximately 10 times less than those of CUDA or OpenCL.Our study provides a highly accurate,efficient,and easy-to-use proton dose calculation engine for fast prototyping,beamlet calculation,and education purposes.

Physical design of scanning gantry for proton therapy facility

A proton therapy facility based on a linac injector and a slow cycling synchrotron is proposed. To achieve effective treatment of cancer, a scanning gantry is required. The flexible transmission of beam and high beam position accuracy are the most basic requirements for a gantry. The designed gantry optics and scanning system are presented. Great efforts are put into studying the sensitivity of the beam position in the isocenter to the element misalignments. It shows that quadrupole shift makes the largest contribution and special attention should be paid to it.

Proton beam therapy of periorbital sinonasal squamous cell carcinoma: Two case reports and review of literature

BACKGROUND Sinonasal malignancies are rare but demanding due to complex anatomy,usually late diagnosis,and inconsistent therapy strategy based on multimodality approaches.Squamous cell carcinoma(SCC)is the most common histology,with poorer prognosis.In the setting of orbital invasion,an orbital exenteration may be required.However,in case of primary rejection of disfiguring surgery or unresectable disease,proton beam therapy(PBT)should be largely considered,allowing for better sparing of neighboring critical structures and improved outcomes by dose escalation.CASE SUMMARY A 62-year-old male presented with a recurrent SCC in the nasal septum abutting frontal skull base and bilateral orbits at 7 mo after primary partial nasal amputation.Because of refusal of face-deforming surgery and considerable adverse effects of conventional radiotherapy,the patient underwent a PBT by hyperfractionated accelerated scheme,resulting in complete response and moderate toxicities.After 2 years,a nasal reconstruction was implemented with satisfactory appearance and recurrence-freedom to date.Another patient with an initially extended sinonasal SCC,invading right orbit and facial soft tissue,declined an orbital exenteration and was treated with a normofractionated PBT to the gross tumor and elective cervical lymphatics.The follow-up showed a continuous tumor remission with reasonable late toxicities,such as cataract and telangiectasia on the right.Despite T4a stage and disapproval of concurrent chemotherapy owing to individual choice,both patients still achieved outstanding treatment outcomes with PBT alone.CONCLUSION PBT enabled orbit preservation and excellent tumor control without severe adverse effects on both presented patients with locally advanced sinonasal SCC.

Complications from Plaque versus Proton Beam Therapy for Choroidal Melanoma: A Qualitative Systematic Review

Plaque brachytherapy has been a mainstay of treatment for choroidal melanoma to achieve intraocular tumor control. The most common radioisotopes used for treating smaller sized tumors are Iodine-125 in North America and Ruthenium-106 in Europe. Proton beam radiotherapy is available at a few centers and may also be used to achieve local tumor control. Both plaque and proton beam therapy are known to be associated with a range of complications that may affect visual outcome and quality of life. These include radiation retinopathy, optic neuropathy, neovascular glaucoma and local treatment failure, requiring enucleation. While differences in the rates of these complications have not been well established in the literature for patients treated with plaque versus proton beam therapy for choroidal melanoma, certain geographic regions prefer one treatment modality over the other. The purpose of this qualitative systematic review was to compare and contrast reported complications that developed with plaque and proton beam therapy for the treatment of choroidal melanoma in studies published over a ten-year period. Reported rates suggest that patients with proton beam therapy had potentially higher rates of complications, including vision loss, enucleation, and neovascular glaucoma compared to those with plaque therapy. The rates of optic neuropathy, radiation retinopathy, and cataract formation were widely variable for the two treatment modalities and rates of metastasis and metastasis-free survival appeared similar with both treatments. The most common reported predictors of ocular complications following both types of therapy were tumor distance from the optic nerve, tumor thickness, and radiation dose, suggesting that inherent tumor characteristics play a role in visual prognosis.

A new imaging mode based on X-ray CT as prior image and sparsely sampled projections for rapid clinical proton CT

Proton computed tomography(CT)has a distinct practical significance in clinical applications.It eliminates 3–5%errors caused by the transformation of Hounsfield unit(HU)to relative stopping power(RSP)values when using X-ray CT for positioning and treatment planning systems(TPSs).Following the development of FLASH proton therapy,there are increased requirements for accurate and rapid positioning in TPSs.Thus,a new rapid proton CT imaging mode is proposed based on sparsely sampled projections.The proton beam was boosted to 350 MeV by a compact proton linear accelerator(LINAC).In this study,the comparisons of the proton scattering with the energy of 350 MeV and 230 MeV are conducted based on GEANT4 simulations.As the sparsely sampled information associated with beam acquisitions at 12 angles is not enough for reconstruction,X-ray CT is used as a prior image.The RSP map generated by converting the X-ray CT was constructed based on Monte Carlo simulations.Considering the estimation of the most likely path(MLP),the prior image-constrained compressed sensing(PICCS)algorithm is used to reconstruct images from two different phantoms using sparse proton projections of 350 MeV parallel proton beam.The results show that it is feasible to realize the proton image reconstruction with the rapid proton CT imaging proposed in this paper.It can produce RSP maps with much higher accuracy for TPSs and fast positioning to achieve ultra-fast imaging for real-time image-guided radiotherapy(IGRT)in clinical proton therapy applications.

In Vivo Dosimetry of an Anthropomorphic Phantom Using the RADPOS for Proton Beam Therapy

The radiation positioning system (RADPOS) combines an electromagnetic positioning sensor with metal oxide semiconductor field-effect transistor (MOSFET) dosimetry, enabling simultaneous online measurement of dose and spatial position. Evaluation points can be determined with the RADPOS. The accuracy of in-vivo proton dosimetry was evaluated using the RADPOS and an anthropomorphic head and neck phantom. MOSFET doses measured at 3D positions obtained with the RADPOS were compared with treatment plan values calculated using a simplified Monte Carlo (SMC) method. MOSFET responses, which depend strongly on the linear energy transfer of the proton beam, were corrected using the SMC method. The SMC method was used to calculate only dose deposition determined by the experimental depth-dose distribution and lateral displacement of protons due to the multiple scattering effect in materials and incident angle. This method thus enabled rapid calculation of accurate doses in even heterogeneities. In vivo dosimetry using the RADPOS, as well as MOSFET doses, agreed with SMC calculations in the range of ?3.0% to 8.3%. Most measurement errors occurred because of uncertainties in dose calculations due to the 1-mm position error. The results indicate that uncertainties in measurement position can be controlled successfully within 1 mm when using the RADPOS with in-vivo proton dosimetry.

Proton Beam Therapy for Hepatocellular Carcinoma after the Fontan Procedure

Background: Hepatocellular carcinoma (HCC) is more likely to occur in patients with a history of Fontan surgery, possibly due to long-term liver congestion. Proton beam therapy (PBT) may be effective for HCC that develops after Fontan surgery. Methods: Six lesions in 5 patients (3 females, 2 males) received PBT. The median age of the patients was 33 (range 21 - 42) years, and the median age at the time of the Fontan procedure was 6 (5 - 13) years. Four patients had multiple HCC at the time of PBT. The median tumor size was 57 (22 - 80) mm and 4 patients were classified as Child-Pugh B. Two patients received transcatheter arterial chemoembolization before PBT. The schedule of PBT was 66 Gy (RBE) in 10 fractions for 2 lesions, 72.6 Gy (RBE) in 22 fractions for 2 lesions, and 74 GyE (RBE) in 37 fractions for 2 lesions. Results: The median follow-up period was 31 (10 - 46) months, and the numbers of survivors, deaths from primary diseases, and deaths from other diseases were 3, 1, and 1, respectively. There were no local recurrences, one intrahepatic metastasis, one lung metastasis, and one intrathoracic metastasis. Conclusion: Although experiences on a small number of patients cannot conclude things, we believe that PBT can be a reasonable choice of radical treatment for HCC occurring after the Fontan procedure.

Technological advances in radiotherapy for esophageal cancer

Radiotherapy with concurrent chemotherapy and surgery represent the main treatment modalities in esophageal cancer.The goal of modern radiotherapy approaches,based on recent technological advances,is to minimize post-treatment complications by improving the gross tumor volume definition (positron emission tomography-based planning),reducing interfraction motion (image-guided radiotherapy) and intrafraction motion (respiratory-gated radiotherapy),and by better dose delivery to the precisely defined planning target volume (intensity-modulated radiotherapy and proton therapy).Reduction of radiotherapy-related toxicity is fundamental to the improvement of clinical results in esophageal cancer,although the dose escalation concept is controversial.

Reformatted method for two-dimensional detector arrays measurement data in proton pencil beam scanning

The spatial resolution of a commercial two-dimensional(2D)ionization chamber(IC)array is limited by the size of the individual detector and the center-to-center distance between sensors.For dose distributions with areas of steep dose gradients,inter-detector dose values are derived by the interpolation of nearby detector readings in the conventional mathematical interpolation of 2D IC array measurements.This may introduce significant errors,particularly in proton spot scanning radiotherapy.In this study,by combining logfile-based reconstructed dose values and detector measurements with the Laplacian pyramid image blending method,a novel method is proposed to obtain a reformatted dose distribution that provides an improved estimation of the delivered dose distribution with high spatial resolution.Meanwhile,the similarity between the measured original data and the downsampled logfilebased reconstructed dose is regarded as the confidence of the reformatted dose distribution.Furthermore,we quantify the performance benefits of this new approach by directly comparing the reformatted dose distributions with 2D IC array detector mathematically interpolated measurements and original low-resolution measurements.The result shows that this new method is better than the mathematical interpolation and achieves gamma pass rates similar to those of the original low-resolution measurements.The reformatted dose distributions generally yield a confidence exceeding 95%.

Investigation of combined degrader for proton facility based on BDSIM/FLUKA Monte Carlo methods

The significant advantage of proton therapy over other particle-based techniques is in the unique physical characteristics of the Bragg peak.It can achieve a highly conformal dose distribution and maximize the probability of tumor control by varying the irradiation energy.Most proton facilities use cyclotrons for fixed energy beam extraction and are equipped with degrader and collimator systems for energy modulation and emittance suppression.However,interactions between charged particles and degrader materials inevitably cause beam loss and divergence and deteriorate beam performance,which present great challenges for downstream transport and clinical treatment.In this work,we investigate a method of energy reduction by combining boron carbide and graphite in a degrader to obtain greater beam transmission at lower energy.The results demonstrate that the beam size and emittance at the exit of the combined degrader diverge less than those of multi-wedge one in the energy range of 70-160 MeV.Correspondingly,the transmission efficiency after the first dipole also shows improvements of 36.26%at 70 MeV and 70.55%at 110 MeV.As a component with a high activity level,the degrader causes additional ambient radiation during operation.Residual induced radiation even remains several hours after system shutdown.Analysis of material activation and induced radiation based on 1 h irradiation with a 400 nA beam current shows that the combined degrader has a definite advantage in shielding despite producing more secondary particles.Both radioactivity and average ambient dose equivalent are reduced by 50%compared with the multiwedge degrader at the important cooling time of 1 h.After 12 h and 24 h of cooling,the radiation levels of degraders decrease slightly due to the presence of long half-life residual nuclides.The average dose generated from the multi-wedge degrader is still 1.25 times higher than that of the combined one.